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Volume 16
Issue 5
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Int. J. Mol. Sci., Volume 16, Issue 5 (May 2015) – 155 articles , Pages 9037-11833

Cover Story: Anti-N-methyl-D-aspartate receptor subunit NR2A/B (anti-NR2A/B) antibodies are produced extrathecally and must cross the blood–brain barrier (BBB) into the cerebrospinal fluid to influence brain function. Matrix metalloproteinase-9 is released by prestimulated low-density granulocytes, leading to the degradation of basal lamina and compromise of the BBB integrity. Anti-NR2A/B antibodies activate the BBB with increased expression of endothelial cell adhesion molecules, facilitating the recruitment, rolling, adhesion and transmigration of neutrophils, leading to further "NETosis" intrathecally. Lastly, the intrathecal release of neutrophil extracellular traps contributes to neurotoxicity by inducing neuronal cell death which subsequently leads to neuropsychiatric manifestations of systemic lupus erythematosus. View the article.
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27 pages, 2124 KiB  
Article
Overexpressing of OsAMT1-3, a High Affinity Ammonium Transporter Gene, Modifies Rice Growth and Carbon-Nitrogen Metabolic Status
by Aili Bao, Zhijun Liang, Zhuqing Zhao and Hongmei Cai
Int. J. Mol. Sci. 2015, 16(5), 9037-9063; https://doi.org/10.3390/ijms16059037 - 23 Apr 2015
Cited by 101 | Viewed by 9109
Abstract
AMT1-3 encodes the high affinity NH4+ transporter in rice roots and is predominantly expressed under nitrogen starvation. In order to evaluate the effect of AMT1-3 gene on rice growth, nitrogen absorption and metabolism, we generated AMT1-3-overexpressing [...] Read more.
AMT1-3 encodes the high affinity NH4+ transporter in rice roots and is predominantly expressed under nitrogen starvation. In order to evaluate the effect of AMT1-3 gene on rice growth, nitrogen absorption and metabolism, we generated AMT1-3-overexpressing plants and analyzed the growth phenotype, yield, carbon and nitrogen metabolic status, and gene expression profiles. Although AMT1-3 mRNA accumulated in transgenic plants, these plants displayed significant decreases in growth when compared to the wild-type plants. The nitrogen uptake assay using a 15N tracer revealed poor nitrogen uptake ability in AMT1-3-overexpressing plants. We found significant decreases in AMT1-3-overexpressing plant leaf carbon and nitrogen content accompanied with a higher leaf C/N ratio. Significant changes in soluble proteins and carbohydrates were also observed in AMT1-3-overexpressing plants. In addition, metabolite profile analysis demonstrated significant changes in individual sugars, organic acids and free amino acids. Gene expression analysis revealed distinct expression patterns of genes that participate in carbon and nitrogen metabolism. Additionally, the correlation between the metabolites and gene expression patterns was consistent in AMT1-3-overexpressing plants under both low and high nitrogen growth conditions. Therefore, we hypothesized that the carbon and nitrogen metabolic imbalance caused by AMT1-3 overexpressing attributed to the poor growth and yield of transgenic plants. Full article
(This article belongs to the Special Issue Regulation of Plant Mineral Nutrition: Transport, Sensing and Signalling)
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14 pages, 1579 KiB  
Article
Chitosan Derivatives as Important Biorefinery Intermediates. Quaternary Tetraalkylammonium Chitosan Derivatives Utilized in Anion Exchange Chromatography for Perchlorate Removal
by Shakeela Sayed and Anwar Jardine
Int. J. Mol. Sci. 2015, 16(5), 9064-9077; https://doi.org/10.3390/ijms16059064 - 23 Apr 2015
Cited by 18 | Viewed by 8555
Abstract
There has recently been great interest in the valorization of biomass waste in the context of the biorefinery. The biopolymer chitosan, derived from chitin, is present in large quantities of crustacean waste. This biomass can be converted into value-added products with applications in [...] Read more.
There has recently been great interest in the valorization of biomass waste in the context of the biorefinery. The biopolymer chitosan, derived from chitin, is present in large quantities of crustacean waste. This biomass can be converted into value-added products with applications in energy, fuel, chemicals and materials manufacturing. The many reported applications of this polymer can be attributed to its unique properties, such as biocompatibility, chemical versatility, biodegradability and low toxicity. Cost effective water filters which decontaminate water by removal of specific impurities and microbes are in great demand. To address this need, the development of ion exchange resins using environmentally friendly, renewable materials such as biopolymers as solid supports was evaluated. The identification and remediation of perchlorate contaminated water using an easy, inexpensive method has come under the spotlight recently. Similarly, the use of a low cost perchlorate selective solid phase extraction (SPE) cartridge that can be rapidly employed in the field is desirable. Chitosan based SPE coupled with colorimetric analytical methods showed promise as a renewable anion exchange support for perchlorate analysis or removal. The polymers displayed perchlorate retention comparable to the commercial standard whereby the quaternized iron loaded polymer TMC-Fe(III) displayed the best activity. Full article
(This article belongs to the Special Issue Green Chemistry and the Biorefinery)
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19 pages, 937 KiB  
Article
Novel Tertiary Amino Containing Blinding Composite Membranes via Raft Polymerization and Their Preliminary CO2 Permeation Performance
by Lifang Zhu, Mali Zhou, Shanshan Yang and Jiangnan Shen
Int. J. Mol. Sci. 2015, 16(5), 9078-9096; https://doi.org/10.3390/ijms16059078 - 23 Apr 2015
Cited by 2 | Viewed by 6962
Abstract
Facile synthesis of poly (N,N-dimethylaminoethyl methacrylate) (PDMAEMA) star polymers on the basis of the prepolymer chains, PDMAEMA as the macro chain transfer agent and divinyl benzene (DVB) as the cross-linking reagent by reversible addition-fragmentation chain transfer (RAFT) polymerization was [...] Read more.
Facile synthesis of poly (N,N-dimethylaminoethyl methacrylate) (PDMAEMA) star polymers on the basis of the prepolymer chains, PDMAEMA as the macro chain transfer agent and divinyl benzene (DVB) as the cross-linking reagent by reversible addition-fragmentation chain transfer (RAFT) polymerization was described. The RAFT polymerizations of DMAEMA at 70 °C using four RAFT agents with different R and Z group were investigated. The RAFT agents used in these polymerizations were dibenzyl trithiocarbonate (DBTTC), s-1-dodecyl-s'-(α,α'-dimethyl-α-acetic acid) trithiocarbonate (MTTCD), s,s'-bis (2-hydroxyethyl-2'-dