International Journal of Molecular Sciences

Research

18 pages, 2946 KiB

Open AccessArticle

AGEs-Induced IL-6 Synthesis Precedes RAGE Up-Regulation in HEK 293 Cells: An Alternative Inflammatory Mechanism?

by Andreea Iren Serban^1,*, Loredana Stanca¹, Ovidiu Ionut Geicu^1,2 and Anca Dinischiotu²

¹ Department of Preclinical Sciences, Faculty of Veterinary Medicine, University of Agronomical Sciences and Veterinary Medicine Bucharest, 105 Splaiul Independentei, district 5, Bucharest 050097, Romania

² Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Bucharest, 91–95 Splaiul Independentei, district 5, Bucharest 050095, Romania

Int. J. Mol. Sci. 2015, 16(9), 20100-20117; https://doi.org/10.3390/ijms160920100 - 25 Aug 2015

Cited by 27 | Viewed by 8202

Abstract

Advanced glycation end products (AGEs) can activate the inflammatory pathways involved in diabetic nephropathy. Understanding these molecular pathways could contribute to therapeutic strategies for diabetes complications. We evaluated the modulation of inflammatory and oxidative markers, as well as the protective mechanisms employed by [...] Read more.

Advanced glycation end products (AGEs) can activate the inflammatory pathways involved in diabetic nephropathy. Understanding these molecular pathways could contribute to therapeutic strategies for diabetes complications. We evaluated the modulation of inflammatory and oxidative markers, as well as the protective mechanisms employed by human embryonic kidney cells (HEK 293) upon exposure to 200 μg/mL bovine serum albumine (BSA) or AGEs–BSA for 12, 24 and 48 h. The mRNA and protein expression levels of AGEs receptor (RAGE) and heat shock proteins (HSPs) 27, 60 and 70, the activity of antioxidant enzymes and the expression levels of eight cytokines were analysed. Cell damage via oxidative mechanisms was evaluated by glutathione and malondialdehyde levels. The data revealed two different time scale responses. First, the up-regulation of interleukin-6 (IL-6), HSP 27 and high catalase activity were detected as early as 12 h after exposure to AGEs–BSA, while the second response, after 24 h, consisted of NF-κB p65, RAGE, HSP 70 and inflammatory cytokine up-regulation, glutathione depletion, malondialdehyde increase and the activation of antioxidant enzymes. IL-6 might be important in the early ignition of inflammatory responses, while the cellular redox imbalance, RAGE activation and NF-κB p65 increased expression further enhance inflammatory signals in HEK 293 cells. Full article

(This article belongs to the Special Issue Mechanism of Action and Applications of Cytokines in Immunotherapy)

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21 pages, 3580 KiB

Open AccessArticle

Insight into the Structural Determinants of Imidazole Scaffold-Based Derivatives as TNF-α Release Inhibitors by in Silico Explorations

by Yuan Wang^1,†, Mingwei Wu^1,†, Chunzhi Ai² and Yonghua Wang^1,*

¹ Lab of Systems Pharmacology, College of Life Sciences, Northwest A&F (Agriculture and Forestry) University, Yangling 712100, China

² Lab of Pharmaceutical Resource Discovery, Dalian Institute of Chemical Physics, Graduate School of the Chinese Academy of Sciences, Dalian 116023, China

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2015, 16(9), 20118-20138; https://doi.org/10.3390/ijms160920118 - 25 Aug 2015

Cited by 5 | Viewed by 5874

Abstract

Presently, 151 widely-diverse pyridinylimidazole-based compounds that show inhibitory activities at the TNF-α release were investigated. By using the distance comparison technique (DISCOtech), comparative molecular field analysis (CoMFA), and comparative molecular similarity index analysis (CoMSIA) methods, the pharmacophore models and the three-dimensional quantitative structure-activity [...] Read more.

Presently, 151 widely-diverse pyridinylimidazole-based compounds that show inhibitory activities at the TNF-α release were investigated. By using the distance comparison technique (DISCOtech), comparative molecular field analysis (CoMFA), and comparative molecular similarity index analysis (CoMSIA) methods, the pharmacophore models and the three-dimensional quantitative structure-activity relationships (3D-QSAR) of the compounds were explored. The proposed pharmacophore model, including two hydrophobic sites, two aromatic centers, two H-bond donor atoms, two H-bond acceptor atoms, and two H-bond donor sites characterizes the necessary structural features of TNF-α release inhibitors. Both the resultant CoMFA and CoMSIA models exhibited satisfactory predictability (with Q² (cross-validated correlation coefficient) = 0.557, R²_ncv (non-cross-validated correlation coefficient) = 0.740, R²_pre (predicted correlation coefficient) = 0.749 and Q² = 0.598, R²_ncv = 0.767, R²_pre = 0.860, respectively). Good consistency was observed between the 3D-QSAR models and the pharmacophore model that the hydrophobic interaction and hydrogen bonds play crucial roles in the mechanism of actions. The corresponding contour maps generated by these models provide more diverse information about the key intermolecular interactions of inhibitors with the surrounding environment. All these models have extended the understanding of imidazole-based compounds in the structure-activity relationship, and are useful for rational design and screening of novel 2-thioimidazole-based TNF-α release inhibitors. Full article

(This article belongs to the Special Issue Chemical Bond and Bonding 2015)

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13 pages, 2627 KiB

Open AccessArticle

Huge Inverse Magnetization Generated by Faraday Induction in Nano-Sized Au@Ni Core@Shell Nanoparticles

by Chen-Chen Kuo, Chi-Yen Li, Chi-Hung Lee, Hsiao-Chi Li and Wen-Hsien Li^*

Department of Physics, National Central University, Jhongli 32001, Taiwan

Int. J. Mol. Sci. 2015, 16(9), 20139-20151; https://doi.org/10.3390/ijms160920139 - 25 Aug 2015

Cited by 4 | Viewed by 5528

Abstract

We report on the design and observation of huge inverse magnetizations pointing in the direction opposite to the applied magnetic field, induced in nano-sized amorphous Ni shells deposited on crystalline Au nanoparticles by turning the applied magnetic field off. The magnitude of the [...] Read more.

We report on the design and observation of huge inverse magnetizations pointing in the direction opposite to the applied magnetic field, induced in nano-sized amorphous Ni shells deposited on crystalline Au nanoparticles by turning the applied magnetic field off. The magnitude of the induced inverse magnetization is very sensitive to the field reduction rate as well as to the thermal and field processes before turning the magnetic field off, and can be as high as 54% of the magnetization prior to cutting off the applied magnetic field. Memory effect of the induced inverse magnetization is clearly revealed in the relaxation measurements. The relaxation of the inverse magnetization can be described by an exponential decay profile, with a critical exponent that can be effectively tuned by the wait time right after reaching the designated temperature and before the applied magnetic field is turned off. The key to these effects is to have the induced eddy current running beneath the amorphous Ni shells through Faraday induction. Full article

(This article belongs to the Special Issue Magnetic Nanoparticles 2015)

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16 pages, 1758 KiB

Open AccessArticle

Avoidance and Potential Remedy Solutions of Chimeras in Reconstructing the Phylogeny of Aphids Using the 16S rRNA Gene of Buchnera: A Case in Lachninae (Hemiptera)

by Rui Chen^1,2,†, Zhe Wang^1,3,†, Jing Chen¹ and Ge-Xia Qiao^1,*

¹ Key Laboratory of Zoological Systematics and Evolution, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China

² College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China

³ Institute of Plant Protection, Liaoning Academy of Agricultural Sciences, Shenyang 110161, China

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2015, 16(9), 20152-20167; https://doi.org/10.3390/ijms160920152 - 25 Aug 2015

Cited by 5 | Viewed by 6474

Abstract

It is known that PCR amplification of highly homologous genes from complex DNA mixtures can generate a significant proportion of chimeric sequences. The 16S rRNA gene is not only widely used in estimating the species diversity of endosymbionts in aphids but also used [...] Read more.

It is known that PCR amplification of highly homologous genes from complex DNA mixtures can generate a significant proportion of chimeric sequences. The 16S rRNA gene is not only widely used in estimating the species diversity of endosymbionts in aphids but also used to explore the co-diversification of aphids and their endosymbionts. Thus, chimeric sequences may lead to the discovery of non-existent endosymbiont species and mislead Buchnera-based phylogenetic analysis that lead to false conclusions. In this study, a high probability (6.49%) of chimeric sequence occurrence was found in the amplified 16S rRNA gene sequences of endosymbionts from aphid species in the subfamily Lachninae. These chimeras are hybrid products of multiple parent sequences from the dominant species of endosymbionts in each corresponding host. It is difficult to identify the chimeric sequences of a new or unidentified species due to the high variability of their main parent, Buchnera aphidicola, and because the chimeric sequences can confuse the phylogenetic analysis of 16S rRNA gene sequences. These chimeras present a challenge to Buchnera-based phylogenetic research in aphids. Thus, our study strongly suggests that using appropriate methods to detect chimeric 16S rRNA sequences may avoid some false conclusions in endosymbiont-based aphid research. Full article

(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)

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15 pages, 1147 KiB

Open AccessArticle

Impact of Single Nucleotide Polymorphisms (SNPs) on Immunosuppressive Therapy in Lung Transplantation

by Jesus Ruiz^1,2,†, María José Herrero^1,3,*,†, Virginia Bosó^1,2, Juan Eduardo Megías^1,2, David Hervás⁴, Jose Luis Poveda², Juan Escrivá⁵, Amparo Pastor⁵, Amparo Solé⁵ and Salvador Francisco Aliño^1,3,6

¹ Unidad de Farmacogenética, Instituto de Investigación Sanitaria La Fe, Hospital Universitario y Politécnico La Fe, Av. Fernando Abril Martorell 106, 46010 Valencia, Spain

² Servicio de Farmacia, Hospital Universitario y Politécnico La Fe, Av. Fernando Abril Martorell 106, 46010 Valencia, Spain

³ Departamento Farmacología, Facultad de Medicina, Universidad de Valencia, Av. Blasco Ibáñez 15, 46010 Valencia, Spain

⁴ Unidad de Bioestadística, Instituto Investigación Sanitaria La Fe. Av. Fernando Abril Martorell 106, 46010 Valencia, Spain

⁵ Unidad de Trasplante Pulmonar, Hospital Universitario y Politécnico La Fe, Av. Fernando Abril Martorell 106, 46010 Valencia, Spain

⁶ Unidad de Farmacología Clínica, Área Clínica del Medicamento, Hospital Universitario y Politécnico La Fe, Av. Fernando Abril Martorell 106, 46010 Valencia, Spain

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2015, 16(9), 20168-20182; https://doi.org/10.3390/ijms160920168 - 25 Aug 2015

Cited by 24 | Viewed by 6619

Abstract

Lung transplant patients present important variability in immunosuppressant blood concentrations during the first months after transplantation. Pharmacogenetics could explain part of this interindividual variability. We evaluated SNPs in genes that have previously shown correlations in other kinds of solid organ transplantation, namely ABCB1 [...] Read more.

Lung transplant patients present important variability in immunosuppressant blood concentrations during the first months after transplantation. Pharmacogenetics could explain part of this interindividual variability. We evaluated SNPs in genes that have previously shown correlations in other kinds of solid organ transplantation, namely ABCB1 and CYP3A5 genes with tacrolimus (Tac) and ABCC2, UGT1A9 and SLCO1B1 genes with mycophenolic acid (MPA), during the first six months after lung transplantation (51 patients). The genotype was correlated to the trough blood drug concentrations corrected for dose and body weight (C₀/D_c). The ABCB1 variant in rs1045642 was associated with significantly higher Tac concentration, at six months post-transplantation (CT vs. CC). In the MPA analysis, CT patients in ABCC2 rs3740066 presented significantly lower blood concentrations than CC or TT, three months after transplantation. Other tendencies, confirming previously expected results, were found associated with the rest of studied SNPs. An interesting trend was recorded for the incidence of acute rejection according to NOD2/CARD15 rs2066844 (CT: 27.9%; CC: 12.5%). Relevant SNPs related to Tac and MPA in other solid organ transplants also seem to be related to the efficacy and safety of treatment in the complex setting of lung transplantation. Full article

(This article belongs to the Special Issue Pharmacogenetics and Personalized Medicine)

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12 pages, 2494 KiB

Open AccessArticle

Perfluoroalkyl-Functionalized Hyperbranched Polyglycerol as Pore Forming Agents and Supramolecular Hosts in Polymer Microspheres

by Olaf Wagner¹, Maximilian Zieringer², Wynter J. Duncanson², David A. Weitz^2,3 and Rainer Haag^1,*

¹ Institute for Chemistry and Biochemistry, Freie Universität Berlin, Takustrasse 3, Berlin 14195, Germany

² School of Engineering and Applied Sciences, Harvard University, 29 Oxford St., Cambridge, MA 02138, USA

³ Department of Physics, Harvard University, 29 Oxford St., Cambridge, MA 02138, USA

Int. J. Mol. Sci. 2015, 16(9), 20183-20194; https://doi.org/10.3390/ijms160920183 - 26 Aug 2015

Cited by 7 | Viewed by 7219

Abstract

Perfluoroalkyl-functionalized, hyperbranched polyglycerols that produce stable microbubbles are integrated into a microfluidic emulsion to create porous microspheres. In a previously-presented work a dendrimer with a perfluorinated shell was used. By replacing this dendrimer core with a hyperbranched core and evaluating different core sizes [...] Read more.

Perfluoroalkyl-functionalized, hyperbranched polyglycerols that produce stable microbubbles are integrated into a microfluidic emulsion to create porous microspheres. In a previously-presented work a dendrimer with a perfluorinated shell was used. By replacing this dendrimer core with a hyperbranched core and evaluating different core sizes and degrees of fluorinated shell functionalization, we optimized the process to a more convenient synthesis and higher porosities. The new hyperbranched polyglycerol porogens produced more pores and can be used to prepare microspheres with porosity up to 12% (v/v). The presented preparation forms pores with a perfluoroalkyl-functionalized surface that enables the resulting microspheres to act as supramolecular host systems. The microspheres can incorporate gases into the pores and actives in the polymer matrix, while the perfluoroalkylated pore surface can be used to immobilize perfluoro-tagged molecules onto the pores by fluorous-fluorous interaction. Full article

(This article belongs to the Special Issue Supramolecular Interactions)

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17 pages, 3028 KiB

Open AccessArticle

Glucagon Like Peptide-1 (GLP-1) Modulates OVA-Induced Airway Inflammation and Mucus Secretion Involving a Protein Kinase A (PKA)-Dependent Nuclear Factor-κB (NF-κB) Signaling Pathway in Mice

by Tao Zhu^1,2,†, Xiao-ling Wu^2,†, Wei Zhang^3,† and Min Xiao^2,*

¹ Department of Respiratory Medicine, ZhuJiang Hospital, Southern Medical University, Guangzhou 510280, China

² Department of Respiratory Medicine, and Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, West China Hospital of Sichuan University, Chengdu 610041, China

³ Department of Respiratory Medicine, First Affiliated Hospital of Chengdu Medical College, Chengdu 610500, China

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2015, 16(9), 20195-20211; https://doi.org/10.3390/ijms160920195 - 26 Aug 2015

Cited by 87 | Viewed by 9777

Abstract

Asthma is a common chronic pulmonary inflammatory disease, featured with mucus hyper-secretion in the airway. Recent studies found that glucagon like peptide-1 (GLP-1) analogs, including liraglutide and exenatide, possessed a potent anti-inflammatory property through a protein kinase A (PKA)-dependent signaling pathway. Therefore, the [...] Read more.

Asthma is a common chronic pulmonary inflammatory disease, featured with mucus hyper-secretion in the airway. Recent studies found that glucagon like peptide-1 (GLP-1) analogs, including liraglutide and exenatide, possessed a potent anti-inflammatory property through a protein kinase A (PKA)-dependent signaling pathway. Therefore, the aim of current study was to investigate the value of GLP-1 analog therapy liraglutide in airway inflammation and mucus secretion in a murine model of ovalbumin (OVA)-induced asthma, and its underlying molecular mechanism. In our study, BALB/c mice were sensitized and challenged by OVA to induce chronic asthma. Pathological alterations, the number of cells and the content of inflammatory mediators in bronchoalveolar lavage fluid (BALF), and mucus secretion were observed and measured. In addition, the mRNA and protein expression of E-selectin and MUC5AC were analyzed by qPCR and Western blotting. Then, the phosphorylation of PKA and nuclear factor-κB (NF-κB) p65 were also measured by Western blotting. Further, NF-κB p65 DNA binding activity was detected by ELISA. OVA-induced airway inflammation, airway mucus hyper-secretion, the up-regulation of E-selectin and MUC5AC were remarkably inhibited by GLP-1 in mice (all p < 0.01). Then, we also found that OVA-reduced phosphorylation of PKA, and OVA-enhanced NF-κB p65 activation and NF-κB p65 DNA binding activity were markedly improved by GLP-1 (all p < 0.01). Furthermore, our data also figured out that these effects of GLP-1 were largely abrogated by the PKA inhibitor H-89 (all p < 0.01). Taken together, our results suggest that OVA-induced asthma were potently ameliorated by GLP-1 possibly through a PKA-dependent inactivation of NF-κB in mice, indicating that GLP-1 analogs may be considered an effective and safe drug for the potential treatment of asthma in the future. Full article

(This article belongs to the Section Biochemistry)

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13 pages, 3830 KiB

Open AccessArticle

Monitoring of Intracellular Tau Aggregation Regulated by OGA/OGT Inhibitors

by Sungsu Lim¹, Md. Mamunul Haque^1,2

, Ghilsoo Nam¹, Nayeon Ryoo³, Hyewhon Rhim^3,4,* and Yun Kyung Kim^1,2,*

¹ Center for Neuro-Medicine, Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul 136-791, South Korea

² Biological Chemistry, University of Science and Technology (UST), Daejeon 305-333, South Korea

³ Center for Neuroscience, Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul 136-791, South Korea

⁴ Department of Neuroscience, University of Science and Technology (UST), Daejeon 305-333, South Korea

Int. J. Mol. Sci. 2015, 16(9), 20212-20224; https://doi.org/10.3390/ijms160920212 - 26 Aug 2015

Cited by 38 | Viewed by 11329

Abstract

Abnormal phosphorylation of tau has been considered as a key pathogenic mechanism inducing tau aggregation in multiple neurodegenerative disorders, collectively called tauopathies. Recent evidence showed that tau phosphorylation sites are protected with O-linked β-N-acetylglucosamine (O-GlcNAc) in normal brain. [...] Read more.

Abnormal phosphorylation of tau has been considered as a key pathogenic mechanism inducing tau aggregation in multiple neurodegenerative disorders, collectively called tauopathies. Recent evidence showed that tau phosphorylation sites are protected with O-linked β-N-acetylglucosamine (O-GlcNAc) in normal brain. In pathological condition, tau is de-glycosylated and becomes a substrate for kinases. Despite the importance of O-GlcNAcylation in tau pathology, O-GlcNAc transferase (OGT), and an enzyme catalyzing O-GlcNAc to tau, has not been carefully investigated in the context of tau aggregation. Here, we investigated intracellular tau aggregation regulated by BZX2, an inhibitor of OGT. Upon the inhibition of OGT, tau phosphorylation increased 2.0-fold at Ser199 and 1.5-fold at Ser396, resulting in increased tau aggregation. Moreover, the BZX2 induced tau aggregation was efficiently reduced by the treatment of Thiamet G, an inhibitor of O-GlcNAcase (OGA). Our results demonstrated the protective role of OGT in tau aggregation and also suggest the counter-regulatory mechanism of OGA and OGT in tau pathology. Full article

(This article belongs to the Special Issue Protein Folding)

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14 pages, 11042 KiB

Open AccessArticle

Visualization of Biosurfactant Film Flow in a Bacillus subtilis Swarm Colony on an Agar Plate

by Kyunghoon Kim^1,2 and Jung Kyung Kim^2,3,*

¹ Department of Mechanical and Aerospace Engineering, North Carolina State University, Raleigh, NC 27695, USA

² Department of Mechanical Engineering, Kookmin University, Seoul 02707, Korea

³ Department of Integrative Biomedical Science and Engineering, Kookmin University, Seoul 02707, Korea

Int. J. Mol. Sci. 2015, 16(9), 20225-20238; https://doi.org/10.3390/ijms160920225 - 26 Aug 2015

Cited by 1 | Viewed by 5710

Abstract

Collective bacterial dynamics plays a crucial role in colony development. Although many research groups have studied the behavior of fluidic swarm colonies, the detailed mechanics of its motion remains elusive. Here, we developed a visualization method using submicron fluorescent beads for investigating the [...] Read more.

Collective bacterial dynamics plays a crucial role in colony development. Although many research groups have studied the behavior of fluidic swarm colonies, the detailed mechanics of its motion remains elusive. Here, we developed a visualization method using submicron fluorescent beads for investigating the flow field in a thin layer of fluid that covers a Bacillus subtilis swarm colony growing on an agar plate. The beads were initially embedded in the agar plate and subsequently distributed spontaneously at the upper surface of the expanding colony. We conducted long-term live cell imaging of the B. subtilis colony using the fluorescent tracers, and obtained high-resolution velocity maps of microscale vortices in the swarm colony using particle image velocimetry. A distinct periodic fluctuation in the average speed and vorticity of flow in swarm colony was observed at the inner region of the colony, and correlated with the switch between bacterial swarming and growth phases. At the advancing edge of the colony, both the magnitudes of velocity and vorticity of flow in swarm colony were inversely correlated with the spreading speed of the swarm edge. The advanced imaging tool developed in this study would facilitate further understanding of the effect of micro vortices in swarm colony on the collective dynamics of bacteria. Full article

(This article belongs to the Section Biochemistry)

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18 pages, 2587 KiB

Open AccessArticle

4-(Phenylsulfanyl)butan-2-One Suppresses Melanin Synthesis and Melanosome Maturation In Vitro and In Vivo

by Shing-Yi Sean Wu^1,†, Hui-Min David Wang^1,2,3,4,†

, Yi-Shan Wen¹, Wangta Liu^5,6

, Pin-Hui Li², Chien-Chih Chiu^5,7,8

, Pei-Chin Chen⁹, Chiung-Yao Huang¹, Jyh-Horng Sheu^1,3,10,* and Zhi-Hong Wen^1,9,*

¹ Department of Marine Biotechnology and Resources, National Sun Yat-Sen University, Kaohsiung 804, Taiwan, ROC

² Department of Fragrance and Cosmetic Science, Kaohsiung Medical University, Kaohsiung 807, Taiwan, ROC

³ Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 807, Taiwan, ROC

⁴ Center for Stem Cell Research, Kaohsiung Medical University, Kaohsiung 807, Taiwan, ROC

⁵ Department of Biotechnology, Kaohsiung Medical University, Kaohsiung 807, Taiwan, ROC

⁶ Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung 807, Taiwan, ROC

⁷ Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung 804, Taiwan, ROC

⁸ Translational Research Center, Cancer Center, Department of Medical Research, and Department of Obstetrics and Gynecology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan, ROC

⁹ Doctoral Degree Program in Marine Biotechnology, National Sun Yat-sen University and Academia Sinica, Kaohsiung 804, Taiwan, ROC

¹⁰ Department of Medical research, China Medical University Hospital, China Medical University, Taichung 404, Taiwan, ROC

^† These authors contributed equally to this work.

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Int. J. Mol. Sci. 2015, 16(9), 20240-20257; https://doi.org/10.3390/ijms160920240 - 26 Aug 2015

Cited by 30 | Viewed by 9633

Abstract

In this study, we screened compounds with skin whitening properties and favorable safety profiles from a series of marine related natural products, which were isolated from Formosan soft coral Cladiella australis. Our results indicated that 4-(phenylsulfanyl)butan-2-one could successfully inhibit pigment generation processes [...] Read more.

In this study, we screened compounds with skin whitening properties and favorable safety profiles from a series of marine related natural products, which were isolated from Formosan soft coral Cladiella australis. Our results indicated that 4-(phenylsulfanyl)butan-2-one could successfully inhibit pigment generation processes in mushroom tyrosinase platform assay, probably through the suppression of tyrosinase activity to be a non-competitive inhibitor of tyrosinase. In cell-based viability examinations, it demonstrated low cytotoxicity on melanoma cells and other normal human cells. It exhibited stronger inhibitions of melanin production and tyrosinase activity than arbutin or 1-phenyl-2-thiourea (PTU). Also, we discovered that 4-(phenylsulfanyl)butan-2-one reduces the protein expressions of melanin synthesis-related proteins, including the microphthalmia-associated transcription factor (MITF), tyrosinase-related protein-1 (Trp-1), dopachrome tautomerase (DCT, Trp-2), and glycoprotein 100 (GP100). In an in vivo zebrafish model, it presented a remarkable suppression in melanogenesis after 48 h. In summary, our in vitro and in vivo biological assays showed that 4-(phenylsulfanyl)butan-2-one possesses anti-melanogenic properties that are significant in medical cosmetology. Full article

(This article belongs to the Special Issue Bioactivity of Marine Natural Products)

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19 pages, 2022 KiB

Open AccessArticle

Interaction of High Flash Point Electrolytes and PE-Based Separators for Li-Ion Batteries

by Andreas Hofmann^1,*, Christoph Kaufmann¹, Marcus Müller² and Thomas Hanemann^1,3

¹ Institut für Angewandte Materialien-Werkstoffkunde, Karlsruher Institut für Technologie (KIT), Hermann-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen, Germany

² Institut für Angewandte Materialien-Keramische Werkstoffe und Technologien, Hermann-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen, Germany

³ Institut für Mikrosystemtechnik, Universität Freiburg, Georges-Köhler-Allee 102, 79110 Freiburg, Germany

Int. J. Mol. Sci. 2015, 16(9), 20258-20276; https://doi.org/10.3390/ijms160920258 - 27 Aug 2015

Cited by 12 | Viewed by 8716

Abstract

In this study, promising electrolytes for use in Li-ion batteries are studied in terms of interacting and wetting polyethylene (PE) and particle-coated PE separators. The electrolytes are characterized according to their physicochemical properties, where the flow characteristics and the surface tension are of [...] Read more.

In this study, promising electrolytes for use in Li-ion batteries are studied in terms of interacting and wetting polyethylene (PE) and particle-coated PE separators. The electrolytes are characterized according to their physicochemical properties, where the flow characteristics and the surface tension are of particular interest for electrolyte–separator interactions. The viscosity of the electrolytes is determined to be in a range of η = 4–400 mPa∙s and surface tension is finely graduated in a range of γ_L = 23.3–38.1 mN∙m⁻¹. It is verified that the technique of drop shape analysis can only be used in a limited matter to prove the interaction, uptake and penetration of electrolytes by separators. Cell testing of Li|NMC half cells reveals that those cell results cannot be inevitably deduced from physicochemical electrolyte properties as well as contact angle analysis. On the other hand, techniques are more suitable which detect liquid penetration into the interior of the separator. It is expected that the results can help fundamental researchers as well as users of novel electrolytes in current-day Li-ion battery technologies for developing and using novel material combinations. Full article

(This article belongs to the Section Materials Science)

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13 pages, 976 KiB

Open AccessArticle

The Effect of Cationic Polyamidoamine Dendrimers on Physicochemical Characteristics of Hydrogels with Erythromycin

by Magdalena Wróblewska and Katarzyna Winnicka^*

Department of Pharmaceutical Technology, Faculty of Pharmacy, Medical University of Białystok, Mickiewicza 2c, 15-222 Białystok, Poland

Int. J. Mol. Sci. 2015, 16(9), 20277-20289; https://doi.org/10.3390/ijms160920277 - 27 Aug 2015

Cited by 30 | Viewed by 5688

Abstract

Polyamidoamine dendrimers (PAMAM) represent a new class of hyperbranched, monodisperse, three-dimensional polymers with unique properties, which make them very promising carriers of antimicrobial agents. The present study aimed to evaluate the influence of PAMAM-NH₂ dendrimers generation two (G2) or three (G3) on [...] Read more.

Polyamidoamine dendrimers (PAMAM) represent a new class of hyperbranched, monodisperse, three-dimensional polymers with unique properties, which make them very promising carriers of antimicrobial agents. The present study aimed to evaluate the influence of PAMAM-NH₂ dendrimers generation two (G2) or three (G3) on physicochemical characteristics and structure of hydrogels with a model antibacterial lipophilic drug—erythromycin—commonly used in topical applications. From the obtained rheograms, it can be concluded that tested hydrogels were non-Newtonian thixotropic systems with shear-thinning behaviour. The dissolution tests revealed that erythromycin was definitely faster released from formulations containing PAMAM-NH₂ in concentration and generation dependent manner. However, the addition of PAMAM-NH₂ to hydrogels evoked only slight improvement of their antibacterial activity. It was also shown that the structure of hydrogels changed in the presence of PAMAM-NH₂ becoming less compact, diversified and more porous. Designed hydrogels with PAMAM-NH₂ G2 or G3 were stable stored up to three months at 40 ± 2 °C and 75% ± 5% RH. Full article

(This article belongs to the Special Issue Drug Delivery and Antimicrobial Agents)

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18 pages, 1679 KiB

Open AccessArticle

Rapid Bioassay-Guided Isolation of Antibacterial Clerodane Type Diterpenoid from Dodonaea viscosa (L.) Jaeq.

by Muhammad Khurram^1,2,3,*,†, Linda A. Lawton^2,†, Christine Edwards^2,†, Marcello Iriti^4,*

, Abdul Hameed^3,5, Murad A. Khan⁶, Farman A. Khan⁷

and Shafiq Ur Rahman¹

¹ Department of Pharmacy, Shaheed Benazir Bhutto University, Sheringal, Dir Upper 18000, Pakistan

² School of Pharmacy and Life Sciences, the Robert Gordon University, Aberdeen AB25 1HG, UK

³ Department of Microbiology, Quaid-i-Azam University, Islamabad 45320, Pakistan

⁴ Department of Agricultural and Environmental Sciences, Milan State University, Milan 20133, Italy

⁵ Centre for Interdisciplinary Research in Basic Sciences, International Islamic University, Islamabad 44000, Pakistan

⁶ Department of Chemistry, Kohat University of Science & Technology, Kohat 26000, Pakistan

⁷ Department of Chemistry, Shaheed Benazir Bhutto University, Sheringal, Dir Upper 18000, Pakistan

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2015, 16(9), 20290-20307; https://doi.org/10.3390/ijms160920290 - 27 Aug 2015

Cited by 12 | Viewed by 8197

Abstract

Plant extracts are complex matrices and, although crude extracts are widely in use, purified compounds are pivotal in drug discovery. This study describes the application of automated preparative-HPLC combined with a rapid off-line bacterial bioassay, using reduction of a tetrazolium salt as an [...] Read more.

Plant extracts are complex matrices and, although crude extracts are widely in use, purified compounds are pivotal in drug discovery. This study describes the application of automated preparative-HPLC combined with a rapid off-line bacterial bioassay, using reduction of a tetrazolium salt as an indicator of bacterial metabolism. This approach enabled the identification of fractions from Dodonaea viscosa that were active against Staphylococcus aureus and Escherichia coli, which, ultimately, resulted in the identification of a clerodane type diterpenoid, 6β-hydroxy-15,16-epoxy-5β, 8β, 9β, 10α-cleroda-3, 13(16), 14-trien-18-oic acid, showing bacteriostatic activity (minimum inhibitory concentration (MIC) = 64–128 µg/mL) against test bacteria. To the best of our knowledge, this is the first report on antibacterial activity of this metabolite from D. viscosa. Full article

(This article belongs to the Special Issue Molecular Research in Plant Secondary Metabolism 2015)

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18 pages, 2289 KiB

Open AccessArticle

Classification of Magnetic Nanoparticle Systems—Synthesis, Standardization and Analysis Methods in the NanoMag Project

by Sara Bogren¹, Andrea Fornara², Frank Ludwig³, Maria Del Puerto Morales⁴, Uwe Steinhoff⁵, Mikkel Fougt Hansen⁶, Olga Kazakova⁷ and Christer Johansson^1,*

¹ Acreo Swedish ICT AB, Arvid Hedvalls Backe 4, Box 53071, SE-400 14 Göteborg, Sweden

² SP Technical Research Institute of Sweden, Box 5607, SE-114 86 Stockholm, Sweden

³ Institute of Electrical Measurement and Fundamental Electrical Engineering, TU Braunschweig D-38106, Germany

⁴ Instituto de Ciencia de Materiales de Madrid, ICMM-CSIC, Cantoblanco, 28049 Madrid, Spain

⁵ Physikalisch-Technische Bundesanstalt, D-10587 Berlin, Germany

⁶ Department of Micro and Nanotechnology, Technical University of Denmark, DTU Nanotech, Building 345 East, Kgs. Lyngby DK-2800, Denmark

⁷ National Physical Laboratory, TW11 0LW Teddington, UK

Int. J. Mol. Sci. 2015, 16(9), 20308-20325; https://doi.org/10.3390/ijms160920308 - 27 Aug 2015

Cited by 67 | Viewed by 13190

Abstract

This study presents classification of different magnetic single- and multi-core particle systems using their measured dynamic magnetic properties together with their nanocrystal and particle sizes. The dynamic magnetic properties are measured with AC (dynamical) susceptometry and magnetorelaxometry and the size parameters are determined [...] Read more.

This study presents classification of different magnetic single- and multi-core particle systems using their measured dynamic magnetic properties together with their nanocrystal and particle sizes. The dynamic magnetic properties are measured with AC (dynamical) susceptometry and magnetorelaxometry and the size parameters are determined from electron microscopy and dynamic light scattering. Using these methods, we also show that the nanocrystal size and particle morphology determines the dynamic magnetic properties for both single- and multi-core particles. The presented results are obtained from the four year EU NMP FP7 project, NanoMag, which is focused on standardization of analysis methods for magnetic nanoparticles. Full article

(This article belongs to the Special Issue Magnetic Nanoparticles 2015)

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18 pages, 2315 KiB

Open AccessArticle

Rational Design of Diketopyrrolopyrrole-Based Small Moleculesas Donating Materials for Organic Solar Cells

by Ruifa Jin^* and Kai Wang

Inner Mongolia Key Laboratory of Photoelectric Functional Materials and College of Chemistry and Chemical Engineering, Chifeng University, Chifeng 024000, China

Int. J. Mol. Sci. 2015, 16(9), 20326-20343; https://doi.org/10.3390/ijms160920326 - 27 Aug 2015

Cited by 25 | Viewed by 5756

Abstract

A series of diketopyrrolopyrrole-based small molecules have been designed toexplore their optical, electronic, and charge transport properties as organic solar cell(OSCs) materials. The calculation results showed that the designed molecules can lowerthe band gap and extend the absorption spectrum towards longer wavelengths.The designed [...] Read more.

A series of diketopyrrolopyrrole-based small molecules have been designed toexplore their optical, electronic, and charge transport properties as organic solar cell(OSCs) materials. The calculation results showed that the designed molecules can lowerthe band gap and extend the absorption spectrum towards longer wavelengths.The designed molecules own the large longest wavelength of absorption spectra,the oscillator strength, and absorption region values. The optical, electronic, and chargetransport properties of the designed molecules are affected by the introduction of differentπ-bridges and end groups. We have also predicted the mobility of the designed moleculewith the lowest total energies. Our results reveal that the designed molecules are expectedto be promising candidates for OSC materials. Additionally, the designed molecules areexpected to be promising candidates for electron and/or hole transport materials. On thebasis of our results, we suggest that molecules under investigation are suitable donors for[6,6]-phenyl-C61-butyric acid methyl ester (PCBM) and its derivatives as acceptors of OSCs. Full article

(This article belongs to the Section Physical Chemistry, Theoretical and Computational Chemistry)

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16 pages, 2055 KiB

Open AccessArticle

BMP3 Alone and Together with TGF-β Promote the Differentiation of Human Mesenchymal Stem Cells into a Nucleus Pulposus-Like Phenotype

by Xiaopeng Zhou, Yiqing Tao, Chengzhen Liang, Yujie Zhang, Hao Li and Qixin Chen^*

Department of Orthopedic Surgery, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Road, 310009 Hangzhou, China

Int. J. Mol. Sci. 2015, 16(9), 20344-20359; https://doi.org/10.3390/ijms160920344 - 27 Aug 2015

Cited by 29 | Viewed by 6693

Abstract

Human mesenchymal stem cells (MSCs) have the potential to differentiate into nucleus pulposus (NP)-like cells under specific stimulatory conditions. Thus far, the effects of bone morphogenetic protein 3 (BMP3) and the cocktail effects of BMP3 and transforming growth factor (TGF)-β on MSC proliferation [...] Read more.

Human mesenchymal stem cells (MSCs) have the potential to differentiate into nucleus pulposus (NP)-like cells under specific stimulatory conditions. Thus far, the effects of bone morphogenetic protein 3 (BMP3) and the cocktail effects of BMP3 and transforming growth factor (TGF)-β on MSC proliferation and differentiation remain obscure. Therefore, this study was designed to clarify these unknowns. MSCs were cultured with various gradients of BMP3 and BMP3/TGF-β, and compared with cultures in basal and TGF-β media. Cell proliferation, glycosaminoglycan (GAG) content, gene expression, and signaling proteins were measured to assess the effects of BMP3 and BMP3/TGF-β on MSCs. Cell number and GAG content increased upon the addition of BMP3 in a dose-dependent manner. The expression of COL2A1, ACAN, SOX9, and KRT19 increased following induction with BMP3 and TGF-β, in contrast to that of COL1A1, ALP, OPN, and COMP. Smad3 phosphorylation was upregulated by BMP3 and TGF-β, but BMP3 did not affect the phosphorylation of extracellular-signal regulated kinase (ERK) 1/2 or c-Jun N-terminal kinase (JNK). Our results reveal that BMP3 enhances MSC proliferation and differentiation into NP-like cells, as indicated by increased cell numbers and specific gene expressions, and may also cooperate with TGF-β induced positive effects. These actions are likely related to the activation of TGF-β signaling pathway. Full article

(This article belongs to the Special Issue Stem Cell Activation in Adult Organism)

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15 pages, 1917 KiB

Open AccessArticle

Detection of Selection Signatures on the X Chromosome in Three Sheep Breeds

by Caiye Zhu^1,2, Hongying Fan^1,3, Zehu Yuan¹, Shijin Hu¹, Li Zhang¹, Caihong Wei¹, Qin Zhang², Fuping Zhao^1,*

and Lixin Du^1,*

¹ National Center for Molecular Genetics and Breeding of Animal, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, No. 2 Yuanmingyuan West Rd., Haidian, Beijing 100193, China

² College of Animal Science and Technology, China Agricultural University, Beijing 100193, China

³ College of Animal Science and Technology, Gansu Agricultural University, Lanzhou 730070, China

Int. J. Mol. Sci. 2015, 16(9), 20360-20374; https://doi.org/10.3390/ijms160920360 - 28 Aug 2015

Cited by 12 | Viewed by 7630

Abstract

Artificial selection has played a critical role in animal breeding. Detection of artificial selection footprints in genomic regions can provide insights for understanding the function of specific phenotypic traits and better guide animal breeding. To more fully understand the relationship between genomic composition [...] Read more.

Artificial selection has played a critical role in animal breeding. Detection of artificial selection footprints in genomic regions can provide insights for understanding the function of specific phenotypic traits and better guide animal breeding. To more fully understand the relationship between genomic composition and phenotypic diversity arising from breed development, a genome-wide scan was conducted using an OvineSNP50 BeadChip and integrated haplotype score and fixation index analyses to detect selection signatures on the X chromosome in three sheep breeds. We identified 49, 34, and 55 candidate selection regions with lengths of 27.49, 16.47, and 25.42 Mb in German Mutton, Dorper, and Sunit sheep, respectively. Bioinformatics analysis showed that some of the genes in these regions with selection signatures, such as BMP15, were relevant to reproduction. We also identified some selection regions harboring genes that had human orthologs, including BKT, CENPI, GUCY2F, MSN, PCDH11X, PLP1, VSIG4, PAK3, WAS, PCDH19, PDHA1, and SRPX2. The VSIG4 and PCDH11X genes are associated with the immune system and disease, PDHA1 is associated with biosynthetic related pathways, and PCDH19 is expressed in the nervous system and skin. These genes may be useful as candidate genes for molecular breeding. Full article

(This article belongs to the Section Biochemistry)

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17 pages, 1295 KiB

Open AccessArticle

Mitochondrial Malfunctioning, Proteasome Arrest and Apoptosis in Cancer Cells by Focused Intracellular Generation of Oxygen Radicals

by Ilaria Postiglione^1,†, Angela Chiaviello^1,†, Federica Barra¹

, Emanuela Roscetto¹, Amata A. Soriano¹, Maria Rosaria Catania¹, Giuseppe Palumbo^1,*

and Giovanna Maria Pierantoni^1,2

¹ Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples 80131, Italy

² Institute of Experimental Endocrinology and Oncology (IEOS), National Research Council (CNR), Naples 80131, Italy

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2015, 16(9), 20375-20391; https://doi.org/10.3390/ijms160920375 - 28 Aug 2015

Cited by 2 | Viewed by 5857

Abstract

Photofrin/photodynamic therapy (PDT) at sub-lethal doses induced a transient stall in proteasome activity in surviving A549 (p53^+/+) and H1299 (p53^−/−) cells as indicated by the time-dependent decline/recovery of chymotrypsin-like activity. Indeed, within 3 h of incubation, Photofrin invaded the [...] Read more.

Photofrin/photodynamic therapy (PDT) at sub-lethal doses induced a transient stall in proteasome activity in surviving A549 (p53^+/+) and H1299 (p53^−/−) cells as indicated by the time-dependent decline/recovery of chymotrypsin-like activity. Indeed, within 3 h of incubation, Photofrin invaded the cytoplasm and localized preferentially within the mitochondria. Its light activation determined a decrease in mitochondrial membrane potential and a reversible arrest in proteasomal activity. A similar result is obtained by treating cells with Antimycin and Rotenone, indicating, as a common denominator of this effect, the ATP decrease. Both inhibitors, however, were more toxic to cells as the recovery of proteasomal activity was incomplete. We evaluated whether combining PDT (which is a treatment for killing tumor cells, per se, and inducing proteasome arrest in the surviving ones) with Bortezomib doses capable of sustaining the stall would protract the arrest with sufficient time to induce apoptosis in remaining cells. The evaluation of the mitochondrial membrane depolarization, residual proteasome and mitochondrial enzymatic activities, colony-forming capabilities, and changes in protein expression profiles in A549 and H1299 cells under a combined therapeutic regimen gave results consistent with our hypothesis. Full article

(This article belongs to the Special Issue Advances in Photodynamic Therapy)

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14 pages, 5568 KiB

Open AccessArticle

Photodynamic and Antibiotic Therapy in Combination to Fight Biofilms and Resistant Surface Bacterial Infections

by Federica Barra^1,†

, Emanuela Roscetto^1,†, Amata A. Soriano¹, Adriana Vollaro¹, Ilaria Postiglione¹, Giovanna Maria Pierantoni^1,2, Giuseppe Palumbo^1,*

and Maria Rosaria Catania¹

¹ Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples 80131, Italy

² Institute of Experimental Endocrinology and Oncology (IEOS), National Research Council (CNR), Naples 80131, Italy

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2015, 16(9), 20417-20430; https://doi.org/10.3390/ijms160920417 - 28 Aug 2015

Cited by 90 | Viewed by 7356

Abstract

Although photodynamic therapy (PDT), a therapeutic approach that involves a photosensitizer, light and O₂, has been principally considered for the treatment of specific types of cancers, other applications exist, including the treatment of infections. Unfortunately, PDT does not always guarantee full [...] Read more.

Although photodynamic therapy (PDT), a therapeutic approach that involves a photosensitizer, light and O₂, has been principally considered for the treatment of specific types of cancers, other applications exist, including the treatment of infections. Unfortunately, PDT does not always guarantee full success since it exerts lethal effects only in cells that have taken up a sufficient amount of photosensitizer and have been exposed to adequate light doses, conditions that are not always achieved. Based on our previous experience on the combination PDT/chemotherapy, we have explored the possibility of fighting bacteria that commonly crowd infected surfaces by combining PDT with an antibiotic, which normally does not harm the strain at low concentrations. To this purpose, we employed 5-aminolevulinic acid (5-ALA), a pro-drug that, once absorbed by proliferating bacteria, is converted into the natural photosensitizer Protoporphyrin IX (PpIX), followed by Gentamicin. Photoactivation generates reactive oxygen species (ROS) which damage or kill the cell, while Gentamicin, even at low doses, ends the work. Our experiments, in combination, have been highly successful against biofilms produced by several Gram positive bacteria (i.e., Staphylococcus aureus, Staphylococcus epidermidis, etc.). This original approach points to potentially new and wide applications in the therapy of infections of superficial wounds and sores. Full article

(This article belongs to the Special Issue Advances in Photodynamic Therapy)

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18 pages, 1474 KiB

Open AccessArticle

BMP9-Induced Survival Effect in Liver Tumor Cells Requires p38MAPK Activation

by María García-Álvaro¹, Annalisa Addante¹, Cesáreo Roncero¹, Margarita Fernández¹, Isabel Fabregat², Aránzazu Sánchez¹ and Blanca Herrera^1,*

¹ Department of Biochemistry and Molecular Biology II, Faculty of Pharmacy, Complutense University of Madrid. San Carlos Clinical Hospital Health Research Institute (IdISSC), Plaza Ramón y Cajal S/N, Madrid 28040, Spain

² Bellvitge Biomedical Research Institute (IDIBELL) and University of Barcelona (UB), L'Hospitalet de Llobregat, Barcelona 08908, Spain

Int. J. Mol. Sci. 2015, 16(9), 20431-20448; https://doi.org/10.3390/ijms160920431 - 28 Aug 2015

Cited by 24 | Viewed by 5825

Abstract

The study of bone morphogenetic proteins (BMPs) role in tumorigenic processes, and specifically in the liver, has gathered importance in the last few years. Previous studies have shown that BMP9 is overexpressed in about 40% of hepatocellular carcinoma (HCC) patients. In vitro data [...] Read more.

The study of bone morphogenetic proteins (BMPs) role in tumorigenic processes, and specifically in the liver, has gathered importance in the last few years. Previous studies have shown that BMP9 is overexpressed in about 40% of hepatocellular carcinoma (HCC) patients. In vitro data have also shown evidence that BMP9 has a pro-tumorigenic action, not only by inducing epithelial to mesenchymal transition (EMT) and migration, but also by promoting proliferation and survival in liver cancer cells. However, the precise mechanisms driving these effects have not yet been established. In the present work, we deepened our studies into the intracellular mechanisms implicated in the BMP9 proliferative and pro-survival effect on liver tumor cells. In HepG2 cells, BMP9 induces both Smad and non-Smad signaling cascades, specifically PI3K/AKT and p38MAPK. However, only the p38MAPK pathway contributes to the BMP9 growth-promoting effect on these cells. Using genetic and pharmacological approaches, we demonstrate that p38MAPK activation, although dispensable for the BMP9 proliferative activity, is required for the BMP9 protective effect on serum withdrawal-induced apoptosis. These findings contribute to a better understanding of the signaling pathways involved in the BMP9 pro-tumorigenic role in liver tumor cells. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Human Liver Diseases)

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19 pages, 993 KiB

Open AccessArticle

Mechanistic and Kinetic Studies on the Homogeneous Gas-Phase Formation of PCTA/DTs from 2,4-Dichlorothiophenol and 2,4,6-Trichlorothiophenol

by Fei Xu, Xiangli Shi, Yunfeng Li and Qingzhu Zhang^*

Environment Research Institute, Shandong University, Jinan 250100, China

Int. J. Mol. Sci. 2015, 16(9), 20449-20467; https://doi.org/10.3390/ijms160920449 - 28 Aug 2015

Cited by 12 | Viewed by 4718

Abstract

Polychlorinated thianthrene/dibenzothiophenes (PCTA/DTs) are sulfur analogues compounds to polychlorinated dibenzo-p-dioxin/dibenzofurans (PCDD/Fs). Chlorothiophenols (CTPs) are key precursors to form PCTA/DTs. 2,4-DCTP has the minimum number of Cl atoms to form 2,4,6,8-tetrachlorinated dibenzothiophenes (2,4,6,8-TeCDT), which is the most important and widely detected of the PCDTs. [...] Read more.

Polychlorinated thianthrene/dibenzothiophenes (PCTA/DTs) are sulfur analogues compounds to polychlorinated dibenzo-p-dioxin/dibenzofurans (PCDD/Fs). Chlorothiophenols (CTPs) are key precursors to form PCTA/DTs. 2,4-DCTP has the minimum number of Cl atoms to form 2,4,6,8-tetrachlorinated dibenzothiophenes (2,4,6,8-TeCDT), which is the most important and widely detected of the PCDTs. In this paper, quantum chemical calculations were carried out to investigate the homogeneous gas-phase formation of PCTA/DTs from 2,4-DCTP and 2,4,6-TCTP precursors at the MPWB1K/6-311+G(3df,2p)//MPWB1K/6-31+G(d,p) level. Several energetically feasible pathways were revealed to compare the formation potential of PCTA/DT products. The rate constants of the crucial elementary reactions were evaluated by the canonical variational transition-state (CVT) theory with the small curvature tunneling (SCT) correction over a wide temperature range of 600–1200 K. This study shows that pathways that ended with elimination of Cl step were dominant over pathways ended with elimination of the H step. The water molecule has a negative catalytic effect on the H-shift step and hinders the formation of PCDTs from 2,4-DCTP. This study, together with works already published from our group, clearly illustrates an increased propensity for the dioxin formation from CTPs over the analogous CPs. Full article

(This article belongs to the Section Physical Chemistry, Theoretical and Computational Chemistry)

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24 pages, 1226 KiB

Open AccessArticle

Evaluation of Appropriate Reference Genes for Reverse Transcription-Quantitative PCR Studies in Different Tissues of a Desert Poplar via Comparision of Different Algorithms

by Hou-Ling Wang^1,2,†

, Lan Li^1,†, Sha Tang³, Chao Yuan¹, Qianqian Tian¹, Yanyan Su¹, Hui-Guang Li¹, Lin Zhao¹, Weilun Yin^1,2, Rui Zhao^1,* and Xinli Xia^1,*

¹ National Engineering Laboratory for Tree Breeding, College of Biological Sciences and Technology, Beijing Forestry University, Beijing 100083, China

² The Key Laboratory for Silviculture and Conservation of Ministry Education, College of Forestry, Beijing Forestry University, Beijing 100083, China

³ Institute of Crop Sciences, Chinese Academy of Agricultural Sciences, Beijing 100081, China

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2015, 16(9), 20468-20491; https://doi.org/10.3390/ijms160920468 - 28 Aug 2015

Cited by 36 | Viewed by 7178

Abstract

Despite the unshakable status of reverse transcription-quantitative PCR in gene expression analysis, it has certain disadvantages, including that the results are highly dependent on the reference genes selected for data normalization. Since inappropriate endogenous control genes will lead to inaccurate target gene expression [...] Read more.

Despite the unshakable status of reverse transcription-quantitative PCR in gene expression analysis, it has certain disadvantages, including that the results are highly dependent on the reference genes selected for data normalization. Since inappropriate endogenous control genes will lead to inaccurate target gene expression profiles, the validation of suitable internal reference genes is essential. Given the increasing interest in functional genes and genomics of Populus euphratica, a desert poplar showing extraordinary adaptation to salt stress, we evaluated the expression stability of ten candidate reference genes in P. euphratica roots, stems, and leaves under salt stress conditions. We used five algorithms, namely, ΔC_t, NormFinder, geNorm, GrayNorm, and a rank aggregation method (RankAggreg) to identify suitable normalizers. To support the suitability of the identified reference genes and to compare the relative merits of these different algorithms, we analyzed and compared the relative expression levels of nine P. euphratica functional genes in different tissues. Our results indicate that a combination of multiple reference genes recommended by GrayNorm algorithm (e.g., a combination of Actin, EF1α, GAPDH, RP, UBQ in root) should be used instead of a single reference gene. These results are valuable for research of gene identification in different P. euphratica tissues. Full article

(This article belongs to the Special Issue Abiotic Stress and Gene Networks in Plants)

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19 pages, 1510 KiB

Open AccessArticle

Influence of Parathyroid Hormone-Loaded PLGA Nanoparticles in Porous Scaffolds for Bone Regeneration

by Piergiorgio Gentile^1,†, Vijay Kumar Nandagiri^2,3,†, Ritesh Pabari³, Jacqueline Daly⁴, Chiara Tonda-Turo², Gianluca Ciardelli² and Zebunnissa Ramtoola^3,*

¹ School of Clinical Dentistry, University of Sheffield, Sheffield S10 2TA, UK

² Department of Mechanical and Aerospace Engineering, Politecnico di Torino, Turin 10129, Italy

³ School of Pharmacy, Royal College of Surgeons in Ireland, Dublin 2, Ireland

⁴ Division of Biology, Department of Anatomy, Royal College of Surgeons in Ireland, Dublin 2, Ireland

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2015, 16(9), 20492-20510; https://doi.org/10.3390/ijms160920492 - 28 Aug 2015

Cited by 29 | Viewed by 6796

Abstract

Biodegradable poly(lactide-co-glycolide) (PLGA) nanoparticles, containing human parathyroid hormone (PTH (1–34)), prepared by a modified double emulsion-solvent diffusion-evaporation method, were incorporated in porous freeze-dried chitosan-gelatin (CH-G) scaffolds. The PTH-loaded nanoparticles (NPTH) were characterised in terms of morphology, size, protein loading, release kinetics [...] Read more.

Biodegradable poly(lactide-co-glycolide) (PLGA) nanoparticles, containing human parathyroid hormone (PTH (1–34)), prepared by a modified double emulsion-solvent diffusion-evaporation method, were incorporated in porous freeze-dried chitosan-gelatin (CH-G) scaffolds. The PTH-loaded nanoparticles (NPTH) were characterised in terms of morphology, size, protein loading, release kinetics and in vitro assessment of biological activity of released PTH and cytocompatibility studies against clonal human osteoblast (hFOB) cells. Structural integrity of incorporated and released PTH from nanoparticles was found to be intact by using Tris-tricine SDS-PAGE. In vitro PTH release kinetics from PLGA nanoparticles were characterised by a burst release followed by a slow release phase for 3–4 weeks. The released PTH was biologically active as evidenced by the stimulated release of cyclic AMP from hFOB cells as well as increased mineralisation studies. in vitro and cell studies demonstrated that the PTH bioactivity was maintained during the fabrication of PLGA nanoparticles and upon release. Finally, a content of 33.3% w/w NPTHs was incorporated in CH-G scaffolds, showing an intermittent release during the first 10 days and, followed by a controlled release over 28 days of observation time. The increased expression of Alkaline Phosphatase levels on hFOB cells further confirmed the activity of intermittently released PTH from scaffolds. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

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12 pages, 1265 KiB

Open AccessCommunication

Supracolloidal Assemblies as Sacrificial Templates for Porous Silk-Based Biomaterials

by John G. Hardy^1,2,3,*

, Chiara E. Ghezzi³, Richard J. Saballos¹, David L. Kaplan^3,* and Christine E. Schmidt^1,2,*

¹ J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Biomedical Sciences Building JG-53, P.O. Box 116131, Gainesville, FL 32611-6131, USA

² Department of Biomedical Engineering, the University of Texas at Austin, Austin, TX 78712, USA

³ Department of Biomedical Engineering, Tufts University, Medford, MA 02155, USA

Int. J. Mol. Sci. 2015, 16(9), 20511-20522; https://doi.org/10.3390/ijms160920511 - 28 Aug 2015

Cited by 6 | Viewed by 6844

Abstract

Tissues in the body are hierarchically structured composite materials with tissue-specific properties. Urea self-assembles via hydrogen bonding interactions into crystalline supracolloidal assemblies that can be used to impart macroscopic pores to polymer-based tissue scaffolds. In this communication, we explain the solvent interactions governing [...] Read more.

Tissues in the body are hierarchically structured composite materials with tissue-specific properties. Urea self-assembles via hydrogen bonding interactions into crystalline supracolloidal assemblies that can be used to impart macroscopic pores to polymer-based tissue scaffolds. In this communication, we explain the solvent interactions governing the solubility of urea and thereby the scope of compatible polymers. We also highlight the role of solvent interactions on the morphology of the resulting supracolloidal crystals. We elucidate the role of polymer-urea interactions on the morphology of the pores in the resulting biomaterials. Finally, we demonstrate that it is possible to use our urea templating methodology to prepare Bombyx mori silk protein-based biomaterials with pores that human dermal fibroblasts respond to by aligning with the long axis of the pores. This methodology has potential for application in a variety of different tissue engineering niches in which cell alignment is observed, including skin, bone, muscle and nerve. Full article

(This article belongs to the Special Issue Supramolecular Interactions)

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19 pages, 1326 KiB

Open AccessArticle

Impact of Chronic Hepatitis C Virus Genotype 1b Infection on Triglyceride Concentration in Serum Lipoprotein Fractions

by Tomohisa Nagano^1,*, Nobuyoshi Seki¹, Yoichi Tomita¹, Tomonori Sugita¹, Yuta Aida¹, Munenori Itagaki¹, Satoshi Sutoh¹, Hiroshi Abe¹, Akihito Tsubota²

and Yoshio Aizawa¹

¹ Department of Gastroenterology and Hepatology Internal Medicine, Jikei University Katsushika Medical Center, 6-41-2 Aoto, Katsushika-ku, Tokyo 125-8506, Japan

² Core Research Facilities for Basic Science, Research Center for Medical Science, Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo 105-8461, Japan

Int. J. Mol. Sci. 2015, 16(9), 20576-20594; https://doi.org/10.3390/ijms160920576 - 31 Aug 2015

Cited by 14 | Viewed by 6754

Abstract

Reduced low-density lipoprotein (LDL) cholesterol level is a characteristic feature of dyslipidemia in chronic hepatitis C virus (HCV) infection. However, abnormality in serum triglyceride (TG) has not been fully investigated. To clarify the impact of HCV genotype 1b (G1b) infection and advanced fibrosis [...] Read more.

Reduced low-density lipoprotein (LDL) cholesterol level is a characteristic feature of dyslipidemia in chronic hepatitis C virus (HCV) infection. However, abnormality in serum triglyceride (TG) has not been fully investigated. To clarify the impact of HCV genotype 1b (G1b) infection and advanced fibrosis on serum TG profiles, TG concentrations in lipoprotein fractions were examined in fasting sera from 185 subjects with active or cleared HCV infection by high-performance liquid chromatography. Serum lipoproteins were fractionated into four classes: chylomicron, very low-density lipoprotein (VLDL), LDL, and high-density lipoprotein (HDL). Then, the significance of HCV G1b infection on TG levels in each lipoprotein fraction was determined using multiple regression models. We found that active HCV G1b infection was positively associated with high HDL-TG levels and low VLDL-TG levels, independent of other factors included in the regression model. In VLDL sub-fractions, active HCV infection was only found to be associated with low levels of large VLDL-TG. Similarly, advanced liver fibrosis in chronic HCV G1b infection was associated with high levels of LDL-TG, HDL-TG, and small VLDL-TG, independent of other clinical factors. These findings indicate that active HCV G1b infection and advanced fibrosis are closely associated with abnormal serum TG profiles. Full article

(This article belongs to the Special Issue Viral Hepatitis Research)

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14 pages, 1542 KiB

Open AccessArticle

Exogenous Carbon Monoxide Decreases Sepsis-Induced Acute Kidney Injury and Inhibits NLRP3 Inflammasome Activation in Rats

by Peng Wang^1,2,†, Jian Huang^3,†, Yi Li^1,2, Ruiming Chang¹, Haidong Wu¹, Jiali Lin^1,2 and Zitong Huang^1,2,*

¹ Department of Emergency Medicine, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou 510120, China

² Institute of Cardiopulmonary Cerebral Resuscitation, Sun Yat-sen University, Guangzhou 510120, China

³ Department of Nephrology, the Fourth Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2015, 16(9), 20595-20608; https://doi.org/10.3390/ijms160920595 - 31 Aug 2015

Cited by 67 | Viewed by 6947

Abstract

Carbon monoxide (CO) has shown various physiological effects including anti-inflammatory activity in several diseases, whereas the therapeutic efficacy of CO on sepsis-induced acute kidney injury (AKI) has not been reported as of yet. The purpose of the present study was to explore the [...] Read more.

Carbon monoxide (CO) has shown various physiological effects including anti-inflammatory activity in several diseases, whereas the therapeutic efficacy of CO on sepsis-induced acute kidney injury (AKI) has not been reported as of yet. The purpose of the present study was to explore the effects of exogenous CO on sepsis-induced AKI and nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome activation in rats. Male rats were subjected to cecal ligation and puncture (CLP) to induce sepsis and AKI. Exogenous CO delivered from CO-releasing molecule 2 (CORM-2) was used intraperitoneally as intervention after CLP surgery. Therapeutic effects of CORM-2 on sepsis-induced AKI were assessed by measuring serum creatinine (Scr) and blood urea nitrogen (BUN), kidney histology scores, apoptotic cell scores, oxidative stress, levels of cytokines TNF-α and IL-1β, and NLRP3 inflammasome expression. CORM-2 treatment protected against the sepsis-induced AKI as evidenced by reducing serum Scr/BUN levels, apoptotic cells scores, increasing survival rates, and decreasing renal histology scores. Furthermore, treatment with CORM-2 significantly reduced TNF-α and IL-1β levels and oxidative stress. Moreover, CORM-2 treatment significantly decreased NLRP3 inflammasome protein expressions. Our study provided evidence that CORM-2 treatment protected against sepsis-induced AKI and inhibited NLRP3 inflammasome activation, and suggested that CORM-2 could be a potential therapeutic candidate for treating sepsis-induced AKI. Full article

(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)

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11 pages, 688 KiB

Open AccessArticle

SLCO1B1 c.388A>G Polymorphism Is Associated with HDL-C Levels in Response to Atorvastatin in Chilean Individuals

by Yalena Prado, Nicolás Saavedra, Tomás Zambrano, Jenny Lagos, Alexy Rosales and Luis A. Salazar^*

Center of Molecular Biology and Pharmacogenetics, Department of Basic Sciences, Scientific and Technological Bioresource Nucleus (BIOREN), Universidad de La Frontera, Temuco 4811230, Chile

Int. J. Mol. Sci. 2015, 16(9), 20609-20619; https://doi.org/10.3390/ijms160920609 - 31 Aug 2015

Cited by 31 | Viewed by 6789

Abstract

The use of statins as the preferred lipid-lowering therapy has clearly demonstrated its efficacy in the treatment of hypercholesterolemia, reducing also the risk of coronary events and cardiovascular disease mortality. In this study, we assessed single nucleotide polymorphisms (SNPs) in the SLCO1B1 gene [...] Read more.

The use of statins as the preferred lipid-lowering therapy has clearly demonstrated its efficacy in the treatment of hypercholesterolemia, reducing also the risk of coronary events and cardiovascular disease mortality. In this study, we assessed single nucleotide polymorphisms (SNPs) in the SLCO1B1 gene and their effect on atorvastatin response. We included 129 Chilean hypercholesterolemic patients undergoing 10 mg/day of atorvastatin therapy during 4 weeks. Lipid profile was determined before and after drug administration. Genotyping of SLCO1B1 rs4149056 (c.521T>C) SNP was performed with allele-specific polymerase chain reaction, whilst polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used for genotyping the SLCO1B1 rs2306283 (c.388A>G) variant. After statin therapy, concentrations of TC, LDL-C and TG had a decrease from baseline (p < 0.05). Also, HDL-C levels increased (p < 0.05). Minor allele frequencies for the rs2306283 and rs4149056 variants were 0.547 and 0.136, respectively. LDL-C response to atorvastatin was not associated with the SLCO1B1 rs4149056 nor the rs2306283 polymorphisms (p > 0.05). However, the latter SNP was associated with HDL-C variability after atorvastatin medication (p = 0.02). This study indicates that LDL-C reduction following atorvastatin therapy is not influenced by the SNPs evaluated. In addition, the polymorphism rs2306283 at the SLCO1B1 gene determines greater HDL-C concentrations in response to atorvastatin medication in Chilean hypercholesterolemic subjects. Full article

(This article belongs to the Special Issue Human Single Nucleotide Polymorphisms and Disease Diagnostics)

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21 pages, 1136 KiB

Open AccessArticle

Quantum Chemical and Kinetic Study on Polychlorinated Naphthalene Formation from 3-Chlorophenol Precursor

by Fei Xu, Xiangli Shi and Qingzhu Zhang^*

Environment Research Institute, Shandong University, Jinan 250100, China

Int. J. Mol. Sci. 2015, 16(9), 20620-20640; https://doi.org/10.3390/ijms160920620 - 31 Aug 2015

Cited by 5 | Viewed by 6754

Abstract

Polychlorinated naphthalenes (PCNs) are the smallest chlorinated polycyclic aromatic hydrocarbons (Cl-PAHs) and are often called dioxin-like compounds. Chlorophenols (CPs) are important precursors of PCN formation. In this paper, mechanistic and kinetic studies on the homogeneous gas-phase formation mechanism of PCNs from 3-CP precursor [...] Read more.

Polychlorinated naphthalenes (PCNs) are the smallest chlorinated polycyclic aromatic hydrocarbons (Cl-PAHs) and are often called dioxin-like compounds. Chlorophenols (CPs) are important precursors of PCN formation. In this paper, mechanistic and kinetic studies on the homogeneous gas-phase formation mechanism of PCNs from 3-CP precursor were investigated theoretically by using the density functional theory (DFT) method and canonical variational transition-state theory (CVT) with small curvature tunneling contribution (SCT). The reaction priority of different PCN formation pathways were disscussed. The rate constants of crucial elementary steps were deduced over a wide temperature range of 600−1200 K. The mechanisms were compared with the experimental observation and our previous works on the PCN formation from 2-CP and 4-CP. This study shows that pathways ended with Cl elimination are favored over those ended with H elimination from the 3-CP precursor. The formation potential of MCN is larger than that of DCN. The chlorine substitution pattern of monochlorophenols has a significant effect on isomer patterns and formation potential of PCN products. The results can be input into the environmental PCN controlling and prediction models as detailed parameters, which can be used to confirm the formation routes of PCNs, reduce PCN emission and establish PCN controlling strategies. Full article

(This article belongs to the Section Physical Chemistry, Theoretical and Computational Chemistry)

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16 pages, 2370 KiB

Open AccessArticle

NMR Studies on Li⁺, Na⁺ and K⁺ Complexes of Orthoester Cryptand o-Me₂-1.1.1

by René-Chris Brachvogel, Harald Maid and Max Von Delius^*

Department of Chemistry and Pharmacy, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Henkestr. 42, 91054 Erlangen, Germany

Int. J. Mol. Sci. 2015, 16(9), 20641-20656; https://doi.org/10.3390/ijms160920641 - 31 Aug 2015

Cited by 25 | Viewed by 11961

Abstract

Cryptands, a class of three-dimensional macrobicyclic hosts ideally suited for accommodating small guest ions, have played an important role in the early development of supramolecular chemistry. In contrast to related two-dimensional crown ethers, cryptands have so far only found limited applications, owing in [...] Read more.

Cryptands, a class of three-dimensional macrobicyclic hosts ideally suited for accommodating small guest ions, have played an important role in the early development of supramolecular chemistry. In contrast to related two-dimensional crown ethers, cryptands have so far only found limited applications, owing in large part to their relatively inefficient multistep synthesis. We have recently described a convenient one-pot, template synthesis of cryptands based on O,O,O-orthoesters acting as bridgeheads. Here we report variable-temperature, ¹H-1D EXSY and titration NMR studies on lithium, sodium, and potassium complexes of one such cryptand (o-Me₂-1.1.1). Our results indicate that lithium and sodium ions fit into the central cavity of the cryptand, resulting in a comparably high binding affinity and slow exchange with the bulk. The potassium ion binds instead in an exo fashion, resulting in relatively weak binding, associated with fast exchange kinetics. Collectively, these results indicate that orthoester cryptands such as o-Me₂-1.1.1 exhibit thermodynamic and kinetic properties in between those typically found for classical crown ethers and cryptands and that future efforts should be directed towards increasing the binding constants. Full article

(This article belongs to the Special Issue Supramolecular Interactions)

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17 pages, 1918 KiB

Open AccessArticle

A Novel Sucrose-Regulatory MADS-Box Transcription Factor GmNMHC5 Promotes Root Development and Nodulation in Soybean (Glycine max [L.] Merr.)

by Wei Liu¹, Xiangdong Han^1,2, Ge Zhan^1,2, Zhenfang Zhao^1,2, Yongjun Feng^2,* and Cunxiang Wu^1,*

¹ The National Key Facility for Crop Gene Resources and Genetic Improvement and MOA Key Lab of Soybean Biology (Beijing), Institute of Crop Sciences, the Chinese Academy of Agricultural Sciences, 12 Zhongguancun South Street, Haidian District, Beijing 100081, China

² School of Life Science, Beijing Institute of Technology, 5 Zhongguancun South Street, Haidian District, Beijing 100081, China

Int. J. Mol. Sci. 2015, 16(9), 20657-20673; https://doi.org/10.3390/ijms160920657 - 31 Aug 2015

Cited by 31 | Viewed by 6874

Abstract

The MADS-box protein family includes many transcription factors that have a conserved DNA-binding MADS-box domain. The proteins in this family were originally recognized to play prominent roles in floral development. Recent findings, especially with regard to the regulatory roles of the AGL17 subfamily [...] Read more.

The MADS-box protein family includes many transcription factors that have a conserved DNA-binding MADS-box domain. The proteins in this family were originally recognized to play prominent roles in floral development. Recent findings, especially with regard to the regulatory roles of the AGL17 subfamily in root development, have greatly broadened their known functions. In this study, a gene from soybean (Glycine max [L.] Merr.), GmNMHC5, was cloned from the Zigongdongdou cultivar and identified as a member of the AGL17 subfamily. Real-time fluorescence quantitative PCR analysis showed that GmNMHC5 was expressed at much higher levels in roots and nodules than in other organs. The activation of expression was first examined in leaves and roots, followed by shoot apexes. GmNMHC5 expression levels rose sharply when the plants were treated under short-day conditions (SD) and started to pod, whereas low levels were maintained in non-podding plants under long-day conditions (LD). Furthermore, overexpression of GmNMHC5 in transgenic soybean significantly promoted lateral root development and nodule building. Moreover, GmNMHC5 is upregulated by exogenous sucrose. These results indicate that GmNMHC5 can sense the sucrose signal and plays significant roles in lateral root development and nodule building. Full article

(This article belongs to the Special Issue Plant Molecular Biology)

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11 pages, 1328 KiB

Open AccessArticle

Use of Copper to Selectively Inhibit Brachionus calyciflorus (Predator) Growth in Chlorella kessleri (Prey) Mass Cultures for Algae Biodiesel Production

by Vishnupriya Pradeep¹, Steven W. Van Ginkel¹, Sichoon Park¹, Thomas Igou¹, Christine Yi¹, Hao Fu¹, Rachel Johnston², Terry Snell² and Yongsheng Chen^1,*

¹ School of Civil and Environmental Engineering, Georgia Institute of Technology, 200 Bobby Dodd Way, Atlanta, GA 30313, USA

² School of Biology, Georgia Institute of Technology, 310 Ferst Drive, Atlanta, GA 30313, USA

Int. J. Mol. Sci. 2015, 16(9), 20674-20684; https://doi.org/10.3390/ijms160920674 - 31 Aug 2015

Cited by 27 | Viewed by 7719

Abstract

A single Brachionus rotifer can consume thousands of algae cells per hour causing an algae pond to crash within days of infection. Thus, there is a great need to reduce rotifers in order for algal biofuel production to become reality. Copper can selectively [...] Read more.

A single Brachionus rotifer can consume thousands of algae cells per hour causing an algae pond to crash within days of infection. Thus, there is a great need to reduce rotifers in order for algal biofuel production to become reality. Copper can selectively inhibit rotifers in algae ponds, thereby protecting the algae crop. Differential toxicity tests were conducted to compare the copper sensitivity of a model rotifer—B. calyciflorus and an alga, C. kessleri. The rotifer LC₅₀ was <0.1 ppm while the alga was not affected up to 5 ppm Cu(II). The low pH of the rotifer stomach may make it more sensitive to copper. However, when these cultures were combined, a copper concentration of 1.5 ppm was needed to inhibit the rotifer as the alga bound the copper, decreasing its bioavailability. Copper (X ppm) had no effect on downstream fatty acid methyl ester extraction. Full article

(This article belongs to the Special Issue Microalgal Biotechnology)

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19 pages, 1692 KiB

Open AccessArticle

Biogas Production from Sugarcane Waste: Assessment on Kinetic Challenges for Process Designing

by Leandro Janke^1,2,*, Athaydes Leite³, Marcell Nikolausz³, Thomas Schmidt¹, Jan Liebetrau¹, Michael Nelles^1,2 and Walter Stinner¹

¹ Department of Biochemical Conversion, Deutsches Biomasseforschungszentrum Gemeinnützige GmbH, Torgauer Straße 116, 04347 Leipzig, Germany

² Faculty of Agricultural and Environmental Sciences, Chair of Waste Management, University of Rostock, Justus-von-Liebig-Weg 6, 18059 Rostock, Germany

³ Department of Environmental Microbiology, UFZ-Helmholtz Centre for Environmental Research, Permoserstraße 15, 04318 Leipzig, Germany

Int. J. Mol. Sci. 2015, 16(9), 20685-20703; https://doi.org/10.3390/ijms160920685 - 31 Aug 2015

Cited by 150 | Viewed by 13441

Abstract

Biogas production from sugarcane waste has large potential for energy generation, however, to enable the optimization of the anaerobic digestion (AD) process each substrate characteristic should be carefully evaluated. In this study, the kinetic challenges for biogas production from different types of sugarcane [...] Read more.

Biogas production from sugarcane waste has large potential for energy generation, however, to enable the optimization of the anaerobic digestion (AD) process each substrate characteristic should be carefully evaluated. In this study, the kinetic challenges for biogas production from different types of sugarcane waste were assessed. Samples of vinasse, filter cake, bagasse, and straw were analyzed in terms of total and volatile solids, chemical oxygen demand, macronutrients, trace elements, and nutritional value. Biochemical methane potential assays were performed to evaluate the energy potential of the substrates according to different types of sugarcane plants. Methane yields varied considerably (5–181 Nm³·ton_FM⁻¹), mainly due to the different substrate characteristics and sugar and/or ethanol production processes. Therefore, for the optimization of AD on a large-scale, continuous stirred-tank reactor with long hydraulic retention times (>35 days) should be used for biogas production from bagasse and straw, coupled with pre-treatment process to enhance the degradation of the fibrous carbohydrates. Biomass immobilization systems are recommended in case vinasse is used as substrate, due to its low solid content, while filter cake could complement the biogas production from vinasse during the sugarcane offseason, providing a higher utilization of the biogas system during the entire year. Full article

(This article belongs to the Special Issue Bioprocess Engineering)

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17 pages, 9018 KiB

Open AccessArticle

Regeneration of Articular Cartilage in Lizard Knee from Resident Stem/Progenitor Cells

by Lorenzo Alibardi

Comparative Histolab and Department of Bigea, University of Bologna, via Selmi 3, 40126 Bologna, Italy

Int. J. Mol. Sci. 2015, 16(9), 20731-20747; https://doi.org/10.3390/ijms160920731 - 1 Sep 2015

Cited by 14 | Viewed by 6410

Abstract

The epiphysis of femur and tibia in the lizard Podarcis muralis can extensively regenerate after injury. The process involves the articular cartilage and metaphyseal (growth) plate after damage. The secondary ossification center present between the articular cartilage and the growth plate is replaced [...] Read more.

The epiphysis of femur and tibia in the lizard Podarcis muralis can extensively regenerate after injury. The process involves the articular cartilage and metaphyseal (growth) plate after damage. The secondary ossification center present between the articular cartilage and the growth plate is replaced by cartilaginous epiphyses after about one month of regeneration at high temperature. The present study analyzes the origin of the chondrogenic cells from putative stem cells located in the growing centers of the epiphyses. The study is carried out using immunocytochemistry for the detection of 5BrdU-labeled long retaining cells and for the localization of telomerase, an enzyme that indicates stemness. The observations show that putative stem cells retaining 5BrdU and positive for telomerase are present in the superficial articular cartilage and metaphyseal growth plate located in the epiphyses. This observation suggests that these areas represent stem cell niches lasting for most of the lifetime of lizards. In healthy long bones of adult lizards, the addition of new chondrocytes from the stem cells population in the articular cartilage and the metaphyseal growth plate likely allows for slow, continuous longitudinal growth. When the knee is injured in the adult lizard, new populations of chondrocytes actively producing chondroitin sulfate proteoglycan are derived from these stem cells to allow for the formation of completely new cartilaginous epiphyses, possibly anticipating the re-formation of secondary centers in later stages. The study suggests that in this lizard species, the regenerative ability of the epiphyses is a pre-adaptation to the regeneration of the articular cartilage. Full article

(This article belongs to the Special Issue Molecular and Cellular Basis of Regeneration and Tissue Repair)

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14 pages, 1156 KiB

Open AccessArticle

Optimization and Evaluation of a Chitosan/Hydroxypropyl Methylcellulose Hydrogel Containing Toluidine Blue O for Antimicrobial Photodynamic Inactivation

by Chueh-Pin Chen^1,†, Chien-Ming Hsieh^2,†, Tsuimin Tsai³, Jen-Chang Yang⁴ and Chin-Tin Chen^1,*

¹ Department of Biochemical Science and Technology, National Taiwan University, Taipei 106, Taiwan

² Department of Cosmetic Science, Providence University, Taichung City 433, Taiwan

³ Graduate Institute of Biomedical Materials and Tissue Engineering, College of Oral Medicine, Taipei Medical University, Taipei 110, Taiwan

⁴ School of Dental Technology, College of Oral Medicine, Taipei Medical University, Taipei 110, Taiwan

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2015, 16(9), 20859-20872; https://doi.org/10.3390/ijms160920859 - 1 Sep 2015

Cited by 43 | Viewed by 8671

Abstract

Photodynamic inactivation (PDI) combined with chitosan has been shown as a promising antimicrobial approach. The purpose of this study was to develop a chitosan hydrogel containing hydroxypropyl methylcellulose (HPMC), chitosan and toluidine blue O (TBO) to improve the bactericidal efficacy for topical application [...] Read more.

Photodynamic inactivation (PDI) combined with chitosan has been shown as a promising antimicrobial approach. The purpose of this study was to develop a chitosan hydrogel containing hydroxypropyl methylcellulose (HPMC), chitosan and toluidine blue O (TBO) to improve the bactericidal efficacy for topical application in clinics. The PDI efficacy of hydrogel was examined in vitro against the biofilms of Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa). Confocal scanning laser microscopy (CSLM) was performed to investigate the penetration level of TBO into viable S. aureus biofilms. Incorporation of HMPC could increase the physicochemical properties of chitosan hydrogel including the hardness, viscosity as well as bioadhesion; however, higher HMPC concentration also resulted in reduced antimicrobial effect. CSLM analysis further demonstrated that higher HPMC concentration constrained TBO diffusion into the biofilm. The incubation of biofilm and hydrogel was further performed at an angle of 90 degrees. After light irradiation, compared to the mixture of TBO and chitosan, the hydrogel treated sample showed increased PDI efficacy indicated that incorporation of HPMC did improve antimicrobial effect. Finally, the bactericidal efficacy could be significantly augmented by prolonged retention of hydrogel in the biofilm as well as in the animal model of rat skin burn wounds after light irradiation. Full article

(This article belongs to the Special Issue Advances in Photodynamic Therapy)

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17 pages, 1691 KiB

Open AccessArticle

A Simple and Effective Mass Spectrometric Approach to Identify the Adulteration of the Mediterranean Diet Component Extra-Virgin Olive Oil with Corn Oil

by Francesco Di Girolamo^1,*, Andrea Masotti², Isabella Lante³, Margherita Scapaticci³, Cosima Damiana Calvano⁴, Carlo Zambonin⁴

, Maurizio Muraca⁵ and Lorenza Putignani^6,7,*

¹ Department of Laboratory Medicine, Bambino Gesù Children's Hospital, Scientific Institute for Research, Hospitalization and Health Care (IRCCS), Piazza Sant'Onofrio 4, Rome 00165, Italy

² Gene Expression-Microarrays Laboratory, Bambino Gesù Children's Hospital, Scientific Institute for Research, Hospitalization and Health Care (IRCCS), Piazza Sant'Onofrio 4, Rome 00165, Italy

³ Department of Laboratory Medicine, San Camillo Hospital, Viale Vittorio Veneto 18, Treviso 31100, Italy

⁴ Dipartimento di Chimica, Università degli Studi di Bari "Aldo Moro", Via Orabona 4, Bari 70126, Italy

⁵ Department of Women's and Children's Health, University of Padova, Via Giustiniani 3, Padova 35122, Italy

⁶ Parasitology Unit, Bambino Gesù Children's Hospital, Scientific Institute for Research, Hospitalization and Health Care (IRCCS), Piazza Sant'Onofrio 4, Rome 00165, Italy

⁷ Metagenomics Unit, Bambino Gesù Children's Hospital, Scientific Institute for Research, Hospitalization and Health Care (IRCCS), Piazza Sant'Onofrio 4, Rome 00165, Italy

Int. J. Mol. Sci. 2015, 16(9), 20896-20912; https://doi.org/10.3390/ijms160920896 - 1 Sep 2015

Cited by 27 | Viewed by 6314

Abstract

Extra virgin olive oil (EVOO) with its nutraceutical characteristics substantially contributes as a major nutrient to the health benefit of the Mediterranean diet. Unfortunately, the adulteration of EVOO with less expensive oils (e.g., peanut and corn oils), has become one of the biggest [...] Read more.

Extra virgin olive oil (EVOO) with its nutraceutical characteristics substantially contributes as a major nutrient to the health benefit of the Mediterranean diet. Unfortunately, the adulteration of EVOO with less expensive oils (e.g., peanut and corn oils), has become one of the biggest source of agricultural fraud in the European Union, with important health implications for consumers, mainly due to the introduction of seed oil-derived allergens causing, especially in children, severe food allergy phenomena. In this regard, revealing adulterations of EVOO is of fundamental importance for health care and prevention reasons, especially in children. To this aim, effective analytical methods to assess EVOO purity are necessary. Here, we propose a simple, rapid, robust and very sensitive method for non-specialized mass spectrometric laboratory, based on the matrix-assisted laser desorption/ionization mass spectrometry (MALDI-TOF MS) coupled to unsupervised hierarchical clustering (UHC), principal component (PCA) and Pearson’s correlation analyses, to reveal corn oil (CO) adulterations in EVOO at very low levels (down to 0.5%). Full article

(This article belongs to the Special Issue Bioactive Lipids and Lipidomics)

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26 pages, 2165 KiB

Open AccessArticle

Synthesis and Characterization of Chitosan-Coated Near-Infrared (NIR) Layered Double Hydroxide-Indocyanine Green Nanocomposites for Potential Applications in Photodynamic Therapy

by Pei-Ru Wei, Yaswanth Kuthati, Ranjith Kumar Kankala and Chia-Hung Lee^*

Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Hualien 974, Taiwan

Int. J. Mol. Sci. 2015, 16(9), 20943-20968; https://doi.org/10.3390/ijms160920943 - 1 Sep 2015

Cited by 43 | Viewed by 9036

Abstract

We designed a study for photodynamic therapy (PDT) using chitosan coated Mg–Al layered double hydroxide (LDH) nanoparticles as the delivery system. A Food and Drug Administration (FDA) approved near-infrared (NIR) fluorescent dye, indocyanine green (ICG) with photoactive properties was intercalated into amine modified [...] Read more.

We designed a study for photodynamic therapy (PDT) using chitosan coated Mg–Al layered double hydroxide (LDH) nanoparticles as the delivery system. A Food and Drug Administration (FDA) approved near-infrared (NIR) fluorescent dye, indocyanine green (ICG) with photoactive properties was intercalated into amine modified LDH interlayers by ion-exchange. The efficient positively charged polymer (chitosan (CS)) coating was achieved by the cross linkage using surface amine groups modified on the LDH nanoparticle surface with glutaraldehyde as a spacer. The unique hybridization of organic-inorganic nanocomposites rendered more effective and successful photodynamic therapy due to the photosensitizer stabilization in the interlayer of LDH, which prevents the leaching and metabolization of the photosensitizer in the physiological conditions. The results indicated that the polymer coating and the number of polymer coats have a significant impact on the photo-toxicity of the nano-composites. The double layer chitosan coated LDH–NH₂–ICG nanoparticles exhibited enhanced photo therapeutic effect compared with uncoated LDH–NH₂–ICG and single layer chitosan-coated LDH–NH₂–ICG due to the enhanced protection to photosensitizers against photo and thermal degradations. This new class of organic-inorganic hybrid nanocomposites can potentially serve as a platform for future non-invasive cancer diagnosis and therapy. Full article

(This article belongs to the Special Issue Chitins 2015)

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13 pages, 1409 KiB

Open AccessArticle

Treadmill Exercise Attenuates Retinal Oxidative Stress in Naturally-Aged Mice: An Immunohistochemical Study

by Chan-Sik Kim^1,†, Sok Park^2,†, Yoonseok Chun³, Wook Song⁴, Hee-Jae Kim⁴ and Junghyun Kim^1,*

¹ Korean Medicine Convergence Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, Korea

² Department of Sports and Health Management, Mokwon University, Daejeon 35349, Korea

³ Sports Wellness Center, Yong In University, Gyeonggi-do 17092, Korea

⁴ Health and Exercise Science Laboratory, Seoul National University, Seoul 08826, Korea

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2015, 16(9), 21008-21020; https://doi.org/10.3390/ijms160921008 - 2 Sep 2015

Cited by 27 | Viewed by 7565

Abstract

In the retina, a number of degenerative diseases, including glaucoma, diabetic retinopathy, and age-related macular degeneration, may occur as a result of aging. Oxidative damage is believed to contribute to the pathogenesis of aging as well as to age-related retinal disease. Although physiological [...] Read more.

In the retina, a number of degenerative diseases, including glaucoma, diabetic retinopathy, and age-related macular degeneration, may occur as a result of aging. Oxidative damage is believed to contribute to the pathogenesis of aging as well as to age-related retinal disease. Although physiological exercise has been shown to reduce oxidative stress in rats and mice, it is not known whether it has a similar effect in retinal tissues. The aim of this study was to evaluate retinal oxidative stress in naturally-aged mice. In addition, we evaluated the effects of aerobic training on retinal oxidative stress by immunohistochemically evaluating oxidative stress markers. A group of twelve-week-old male mice were not exercised (young control). Two groups of twenty-two-month-old male mice were created: an old control group and a treadmill exercise group. The old control group mice were not exercised. The treadmill exercise group mice ran on a treadmill (5 to 12 m/min, 30 to 60 min/day, 3 days/week for 12 weeks). The retinal thickness and number of cells in the ganglion cell layer of the naturally-aged mice were reduced compared to those in the young control mice. However, treadmill exercise reversed these morphological changes in the retinas. We evaluated retinal expression of carboxymethyllysine (CML), 8-hydroxy-2′-deoxyguanosine (8-OHdG) and nitrotyrosine. The retinas from the aged mice showed increased CML, 8-OHdG, and nitrotyrosine immunostaining intensities compared to young control mice. The exercise group exhibited significantly lower CML levels and nitro-oxidative stress than the old control group. These results suggest that regular exercise can reduce retinal oxidative stress and that physiological exercise may be distinctly advantageous in reducing retinal oxidative stress. Full article

(This article belongs to the Section Biochemistry)

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14 pages, 2755 KiB

Open AccessArticle

Chlorella vulgaris Attenuates Dermatophagoides Farinae-Induced Atopic Dermatitis-Like Symptoms in NC/Nga Mice

by Heerim Kang^1,†, Chang Hyung Lee^1,†, Jong Rhan Kim^1,2, Jung Yeon Kwon², Sang Gwon Seo^1,2, Jae Gab Han^3,4, Byung Gon Kim^4,5, Jong-Eun Kim^1,2,6,* and Ki Won Lee^1,2,6,*

¹ WCU Biomodulation Major, Department of Agricultural Biotechnology, Seoul National University, Seoul 151-921, Korea

² Advanced Institutes of Convergence Technology, Seoul National University, Suwon 443-270, Korea

³ Department of Biomaterials Science and Engineering, Yonsei University, Seoul 120-749, Korea

⁴ Department of Health Food Research & Development of Daesang Corp., Icheon 467-813, Korea

⁵ Interdisplinary course of Science for Aging, Graduate School, Yonsei University, Seoul 120-749, Korea

⁶ Research Institute of Bio-Food Industry, Institute of Green Bio-Science and Technology, Seoul National University, Pyeongchang 232-916, Korea

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2015, 16(9), 21021-21034; https://doi.org/10.3390/ijms160921021 - 2 Sep 2015

Cited by 27 | Viewed by 14273

Abstract

Atopic dermatitis (AD) is a chronic and inflammatory skin disease that can place a significant burden on quality of life for patients. AD most frequently appears under the age of six and although its prevalence is increasing worldwide, therapeutic treatment options are limited. [...] Read more.

Atopic dermatitis (AD) is a chronic and inflammatory skin disease that can place a significant burden on quality of life for patients. AD most frequently appears under the age of six and although its prevalence is increasing worldwide, therapeutic treatment options are limited. Chlorella vulgaris (CV) is a species of the freshwater green algae genus chlorella, and has been reported to modulate allergy-inducible factors when ingested. Here, we examined the effect of CV supplementation on AD-like symptoms in NC/Nga mice. CV was orally administrated for six weeks while AD-like symptoms were induced via topical application of Dermatophagoides farinae extract (DFE). CV treatment reduced dermatitis scores, epidermal thickness, and skin hydration. Histological analysis also revealed that CV treatment reduced DFE-induced eosinophil and mast cell infiltration into the skin, while analysis of serum chemokine levels indicated that CV treatment downregulated thymus- and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC) levels. In addition, CV treatment downregulated mRNA expression levels of IL-4 and IFN-γ. Taken together, these results suggest that CV extract may have potential as a nutraceutical ingredient for the prevention of AD. Full article

(This article belongs to the Section Biochemistry)

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21 pages, 2631 KiB

Open AccessArticle

A Series of New Ligustrazine-Triterpenes Derivatives as Anti-Tumor Agents: Design, Synthesis, and Biological Evaluation

by Bing Xu^1,†

, Fuhao Chu^1,†

, Yuzhong Zhang², Xiaobo Wang³, Qiang Li¹, Wei Liu⁴, Xin Xu¹, Yanyi Xing¹, Jing Chen¹, Penglong Wang^1,*

and Haimin Lei^1,*

¹ School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China

² Department of Pathology, Beijing University of Chinese Medicine, Beijing 100102, China

³ Center of Scientific Experiment, Beijing University of Chinese Medicine, Beijing 100102, China

⁴ School of Management, Beijing University of Chinese Medicine, Beijing 100102, China

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2015, 16(9), 21035-21055; https://doi.org/10.3390/ijms160921035 - 2 Sep 2015

Cited by 27 | Viewed by 6277

Abstract

A series of novel ligustrazine-triterpenes derivatives was designed, synthesized and screened for their cytotoxicity against five cancer cell lines (Bel-7402, HepG2, HT-29, Hela, and MCF-7) and Madin-Darby canine kidney (MDCK). Current study suggested that most of the ligustrazine-triterpenes conjunctions showed better cytotoxicity than [...] Read more.

A series of novel ligustrazine-triterpenes derivatives was designed, synthesized and screened for their cytotoxicity against five cancer cell lines (Bel-7402, HepG2, HT-29, Hela, and MCF-7) and Madin-Darby canine kidney (MDCK). Current study suggested that most of the ligustrazine-triterpenes conjunctions showed better cytotoxicity than the starting materials. In particular, compound 4a exhibited better cytotoxic activity (IC₅₀ < 5.23 μM) against Bel-7402, HT-29, MCF-7, Hela, and HepG2 than the standard anticancer drug cisplatin (DDP). The cytotoxicity selectivity detection revealed that 4a exhibited low cytotoxicity (IC₅₀ > 20 μM) towards MDCK cells. A combination of fluorescence staining observation and flow cytometric analysis indicated that 4a could induce HepG2 cell apoptosis. Further studies suggested that 4a-induced apoptosis is mediated through depolarization of the mitochondrial membrane potential and increase of intracellular free Ca²⁺ concentration. In addition, the structure-activity relationships of these derivatives were briefly discussed. Full article

(This article belongs to the Section Biochemistry)

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14 pages, 3600 KiB

Open AccessArticle

Weekly Treatment of 2-Hydroxypropyl-β-cyclodextrin Improves Intracellular Cholesterol Levels in LDL Receptor Knockout Mice

by Sofie M. A. Walenbergh¹, Tom Houben¹, Tim Hendrikx¹, Mike L. J. Jeurissen¹, Patrick J. Van Gorp¹, Nathalie Vaes¹, Steven W. M. Olde Damink^2,3, Fons Verheyen⁴, Ger H. Koek⁵, Dieter Lütjohann⁶, Alena Grebe⁷, Eicke Latz^7,8,9 and Ronit Shiri-Sverdlov^1,*

¹ Department of Molecular Genetics, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht 6229ER, The Netherlands

² Department of General Surgery, Maastricht University, Maastricht 6229ER, The Netherlands

³ Department of HPB and Liver Transplantation Surgery, Royal Free Hospital, University College London, London NW3 2PF, UK

⁴ Department of Molecular Cell Biology and Electron Microscopy, Maastricht University, Maastricht 6229ER, The Netherlands

⁵ Department of Internal Medicine, Division of Gastroenterology and Hepatology, Maastricht University Medical Center (MUMC), Maastricht 6202AZ, The Netherlands

⁶ Institute of Clinical Chemistry and Clinical Pharmacology, University of Bonn, Bonn D-53105, Germany

⁷ Institute of Innate Immunity, University Hospital, University of Bonn, Bonn D-53127, Germany

⁸ German Center for Neurodegenerative Diseases (DZNE), Bonn D-53127, Germany

⁹ Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA 01605, USA

Int. J. Mol. Sci. 2015, 16(9), 21056-21069; https://doi.org/10.3390/ijms160921056 - 2 Sep 2015

Cited by 17 | Viewed by 8498

Abstract

Recently, the importance of lysosomes in the context of the metabolic syndrome has received increased attention. Increased lysosomal cholesterol storage and cholesterol crystallization inside macrophages have been linked to several metabolic diseases, such as atherosclerosis and non-alcoholic fatty liver disease (NAFLD). Two-hydroxypropyl-β-cyclodextrin (HP-B-CD) [...] Read more.

Recently, the importance of lysosomes in the context of the metabolic syndrome has received increased attention. Increased lysosomal cholesterol storage and cholesterol crystallization inside macrophages have been linked to several metabolic diseases, such as atherosclerosis and non-alcoholic fatty liver disease (NAFLD). Two-hydroxypropyl-β-cyclodextrin (HP-B-CD) is able to redirect lysosomal cholesterol to the cytoplasm in Niemann-Pick type C1 disease, a lysosomal storage disorder. We hypothesize that HP-B-CD ameliorates liver cholesterol and intracellular cholesterol levels inside Kupffer cells (KCs). Hyperlipidemic low-density lipoprotein receptor knockout (Ldlr^−/−) mice were given weekly, subcutaneous injections with HP-B-CD or control PBS. In contrast to control injections, hyperlipidemic mice treated with HP-B-CD demonstrated a shift in intracellular cholesterol distribution towards cytoplasmic cholesteryl ester (CE) storage and a decrease in cholesterol crystallization inside KCs. Compared to untreated hyperlipidemic mice, the foamy KC appearance and liver cholesterol remained similar upon HP-B-CD administration, while hepatic campesterol and 7α-hydroxycholesterol levels were back increased. Thus, HP-B-CD could be a useful tool to improve intracellular cholesterol levels in the context of the metabolic syndrome, possibly through modulation of phyto- and oxysterols, and should be tested in the future. Additionally, these data underline the existence of a shared etiology between lysosomal storage diseases and NAFLD. Full article

(This article belongs to the Special Issue Non-Alcoholic Fatty Liver Disease Research 2016)

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17 pages, 3113 KiB

Open AccessArticle

Preparation and Characterization of Lanthanum-Incorporated Hydroxyapatite Coatings on Titanium Substrates

by Weiwei Lou^1,2,†, Yiwen Dong^1,†, Hualin Zhang^3,†, Yifan Jin¹, Xiaohui Hu¹, Jianfeng Ma^1,*, Jinsong Liu^1,* and Gang Wu⁴

¹ School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou 325027, China

² Department of Prosthetic Dentistry, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310006, China

³ Department of Prosthetic Dentistry, College of Stomatology, Ningxia Medical University, Yinchuan 750004, China

⁴ Department of Oral Implantology and Prosthetic Dentistry, Academic Centre for Dentistry Amsterdam (ACTA), Research Institute MOVE, VU University and University of Amsterdam, Amsterdam 1081 HV, The Netherlands

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2015, 16(9), 21070-21086; https://doi.org/10.3390/ijms160921070 - 2 Sep 2015

Cited by 52 | Viewed by 6241

Abstract

Titanium (Ti) has been widely used in clinical applications for its excellent biocompatibility and mechanical properties. However, the bioinertness of the surface of Ti has motivated researchers to improve the physicochemical and biological properties of the implants through various surface modifications, such as [...] Read more.

Titanium (Ti) has been widely used in clinical applications for its excellent biocompatibility and mechanical properties. However, the bioinertness of the surface of Ti has motivated researchers to improve the physicochemical and biological properties of the implants through various surface modifications, such as coatings. For this purpose, we prepared a novel bioactive material, a lanthanum-incorporated hydroxyapatite (La-HA) coating, using a dip-coating technique with a La-HA sol along with post-heat treatment. The XRD, FTIR and EDX results presented in this paper confirmed that lanthanum was successfully incorporated into the structure of HA. The La-HA coating was composed of rod-like particles which densely compacted together without microcracks. The results of the interfacial shear strength test indicated that the incorporation of lanthanum increased the bonding strength of the HA coating. The mass loss ratios under acidic conditions (pH = 5.5) suggested that the La-HA coatings have better acid resistance. The cytocompatibility of the La-HA coating was also revealed by the relative activity of alkaline phosphatase, cellular morphology and cell proliferation assay in vitro. The present study suggested that La-HA coated on Ti has promising potential for applications in the development of a new type of bioactive coating for metal implants. Full article

(This article belongs to the Section Materials Science)

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22 pages, 3274 KiB

Open AccessArticle

Exploring the Molecular Interactions of 7,8-Dihydroxyflavone and Its Derivatives with TrkB and VEGFR2 Proteins

by Nitin Chitranshi^1,*,†, Vivek Gupta^1,†, Sanjay Kumar² and Stuart L. Graham^1,3

¹ Faculty of Medicine and Health Sciences, Macquarie University, F10A, 2 Technology Place, North Ryde, NSW 2109, Australia

² Bioinformatics Centre, Biotech Park, Lucknow, Uttar Pradesh 226021, India

³ Save Sight Institute, Sydney University, Sydney NSW 2109, Australia

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2015, 16(9), 21087-21108; https://doi.org/10.3390/ijms160921087 - 3 Sep 2015

Cited by 45 | Viewed by 8314

Abstract

7,8-dihydroxyflavone (7,8-DHF) is a TrkB receptor agonist, and treatment with this flavonoid derivative brings about an enhanced TrkB phosphorylation and promotes downstream cellular signalling. Flavonoids are also known to exert an inhibitory effect on the vascular endothelial growth factor receptor (VEGFR) family of [...] Read more.

7,8-dihydroxyflavone (7,8-DHF) is a TrkB receptor agonist, and treatment with this flavonoid derivative brings about an enhanced TrkB phosphorylation and promotes downstream cellular signalling. Flavonoids are also known to exert an inhibitory effect on the vascular endothelial growth factor receptor (VEGFR) family of tyrosine kinase receptors. VEGFR2 is one of the important receptors involved in the regulation of vasculogenesis and angiogenesis and has also been implicated to exhibit various neuroprotective roles. Its upregulation and uncontrolled activity is associated with a range of pathological conditions such as age-related macular degeneration and various proliferative disorders. In this study, we investigated molecular interactions of 7,8-DHF and its derivatives with both the TrkB receptor as well as VEGFR2. Using a combination of molecular docking and computational mapping tools involving molecular dynamics approaches we have elucidated additional residues and binding energies involved in 7,8-DHF interactions with the TrkB Ig2 domain and VEGFR2. Our investigations have revealed for the first time that 7,8-DHF has dual biochemical action and its treatment may have divergent effects on the TrkB via its extracellular Ig2 domain and on the VEGFR2 receptor through the intracellular kinase domain. Contrary to its agonistic effects on the TrkB receptor, 7,8-DHF was found to downregulate VEGFR2 phosphorylation both in 661W photoreceptor cells and in retinal tissue. Full article

(This article belongs to the Section Physical Chemistry, Theoretical and Computational Chemistry)

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19 pages, 1737 KiB

Open AccessArticle

Phytochemical Characterization of Veronica officinalis L., V. teucrium L. and V. orchidea Crantz from Romania and Their Antioxidant and Antimicrobial Properties

by Andrei Mocan¹, Dan Cristian Vodnar²

, Laurian Vlase^3,*

, Ovidiu Crișan^4,*, Ana-Maria Gheldiu³ and Gianina Crișan¹

¹ Department of Pharmaceutical Botany, Iuliu Hațieganu University of Medicine and Pharmacy, 23 Ghe. Marinescu Street, Cluj-Napoca 400010, Romania

² Department of Food Science, University of Agricultural Sciences and Veterinary Medicine, 3-5 Manăştur Street, Cluj-Napoca 400372, Romania

³ Department of Pharmaceutical Technology and Biopharmaceutics, Iuliu Hațieganu University of Medicine and Pharmacy, 12 I. Creangă Street, Cluj-Napoca 400010, Romania

⁴ Department of Organic Chemistry, Iuliu Hațieganu University of Medicine and Pharmacy, 12 I. Creangă Street, Cluj- Napoca 400010, Romania

Int. J. Mol. Sci. 2015, 16(9), 21109-21127; https://doi.org/10.3390/ijms160921109 - 3 Sep 2015

Cited by 53 | Viewed by 9530

Abstract

Aerial parts of Veronica species are used in Romanian traditional medicine for the treatment of various conditions like kidney diseases, cough, and catarrh, and are known for their wound-healing properties. In the present study, the phenolic and sterolic content and the antioxidant and [...] Read more.

Aerial parts of Veronica species are used in Romanian traditional medicine for the treatment of various conditions like kidney diseases, cough, and catarrh, and are known for their wound-healing properties. In the present study, the phenolic and sterolic content and the antioxidant and antimicrobial activities of three Veronica species (Plantaginaceae), V. officinalis L., V. teucrium L. and V. orchidea Crantz, were studied. The identification and quantification of several phenolic compounds and phytosterols were performed using LC/MS techniques and the main components were p-coumaric acid, ferulic acid, luteoline, hispidulin and β-sitosterol. More than that, hispidulin, eupatorin and eupatilin were detected for the first time in the Veronica genus. Nevertheless, representatives of the Veronica genus were never investigated in terms of their phytosterol content. The antioxidant potential investigated by Trolox equivelents antioxidant capacity (TEAC) and EPR spectroscopy revealed that V. officinalis and V. orchidea extracts presented similar antioxidant capacities, whilst the values registered for V. teucrium extract are lower. Regarding the antimicrobial activity of the investigated species, Staphylococcus aureus, Listeria monocytogenes and Listeria ivanovii were the most sensitive strains with MIC values between 3.9 and 15.62 mg/mL. The results obtained by this study may serve to promote better use of representatives from the genus Veronica as antioxidant and antimicrobial agents. Full article

(This article belongs to the Special Issue Bioactive Phytochemicals and Functional Food Ingredients in Fruits and Vegetables)

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24 pages, 5240 KiB

Open AccessArticle

Different Roles of GRP78 on Cell Proliferation and Apoptosis in Cartilage Development

by Zhangyuan Xiong¹, Rong Jiang², Xiangzhu Li¹, Yanna Liu¹ and Fengjin Guo^1,*

¹ Department of Cell Biology and Genetics, Core Facility of Development Biology, Chongqing Medical University, Chongqing 400016, China

² Laboratory of Stem Cells and Tissue Engineering, Chongqing Medical University, Chongqing 400016, China

Int. J. Mol. Sci. 2015, 16(9), 21153-21176; https://doi.org/10.3390/ijms160921153 - 7 Sep 2015

Cited by 28 | Viewed by 7325 | Correction

Abstract

Eukaryotic cells possess several mechanisms to adapt to endoplasmic reticulum (ER) stress and thereby survive. ER stress activates a set of signaling pathways collectively termed as the unfolded protein response (UPR). We previously reported that Bone morphogenetic protein 2 (BMP2) mediates mild ER [...] Read more.

Eukaryotic cells possess several mechanisms to adapt to endoplasmic reticulum (ER) stress and thereby survive. ER stress activates a set of signaling pathways collectively termed as the unfolded protein response (UPR). We previously reported that Bone morphogenetic protein 2 (BMP2) mediates mild ER stress and activates UPR signal molecules in chondrogenesis. The mammalian UPR protects the cell against the stress of misfolded proteins in the endoplasmic reticulum. Failure to adapt to ER stress causes the UPR to trigger apoptosis. Glucose regulated protein 78 (GRP78), as an important molecular chaperone in UPR signaling pathways, is responsible for binding to misfolded or unfolded protein during ER stress. However the influence on GRP78 in BMP2-induced chondrocyte differentiation has not yet been elucidated and the molecular mechanism underlyng these processes remain unexplored. Herein we demonstrate that overexpression of GRP78 enhanced cell proliferation in chondrocyte development with G1 phase advance, S phase increasing and G2-M phase transition. Furthermore, overexpression of GRP78 inhibited ER stress-mediated apoptosis and then reduced apoptosis in chondrogenesis induced by BMP2, as assayed by cleaved caspase3, caspase12, C/EBP homologous protein (CHOP/DDIT3/GADD153), p-JNK (phosphorylated c-Jun N-terminal kinase) expression during the course of chondrocyte differentiation by Western blot. In addition, flow cytometry (FCM) assay, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling (TUNEL) assay and immune-histochemistry analysis also proved this result in vitro and in vivo. It was demonstrated that GRP78 knockdown via siRNA activated the ER stress-specific caspase cascade in developing chondrocyte tissue. Collectively, these findings reveal a novel critical role of GRP78 in regulating ER stress-mediated apoptosis in cartilage development and the molecular mechanisms involved. Full article

(This article belongs to the Section Biochemistry)

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14 pages, 955 KiB

Open AccessArticle

Effect of Hepatitis C Virus Genotype 1b Core and NS5A Mutations on Response to Peginterferon Plus Ribavirin Combination Therapy

by Shingo Nakamoto^*, Fumio Imazeki, Makoto Arai, Shin Yasui, Masato Nakamura, Yuki Haga, Reina Sasaki, Tatsuo Kanda

, Hiroshi Shirasawa and Osamu Yokosuka

Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba 260-8677, Japan

Int. J. Mol. Sci. 2015, 16(9), 21177-21190; https://doi.org/10.3390/ijms160921177 - 7 Sep 2015

Cited by 2 | Viewed by 5656

Abstract

We examined whether hepatitis C virus (HCV) genotype 1b core- and NS5A-region mutations are associated with response to peginterferon α-2b plus ribavirin combination therapy. A total of 103 patients with high HCV genotype 1b viral loads (≥100 KIU/mL) were treated with the combination [...] Read more.

We examined whether hepatitis C virus (HCV) genotype 1b core- and NS5A-region mutations are associated with response to peginterferon α-2b plus ribavirin combination therapy. A total of 103 patients with high HCV genotype 1b viral loads (≥100 KIU/mL) were treated with the combination therapy. Pretreatment mutations in the core region and interferon sensitivity determining region (ISDR) in the NS5A region were analyzed. In univariate analysis, arginine and leucine at positions 70 and 91 in the core region, defined as double wild (DW)-type, were associated with early virologic response (p = 0.002), sustained virologic response (SVR) (p = 0.004), and non-response (p = 0.005). Non-threonine at position 110 was associated with SVR (p = 0.004). Multivariate analysis showed the following pretreatment predictors of SVR: hemoglobin level ≥ 14 g/dL (odds ratio (OR) 6.2, p = 0.04); platelet count ≥ 14 × 10⁴/mm³ (OR 5.2, p = 0.04); aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio < 0.9 (OR 6.17, p = 0.009); DW-type (OR 6.8, p = 0.02); non-threonine at position 110 (OR 14.5, p = 0.03); and ≥2 mutations in the ISDR (OR 12.3, p = 0.02). Patients with non-DW-type, non-threonine at position 110, and <2 ISDR mutations showed significantly lower SVR rates than others (11/45 (24.4%) vs. 27/37 (73.0%), respectively; p < 0.001). SVR can be predicted through core and NS5A region mutations and host factors like hemoglobin, platelet count, and AST/ALT ratio in HCV genotype 1b-infected patients treated with peginterferon and ribavirin combination therapy. Full article

(This article belongs to the Special Issue Viral Hepatitis Research)

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24 pages, 423 KiB

Open AccessArticle

An Effective Antifreeze Protein Predictor with Ensemble Classifiers and Comprehensive Sequence Descriptors

by Runtao Yang¹, Chengjin Zhang^1,2,*

, Rui Gao¹ and Lina Zhang¹

¹ School of Control Science and Engineering, Shandong University, Jinan 250061, China

² School of Mechanical, Electrical and Information Engineering, Shandong University, Weihai 264209, China

Int. J. Mol. Sci. 2015, 16(9), 21191-21214; https://doi.org/10.3390/ijms160921191 - 7 Sep 2015

Cited by 24 | Viewed by 5594

Abstract

Antifreeze proteins (AFPs) play a pivotal role in the antifreeze effect of overwintering organisms. They have a wide range of applications in numerous fields, such as improving the production of crops and the quality of frozen foods. Accurate identification of AFPs may provide [...] Read more.

Antifreeze proteins (AFPs) play a pivotal role in the antifreeze effect of overwintering organisms. They have a wide range of applications in numerous fields, such as improving the production of crops and the quality of frozen foods. Accurate identification of AFPs may provide important clues to decipher the underlying mechanisms of AFPs in ice-binding and to facilitate the selection of the most appropriate AFPs for several applications. Based on an ensemble learning technique, this study proposes an AFP identification system called AFP-Ensemble. In this system, random forest classifiers are trained by different training subsets and then aggregated into a consensus classifier by majority voting. The resulting predictor yields a sensitivity of 0.892, a specificity of 0.940, an accuracy of 0.938 and a balanced accuracy of 0.916 on an independent dataset, which are far better than the results obtained by previous methods. These results reveal that AFP-Ensemble is an effective and promising predictor for large-scale determination of AFPs. The detailed feature analysis in this study may give useful insights into the molecular mechanisms of AFP-ice interactions and provide guidance for the related experimental validation. A web server has been designed to implement the proposed method. Full article

(This article belongs to the Section Physical Chemistry, Theoretical and Computational Chemistry)

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40 pages, 3290 KiB

Open AccessArticle

Introducing DInaMo: A Package for Calculating Protein Circular Dichroism Using Classical Electromagnetic Theory

by Igor V. Uporov^1,2, Neville Y. Forlemu^1,3, Rahul Nori¹, Tsvetan Aleksandrov¹, Boris A. Sango¹, Yvonne E. Bongfen Mbote^1,4, Sandeep Pothuganti¹ and Kathryn A. Thomasson^1,*

¹ Chemistry Department, University of North Dakota, 151 Cornell St. Stop 9024, Grand Forks, ND 58202, USA

² Faculty of Chemistry, M. V. Lomonosov Moscow State University, GSP-1, 1-3 Leninskiye Gory, 119991 Moscow, Russia

³ Georgia Gwinnett College, 1000 University Center Lane, Lawrenceville, GA 30043, USA

⁴ James E. Hurley College of Science & Mathematics, Oklahoma Baptist University, OBU Box 61772, 500 W. University, Shawnee, OK 74804, USA

Int. J. Mol. Sci. 2015, 16(9), 21237-21276; https://doi.org/10.3390/ijms160921237 - 7 Sep 2015

Cited by 4 | Viewed by 8380

Abstract

The dipole interaction model is a classical electromagnetic theory for calculating circular dichroism (CD) resulting from the π-π* transitions of amides. The theoretical model, pioneered by J. Applequist, is assembled into a package, DInaMo, written in Fortran allowing for treatment of proteins. DInaMo [...] Read more.

The dipole interaction model is a classical electromagnetic theory for calculating circular dichroism (CD) resulting from the π-π* transitions of amides. The theoretical model, pioneered by J. Applequist, is assembled into a package, DInaMo, written in Fortran allowing for treatment of proteins. DInaMo reads Protein Data Bank formatted files of structures generated by molecular mechanics or reconstructed secondary structures. Crystal structures cannot be used directly with DInaMo; they either need to be rebuilt with idealized bond angles and lengths, or they need to be energy minimized to adjust bond lengths and bond angles because it is common for crystal structure geometries to have slightly short bond lengths, and DInaMo is sensitive to this. DInaMo reduces all the amide chromophores to points with anisotropic polarizability and all nonchromophoric aliphatic atoms including hydrogens to points with isotropic polarizability; all other atoms are ignored. By determining the interactions among the chromophoric and nonchromophoric parts of the molecule using empirically derived polarizabilities, the rotational and dipole strengths are determined leading to the calculation of CD. Furthermore, ignoring hydrogens bound to methyl groups is initially explored and proves to be a good approximation. Theoretical calculations on 24 proteins agree with experiment showing bands with similar morphology and maxima. Full article

(This article belongs to the Section Biochemistry)

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16 pages, 747 KiB

Open AccessArticle

MicroRNAs in Salivary Exosome as Potential Biomarkers of Aging

by Tatsuya Machida^1,*, Takaaki Tomofuji^1,2, Daisuke Ekuni¹

, Takayuki Maruyama³, Toshiki Yoneda¹, Yuya Kawabata¹, Hirofumi Mizuno¹, Hisataka Miyai¹, Muneyoshi Kunitomo¹ and Manabu Morita¹

¹ Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan

² Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Dental School, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan

³ Center for Innovative Clinical Medicine, Okayama University Hospital, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan

Int. J. Mol. Sci. 2015, 16(9), 21294-21309; https://doi.org/10.3390/ijms160921294 - 7 Sep 2015

Cited by 130 | Viewed by 10296

Abstract

The aim of this study was to examine whether salivary exosomal miRNAs could be identified as aging biomarkers. Fifteen young healthy volunteers (median age, 21.0 years) and 13 old individuals (median age, 66.0 years) were recruited. Unstimulated whole saliva was collected, salivary exosomes [...] Read more.

The aim of this study was to examine whether salivary exosomal miRNAs could be identified as aging biomarkers. Fifteen young healthy volunteers (median age, 21.0 years) and 13 old individuals (median age, 66.0 years) were recruited. Unstimulated whole saliva was collected, salivary exosomes were isolated, and total RNA was extracted. In a microarray, 242 miRNAs were commonly detected in these two mixed samples. Based on the cut-off values of 2- or 0.5-fold changes (FC) and regulatory power for aging process, six candidate miRNAs (miR-24-3p, miR-371a-5p, miR-3175, miR-3162-5p, miR-671-5p, and miR-4667-5p) were selected. After comparing each total RNA obtained by the 15 young and 13 old individuals to validate the FC values using quantitative real-time PCR, miR-24-3p was identified as a novel candidate aging biomarker. This pilot study suggested that salivary exosomal miRNAs could be identified as candidate aging biomarkers. To confirm whether miR-24-3p in salivary exosomes are suitable biomarkers of aging, further validation research is required. Full article

(This article belongs to the Special Issue MicroRNA in Various Disease States as Biomarkers)

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20 pages, 1930 KiB

Open AccessArticle

Gene Expression Variations of Red—White Skin Coloration in Common Carp (Cyprinus carpio)

by Xiao-Min Li^1,†, Ying-Nan Song^1,2,†, Gui-Bao Xiao¹, Bai-Han Zhu^1,2, Gui-Cai Xu¹, Ming-Yuan Sun^1,2, Jun Xiao^1,2, Shahid Mahboob³, Khalid A. Al-Ghanim³, Xiao-Wen Sun¹ and Jiong-Tang Li^1,*

¹ CAFS Key Laboratory of Aquatic Genomics and Beijing Key Laboratory of Fishery Biotechnology, Centre for Applied Aquatic Genomics, Chinese Academy of Fishery Sciences, Beijing 10014, China

² College of Fisheries and Life Science, Shanghai Ocean University, Shanghai 201306, China

³ Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2015, 16(9), 21310-21329; https://doi.org/10.3390/ijms160921310 - 7 Sep 2015

Cited by 27 | Viewed by 7604

Abstract

Teleosts have more types of chromatophores than other vertebrates and the genetic basis for pigmentation is highly conserved among vertebrates. Therefore, teleosts are important models to study the mechanism of pigmentation. Although functional genes and genetic variations of pigmentation have been studied, the [...] Read more.

Teleosts have more types of chromatophores than other vertebrates and the genetic basis for pigmentation is highly conserved among vertebrates. Therefore, teleosts are important models to study the mechanism of pigmentation. Although functional genes and genetic variations of pigmentation have been studied, the mechanisms of different skin coloration remains poorly understood. The koi strain of common carp has various colors and patterns, making it a good model for studying the genetic basis of pigmentation. We performed RNA-sequencing for red skin and white skin and identified 62 differentially expressed genes (DEGs). Most of them were validated with RT-qPCR. The up-regulated DEGs in red skin were enriched in Kupffer’s vesicle development while the up-regulated DEGs in white skin were involved in cytoskeletal protein binding, sarcomere organization and glycogen phosphorylase activity. The distinct enriched activity might be associated with different structures and functions in erythrophores and iridophores. The DNA methylation levels of two selected DEGs inversely correlated with gene expression, indicating the participation of DNA methylation in the coloration. This expression characterization of red—white skin along with the accompanying transcriptome-wide expression data will be a useful resource for further studies of pigment cell biology. Full article

(This article belongs to the Special Issue Fish Molecular Biology)

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12 pages, 1668 KiB

Open AccessArticle

Development of Seven Microsatellite Markers Using Next Generation Sequencing for the Conservation on the Korean Population of Dorcus hopei (E. Saunders, 1854) (Coleoptera, Lucanidae)

by Tae Hwa Kang^1,*,†, Sang Hoon Han^2,*,† and Sun Jae Park^3,*,†

¹ Plant Quarantine Technology Center, Animal and Plant Quarantine Agency, 234-3, Mangpo-dong, Yeongtong-gu, Suwon, Gyeonggi-do 443-400, Korea

² Department of Life Science, College of Natural Science, Kyonggi University, 154-42, Gwanggyeongsan-ro, Yeongtong-gu, Suwon, Gyeonggi-do 443-780, Korea

³ Biological Resources Research Department, National Institute of Biological Resources, 42, Hwangyeong-ro, Seo-gu, Incheon 404-170, Korea

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2015, 16(9), 21330-21341; https://doi.org/10.3390/ijms160921330 - 7 Sep 2015

Cited by 10 | Viewed by 7232

Abstract

We developed microsatellite markers for genetic structural analyses of Dorcus hopei, a stag beetle species, using next generation sequencing and polymerase chain reaction (PCR)-based genotyping for regional populations. A total of 407,070,351 base pairs of genomic DNA containing >4000 microsatellite loci [...] Read more.

We developed microsatellite markers for genetic structural analyses of Dorcus hopei, a stag beetle species, using next generation sequencing and polymerase chain reaction (PCR)-based genotyping for regional populations. A total of 407,070,351 base pairs of genomic DNA containing >4000 microsatellite loci except AT repeats were sequenced. From 76 loci selected for primer design, 27 were polymorphic. Of these 27 markers, 10 were tested on three regional populations: two Chinese (Shichuan and Guangxi) and one Korean (Wanju). Three markers were excluded due to inconsistent amplification, genotyping errors, and Hardy-Weinberg equilibrium (HWE). By multi-locus genotyping, the allele number, observed heterozygosity and polymorphism information content of seven microsatellite loci were ranged 2‒10, 0.1333‒1.0000, and 0.1228‒0.8509, respectively. In an analysis on the genetic differentiation among regional populations including one Japanese population and one cross-breeding population, the individual colored bar-plots showed that both Chinese populations were closer to each other than to the Far East Asian populations. In Far East Asian populations, Wanju and Nirasaki populations could not be distinguished from each other because the frequency of genetic contents was very similar in some individuals of two populations. Moreover, the cross-breeding population contained all patterns of genetic contents shown in Chinese, Korean, and Japanese populations, compared with the genetic content frequency of each regional population. As a result, we examined whether the cross-breeding population might be a hybrid population, and might contain a possibility of interbreeding with Chinese populations in parental generations. Therefore, these markers will be useful for analyses of genetic diversity in populations, genetic relationships between regional populations, genetic structure analyses, and origin tests. Full article

(This article belongs to the Section Biochemistry)

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21 pages, 1399 KiB

Open AccessArticle

New Anti-Nodal Monoclonal Antibodies Targeting the Nodal Pre-Helix Loop Involved in Cripto-1 Binding

by Annalia Focà^1,2, Luca Sanguigno³, Giuseppina Focà^1,2, Luigi Strizzi⁴, Roberta Iannitti¹, Rosanna Palumbo¹, Mary J. C. Hendrix⁴, Antonio Leonardi^5,*, Menotti Ruvo^1,* and Annamaria Sandomenico^1,*

¹ Institute of Biostructure and Bioimaging, National Research Council (IBB-CNR) and Centro Interuniversitario di Ricerca sui Peptidi Bioattivi (CIRPeB), Università degli Studi di Napoli "Federico II", Naples 80134, Italy

² Department of Pharmacy, Università degli Studi di Napoli "Federico II", Naples 80131, Italy

³ Bioker Multimedica, Naples 80131, Italy

⁴ Program in Cancer Biology and Epigenomics, Stanley Manne Children's Research Institute at Ann and Robert H. Lurie Children's Hospital of Chicago, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA

⁵ Department of Molecular Medicine and Medical Biotechnologies, Università degli Studi di Napoli "Federico II", Naples 80131, Italy

Int. J. Mol. Sci. 2015, 16(9), 21342-21362; https://doi.org/10.3390/ijms160921342 - 7 Sep 2015

Cited by 15 | Viewed by 5947

Abstract

Nodal is a potent embryonic morphogen belonging to the TGF-β superfamily. Typically, it also binds to the ALK4/ActRIIB receptor complex in the presence of the co-receptor Cripto-1. Nodal expression is physiologically restricted to embryonic tissues and human embryonic stem cells, is absent in [...] Read more.

Nodal is a potent embryonic morphogen belonging to the TGF-β superfamily. Typically, it also binds to the ALK4/ActRIIB receptor complex in the presence of the co-receptor Cripto-1. Nodal expression is physiologically restricted to embryonic tissues and human embryonic stem cells, is absent in normal cells but re-emerges in several human cancers, including melanoma, breast, and colon cancer. Our aim was to obtain mAbs able to recognize Nodal on a major CBR (Cripto-Binding-Region) site and to block the Cripto-1-mediated signalling. To achieve this, antibodies were raised against hNodal(44–67) and mAbs generated by the hybridoma technology. We have selected one mAb, named 3D1, which strongly associates with full-length rhNodal (K_D 1.4 nM) and recognizes the endogenous protein in a panel of human melanoma cell lines by western blot and FACS analyses. 3D1 inhibits the Nodal-Cripto-1 binding and blocks Smad2/3 phosphorylation. Data suggest that inhibition of the Nodal-Cripto-1 axis is a valid therapeutic approach against melanoma and 3D1 is a promising and interesting agent for blocking Nodal-Cripto mediated tumor development. These findings increase the interest for Nodal as both a diagnostic and prognostic marker and as a potential new target for therapeutic intervention. Full article

(This article belongs to the Section Biochemistry)

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15 pages, 1042 KiB

Open AccessArticle

Ile-1781-Leu and Asp-2078-Gly Mutations in ACCase Gene, Endow Cross-resistance to APP, CHD, and PPZ in Phalaris minor from Mexico

by Hugo Cruz-Hipolito¹, Pablo Fernandez², Ricardo Alcantara², Javid Gherekhloo³, Maria Dolores Osuna⁴ and Rafael De Prado^2,*

¹ Bayer CropScience, Col. Ampl. Granada

² Department of Agricultural Chemistry and Edaphology, University of Cordoba, 14071 Cordoba, Spain

³ Deparment of Agronomy, Gorgan University of Agricultural Sciences and Natural Resources, 49189-43464 Gorgan, Iran

⁴ Finca La Orden-Valdesequera Research Centre, 06187 Badajoz, Spain

Int. J. Mol. Sci. 2015, 16(9), 21363-21377; https://doi.org/10.3390/ijms160921363 - 7 Sep 2015

Cited by 18 | Viewed by 5990

Abstract

Herbicides that inhibit acetyl coenzyme A carboxylase (ACCase) are commonly used in Mexico to control weedy grasses such as little seed canarygrass (Phalaris minor). These herbicides are classified into three major families (ariloxyphenoxypropionates (APP), cyclohexanodiones (CHD), and, recently, phenylpyrazolines (PPZ)). In [...] Read more.

Herbicides that inhibit acetyl coenzyme A carboxylase (ACCase) are commonly used in Mexico to control weedy grasses such as little seed canarygrass (Phalaris minor). These herbicides are classified into three major families (ariloxyphenoxypropionates (APP), cyclohexanodiones (CHD), and, recently, phenylpyrazolines (PPZ)). In this work, the resistance to ACCase (APP, CHD, and PPZ) inhibiting herbicides was studied in a biotype of Phalaris minor (P. minor) from Mexico, by carrying out bioassays at the whole-plant level and investigating the mechanism behind this resistance. Dose-response and ACCase in vitro activity assays showed cross-resistance to all ACCase herbicides used. There was no difference in the absorption, translocation, and metabolism of the ¹⁴C-diclofop-methyl between the R and S biotypes. The PCR generated CT domain fragments of ACCase from the R biotype and an S reference were sequenced and compared. The Ile-1781-Leu and Asp-2078-Gly point mutations were identified. These mutations could explain the loss of affinity for ACCase by the ACCase-inhibing herbicides. This is the ﬁrst report showing that this substitution confers resistance to APP, CHD, and PPZ herbicides in P. minor from Mexico. The mutations have been described previously only in a few cases; however, this is the first study reporting on a pattern of cross-resistance with these mutations in P. minor. The findings could be useful for better management of resistant biotypes carrying similar mutations. Full article

(This article belongs to the Section Biochemistry)

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14 pages, 1306 KiB

Open AccessArticle

Can Clethra barbinervis Distinguish Nickel and Cobalt in Uptake and Translocation?

by Tsuyoshi Yamaguchi^*, Rie Tomioka and Chisato Takenaka

Graduate School of Bioagricultural Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan

Int. J. Mol. Sci. 2015, 16(9), 21378-21391; https://doi.org/10.3390/ijms160921378 - 7 Sep 2015

Cited by 6 | Viewed by 8482

Abstract

Clethra barbinervis Sieb. et Zucc. accumulates Nickel (Ni) and Cobalt (Co) at high concentrations., We hypothesized that C. barbinervis cannot distinguish between Ni and Co because of the similar chemical properties of these two elements. To confirm this hypothesis and understand the [...] Read more.

Clethra barbinervis Sieb. et Zucc. accumulates Nickel (Ni) and Cobalt (Co) at high concentrations., We hypothesized that C. barbinervis cannot distinguish between Ni and Co because of the similar chemical properties of these two elements. To confirm this hypothesis and understand the role of these elements in C. barbinervis, we conducted a hydroponic split-root experiment using Ni and Co solutions. We found that the bioconcentration factor (BCF; metal concentration of each tissue/metal concentrations of each treatment solution) of Ni and Co did not significantly differ in the roots, but the BCF for Co was higher than that for Ni in the leaves. The leaves of C. barbinervis accumulated Ni or Co at high concentrations. We also found the simultaneous accumulation of Ni and Co by the multiple heavy metal treatments (Ni and Co) at high concentrations similar to those for the single treatments (Ni or Co). Elevated sulfur concentrations occurred in the roots and leaves of Co-treated seedlings but not in Ni. This result indicates that S was related to Co accumulation in the leaves. These results suggest that C. barbinervis distinguishes between Ni and Co during transport and accumulation in the leaves but not during root uptake. Full article

(This article belongs to the Special Issue Regulation of Plant Mineral Nutrition: Transport, Sensing and Signalling)

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18 pages, 2159 KiB

Open AccessArticle

Cisplatin Targeting of Bacterial Ribosomal RNA Hairpins

by Gayani N. P. Dedduwa-Mudalige and Christine S. Chow^*

Department of Chemistry, Wayne State University, Detroit, MI 48202, USA

Int. J. Mol. Sci. 2015, 16(9), 21392-21409; https://doi.org/10.3390/ijms160921392 - 7 Sep 2015

Cited by 21 | Viewed by 9458

Abstract

Cisplatin is a clinically important chemotherapeutic agent known to target purine bases in nucleic acids. In addition to major deoxyribonucleic acid (DNA) intrastrand cross-links, cisplatin also forms stable adducts with many types of ribonucleic acid (RNA) including siRNA, spliceosomal RNAs, tRNA, and rRNA. [...] Read more.

Cisplatin is a clinically important chemotherapeutic agent known to target purine bases in nucleic acids. In addition to major deoxyribonucleic acid (DNA) intrastrand cross-links, cisplatin also forms stable adducts with many types of ribonucleic acid (RNA) including siRNA, spliceosomal RNAs, tRNA, and rRNA. All of these RNAs play vital roles in the cell, such as catalysis of protein synthesis by rRNA, and therefore serve as potential drug targets. This work focused on platination of two highly conserved RNA hairpins from E. coli ribosomes, namely pseudouridine-modified helix 69 from 23S rRNA and the 790 loop of helix 24 from 16S rRNA. RNase T1 probing, MALDI mass spectrometry, and dimethyl sulfate mapping revealed platination at GpG sites. Chemical probing results also showed platination-induced RNA structural changes. These findings reveal solvent and structural accessibility of sites within bacterial RNA secondary structures that are functionally significant and therefore viable targets for cisplatin as well as other classes of small molecules. Identifying target preferences at the nucleotide level, as well as determining cisplatin-induced RNA conformational changes, is important for the design of more potent drug molecules. Furthermore, the knowledge gained through studies of RNA-targeting by cisplatin is applicable to a broad range of organisms from bacteria to human. Full article

(This article belongs to the Special Issue Low Molecular Weight DNA and RNA Binding Agents)

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18 pages, 2157 KiB

Open AccessArticle

The Effects of Cadmium at Low Environmental Concentrations on THP-1 Macrophage Apoptosis

by Tomasz Olszowski¹, Irena Baranowska-Bosiacka^2,*

, Izabela Gutowska^3,†

, Katarzyna Piotrowska^4,†, Katarzyna Mierzejewska⁴, Jan Korbecki², Mateusz Kurzawski⁵, Maciej Tarnowski⁴ and Dariusz Chlubek²

¹ Department of Hygiene and Epidemiology, Pomeranian Medical University, Szczecin 70-111, Poland

² Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Szczecin 70-111, Poland

³ Department of Biochemistry and Human Nutrition, Pomeranian Medical University, Szczecin 71-460, Poland

⁴ Department of Physiology, Pomeranian Medical University, Szczecin 70-111, Poland

⁵ Department of Experimental and Clinical Pharmacology, Pomeranian Medical University, Szczecin 70-111, Poland

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2015, 16(9), 21410-21427; https://doi.org/10.3390/ijms160921410 - 7 Sep 2015

Cited by 30 | Viewed by 7121

Abstract

Cadmium at environmental concentrations is a risk factor for many diseases, including cardiovascular and neurodegenerative diseases, in which macrophages play an important role. The aim of this study was to evaluate the effects of cadmium at low environmental (nanomolar) concentrations on apoptotic processes [...] Read more.

Cadmium at environmental concentrations is a risk factor for many diseases, including cardiovascular and neurodegenerative diseases, in which macrophages play an important role. The aim of this study was to evaluate the effects of cadmium at low environmental (nanomolar) concentrations on apoptotic processes in THP-1(acute monocytic leukemia cells line)-derived macrophages, with special focus on mitochondrial events involved. Macrophages were incubated with various cadmium chloride (CdCl₂) solutions for 48 h at final concentrations of 5 nM, 20 nM, 200 nM and 2 µM CdCl₂. Cell viability was measured using flow cytometry. Flow cytometric measurement (annexin V/FITC (annexin V/fluorescein isothiocyanate) and PI (propidium iodide) double staining) was used to quantify the extent of apoptosis. Fluorescence and confocal microscopy were used for imaging of apoptosis process. Changes in mitochondrial membrane potential were monitored using cytofluorimetry after cell staining with JC-1(5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazol-carbocyane iodide) probe. Mitochondrial ROS (reactive oxygen species) levels were measured cytofluorimetrically after incubation of cells with mitochondrial superoxide indicator (MitoSOX) red fluorescent marker. The mRNA expression of Bcl-2 and Bax was analysed with qRT-PCR. Our study demonstrates that cadmium, even at low environmental concentrations, exerts mitochondrial toxicity in THP-1 macrophages. Forty-eight-hour exposure to very low concentrations reduces cell viability and results in cell death by apoptosis and necrosis. The decrease in mitochondrial membrane potential, increased ROS production, increased Bax and decreased Bcl-2 mRNA expression are mitochondrial events involved in cadmium-induced apoptosis. Full article

(This article belongs to the Section Molecular Toxicology)

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14 pages, 688 KiB

Open AccessArticle

Nutritive Evaluation of the Bambara Groundnut Ci12 Landrace [Vigna subterranea (L.) Verdc. (Fabaceae)] Produced in Côte d’Ivoire

by Denis N'Dri Yao¹, Kouakou Nestor Kouassi¹, Daniela Erba²

, Francesca Scazzina³

, Nicoletta Pellegrini^3,*

and Maria Cristina Casiraghi²

¹ Laboratory of Food Biochemical and Tropical Products Technology, Nangui Abrogoua University, 02 BP 801 Abidjan, Côte d'Ivoire

² Department of Food, Environmental and Nutritional Sciences DEFENS, University of Milan, Via Celoria 2, 20133 Milano, Italy

³ Department of Food Science, University of Parma, Parco Area delle Scienze 47/A, 43124 Parma, Italy

Int. J. Mol. Sci. 2015, 16(9), 21428-21441; https://doi.org/10.3390/ijms160921428 - 7 Sep 2015

Cited by 83 | Viewed by 9081

Abstract

The nutritional evaluation of the Bambara groundnut Ci12 landrace (Vigna subterranea (L.) Verdc.) seeds produced in Côte d’Ivoire shows a 19% content of protein, containing all the essential amino acids with tryptophan as the limiting amino acid, a total dietary fiber [...] Read more.

The nutritional evaluation of the Bambara groundnut Ci12 landrace (Vigna subterranea (L.) Verdc.) seeds produced in Côte d’Ivoire shows a 19% content of protein, containing all the essential amino acids with tryptophan as the limiting amino acid, a total dietary fiber level of 10%, with a low soluble fraction content, and a fat content of 1.4%, with a high proportion of total unsaturated fatty acids (61%) of which 36% were n-6 fatty acids. This legume contains phosphorus, as the major mineral, followed by magnesium and calcium, and trace elements (iron, copper and zinc). It is characterized by the same amount of α-tocopherol and antioxidant capacity as common legumes. The high concentration of essential amino acids, n-6 fatty acids and minerals, mainly Fe, in the Ci12 landrace of Bambara groundnut indicates that this local legume has the potentiality to improve the nutritional status in Côte d’Ivoire and it could be regarded as a nutrient dense food. Full article

(This article belongs to the Special Issue Bioactive Phytochemicals and Functional Food Ingredients in Fruits and Vegetables)

12 pages, 1551 KiB

Open AccessArticle

MicroRNA, Pm-miR-2305, Participates in Nacre Formation by Targeting Pearlin in Pearl Oyster Pinctada martensii

by Yu Jiao¹, Zhe Zheng¹, Rongrong Tian¹, Xiaodong Du^1,2,*, Qingheng Wang¹ and Ronglian Huang¹

¹ Fishery College, Guangdong Ocean University, Zhanjiang 524025, Guangdong, China

² Guangdong Technology Research Center for Pearl Aquaculutre and Process, Guangdong Ocean University, Zhanjiang 524025, China

Int. J. Mol. Sci. 2015, 16(9), 21442-21453; https://doi.org/10.3390/ijms160921442 - 7 Sep 2015

Cited by 25 | Viewed by 6533

Abstract

MicroRNAs (miRNAs) are noncoding RNA molecules that function as negative regulators of target genes. In our previous research, 258 pm-miRNAs were identified in Pinctada martensii by Solexa deep sequencing. Pm-miR-2305 was one of the identified pm-miRNAs with a potential function in biomineralization. In [...] Read more.

MicroRNAs (miRNAs) are noncoding RNA molecules that function as negative regulators of target genes. In our previous research, 258 pm-miRNAs were identified in Pinctada martensii by Solexa deep sequencing. Pm-miR-2305 was one of the identified pm-miRNAs with a potential function in biomineralization. In the present study, the precursor of pm-miR-2305 was predicted with 96 bp, containing a characteristic hairpin structure. Stem-loop qRT-PCR analysis indicated that pm-miR-2305 was constitutively expressed in all the tissues (adductor muscle, gill, mantle, hepatopancreas, foot, and gonad) of P. martensii and was highly expressed in the foot. After the over-expression of pm-miR-2305 in the mantle by mimics injection into the muscle of P. martensii, nacre demonstrated disorderly growth, as detected by scanning electron microscopy. Dual luciferase reporter gene assay indicated that pm-miR-2305 mimics could significantly inhibit the luciferase activity of the reporter containing the 3′UTR of the pearlin gene. Western blot analysis demonstrated that the protein expression of pearlin was down-regulated in the mantle tissue after the over-expression of pm-miR-2305. Therefore, our data showed that pm-miR-2305 participated in nacre formation by targeting pearlin in P. martensii. Full article

(This article belongs to the Section Biochemistry)

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32 pages, 2208 KiB

Open AccessArticle

The Proteome Profiles of the Cerebellum of Juvenile, Adult and Aged Rats—An Ontogenetic Study

by Michael Wille¹, Antje Schümann¹, Andreas Wree¹, Michael Kreutzer², Michael O. Glocker², Grit Mutzbauer³ and Oliver Schmitt^1,*

¹ Department of Anatomy, Gertrudenstr. 9, 18055 Rostock, Germany

² Proteome Center Rostock, Schillingallee 69, 18055 Rostock, Germany

³ Department of Pathology, Josef-Schneider-Str. 2, 97080 Würzburg, Germany

Int. J. Mol. Sci. 2015, 16(9), 21454-21485; https://doi.org/10.3390/ijms160921454 - 7 Sep 2015

Cited by 4 | Viewed by 7508

Abstract

In this study, we searched for proteins that change their expression in the cerebellum (Ce) of rats during ontogenesis. This study focuses on the question of whether specific proteins exist which are differentially expressed with regard to postnatal stages of development. A better [...] Read more.

In this study, we searched for proteins that change their expression in the cerebellum (Ce) of rats during ontogenesis. This study focuses on the question of whether specific proteins exist which are differentially expressed with regard to postnatal stages of development. A better characterization of the microenvironment and its development may result from these study findings. A differential two-dimensional polyacrylamide gel electrophoresis (2DE) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) analysis of the samples revealed that the number of proteins of the functional classes differed depending on the developmental stages. Especially members of the functional classes of biosynthesis, regulatory proteins, chaperones and structural proteins show the highest differential expression within the analyzed stages of development. Therefore, members of these functional protein groups seem to be involved in the development and differentiation of the Ce within the analyzed development stages. In this study, changes in the expression of proteins in the Ce at different postnatal developmental stages (postnatal days (P) 7, 90, and 637) could be observed. At the same time, an identification of proteins which are involved in cell migration and differentiation was possible. Especially proteins involved in processes of the biosynthesis and regulation, the dynamic organization of the cytoskeleton as well as chaperones showed a high amount of differentially expressed proteins between the analyzed dates. Full article

(This article belongs to the Special Issue Advances in Proteomic Research)

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19 pages, 1105 KiB

Open AccessArticle

First Trimester Urine and Serum Metabolomics for Prediction of Preeclampsia and Gestational Hypertension: A Prospective Screening Study

by Marie Austdal^1,2, Line H. Tangerås^2,3, Ragnhild B. Skråstad^4,5, Kjell Salvesen^5,6, Rigmor Austgulen³, Ann-Charlotte Iversen³ and Tone F. Bathen^1,*

¹ Department of Circulation and Medical Imaging, Faculty of Medicine, Norwegian University of Science and Technology, 7491 Trondheim, Norway

² St. Olavs Hospital, Trondheim University Hospital, 7006 Trondheim, Norway

³ Centre of Molecular Inflammation Research, Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, 7491 Trondheim, Norway

⁴ Department of Laboratory Medicine Children's and Women's Health, Faculty of Medicine, Norwegian University of Science and Technology, 7491 Trondheim, Norway

⁵ National Center for Fetal Medicine, Department of Obstetrics and Gynecology, St. Olavs Hospital, Trondheim University Hospital, 7030 Trondheim, Norway

⁶ Department of Obstetrics and Gynecology, Clinical Sciences, Lund University, 221 00 Lund, Sweden

Int. J. Mol. Sci. 2015, 16(9), 21520-21538; https://doi.org/10.3390/ijms160921520 - 8 Sep 2015

Cited by 62 | Viewed by 10084

Abstract

Hypertensive disorders of pregnancy, including preeclampsia, are major contributors to maternal morbidity. The goal of this study was to evaluate the potential of metabolomics to predict preeclampsia and gestational hypertension from urine and serum samples in early pregnancy, and elucidate the metabolic changes [...] Read more.

Hypertensive disorders of pregnancy, including preeclampsia, are major contributors to maternal morbidity. The goal of this study was to evaluate the potential of metabolomics to predict preeclampsia and gestational hypertension from urine and serum samples in early pregnancy, and elucidate the metabolic changes related to the diseases. Metabolic profiles were obtained by nuclear magnetic resonance spectroscopy of serum and urine samples from 599 women at medium to high risk of preeclampsia (nulliparous or previous preeclampsia/gestational hypertension). Preeclampsia developed in 26 (4.3%) and gestational hypertension in 21 (3.5%) women. Multivariate analyses of the metabolic profiles were performed to establish prediction models for the hypertensive disorders individually and combined. Urinary metabolomic profiles predicted preeclampsia and gestational hypertension at 51.3% and 40% sensitivity, respectively, at 10% false positive rate, with hippurate as the most important metabolite for the prediction. Serum metabolomic profiles predicted preeclampsia and gestational hypertension at 15% and 33% sensitivity, respectively, with increased lipid levels and an atherogenic lipid profile as most important for the prediction. Combining maternal characteristics with the urinary hippurate/creatinine level improved the prediction rates of preeclampsia in a logistic regression model. The study indicates a potential future role of clinical importance for metabolomic analysis of urine in prediction of preeclampsia. Full article

(This article belongs to the Special Issue Prediction, Diagnostics and Prevention of Pregnancy Complications)

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16 pages, 1010 KiB

Open AccessArticle

Polymorphisms in the LPL and CETP Genes and Haplotype in the ESR1 Gene Are Associated with Metabolic Syndrome in Women from Southwestern Mexico

by José Ángel Cahua-Pablo¹, Miguel Cruz², Abigail Méndez-Palacios¹, Diana Lizzete Antúnez-Ortiz¹, Amalia Vences-Velázquez¹, Luz Del Carmen Alarcón-Romero³, Esteban Juan Parra⁴, Vianet Argelia Tello-Flores¹, Marco Antonio Leyva-Vázquez³, Adán Valladares-Salgado²

, Claudia Paola Pérez-Macedonio¹ and Eugenia Flores-Alfaro^1,*

¹ Laboratorio de Investigación en Epidemiología Clínica y Molecular, Unidad Académica de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero, Chilpancingo, Guerrero 39089, Mexico

² Unidad de Investigación Médica en Bioquímica, Hospital de Especialidades "Bernardo Sepúlveda", Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Distrito Federal 06725, Mexico

³ Laboratorio de Biomedicina Molecular, Unidad Académica de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero, Chilpancingo, Guerrero 39089, Mexico

⁴ Department of Anthropology, University of Toronto at Mississauga, Mississauga, ON L5L 1C6, Canada

Int. J. Mol. Sci. 2015, 16(9), 21539-21554; https://doi.org/10.3390/ijms160921539 - 8 Sep 2015

Cited by 22 | Viewed by 7731

Abstract

Metabolic syndrome (MetS) is a combination of metabolic disorders associated with an increased risk for cardiovascular disease (CVD). Studies in women reported associations between polymorphisms in ESR1, LPL and CETP genes and MetS. Our aim was to evaluate the association between variants [...] Read more.

Metabolic syndrome (MetS) is a combination of metabolic disorders associated with an increased risk for cardiovascular disease (CVD). Studies in women reported associations between polymorphisms in ESR1, LPL and CETP genes and MetS. Our aim was to evaluate the association between variants in ESR1, LPL and CETP genes with MetS and its components. Four hundred and eighty women were analyzed, anthropometric features and biochemical profiles were evaluated, and genotyping was performed by real-time PCR. We found an association with elevated glucose levels (odds ratio (OR) = 2.9; p = 0.013) in carrying the AA genotype of rs1884051 in the ESR1 gene compared with the GG genotype, and the CC genotype of rs328 in the LPL gene was associated with MetS compared to the CG or GG genotype (OR = 2.8; p = 0.04). Moreover, the GA genotype of rs708272 in the CETP gene is associated with MetS compared to the GG or AA genotype (OR = 1.8; p = 0.006). In addition the ACTCCG haplotype in the ESR1 gene is associated with a decrease in the risk of MetS (OR = 0.02; p < 0.001). In conclusion, our results show the involvement of the variants of ESR1, LPL and CETP genes in metabolic events related to MetS or some of its features. Full article

(This article belongs to the Special Issue Human Single Nucleotide Polymorphisms and Disease Diagnostics)

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16 pages, 757 KiB

Open AccessArticle

Effects of Low Molecular Weight Yeast β-Glucan on Antioxidant and Immunological Activities in Mice

by Na Lei, Mi Wang^*, Lifang Zhang, Sui Xiao, Chengzhong Fei, Xiaoyang Wang, Keyu Zhang, Wenli Zheng, Chunmei Wang, Ruile Yang and Feiqun Xue^*

Department of Pharmacy, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China

Int. J. Mol. Sci. 2015, 16(9), 21575-21590; https://doi.org/10.3390/ijms160921575 - 8 Sep 2015

Cited by 63 | Viewed by 7175

Abstract

To evaluate the antioxidant and immune effects of low molecular yeast β-glucan on mice, three sulfated glucans from Saccharomyces cerevisiae (sGSCs) with different molecular weight (M_W) and degrees of sulfation (DS) were prepared. The structures of the sGSCs were analyzed [...] Read more.

To evaluate the antioxidant and immune effects of low molecular yeast β-glucan on mice, three sulfated glucans from Saccharomyces cerevisiae (sGSCs) with different molecular weight (M_W) and degrees of sulfation (DS) were prepared. The structures of the sGSCs were analyzed through high performance liquid chromatography-gel permeation chromatography (HPLC-GPC) and Fourier transform infrared spectroscopy (FTIR). sGSC1, sGSC2, and sGSC3 had M_W of 12.9, 16.5 and 19.2 kDa, respectively, and DS of 0.16, 0.24 and 0.27, respectively. In vitro and in vivo experiments were conducted to evaluate the antioxidant and immunological activities of the sGSCs. In vitro experiment, the reactive oxygen species (ROS) scavenging activities were determined. In vivo experiment, 50 male BALB/c mice were divided into five groups. The sGSC1, sGSC2 and sGSC3 treatment groups received the corresponding sGSCs at 50 mg/kg/day each. The GSC (glucans from Saccharomyces cerevisiae) treatment group received 50 mg/kg/day GSC. The normal control group received equal volume of physiological saline solution. All treatments were administered intragastrically for 14 day. Results showed that sGSC1, sGSC2 and sGSC3 can scavenge 1,1-diphenyl-2-picryl-hydrazyl (DPPH), superoxide, and hydroxyl radicals in vitro. The strength of the radical scavenging effects of the sGSCs was in the order of sGSC1 > sGSC2 > sGSC3. Oral administration of sGSC1 significantly improved serum catalase (CAT) and glutathione peroxidase (GSH-Px) activities and decreased malondialdehyde (MDA) level in mice. sGSC1 significantly improved the spleen and thymus indexes and the lymphocyte proliferation, effectively enhanced the percentage of CD4⁺ T cells, decreased the percentage of CD8⁺ T cells, and elevated the CD4⁺/CD8⁺ ratio. sGSC1 significantly promoted the secretion of IL-2 and IFN-γ. These results indicate that sGSC1 with low M_W and DS has better antioxidant and immunological activities than the other sGSCs, and sGSC1 could be used as a new antioxidant and immune-enhancing agent. Full article

(This article belongs to the Section Biochemistry)

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15 pages, 1460 KiB

Open AccessArticle

Identification and Characterization of Reference Genes for Normalizing Expression Data from Red Swamp Crawfish Procambarus clarkii

by Hucheng Jiang^1,†, Zhaojun Qian^1,†, Wei Lu², Huaiyu Ding³, Hongwei Yu², Hui Wang³ and Jiale Li^1,*

¹ Key Laboratory of Freshwater Fishery Germplasm Resources, Ministry of Agriculture, Shanghai Ocean University, Shanghai 201306, China

² Jiangsu Xuyi Riverred Crawfish Eco-Park Co., Ltd., Xuyi 211700, China

³ Jiangsu Key Laboratory for Eco-Agricultural Biotechnoology Around Hongze Lake, Huaiyin Normal University, Huaian 223300, China

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2015, 16(9), 21591-21605; https://doi.org/10.3390/ijms160921591 - 8 Sep 2015

Cited by 45 | Viewed by 6020

Abstract

qRT-PCR is a widely used technique for rapid and accurate quantification of gene expression data. The use of reference genes for normalization of the expression levels is crucial for accuracy. Several studies have shown that there is no perfect reference gene that is [...] Read more.

qRT-PCR is a widely used technique for rapid and accurate quantification of gene expression data. The use of reference genes for normalization of the expression levels is crucial for accuracy. Several studies have shown that there is no perfect reference gene that is appropriate for use in all experimental conditions, and research on suitable reference genes in red swamp crawfish (Procambarus clarkii) is particularly scarce. In this study, eight commonly used crustacean reference genes were chosen from P. clarkii transcriptome data and investigated as potential candidates for normalization of qRT-PCR data. Expression of these genes under different experimental conditions was examined by qRT-PCR, and the stability of their expression was evaluated using three commonly used statistical algorithms, geNorm, NormFinder and BestKeeper. A final comprehensive ranking determined that EIF and 18S were the optimal reference genes for expression data from different tissues, while TBP and EIF were optimal for expression data from different ovarian developmental stages. To our knowledge, this is the first systematic analysis of reference genes for normalization of qRT-PCR data in P. clarkii. These results will facilitate more accurate and reliable expression studies of this and other crustacean species. Full article

(This article belongs to the Special Issue Fish Molecular Biology)

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20 pages, 1661 KiB

Open AccessArticle

Physiological, Ultrastructural and Proteomic Responses in the Leaf of Maize Seedlings to Polyethylene Glycol-Stimulated Severe Water Deficiency

by Ruixin Shao^1,2, Longfei Xin², Jun Mao², Leilei Li², Guozhang Kang^1,* and Qinghua Yang^2,*

¹ The Collaborative Innovation Center of Henan Grain Crops, Henan Agricultural University, Zhengzhou 450002, China

² The National Key Laboratory of Wheat and Maize Crop Science, Henan Agricultural University, Zhengzhou 450002, China

Int. J. Mol. Sci. 2015, 16(9), 21606-21625; https://doi.org/10.3390/ijms160921606 - 8 Sep 2015

Cited by 14 | Viewed by 6436

Abstract

After maize seedlings grown in full-strength Hoagland solution for 20 days were exposed to 20% polyethylene glycol (PEG)-stimulated water deficiency for two days, plant height, shoot fresh and dry weights, and pigment contents significantly decreased, whereas malondialdehyde (MDA) content greatly increased. Using transmission [...] Read more.

After maize seedlings grown in full-strength Hoagland solution for 20 days were exposed to 20% polyethylene glycol (PEG)-stimulated water deficiency for two days, plant height, shoot fresh and dry weights, and pigment contents significantly decreased, whereas malondialdehyde (MDA) content greatly increased. Using transmission electron microscopy, we observed that chloroplasts of mesophyll cells in PEG-treated maize seedlings were swollen, with a disintegrating envelope and disrupted grana thylakoid lamellae. Using two-dimensional gel electrophoresis (2-DE) method, we were able to identify 22 protein spots with significantly altered abundance in the leaves of treated seedlings in response to water deficiency, 16 of which were successfully identified. These protein species were functionally classified into signal transduction, stress defense, carbohydrate metabolism, protein metabolism, and unknown categories. The change in the abundance of the identified protein species may be closely related to the phenotypic and physiological changes due to PEG-stimulated water deficiency. Most of the identified protein species were putatively located in chloroplasts, indicating that chloroplasts may be prone to damage by PEG stimulated-water deficiency in maize seedlings. Our results help clarify the molecular mechanisms of the responses of higher plants to severe water deficiency. Full article

(This article belongs to the Section Biochemistry)

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15 pages, 7087 KiB

Open AccessArticle

SOX2 Promotes the Epithelial to Mesenchymal Transition of Esophageal Squamous Cells by Modulating Slug Expression through the Activation of STAT3/HIF-α Signaling

by Hui Gao^1,†, Chunyuan Teng^2,†, Wenjing Huang³, Jianjun Peng^4,* and Chunbo Wang^1,*

¹ Department of Pharmacology, Medical College Qingdao University, Qingdao 266071, China

² Department of Gastroenterology, Qingdao Hiser Medical Center, Qingdao 266033, China

³ Department of Paediatrics, the Affiliated Hospital of Medical College Qingdao University, Qingdao 266003, China

⁴ College of Life Sciences, Chongqing Normal University, Chongqing 401331, China

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2015, 16(9), 21643-21657; https://doi.org/10.3390/ijms160921643 - 8 Sep 2015

Cited by 61 | Viewed by 7837

Abstract

The transcription factor sex determining region (Y SRY)-box 2 (SOX2) is known to play a crucial role in the maintenance of self renewal or pluripotency of undifferentiated embryonic and neuronal stem cells. An elevated expression of SOX2 has been correlated with poor prognosis [...] Read more.

The transcription factor sex determining region (Y SRY)-box 2 (SOX2) is known to play a crucial role in the maintenance of self renewal or pluripotency of undifferentiated embryonic and neuronal stem cells. An elevated expression of SOX2 has been correlated with poor prognosis of esophageal squamous cell carcinoma (ESCC). We sought to investigate the mechanism(s) by which SOX2 modulates the ESCC metastasis. The SOX2 coding DNA sequence was inserted into pCMV vector and stably transfected in ESCC cells (Eca-109). The effect of SOX2 over expression was evaluated on cell migration, invasion and epithelial to mesenchymal transition (EMT). We also measured the expression of Slug to explore if this transcription factor is involved in SOX2-mediated regulation of cell migration/invasion and EMT. In addition, we determined the role of STAT3/HIF-1α to further probe the mechanism of SOX2-mediated metastasis via Slug. Our results demonstrated that SOX2 over expressing Eca-109 cells showed an enhanced cell migration/invasion. Moreover, these cells exhibited the EMT characteristics, that is, a significantly suppressed expression of the epithelial cells marker with a concomitant enhancement of those of the mesenchymal markers. An increased expression of Slug in SOX2 over expressing cells suggested the involvement of this transcription factor in SOX2-regulated metastasis. Whereas the expressions of STAT3/HIF-1α were found to be up-regulated in SOX2 expressing cells, blockade of these transcription factors resulted in the inhibition of Slug expression at both protein and mRNA levels. Conclusion: These results suggest that SOX2 promoted the metastasis of ESCC, at least in part, by modulating Slug expression through the activation of STAT3/HIF-1α signaling. Full article

(This article belongs to the Section Biochemistry)

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23 pages, 5650 KiB

Open AccessArticle

A Novel Nanoprobe for Multimodal Imaging Is Effectively Incorporated into Human Melanoma Metastatic Cell Lines

by Synnøve Nymark Aasen¹, Aneta Pospisilova², Tilo Wolf Eichler³, Jiri Panek², Martin Hruby², Petr Stepanek², Endy Spriet⁴, Daniel Jirak^5,6, Kai Ove Skaftnesmo¹ and Frits Thorsen^1,4,7,*

¹ NorLux Neuro-Oncology Laboratory, Department of Biomedicine, University of Bergen, 5020 Bergen, Norway

² Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, 162 06 Prague, Czech Republic

³ Department of Clinical Medicine, University of Bergen, 5020 Bergen, Norway

⁴ Molecular Imaging Center, Department of Biomedicine, University of Bergen, 5020 Bergen, Norway

⁵ Department of Diagnostic and Interventional Radiology, Institute for Clinical and Experimental Medicine, 140 21 Prague, Czech Republic

⁶ Institute of Biophysics and Informatics, 1st Medicine Faculty, Charles University, 120 00 Prague, Czech Republic

⁷ Kristian Gerhard Jebsen Brain Tumour Research Centre, Department of Biomedicine, University of Bergen, 5020 Bergen, Norway

Int. J. Mol. Sci. 2015, 16(9), 21658-21680; https://doi.org/10.3390/ijms160921658 - 8 Sep 2015

Cited by 10 | Viewed by 8011

Abstract

To facilitate efficient drug delivery to tumor tissue, several nanomaterials have been designed, with combined diagnostic and therapeutic properties. In this work, we carried out fundamental in vitro and in vivo experiments to assess the labeling efficacy of our novel theranostic nanoprobe, consisting [...] Read more.

To facilitate efficient drug delivery to tumor tissue, several nanomaterials have been designed, with combined diagnostic and therapeutic properties. In this work, we carried out fundamental in vitro and in vivo experiments to assess the labeling efficacy of our novel theranostic nanoprobe, consisting of glycogen conjugated with a red fluorescent probe and gadolinium. Microscopy and resazurin viability assays were used to study cell labeling and cell viability in human metastatic melanoma cell lines. Fluorescence lifetime correlation spectroscopy (FLCS) was done to investigate nanoprobe stability. Magnetic resonance imaging (MRI) was performed to study T₁ relaxivity in vitro, and contrast enhancement in a subcutaneous in vivo tumor model. Efficient cell labeling was demonstrated, while cell viability, cell migration, and cell growth was not affected. FLCS showed that the nanoprobe did not degrade in blood plasma. MRI demonstrated that down to 750 cells/μL of labeled cells in agar phantoms could be detected. In vivo MRI showed that contrast enhancement in tumors was comparable between Omniscan contrast agent and the nanoprobe. In conclusion, we demonstrate for the first time that a non-toxic glycogen-based nanoprobe may effectively visualize tumor cells and tissue, and, in future experiments, we will investigate its therapeutic potential by conjugating therapeutic compounds to the nanoprobe. Full article

(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)

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14 pages, 1460 KiB

Open AccessArticle

A New HPLC-MS Method for Measuring Maslinic Acid and Oleanolic Acid in HT29 and HepG2 Human Cancer Cells

by Juan Peragón^1,*, Eva E. Rufino-Palomares²

, Irene Muñoz-Espada¹, Fernando J. Reyes-Zurita² and José A. Lupiáñez²

¹ Biochemistry and Molecular Biology Section, Department of Experimental Biology, University of Jaén, Campus Las Lagunillas, E-23071 Jaén, Spain

² Department of Biochemistry and Molecular Biology I, Faculty of Sciences, University of Granada, Campus Fuentenueva, E-18001 Granada, Spain

Int. J. Mol. Sci. 2015, 16(9), 21681-21694; https://doi.org/10.3390/ijms160921681 - 9 Sep 2015

Cited by 32 | Viewed by 6754

Abstract

Maslinic acid (MA) and oleanolic acid (OA), the main triterpenic acids present in olive, have important properties for health and disease prevention. MA selectively inhibits cell proliferation of the HT29 human colon-cancer cell line by inducing selective apoptosis. For measuring the MA and [...] Read more.

Maslinic acid (MA) and oleanolic acid (OA), the main triterpenic acids present in olive, have important properties for health and disease prevention. MA selectively inhibits cell proliferation of the HT29 human colon-cancer cell line by inducing selective apoptosis. For measuring the MA and OA concentration inside the cell and in the culture medium, a new HPLC-MS procedure has been developed. With this method, a determination of the amount of MA and OA incorporated into HT29 and HepG2 human cancer-cell lines incubated with different concentrations of MA corresponding to 50% growth inhibitory concentration (IC₅₀), IC_50/2, IC_50/4, and IC_50/8 has been made. The results demonstrate that this method is appropriate for determining the MA and OA concentration in different types of cultured cells and reveals the specific dynamics of entry of MA into HT29 and HepG2 cells. Full article

(This article belongs to the Section Biochemistry)

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16 pages, 3094 KiB

Open AccessArticle

CrWSKP1, an SKP1-like Gene, Is Involved in the Self-Incompatibility Reaction of “Wuzishatangju” (Citrus reticulata Blanco)

by Peng Li^1,†, Hongxia Miao^1,2,†, Yuewen Ma¹, Lu Wang¹, Guibing Hu¹, Zixing Ye¹, Jietang Zhao¹ and Yonghua Qin^1,*

¹ State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources/ Key Laboratory of Biology and Genetic Improvement of Horticultural Crops-South China, Ministry of Agriculture, College of Horticulture, South China Agricultural University, Guangzhou 510642, China

² Institute of Tropical Bioscience and Biotechnology, Chinese Academy of Tropical Agricultural Sciences/Key Laboratory of Tropical Crop Bioscience and Biotechnology, Ministry of Agriculture, Haikou 571101, China

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2015, 16(9), 21695-21710; https://doi.org/10.3390/ijms160921695 - 9 Sep 2015

Cited by 15 | Viewed by 5846

Abstract

Plant S-phase kinase-associated protein 1 (SKP1) genes play crucial roles in plant development and differentiation. However, the role of SKP1 in citrus is unclear. Herein, we described a novel SKP1-like gene, designated as CrWSKP1, from “Wuzishatangju” (Citrus reticulata Blanco). [...] Read more.

Plant S-phase kinase-associated protein 1 (SKP1) genes play crucial roles in plant development and differentiation. However, the role of SKP1 in citrus is unclear. Herein, we described a novel SKP1-like gene, designated as CrWSKP1, from “Wuzishatangju” (Citrus reticulata Blanco). The cDNA sequence of CrWSKP1 is 779 base pairs (bp) and contains an open reading frame (ORF) of 477 bp. The genomic sequence of the CrWSKP1 gene is 1296 bp with two exons and one intron. CrWSKP1 has high identity with SKP1-like genes from other plant species within two conserved regions. Approximately 85% of pollen tubes of self-pollinated CrWSKP1 transgenic tobaccos became twisted at four days after self-pollination. Pollen tube numbers of self-pollinated CrWSKP1 transformants entering into ovules were significantly fewer than that of the control. Seed number of self-pollinated CrWSKP1 transformants was significantly reduced. These results suggested that the CrWSKP1 is involved in the self-incompatibility (SI) reaction of “Wuzishatangju”. Full article

(This article belongs to the Section Biochemistry)

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25 pages, 737 KiB

Open AccessArticle

An Ensemble Method to Distinguish Bacteriophage Virion from Non-Virion Proteins Based on Protein Sequence Characteristics

by Lina Zhang¹, Chengjin Zhang^1,2,*

, Rui Gao¹ and Runtao Yang¹

¹ School of Control Science and Engineering, Shandong University, Jinan 250061, China

² School of Mechanical, Electrical and Information Engineering, Shandong University, Weihai 264209, China

Int. J. Mol. Sci. 2015, 16(9), 21734-21758; https://doi.org/10.3390/ijms160921734 - 9 Sep 2015

Cited by 36 | Viewed by 5669

Abstract

Bacteriophage virion proteins and non-virion proteins have distinct functions in biological processes, such as specificity determination for host bacteria, bacteriophage replication and transcription. Accurate identification of bacteriophage virion proteins from bacteriophage protein sequences is significant to understand the complex virulence mechanism in host [...] Read more.

Bacteriophage virion proteins and non-virion proteins have distinct functions in biological processes, such as specificity determination for host bacteria, bacteriophage replication and transcription. Accurate identification of bacteriophage virion proteins from bacteriophage protein sequences is significant to understand the complex virulence mechanism in host bacteria and the influence of bacteriophages on the development of antibacterial drugs. In this study, an ensemble method for bacteriophage virion protein prediction from bacteriophage protein sequences is put forward with hybrid feature spaces incorporating CTD (composition, transition and distribution), bi-profile Bayes, PseAAC (pseudo-amino acid composition) and PSSM (position-specific scoring matrix). When performing on the training dataset 10-fold cross-validation, the presented method achieves a satisfactory prediction result with a sensitivity of 0.870, a specificity of 0.830, an accuracy of 0.850 and Matthew’s correlation coefficient (MCC) of 0.701, respectively. To evaluate the prediction performance objectively, an independent testing dataset is used to evaluate the proposed method. Encouragingly, our proposed method performs better than previous studies with a sensitivity of 0.853, a specificity of 0.815, an accuracy of 0.831 and MCC of 0.662 on the independent testing dataset. These results suggest that the proposed method can be a potential candidate for bacteriophage virion protein prediction, which may provide a useful tool to find novel antibacterial drugs and to understand the relationship between bacteriophage and host bacteria. For the convenience of the vast majority of experimental Int. J. Mol. Sci. 2015, 16 21735 scientists, a user-friendly and publicly-accessible web-server for the proposed ensemble method is established. Full article

(This article belongs to the Section Biochemistry)

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16 pages, 6938 KiB

Open AccessArticle

A Novel Ligustrazine Derivative T-VA Prevents Neurotoxicity in Differentiated PC12 Cells and Protects the Brain against Ischemia Injury in MCAO Rats

by Guoliang Li^1,†, Yufei Tian^1,†, Yuzhong Zhang², Ying Hong¹, Yingzhi Hao¹, Chunxiao Chen², Penglong Wang^1,*

and Haimin Lei^1,*

¹ School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China

² Department of Pathology, Beijing University of Chinese Medicine, Beijing 100029, China

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2015, 16(9), 21759-21774; https://doi.org/10.3390/ijms160921759 - 9 Sep 2015

Cited by 21 | Viewed by 5981 | Correction

Abstract

Broad-spectrum drugs appear to be more promising for the treatment of acute ischemic stroke. In our previous work, a new ligustrazine derivative (3,5,6-trimethylpyrazin-2-yl) methyl 3-methoxy-4-[(3,5,6-trimethylpyrazin-2-yl)methoxy]benzoate (T-VA) showed neuroprotective effect on injured PC12 cells (EC₅₀ = 4.249 µM). In the current study, we [...] Read more.

Broad-spectrum drugs appear to be more promising for the treatment of acute ischemic stroke. In our previous work, a new ligustrazine derivative (3,5,6-trimethylpyrazin-2-yl) methyl 3-methoxy-4-[(3,5,6-trimethylpyrazin-2-yl)methoxy]benzoate (T-VA) showed neuroprotective effect on injured PC12 cells (EC₅₀ = 4.249 µM). In the current study, we show that this beneficial effect was due to the modulation of nuclear transcription factor-κB/p65 (NF-κB/p65) and cyclooxygenase-2 (COX-2) expressions. We also show that T-VA exhibited neuroprotective effect in a rat model of ischemic stroke with concomitant improvement of motor functions. We propose that the protective effect observed in vivo is owing to increased vascular endothelial growth factor (VEGF) expression, decreased oxidative stress, and up-regulation of Ca²⁺–Mg²⁺ ATP enzyme activity. Altogether, our results warrant further studies on the utility of T-VA for the potential treatment of ischemic brain injuries, such as stroke. Full article

(This article belongs to the Special Issue Neuroprotective Strategies 2022)

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16 pages, 1367 KiB

Open AccessArticle

Tetramethylpyrazine Protects Retinal Capillary Endothelial Cells (TR-iBRB2) against IL-1β-Induced Nitrative/Oxidative Stress

by Xue Zhu^1,†, Ke Wang^1,†, Kai Zhang¹, Xuhua Tan², Zhifeng Wu^2,*, Song Sun², Fanfan Zhou³ and Ling Zhu⁴

¹ Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063, China

² Department of Ophthalmology, Wuxi No. 2 People's Hospital, Nanjing Medical University, Wuxi 214002, China

³ Faculty of Pharmacy, University of Sydney, New South Wales 2006, Australia

⁴ Save Sight Institute, University of Sydney, New South Wales 2000, Australia

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2015, 16(9), 21775-21790; https://doi.org/10.3390/ijms160921775 - 9 Sep 2015

Cited by 29 | Viewed by 5863

Abstract

Blood-retinal barrier (BRB) breakdown is one of the primary causes of diabetic retinopathy (DR). The pro-inflammatory factor interleukin-1β (IL-1β) was reported to be involved in the induction of BRB breakdown during the pathogenesis of DR. In the present study, we investigated the protective [...] Read more.

Blood-retinal barrier (BRB) breakdown is one of the primary causes of diabetic retinopathy (DR). The pro-inflammatory factor interleukin-1β (IL-1β) was reported to be involved in the induction of BRB breakdown during the pathogenesis of DR. In the present study, we investigated the protective effect of tetramethylpyrazine (TMP), a major active component of the traditional herb Ligusticum chuanxiong, on IL-1β-induced cell death of the rat retinal capillary endothelial TR-iBRB2 cells. Our results showed that IL-1β-induced cell dysfunction in TR-iBRB2 cells via inducing nitrative/oxidative stress; however, such effect was attenuated with the pre-treatment of TMP. The cellular protective effect of TMP was likely to be mediated through the inhibition of inducible nitric oxide synthase (iNOS) expression and leukostasis as well as suppression of reactive oxygen species (ROS) generation, mitochondrial dysfunction and MAPKs activation. These findings significantly contribute to a better understanding of the protective effect of TMP in DR and form the basis of the therapeutic development of TMP in treating such disease in the future. Full article

(This article belongs to the Section Molecular Toxicology)

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11 pages, 2338 KiB

Open AccessArticle

Homozygous ALOXE3 Nonsense Variant Identified in a Patient with Non-Bullous Congenital Ichthyosiform Erythroderma Complicated by Superimposed Bullous Majocchi’s Granuloma: The Consequences of Skin Barrier Dysfunction

by Tao Wang¹, Chenchen Xu¹, Xiping Zhou¹, Chunjia Li², Hongbing Zhang², Bill Q. Lian³, Jonathan J. Lee⁴, Jun Shen⁴, Yuehua Liu^1,* and Christine Guo Lian^4,*

¹ Department of Dermatology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100730, China

² State Key Laboratory of Medical Molecular Biology, Department of Physiology, Institute of Basic Medical Sciences and School of Basic Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China

³ Department of Medicine, University of Massachusetts, Worcester, MA 01655, USA

⁴ Department of Pathology, Brigham & Women's Hospital, Harvard Medical School, 221 Longwood Ave. EBRC 401, Boston, MA 02115, USA

Int. J. Mol. Sci. 2015, 16(9), 21791-21801; https://doi.org/10.3390/ijms160921791 - 9 Sep 2015

Cited by 14 | Viewed by 8359

Abstract

Non-bullous congenital ichthyosiform erythroderma (NBCIE) is a hereditary disorder of keratinization caused by pathogenic variants in genes encoding enzymes important to lipid processing and terminal keratinocyte differentiation. Impaired function of these enzymes can cause pathologic epidermal scaling, significantly reduced skin barrier function. In [...] Read more.

Non-bullous congenital ichthyosiform erythroderma (NBCIE) is a hereditary disorder of keratinization caused by pathogenic variants in genes encoding enzymes important to lipid processing and terminal keratinocyte differentiation. Impaired function of these enzymes can cause pathologic epidermal scaling, significantly reduced skin barrier function. In this study, we have performed a focused, genetic analysis of a probrand affected by NBCIE and extended this to his consanguineous parents. Targeted capture and next-generation sequencing was performed on NBCIE associated genes in the proband and his unaffected consanguineous parents. We identified a homozygous nonsense variant c.814C>T (p.Arg272*) in ALOXE3 (NM_001165960.1) in the proband and discovered that his parents are both heterozygous carriers of the variant. The clinical manifestations of the proband’s skin were consistent with NBCIE, and detailed histopathological assessment revealed epidermal bulla formation and Majocchi’s granuloma. Infection with Trichophyton rubrum was confirmed by culture. The patient responded to oral terbinafine antifungal treatment. Decreased skin barrier function, such as that caused by hereditary disorders of keratinization, can increase the risk of severe cutaneous fungal infections and the formation of Majocchi’s granuloma and associated alopecia. Patients with NBCIE should be alerted to the possible predisposition for developing dermatophytoses and warrant close clinical follow-up. Full article

(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)

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19 pages, 4089 KiB

Open AccessArticle

Surface Properties of Squalene/Meibum Films and NMR Confirmation of Squalene in Tears

by Slavyana Ivanova¹, Vesselin Tonchev^2,†

, Norihiko Yokoi^3,†, Marta C. Yappert^4,†, Douglas Borchman^5,* and Georgi As. Georgiev^1,6

¹ Department of Biochemistry, Faculty of Biology, St. Kliment Ohridski University of Sofia, 1164 Sofia, Bulgaria

² Institute of Physical Chemistry "R. Kaischew"-BAS, Phase Formation, Crystals and Amorphous Materials Department, 1113 Sofia, Bulgaria

³ Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto 602-0841, Japan

⁴ Department of Chemistry, University of Louisville, Louisville, KY 40202, USA

⁵ Department of Ophthalmology and Visual Sciences, University of Louisville, Louisville, KY 40202, USA

⁶ Biointerfaces and Biomaterials Laboratory, Department of Optics and Spectroscopy, Faculty of Physics, St. Kliment Ohridski University of Sofia, 1164 Sofia, Bulgaria

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2015, 16(9), 21813-21831; https://doi.org/10.3390/ijms160921813 - 9 Sep 2015

Cited by 43 | Viewed by 7370

Abstract

Squalene (SQ) possesses a wide range of pharmacological activities (antioxidant, drug carrier, detoxifier, hydrating, emollient) that can be of benefit to the ocular surface. It can come in contact with human meibum (hMGS; the most abundant component of the tear film lipid layer) [...] Read more.

Squalene (SQ) possesses a wide range of pharmacological activities (antioxidant, drug carrier, detoxifier, hydrating, emollient) that can be of benefit to the ocular surface. It can come in contact with human meibum (hMGS; the most abundant component of the tear film lipid layer) as an endogenous tear lipid or from exogenous sources as eyelid sebum or pharmaceuticals. The aims of this study were to determine (i) if SQ is in tear lipids and (ii) its influence on the surface properties of hMGS films. Heteronuclear single quantum correlation NMR confirmed 7 mol % SQ in Schirmer’s strips extracts. The properties of SQ/hMGS pseudo-binary films at the air/water interface were studied with Langmuir surface balance, stress-relaxation dilatational rheology and Brewster angle microscopy. SQ does not possess surfactant properties. When mixed with hMGS squalene (i) localized over the layers’ thinner regions and (ii) did not affect the film pressure at high compression. Therefore, tear SQ is unlikely to instigate dry eye, and SQ can be used as a safe and “inert” ingredient in formulations to protect against dry eye. The layering of SQ over the thinner film regions in addition to its pharmacological properties could contribute to the protection of the ocular surface. Full article

(This article belongs to the Section Biochemistry)

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14 pages, 1779 KiB

Open AccessArticle

Adaptive Immune Responses in a Multiple Sclerosis Patient with Acute Varicella-Zoster Virus Reactivation during Treatment with Fingolimod

by Andrea Harrer¹, Peter Wipfler¹, Georg Pilz¹, Katrin Oppermann¹, Elisabeth Haschke-Becher², Shahrzad Afazel², Jörg Kraus^3,4, Eugen Trinka¹ and Johann Sellner^1,5,*

¹ Department of Neurology, Christian Doppler Medical Center, Paracelsus Medical University, 5020 Salzburg, Austria

² Department of Laboratory Medicine, Paracelsus Medical University, 5020 Salzburg, Austria

³ Department of Neurology, A.ö. Krankenhaus Zell am See, Teaching Hospital of the Paracelsus Medical University, 5700 Zell am See, Austria

⁴ Research Institute of Neurointervention, Paracelsus Medical University, 5020 Salzburg, Austria

⁵ Department of Neurology, Klinikum rechts der Isar, Technische Universität, 81675 München, Germany

Int. J. Mol. Sci. 2015, 16(9), 21832-21845; https://doi.org/10.3390/ijms160921832 - 10 Sep 2015

Cited by 10 | Viewed by 6755

Abstract

Fingolimod, an oral sphingosine 1-phosphate (S1P) receptor modulator, is approved for the treatment of relapsing forms of multiple sclerosis (MS). The interference with S1P signaling leads to retention particularly of chemokine receptor-7 (CCR7) expressing T cells in lymph nodes. The immunological basis of [...] Read more.

Fingolimod, an oral sphingosine 1-phosphate (S1P) receptor modulator, is approved for the treatment of relapsing forms of multiple sclerosis (MS). The interference with S1P signaling leads to retention particularly of chemokine receptor-7 (CCR7) expressing T cells in lymph nodes. The immunological basis of varicella zoster virus (VZV) infections during fingolimod treatment is unclear. Here, we studied the dynamics of systemic and intrathecal immune responses associated with symptomatic VZV reactivation including cessation of fingolimod and initiation of antiviral therapy. Key features in peripheral blood were an about two-fold increase of VZV-specific IgG at diagnosis of VZV reactivation as compared to the previous months, a relative enrichment of effector CD4+ T cells (36% versus mean 12% in controls), and an accelerated reconstitution of absolute lymphocytes counts including a normalized CD4+/CD8+ ratio and reappearance of CCR7+ T cells. In cerebrospinal fluid (CSF) the lymphocytic pleocytosis and CD4+/CD8+ ratios at diagnosis of reactivation and after nine days of fingolimod discontinuation remained unchanged. During this time CCR7+ T cells were not observed in CSF. Further research into fingolimod-associated VZV reactivation and immune reconstitution is mandatory to prevent morbidity and mortality associated with this potentially life-threatening condition. Full article

(This article belongs to the Special Issue Advances in Multiple Sclerosis)

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12 pages, 4761 KiB

Open AccessArticle

A Novel Function of TET2 in CNS: Sustaining Neuronal Survival

by Yajing Mi^1,2,†, Xingchun Gao^2,3,†

, Jinxiang Dai⁴, Yue Ma⁵, Lixian Xu^1,* and Weilin Jin^3,5,*

¹ State Key Laboratory of Military Stomatology, Department of Anesthesiology, School of Stomatology, the Fourth Military Medical University, Xi'an 710032, China

² Institute of Basic Medicine Science, Xi'an Medical University, Xi'an 710021, China

³ School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China

⁴ Department of Cell and Developmental Biology, University of Colorado Denver, Denver, CO 80045, USA

⁵ Institute of Nano Biomedicine and Engineering, Department of Instrument Science and Engineering, Key Laboratory for Thin Film and Microfabrication Technology of Ministry of Education, School of Electronic Information and Electronic Engineering, Shanghai Jiao Tong University, Shanghai 200240, China

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2015, 16(9), 21846-21857; https://doi.org/10.3390/ijms160921846 - 10 Sep 2015

Cited by 38 | Viewed by 6976

Abstract

DNA dioxygenases Ten-Eleven Translocation (TET) proteins can catalyze the conversion of 5-methylcytosine (5mC) of DNA to 5-hydroxymethylcytosine (5hmC), and thereby alter the epigenetic state of DNA. The TET family includes TET1, TET2 and TET3 members in mammals. Recently, accumulative research uncovered that TET1–3 [...] Read more.

DNA dioxygenases Ten-Eleven Translocation (TET) proteins can catalyze the conversion of 5-methylcytosine (5mC) of DNA to 5-hydroxymethylcytosine (5hmC), and thereby alter the epigenetic state of DNA. The TET family includes TET1, TET2 and TET3 members in mammals. Recently, accumulative research uncovered that TET1–3 occur abundantly in the central nervous system (CNS), and their biological functions have just begun to be investigated. In the present study, we demonstrated that mRNA and protein of TET2 were highly expressed in the cerebral cortex and hippocampus along the whole brain-development process. Further studies showed that TET2 was expressed in various types of cells, especially in most neurons. Subcellular distribution pattern implicated that TET2 is localized in both nucleus and cytoplasm of neurons. Down-regulation of TET2 in cultured cortical neurons with RNA interference implied that TET2 was required for cell survival. In all, our results indicate that neuronal TET2 is positively involved in the regulation of cell survival. Full article

(This article belongs to the Section Biochemistry)

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15 pages, 2480 KiB

Open AccessArticle

Simultaneous Disulfide and Boronic Acid Ester Exchange in Dynamic Combinatorial Libraries

by Sanna L. Diemer¹, Morten Kristensen¹, Brian Rasmussen¹, Sophie R. Beeren^2,* and Michael Pittelkow^1,*

¹ Department of Chemistry, University of Copenhagen, Universitetsparken 5, DK-2100 Copenhagen Ø, Denmark

² Department of Chemistry, Technical University of Denmark, DK-2800 Kgs. Lyngby, Denmark

Int. J. Mol. Sci. 2015, 16(9), 21858-21872; https://doi.org/10.3390/ijms160921858 - 10 Sep 2015

Cited by 26 | Viewed by 10907

Abstract

Dynamic combinatorial chemistry has emerged as a promising tool for the discovery of complex receptors in supramolecular chemistry. At the heart of dynamic combinatorial chemistry are the reversible reactions that enable the exchange of building blocks between library members in dynamic combinatorial libraries [...] Read more.

Dynamic combinatorial chemistry has emerged as a promising tool for the discovery of complex receptors in supramolecular chemistry. At the heart of dynamic combinatorial chemistry are the reversible reactions that enable the exchange of building blocks between library members in dynamic combinatorial libraries (DCLs) ensuring thermodynamic control over the system. If more than one reversible reaction operates in a single dynamic combinatorial library, the complexity of the system increases dramatically, and so does its possible applications. One can imagine two reversible reactions that operate simultaneously or two reversible reactions that operate independently. Both these scenarios have advantages and disadvantages. In this contribution, we show how disulfide exchange and boronic ester transesterification can function simultaneous in dynamic combinatorial libraries under appropriate conditions. We describe the detailed studies necessary to establish suitable reaction conditions and highlight the analytical techniques appropriate to study this type of system. Full article

(This article belongs to the Special Issue Supramolecular Interactions)

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24 pages, 2836 KiB

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Identification of Genes Putatively Involved in Chitin Metabolism and Insecticide Detoxification in the Rice Leaf Folder (Cnaphalocrocis medinalis) Larvae through Transcriptomic Analysis

by Hai-Zhong Yu¹, De-Fu Wen¹, Wan-Lin Wang², Lei Geng¹, Yan Zhang³ and Jia-Ping Xu^1,*

¹ School of Life Sciences, Anhui Agricultural University, Hefei 230036, China

² Rice Research Institute, Anhui Academy of Agricultural Sciences, Hefei 230031, China

³ Institute of Sericulture, Anhui Academy of Agricultural Sciences, Hefei 230061, China

Int. J. Mol. Sci. 2015, 16(9), 21873-21896; https://doi.org/10.3390/ijms160921873 - 10 Sep 2015

Cited by 18 | Viewed by 6721

Abstract

The rice leaf roller (Cnaphalocrocis medinalis) is one of the most destructive agricultural pests. Due to its migratory behavior, it is difficult to control worldwide. To date, little is known about major genes of C. medinalis involved in chitin metabolism and [...] Read more.

The rice leaf roller (Cnaphalocrocis medinalis) is one of the most destructive agricultural pests. Due to its migratory behavior, it is difficult to control worldwide. To date, little is known about major genes of C. medinalis involved in chitin metabolism and insecticide detoxification. In order to obtain a comprehensive genome dataset of C. medinalis, we conducted de novo transcriptome sequencing which focused on the major feeding stage of fourth-instar larvae, and our work revealed useful information on chitin metabolism and insecticide detoxification and target genes of C. medinalis. We acquired 29,367,797 Illumina reads and assembled these reads into 63,174 unigenes with an average length of 753 bp. Among these unigenes, 31,810 were annotated against the National Center for Biotechnology Information non-redundant (NCBI nr) protein database, resulting in 24,246, 8669 and 18,176 assigned to Swiss-Prot, clusters of orthologous group (COG), and gene ontology (GO), respectively. We were able to map 10,043 unigenes into 285 pathways using the Kyoto Encyclopedia of Genes and Genomes Pathway database (KEGG). Specifically, 16 genes, including five chitin deacetylases, two chitin synthases, five chitinases and four other related enzymes, were identified to be putatively involved in chitin biosynthesis and degradation, whereas 360 genes, including cytochrome P450s, glutathione S-transferases, esterases, and acetylcholinesterases, were found to be potentially involved in insecticide detoxification or as insecticide targets. The reliability of the transcriptome data was determined by reverse transcription quantitative PCR (RT-qPCR) for the selected genes. Our data serves as a new and valuable sequence resource for genomic studies on C. medinalis. The findings should improve our understanding of C. medinalis genetics and contribute to management of this important agricultural pest. Full article

(This article belongs to the Section Biochemistry)

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14 pages, 2099 KiB

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GCN5 Potentiates Glioma Proliferation and Invasion via STAT3 and AKT Signaling Pathways

by Kun Liu^1,2,†, Qing Zhang^1,2,†, Haitao Lan^3,†, Liping Wang^2,†, Pengfei Mou^1,2, Wei Shao^1,2, Dan Liu^1,2, Wensheng Yang^1,2, Zhen Lin^1,2, Qingyuan Lin^1,2 and Tianhai Ji^1,2,*

¹ Department of Pathology, Affiliated Chenggong Hospital, Xiamen University, Xiamen 361000, China

² Chinese People's Liberation Army No. 174 Clinical College, Anhui Medical University, Xiamen 361000, China

³ Department of Oncology, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu 610072, China

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2015, 16(9), 21897-21910; https://doi.org/10.3390/ijms160921897 - 10 Sep 2015

Cited by 41 | Viewed by 6911

Abstract

The general control of nucleotide synthesis 5 (GCN5), which is one kind of lysine acetyltransferases, regulates a number of cellular processes, such as cell proliferation, differentiation, cell cycle and DNA damage repair. However, its biological role in human glioma development remains elusive. In [...] Read more.

The general control of nucleotide synthesis 5 (GCN5), which is one kind of lysine acetyltransferases, regulates a number of cellular processes, such as cell proliferation, differentiation, cell cycle and DNA damage repair. However, its biological role in human glioma development remains elusive. In the present study, we firstly reported that GCN5 was frequently overexpressed in human glioma tissues and GCN5 was positively correlated with proliferation of cell nuclear antigen PCNA and matrix metallopeptidase MMP9. Meanwhile, down-regulation of GCN5 by siRNA interfering inhibited glioma cell proliferation and invasion. In addition, GCN5 knockdown reduced expression of p-STAT3, p-AKT, PCNA and MMP9 and increased the expression of p21 in glioma cells. In conclusion, GCN5 exhibited critical roles in glioma development by regulating cell proliferation and invasion, which suggested that GCN5 might be a potential molecular target for glioma treatment. Full article

(This article belongs to the Section Biochemistry)

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20 pages, 13410 KiB

Open AccessArticle

Ghrelin Attenuates Liver Fibrosis through Regulation of TGF-β1 Expression and Autophagy

by Yuqing Mao¹, Shaoren Zhang¹, Fujun Yu¹, Huanqing Li¹, Chuanyong Guo^2,* and Xiaoming Fan^1,*

¹ Department of Gastroenterology and Hepatology, Jinshan Hospital of Fudan University, Shanghai 201508, China

² Department of Gastroenterology and Hepatology, Shanghai Tenth People's Hospital of Tongji University, Shanghai 200072, China

Int. J. Mol. Sci. 2015, 16(9), 21911-21930; https://doi.org/10.3390/ijms160921911 - 10 Sep 2015

Cited by 71 | Viewed by 9058

Abstract

Ghrelin is a stomach-derived growth hormone secretagogue that promotes various physiological effects, including energy metabolism and amelioration of inflammation. The purpose of this study was to investigate the protective mechanism of ghrelin against liver fibrosis. Liver fibrosis was induced in C57BL/6 mice by [...] Read more.

Ghrelin is a stomach-derived growth hormone secretagogue that promotes various physiological effects, including energy metabolism and amelioration of inflammation. The purpose of this study was to investigate the protective mechanism of ghrelin against liver fibrosis. Liver fibrosis was induced in C57BL/6 mice by intraperitoneal injection of CCl₄ (2.0 mL/kg of 10% CCl₄ v/v solution in peanut oil) two times per week for eight weeks. Ghrelin (10 μg/kg) was intraperitoneally injected two times per week for eight weeks. A second murine liver fibrosis model was induced by bile duct ligation (BDL) and concurrent ghrelin administration for four weeks. Hematoxylin eosin (H&E), and Masson’s trichrome were used to detect pathological changes to liver tissue. Western blotting was used to detect protein levels of transforming growth factor (TGF)-β1, phosphorylated Smad3 (p-Smad3), I-collage, α-smooth muscle actin (α-SMA), matrix metalloproteinases (MMPs) 2, tissue inhibitor of matrix metalloproteinases (TIMPs) 1, phosphorylated NF-κB (p-NF-κB), and microtubule-associated protein light chain 3 (LC3). In addition, qRT-PCR was used to detect mRNA levels of TGF-β1, I-collage, α-SMA, MMP2, TIMP1 and LC3, while levels of TGF-β1, p-Smad3, I-collage, α-SMA, and LC3 were detected immunohistochemically. Levels of aspartate aminotransferase and alanine aminotransferase were significantly decreased by ghrelin treatment. Ghrelin administration also significantly reduced the extent of pathological changes in both murine liver fibrosis models. Expression levels of I-collage and α-SMA in both models were clearly reduced by ghrelin administration. Furthermore, ghrelin treatment decreased protein expression of TGF-β1 and p-Smad3. The protein levels of NF-κB and LC3 were increased in the CCl₄- and BDL-treatment groups but were significantly reduced following ghrelin treatment. In addition, ghrelin inhibited extracellular matrix formation by decreasing NF-κB expression and maintaining the balance between MMP2 and TIMP1. Our results demonstrated that ghrelin attenuates liver fibrosis via inhibition of the TGF-β1/Smad3 and NF-κB signaling pathways, as well as autophagy suppression. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Human Liver Diseases)

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19 pages, 1456 KiB

Open AccessArticle

Effects of Oral Administration of Chitin Nanofiber on Plasma Metabolites and Gut Microorganisms

by Kazuo Azuma^1,*, Ryotaro Izumi², Mari Kawata², Tomone Nagae², Tomohiro Osaki¹, Yusuke Murahata¹, Takeshi Tsuka¹, Tomohiro Imagawa¹, Norihiko Ito¹, Yoshiharu Okamoto¹, Minoru Morimoto³, Hironori Izawa², Hiroyuki Saimoto² and Shinsuke Ifuku^2,*

¹ Department of Clinical Veterinary Medicine, Faculty of Agriculture, Tottori University, Tottori 680-8533, Japan

² Graduate School of Engineering, Tottori University, Tottori 680-8552, Japan

³ Division of Instrumental Analysis, Research Center for Bioscience and Technology, Tottori University, Tottori 680-8550, Japan

Int. J. Mol. Sci. 2015, 16(9), 21931-21949; https://doi.org/10.3390/ijms160921931 - 10 Sep 2015

Cited by 16 | Viewed by 9700

Abstract

The aim of this study was to examine the effects of oral administration of chitin nanofibers (CNFs) and surface-deacetylated (SDA) CNFs on plasma metabolites using metabolome analysis. Furthermore, we determined the changes in gut microbiota and fecal organic acid concentrations following oral administrations [...] Read more.

The aim of this study was to examine the effects of oral administration of chitin nanofibers (CNFs) and surface-deacetylated (SDA) CNFs on plasma metabolites using metabolome analysis. Furthermore, we determined the changes in gut microbiota and fecal organic acid concentrations following oral administrations of CNFs and SDACNFs. Healthy female mice (six-week-old) were fed a normal diet and administered tap water with 0.1% (v/v) CNFs or SDACNFs for 28 days. Oral administration of CNFs increased plasma levels of adenosine triphosphate (ATP), adenosine diphosphate (ADP), and serotonin (5-hydroxytryptamine, 5-HT). Oral administration of SDACNFs affected the metabolisms of acyl-carnitines and fatty acids. The fecal organic level analysis indicated that oral administration of CNFs stimulated and activated the functions of microbiota. These results indicate that oral administration of CNFs increases plasma levels of ATP and 5-HT via activation of gut microbiota. Full article

(This article belongs to the Special Issue Chitins 2015)

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9 pages, 764 KiB

Open AccessArticle

New Cytotoxic 24-Homoscalarane Sesterterpenoids from the Sponge Ircinia felix

by Ya-Yuan Lai^1,2,†, Li-Chai Chen^3,4,†, Chug-Fung Wu⁵, Mei-Chin Lu^1,2, Zhi-Hong Wen⁴

, Tung-Ying Wu⁶, Lee-Shing Fang⁷, Li-Hsueh Wang^1,2, Yang-Chang Wu^6,8,9,10,* and Ping-Jyun Sung^1,2,4,6,10,*

¹ Graduate Institute of Marine Biology, National Dong Hwa University, Pingtung 944, Taiwan

² National Museum of Marine Biology & Aquarium, Pingtung 944, Taiwan

³ Department of Pharmacy of Zuoying Branch of Kaohsiung Armed Forces General Hospital, Kaohsiung 813, Taiwan

⁴ Department of Marine Biotechnology and Resources, Asia-Pacific Ocean Research Center, National Sun Yat-sen University, Kaohsiung 804, Taiwan

⁵ Division of Surgical Oncology, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan

⁶ Chinese Medicine Research and Development Center, China Medical University Hospital, Taichung 404, Taiwan

⁷ Department of Sport, Health and Leisure, Cheng Shiu University, Kaohsiung 833, Taiwan

⁸ School of Pharmacy, College of Pharmacy, China Medical University, Taichung 404, Taiwan

⁹ Center for Molecular Medicine, China Medical University Hospital, Taichung 404, Taiwan

¹⁰ Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 807, Taiwan

^† These authors contributed equally to this work.

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Int. J. Mol. Sci. 2015, 16(9), 21950-21958; https://doi.org/10.3390/ijms160921950 - 11 Sep 2015

Cited by 9 | Viewed by 5669

Abstract

Two new 24-homoscalarane sesterterpenoids, felixins F (1) and G (2), were isolated from the sponge Ircinia felix. The structures of new homoscalaranes 1 and 2 were elucidated by extensive spectroscopic methods, particularly with one-dimensional (1D) and two-dimensional (2D) [...] Read more.

Two new 24-homoscalarane sesterterpenoids, felixins F (1) and G (2), were isolated from the sponge Ircinia felix. The structures of new homoscalaranes 1 and 2 were elucidated by extensive spectroscopic methods, particularly with one-dimensional (1D) and two-dimensional (2D) NMR, and, by comparison, the spectral data with those of known analogues. The cytotoxicity of 1 and 2 against the proliferation of a limited panel of tumor cell lines was evaluated and 1 was found to show cytotoxicity toward the leukemia K562, MOLT-4, and SUP-T1 cells (IC₅₀ ≤ 5.0 μM). Full article

(This article belongs to the Special Issue Bioactivity of Marine Natural Products)

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16 pages, 951 KiB

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Metabolite Profiling of Diverse Rice Germplasm and Identification of Conserved Metabolic Markers of Rice Roots in Response to Long-Term Mild Salinity Stress

by Myung Hee Nam^1,†, Eunjung Bang^2,†, Taek Yun Kwon³, Yuran Kim¹, Eun Hee Kim⁴, Kyungwon Cho^1,‡, Woong June Park⁵, Beom-Gi Kim³ and In Sun Yoon^3,*

¹ Environmental Risk and Welfare Research Team, Korea Basic Science Institute, Seoul 02855, Korea

² Omics System Research Team, Korea Basic Science Institute, Seoul 03759, Korea

³ Molecular Breeding Division, National Academy of Agricultural Science, Jeonju 565-851, Korea

⁴ Protein Structure Team, Korea Basic Science Institute, Cheongju 28119, Korea

⁵ Department of Molecular Biology, Institute of Nanosensor and Biotechnology, Dankook University, Yongin-si, Gyeonggi-do 448-701, Korea

^† These authors contributed equally to this work.

^‡ Present address: Metabolic Engineering Division, National Academy of Agricultural Science, Jeonju 565-851, Korea;

Int. J. Mol. Sci. 2015, 16(9), 21959-21974; https://doi.org/10.3390/ijms160921959 - 11 Sep 2015

Cited by 84 | Viewed by 7578

Abstract

The sensitivity of rice to salt stress greatly depends on growth stages, organ types and cultivars. Especially, the roots of young rice seedlings are highly salt-sensitive organs that limit plant growth, even under mild soil salinity conditions. In an attempt to identify metabolic [...] Read more.

The sensitivity of rice to salt stress greatly depends on growth stages, organ types and cultivars. Especially, the roots of young rice seedlings are highly salt-sensitive organs that limit plant growth, even under mild soil salinity conditions. In an attempt to identify metabolic markers of rice roots responding to salt stress, metabolite profiling was performed by ¹H-NMR spectroscopy in 38 rice genotypes that varied in biomass accumulation under long-term mild salinity condition. Multivariate statistical analysis showed separation of the control and salt-treated rice roots and rice genotypes with differential growth potential. By quantitative analyses of ¹H-NMR data, five conserved salt-responsive metabolic markers of rice roots were identified. Sucrose, allantoin and glutamate accumulated by salt stress, whereas the levels of glutamine and alanine decreased. A positive correlation of metabolite changes with growth potential and salt tolerance of rice genotypes was observed for allantoin and glutamine. Adjustment of nitrogen metabolism in rice roots is likely to be closely related to maintain the growth potential and increase the stress tolerance of rice. Full article

(This article belongs to the Special Issue Metabolomics in the Plant Sciences)

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14 pages, 876 KiB

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Molecular Identification of Dendrobium Species (Orchidaceae) Based on the DNA Barcode ITS2 Region and Its Application for Phylogenetic Study

by Shangguo Feng^1,2,*, Yan Jiang³, Shang Wang¹, Mengying Jiang¹, Zhe Chen¹, Qicai Ying¹ and Huizhong Wang^1,*

¹ Zhejiang Provincial Key Laboratory for Genetic Improvement and Quality Control of Medicinal Plants, Hangzhou Normal University, Hangzhou 310018, China

² College of Bioscience & Biotechnology, Hunan Agricultural University, Changsha 410128, China

³ Zhejiang Institute of Chinese Meteria Medica, Hangzhou 310023, China

Int. J. Mol. Sci. 2015, 16(9), 21975-21988; https://doi.org/10.3390/ijms160921975 - 11 Sep 2015

Cited by 66 | Viewed by 9031

Abstract

The over-collection and habitat destruction of natural Dendrobium populations for their commercial medicinal value has led to these plants being under severe threat of extinction. In addition, many Dendrobium plants are similarly shaped and easily confused during the absence of flowering stages. In [...] Read more.

The over-collection and habitat destruction of natural Dendrobium populations for their commercial medicinal value has led to these plants being under severe threat of extinction. In addition, many Dendrobium plants are similarly shaped and easily confused during the absence of flowering stages. In the present study, we examined the application of the ITS2 region in barcoding and phylogenetic analyses of Dendrobium species (Orchidaceae). For barcoding, ITS2 regions of 43 samples in Dendrobium were amplified. In combination with sequences from GenBank, the sequences were aligned using Clustal W and genetic distances were computed using MEGA V5.1. The success rate of PCR amplification and sequencing was 100%. There was a significant divergence between the inter- and intra-specific genetic distances of ITS2 regions, while the presence of a barcoding gap was obvious. Based on the BLAST1, nearest distance and TaxonGAP methods, our results showed that the ITS2 regions could successfully identify the species of most Dendrobium samples examined; Second, we used ITS2 as a DNA marker to infer phylogenetic relationships of 64 Dendrobium species. The results showed that cluster analysis using the ITS2 region mainly supported the relationship between the species of Dendrobium established by traditional morphological methods and many previous molecular analyses. To sum up, the ITS2 region can not only be used as an efficient barcode to identify Dendrobium species, but also has the potential to contribute to the phylogenetic analysis of the genus Dendrobium. Full article

(This article belongs to the Special Issue Plant Molecular Biology)

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19 pages, 1187 KiB

Open AccessArticle

Identification of Ramie Genes in Response to Pratylenchus coffeae Infection Challenge by Digital Gene Expression Analysis

by Yongting Yu

, Liangbin Zeng, Zhun Yan, Touming Liu, Kai Sun, Taotao Zhu and Aiguo Zhu^*

Institute of Bast Fiber Crops, Chinese Academy of Agricultural Sciences, Changsha 410205, China

Int. J. Mol. Sci. 2015, 16(9), 21989-22007; https://doi.org/10.3390/ijms160921989 - 11 Sep 2015

Cited by 20 | Viewed by 6578

Abstract

Root lesion disease, caused by Pratylenchus coffeae, seriously impairs the growth and yield of ramie, an important natural fiber crop. The ramie defense mechanism against P. coffeae infection is poorly understood, which hinders efforts to improve resistance via breeding programs. In this [...] Read more.

Root lesion disease, caused by Pratylenchus coffeae, seriously impairs the growth and yield of ramie, an important natural fiber crop. The ramie defense mechanism against P. coffeae infection is poorly understood, which hinders efforts to improve resistance via breeding programs. In this study, the transcriptome of the resistant ramie cultivar Qingdaye was characterized using Illumina sequence technology. About 46.3 million clean pair end (PE) reads were generated and assembled into 40,826 unigenes with a mean length of 830 bp. Digital gene expression (DGE) analysis was performed on both the control roots (CK) and P. coffeae-challenged roots (CH), and the differentially expressed genes (DEGs) were identified. Approximately 10.16 and 8.07 million cDNA reads in the CK and CH cDNA libraries were sequenced, respectively. A total of 137 genes exhibited different transcript abundances between the two libraries. Among them, the expressions of 117 and 20 DEGs were up- and down-regulated in P. coffeae-challenged ramie, respectively. The expression patterns of 15 candidate genes determined by qRT-PCR confirmed the results of DGE analysis. Time-course expression profiles of eight defense-related genes in susceptible and resistant ramie cultivars were different after P. coffeae inoculation. The differential expression of protease inhibitors, pathogenesis-related proteins (PRs), and transcription factors in resistant and susceptible ramie during P. coffeae infection indicated that cystatin likely plays an important role in nematode resistance. Full article

(This article belongs to the Special Issue Plant Microbe Interaction)

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19 pages, 1457 KiB

Open AccessArticle

Gene Expression of Type VI Secretion System Associated with Environmental Survival in Acidovorax avenae subsp. avenae by Principle Component Analysis

by Zhouqi Cui^1,†, Guoqiang Jin^2,†, Bin Li^1,*, Kaleem Ullah Kakar¹, Mohammad Reza Ojaghian¹, Yangli Wang³, Guanlin Xie¹ and Guochang Sun^3,*

¹ State Key Laboratory of Rice Biology, Institute of Biotechnology, Zhejiang University, Hangzhou 310058, China

² Yuhang Extension and Service Center of Agriculture Technical, Hangzhou 311100, China

³ State Key Laboratory Breeding Base for Zhejiang Sustainable Plant Pest and Disease Control, Key Laboratory of Detection for Pesticide Residues, Ministry of Agriculture, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, China

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2015, 16(9), 22008-22026; https://doi.org/10.3390/ijms160922008 - 11 Sep 2015

Cited by 13 | Viewed by 5527

Abstract

Valine glycine repeat G (VgrG) proteins are regarded as one of two effectors of Type VI secretion system (T6SS) which is a complex multi-component secretion system. In this study, potential biological roles of T6SS structural and VgrG genes in a rice bacterial pathogen, [...] Read more.

Valine glycine repeat G (VgrG) proteins are regarded as one of two effectors of Type VI secretion system (T6SS) which is a complex multi-component secretion system. In this study, potential biological roles of T6SS structural and VgrG genes in a rice bacterial pathogen, Acidovorax avenae subsp. avenae (Aaa) RS-1, were evaluated under seven stress conditions using principle component analysis of gene expression. The results showed that growth of the pathogen was reduced by H₂O₂ and paraquat-induced oxidative stress, high salt, low temperature, and vgrG mutation, compared to the control. However, pathogen growth was unaffected by co-culture with a rice rhizobacterium Burkholderia seminalis R456. In addition, expression of 14 T6SS structural and eight vgrG genes was significantly changed under seven conditions. Among different stress conditions, high salt, and low temperature showed a higher effect on the expression of T6SS gene compared with host infection and other environmental conditions. As a first report, this study revealed an association of T6SS gene expression of the pathogen with the host infection, gene mutation, and some common environmental stresses. The results of this research can increase understanding of the biological function of T6SS in this economically-important pathogen of rice. Full article

(This article belongs to the Section Biochemistry)

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19 pages, 6002 KiB

Open AccessArticle

Size Does Matter: Staging of Silene latifolia Floral Buds for Transcriptome Studies

by Su San Toh^* and Michael H. Perlin^*

Department of Biology, Program on Disease Resistance, University of Louisville, Louisville, KY 40292, USA

Int. J. Mol. Sci. 2015, 16(9), 22027-22045; https://doi.org/10.3390/ijms160922027 - 11 Sep 2015

Cited by 5 | Viewed by 5290

Abstract

Dioecious plants in the Caryophyllaceae family are susceptible to infection by members of the anthericolous smut fungi. In our studies of the Silene latifolia/Microbotryum lychnidis-dioicae pathosystem, we were interested in characterizing the plant-pathogen interaction at the molecular level before and during teliosporogenesis. This [...] Read more.

Dioecious plants in the Caryophyllaceae family are susceptible to infection by members of the anthericolous smut fungi. In our studies of the Silene latifolia/Microbotryum lychnidis-dioicae pathosystem, we were interested in characterizing the plant-pathogen interaction at the molecular level before and during teliosporogenesis. This takes place during floral bud development, and we hoped to capture the interaction by Illumina Next-Gen RNA-Sequencing. Using previous literature that documented the stages of the floral buds for S. latifolia, we examined the floral buds from plants grown and infected under growth chamber conditions, using the disserting microscope to determine the stage of floral buds based on the morphology. We compiled the information and determined the size of floral buds that correspond to the desired stages of development for tissue collection, for the purpose of RNA-sequencing. This offers a practical approach for researchers who require a large number of floral buds/tissue categorized by stages of development, ascertaining whether infected/uninfected buds are at comparable stages of development and whether this also holds true for male vs. female buds. We also document our experience in infecting the plants and some of the unusual morphologies we observed after infection. Full article

(This article belongs to the Special Issue Plant Microbe Interaction)

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16 pages, 4427 KiB

Open AccessArticle

Identification of Conserved and Novel MicroRNAs during Tail Regeneration in the Mexican Axolotl

by Micah D. Gearhart¹, Jami R. Erickson¹, Andrew Walsh^2,3 and Karen Echeverri^1,*

¹ Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN 55455, USA

² Cenix BioScience GmbH, Dresden 01307, Germany

³ Sitools Biotech GmbH, Planegg-Martinsried 82152, Germany

Int. J. Mol. Sci. 2015, 16(9), 22046-22061; https://doi.org/10.3390/ijms160922046 - 11 Sep 2015

Cited by 19 | Viewed by 7223

Abstract

The Mexican axolotl salamander (Ambystoma mexicanum) is one member of a select group of vertebrate animals that have retained the amazing ability to regenerate multiple body parts. In addition to being an important model system for regeneration, the axolotl has also [...] Read more.

The Mexican axolotl salamander (Ambystoma mexicanum) is one member of a select group of vertebrate animals that have retained the amazing ability to regenerate multiple body parts. In addition to being an important model system for regeneration, the axolotl has also contributed extensively to studies of basic development. While many genes known to play key roles during development have now been implicated in various forms of regeneration, much of the regulatory apparatus controlling the underlying molecular circuitry remains unknown. In recent years, microRNAs have been identified as key regulators of gene expression during development, in many diseases and also, increasingly, in regeneration. Here, we have used deep sequencing combined with qRT-PCR to undertake a comprehensive identification of microRNAs involved in regulating regeneration in the axolotl. Specifically, among the microRNAs that we have found to be expressed in axolotl tissues, we have identified 4564 microRNA families known to be widely conserved among vertebrates, as well as 59,811 reads of putative novel microRNAs. These findings support the hypothesis that microRNAs play key roles in managing the precise spatial and temporal patterns of gene expression that ensures the correct regeneration of missing tissues. Full article

(This article belongs to the Special Issue Molecular and Cellular Basis of Regeneration and Tissue Repair)

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19 pages, 984 KiB

Open AccessArticle

Inhibition of Hepatocyte Apoptosis: An Important Mechanism of Corn Peptides Attenuating Liver Injury Induced by Ethanol

by Zhili Ma, Tao Hou, Wen Shi, Weiwei Liu and Hui He^*

College of Food Science and Technology, Huazhong Agricultural University & Key Laboratory of Environment Correlative Dietology, Ministry of Education, Wuhan 430070, China

Int. J. Mol. Sci. 2015, 16(9), 22062-22080; https://doi.org/10.3390/ijms160922062 - 11 Sep 2015

Cited by 33 | Viewed by 6642

Abstract

In this study, the effects of mixed corn peptides and synthetic pentapeptide (QLLPF) on hepatocyte apoptosis induced by ethanol were investigated in vivo. QLLPF, was previously characterized from corn protein hydrolysis, which had been shown to exert good facilitating alcohol metabolism activity. [...] Read more.

In this study, the effects of mixed corn peptides and synthetic pentapeptide (QLLPF) on hepatocyte apoptosis induced by ethanol were investigated in vivo. QLLPF, was previously characterized from corn protein hydrolysis, which had been shown to exert good facilitating alcohol metabolism activity. Mice were pre-treated with the mixed corn peptides and the pentapeptide for 1 week and then treated with ethanol. After treatment of three weeks, the biochemical indices and the key ethanol metabolizing enzymes, the serum TNF-α, liver TGF-β1 concentrations and the protein expressions related to apoptosis were determined. We found that the Bcl-2, Bax and cytochrome c expressions in the intrinsic pathway and the Fas, FasL and NF-κB expressions in the extrinsic pathway together with higher TNF-α and TGF-β1 concentrations were reversed compared with the model group by both the mixed corn peptides and the pentapeptide. The activation of caspase3 was also suppressed. Additionally, apoptosis was further confirmed with terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and the TUNEL assay demonstrated peptides suppressed hepatocyte apoptosis. Our results suggest that apoptosis induced by ethanol is alleviated in response to the treatment of corn peptides, potentially due to reversing the related protein expression. Full article

(This article belongs to the Section Biochemistry)

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13 pages, 1501 KiB

Open AccessArticle

Maternal PUFA ω-3 Supplementation Prevents Neonatal Lung Injuries Induced by Hyperoxia in Newborn Rats

by Dyuti Sharma^1,2, Armande Subayi Nkembi¹, Estelle Aubry^1,2, Ali Houeijeh^1,3, Laura Butruille¹, Véronique Houfflin-Debarge^1,4, Rémi Besson^1,2, Philippe Deruelle^1,4 and Laurent Storme^1,3,*

¹ EA 4489 Environnement Périnatal et Santé, Pôle Recherche Faculté de Médecine, Université Lille Nord de France, Lille 59045, France

² Clinique de Chirurgie et Orthopédie de l'Enfant, Pôle Enfant, Hôpital Jeanne de Flandre, CHRU Lille, Lille 59037, France

³ Clinique de Néonatologie, Pôle Femme, Mère et Nouveau-Né, Hôpital Jeanne de Flandre, CHRU Lille, Lille 59037, France

⁴ Clinique de Gynécologie-Obstétrique, Pôle Femme, Mère et Nouveau-Né, Hôpital Jeanne de Flandre, CHRU Lille, Lille 59037, France

Int. J. Mol. Sci. 2015, 16(9), 22081-22093; https://doi.org/10.3390/ijms160922081 - 14 Sep 2015

Cited by 21 | Viewed by 5566

Abstract

Bronchopulmonary dysplasia (BPD) is one of the most common complications of prematurity, occurring in 30% of very low birth weight infants. The benefits of dietary intake of polyunsaturated fatty acids ω-3 (PUFA ω-3) during pregnancy or the perinatal period have been reported. The [...] Read more.

Bronchopulmonary dysplasia (BPD) is one of the most common complications of prematurity, occurring in 30% of very low birth weight infants. The benefits of dietary intake of polyunsaturated fatty acids ω-3 (PUFA ω-3) during pregnancy or the perinatal period have been reported. The aim of this study was to assess the effects of maternal PUFA ω-3 supplementation on lung injuries in newborn rats exposed to prolonged hyperoxia. Pregnant female Wistar rats (n = 14) were fed a control diet (n = 2), a PUFA ω-6 diet (n = 6), or a PUFA ω-3 diet (n = 6), starting with the 14th gestation day. At Day 1, female and newborn rats (10 per female) were exposed to hyperoxia (O₂, n = 70)or to the ambient air (Air, n = 70). Six groups of newborns rats were obtained: PUFA ω-6/O₂ (n = 30), PUFA ω-6/air (n = 30), PUFA ω-3/O₂ (n = 30), PUFA ω-3/air (n = 30), control/O₂ (n = 10), and control/air (n = 10). After 10 days, lungs were removed for analysis of alveolarization and pulmonary vascular development. Survival rate was 100%. Hyperoxia reduced alveolarization and increased pulmonary vascular wall thickness in both control (n = 20) and PUFA ω-6 groups (n = 60). Maternal PUFA ω-3 supplementation prevented the decrease in alveolarization caused by hyperoxia (n = 30) compared to PUFA ω-6/O₂ (n = 30) or to the control/O₂ (n = 10), but did not significantly increase the thickness of the lung vascular wall. Therefore, maternal PUFA ω-3 supplementation may protect newborn rats from lung injuries induced by hyperoxia. In clinical settings, maternal PUFA ω-3 supplementation during pregnancy and during lactation may prevent BPD development after premature birth. Full article

(This article belongs to the Special Issue Omega-3 Fatty Acids in Health and Diseases)

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14 pages, 3084 KiB

Open AccessArticle

RETRACTED: MiR-122 Induces Radiosensitization in Non-Small Cell Lung Cancer Cell Line

by Debin Ma¹, Hui Jia², Mengmeng Qin¹, Wenjie Dai³, Tao Wang⁴, Erguang Liang⁴, Guofu Dong⁵, Zuojun Wang², Zhiyuan Zhang^1,* and Fan Feng^2,*

¹ Department of Respiratory Diseases, General Hospital of Shenyang Military Command, Shenyang 110016, China

² Department of Pharmacy, General Hospital of Shenyang Military Command, Shenyang 110016, China

³ Department of Pharmacy, Beijing Chuiyangliu Hospital Affiliated to Tsinghua University, Beijing 100022, China

⁴ Institute of Toxicology and Pharmacology, Medicine Military Medical Science Academy of the Chinese PLA, Beijing 100850, China

⁵ Institute of Radiation, Medicine Military Medical Science Academy of the Chinese PLA, Beijing 100850, China

Int. J. Mol. Sci. 2015, 16(9), 22137-22150; https://doi.org/10.3390/ijms160922137 - 14 Sep 2015

Cited by 46 | Viewed by 6026 | Retraction

Abstract

MiR-122 is a novel tumor suppresser and its expression induces cell cycle arrest, or apoptosis, and inhibits cell proliferation in multiple cancer cells, including non-small cell lung cancer (NSCLC) cells. Radioresistance of cancer cell leads to the major drawback of radiotherapy for NSCLC [...] Read more.

MiR-122 is a novel tumor suppresser and its expression induces cell cycle arrest, or apoptosis, and inhibits cell proliferation in multiple cancer cells, including non-small cell lung cancer (NSCLC) cells. Radioresistance of cancer cell leads to the major drawback of radiotherapy for NSCLC and the induction of radiosensitization could be a useful strategy to fix this problem. The present work investigates the function of miR-122 in inducing radiosensitization in A549 cell, a type of NSCLC cells. MiR-122 induces the radiosensitization of A549 cells. MiR-122 also boosts the inhibitory activity of ionizing radiation (IR) on cancer cell anchor-independent growth and invasion. Moreover, miR-122 reduced the expression of its targeted genes related to tumor-survival or cellular stress response. These results indicate that miR-122 would be a novel strategy for NSCLC radiation-therapy. Full article

(This article belongs to the Special Issue MicroRNA Regulation)

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15 pages, 5454 KiB

Open AccessArticle

In Silico Analysis and Experimental Validation of Active Compounds from Cichorium intybus L. Ameliorating Liver Injury

by Guo-Yu Li¹, Ya-Xin Zheng², Fu-Zhou Sun², Jian Huang², Meng-Meng Lou³, Jing-Kai Gu^1,* and Jin-Hui Wang^2,3,*

¹ Research Center for Drug Metabolism, College of Life Science, Jilin University, Changchun 130012, China

² School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China

³ School of Pharmacy, Shihezi University, Shihezi 832002, China

Int. J. Mol. Sci. 2015, 16(9), 22190-22204; https://doi.org/10.3390/ijms160922190 - 14 Sep 2015

Cited by 12 | Viewed by 7478

Abstract

This study aimed at investigating the possible mechanisms of hepatic protective activity of Cichorium intybus L. (chicory) in acute liver injury. Pathological observation, reactive oxygen species (ROS) detection and measurements of biochemical indexes on mouse models proved hepatic protective effect of Cichorium intybus [...] Read more.

This study aimed at investigating the possible mechanisms of hepatic protective activity of Cichorium intybus L. (chicory) in acute liver injury. Pathological observation, reactive oxygen species (ROS) detection and measurements of biochemical indexes on mouse models proved hepatic protective effect of Cichorium intybus L. Identification of active compounds in Cichorium intybus L. was executed through several methods including ultra performance liquid chromatography/time of flight mass spectrometry (UPLC-TOF-MS). Similarity ensemble approach (SEA) docking, molecular modeling, molecular docking, and molecular dynamics (MD) simulation were applied in this study to explore possible mechanisms of the hepato-protective potential of Cichorium intybus L. We then analyzed the chemical composition of Cichorium intybus L., and found their key targets. Furthermore, in vitro cytological examination and western blot were used for validating the efficacy of the selected compounds. In silico analysis and western blot together demonstrated that selected compound 10 in Cichorium intybus L. targeted Akt-1 in hepatocytes. Besides, compound 13 targeted both caspase-1 and Akt-1. These small compounds may ameliorate liver injury by acting on their targets, which are related to apoptosis or autophagy. The conclusions above may shed light on the complex molecular mechanisms of Cichorium intybus L. acting on hepatocytes and ameliorating liver injury. Full article

(This article belongs to the Special Issue Bioactive Phytochemicals and Functional Food Ingredients in Fruits and Vegetables)

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18 pages, 13382 KiB

Open AccessArticle

Selenium-Substituted Hydroxyapatite/Biodegradable Polymer/Pamidronate Combined Scaffold for the Therapy of Bone Tumour

by Ewa Oledzka^1,*

, Marcin Sobczak¹, Joanna Kolmas¹

and Grzegorz Nalecz-Jawecki²

¹ Department of Inorganic and Analytical Chemistry, Faculty of Pharmacy with the Laboratory Medicine Division, Medical University of Warsaw, Banacha 1, Warsaw 02-097, Poland

² Department of Environmental Health Science, Faculty of Pharmacy with the Laboratory Medicine Division, Medical University of Warsaw, Banacha 1,Warsaw 02-097, Poland

Int. J. Mol. Sci. 2015, 16(9), 22205-22222; https://doi.org/10.3390/ijms160922205 - 14 Sep 2015

Cited by 16 | Viewed by 6032

Abstract

The present study evaluated a new concept of combined scaffolds as a promising bone replacement material for patients with a bone tumour or bone metastasis. The scaffolds were composed of hydroxyapatite doped with selenium ions and a biodegradable polymer (linear or branched), and [...] Read more.

The present study evaluated a new concept of combined scaffolds as a promising bone replacement material for patients with a bone tumour or bone metastasis. The scaffolds were composed of hydroxyapatite doped with selenium ions and a biodegradable polymer (linear or branched), and contained an active substance—bisphosphonate. For this purpose, a series of biodegradable polyesters were synthesized through a ring-opening polymerization of ε-caprolactone or d,l-lactide in the presence of 2-hydroxyethyl methacrylate (HEMA) or hyperbranched 2,2-bis(hydroxymethyl)propionic acid polyester-16-hydroxyl (bis-MPA) initiators, substances often used in the synthesis of medical materials. The polymers were obtained with a high yield and a number-average molecular weight up to 45,300 (g/mol). The combined scaffolds were then manufactured by a direct compression of pre-synthesized hydroxyapatite doped with selenite or selenate ions, obtained polymer and pamidronate as a model drug. It was found that the kinetic release of the drug from the scaffolds tested in vitro under physiological conditions is strongly dependent on the physicochemical properties and average molecular weight of the polymers. Furthermore, there was good correlation with the hydrolytic biodegradation results of the scaffolds fabricated without drug. The preliminary findings suggest that the fabricated combined scaffolds could be effectively used for the sustained delivery of bioactive molecules at bone defect sites. Full article

(This article belongs to the Special Issue Biomaterials for Tissue Engineering)

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20 pages, 8853 KiB

Open AccessArticle

Duplex High-Resolution Melting Assay for the Simultaneous Genotyping of IL28B rs12979860 and PNPLA3 rs738409 Polymorphisms in Chronic Hepatitis C Patients

by Elena L. Enache¹, Anca Sin^1,2, Ligia Bancu^1,2,*, Christophe Ramière^3,4,5,6,7,8, Olivier Diaz^3,4,5,6,7, Patrice André^3,4,5,6,7,8 and Liviu S. Enache^1,2

¹ University of Medicine and Pharmacy Tirgu Mures, 38 Gh. Marinescu st., Tirgu Mures 540142, Romania

² Emergency County Clinical Hospital, 50 Gh. Marinescu st., Tirgu Mures 540136, Romania

³ Université de Lyon, Université Lyon 1, Lyon F-69008, France

⁴ Inserm U1111, 21 Avenue Tony Garnier, Lyon F-69007, France

⁵ CIRI, Centre International de Recherche en Infectiologie, Université de Lyon, 21 Avenue Tony Garnier, 69365 Lyon Cedex 07, France

⁶ Ecole Normale Supérieure de Lyon, 15 parvis René Descartes, BP 7000 69342 Lyon Cedex 07, France

⁷ CNRS, UMR5308, 21 avenue Tony Garnier, 69365 Lyon Cedex 07, France

⁸ Hospices Civils de Lyon, Hôpital de la Croix Rousse, Laboratoire de Virologie, Lyon F-69004, France

Int. J. Mol. Sci. 2015, 16(9), 22223-22242; https://doi.org/10.3390/ijms160922223 - 14 Sep 2015

Cited by 4 | Viewed by 6276

Abstract

Chronic hepatitis C (CHC) is a major burden for public health worldwide. Although newer direct-acting antivirals show good efficacy, their cost precludes their wide adoption in resource-limited regions. Thus, strategies are being developed to help identify patients with high susceptibility to response to [...] Read more.

Chronic hepatitis C (CHC) is a major burden for public health worldwide. Although newer direct-acting antivirals show good efficacy, their cost precludes their wide adoption in resource-limited regions. Thus, strategies are being developed to help identify patients with high susceptibility to response to classic PEG-interferon + ribavirin therapy. IL28B polymorphism rs12979860 C/T is an important predictor for an efficient response to interferon-based therapy. A genetic variant in adiponutrin (PNPLA3) gene, rs738409 C/G, is associated with steatosis, severity, and progression of liver fibrosis in CHC patients, and predicts treatment outcome in difficult-to-cure HCV-infected patients with advanced fibrosis. We developed a rapid and inexpensive assay based on duplex high-resolution melting (HRM) for the simultaneous genotyping of these two polymorphisms. The assay validation was performed on synthetic DNA templates and 132 clinical samples from CHC patients. When compared with allele-specific PCR and sequencing, our assay showed 100% (95% CI: 0.9724–1) accuracy, with 100% sensitivity and specificity. Our assay was robust against concentration and quality of DNA samples, melting curve normalization intervals, HRM analysis algorithm, and sequence variations near the targeted SNPs (single nucleotide polymorphism). This duplex assay should provide useful information for patient-oriented management and clinical decision-making in CHC. Full article

(This article belongs to the Special Issue Human Single Nucleotide Polymorphisms and Disease Diagnostics)

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15 pages, 2340 KiB

Open AccessArticle

Characterization, Quantification, and Determination of the Toxicity of Iron Oxide Nanoparticles to the Bone Marrow Cells

by Sae-Yeol-Rim Paik^1,†, Jong-Seok Kim^2,†, Sung Jae Shin² and Sanghoon Ko^1,*

¹ Department of Food Science and Technology, Sejong University, 209 Neungdong-ro, Gwangjin-gu, Seoul 143-747, Korea

² Department of Microbiology and Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Korea

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2015, 16(9), 22243-22257; https://doi.org/10.3390/ijms160922243 - 14 Sep 2015

Cited by 34 | Viewed by 6373

Abstract

Iron oxide nanoparticles (IONPs) have been used to develop iron supplements for improving the bioavailability of iron in patients with iron deficiency, which is one of the most serious nutritional deficiencies in the world. Accurate information about the characteristics, concentration, and cytotoxicity of [...] Read more.

Iron oxide nanoparticles (IONPs) have been used to develop iron supplements for improving the bioavailability of iron in patients with iron deficiency, which is one of the most serious nutritional deficiencies in the world. Accurate information about the characteristics, concentration, and cytotoxicity of IONPs to the developmental and reproductive cells enables safe use of IONPs in the supplement industry. The objective of this study was to analyze the physicochemical properties and cytotoxicity of IONPs in bone marrow cells. We prepared three different types of iron samples (surface-modified iron oxide nanoparticles (SMNPs), IONPs, and iron citrate) and analyzed their physicochemical properties such as particle size distribution, zeta potential, and morphology. In addition, we examined the cytotoxicity of the IONPs in various kinds of bone marrow cells. We analyzed particle size distribution, zeta potential, iron levels, and subcellular localization of the iron samples in bone marrow cells. Our results showed that the iron samples were not cytotoxic to the bone marrow cells and did not affect the expression of cell surface markers and lipopolysaccharide (LPS)-induced the secretion of cytokines by murine bone marrow-derived dendritic cells (BMDCs). Our results may be used to investigate the interactions between nanoparticles and cells and tissues and the developmental toxicity of nanoparticles. Full article

(This article belongs to the Special Issue Developmental and Reproductive Toxicity of Iron Oxide Nanoparticles)

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22 pages, 5706 KiB

Open AccessArticle

Genomic Resources of Three Pulsatilla Species Reveal Evolutionary Hotspots, Species-Specific Sites and Variable Plastid Structure in the Family Ranunculaceae

by Monika Szczecińska^1,* and Jakub Sawicki^1,2

¹ Department of Botany and Nature Protection, University of Warmia and Mazury, 10-728 Olsztyn, Poland

² Department of Biology and Ecology, University of Ostrava, 71000 Ostrava, Czech Republic

Int. J. Mol. Sci. 2015, 16(9), 22258-22279; https://doi.org/10.3390/ijms160922258 - 15 Sep 2015

Cited by 32 | Viewed by 7909

Abstract

Background: The European continent is presently colonized by nine species of the genus Pulsatilla, five of which are encountered only in mountainous regions of southwest and south-central Europe. The remaining four species inhabit lowlands in the north-central and eastern parts of the [...] Read more.

Background: The European continent is presently colonized by nine species of the genus Pulsatilla, five of which are encountered only in mountainous regions of southwest and south-central Europe. The remaining four species inhabit lowlands in the north-central and eastern parts of the continent. Most plants of the genus Pulsatilla are rare and endangered, which is why most research efforts focused on their biology, ecology and hybridization. The objective of this study was to develop genomic resources, including complete plastid genomes and nuclear rRNA clusters, for three sympatric Pulsatilla species that are most commonly found in Central Europe. The results will supply valuable information about genetic variation, which can be used in the process of designing primers for population studies and conservation genetics research. The complete plastid genomes together with the nuclear rRNA cluster can serve as a useful tool in hybridization studies. Methodology/principal findings: Six complete plastid genomes and nuclear rRNA clusters were sequenced from three species of Pulsatilla using the Illumina sequencing technology. Four junctions between single copy regions and inverted repeats and junctions between the identified locally-collinear blocks (LCB) were confirmed by Sanger sequencing. Pulsatilla genomes of 120 unique genes had a total length of approximately 161–162 kb, and 21 were duplicated in the inverted repeats (IR) region. Comparative plastid genomes of newly-sequenced Pulsatilla and the previously-identified plastomes of Aconitum and Ranunculus species belonging to the family Ranunculaceae revealed several variations in the structure of the genome, but the gene content remained constant. The nuclear rRNA cluster (18S-ITS1-5.8S-ITS2-26S) of studied Pulsatilla species is 5795 bp long. Among five analyzed regions of the rRNA cluster, only Internal Transcribed Spacer 2 (ITS2) enabled the molecular delimitation of closely-related Pulsatilla patens and Pulsatilla vernalis. Conclusions/significance: The determination of complete plastid genome and nuclear rRNA cluster sequences in three species of the genus Pulsatilla is an important contribution to our knowledge of the evolution and phylogeography of those endangered taxa. The resulting data can be used to identify regions that are particularly useful for barcoding, phylogenetic and phylogeographic studies. The investigated taxa can be identified at each stage of development based on their species-specific SNPs. The nuclear and plastid genomic resources enable advanced studies on hybridization, including identification of parent species, including their roles in that process. The identified nonsynonymous mutations could play an important role in adaptations to changing environments. The results of the study will also provide valuable information about the evolution of the plastome structure in the family Ranunculaceae. Full article

(This article belongs to the Special Issue Plant Molecular Biology)

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19 pages, 2904 KiB

Open AccessArticle

Physcomitrella patens Activates Defense Responses against the Pathogen Colletotrichum gloeosporioides

by Guillermo Reboledo¹, Raquel Del Campo¹, Alfonso Alvarez^1,2, Marcos Montesano², Héctor Mara¹ and Inés Ponce de León^1,*

¹ Department of Molecular Biology, Clemente Estable Biological Research Institute, Avenida Italia 3318, CP 11600 Montevideo, Uruguay

² Laboratory of Plant Physiology, Nuclear Research Center, Faculty of Sciences, Mataojo 2055, CP 11400 Montevideo, Uruguay

Int. J. Mol. Sci. 2015, 16(9), 22280-22298; https://doi.org/10.3390/ijms160922280 - 15 Sep 2015

Cited by 53 | Viewed by 9350

Abstract

The moss Physcomitrella patens is a suitable model plant to analyze the activation of defense mechanisms after pathogen assault. In this study, we show that Colletotrichum gloeosporioides isolated from symptomatic citrus fruit infects P. patens and cause disease symptoms evidenced by browning and [...] Read more.

The moss Physcomitrella patens is a suitable model plant to analyze the activation of defense mechanisms after pathogen assault. In this study, we show that Colletotrichum gloeosporioides isolated from symptomatic citrus fruit infects P. patens and cause disease symptoms evidenced by browning and maceration of tissues. After C. gloeosporioides infection, P. patens reinforces the cell wall by the incorporation of phenolic compounds and induces the expression of a Dirigent-protein-like encoding gene that could lead to the formation of lignin-like polymers. C. gloeosporioides-inoculated protonemal cells show cytoplasmic collapse, browning of chloroplasts and modifications of the cell wall. Chloroplasts relocate in cells of infected tissues toward the initially infected C. gloeosporioides cells. P. patens also induces the expression of the defense genes PAL and CHS after fungal colonization. P. patens reporter lines harboring the auxin-inducible promoter from soybean (GmGH3) fused to β-glucuronidase revealed an auxin response in protonemal tissues, cauloids and leaves of C. gloeosporioides-infected moss tissues, indicating the activation of auxin signaling. Thus, P. patens is an interesting plant to gain insight into defense mechanisms that have evolved in primitive land plants to cope with microbial pathogens. Full article

(This article belongs to the Special Issue Plant Microbe Interaction)

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20 pages, 965 KiB

Open AccessArticle

Association of Nicotinamide Phosphoribosyltransferase (NAMPT) Gene Polymorphisms and of Serum NAMPT Levels with Dilated Cardiomyopathy in a Chinese Population

by Qingyu Dou^1,†, Ying Peng^1,†, Bin Zhou^2,3, Kui Zhang⁴, Jing Lin¹, Xiaohui Dai¹, Lin Zhang^2,3 and Li Rao^1,*

¹ Department of Cardiology, West China Hospital of Sichuan University, Chengdu 610041, China

² Key Laboratory of Obstetric & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu 610041, China

³ Laboratory of Molecular Translational Medicine, West China Institute of Women and Children's Health, West China Second University Hospital, Sichuan University, Chengdu 610041, China

⁴ Department of Forensic Pathology, Sichuan University, Chengdu 610041, China

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2015, 16(9), 22299-22318; https://doi.org/10.3390/ijms160922299 - 15 Sep 2015

Cited by 10 | Viewed by 6196

Abstract

Nicotinamide phosphoribosyltransferase (NAMPT) has crucial roles for myocardial development, cardiomyocyte energy metabolism and cell death/survival by regulating NAD⁺-dependent sirtuin-1 (SIRT1) deacetylase. This study aimed to determine if the single nucleotide polymorphisms (SNPs) of the NAMPT gene may affect the susceptibility and [...] Read more.

Nicotinamide phosphoribosyltransferase (NAMPT) has crucial roles for myocardial development, cardiomyocyte energy metabolism and cell death/survival by regulating NAD⁺-dependent sirtuin-1 (SIRT1) deacetylase. This study aimed to determine if the single nucleotide polymorphisms (SNPs) of the NAMPT gene may affect the susceptibility and prognosis for patients with dilated cardiomyopathy (DCM) and to describe the association of serum NAMPT levels with clinical features of DCM. Three SNPs (rs61330082, rs2505568, and rs9034) were analyzed by the polymerase chain reaction-restriction fragment length polymorphism method in a case-control study of 394 DCM patients and 395 controls from China. Serum NAMPT levels were measured by enzyme-linked immunosorbent assay kits. The homozygote for the minor allele at rs2505568 and rs9034 could not be detected in this study. Rs9034 T allele and CT genotype were associated with increased DCM risk (OR: 1.63, 95% CI = 1.16–2.27, p = 0.005 and OR: 1.72, 95% CI = 1.20–2.50, p = 0.0027, respectively). Nominally significant decreased DCM risk was found to be associated with the A allele and AT genotype of rs2505568 (OR: 0.48, 95% CI = 0.35–0.67, p < 0.0001 and OR: 0.44, 95% CI = 0.31–0.62, p < 0.0001, respectively), but it should be interpreted with caution because of Hardy-Weinberg disequilibrium in the control group. Of five haplotypes constructed, TAC (rs61330082-rs2505568-rs9034) was a protective haplotype to DCM (OR: 0.22, 95% CI = 0.13–0.39, p = 1.84 × 10⁻⁸). The Cox multivariate survival analysis indicated that the rs9034 CT genotype (hazard ratio (HR): 0.59, 95% CI = 0.37–0.96, p = 0.03) was an independently multivariate predictor for longer overall survival in DCM patients. Serum NAMPT levels were significantly higher in the DCM group than controls (p < 0.0001) and gradually increased with the increase of New York Heart Association grade in DCM patients. However, there was a lack of association of the three SNPs with serum NAMPT levels. Spearman correlation test revealed that the NAMPT level was positively associated with brain natriuretic peptide (r = 0.56, p = 0.001), left ventricular end-diastolic diameter (r = 0.293, p = 0.011) and left ventricular end-diastolic volume (r = 0.294, p = 0.011). Our study suggested that NAMPT may play an important role in the development of DCM. Full article

(This article belongs to the Special Issue Human Single Nucleotide Polymorphisms and Disease Diagnostics)

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18 pages, 1234 KiB

Open AccessArticle

Gardenamide A Protects RGC-5 Cells from H₂O₂-Induced Oxidative Stress Insults by Activating PI3K/Akt/eNOS Signaling Pathway

by Rikang Wang^1,†, Lizhi Peng^2,†, Jiaqiang Zhao², Laitao Zhang², Cuiping Guo², Wenhua Zheng^3,* and Heru Chen^2,4,*

¹ National Pharmaceutical Engineering Center for Solid Preparation in Chinese Herbal Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang 330006, China

² Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou 510632, China

³ Faculty of Health Sciences, University of Macao, Macao, China

⁴ Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Guangzhou 510632, China

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2015, 16(9), 22350-22367; https://doi.org/10.3390/ijms160922350 - 15 Sep 2015

Cited by 40 | Viewed by 6414

Abstract

Gardenamide A (GA) protects the rat retinal ganglion (RGC-5) cells against cell apoptosis induced by H₂O₂. The protective effect of GA was completely abrogated by the specific phosphoinositide 3-kinase (PI3K) inhibitor LY294002, and the specific protein kinase B (Akt) [...] Read more.

Gardenamide A (GA) protects the rat retinal ganglion (RGC-5) cells against cell apoptosis induced by H₂O₂. The protective effect of GA was completely abrogated by the specific phosphoinositide 3-kinase (PI3K) inhibitor LY294002, and the specific protein kinase B (Akt) inhibitor Akt VIII respectively, indicating that the protective mechanism of GA is mediated by the PI3K/Akt signaling pathway. The specific extracellular signal-regulated kinase (ERK1/2) inhibitor PD98059 could not block the neuroprotection of GA. GA attenuated the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) induced by H₂O₂. Western blotting showed that GA promoted the phosphorylation of ERK1/2, Akt and endothelial nitric oxide synthase (eNOS), respectively, and effectively reversed the H₂O₂-inhibited phosphorylation of these three proteins. LY294002 completely inhibited the GA-activated phosphorylation of Akt, while only partially inhibiting eNOS. This evidence implies that eNOS may be activated directly by GA. PD98059 attenuated only partially the GA-induced phosphorylation of ERK1/2 with/without the presence of H₂O₂, indicating that GA may activate ERK1/2 directly. All these results put together confirm that GA protects RGC-5 cells from H₂O₂ insults via the activation of PI3K/Akt/eNOS signaling pathway. Whether the ERK1/2 signaling pathway is involved requires further investigations. Full article

(This article belongs to the Section Biochemistry)

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13 pages, 10557 KiB

Open AccessArticle

Structure Conservation and Differential Expression of Farnesyl Diphosphate Synthase Genes in Euphorbiaceous Plants

by Dong Guo, Hui-Liang Li and Shi-Qing Peng^*

Key Laboratory of Tropical Crop Biotechnology, Ministry of Agriculture, Institute of Tropical Bioscience and Biotechnology, Chinese Academy of Tropical Agricultural Sciences, Haikou 571101, China

Int. J. Mol. Sci. 2015, 16(9), 22402-22414; https://doi.org/10.3390/ijms160922402 - 15 Sep 2015

Cited by 11 | Viewed by 5691

Abstract

Farnesyl diphosphate synthase (FPS) is a key enzyme of isoprenoids biosynthesis. However, knowledge of the FPSs of euphorbiaceous species is limited. In this study, ten FPSs were identified in four euphorbiaceous plants. These FPSs exhibited similar exon/intron structure. The deduced FPS proteins [...] Read more.

Farnesyl diphosphate synthase (FPS) is a key enzyme of isoprenoids biosynthesis. However, knowledge of the FPSs of euphorbiaceous species is limited. In this study, ten FPSs were identified in four euphorbiaceous plants. These FPSs exhibited similar exon/intron structure. The deduced FPS proteins showed close identities and exhibited the typical structure of plant FPS. The members of the FPS family exhibit tissue expression patterns that vary among several euphorbiaceous plant species under normal growth conditions. The expression profiles reveal spatial and temporal variations in the expression of FPSs of different tissues from Euphorbiaceous plants. Our results revealed wide conservation of FPSs and diverse expression in euphorbiaceous plants during growth and development. Full article

(This article belongs to the Special Issue Plant Molecular Biology)

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10 pages, 1423 KiB

Open AccessArticle

The Effect of Coatings on the Affinity of Lanthanide Nanoparticles to MKN45 and HeLa Cancer Cells and Improvement in Photodynamic Therapy Efficiency

by Takashi Sawamura¹, Tatsumi Tanaka¹, Hiroyuki Ishige¹, Masayuki Iizuka¹, Yasutoshi Murayama², Eigo Otsuji², Akihiro Ohkubo¹, Shun-Ichiro Ogura¹ and Hideya Yuasa^1,*

¹ Department of Life Science, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, J2-10, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan

² Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto 602-8566, Japan

Int. J. Mol. Sci. 2015, 16(9), 22415-22424; https://doi.org/10.3390/ijms160922415 - 16 Sep 2015

Cited by 13 | Viewed by 7078

Abstract

An improvement in photodynamic therapy (PDT) efficiency against a human gastric cancer cell line (MKN45) with 5-aminolevulinic acid (ALA) and lanthanide nanoparticles (LNPs) is described. An endogenous photosensitizer, protoporphyrin IX, biosynthesized from ALA and selectively accumulated in cancer cells, is sensitizable by the [...] Read more.

An improvement in photodynamic therapy (PDT) efficiency against a human gastric cancer cell line (MKN45) with 5-aminolevulinic acid (ALA) and lanthanide nanoparticles (LNPs) is described. An endogenous photosensitizer, protoporphyrin IX, biosynthesized from ALA and selectively accumulated in cancer cells, is sensitizable by the visible lights emitted from up-conversion LNPs, which can be excited by a near-infrared light. Ten kinds of surface modifications were performed on LNPs, NaYF₄(Sc/Yb/Er) and NaYF₄(Yb/Tm), in an aim to distribute these irradiation light sources near cancer cells. Among these LNPs, only the amino-functionalized LNPs showed affinity to MKN45 and HeLa cancer cells. A PDT assay with MKN45 demonstrated that amino-modified NaYF₄(Sc/Yb/Er) gave rise to a dramatically enhanced PDT effect, reaching almost perfect lethality, whereas NaYF₄(Yb/Tm)-based systems caused little improvement in PDT efficiency. The improvement of PDT effect with the amino-modified NaYF₄(Sc/Yb/Er) is promising for a practical PDT against deep cancer cells that are reachable only by near-infrared lights. Full article

(This article belongs to the Special Issue Advances in Photodynamic Therapy)

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13 pages, 2151 KiB

Open AccessArticle

K88 Fimbrial Adhesin Targeting of Microspheres Containing Gentamicin Made with Albumin Glycated with Lactose

by Andre-i Sarabia-Sainz^1,2, Hector Manuel Sarabia-Sainz^2,3, Gabriela Ramos-Clamont Montfort²

, Veronica Mata-Haro²

, Ana María Guzman-Partida², Roberto Guzman⁴, Mariano Garcia-Soto⁴ and Luz Vazquez-Moreno^2,*

¹ Departamento de Investigacion en Fisica, Universidad de Sonora, Hermosillo Sonora 83000, Mexico

² Laboratorio de Bioquimica de Proteinas y Glicanos, Coordinacion de Ciencia de los Alimentos, Centro de Investigacion en Alimentacion y Desarrollo A.C., Hermosillo Sonora 83304, Mexico

³ Departamento de Investigacion y Posgrado en Alimentos, Universidad de Sonora, Hermosillo Sonora 83000, Mexico

⁴ Department of Chemical and Environmental Engineering, the University of Arizona, Tucson, AZ 85721, USA

Int. J. Mol. Sci. 2015, 16(9), 22425-22437; https://doi.org/10.3390/ijms160922425 - 16 Sep 2015

Cited by 2 | Viewed by 5886

Abstract

The formulation and characterization of gentamicin-loaded microspheres as a delivery system targeting enterotoxigenic Escherichia coli K88 (E. coli K88) was investigated. Glycated albumin with lactose (BSA-glucose-β (4-1) galactose) was used as the microsphere matrix (MS-Lac) and gentamicin included as the transported antibiotic. [...] Read more.

The formulation and characterization of gentamicin-loaded microspheres as a delivery system targeting enterotoxigenic Escherichia coli K88 (E. coli K88) was investigated. Glycated albumin with lactose (BSA-glucose-β (4-1) galactose) was used as the microsphere matrix (MS-Lac) and gentamicin included as the transported antibiotic. The proposed target strategy was that exposed galactoses of MS-Lac could be specifically recognized by E. coli K88 adhesins, and the delivery of gentamicin would inhibit bacterial growth. Lactosylated microspheres (MS-Lac1, MS-Lac2 and MS-Lac3) were obtained using a water-in-oil emulsion, containing gentamicin, followed by crosslinking with different concentrations of glutaraldehyde. Electron microscopy displayed spherical particles with a mean size of 10–17 µm. In vitro release of gentamicin from MS-Lac was best fitted to a first order model, and the antibacterial activity of encapsulated and free gentamicin was comparable. MS-Lac treatments were recognized by plant galactose-specific lectins from Ricinus communis and Sophora japonica and by E. coli K88 adhesins. Results indicate MS-Lac1, produced with 4.2 mg/mL of crosslinker, as the best treatment and that lactosylated microsphere are promising platforms to obtain an active, targeted system against E. coli K88 infections. Full article

(This article belongs to the Special Issue Drug Delivery and Antimicrobial Agents)

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18 pages, 6152 KiB

Open AccessArticle

Analysis of MicroRNA Expression Profiles in Weaned Pig Skeletal Muscle after Lipopolysaccharide Challenge

by Jing Zhang^1,†

, Shu-Lin Fu^2,†, Yan Liu^1,3, Yu-Lan Liu^1,*

and Wen-Jun Wang^3,*

¹ Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan 430023, China

² Wuhan Institute of Animal Husbandry and Veterinary Science, Wuhan Academy of Agricultural Science & Technology, Wuhan 430208, China

³ College of Life Sciences, South-Central University for Nationalities, Wuhan 430074, China

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2015, 16(9), 22438-22455; https://doi.org/10.3390/ijms160922438 - 16 Sep 2015

Cited by 23 | Viewed by 7439

Abstract

MicroRNAs (miRNAs) constitute a class of non-coding RNAs that play a crucial regulatory role in skeletal muscle development and disease. Several acute inflammation conditions including sepsis and cancer are characterized by a loss of skeletal muscle due primarily to excessive muscle catabolism. As [...] Read more.

MicroRNAs (miRNAs) constitute a class of non-coding RNAs that play a crucial regulatory role in skeletal muscle development and disease. Several acute inflammation conditions including sepsis and cancer are characterized by a loss of skeletal muscle due primarily to excessive muscle catabolism. As a well-known inducer of acute inflammation, a lipopolysaccharide (LPS) challenge can cause serious skeletal muscle wasting. However, knowledge of the role of miRNAs in the course of inflammatory muscle catabolism is still very limited. In this study, RNA extracted from the skeletal muscle of pigs injected with LPS or saline was subjected to small RNA deep sequencing. We identified 304 conserved and 114 novel candidate miRNAs in the pig. Of these, four were significantly increased in the LPS-challenged samples and five were decreased. The expression of five miRNAs (ssc-miR-146a-5p, ssc-miR-221-5p, ssc-miR-148b-3p, ssc-miR-215 and ssc-miR-192) were selected for validation by quantitative polymerase chain reaction (qPCR), which found that ssc-miR-146a-5p and ssc-miR-221-5p were significantly upregulated in LPS-challenged pig skeletal muscle. Moreover, we treated mouse C2C12 myotubes with 1000 ng/mL LPS as an acute inflammation cell model. Expression of TNF-α, IL-6, muscle atrophy F-box (MAFbx) and muscle RING finger 1 (MuRF1) mRNA was strongly induced by LPS. Importantly, miR-146a-5p and miR-221-5p also showed markedly increased expression in LPS-treated C2C12 myotubes, suggesting the two miRNAs may be involved in muscle catabolism systems in response to acute inflammation caused by a LPS challenge. To our knowledge, this study is the first to examine miRNA expression profiles in weaned pig skeletal muscle challenged with LPS, and furthers our understanding of miRNA function in the regulation of inflammatory muscle catabolism. Full article

(This article belongs to the Special Issue MicroRNA Regulation)

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17 pages, 2740 KiB

Open AccessArticle

Isolation of Endogenously Assembled RNA-Protein Complexes Using Affinity Purification Based on Streptavidin Aptamer S1

by Yangchao Dong^†, Jing Yang^†, Wei Ye^†

, Yuan Wang, Chuantao Ye, Daihui Weng, Huan Gao, Fanglin Zhang, Zhikai Xu^* and Yingfeng Lei^*

¹ Department of Microbiology, Faculty of Preclinical Medicine, the Fourth Military Medical University, Xi'an 710032, China

^† These authors contributed equally to this manuscript.

Int. J. Mol. Sci. 2015, 16(9), 22456-22472; https://doi.org/10.3390/ijms160922456 - 16 Sep 2015

Cited by 20 | Viewed by 9090

Abstract

Efficient isolation of endogenously assembled viral RNA-protein complexes is essential for understanding virus replication mechanisms. We have developed an affinity purification strategy based on an RNA affinity tag that allows large-scale preparation of native viral RNA-binding proteins (RBPs). The streptavidin-binding aptamer S1 sequence [...] Read more.

Efficient isolation of endogenously assembled viral RNA-protein complexes is essential for understanding virus replication mechanisms. We have developed an affinity purification strategy based on an RNA affinity tag that allows large-scale preparation of native viral RNA-binding proteins (RBPs). The streptavidin-binding aptamer S1 sequence was inserted into the 3′ end of dengue virus (DENV) 5′–3′ UTR RNA, and the DENV RNA UTR fused to the S1 RNA aptamer was expressed in living mammalian cells. This allowed endogenous viral ribonucleoprotein (RNP) assembly and isolation of RNPs from whole cell extract, through binding the S1 aptamer to streptavidin magnetic beads. Several novel host DENV RBPs were subsequently identified by liquid chromatography with tandem mass spectrometry (LC-MS/MS), including RPS8, which we further implicate in DENV replication. We proposed efficient S1 aptamer-based isolation of viral assembled RNPs from living mammalian cells will be generally applicable to the purification of high- and low-affinity RBPs and RNPs under endogenous conditions. Full article

(This article belongs to the Section Biochemistry)

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12 pages, 5438 KiB

Open AccessArticle

Protective Effects of MDG-1, a Polysaccharide from Ophiopogon japonicus on Diabetic Nephropathy in Diabetic KKA^y Mice

by Yuan Wang^1,†, Lin-Lin Shi^1,†, Ling-Yi Wang¹, Jin-Wen Xu^2,* and Yi Feng^1,*

¹ Engineering Research Center of Modern Preparation Technology of TCM, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China

² Murad Research Institute for Modernized Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2015, 16(9), 22473-22484; https://doi.org/10.3390/ijms160922473 - 17 Sep 2015

Cited by 25 | Viewed by 6564

Abstract

Ophiopogon japonicus is a traditional Chinese medicine that might be effective for treating type 2 diabetes. Recent research confirmed that MDG-1, a polysaccharide from O. japonicas, activates the PI3K/Akt signaling pathway and improves insulin sensitivity in a diabetic KKA^y mouse model, [...] Read more.

Ophiopogon japonicus is a traditional Chinese medicine that might be effective for treating type 2 diabetes. Recent research confirmed that MDG-1, a polysaccharide from O. japonicas, activates the PI3K/Akt signaling pathway and improves insulin sensitivity in a diabetic KKA^y mouse model, but little is known about its effects on diabetic nephropathy. In this study, KKA^y mice were orally administered distilled water (control group), MDG-1, or rosiglitazone for 12 weeks. Blood glucose levels were tested every two weeks for the fed mice. At 6 and 12 weeks, blood samples were collected for biochemical examination. At the end of the experiment, all kidney tissues were collected for histological examination and western blot analysis. Results show that MDG-1 (300 mg/kg) significantly decreased the levels of blood glucose, triglycerides, blood urine nitrogen and albumin, and significantly inhibited the expression of transforming growth factor-beta 1 and connective tissue growth factor. Moreover, MDG-1 could alleviate glomerular mesangial expansion and tubulointerstitial fibrosis in the diabetic mice, as confirmed by histopathological examination. These data indicated that MDG-1 ameliorates renal disease in diabetic mice by reducing hyperglycemia, hyperinsulinemia, and hyperlipidemia, and by inhibiting intracellular signaling pathways. Full article

(This article belongs to the Special Issue Molecular Research on Obesity and Diabetes)

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18 pages, 2920 KiB

Open AccessArticle

Mitochondrial Optic Atrophy (OPA) 1 Processing Is Altered in Response to Neonatal Hypoxic-Ischemic Brain Injury

by Ana A. Baburamani^1,†, Chloe Hurling^1,†, Helen Stolp¹, Kristina Sobotka², Pierre Gressens^1,3,4, Henrik Hagberg^1,2 and Claire Thornton^1,*

¹ Centre for the Developing Brain, Division of Imaging Sciences and Biomedical Engineering, King's College London, St. Thomas' Hospital, SE1 7EH London, UK

² Perinatal Center, Institute for Clinical Sciences and Physiology & Neuroscience, Sahlgrenska Academy, University of Gothenburg, 41685 Gothenburg, Sweden

³ Inserm, U 1141, 75019 Paris, France

⁴ University Paris Diderot, Sorbonne Paris Cité, UMRS 1141, 75019 Paris, France

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2015, 16(9), 22509-22526; https://doi.org/10.3390/ijms160922509 - 17 Sep 2015

Cited by 48 | Viewed by 9536

Abstract

Perturbation of mitochondrial function and subsequent induction of cell death pathways are key hallmarks in neonatal hypoxic-ischemic (HI) injury, both in animal models and in term infants. Mitoprotective therapies therefore offer a new avenue for intervention for the babies who suffer life-long disabilities [...] Read more.

Perturbation of mitochondrial function and subsequent induction of cell death pathways are key hallmarks in neonatal hypoxic-ischemic (HI) injury, both in animal models and in term infants. Mitoprotective therapies therefore offer a new avenue for intervention for the babies who suffer life-long disabilities as a result of birth asphyxia. Here we show that after oxygen-glucose deprivation in primary neurons or in a mouse model of HI, mitochondrial protein homeostasis is altered, manifesting as a change in mitochondrial morphology and functional impairment. Furthermore we find that the mitochondrial fusion and cristae regulatory protein, OPA1, is aberrantly cleaved to shorter forms. OPA1 cleavage is normally regulated by a balanced action of the proteases Yme1L and Oma1. However, in primary neurons or after HI in vivo, protein expression of YmelL is also reduced, whereas no change is observed in Oma1 expression. Our data strongly suggest that alterations in mitochondria-shaping proteins are an early event in the pathogenesis of neonatal HI injury. Full article

(This article belongs to the Special Issue Mitochondrial Dysfunction in Ageing and Diseases)

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14 pages, 3349 KiB

Open AccessArticle

Identification and Evaluation of 21 Novel Microsatellite Markers from the Autumnal Moth (Epirrita autumnata) (Lepidoptera: Geometridae)

by Siv Grethe Aarnes^1,*, Ida Fløystad¹

, Julia Schregel¹, Ole Petter Laksforsmo Vindstad², Jane Uhd Jepsen³, Hans Geir Eiken¹, Rolf A. Ims² and Snorre B. Hagen^1,*

¹ Norwegian Institute for Bioeconomy Research (NIBIO), Norwegian Institute for Bioeconomy Research, Svanhovd, 9925 Svanvik, Norway

² Department of Arctic and Marine Biology, University of Tromsø, 9294 Tromsø, Norway

³ Norwegian Institute for Nature Research (NINA), 9296 Tromsø, Norway

Int. J. Mol. Sci. 2015, 16(9), 22541-22554; https://doi.org/10.3390/ijms160922541 - 17 Sep 2015

Cited by 1 | Viewed by 5859

Abstract

The autumnal moth (Epirrita autumnata) is a cyclically outbreaking forest Lepidoptera with circumpolar distribution and substantial impact on Northern ecosystems. We have isolated 21 microsatellites from the species to facilitate population genetic studies of population cycles, outbreaks, and crashes. First, PCR [...] Read more.

The autumnal moth (Epirrita autumnata) is a cyclically outbreaking forest Lepidoptera with circumpolar distribution and substantial impact on Northern ecosystems. We have isolated 21 microsatellites from the species to facilitate population genetic studies of population cycles, outbreaks, and crashes. First, PCR primers and PCR conditions were developed to amplify 19 trinucleotide loci and two tetranucleotide loci in six multiplex PCR approaches and then analyzed for species specificity, sensitivity and precision. Twelve of the loci showed simple tandem repeat array structures while nine loci showed imperfect repeat structures, and repeat numbers varied in our material between six and 15. The application in population genetics for all the 21 microsatellites were further validated in 48 autumnal moths sampled from Northern Norway, and allelic variation was detected in 19 loci. The detected numbers of alleles per locus ranged from two to 13, and the observed and expected heterozygosities varied from 0.04 to 0.69 and 0.04 to 0.79, respectively. Evidence for linkage disequilibrium was found for six loci as well as indication of one null allele. We find that these novel microsatellites and their multiplex-PCR assays are suitable for further research on fine- and large-scale population-genetic studies of Epirrita autumnata. Full article

(This article belongs to the Section Biochemistry)

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29 pages, 3514 KiB

Open AccessArticle

Attenuation of Combined Nickel(II) Oxide and Manganese(II, III) Oxide Nanoparticles’ Adverse Effects with a Complex of Bioprotectors

by Ilzira A. Minigalieva¹, Boris A. Katsnelson^1,*, Larisa I. Privalova¹, Marina P. Sutunkova¹, Vladimir B. Gurvich¹, Vladimir Y. Shur²

, Ekaterina V. Shishkina², Irene E. Valamina³, Oleg H. Makeyev³, Vladimir G. Panov⁴, Anatoly N. Varaksin⁴, Ekaterina V. Grigoryeva¹ and Ekaterina Y. Meshtcheryakova³

¹ The Medical Research Center for Prophylaxis and Health Protection in Industrial Workers, 30 Popov Str., Ekaterinburg 620014, Russia

² The Institute of Natural Sciences, The Ural Federal University, Ekaterinburg 620000, Russia

³ The Central Research Laboratory, The Ural State Medical University, 17 Klyuchevskaya Str., Ekaterinburg 620109, Russia

⁴ Institute of Industrial Ecology, the Urals Branch of the Russian Academy of Sciences, 20 Sofia Kovalevskaya Str., Ekaterinburg 620990, Russia

Int. J. Mol. Sci. 2015, 16(9), 22555-22583; https://doi.org/10.3390/ijms160922555 - 17 Sep 2015

Cited by 53 | Viewed by 7798

Abstract

Stable suspensions of NiO and Mn₃O₄ nanoparticles (NPs) with a mean (±s.d.) diameter of 16.7 ± 8.2 and 18.4 ± 5.4 nm, respectively, purposefully prepared by laser ablation of 99.99% pure nickel or manganese in de-ionized water, were repeatedly injected [...] Read more.

Stable suspensions of NiO and Mn₃O₄ nanoparticles (NPs) with a mean (±s.d.) diameter of 16.7 ± 8.2 and 18.4 ± 5.4 nm, respectively, purposefully prepared by laser ablation of 99.99% pure nickel or manganese in de-ionized water, were repeatedly injected intraperitoneally (IP) to rats at a dose of 2.5 mg/kg 3 times a week up to 18 injections, either alone or in combination. A group of rats was injected with this combination with the background oral administration of a “bio-protective complex” (BPC) comprising pectin, vitamins A, C, E, glutamate, glycine, N-acetylcysteine, selenium, iodide and omega-3 PUFA, this composition having been chosen based on mechanistic considerations and previous experience. After the termination of injections, many functional and biochemical indices and histopathological features (with morphometric assessment) of the liver, spleen, kidneys and brain were evaluated for signs of toxicity. The Ni and Mn content of these organs was measured with the help of the atomic emission and electron paramagnetic resonance spectroscopies. We obtained blood leukocytes for performing the RAPD (Random Amplified Polymorphic DNA) test. Although both metallic NPs proved adversely bio-active in many respects considered in this study, Mn₃O₄-NPswere somewhat more noxious than NiO-NPs as concerns most of the non-specific toxicity manifestations and they induced more marked damage to neurons in the striatum and the hippocampus, which may be considered an experimental correlate of the manganese-induced Parkinsonism. The comparative solubility of the Mn₃O₄-NPs and NiO-NPs in a biological medium is discussed as one of the factors underlying the difference in their toxicokinetics and toxicities. The BPC has attenuated both the organ-systemic toxicity and the genotoxicity of Mn₃O₄-NPs in combination with NiO-NPs. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

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22 pages, 2667 KiB

Open AccessArticle

Expression of PD-1 Molecule on Regulatory T Lymphocytes in Patients with Insulin-Dependent Diabetes Mellitus

by Valentina Perri¹, Benedetta Russo¹, Antonino Crinò², Riccardo Schiaffini²

, Ezio Giorda³, Marco Cappa², Maria Manuela Rosado⁴ and Alessandra Fierabracci^1,*

¹ Immunology and Pharmacotherapy Area, Children's Hospital Bambino Gesù, Viale S. Paolo 15, 00146 Rome, Italy

² Division of Endocrinology, Children's Hospital Bambino Gesù, Piazza S. Onofrio 4, 00165 Rome, Italy

³ Research Laboratories, Children's Hospital Bambino Gesù, Viale S. Paolo 15, 00146 Rome, Italy

⁴ Consultant in Immunology, 00100 Rome, Italy

Int. J. Mol. Sci. 2015, 16(9), 22584-22605; https://doi.org/10.3390/ijms160922584 - 18 Sep 2015

Cited by 41 | Viewed by 7046

Abstract

Type 1 diabetes is caused by autoreactive T cells that destroy pancreatic beta cells. Animal models suggested that a CD4⁺CD25⁺ population has a regulatory function capable of preventing activation and effector functions of autoreactive T cells. However, the role of [...] Read more.

Type 1 diabetes is caused by autoreactive T cells that destroy pancreatic beta cells. Animal models suggested that a CD4⁺CD25⁺ population has a regulatory function capable of preventing activation and effector functions of autoreactive T cells. However, the role of CD4⁺CD25^high T cells in autoimmunity and their molecular mechanisms remain the subject of investigation. We therefore evaluated T regulatory cell frequencies and their PD-1 expression in the peripheral blood of long-standing diabetics under basal conditions and after CD3/CD28 stimulation. Under basal conditions, the percentages of T regulatory cells were significantly higher while that of T effector cells were significantly lower in patients than in controls. The ratio of regulatory to effector T cells was higher in patients than that in controls, suggesting that T regulatory cells were functional in patients. Percentages of total PD-1⁺, PD-1^low and PD-1^high expressing T regulatory cells did not change in patients and in controls. After stimulation, a defect in T regulatory cell proliferation was observed in diabetics and the percentages of total PD-1⁺, PD-1^low and PD-1^high expressing cells were lower in patients. Our data suggest a defective activation of T regulatory cells in long-standing diabetics due to a lower expression of PD-1 on their surface. Full article

(This article belongs to the Special Issue Molecular Research on Obesity and Diabetes)

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15 pages, 1728 KiB

Open AccessArticle

Identification and Characterization of CYP9A40 from the Tobacco Cutworm Moth (Spodoptera litura), a Cytochrome P450 Gene Induced by Plant Allelochemicals and Insecticides

by Rui-Long Wang^1,2, Christian Staehelin³

, Qing-Qing Xia^1,4, Yi-Juan Su^1,4 and Ren-Sen Zeng^1,2,4,*

¹ Key Laboratory of Tropical Agro-Environment, Ministry of Agriculture, College of Natural Resources and Environment, South China Agricultural University, Guangzhou 510642, China

² Key Laboratory of Agroecology and Rural Environment of Guangdong Regular Higher Education Institutions, South China Agricultural University, Guangzhou 510642, China

³ State Key Laboratory of Biocontrol and Guangdong Key Laboratory of Plant Resources, School of Life Sciences, Sun Yat-sen University (East Campus), Guangzhou 510006, China

⁴ College of Life Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China

Int. J. Mol. Sci. 2015, 16(9), 22606-22620; https://doi.org/10.3390/ijms160922606 - 18 Sep 2015

Cited by 59 | Viewed by 6548

Abstract

Cytochrome P450 monooxygenases (P450s) of insects play crucial roles in the metabolism of endogenous and dietary compounds. Tobacco cutworm moth (Spodoptera litura), an important agricultural pest, causes severe yield losses in many crops. In this study, we identified CYP9A40, a [...] Read more.

Cytochrome P450 monooxygenases (P450s) of insects play crucial roles in the metabolism of endogenous and dietary compounds. Tobacco cutworm moth (Spodoptera litura), an important agricultural pest, causes severe yield losses in many crops. In this study, we identified CYP9A40, a novel P450 gene of S. litura, and investigated its expression profile and potential role in detoxification of plant allelochemicals and insecticides. The cDNA contains an open reading frame encoding 529 amino acid residues. CYP9A40 transcripts were found to be accumulated during various development stages of S. litura and were highest in fifth and sixth instar larvae. CYP9A40 was mainly expressed in the midgut and fat body. Larval consumption of xenobiotics, namely plant allelochemicals (quercetin and cinnamic acid) and insecticides (deltamethrin and methoxyfenozide) induced accumulation of CYP9A40 transcripts in the midgut and fat body. Injection of dsCYP9A40 (silencing of CYP9A40 by RNA interference) significantly increased the susceptibility of S. litura larvae to the tested plant allelochemicals and insecticides. These results indicate that CYP9A40 expression in S. litura is related to consumption of xenobiotics and suggest that CYP9A40 is involved in detoxification of these compounds. Full article

(This article belongs to the Section Biochemistry)

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15 pages, 1710 KiB

Open AccessArticle

Biliverdin Reductase A (BVRA) Mediates Macrophage Expression of Interleukin-10 in Injured Kidney

by Zhizhi Hu¹, Guangchang Pei¹, Pengge Wang¹, Juan Yang¹, Fengmin Zhu¹, Yujiao Guo¹, Meng Wang¹, Ying Yao¹, Rui Zeng^1,*, Wenhui Liao^2,* and Gang Xu¹

¹ Division of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan 430030, Hubei, China

² Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan 430030, Hubei, China

Int. J. Mol. Sci. 2015, 16(9), 22621-22635; https://doi.org/10.3390/ijms160922621 - 18 Sep 2015

Cited by 20 | Viewed by 8684

Abstract

Biliverdin reductase A is an enzyme, with serine/threonine/tyrosine kinase activation, converting biliverdin (BV) to bilirubin (BR) in heme degradation pathway. It has been reported to have anti-inflammatory and antioxidant effect in monocytes and human glioblastoma. However, the function of BVRA in polarized macrophage [...] Read more.

Biliverdin reductase A is an enzyme, with serine/threonine/tyrosine kinase activation, converting biliverdin (BV) to bilirubin (BR) in heme degradation pathway. It has been reported to have anti-inflammatory and antioxidant effect in monocytes and human glioblastoma. However, the function of BVRA in polarized macrophage was unknown. This study aimed to investigate the effect of BVRA on macrophage activation and polarization in injured renal microenvironment. Classically activated macrophages (M1macrophages) and alternative activation of macrophages (M2 macrophages) polarization of murine bone marrow derived macrophage was induced by GM-CSF and M-CSF. M1 polarization was associated with a significant down-regulation of BVRA and Interleukin-10 (IL-10), and increased secretion of TNF-α. We also found IL-10 expression was increased in BVRA over-expressed macrophages, while it decreased in BVRA knockdown macrophages. In contrast, BVRA over-expressed or knockdown macrophages had no effect on TNF-α expression level, indicating BVRA mediated IL-10 expression in macrophages. Furthermore, we observed in macrophages infected with recombinant adenoviruses BVRA gene, which BVRA over-expressed enhanced both INOS and ARG-1 mRNA expression, resulting in a specific macrophage phenotype. Through in vivo study, we found BVRA positive macrophages largely existed in mice renal ischemia perfusion injury. With the treatment of the regular cytokines GM-CSF, M-CSF or LPS, excreted in the injured renal microenvironment, IL-10 secretion was significantly increased in BVRA over-expressed macrophages. In conclusion, the BVRA positive macrophage is a source of anti-inflammatory cytokine IL-10 in injured kidney, which may provide a potential target for treatment of kidney disease. Full article

(This article belongs to the Section Biochemistry)

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14 pages, 1634 KiB

Open AccessArticle

SOCS3 Methylation Predicts a Poor Prognosis in HBV Infection-Related Hepatocellular Carcinoma

by Xin Zhang¹, Qingshan You^1,*, Xiaolei Zhang^2,† and Xiangmei Chen^2,†

¹ Department of Radiotherapy, Harbin Medical University Cancer Hospital, Harbin 150081, China

² Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2015, 16(9), 22662-22675; https://doi.org/10.3390/ijms160922662 - 18 Sep 2015

Cited by 28 | Viewed by 5803

Abstract

Suppressor of cytokine signaling 3 (SOCS3) plays crucial roles in JAK/STAT signaling pathway inhibition in hepatocellular carcinoma (HCC). However, the methylation status of SOCS3 in HBV infection-related HCC and the relationship between SOCS3 methylation and the clinical outcome remain unknown. Here, [...] Read more.

Suppressor of cytokine signaling 3 (SOCS3) plays crucial roles in JAK/STAT signaling pathway inhibition in hepatocellular carcinoma (HCC). However, the methylation status of SOCS3 in HBV infection-related HCC and the relationship between SOCS3 methylation and the clinical outcome remain unknown. Here, we reported that in HCC tumor tissues, two regions of the CpG island (CGI) in the SOCS3 promoter were subjected to methylation analysis and only the region close to the translational start site of SOCS3 was hypermethylated. In HCC tumor tissues, SOCS3 showed an increased methylation frequency and intensity compared with that in the adjacent non-tumor tissues. Moreover, SOCS3 expression was significantly down-regulated in HCC cell lines and tumor tissues, and this was inversely correlated with methylation. Kaplan–Meier curve analysis revealed that in patients with an hepatitis B virus (HBV) infection background, SOCS3 hypermethylation was significantly correlated with a poor clinical outcome of HCC patients. Our findings indicated that SOCS3 hypermethylation has already happened in non-tumor tissues and increased in both frequency and intensity in tumor tissues. This suggests that the methylation of SOCS3 could predict a poor prognosis in HBV infection-related HCC patients. Full article

(This article belongs to the Special Issue Molecular Classification of Human Cancer: Diagnosis and Treatment)

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16 pages, 2262 KiB

Open AccessArticle

Poncirin Induces Apoptosis in AGS Human Gastric Cancer Cells through Extrinsic Apoptotic Pathway by up-Regulation of Fas Ligand

by Venu Venkatarame Gowda Saralamma¹, Arulkumar Nagappan²

, Gyeong Eun Hong¹, Ho Jeong Lee¹, Silvia Yumnam¹, Suchismita Raha¹, Jeong Doo Heo³, Sang Joon Lee³, Won Sup Lee², Eun Hee Kim⁴

and Gon Sup Kim^1,*

¹ Research Institute of Life Science and College of Veterinary Medicine (BK21 Plus Project), Gyeongsang National University, Gazwa, Jinju 660-701, Korea

² Department of Internal Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 660-702, Korea

³ Gyeongnam Department of Environment Toxicology and Chemistry, Toxicity Screening Research Center, Korea Institute of Toxicology, Jinju 666-844, Korea

⁴ Department of Nursing Science, International University of Korea, Jinju 660-759, Korea

Int. J. Mol. Sci. 2015, 16(9), 22676-22691; https://doi.org/10.3390/ijms160922676 - 18 Sep 2015

Cited by 38 | Viewed by 9743

Abstract

Poncirin, a natural bitter flavanone glycoside abundantly present in many species of citrus fruits, has various biological benefits such as anti-oxidant, anti-microbial, anti-inflammatory and anti-cancer activities. The anti-cancer mechanism of Poncirin remains elusive to date. In this study, we investigated the anti-cancer effects [...] Read more.

Poncirin, a natural bitter flavanone glycoside abundantly present in many species of citrus fruits, has various biological benefits such as anti-oxidant, anti-microbial, anti-inflammatory and anti-cancer activities. The anti-cancer mechanism of Poncirin remains elusive to date. In this study, we investigated the anti-cancer effects of Poncirin in AGS human gastric cancer cells (gastric adenocarcinoma). The results revealed that Poncirin could inhibit the proliferation of AGS cells in a dose-dependent manner. It was observed Poncirin induced accumulation of sub-G1 DNA content, apoptotic cell population, apoptotic bodies, chromatin condensation, and DNA fragmentation in a dose-dependent manner in AGS cells. The expression of Fas Ligand (FasL) protein was up-regulated dose dependently in Poncirin-treated AGS cells Moreover, Poncirin in AGS cells induced activation of Caspase-8 and -3, and subsequent cleavage of poly(ADP-ribose) polymerase (PARP). Inhibitor studies’ results confirm that the induction of caspase-dependent apoptotic cell death in Poncirin-treated AGS cells was led by the Fas death receptor. Interestingly, Poncirin did not show any effect on mitochondrial membrane potential (ΔΨm), pro-apoptotic proteins (Bax and Bak) and anti-apoptotic protein (Bcl-xL) in AGS-treated cells followed by no activation in the mitochondrial apoptotic protein caspase-9. This result suggests that the mitochondrial-mediated pathway is not involved in Poncirin-induced cell death in gastric cancer. These findings suggest that Poncirin has a potential anti-cancer effect via extrinsic pathway-mediated apoptosis, possibly making it a strong therapeutic agent for human gastric cancer. Full article

(This article belongs to the Special Issue Bioactive Phytochemicals and Functional Food Ingredients in Fruits and Vegetables)

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19 pages, 2480 KiB

Open AccessArticle

Transcriptome Analysis Revealed the Embryo-Induced Gene Expression Patterns in the Endometrium from Meishan and Yorkshire Pigs

by Jiangnan Huang^1,2, Ruize Liu¹, Lijie Su¹, Qian Xiao¹ and Mei Yu^1,*

¹ Key Lab of Agricultural Animal Genetics, Breeding, and Reproduction of Ministry and the Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan 430070, China

² Institute of Animal Husbandry and Veterinary, Jiangxi Academy of Agricultural Sciences, Nanchang 330200, China

Int. J. Mol. Sci. 2015, 16(9), 22692-22710; https://doi.org/10.3390/ijms160922692 - 18 Sep 2015

Cited by 15 | Viewed by 6078

Abstract

The expression patterns in Meishan- and Yorkshire-derived endometrium during early (gestational day 15) and mid-gestation (gestational days 26 and 50) were investigated, respectively. Totally, 689 and 1649 annotated genes were identified to be differentially expressed in Meishan and Yorkshire endometrium during the three [...] Read more.

The expression patterns in Meishan- and Yorkshire-derived endometrium during early (gestational day 15) and mid-gestation (gestational days 26 and 50) were investigated, respectively. Totally, 689 and 1649 annotated genes were identified to be differentially expressed in Meishan and Yorkshire endometrium during the three gestational stages, respectively. Hierarchical clustering analysis identified that, of the annotated differentially expressed genes (DEGs), 73 DEGs were unique to Meishan endometrium, 536 DEGs were unique to Yorkshire endometrium, and 228 DEGs were common in Meishan and Yorkshire endometriums. Subsequently, DEGs in each of the three types of expression patterns were grouped into four distinct categories according to the similarities in their temporal expression patterns. The expression patterns identified from the microarray analysis were validated by quantitative RT-PCR. The functional enrichment analysis revealed that the common DEGs were enriched in pathways of steroid metabolic process and regulation of retinoic acid receptor signaling. These unique DEGs in Meishan endometrium were involved in cell cycle and adherens junction. The DEGs unique to Yorkshire endometrium were associated with regulation of Rho protein signal transduction, maternal placenta development and cell proliferation. This study revealed the different gene expression patterns or pathways related to the endometrium remodeling in Meishan and Yorkshire pigs, respectively. These unique DEGs in either Meishan or Yorkshire endometriums may contribute to the divergence of the endometrium environment in the two pig breeds. Full article

(This article belongs to the Section Biochemistry)

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24 pages, 3582 KiB

Open AccessArticle

The Use of a Liposomal Formulation Incorporating an Antimicrobial Peptide from Tilapia as a New Adjuvant to Epirubicin in Human Squamous Cell Carcinoma and Pluripotent Testicular Embryonic Carcinoma Cells

by Yu-Li Lo^1,*, Hsin-Pin Lee² and Wei-Chen Tu²

¹ Department and Institute of Pharmacology, National Yang-Ming University, No. 155, Sec. 2, Linong Street, Taipei 112, Taiwan

² Department of Biological Sciences and Technology, National University of Tainan, Tainan 700, Taiwan

Int. J. Mol. Sci. 2015, 16(9), 22711-22734; https://doi.org/10.3390/ijms160922711 - 18 Sep 2015

Cited by 13 | Viewed by 6514

Abstract

This study aims to explore the effects and mechanisms of hepcidin, a potential antimicrobial peptide from Tilapia, and epirubicin (Epi), an antineoplastic agent, on the generation of reactive oxygen species (ROS) and link the ROS levels to the reversal mechanisms of multidrug resistance [...] Read more.

This study aims to explore the effects and mechanisms of hepcidin, a potential antimicrobial peptide from Tilapia, and epirubicin (Epi), an antineoplastic agent, on the generation of reactive oxygen species (ROS) and link the ROS levels to the reversal mechanisms of multidrug resistance (MDR) by epirubicin and hepcidin in human squamous cell carcinoma SCC15 and human embryonal carcinoma NT2D1 cells. The cells, pretreated with hepcidin, epirubicin, or a combination of these compounds in PEGylated liposomes, were used to validate the molecular mechanisms involved in inhibiting efflux transporters and inducing apoptosis as evaluated by cytotoxicity, intracellular accumulation, mRNA levels, cell cycle distribution, and caspase activity of this combination. We found that hepcidin significantly enhanced the cytotoxicity of epirubicin in liposomes. The co-incubation of epirubicin with hepcidin in liposomes intensified the ROS production, including hydrogen peroxide and superoxide free radicals. Hepcidin significantly increased epirubicin intracellular uptake into NT2D1 and SCC15 cells, as supported by the diminished mRNA expressions of MDR1, MDR-associated protein (MRP) 1, and MRP2. Hepcidin and/or epirubicin in liposomes triggered apoptosis, as verified by the reduced mitochondrial membrane potential, increased sub-G1 phase of cell cycle, incremental populations of apoptosis using annexin V/PI assay, and chromatin condensation. As far as we know, this is the first example showing that PEGylated liposomal TH1-5 and epirubicin gives rise to cell death in human squamous carcinoma and testicular embryonic carcinoma cells through the reduced epirubicin efflux via ROS-mediated suppression of P-gp and MRPs and concomitant initiation of mitochondrial apoptosis pathway. Hence, hepcidin in PEGylated liposomes may function as an adjuvant to anticancer drugs, thus demonstrating a novel strategy for reversing MDR. Full article

(This article belongs to the Special Issue Bioactivity of Marine Natural Products)

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19 pages, 1323 KiB

Open AccessArticle

Effects of Non-Natural Amino Acid Incorporation into the Enzyme Core Region on Enzyme Structure and Function

by H. Edward Wong¹ and Inchan Kwon^1,2,*

¹ Department of Chemical Engineering, University of Virginia, Charlottesville, VA 22904, USA

² School of Materials Science and Engineering, Gwangju Institute of Science and Technology (GIST), Gwangju 61005, Korea

Int. J. Mol. Sci. 2015, 16(9), 22735-22753; https://doi.org/10.3390/ijms160922735 - 21 Sep 2015

Cited by 6 | Viewed by 7238

Abstract

Techniques to incorporate non-natural amino acids (NNAAs) have enabled biosynthesis of proteins containing new building blocks with unique structures, chemistry, and reactivity that are not found in natural amino acids. It is crucial to understand how incorporation of NNAAs affects protein function because [...] Read more.

Techniques to incorporate non-natural amino acids (NNAAs) have enabled biosynthesis of proteins containing new building blocks with unique structures, chemistry, and reactivity that are not found in natural amino acids. It is crucial to understand how incorporation of NNAAs affects protein function because NNAA incorporation may perturb critical function of a target protein. This study investigates how the site-specific incorporation of NNAAs affects catalytic properties of an enzyme. A NNAA with a hydrophobic and bulky sidechain, 3-(2-naphthyl)-alanine (2Nal), was site-specifically incorporated at six different positions in the hydrophobic core of a model enzyme, murine dihydrofolate reductase (mDHFR). The mDHFR variants with a greater change in van der Waals volume upon 2Nal incorporation exhibited a greater reduction in the catalytic efficiency. Similarly, the steric incompatibility calculated using RosettaDesign, a protein stability calculation program, correlated with the changes in the catalytic efficiency. Full article

(This article belongs to the Special Issue Protein Engineering)

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14 pages, 1021 KiB

Open AccessArticle

Enantioselective Pharmacokinetics of α-Lipoic Acid in Rats

by Ryota Uchida¹, Hinako Okamoto^2,3, Naoko Ikuta³, Keiji Terao^2,3 and Takashi Hirota^1,*

¹ Department of Biopharmaceutics, Faculty of Pharmaceutical Science, Tokyo University of Science, 2641 Yamazaki, Noda-shi, Chiba 278-8510, Japan

² CycloChem Bio Co., Ltd., KIBC654R 5-5-2 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan

³ Graduate School of Medicine, Kobe University, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan

Int. J. Mol. Sci. 2015, 16(9), 22781-22794; https://doi.org/10.3390/ijms160922781 - 21 Sep 2015

Cited by 36 | Viewed by 7230

Abstract

α-Lipoic acid (LA) is widely used for nutritional supplements as a racemic mixture, even though the R enantiomer is biologically active. After oral administration of the racemic mixture (R-α-lipoic acid (RLA) and S-α-lipoic acid (SLA) mixed at the ratio of [...] Read more.

α-Lipoic acid (LA) is widely used for nutritional supplements as a racemic mixture, even though the R enantiomer is biologically active. After oral administration of the racemic mixture (R-α-lipoic acid (RLA) and S-α-lipoic acid (SLA) mixed at the ratio of 50:50) to rats, RLA showed higher plasma concentration than SLA, and its area under the plasma concentration-time curve from time zero to the last (AUC) was significantly about 1.26 times higher than that of SLA. However, after intravenous administration of the racemic mixture, the pharmacokinetic profiles, initial concentration (C₀), AUC, and half-life (T_1/2) of the enantiomers were not significantly different. After oral and intraduodenal administration of the racemic mixture to pyrolus-ligated rats, the AUCs of RLA were significantly about 1.24 and 1.32 times higher than that of SLA, respectively. In addition, after intraportal administration the AUC of RLA was significantly 1.16 times higher than that of SLA. In conclusion, the enantioselective pharmacokinetics of LA in rats arose from the fraction absorbed multiplied by gastrointestinal availability (F_aF_g) and hepatic availability (F_h), and not from the total clearance. Full article

(This article belongs to the Section Biochemistry)

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16 pages, 899 KiB

Open AccessArticle

Chemically Bonding of Amantadine with Gardenamide A Enhances the Neuroprotective Effects against Corticosterone-Induced Insults in PC12 Cells

by Jiaqiang Zhao^1,†, Lizhi Peng^1,†, Wenhua Zheng^2,*, Rikang Wang^3,†, Lei Zhang¹, Jian Yang¹ and Heru Chen^1,4,*

¹ Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou 510632, China

² Faculty of Health Sciences, University of Macao, Taipa, Macao, China

³ National Pharmaceutical Engineering Center for Solid Preparation in Chinese Herbal Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang 330006, China

⁴ Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Guangzhou 510632, China

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2015, 16(9), 22795-22810; https://doi.org/10.3390/ijms160922795 - 21 Sep 2015

Cited by 11 | Viewed by 6193

Abstract

Two amantadine (ATD)-gardenamide A (GA) ligands have been designed and synthesized. The bonding of ATD with GA through a methylene carbonyl brigde (L1) enhances the neuroprotective effect against corticosterone (CORT)-induced impairments in PC12 cells; while the bonding through a succinyl brigde [...] Read more.

Two amantadine (ATD)-gardenamide A (GA) ligands have been designed and synthesized. The bonding of ATD with GA through a methylene carbonyl brigde (L1) enhances the neuroprotective effect against corticosterone (CORT)-induced impairments in PC12 cells; while the bonding through a succinyl brigde (L2) does not. L1 reduces the level of reactive oxygen species (ROS) and cell apoptosis generated by CORT. It restores CORT-changed cell morphology to a state that is closed to normal PC12 cells. One mechanism of L1 to attenuate CORT-induced cell apoptosis is through the adjustment of both caspase-3 and Bcl-2 proteins. Like GA, both nNOS and eNOS might be involved in the neuroprotective mechanism of L1. All the evidences suggest that L1 may be a potential agent to treat depression. Full article

(This article belongs to the Section Biochemistry)

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14 pages, 4330 KiB

Open AccessArticle

The Role of PTP1B O-GlcNAcylation in Hepatic Insulin Resistance

by Yun Zhao^1,2,†, Zhuqi Tang^1,†, Aiguo Shen^2,3, Tao Tao², Chunhua Wan², Xiaohui Zhu¹, Jieru Huang^1,2, Wanlu Zhang^1,2, Nana Xia^1,2, Suxin Wang^1,2, Shiwei Cui^1,* and Dongmei Zhang^2,*

¹ Department of Endocrinology, Affiliated Hospital of Nantong University, Nantong 226001, China

² Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong 226001, China

³ Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2015, 16(9), 22856-22869; https://doi.org/10.3390/ijms160922856 - 22 Sep 2015

Cited by 30 | Viewed by 7183

Abstract

Protein tyrosine phosphatase 1B (PTP1B), which can directly dephosphorylate both the insulin receptor and insulin receptor substrate 1 (IRS-1), thereby terminating insulin signaling, reportedly plays an important role in insulin resistance. Accumulating evidence has demonstrated that O-GlcNAc modification regulates functions of several [...] Read more.

Protein tyrosine phosphatase 1B (PTP1B), which can directly dephosphorylate both the insulin receptor and insulin receptor substrate 1 (IRS-1), thereby terminating insulin signaling, reportedly plays an important role in insulin resistance. Accumulating evidence has demonstrated that O-GlcNAc modification regulates functions of several important components of insulin signal pathway. In this study, we identified that PTP1B is modified by O-GlcNAcylation at three O-GlcNAc sites (Ser104, Ser201, and Ser386). Palmitate acid (PA) impaired the insulin signaling, indicated by decreased phosphorylation of both serine/threonine-protein kinase B (Akt) and glycogen synthase kinase 3 beta (GSK3β) following insulin administration, and upregulated PTP1B O-GlcNAcylation in HepG2 cells. Compared with the wild-type, intervention PTP1B O-GlcNAcylation by site-directed gene mutation inhibited PTP1B phosphatase activity, resulted in a higher level of phosphorylated Akt and GSK3β, recovered insulin sensitivity, and improved lipid deposition in HepG2 cells. Taken together, our research showed that O-GlcNAcylation of PTP1B can influence insulin signal transduction by modulating its own phosphatase activity, which participates in the process of hepatic insulin resistance. Full article

(This article belongs to the Special Issue Glycosylation and Glycoproteins)

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16 pages, 3338 KiB

Open AccessArticle

Roles of NlAKTIP in the Growth and Eclosion of the Rice Brown Planthopper, Nilaparvata lugens Stål, as Revealed by RNA Interference

by Peiying Hao^*,†, Chaofeng Lu^†, Yan Ma, Lingbo Xu, Jiajun Zhu and Xiaoping Yu^*

¹ Zhejiang Provincial Key Laboratory of Biometrology and Inspection & Quarantine, College of Life Sciences, China Jiliang University, Hangzhou 310018, China

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2015, 16(9), 22888-22903; https://doi.org/10.3390/ijms160922888 - 22 Sep 2015

Cited by 10 | Viewed by 6284

Abstract

AKT-interacting protein (AKTIP) interacts with serine/threonine protein kinase B (PKB)/AKT. AKTIP modulates AKT’s activity by enhancing the phosphorylation of the regulatory site and plays a crucial role in multiple biological processes. In this study, the full length cDNA of NlAKTIP, a novel [...] Read more.

AKT-interacting protein (AKTIP) interacts with serine/threonine protein kinase B (PKB)/AKT. AKTIP modulates AKT’s activity by enhancing the phosphorylation of the regulatory site and plays a crucial role in multiple biological processes. In this study, the full length cDNA of NlAKTIP, a novel AKTIP gene in the brown planthopper (BPH) Nilaparvata lugens, was cloned. The reverse transcription quantitive PCR (RT-qPCR) results showed that the NlAKTIP gene was strongly expressed in gravid female adults, but was relatively weakly expressed in nymphs and male adult BPH. In female BPH, treatment with dsAKTIP resulted in the efficient silencing of NlAKTIP, leading to a significant reduction of mRNA levels, about 50% of those of the untreated control group at day 7 of the study. BPH fed with dsAKTIP had reduced growth with lower body weights and smaller sizes, and the body weight of BPH treated with dsAKTIP at day 7 decreased to about 30% of that of the untreated control. Treatment of dsAKTIP significantly delayed the eclosion for over 7 days relative to the control group and restricted ovarian development to Grade I (transparent stage), whereas the controls developed to Grade IV (matured stage). These results indicated that NlAKTIP is crucial to the growth and development of female BPH. This study provided a valuable clue of a potential target NlAKTIP for inhibiting the BPH, and also provided a new point of view on the interaction between BPH and resistant rice. Full article

(This article belongs to the Section Biochemistry)

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23 pages, 3456 KiB

Open AccessArticle

Transcriptome Analysis and Identification of Differentially Expressed Transcripts of Immune-Related Genes in Spleen of Gosling and Adult Goose

by Anqi Wang^1,†, Fei Liu^2,†, Shun Chen^1,2,3,*,†, Mingshu Wang^1,2,3, Renyong Jia^1,2,3, Dekang Zhu^2,3, Mafeng Liu¹, Kunfeng Sun^1,2,3, Ying Wu^1,2,3, Xiaoyue Chen^2,3 and Anchun Cheng^1,2,3,*

¹ Institute for Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China

² Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China

³ Avian Disease Research Center, College of Veterinary Medicine of Sichuan Agricultural University, Chengdu 611130, China

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2015, 16(9), 22904-22926; https://doi.org/10.3390/ijms160922904 - 22 Sep 2015

Cited by 21 | Viewed by 7079

Abstract

The goose (Anser cygnoides), having high nutritional value, high-quality feathers and high economic benefit, is an economically important poultry species. However, the molecular mechanisms underlying the higher susceptibility to pathogens in goslings than in adult geese remains poorly understood. In this [...] Read more.

The goose (Anser cygnoides), having high nutritional value, high-quality feathers and high economic benefit, is an economically important poultry species. However, the molecular mechanisms underlying the higher susceptibility to pathogens in goslings than in adult geese remains poorly understood. In this study, the histological sections of spleen tissue from a two-week-old gosling and an adult goose, respectively, were subjected to comparative analysis. The spleen of gosling was mainly composed of mesenchyma, accompanied by scattered lymphocytes, whereas the spleen parenchyma was well developed in the adult goose. To investigate goose immune-related genes, we performed deep transcriptome and gene expression analyses of the spleen samples using paired-end sequencing technology (Illumina). In total, 50,390 unigenes were assembled using Trinity software and TGICL software. Moreover, these assembled unigenes were annotated with gene descriptions and gene ontology (GO) analysis was performed. Through Kyoto encyclopedia of genes and genomes (KEGG) analysis, we investigated 558 important immune-relevant unigenes and 23 predicted cytokines. In addition, 22 immune-related genes with differential expression between gosling and adult goose were identified, among which the three genes showing largest differences in expression were immunoglobulin alpha heavy chain (IgH), mannan-binding lectin serine protease 1 isoform X1 (MASP1) and C–X–C chemokine receptor type 4 (CXCR4). Finally, of these 22 differentially expressed immune-related genes, seven genes, including tumor necrosis factor receptor superfamily member 13B (TNFRSF13B), C-C motif chemokine 4-like (CCL4), CXCR4, interleukin 2 receptor alpha (IL2RA), MHC class I heavy chain (MHCIα), transporter of antigen processing 2 (TAP2), IgH, were confirmed by quantitative real-time PCR (qRT-PCR). The expression levels of all the candidate unigenes were up-regulated in adult geese other than that of TNFRSF13B. The comparative analysis of the spleen transcriptomes of gosling and adult goose may promote better understanding of immune molecular development in goose. Full article

(This article belongs to the Section Biochemistry)

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11 pages, 229 KiB

Open AccessArticle

Effects of Microcystin-LR Exposure on Spermiogenesis in Nematode Caenorhabditis elegans

by Yunhui Li^1,*, Minhui Zhang¹, Pan Chen², Ran Liu¹, Geyu Liang¹, Lihong Yin¹ and Yuepu Pu¹

¹ Key Laboratory of Environmental Medicine Engineering Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China

² Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461, USA

Int. J. Mol. Sci. 2015, 16(9), 22927-22937; https://doi.org/10.3390/ijms160922927 - 22 Sep 2015

Cited by 9 | Viewed by 5422

Abstract

Little is known about the effect on spermiogenesis induced by microcystin-leucine arginine (MC-LR), even though such data are very important to better elucidate reproductive health. In the current work, with the aid of nematode Caenorhabditis elegans (C. elegans) as an animal [...] Read more.

Little is known about the effect on spermiogenesis induced by microcystin-leucine arginine (MC-LR), even though such data are very important to better elucidate reproductive health. In the current work, with the aid of nematode Caenorhabditis elegans (C. elegans) as an animal model, we investigated the defects on spermiogenesis induced by MC-LR. Our results showed that MC-LR exposure induced sperm morphology abnormality and caused severe defects of sperm activation, trans-activation, sperm behavior and competition. Additionally, the expression levels of spe-15 were significantly decreased in C. elegans exposed to MC-LR lower than 16.0 μg/L, while the expression levels of spe-10 and fer-1 could be significantly lowered in C. elegans even exposed to 1.0 μg/L of MC-LR. Therefore, the present study reveals that MC-LR can induce adverse effects on spermiogenesis, and those defects of sperm functions may be induced by the decreases of spe-10, spe-15 and fer-1 gene expressions in C. elegans. Full article

(This article belongs to the Section Molecular Toxicology)

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19 pages, 1337 KiB

Open AccessArticle

Phenotypic and Transcriptomic Analyses of Autotetraploid and Diploid Mulberry (Morus alba L.)

by Fanwei Dai, Zhenjiang Wang, Guoqing Luo and Cuiming Tang^*

Sericultural & Agri-Food Research Institute Guangdong Academy of Agricultural Sciences, 133 Yiheng Road, Dongguan Village, Tianhe District, Guangzhou 510610, Guangdong, China

Int. J. Mol. Sci. 2015, 16(9), 22938-22956; https://doi.org/10.3390/ijms160922938 - 22 Sep 2015

Cited by 62 | Viewed by 8191

Abstract

Autopolyploid plants and their organs are often larger than their diploid counterparts, which makes them attractive to plant breeders. Mulberry (Morus alba L.) is an important commercial woody plant in many tropical and subtropical areas. In this study, we obtained a series [...] Read more.

Autopolyploid plants and their organs are often larger than their diploid counterparts, which makes them attractive to plant breeders. Mulberry (Morus alba L.) is an important commercial woody plant in many tropical and subtropical areas. In this study, we obtained a series of autotetraploid mulberry plants resulting from a colchicine treatment. To evaluate the effects of genome duplications in mulberry, we compared the phenotypes and transcriptomes of autotetraploid and diploid mulberry trees. In the autotetraploids, the height, breast-height diameter, leaf size, and fruit size were larger than those of diploids. Transcriptome data revealed that of 21,229 expressed genes only 609 (2.87%) were differentially expressed between diploids and autotetraploids. Among them, 30 genes were associated with the biosynthesis and signal transduction of plant hormones, including cytokinin, gibberellins, ethylene, and auxin. In addition, 41 differentially expressed genes were involved in photosynthesis. These results enhance our understanding of the variations that occur in mulberry autotetraploids and will benefit future breeding work. Full article

(This article belongs to the Special Issue Plant Molecular Biology)

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16 pages, 2896 KiB

Open AccessArticle

Exogenous GA₃ Application Enhances Xylem Development and Induces the Expression of Secondary Wall Biosynthesis Related Genes in Betula platyphylla

by Huiyan Guo^1,2, Yucheng Wang¹, Huizi Liu¹, Ping Hu¹, Yuanyuan Jia¹, Chunrui Zhang¹, Yanmin Wang^1,3, Shan Gu², Chuanping Yang^1,* and Chao Wang^1,*

¹ State Key Laboratory of Tree Genetics and Breeding, Northeast Forestry University, 26 Hexing Road, Harbin 150040, China

² Department of Life Science and Technology, Mudanjiang Normal College, Mudanjiang 157012, China

³ Forestry Science Research Institute of Heilongjiang Province, Harbin 150081, China

Int. J. Mol. Sci. 2015, 16(9), 22960-22975; https://doi.org/10.3390/ijms160922960 - 23 Sep 2015

Cited by 51 | Viewed by 7846

Abstract

Gibberellin (GA) is a key signal molecule inducing differentiation of tracheary elements, fibers, and xylogenesis. However the molecular mechanisms underlying the effect of GA on xylem elongation and secondary wall development in tree species remain to be determined. In this study, Betula platyphylla [...] Read more.

Gibberellin (GA) is a key signal molecule inducing differentiation of tracheary elements, fibers, and xylogenesis. However the molecular mechanisms underlying the effect of GA on xylem elongation and secondary wall development in tree species remain to be determined. In this study, Betula platyphylla (birch) seeds were treated with 300 ppm GA₃ and/or 300 ppm paclobutrazol (PAC), seed germination was recorded, and transverse sections of hypocotyls were stained with toluidine blue; the two-month-old seedlings were treated with 50 μM GA₃ and/or 50 μM PAC, transverse sections of seedling stems were stained using phloroglucinol–HCl, and secondary wall biosynthesis related genes expression was analyzed by real-time quantitative PCR. Results indicated that germination percentage, energy and time of seeds, hypocotyl height and seedling fresh weight were enhanced by GA₃, and reduced by PAC; the xylem development was wider in GA₃-treated plants than in the control; the expression of NAC and MYB transcription factors, CESA, PAL, and GA oxidase was up-regulated during GA₃ treatment, suggesting their role in GA₃-induced xylem development in the birch. Our results suggest that GA₃ induces the expression of secondary wall biosynthesis related genes to trigger xylogenesis in the birch plants. Full article

(This article belongs to the Special Issue Molecular Research in Plant Secondary Metabolism 2015)

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23 pages, 9388 KiB

Open AccessArticle

Modulation of the PI3K/Akt Pathway and Bcl-2 Family Proteins Involved in Chicken’s Tubular Apoptosis Induced by Nickel Chloride (NiCl₂)

by Hongrui Guo¹, Hengmin Cui^1,2,*

, Xi Peng^1,2, Jing Fang^1,2, Zhicai Zuo^1,2, Junliang Deng^1,2, Xun Wang^1,2, Bangyuan Wu¹, Kejie Chen¹ and Jie Deng¹

¹ Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Sichuan Agricultural University, Ya’an 625014, China

² College of Veterinary Medicine, Sichuan Agricultural University, Ya’an 625014, China

Int. J. Mol. Sci. 2015, 16(9), 22989-23011; https://doi.org/10.3390/ijms160922989 - 23 Sep 2015

Cited by 52 | Viewed by 8808

Abstract

Exposure of people and animals to environments highly polluted with nickel (Ni) can cause pathologic effects. Ni compounds can induce apoptosis, but the mechanism and the pathway of Ni compounds-induced apoptosis are unclear. We evaluated the alterations of apoptosis, mitochondrial membrane potential (MMP), [...] Read more.

Exposure of people and animals to environments highly polluted with nickel (Ni) can cause pathologic effects. Ni compounds can induce apoptosis, but the mechanism and the pathway of Ni compounds-induced apoptosis are unclear. We evaluated the alterations of apoptosis, mitochondrial membrane potential (MMP), phosphoinositide-3-kinase (PI3K)/serine-threonine kinase (Akt) pathway, and Bcl-2 family proteins induced by nickel chloride (NiCl₂) in the kidneys of broiler chickens, using flow cytometry, terminal deoxynucleotidyl transferase 2ʹ-deoxyuridine 5ʹ-triphosphate dUTP nick end-labeling (TUNEL), immunohistochemstry and quantitative real-time polymerase chain reaction (qRT-PCR). We found that dietary NiCl₂ in excess of 300 mg/kg resulted in a significant increase in apoptosis, which was associated with decrease in MMP, and increase in apoptosis inducing factor (AIF) and endonuclease G (EndoG) protein and mRNA expression. Concurrently, NiCl₂ inhibited the PI3K/Akt pathway, which was characterized by decreasing PI3K, Akt1 and Akt2 mRNA expression levels. NiCl₂ also reduced the protein and mRNA expression of anti-apoptotic Bcl-2 and Bcl-xL and increased the protein and mRNA expression of pro-apoptotic Bax and Bak. These results show that NiCl₂ causes mitochondrial-mediated apoptosis by disruption of MMP and increased expression of AIF and EndoG mRNA and protein, and that the underlying mechanism of MMP loss involves the Bcl-2 family proteins modulation and PI3K/Akt pathway inhibition. Full article

(This article belongs to the Special Issue Metal Metabolism in Animals)

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19 pages, 2102 KiB

Open AccessArticle

Reference Genes in the Pathosystem Phakopsora pachyrhizi/ Soybean Suitable for Normalization in Transcript Profiling

by Daniela Hirschburger^†, Manuel Müller^†, Ralf T. Voegele and Tobias Link^*

¹ Department of Phytopathology, Institute of Phytomedicine, Faculty of Agricultural Sciences, University of Hohenheim, Otto-Sander-Straße 5, 70599 Stuttgart, Germany

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2015, 16(9), 23057-23075; https://doi.org/10.3390/ijms160923057 - 23 Sep 2015

Cited by 16 | Viewed by 7065

Abstract

Phakopsora pachyrhizi is a devastating pathogen on soybean, endangering soybean production worldwide. Use of Host Induced Gene Silencing (HIGS) and the study of effector proteins could provide novel strategies for pathogen control. For both approaches quantification of transcript abundance by RT-qPCR is essential. [...] Read more.

Phakopsora pachyrhizi is a devastating pathogen on soybean, endangering soybean production worldwide. Use of Host Induced Gene Silencing (HIGS) and the study of effector proteins could provide novel strategies for pathogen control. For both approaches quantification of transcript abundance by RT-qPCR is essential. Suitable stable reference genes for normalization are indispensable to obtain accurate RT-qPCR results. According to the Minimum Information for Publication of Quantitative Real-Time PCR Experiments (MIQE) guidelines and using algorithms geNorm and NormFinder we tested candidate reference genes from P. pachyrhizi and Glycine max for their suitability in normalization of transcript levels throughout the infection process. For P. pachyrhizi we recommend a combination of CytB and PDK or GAPDH for in planta experiments. Gene expression during in vitro stages and over the whole infection process was found to be highly unstable. Here, RPS14 and UbcE2 are ranked best by geNorm and NormFinder. Alternatively CytB that has the smallest Cq range (Cq: quantification cycle) could be used. We recommend specification of gene expression relative to the germ tube stage rather than to the resting urediospore stage. For studies omitting the resting spore and the appressorium stages a combination of Elf3 and RPS9, or PKD and GAPDH should be used. For normalization of soybean genes during rust infection Ukn2 and cons7 are recommended. Full article

(This article belongs to the Special Issue Plant Microbe Interaction)

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16 pages, 1075 KiB

Open AccessArticle

Multiple Factors Drive Replicating Strand Composition Bias in Bacterial Genomes

by Hai-Long Zhao^1,2,†, Zhong-Kui Xia^1,2,†, Fa-Zhan Zhang^1,2, Yuan-Nong Ye^1,2,* and Feng-Biao Guo^1,2,*

¹ Center of Bioinformatics, Key Laboratory for NeuroInformation of the Ministry of Education, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, China

² Center for Information in BioMedicine, University of Electronic Science and Technology of China, Chengdu 610054, China

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2015, 16(9), 23111-23126; https://doi.org/10.3390/ijms160923111 - 23 Sep 2015

Cited by 9 | Viewed by 5306

Abstract

Composition bias from Chargaff’s second parity rule (PR2) has long been found in sequenced genomes, and is believed to relate strongly with the replication process in microbial genomes. However, some disagreement on the underlying reason for strand composition bias remains. We performed an [...] Read more.

Composition bias from Chargaff’s second parity rule (PR2) has long been found in sequenced genomes, and is believed to relate strongly with the replication process in microbial genomes. However, some disagreement on the underlying reason for strand composition bias remains. We performed an integrative analysis of various genomic features that might influence composition bias using a large-scale dataset of 1111 genomes. Our results indicate (1) the bias was stronger in obligate intracellular bacteria than in other free-living species (p-value = 0.0305); (2) Fusobacteria and Firmicutes had the highest average bias among the 24 microbial phyla analyzed; (3) the strength of selected codon usage bias and generation times were not observably related to strand composition bias (p-value = 0.3247); (4) significant negative relationships were found between GC content, genome size, rearrangement frequency, Clusters of Orthologous Groups (COG) functional subcategories A, C, I, Q, and composition bias (p-values < 1.0 × 10⁻⁸); (5) gene density and COG functional subcategories D, F, J, L, and V were positively related with composition bias (p-value < 2.2 × 10⁻¹⁶); and (6) gene density made the most important contribution to composition bias, indicating transcriptional bias was associated strongly with strand composition bias. Therefore, strand composition bias was found to be influenced by multiple factors with varying weights. Full article

(This article belongs to the Special Issue Microbial Genomics and Metabolomics)

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25 pages, 1533 KiB

Open AccessReview

Abiotic Stresses: Insight into Gene Regulation and Protein Expression in Photosynthetic Pathways of Plants

by Mohammad-Zaman Nouri^1,*, Ali Moumeni¹ and Setsuko Komatsu^2,*

¹ Rice Research Institute of Iran, Mazandaran Branch, Agricultural Research, Education and Extension Organization (AREEO), Amol 46191-91951, Iran

² National Institute of Crop Science, National Agriculture and Food Research Organization, Tsukuba 305-8518, Japan

Int. J. Mol. Sci. 2015, 16(9), 20392-20416; https://doi.org/10.3390/ijms160920392 - 28 Aug 2015

Cited by 128 | Viewed by 10366

Abstract

Global warming and climate change intensified the occurrence and severity of abiotic stresses that seriously affect the growth and development of plants,especially, plant photosynthesis. The direct impact of abiotic stress on the activity of photosynthesis is disruption of all photosynthesis components such as [...] Read more.

Global warming and climate change intensified the occurrence and severity of abiotic stresses that seriously affect the growth and development of plants,especially, plant photosynthesis. The direct impact of abiotic stress on the activity of photosynthesis is disruption of all photosynthesis components such as photosystem I and II, electron transport, carbon fixation, ATP generating system and stomatal conductance. The photosynthetic system of plants reacts to the stress differently, according to the plant type, photosynthetic systems (C₃ or C₄), type of the stress, time and duration of the occurrence and several other factors. The plant responds to the stresses by a coordinate chloroplast and nuclear gene expression. Chloroplast, thylakoid membrane, and nucleus are the main targets of regulated proteins and metabolites associated with photosynthetic pathways. Rapid responses of plant cell metabolism and adaptation to photosynthetic machinery are key factors for survival of plants in a fluctuating environment. This review gives a comprehensive view of photosynthesis-related alterations at the gene and protein levels for plant adaptation or reaction in response to abiotic stress. Full article

(This article belongs to the Special Issue Plant Proteomic Research)

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37 pages, 1663 KiB

Open AccessReview

Photodynamic Efficiency: From Molecular Photochemistry to Cell Death

by Isabel O. L. Bacellar¹, Tayana M. Tsubone¹, Christiane Pavani² and Mauricio S. Baptista^1,*

¹ Instituto de Química, Universidade de São Paulo, São Paulo 05508-900, Brazil

² Programa de Pós Graduação em Biofotônica Aplicada às Ciências da Saúde, Universidade Nove de Julho, São Paulo 01504-001, Brazil

Int. J. Mol. Sci. 2015, 16(9), 20523-20559; https://doi.org/10.3390/ijms160920523 - 31 Aug 2015

Cited by 339 | Viewed by 14902

Abstract

Photodynamic therapy (PDT) is a clinical modality used to treat cancer and infectious diseases. The main agent is the photosensitizer (PS), which is excited by light and converted to a triplet excited state. This latter species leads to the formation of singlet oxygen [...] Read more.

Photodynamic therapy (PDT) is a clinical modality used to treat cancer and infectious diseases. The main agent is the photosensitizer (PS), which is excited by light and converted to a triplet excited state. This latter species leads to the formation of singlet oxygen and radicals that oxidize biomolecules. The main motivation for this review is to suggest alternatives for achieving high-efficiency PDT protocols, by taking advantage of knowledge on the chemical and biological processes taking place during and after photosensitization. We defend that in order to obtain specific mechanisms of cell death and maximize PDT efficiency, PSes should oxidize specific molecular targets. We consider the role of subcellular localization, how PS photochemistry and photophysics can change according to its nanoenvironment, and how can all these trigger specific cell death mechanisms. We propose that in order to develop PSes that will cause a breakthrough enhancement in the efficiency of PDT, researchers should first consider tissue and intracellular localization, instead of trying to maximize singlet oxygen quantum yields in in vitro tests. In addition to this, we also indicate many open questions and challenges remaining in this field, hoping to encourage future research. Full article

(This article belongs to the Special Issue Advances in Photodynamic Therapy)

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16 pages, 1293 KiB

Open AccessReview

Biomarkers of Chondrocyte Apoptosis and Autophagy in Osteoarthritis

by Giuseppe Musumeci^1,*

, Paola Castrogiovanni¹

, Francesca Maria Trovato²

, Annelie Martina Weinberg³, Mohammad K. Al-Wasiyah^4,5, Mohammed H. Alqahtani⁴ and Ali Mobasheri^5,6,7

¹ Department of Biomedical and Biotechnological Sciences, Human Anatomy and Histology Section, School of Medicine, University of Catania, Catania 95123, Italy

² Department of Clinical and Experimental Medicine, Internal Medicine Division, School of Medicine, University of Catania, Catania 95123, Italy

³ Department of Orthopaedic Surgery, Medical University of Graz, 8036 Graz, Austria

⁴ Aziziah Maternity and Children's Hospital, Jeddah 50204, Saudi Arabia

⁵ King Fahd Medical Research Center (KFMRC), King AbdulAziz University, Jeddah 21589, Saudi Arabia

⁶ The D-BOARD European Consortium for Biomarker Discovery, Department of Veterinary Preclinical Sciences, School of Veterinary Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH, UK

⁷ Arthritis Research UK Centre for Sport, Exercise and Osteoarthritis, Arthritis Research UK Pain Centre, Medical Research Council and Arthritis Research UK Centre for Musculoskeletal Ageing Research, University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, UK

Int. J. Mol. Sci. 2015, 16(9), 20560-20575; https://doi.org/10.3390/ijms160920560 - 31 Aug 2015

Cited by 249 | Viewed by 18688

Abstract

Cell death with morphological and molecular features of apoptosis has been detected in osteoarthritic (OA) cartilage, which suggests a key role for chondrocyte death/survival in the pathogenesis of OA. Identification of biomarkers of chondrocyte apoptosis may facilitate the development of novel therapies that [...] Read more.

Cell death with morphological and molecular features of apoptosis has been detected in osteoarthritic (OA) cartilage, which suggests a key role for chondrocyte death/survival in the pathogenesis of OA. Identification of biomarkers of chondrocyte apoptosis may facilitate the development of novel therapies that may eliminate the cause or, at least, slow down the degenerative processes in OA. The aim of this review was to explore the molecular markers and signals that induce chondrocyte apoptosis in OA. A literature search was conducted in PubMed, Scopus, Web of Science and Google Scholar using the keywords chondrocyte death, apoptosis, osteoarthritis, autophagy and biomarker. Several molecules considered to be markers of chondrocyte apoptosis will be discussed in this brief review. Molecular markers and signalling pathways associated with chondroycte apoptosis may turn out to be therapeutic targets in OA and approaches aimed at neutralizing apoptosis-inducing molecules may at least delay the progression of cartilage degeneration in OA. Full article

(This article belongs to the Special Issue Apoptotic Chondrocytes and Osteoarthritis)

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27 pages, 727 KiB

Open AccessReview

Mitochondria: A Therapeutic Target for Parkinson’s Disease?

by Yu Luo^1,*, Alan Hoffer¹, Barry Hoffer¹ and Xin Qi^2,*

¹ Department of Neurological Surgery, Case Western Reserve University, Cleveland, OH 44106, USA

² Department of Physiology, Case Western Reserve University, Cleveland, OH 44106, USA

Int. J. Mol. Sci. 2015, 16(9), 20704-20730; https://doi.org/10.3390/ijms160920704 - 1 Sep 2015

Cited by 84 | Viewed by 10787

Abstract

Parkinson’s disease (PD) is one of the most common neurodegenerative disorders. The exact causes of neuronal damage are unknown, but mounting evidence indicates that mitochondrial-mediated pathways contribute to the underlying mechanisms of dopaminergic neuronal cell death both in PD patients and in PD [...] Read more.

Parkinson’s disease (PD) is one of the most common neurodegenerative disorders. The exact causes of neuronal damage are unknown, but mounting evidence indicates that mitochondrial-mediated pathways contribute to the underlying mechanisms of dopaminergic neuronal cell death both in PD patients and in PD animal models. Mitochondria are organized in a highly dynamic tubular network that is continuously reshaped by opposing processes of fusion and fission. Defects in either fusion or fission, leading to mitochondrial fragmentation, limit mitochondrial motility, decrease energy production and increase oxidative stress, thereby promoting cell dysfunction and death. Thus, the regulation of mitochondrial dynamics processes, such as fusion, fission and mitophagy, represents important mechanisms controlling neuronal cell fate. In this review, we summarize some of the recent evidence supporting that impairment of mitochondrial dynamics, mitophagy and mitochondrial import occurs in cellular and animal PD models and disruption of these processes is a contributing mechanism to cell death in dopaminergic neurons. We also summarize mitochondria-targeting therapeutics in models of PD, proposing that modulation of mitochondrial impairment might be beneficial for drug development toward treatment of PD. Full article

(This article belongs to the Special Issue Mitochondrial Dysfunction in Ageing and Diseases)

26 pages, 818 KiB

Open AccessReview

Common Amino Acid Subsequences in a Universal Proteome—Relevance for Food Science

by Piotr Minkiewicz^*

, Małgorzata Darewicz

, Anna Iwaniak, Jolanta Sokołowska, Piotr Starowicz, Justyna Bucholska and Monika Hrynkiewicz

Department of Food Biochemistry, University of Warmia and Mazury in Olsztyn, Plac Cieszyński 1, Olsztyn-Kortowo 10-726, Poland

Int. J. Mol. Sci. 2015, 16(9), 20748-20773; https://doi.org/10.3390/ijms160920748 - 1 Sep 2015

Cited by 27 | Viewed by 7843

Abstract

A common subsequence is a fragment of the amino acid chain that occurs in more than one protein. Common subsequences may be an object of interest for food scientists as biologically active peptides, epitopes, and/or protein markers that are used in comparative proteomics. [...] Read more.

A common subsequence is a fragment of the amino acid chain that occurs in more than one protein. Common subsequences may be an object of interest for food scientists as biologically active peptides, epitopes, and/or protein markers that are used in comparative proteomics. An individual bioactive fragment, in particular the shortest fragment containing two or three amino acid residues, may occur in many protein sequences. An individual linear epitope may also be present in multiple sequences of precursor proteins. Although recent recommendations for prediction of allergenicity and cross-reactivity include not only sequence identity, but also similarities in secondary and tertiary structures surrounding the common fragment, local sequence identity may be used to screen protein sequence databases for potential allergens in silico. The main weakness of the screening process is that it overlooks allergens and cross-reactivity cases without identical fragments corresponding to linear epitopes. A single peptide may also serve as a marker of a group of allergens that belong to the same family and, possibly, reveal cross-reactivity. This review article discusses the benefits for food scientists that follow from the common subsequences concept. Full article

(This article belongs to the Special Issue Advances in Proteomic Research)

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67 pages, 2389 KiB

Open AccessReview

Recombinant Lipases and Phospholipases and Their Use as Biocatalysts for Industrial Applications

by Grazia M. Borrelli and Daniela Trono^*

Consiglio per la Ricerca in Agricoltura e l'Analisi dell'Economia Agraria, Centro di Ricerca per la Cerealicoltura, S.S. 673 Km 25, 200-71122 Foggia, Italy

Int. J. Mol. Sci. 2015, 16(9), 20774-20840; https://doi.org/10.3390/ijms160920774 - 1 Sep 2015

Cited by 298 | Viewed by 22276

Abstract

Lipases and phospholipases are interfacial enzymes that hydrolyze hydrophobic ester linkages of triacylglycerols and phospholipids, respectively. In addition to their role as esterases, these enzymes catalyze a plethora of other reactions; indeed, lipases also catalyze esterification, transesterification and interesterification reactions, and phospholipases also [...] Read more.

Lipases and phospholipases are interfacial enzymes that hydrolyze hydrophobic ester linkages of triacylglycerols and phospholipids, respectively. In addition to their role as esterases, these enzymes catalyze a plethora of other reactions; indeed, lipases also catalyze esterification, transesterification and interesterification reactions, and phospholipases also show acyltransferase, transacylase and transphosphatidylation activities. Thus, lipases and phospholipases represent versatile biocatalysts that are widely used in various industrial applications, such as for biodiesels, food, nutraceuticals, oil degumming and detergents; minor applications also include bioremediation, agriculture, cosmetics, leather and paper industries. These enzymes are ubiquitous in most living organisms, across animals, plants, yeasts, fungi and bacteria. For their greater availability and their ease of production, microbial lipases and phospholipases are preferred to those derived from animals and plants. Nevertheless, traditional purification strategies from microbe cultures have a number of disadvantages, which include non-reproducibility and low yields. Moreover, native microbial enzymes are not always suitable for biocatalytic processes. The development of molecular techniques for the production of recombinant heterologous proteins in a host system has overcome these constraints, as this allows high-level protein expression and production of new redesigned enzymes with improved catalytic properties. These can meet the requirements of specific industrial process better than the native enzymes. The purpose of this review is to give an overview of the structural and functional features of lipases and phospholipases, to describe the recent advances in optimization of the production of recombinant lipases and phospholipases, and to summarize the information available relating to their major applications in industrial processes. Full article

(This article belongs to the Special Issue Molecular Biocatalysis)

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18 pages, 739 KiB

Open AccessReview

Th17 Cells as Potential Probiotic Therapeutic Targets in Inflammatory Bowel Diseases

by Eddy Owaga¹, Rong-Hong Hsieh², Beatrice Mugendi¹, Sakhile Masuku³, Chun-Kuang Shih² and Jung-Su Chang^2,*

¹ Institute of Food and Bioresources Technology, Dedan Kimathi University of Technology, 10100 Nyeri, Kenya

² School of Nutrition and Health Sciences, College of Public Health and Nutrition, Taipei Medical University, 250 Wu-Xing Street, 110 Taipei, Taiwan

³ Community Health Nursing Department, Faculty of Health Sciences, University of Swaziland, H100 Mbabane, Swaziland

Int. J. Mol. Sci. 2015, 16(9), 20841-20858; https://doi.org/10.3390/ijms160920841 - 1 Sep 2015

Cited by 108 | Viewed by 10733

Abstract

Inflammatory bowel diseases (IBD) are characterized by wasting and chronic intestinal inflammation triggered by various cytokine-mediated pathways. In recent years, it was shown that T helper 17 (Th17) cells are involved in the pathogenesis of IBD, which makes them an attractive therapeutic target. [...] Read more.

Inflammatory bowel diseases (IBD) are characterized by wasting and chronic intestinal inflammation triggered by various cytokine-mediated pathways. In recent years, it was shown that T helper 17 (Th17) cells are involved in the pathogenesis of IBD, which makes them an attractive therapeutic target. Th17 cells preferentially produce interleukin (IL)-17A–F as signature cytokines. The role of the interplay between host genetics and intestinal microbiota in the pathogenesis of IBD was demonstrated. Probiotics are live microorganisms that when orally ingested in adequate amounts, confer a health benefit to the host by modulating the enteric flora or by stimulating the local immune system. Several studies indicated the effectiveness of probiotics in preventing and treating IBD (ulcerative colitis, and Crohn’s disease). Furthermore, there is mounting evidence of probiotics selectively targeting the Th17 lineage in the prevention and management of inflammatory and autoimmune diseases such as IBD. This review highlights critical roles of Th17 cells in the pathogenesis of IBD and the rationale for using probiotics as a novel therapeutic approach for IBD through manipulation of Th17 cells. The potential molecular mechanisms by which probiotics modulate Th17 cells differentiation and production are also discussed. Full article

(This article belongs to the Special Issue Mechanism of Action and Applications of Cytokines in Immunotherapy)

23 pages, 892 KiB

Open AccessReview

Two Effective Routes for Removing Lineage Restriction Roadblocks: From Somatic Cells to Hepatocytes

by Chenxia Hu

and Lanjuan Li^*

Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, School of Medicine, First Affiliated Hospital, Zhejiang University, Hangzhou 310058, China

Int. J. Mol. Sci. 2015, 16(9), 20873-20895; https://doi.org/10.3390/ijms160920873 - 1 Sep 2015

Cited by 4 | Viewed by 6470

Abstract

The conversion of somatic cells to hepatocytes has fundamentally re-shaped traditional concepts regarding the limited resources for hepatocyte therapy. With the various induced pluripotent stem cell (iPSC) generation routes, most somatic cells can be effectively directed to functional stem cells, and this strategy [...] Read more.

The conversion of somatic cells to hepatocytes has fundamentally re-shaped traditional concepts regarding the limited resources for hepatocyte therapy. With the various induced pluripotent stem cell (iPSC) generation routes, most somatic cells can be effectively directed to functional stem cells, and this strategy will supply enough pluripotent material to generate promising functional hepatocytes. However, the major challenges and potential applications of reprogrammed hepatocytes remain under investigation. In this review, we provide a summary of two effective routes including direct reprogramming and indirect reprogramming from somatic cells to hepatocytes and the general potential applications of the resulting hepatocytes. Through these approaches, we are striving toward the goal of achieving a robust, mature source of clinically relevant lineages. Full article

(This article belongs to the Special Issue Pluripotent Stem Cell Technology for Disease Modeling, Drug Discovery and Regenerative Medicine)

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30 pages, 956 KiB

Open AccessReview

Biological Networks Underlying Abiotic Stress Tolerance in Temperate Crops—A Proteomic Perspective

by Klára Kosová^1,*, Pavel Vítámvás¹, Milan Oldřich Urban¹, Miroslav Klíma¹, Amitava Roy² and Ilja Tom Prášil¹

¹ Laboratory of Plant Stress Biology and Biotechnology, Division of Crop Genetics and Breeding, Crop Research Institute, Drnovská 507/73, 16106 Prague, Czech Republic

² Research Institute of Agricultural Engineering, Drnovská 507, 16106 Prague, Czech Republic

Int. J. Mol. Sci. 2015, 16(9), 20913-20942; https://doi.org/10.3390/ijms160920913 - 1 Sep 2015

Cited by 126 | Viewed by 10789

Abstract

Abiotic stress factors, especially low temperatures, drought, and salinity, represent the major constraints limiting agricultural production in temperate climate. Under the conditions of global climate change, the risk of damaging effects of abiotic stresses on crop production increases. Plant stress response represents an [...] Read more.

Abiotic stress factors, especially low temperatures, drought, and salinity, represent the major constraints limiting agricultural production in temperate climate. Under the conditions of global climate change, the risk of damaging effects of abiotic stresses on crop production increases. Plant stress response represents an active process aimed at an establishment of novel homeostasis under altered environmental conditions. Proteins play a crucial role in plant stress response since they are directly involved in shaping the final phenotype. In the review, results of proteomic studies focused on stress response of major crops grown in temperate climate including cereals: common wheat (Triticum aestivum), durum wheat (Triticum durum), barley (Hordeum vulgare), maize (Zea mays); leguminous plants: alfalfa (Medicago sativa), soybean (Glycine max), common bean (Phaseolus vulgaris), pea (Pisum sativum); oilseed rape (Brassica napus); potato (Solanum tuberosum); tobacco (Nicotiana tabaccum); tomato (Lycopersicon esculentum); and others, to a wide range of abiotic stresses (cold, drought, salinity, heat, imbalances in mineral nutrition and heavy metals) are summarized. The dynamics of changes in various protein functional groups including signaling and regulatory proteins, transcription factors, proteins involved in protein metabolism, amino acid metabolism, metabolism of several stress-related compounds, proteins with chaperone and protective functions as well as structural proteins (cell wall components, cytoskeleton) are briefly overviewed. Attention is paid to the differences found between differentially tolerant genotypes. In addition, proteomic studies aimed at proteomic investigation of multiple stress factors are discussed. In conclusion, contribution of proteomic studies to understanding the complexity of crop response to abiotic stresses as well as possibilities to identify and utilize protein markers in crop breeding processes are discussed. Full article

(This article belongs to the Special Issue Abiotic Stress and Gene Networks in Plants)

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25 pages, 1213 KiB

Open AccessReview

Role of RUNX2 in Breast Carcinogenesis

by Daniel Wysokinski¹, Janusz Blasiak^1,* and Elzbieta Pawlowska²

¹ Department of Molecular Genetics, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland

² Department of Orthodontics, Medical University of Lodz, Pomorska 251, 92-216 Lodz, Poland

Int. J. Mol. Sci. 2015, 16(9), 20969-20993; https://doi.org/10.3390/ijms160920969 - 2 Sep 2015

Cited by 48 | Viewed by 9920

Abstract

RUNX2 is a transcription factor playing the major role in osteogenesis, but it can be involved in DNA damage response, which is crucial for cancer transformation. RUNX2 can interact with cell cycle regulators: cyclin-dependent kinases, pRB and p21Cip1 proteins, as well as the [...] Read more.

RUNX2 is a transcription factor playing the major role in osteogenesis, but it can be involved in DNA damage response, which is crucial for cancer transformation. RUNX2 can interact with cell cycle regulators: cyclin-dependent kinases, pRB and p21Cip1 proteins, as well as the master regulator of the cell cycle, the p53 tumor suppressor. RUNX2 is involved in many signaling pathways, including those important for estrogen signaling, which, in turn, are significant for breast carcinogenesis. RUNX2 can promote breast cancer development through Wnt and Tgfβ signaling pathways, especially in estrogen receptor (ER)-negative cases. ERα interacts directly with RUNX2 and regulates its activity. Moreover, the ERa gene has a RUNX2 binding site within its promoter. RUNX2 stimulates the expression of aromatase, an estrogen producing enzyme, increasing the level of estrogens, which in turn stimulate cell proliferation and replication errors, which can be turned into carcinogenic mutations. Exploring the role of RUNX2 in the pathogenesis of breast cancer can lead to revealing new therapeutic targets. Full article

(This article belongs to the Special Issue Advances in Molecular Oncology)

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14 pages, 3374 KiB

Open AccessReview

Current Proceedings in the Molecular Dissection of Hepatocellular Adenomas: Review and Hands-on Guide for Diagnosis

by Diane Goltz^* and Hans-Peter Fischer

Institute of Pathology, University Hospital of Bonn, 53127 Bonn, Germany

Int. J. Mol. Sci. 2015, 16(9), 20994-21007; https://doi.org/10.3390/ijms160920994 - 2 Sep 2015

Cited by 4 | Viewed by 6425

Abstract

Molecular dissection of hepatocellular adenomas has brought forward a diversity of well-defined entities. Their distinction is important for routine practice, since prognosis is tightly related to the individual subgroup. Very recent activity has generated new details on the molecular background of hepatocellular adenoma, [...] Read more.

Molecular dissection of hepatocellular adenomas has brought forward a diversity of well-defined entities. Their distinction is important for routine practice, since prognosis is tightly related to the individual subgroup. Very recent activity has generated new details on the molecular background of hepatocellular adenoma, which this article aims to integrate into the current concepts of taxonomy. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Human Liver Diseases)

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10 pages, 888 KiB

Open AccessReview

Single-Base Pair Genome Editing in Human Cells by Using Site-Specific Endonucleases

by Hiroshi Ochiai

Research Center for the Mathematics on Chromatin Live Dynamics (RcMcD), Hiroshima University, Higashi-Hiroshima 739-8530, Japan

Int. J. Mol. Sci. 2015, 16(9), 21128-21137; https://doi.org/10.3390/ijms160921128 - 3 Sep 2015

Cited by 10 | Viewed by 7380

Abstract

Genome-wide association studies have identified numerous single-nucleotide polymorphisms (SNPs) associated with human diseases or phenotypes. However, causal relationships between most SNPs and the associated disease have not been established, owing to technical challenges such as unavailability of suitable cell lines. Recently, efficient editing [...] Read more.

Genome-wide association studies have identified numerous single-nucleotide polymorphisms (SNPs) associated with human diseases or phenotypes. However, causal relationships between most SNPs and the associated disease have not been established, owing to technical challenges such as unavailability of suitable cell lines. Recently, efficient editing of a single base pair in the genome was achieved using programmable site-specific nucleases. This technique enables experimental confirmation of the causality between SNPs and disease, and is potentially valuable in clinical applications. In this review, I introduce the molecular basis and describe examples of single-base pair editing in human cells. I also discuss the challenges associated with the technique, as well as possible solutions. Full article

(This article belongs to the Special Issue Genome Editing)

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15 pages, 2008 KiB

Open AccessReview

PI3K and AKT: Unfaithful Partners in Cancer

by Seraina Faes and Olivier Dormond^*

Department of Visceral Surgery, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Pavillon 4, Av. de Beaumont, Lausanne 1011, Switzerland

Int. J. Mol. Sci. 2015, 16(9), 21138-21152; https://doi.org/10.3390/ijms160921138 - 3 Sep 2015

Cited by 229 | Viewed by 16841

Abstract

The phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway regulates multiple cellular processes. An overactivation of the pathway is frequently present in human malignancies and plays a key role in cancer progression. Hence, its inhibition has become a promising approach in cancer therapy. However, the development [...] Read more.

The phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway regulates multiple cellular processes. An overactivation of the pathway is frequently present in human malignancies and plays a key role in cancer progression. Hence, its inhibition has become a promising approach in cancer therapy. However, the development of resistances, such as the abrogation of negative feedback mechanisms or the activation of other proliferative signaling pathways, has considerably limited the anticancer efficacy of PI3K/AKT inhibitors. In addition, emerging evidence points out that although AKT is acknowledged as the major downstream effector of PI3K, both PI3K and AKT can operate independently of each other in cancer, revealing another level of complexity in this pathway. Here, we highlight the complex relationship between PI3K and AKT in cancer and further discuss the consequences of this relationship for cancer therapy. Full article

(This article belongs to the Special Issue Advances in Molecular Oncology)

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22 pages, 1292 KiB

Open AccessReview

Physiological Dynamics in Demyelinating Diseases: Unraveling Complex Relationships through Computer Modeling

by Jay S. Coggan^1,*, Stefan Bittner², Klaus M. Stiefel¹, Sven G. Meuth² and Steven A. Prescott^3,4

¹ NeuroLinx Research Institute, La Jolla, CA 92039, USA

² Department of Neurology, Institute of Physiology, Universitätsklinikum Münster, 48149 Münster, Germany

³ Neurosciences and Mental Health, the Hospital for Sick Children, Toronto, ON M5G 1X8, Canada

⁴ Department of Physiology and the Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON M5G 1X8, Canada

Int. J. Mol. Sci. 2015, 16(9), 21215-21236; https://doi.org/10.3390/ijms160921215 - 7 Sep 2015

Cited by 28 | Viewed by 19556

Abstract

Despite intense research, few treatments are available for most neurological disorders. Demyelinating diseases are no exception. This is perhaps not surprising considering the multifactorial nature of these diseases, which involve complex interactions between immune system cells, glia and neurons. In the case of [...] Read more.

Despite intense research, few treatments are available for most neurological disorders. Demyelinating diseases are no exception. This is perhaps not surprising considering the multifactorial nature of these diseases, which involve complex interactions between immune system cells, glia and neurons. In the case of multiple sclerosis, for example, there is no unanimity among researchers about the cause or even which system or cell type could be ground zero. This situation precludes the development and strategic application of mechanism-based therapies. We will discuss how computational modeling applied to questions at different biological levels can help link together disparate observations and decipher complex mechanisms whose solutions are not amenable to simple reductionism. By making testable predictions and revealing critical gaps in existing knowledge, such models can help direct research and will provide a rigorous framework in which to integrate new data as they are collected. Nowadays, there is no shortage of data; the challenge is to make sense of it all. In that respect, computational modeling is an invaluable tool that could, ultimately, transform how we understand, diagnose, and treat demyelinating diseases. Full article

(This article belongs to the Special Issue Advances in Multiple Sclerosis)

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17 pages, 1558 KiB

Open AccessReview

To Extinguish the Fire from Outside the Cell or to Shutdown the Gas Valve Inside? Novel Trends in Anti-Inflammatory Therapies

by Annalisa Marcuzzi^1,*

, Elisa Piscianz²

, Erica Valencic², Lorenzo Monasta²

, Liza Vecchi Brumatti² and Alberto Tommasini²

¹ Department of Medicine, Surgery and Health Sciences, University of Trieste, Piazzale Europa 1, Trieste 34128, Italy

² Institute for Maternal and Child Health - IRCCS "Burlo Garofolo" - , via dell'Istria, 65/1, Trieste 34137, Italy

Int. J. Mol. Sci. 2015, 16(9), 21277-21293; https://doi.org/10.3390/ijms160921277 - 7 Sep 2015

Cited by 6 | Viewed by 6001

Abstract

Cytokines are the most important soluble mediators of inflammation. Rare pediatric diseases provided exemplar conditions to study the anti-inflammatory efficacy of new generation therapies (biologics/biopharmaceuticals) selectively targeting single cytokines. Monoclonal antibodies and recombinant proteins have revolutionized anti-inflammatory therapies in the last two decades, [...] Read more.

Cytokines are the most important soluble mediators of inflammation. Rare pediatric diseases provided exemplar conditions to study the anti-inflammatory efficacy of new generation therapies (biologics/biopharmaceuticals) selectively targeting single cytokines. Monoclonal antibodies and recombinant proteins have revolutionized anti-inflammatory therapies in the last two decades, allowing the specific targeting of single cytokines. They are very effective in extinguishing inflammation from outside the cell, even with the risk of an excessive and prolonged immunosuppression. Small molecules can enter the cell and shutdown the valve of inflammation by directly targeting signal proteins involved in cytokine release or in response to cytokines. They are orally-administrable drugs whose dosage can be easily adjusted to obtain the desired anti-inflammatory effect. This could make these drugs more suitable for a wide range of diseases as stroke, gout, or neurological impairment, where inflammatory activation plays a pivotal role as trigger. Autoinflammatory diseases, which have previously put anti-cytokine proteins in the limelight, can again provide a valuable model to measure the real potential of small inhibitors as anti-inflammatory agents. Full article

(This article belongs to the Special Issue Mechanism of Action and Applications of Cytokines in Immunotherapy)

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34 pages, 1027 KiB

Open AccessReview

The Role of Mitochondrial DNA in Mediating Alveolar Epithelial Cell Apoptosis and Pulmonary Fibrosis

by Seok-Jo Kim^1,2, Paul Cheresh^1,2, Renea P. Jablonski^1,2, David B. Williams^1,2 and David W. Kamp^1,2,*

¹ Department of Medicine, Division of Pulmonary and Critical Care Medicine, Jesse Brown VA Medical Center, Chicago, IL 60612, USA

² Division of Pulmonary & Critical Care Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA

Int. J. Mol. Sci. 2015, 16(9), 21486-21519; https://doi.org/10.3390/ijms160921486 - 7 Sep 2015

Cited by 106 | Viewed by 17504

Abstract

Convincing evidence has emerged demonstrating that impairment of mitochondrial function is critically important in regulating alveolar epithelial cell (AEC) programmed cell death (apoptosis) that may contribute to aging-related lung diseases, such as idiopathic pulmonary fibrosis (IPF) and asbestosis (pulmonary fibrosis following asbestos exposure). [...] Read more.

Convincing evidence has emerged demonstrating that impairment of mitochondrial function is critically important in regulating alveolar epithelial cell (AEC) programmed cell death (apoptosis) that may contribute to aging-related lung diseases, such as idiopathic pulmonary fibrosis (IPF) and asbestosis (pulmonary fibrosis following asbestos exposure). The mammalian mitochondrial DNA (mtDNA) encodes for 13 proteins, including several essential for oxidative phosphorylation. We review the evidence implicating that oxidative stress-induced mtDNA damage promotes AEC apoptosis and pulmonary fibrosis. We focus on the emerging role for AEC mtDNA damage repair by 8-oxoguanine DNA glycosylase (OGG1) and mitochondrial aconitase (ACO-2) in maintaining mtDNA integrity which is important in preventing AEC apoptosis and asbestos-induced pulmonary fibrosis in a murine model. We then review recent studies linking the sirtuin (SIRT) family members, especially SIRT3, to mitochondrial integrity and mtDNA damage repair and aging. We present a conceptual model of how SIRTs modulate reactive oxygen species (ROS)-driven mitochondrial metabolism that may be important for their tumor suppressor function. The emerging insights into the pathobiology underlying AEC mtDNA damage and apoptosis is suggesting novel therapeutic targets that may prove useful for the management of age-related diseases, including pulmonary fibrosis and lung cancer. Full article

(This article belongs to the Special Issue Mitochondrial Dysfunction in Ageing and Diseases)

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20 pages, 1026 KiB

Open AccessReview

Anthocyanin Absorption and Metabolism by Human Intestinal Caco-2 Cells—A Review

by Senem Kamiloglu^1,2

, Esra Capanoglu^2,*

, Charlotte Grootaert¹

and John Van Camp¹

¹ Laboratory of Food Chemistry and Human Nutrition (nutriFOODchem), Department of Food Safety and Food Quality, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, B-9000 Ghent, Belgium

² Department of Food Engineering, Faculty of Chemical and Metallurgical Engineering, Istanbul Technical University, 34469 Maslak, Istanbul, Turkey

Int. J. Mol. Sci. 2015, 16(9), 21555-21574; https://doi.org/10.3390/ijms160921555 - 8 Sep 2015

Cited by 207 | Viewed by 18702

Abstract

Anthocyanins from different plant sources have been shown to possess health beneficial effects against a number of chronic diseases. To obtain any influence in a specific tissue or organ, these bioactive compounds must be bioavailable, i.e., effectively absorbed from the gut into [...] Read more.

Anthocyanins from different plant sources have been shown to possess health beneficial effects against a number of chronic diseases. To obtain any influence in a specific tissue or organ, these bioactive compounds must be bioavailable, i.e., effectively absorbed from the gut into the circulation and transferred to the appropriate location within the body while still maintaining their bioactivity. One of the key factors affecting the bioavailability of anthocyanins is their transport through the gut epithelium. The Caco-2 cell line, a human intestinal epithelial cell model derived from a colon carcinoma, has been proven to be a good alternative to animal studies for predicting intestinal absorption of anthocyanins. Studies investigating anthocyanin absorption by Caco-2 cells report very low absorption of these compounds. However, the bioavailability of anthocyanins may be underestimated since the metabolites formed in the course of digestion could be responsible for the health benefits associated with anthocyanins. In this review, we critically discuss recent findings reported on the anthocyanin absorption and metabolism by human intestinal Caco-2 cells. Full article

(This article belongs to the Special Issue Bioactive Phytochemicals and Functional Food Ingredients in Fruits and Vegetables)

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17 pages, 2012 KiB

Open AccessReview

Genetically Encoded Voltage Indicators in Circulation Research

by Lars Kaestner^1,*, Qinghai Tian¹, Elisabeth Kaiser¹

, Wenying Xian¹, Andreas Müller², Martin Oberhofer^1,†, Sandra Ruppenthal¹, Daniel Sinnecker³, Hidekazu Tsutsui^4,5, Atsushi Miyawaki⁵, Alessandra Moretti^3,6 and Peter Lipp¹

¹ Research Centre for Molecular Imaging and Screening, Institute for Molecular Cell Biology, Saarland University, Homburg/Saar 66421, Germany

² Department of Diagnostic and Interventional Radiology, Saarland University Medical Center, Homburg/Saar 66421, Germany

³ Medizinische Klinik und Poliklinik, Klinikum rechts der Isar der Technischen Universität München, Munich 81675, Germany

⁴ Department of Material Science, JAIST, Nomi, Ishikawa 923-1292, Japan

⁵ Cell Function Dynamics, Brain Science Institute, RIKEN, Wako 351-0192, Japan

⁶ DZHK (German Centre for Cardiovascular Research)-partner site Munich Heart Alliance, Munich, Germany

^† Current address: HEKA, Lambrecht/Pfalz 67466, Germany

Int. J. Mol. Sci. 2015, 16(9), 21626-21642; https://doi.org/10.3390/ijms160921626 - 8 Sep 2015

Cited by 24 | Viewed by 11826

Abstract

Membrane potentials display the cellular status of non-excitable cells and mediate communication between excitable cells via action potentials. The use of genetically encoded biosensors employing fluorescent proteins allows a non-invasive biocompatible way to read out the membrane potential in cardiac myocytes and other [...] Read more.

Membrane potentials display the cellular status of non-excitable cells and mediate communication between excitable cells via action potentials. The use of genetically encoded biosensors employing fluorescent proteins allows a non-invasive biocompatible way to read out the membrane potential in cardiac myocytes and other cells of the circulation system. Although the approaches to design such biosensors date back to the time when the first fluorescent-protein based Förster Resonance Energy Transfer (FRET) sensors were constructed, it took 15 years before reliable sensors became readily available. Here, we review different developments of genetically encoded membrane potential sensors. Furthermore, it is shown how such sensors can be used in pharmacological screening applications as well as in circulation related basic biomedical research. Potentials and limitations will be discussed and perspectives of possible future developments will be provided. Full article

(This article belongs to the Special Issue Membrane Protein Based Biosensors)

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23 pages, 1761 KiB

Open AccessReview

The Three Bacterial Lines of Defense against Antimicrobial Agents

by Gang Zhou^1,2,3, Qing-Shan Shi^1,2,3,*

, Xiao-Mo Huang^1,2,3 and Xiao-Bao Xie^1,2,3

¹ Guangdong Institute of Microbiology, Guangzhou 510070, Guangdong, China

² State Key Laboratory of Applied Microbiology Southern China, Guangzhou 510070, Guangdong, China

³ Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, Guangzhou 510070, Guangdong, China

Int. J. Mol. Sci. 2015, 16(9), 21711-21733; https://doi.org/10.3390/ijms160921711 - 9 Sep 2015

Cited by 85 | Viewed by 13262

Abstract

Antimicrobial agents target a range of extra- and/or intracellular loci from cytoplasmic wall to membrane, intracellular enzymes and genetic materials. Meanwhile, many resistance mechanisms employed by bacteria to counter antimicrobial agents have been found and reported in the past decades. Based on their [...] Read more.

Antimicrobial agents target a range of extra- and/or intracellular loci from cytoplasmic wall to membrane, intracellular enzymes and genetic materials. Meanwhile, many resistance mechanisms employed by bacteria to counter antimicrobial agents have been found and reported in the past decades. Based on their spatially distinct sites of action and distribution of location, antimicrobial resistance mechanisms of bacteria were categorized into three groups, coined the three lines of bacterial defense in this review. The first line of defense is biofilms, which can be formed by most bacteria to overcome the action of antimicrobial agents. In addition, some other bacteria employ the second line of defense, the cell wall, cell membrane, and encased efflux pumps. When antimicrobial agents permeate the first two lines of defense and finally reach the cytoplasm, many bacteria will make use of the third line of defense, including alterations of intracellular materials and gene regulation to protect themselves from harm by bactericides. The presented three lines of defense theory will help us to understand the bacterial resistance mechanisms against antimicrobial agents and design efficient strategies to overcome these resistances. Full article

(This article belongs to the Section Biochemistry)

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11 pages, 708 KiB

Open AccessReview

Isolation of Specific Genomic Regions and Identification of Their Associated Molecules by Engineered DNA-Binding Molecule-Mediated Chromatin Immunoprecipitation (enChIP) Using the CRISPR System and TAL Proteins

by Hodaka Fujii^* and Toshitsugu Fujita

Chromatin Biochemistry Research Group, Combined Program on Microbiology and Immunology, Research Institute for Microbial Diseases, Osaka University, Yamadaoka 3-1, Suita City, Osaka 565-0871, Japan

Int. J. Mol. Sci. 2015, 16(9), 21802-21812; https://doi.org/10.3390/ijms160921802 - 9 Sep 2015

Cited by 12 | Viewed by 9511

Abstract

Comprehensive understanding of genome functions requires identification of molecules (proteins, RNAs, genomic regions, etc.) bound to specific genomic regions of interest in vivo. To perform biochemical and molecular biological analysis of specific genomic regions, we developed engineered DNA-binding molecule-mediated chromatin immunoprecipitation [...] Read more.

Comprehensive understanding of genome functions requires identification of molecules (proteins, RNAs, genomic regions, etc.) bound to specific genomic regions of interest in vivo. To perform biochemical and molecular biological analysis of specific genomic regions, we developed engineered DNA-binding molecule-mediated chromatin immunoprecipitation (enChIP) to purify genomic regions of interest. In enChIP, specific genomic regions are tagged for biochemical purification using engineered DNA-binding molecules, such as transcription activator-like (TAL) proteins and a catalytically inactive form of the clustered regularly interspaced short palindromic repeats (CRISPR) system. enChIP is a comprehensive approach that emphasizes non-biased search using next-generation sequencing (NGS), microarrays, mass spectrometry (MS), and other methods. Moreover, this approach is not restricted to cultured cell lines and can be easily extended to organisms. In this review, we discuss applications of enChIP to elucidating the molecular mechanisms underlying genome functions. Full article

(This article belongs to the Special Issue Genome Editing)

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43 pages, 922 KiB

Open AccessReview

Drug Carrier for Photodynamic Cancer Therapy

by Tilahun Ayane Debele¹

, Sydney Peng² and Hsieh-Chih Tsai^1,*

¹ Graduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology, 106 Taipei, Taiwan

² Department of Chemical Engineering, National Tsing Hua University, 300 Hsinchu, Taiwan

Int. J. Mol. Sci. 2015, 16(9), 22094-22136; https://doi.org/10.3390/ijms160922094 - 14 Sep 2015

Cited by 210 | Viewed by 15120

Abstract

Photodynamic therapy (PDT) is a non-invasive combinatorial therapeutic modality using light, photosensitizer (PS), and oxygen used for the treatment of cancer and other diseases. When PSs in cells are exposed to specific wavelengths of light, they are transformed from the singlet ground state [...] Read more.

Photodynamic therapy (PDT) is a non-invasive combinatorial therapeutic modality using light, photosensitizer (PS), and oxygen used for the treatment of cancer and other diseases. When PSs in cells are exposed to specific wavelengths of light, they are transformed from the singlet ground state (S₀) to an excited singlet state (S₁–S_n), followed by intersystem crossing to an excited triplet state (T₁). The energy transferred from T₁ to biological substrates and molecular oxygen, via type I and II reactions, generates reactive oxygen species, (¹O₂, H₂O₂, O₂*, HO*), which causes cellular damage that leads to tumor cell death through necrosis or apoptosis. The solubility, selectivity, and targeting of photosensitizers are important factors that must be considered in PDT. Nano-formulating PSs with organic and inorganic nanoparticles poses as potential strategy to satisfy the requirements of an ideal PDT system. In this review, we summarize several organic and inorganic PS carriers that have been studied to enhance the efficacy of photodynamic therapy against cancer. Full article

(This article belongs to the Special Issue Advances in Photodynamic Therapy)

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18 pages, 856 KiB

Open AccessReview

CRISPR-Cas9: A Revolutionary Tool for Cancer Modelling

by Raul Torres-Ruiz^1,* and Sandra Rodriguez-Perales^2,*

¹ Viral Vector Technical Unit, Fundacion Centro Nacional de Investigaciones Cardiovasculares (CNIC), Melchor Fernandez Almagro, 3, 28029 Madrid, Spain

² Molecular Cytogenetics Group, Human Cancer Genetics Program, Centro Nacional de Investigaciones Oncológicas (CNIO), Melchor Fernandez Almagro, 3, 28029 Madrid, Spain

Int. J. Mol. Sci. 2015, 16(9), 22151-22168; https://doi.org/10.3390/ijms160922151 - 14 Sep 2015

Cited by 35 | Viewed by 11828

Abstract

The cancer-modelling field is now experiencing a conversion with the recent emergence of the RNA-programmable CRISPR-Cas9 system, a flexible methodology to produce essentially any desired modification in the genome. Cancer is a multistep process that involves many genetic mutations and other genome rearrangements. [...] Read more.

The cancer-modelling field is now experiencing a conversion with the recent emergence of the RNA-programmable CRISPR-Cas9 system, a flexible methodology to produce essentially any desired modification in the genome. Cancer is a multistep process that involves many genetic mutations and other genome rearrangements. Despite their importance, it is difficult to recapitulate the degree of genetic complexity found in patient tumors. The CRISPR-Cas9 system for genome editing has been proven as a robust technology that makes it possible to generate cellular and animal models that recapitulate those cooperative alterations rapidly and at low cost. In this review, we will discuss the innovative applications of the CRISPR-Cas9 system to generate new models, providing a new way to interrogate the development and progression of cancers. Full article

(This article belongs to the Special Issue Genome Editing)

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21 pages, 1202 KiB

Open AccessReview

Impacts of Alternative Splicing Events on the Differentiation of Adipocytes

by Jung-Chun Lin

School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, 250 Wu-Hsing Street, Taipei 11031, Taiwan

Int. J. Mol. Sci. 2015, 16(9), 22169-22189; https://doi.org/10.3390/ijms160922169 - 14 Sep 2015

Cited by 22 | Viewed by 7834

Abstract

Alternative splicing was found to be a common phenomenon after the advent of whole transcriptome analyses or next generation sequencing. Over 90% of human genes were demonstrated to undergo at least one alternative splicing event. Alternative splicing is an effective mechanism to spatiotemporally [...] Read more.

Alternative splicing was found to be a common phenomenon after the advent of whole transcriptome analyses or next generation sequencing. Over 90% of human genes were demonstrated to undergo at least one alternative splicing event. Alternative splicing is an effective mechanism to spatiotemporally expand protein diversity, which influences the cell fate and tissue development. The first focus of this review is to highlight recent studies, which demonstrated effects of alternative splicing on the differentiation of adipocytes. Moreover, use of evolving high-throughput approaches, such as transcriptome analyses (RNA sequencing), to profile adipogenic transcriptomes, is also addressed. Full article

(This article belongs to the Special Issue Post-Transcriptional Gene Regulation by Ribonucleoprotein Complexes)

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14 pages, 5369 KiB

Open AccessReview

Digital Microfluidics for Manipulation and Analysis of a Single Cell

by Jie-Long He

, An-Te Chen, Jyong-Huei Lee and Shih-Kang Fan^*

Department of Mechanical Engineering, National Taiwan University, Taipei 10617, Taiwan

Int. J. Mol. Sci. 2015, 16(9), 22319-22332; https://doi.org/10.3390/ijms160922319 - 15 Sep 2015

Cited by 57 | Viewed by 10516

Abstract

The basic structural and functional unit of a living organism is a single cell. To understand the variability and to improve the biomedical requirement of a single cell, its analysis has become a key technique in biological and biomedical research. With a physical [...] Read more.

The basic structural and functional unit of a living organism is a single cell. To understand the variability and to improve the biomedical requirement of a single cell, its analysis has become a key technique in biological and biomedical research. With a physical boundary of microchannels and microstructures, single cells are efficiently captured and analyzed, whereas electric forces sort and position single cells. Various microfluidic techniques have been exploited to manipulate single cells through hydrodynamic and electric forces. Digital microfluidics (DMF), the manipulation of individual droplets holding minute reagents and cells of interest by electric forces, has received more attention recently. Because of ease of fabrication, compactness and prospective automation, DMF has become a powerful approach for biological application. We review recent developments of various microfluidic chips for analysis of a single cell and for efficient genetic screening. In addition, perspectives to develop analysis of single cells based on DMF and emerging functionality with high throughput are discussed. Full article

(This article belongs to the Special Issue Single Cell Analysis in Biotechnology and Systems Biology)

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17 pages, 1310 KiB

Open AccessReview

Allanblackia Oil: Phytochemistry and Use as a Functional Food

by Sara L. Crockett

Department of Pharmacognosy, Institute of Pharmaceutical Sciences, Universitaetsplatz 4/I, University of Graz, Graz 8010, Austria

Int. J. Mol. Sci. 2015, 16(9), 22333-22349; https://doi.org/10.3390/ijms160922333 - 15 Sep 2015

Cited by 19 | Viewed by 7733

Abstract

The consumption and commercial exploitation of Allanblackia (Clusiaceae) seed oils is of current interest. The favorable physicochemical characteristics of Allanblackia oil (solid at room temperature; high stearic acid content) lend food products that contain it (i.e., vegetable-based dairy products, ice cream, [...] Read more.

The consumption and commercial exploitation of Allanblackia (Clusiaceae) seed oils is of current interest. The favorable physicochemical characteristics of Allanblackia oil (solid at room temperature; high stearic acid content) lend food products that contain it (i.e., vegetable-based dairy products, ice cream, spreads) health advantages over others that contain higher levels of lauric, myristic, and/or palmitic acids, which can increase blood cholesterol levels. Such considerations are important for individuals prone to cardiovascular disease or with hypercholesterolemia. Domestication projects of several Allanblackia species in tropical Africa are underway, but wildcrafting of fruits to meet the seed demand still occurs. Proper species authentication is important, since only authenticated oil can be deemed safe for human consumption. The chemical constituency of Allanblackia seed oils, and potential roles of these phytochemicals in preventive strategies (e.g., as part of a healthy diet) and as pharmacological agents used to treat chronic disease were examined in this review. The primary and secondary metabolite constituency of the seed oils of nearly all Allanblackia species is still poorly known. The presence, identity, and quantity of potentially bioactive secondary metabolites in the seed oils, and pharmacological testing of isolated compounds were identified as important directions for future research. Full article

(This article belongs to the Special Issue Bioactive Phytochemicals and Functional Food Ingredients in Fruits and Vegetables)

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34 pages, 2414 KiB

Open AccessReview

Neuroprotective Strategies after Neonatal Hypoxic Ischemic Encephalopathy

by Brandon J. Dixon^1,†, Cesar Reis^1,2,†, Wing Mann Ho^1,3, Jiping Tang¹ and John H. Zhang^1,2,4,*

¹ Department of Physiology and Pharmacology, Loma Linda University School of Medicine, Loma Linda, CA 92354, USA

² Department of Anesthesiology, Loma Linda University Medical Center, Loma Linda, CA 92354, USA

³ Department of Neurosurgery, Medical University Innsbruck, Tyrol 6020, Austria

⁴ Department of Neurosurgery, Loma Linda University School of Medicine, Loma Linda, CA 92354, USA

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2015, 16(9), 22368-22401; https://doi.org/10.3390/ijms160922368 - 15 Sep 2015

Cited by 156 | Viewed by 16942

Abstract

Neonatal hypoxic ischemic encephalopathy (HIE) is a devastating disease that primarily causes neuronal and white matter injury and is among the leading cause of death among infants. Currently there are no well-established treatments; thus, it is important to understand the pathophysiology of the [...] Read more.

Neonatal hypoxic ischemic encephalopathy (HIE) is a devastating disease that primarily causes neuronal and white matter injury and is among the leading cause of death among infants. Currently there are no well-established treatments; thus, it is important to understand the pathophysiology of the disease and elucidate complications that are creating a gap between basic science and clinical translation. In the development of neuroprotective strategies and translation of experimental results in HIE, there are many limitations and challenges to master based on an appropriate study design, drug delivery properties, dosage, and use in neonates. We will identify understudied targets after HIE, as well as neuroprotective molecules that bring hope to future treatments such as melatonin, topiramate, xenon, interferon-beta, stem cell transplantation. This review will also discuss some of the most recent trials being conducted in the clinical setting and evaluate what directions are needed in the future. Full article

(This article belongs to the Special Issue Neurological Injuries’ Monitoring, Tracking and Treatment)

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24 pages, 899 KiB

Open AccessReview

Bioactive Carbohydrates and Peptides in Foods: An Overview of Sources, Downstream Processing Steps and Associated Bioactivities

by Maria Hayes^*,† and Brijesh K. Tiwari^†

¹ The Food BioSciences Department, Teagasc Food Research Centre, Ashtown, Dublin 15, Ireland

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2015, 16(9), 22485-22508; https://doi.org/10.3390/ijms160922485 - 17 Sep 2015

Cited by 82 | Viewed by 11118

Abstract

Bioactive peptides and carbohydrates are sourced from a myriad of plant, animal and insects and have huge potential for use as food ingredients and pharmaceuticals. However, downstream processing bottlenecks hinder the potential use of these natural bioactive compounds and add cost to production [...] Read more.

Bioactive peptides and carbohydrates are sourced from a myriad of plant, animal and insects and have huge potential for use as food ingredients and pharmaceuticals. However, downstream processing bottlenecks hinder the potential use of these natural bioactive compounds and add cost to production processes. This review discusses the health benefits and bioactivities associated with peptides and carbohydrates of natural origin and downstream processing methodologies and novel processes which may be used to overcome these. Full article

(This article belongs to the Special Issue Bioactive Carbohydrates and Peptides)

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14 pages, 917 KiB

Open AccessReview

The Role of HMGB1 Signaling Pathway in the Development and Progression of Hepatocellular Carcinoma: A Review

by Xuanbin Wang^1,2,*, Longchao Xiang^1,2, Hongliang Li^1,2, Ping Chen¹, Yibin Feng³, Jingxuan Zhang^1,2, Nian Yang^1,2, Fei Li^1,2, Ye Wang^1,2, Quifang Zhang^1,2, Fang Li¹ and Fengjun Cao¹

¹ Laboratory of Chinese Herbal Pharmacology, Renmin Hospital, 30 South Renmin Road, Shiyan 442000, Hubei, China

² Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Hubei University of Medicine, 30 South Renmin Road, Shiyan 442000, Hubei, China

³ School of Chinese Medicine, the University of Hong Kong, 10 Sassoon Road, Pokfulam, Hong Kong, China

Int. J. Mol. Sci. 2015, 16(9), 22527-22540; https://doi.org/10.3390/ijms160922527 - 17 Sep 2015

Cited by 64 | Viewed by 10228

Abstract

The story of high mobility group protein B1 (HMGB1) in cancer is complicated and the function of HMGB1 in different cancers is uncertain. This review aims to retrieve literature regarding HMGB1 from English electronic resources, analyze and summarize the role of the HMGB1 [...] Read more.

The story of high mobility group protein B1 (HMGB1) in cancer is complicated and the function of HMGB1 in different cancers is uncertain. This review aims to retrieve literature regarding HMGB1 from English electronic resources, analyze and summarize the role of the HMGB1 signaling pathway in hepatocellular carcinoma (HCC), and provide useful information for carcinogenesis and progression of HCC. Results showed that HMGB1 could induce cell proliferation, differentiation, cell death, angiogenesis, metastasis, inflammation, and enhance immunofunction in in vitro and in vivo HCC models. HMGB1 and its downstream receptors RAGE, TLRs and TREM-1 may be potential anticancer targets. In conclusion, HMGB1 plays an important role in oncogenesis and represents a novel therapeutic target, which deserves further study. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Human Liver Diseases)

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26 pages, 1149 KiB

Open AccessReview

ω-3 Fatty Acids and Cardiovascular Diseases: Effects, Mechanisms and Dietary Relevance

by Hanne K. Maehre^*, Ida-Johanne Jensen, Edel O. Elvevoll

and Karl-Erik Eilertsen

Norwegian College of Fishery Science Faculty of Biosciences, Fisheries and Economics, UIT The Arctic University of Norway, N-9037 Tromsø, Norway

Int. J. Mol. Sci. 2015, 16(9), 22636-22661; https://doi.org/10.3390/ijms160922636 - 18 Sep 2015

Cited by 91 | Viewed by 18917

Abstract

ω-3 fatty acids (n-3 FA) have, since the 1970s, been associated with beneficial health effects. They are, however, prone to lipid peroxidation due to their many double bonds. Lipid peroxidation is a process that may lead to increased oxidative stress, a [...] Read more.

ω-3 fatty acids (n-3 FA) have, since the 1970s, been associated with beneficial health effects. They are, however, prone to lipid peroxidation due to their many double bonds. Lipid peroxidation is a process that may lead to increased oxidative stress, a condition associated with adverse health effects. Recently, conflicting evidence regarding the health benefits of intake of n-3 from seafood or n-3 supplements has emerged. The aim of this review was thus to examine recent literature regarding health aspects of n-3 FA intake from fish or n-3 supplements, and to discuss possible reasons for the conflicting findings. There is a broad consensus that fish and seafood are the optimal sources of n-3 FA and consumption of approximately 2–3 servings per week is recommended. The scientific evidence of benefits from n-3 supplementation has diminished over time, probably due to a general increase in seafood consumption and better pharmacological intervention and acute treatment of patients with cardiovascular diseases (CVD). Full article

(This article belongs to the Special Issue Omega-3 Fatty Acids in Health and Diseases)

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27 pages, 1309 KiB

Open AccessReview

Interaction of DNA with Simple and Mixed Ligand Copper(II) Complexes of 1,10-Phenanthrolines as Studied by DNA-Fiber EPR Spectroscopy

by Makoto Chikira^1,*, Chew Hee Ng² and Mallayan Palaniandavar³

¹ Department of Applied Chemistry, Chuo University, Kasuga, Bunkyou-ku, Tokyo 112-8551, Japan

² Department of Pharmaceutical Chemistry, International Medical University, Kuala Lumpur 57000, Malaysia

³ Department of Chemistry, Indian Institute of Technology Bombay, Powai, Mumbai 400 076, India

Int. J. Mol. Sci. 2015, 16(9), 22754-22780; https://doi.org/10.3390/ijms160922754 - 21 Sep 2015

Cited by 49 | Viewed by 10358

Abstract

The interaction of simple and ternary Cu(II) complexes of 1,10-phenanthrolines with DNA has been studied extensively because of their various interesting and important functions such as DNA cleavage activity, cytotoxicity towards cancer cells, and DNA based asymmetric catalysis. Such functions are closely related [...] Read more.

The interaction of simple and ternary Cu(II) complexes of 1,10-phenanthrolines with DNA has been studied extensively because of their various interesting and important functions such as DNA cleavage activity, cytotoxicity towards cancer cells, and DNA based asymmetric catalysis. Such functions are closely related to the DNA binding modes of the complexes such as intercalation, groove binding, and electrostatic surface binding. A variety of spectroscopic methods have been used to study the DNA binding mode of the Cu(II) complexes. Of all these methods, DNA-fiber electron paramagnetic resonance (EPR) spectroscopy affords unique information on the DNA binding structures of the complexes. In this review we summarize the results of our DNA-fiber EPR studies on the DNA binding structure of the complexes and discuss them together with the data accumulated by using other measurements. Full article

(This article belongs to the Special Issue Low Molecular Weight DNA and RNA Binding Agents)

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19 pages, 693 KiB

Open AccessReview

Pharmacogenetics of BCR/ABL Inhibitors in Chronic Myeloid Leukemia

by Marialuisa Polillo^1,†, Sara Galimberti^2,†, Claudia Baratè², Mario Petrini², Romano Danesi¹

and Antonello Di Paolo^1,*

¹ Department of Clinical and Experimental Medicine, Section of Pharmacology, University of Pisa, Via Roma 55, 56126 Pisa, Italy

² Department of Clinical and Experimental Medicine, Section of Hematology, University of Pisa, Via Roma 57, 56126 Pisa, Italy

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2015, 16(9), 22811-22829; https://doi.org/10.3390/ijms160922811 - 21 Sep 2015

Cited by 33 | Viewed by 9082

Abstract

Chronic myeloid leukemia was the first haematological neoplasia that benefited from a targeted therapy with imatinib nearly 15 years ago. Since then, several studies have investigated the role of genes, their variants (i.e., polymorphisms) and their encoded proteins in the pharmacokinetics [...] Read more.

Chronic myeloid leukemia was the first haematological neoplasia that benefited from a targeted therapy with imatinib nearly 15 years ago. Since then, several studies have investigated the role of genes, their variants (i.e., polymorphisms) and their encoded proteins in the pharmacokinetics and pharmacodynamics of BCR-ABL1 tyrosine kinase activity inhibitors (TKIs). Transmembrane transporters seem to influence in a significant manner the disposition of TKIs, especially that of imatinib at both cellular and systemic levels. In particular, members of the ATP-binding cassette (ABC) family (namely ABCB1 and ABCG2) together with solute carrier (SLC) transporters (i.e., SLC22A1) are responsible for the differences in drug pharmacokinetics. In the case of the newer TKIs, such as nilotinib and dasatinib, the substrate affinity of these drugs for transporters is variable but lower than that measured for imatinib. In this scenario, the investigation of genetic variants as possible predictive markers has led to some discordant results. With the partial exception of imatinib, these discrepancies seem to limit the application of discovered biomarkers in the clinical settings. In order to overcome these issues, larger prospective confirmative trials are needed. Full article

(This article belongs to the Special Issue Pharmacogenetics and Personalized Medicine)

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26 pages, 1046 KiB

Open AccessReview

Targeting Glutamine Induces Apoptosis: A Cancer Therapy Approach

by Lian Chen¹ and Hengmin Cui^1,2,*

¹ Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Sichuan Agriculture University, Ya’an 625014, China

² College of Veterinary Medicine, Sichuan Agricultural University, Ya’an 625014, China

Int. J. Mol. Sci. 2015, 16(9), 22830-22855; https://doi.org/10.3390/ijms160922830 - 22 Sep 2015

Cited by 144 | Viewed by 23425

Abstract

Glutamine metabolism has been proved to be dysregulated in many cancer cells, and is essential for proliferation of most cancer cells, which makes glutamine an appealing target for cancer therapy. In order to be well used by cells, glutamine must be transported to [...] Read more.

Glutamine metabolism has been proved to be dysregulated in many cancer cells, and is essential for proliferation of most cancer cells, which makes glutamine an appealing target for cancer therapy. In order to be well used by cells, glutamine must be transported to cells by specific transporters and converted to glutamate by glutaminase. There are currently several drugs that target glutaminase under development or clinical trials. Also, glutamine metabolism restriction has been proved to be effective in inhibiting tumor growth both in vivo and vitro through inducing apoptosis, growth arrest and/or autophagy. Here, we review recent researches about glutamine metabolism in cancer, and cell death induced by targeting glutamine, and their potential roles in cancer therapy. Full article

(This article belongs to the Collection Programmed Cell Death and Apoptosis)

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18 pages, 740 KiB

Open AccessReview

The Current Role of Omega-3 Fatty Acids in the Management of Atrial Fibrillation

by Georgios A. Christou^1,*, Konstantinos A. Christou², Panagiotis Korantzopoulos³, Evangelos C. Rizos⁴, Dimitrios N. Nikas³ and John A. Goudevenos³

¹ Laboratory of Physiology, Medical School, University of Ioannina, 45110 Ioannina, Greece

² First Department of Internal Medicine, University Hospital of Ioannina, 45110 Ioannina, Greece

³ First Department of Cardiology, University Hospital of Ioannina, 45110 Ioannina, Greece

⁴ Second Medical Department and Outpatient Lipid Clinic, University Hospital of Ioannina, 45110 Ioannina, Greece

Int. J. Mol. Sci. 2015, 16(9), 22870-22887; https://doi.org/10.3390/ijms160922870 - 22 Sep 2015

Cited by 20 | Viewed by 6510

Abstract

Background: The main dietary source of omega-3 polyunsaturated fatty acids (n-3 PUFA) is fish, which contains eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). In the present manuscript, we aimed to review the current evidence regarding the clinical role of n-3 PUFA in the [...] Read more.

Background: The main dietary source of omega-3 polyunsaturated fatty acids (n-3 PUFA) is fish, which contains eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). In the present manuscript, we aimed to review the current evidence regarding the clinical role of n-3 PUFA in the prevention of atrial fibrillation (AF) and the possible underlying mechanisms. Methods: A literature search based on PubMed listings was performed using “Omega-3 fatty acids” and “atrial fibrilation” as key search terms. Results: n-3 PUFA have been shown to attenuate structural atrial remodeling, prolong atrial effective refractory period through the prevention of reentry and suppress ectopic firing from pulmonary veins. Dietary fish intake has been found to have no effect on the incidence of AF in the majority of studies. Circulating DHA has been consistently reported to be inversely associated with AF risk, whereas EPA has no such effect. The majority of studies investigating the impact of n-3 PUFA supplementation on the incidence of AF following cardiac surgery reported no benefit, though most of them did not use n-3 PUFA pretreatment for adequate duration. Studies using adequate four-week pretreatment with n-3 PUFA before cardioversion of AF showed a reduction of the AF incidence. Conclusions: Although n-3 PUFA have antiarrhythmogenic properties, their clinical efficacy on the prevention of AF is not consistently supported. Further well-designed studies are needed to overcome the limitations of the existing studies and provide robust conclusions. Full article

(This article belongs to the Special Issue Omega-3 Fatty Acids in Health and Diseases)

13 pages, 1013 KiB

Open AccessReview

Dual Inhibition of MEK and PI3K Pathway in KRAS and BRAF Mutated Colorectal Cancers

by Sally Temraz^*, Deborah Mukherji and Ali Shamseddine

Department of Internal Medicine, Hematology/Oncology Division, American University of Beirut Medical Center, Beirut 110 72020, Lebanon

Int. J. Mol. Sci. 2015, 16(9), 22976-22988; https://doi.org/10.3390/ijms160922976 - 23 Sep 2015

Cited by 93 | Viewed by 13515

Abstract

Colorectal cancer (CRC) is a heterogeneous disease with multiple underlying causative genetic mutations. Genetic mutations in the phosphatidylinositol-3 kinase (PI3K) and the mitogen activated protein kinase (MAPK) pathways are frequently implicated in CRC. Targeting the downstream substrate MEK in these mutated tumors stands [...] Read more.

Colorectal cancer (CRC) is a heterogeneous disease with multiple underlying causative genetic mutations. Genetic mutations in the phosphatidylinositol-3 kinase (PI3K) and the mitogen activated protein kinase (MAPK) pathways are frequently implicated in CRC. Targeting the downstream substrate MEK in these mutated tumors stands out as a potential target in CRC. Several selective inhibitors of MEK have entered clinical trial evaluation; however, clinical activity with single MEK inhibitors has been rarely observed and acquired resistance seems to be inevitable. Amplification of the driving oncogene KRAS(13D), which increases signaling through the ERK1/2 pathway, upregulation of the noncanonical wingless/calcium signaling pathway (Wnt), and coexisting PIK3CA mutations have all been implicated with resistance against MEK inhibitor therapy in KRAS mutated CRC. The Wnt pathway and amplification of the oncogene have also been associated with resistance to MEK inhibitors in CRCs harboring BRAF mutations. Thus, dual targeted inhibition of MEK and PI3K pathway effectors (mTOR, PI3K, AKT, IGF-1R or PI3K/mTOR inhibitors) presents a potential strategy to overcome resistance to MEK inhibitor therapy. Many clinical trials are underway to evaluate multiple combinations of these pathway inhibitors in solid tumors. Full article

(This article belongs to the Special Issue Molecular Classification of Human Cancer: Diagnosis and Treatment)

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23 pages, 3209 KiB

Open AccessReview

Quo Vadis Clozapine? A Bibliometric Study of 45 Years of Research in International Context

by Francisco López-Muñoz^1,2,3,*, Javier Sanz-Fuentenebro^3,4,5, Gabriel Rubio^3,4,6,7, Pilar García-García² and Cecilio Álamo²

¹ Faculty of Health Sciences and Chair of Genomic Medicine, Camilo José Cela University, C/Castillo de Alarcón, 49, Urb. Villafranca del Castillo, 28692 Villanueva de la Cañada, Madrid, Spain

² Department of Biomedical Sciences (Pharmacology Area), Faculty of Medicine and Health Sciences, University of Alcalá, Campus Universitario-C/19, Ctra. Madrid-Barcelona, Km. 33,600, 28871 Alcalá de Henares, Madrid, Spain

³ Neuropsychopharmacology Unit, “Hospital 12 de Octubre” Research Institute, Avda. Córdoba, s/n, Madrid 28041, Spain

⁴ Department of Psychiatry, 12 de Octubre University Hospital, Avda. Córdoba, s/n, Madrid 28041, Spain

⁵ Biomedical Research Center Network for Mental Health (CIBERSAM), Madrid 28029, Spain

⁶ Department of Psychiatry, Complutense University, Plaza de Ramón y Cajal, s/n, Ciudad Universitaria, Madrid 28040, Spain

⁷ Networks for Cooperative Research in Health (RETICS-Addictive Disorder Network), Institute of Health Carlos III (ISCIII), MICINN and FEDER, Madrid 28029, Spain

Int. J. Mol. Sci. 2015, 16(9), 23012-23034; https://doi.org/10.3390/ijms160923012 - 23 Sep 2015

Cited by 19 | Viewed by 8282

Abstract

We have carried out a bibliometric study about the international scientific publications on clozapine. We have used the EMBASE and MEDLINE databases, and we applied bibliometric indicators of production, as Price’s Law on the increase of scientific literature. We also calculated the participation [...] Read more.

We have carried out a bibliometric study about the international scientific publications on clozapine. We have used the EMBASE and MEDLINE databases, and we applied bibliometric indicators of production, as Price’s Law on the increase of scientific literature. We also calculated the participation index (PI) of the different countries. The bibliometric data have also been correlated with some social and health data from the 12 most productive countries in biomedicine and health sciences. In addition, 5607 original documents dealing with clozapine, published between 1970 and 2013, were downloaded. Our results state non-fulfilment of Price’s Law, with scientific production on clozapine showing linear growth (r = 0.8691, vs. r = 0.8478 after exponential adjustment). Seven of the 12 journals with the highest numbers of publications on clozapine have an Impact Factor > 2. Among the countries generating clozapine research, the most prominent is the USA (PI = 24.32), followed by the UK (PI = 6.27) and Germany (PI = 5.40). The differences among countries on clozapine research are significantly related to economic variables linked to research. The scientific interest in clozapine remains remarkable, although after the application of bibliometric indicators of production, a saturation point is evident in the growth of scientific literature on this topic. Full article

(This article belongs to the Special Issue Antipsychotics)

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22 pages, 2530 KiB

Open AccessReview

Early Pregnancy Biomarkers in Pre-Eclampsia: A Systematic Review and Meta-Analysis

by Pensée Wu^1,2,†,‡, Caroline Van den Berg^3,†,‡, Zarko Alfirevic^4,‡, Shaughn O’Brien^1,2,‡, Maria Röthlisberger^5,‡, Philip Newton Baker^6,‡, Louise C. Kenny^7,‡, Karolina Kublickiene^8,‡

and Johannes J. Duvekot^2,*,‡

¹ Institute for Science and Technology in Medicine-Keele University, Guy Hilton Research Centre, Thornburrow Drive, Hartshill, Stoke-on-Trent ST4 7QB, UK

² Academic Unit of Obstetrics and Gynaecology, Royal Stoke University Hospital, Maternity Centre, Newcastle Road, Hartshill, Stoke-on-Trent ST4 6QG, UK

³ Department of Obstetrics and Gynecology, Subdivision of Obstetrics and Prenatal Medicine, Erasmus MC-University Medical Centre, PO Box 2040, 3000 CA Rotterdam, The Netherlands

⁴ Department of Women’s and Children’s Health, The University of Liverpool, Liverpool L8 7SS, UK

⁵ Department of Obstetrics and Gynecology, University Hospital of Cologne, 50931 Cologne, Germany

⁶ College of Medicine, Biological Sciences and Psychology, University of Leicester, PO Box 138, Leicester LE1 9HN, UK

⁷ Department of Obstetrics and Gynaecology, Cork University Maternity Hospital (5th Floor), Cork University Hospital, Wilton, Cork T12 YE02, Ireland

⁸ Karolinska Institutet, Centre for Gender Medicine, Institutions of Medicine and Clinical Science, Intervention and Technology, Department Ob/Gyn, Karolinska University Hospital, 14186 Stockholm, Sweden

^† These authors contributed equally to this work.

^‡ On behalf of the IMPROvED Consortium.

Int. J. Mol. Sci. 2015, 16(9), 23035-23056; https://doi.org/10.3390/ijms160923035 - 23 Sep 2015

Cited by 94 | Viewed by 17685

Abstract

Pre-eclampsia (PE) complicates 2%–8% of all pregnancies and is an important cause of perinatal morbidity and mortality worldwide. In order to reduce these complications and to develop possible treatment modalities, it is important to identify women at risk of developing PE. The use [...] Read more.

Pre-eclampsia (PE) complicates 2%–8% of all pregnancies and is an important cause of perinatal morbidity and mortality worldwide. In order to reduce these complications and to develop possible treatment modalities, it is important to identify women at risk of developing PE. The use of biomarkers in early pregnancy would allow appropriate stratification into high and low risk pregnancies for the purpose of defining surveillance in pregnancy and to administer interventions. We used formal methods for a systematic review and meta-analyses to assess the accuracy of all biomarkers that have been evaluated so far during the first and early second trimester of pregnancy to predict PE. We found low predictive values using individual biomarkers which included a disintegrin and metalloprotease 12 (ADAM-12), inhibin-A, pregnancy associated plasma protein A (PAPP-A), placental growth factor (PlGF) and placental protein 13 (PP-13). The pooled sensitivity of all single biomarkers was 0.40 (95% CI 0.39–0.41) at a false positive rate of 10%. The area under the Summary of Receiver Operating Characteristics Curve (SROC) was 0.786 (SE 0.02). When a combination model was used, the predictive value improved to an area under the SROC of 0.893 (SE 0.03). In conclusion, although there are multiple potential biomarkers for PE their efficacy has been inconsistent and comparisons are difficult because of heterogeneity between different studies. Therefore, there is an urgent need for high quality, large-scale multicentre research in biomarkers for PE so that the best predictive marker(s) can be identified in order to improve the management of women destined to develop PE. Full article

(This article belongs to the Special Issue Prediction, Diagnostics and Prevention of Pregnancy Complications)

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18 pages, 1087 KiB

Open AccessReview

Critical Issues in the Study of Magnesium Transport Systems and Magnesium Deficiency Symptoms in Plants

by Natsuko I. Kobayashi and Keitaro Tanoi^*

Graduate School of Agricultural and Life Sciences, the University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan

Int. J. Mol. Sci. 2015, 16(9), 23076-23093; https://doi.org/10.3390/ijms160923076 - 23 Sep 2015

Cited by 59 | Viewed by 12071

Abstract

Magnesium (Mg) is the second most abundant cation in living cells. Over 300 enzymes are known to be Mg-dependent, and changes in the Mg concentration significantly affects the membrane potential. As Mg becomes deficient, starch accumulation and chlorosis, bridged by the generation of [...] Read more.

Magnesium (Mg) is the second most abundant cation in living cells. Over 300 enzymes are known to be Mg-dependent, and changes in the Mg concentration significantly affects the membrane potential. As Mg becomes deficient, starch accumulation and chlorosis, bridged by the generation of reactive oxygen species, are commonly found in Mg-deficient young mature leaves. These defects further cause the inhibition of photosynthesis and finally decrease the biomass. Recently, transcriptome analysis has indicated the transcriptinal downregulation of chlorophyll apparatus at the earlier stages of Mg deficiency, and also the potential involvement of complicated networks relating to hormonal signaling and circadian oscillation. However, the processes of the common symptoms as well as the networks between Mg deficiency and signaling are not yet fully understood. Here, for the purpose of defining the missing pieces, several problems are considered and explained by providing an introduction to recent reports on physiological and transcriptional responses to Mg deficiency. In addition, it has long been unclear whether the Mg deficiency response involves the modulation of Mg²⁺ transport system. In this review, the current status of research on Mg²⁺ transport and the relating transporters are also summarized. Especially, the rapid progress in physiological characterization of the plant MRS2 gene family as well as the fundamental investigation about the molecular mechanism of the action of bacterial CorA proteins are described. Full article

(This article belongs to the Special Issue Regulation of Plant Mineral Nutrition: Transport, Sensing and Signalling)

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17 pages, 840 KiB

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Rational Protein Engineering Guided by Deep Mutational Scanning

by HyeonSeok Shin and Byung-Kwan Cho^*

Department of Biological Sciences and KI for the BioCentury, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Korea

Int. J. Mol. Sci. 2015, 16(9), 23094-23110; https://doi.org/10.3390/ijms160923094 - 23 Sep 2015

Cited by 14 | Viewed by 9608

Abstract

Sequence–function relationship in a protein is commonly determined by the three-dimensional protein structure followed by various biochemical experiments. However, with the explosive increase in the number of genome sequences, facilitated by recent advances in sequencing technology, the gap between protein sequences available and [...] Read more.

Sequence–function relationship in a protein is commonly determined by the three-dimensional protein structure followed by various biochemical experiments. However, with the explosive increase in the number of genome sequences, facilitated by recent advances in sequencing technology, the gap between protein sequences available and three-dimensional structures is rapidly widening. A recently developed method termed deep mutational scanning explores the functional phenotype of thousands of mutants via massive sequencing. Coupled with a highly efficient screening system, this approach assesses the phenotypic changes made by the substitution of each amino acid sequence that constitutes a protein. Such an informational resource provides the functional role of each amino acid sequence, thereby providing sufficient rationale for selecting target residues for protein engineering. Here, we discuss the current applications of deep mutational scanning and consider experimental design. Full article

(This article belongs to the Special Issue Protein Engineering)

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1 pages, 592 KiB

Open AccessCorrection

Correction: Subcellular Sequestration and Impact of Heavy Metals on the Ultrastructure and Physiology of the Multicellular Freshwater Alga Desmidium swartzii

by Ancuela Andosch¹, Margit Höftberger¹, Cornelius Lütz² and Ursula Lütz-Meindl^1,*

¹ Plant Physiology Division, Cell Biology Department, University of Salzburg, Hellbrunnerstrasse 34, 5020 Salzburg, Austria

² Institute of Botany, Faculty of Biology, University of Innsbruck, Sternwartestrasse 15, 6020 Innsbruck, Austria

Int. J. Mol. Sci. 2015, 16(9), 20239; https://doi.org/10.3390/ijms160920239 - 26 Aug 2015

Viewed by 3675

Abstract

In this recently published paper [1], the wrong Austrian Science Fund Project Number (210316-B16) was quoted in the Acknowledgment Section. [...] Full article

3 pages, 1211 KiB

Open AccessCorrection

Zhou, N., et al. Exposure of Tumor-Associated Macrophages to ApoptoticMCF-7 Cells Promotes Breast Cancer Growth and Metastasis. Int. J. Mol. Sci. 2015, 16, 11966–11982

by Na Zhou¹, Yizhuang Zhang¹, Xuehui Zhang¹, Zhen Lei², Ruobi Hu¹, Hui Li¹, Yiqing Mao¹, Xi Wang¹, David M. Irwin^1,3,*, Gang Niu^2,* and Huanran Tan^1,*

¹ Department of Pharmacology, Peking University, Health Science Center, Beijing 100191, China

² Beijing N&N Genetech Company, Beijing 100082, China

³ Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada

Int. J. Mol. Sci. 2015, 16(9), 22957-22959; https://doi.org/10.3390/ijms160922957 - 22 Sep 2015

Viewed by 4197

Abstract

The authors wish to change Figure 2 in Section 2 of their paper published in IJMS [1]. In Figure 2C, the tumor tissue of the Mac group was mixed up with that of the CoA group. [...] Full article

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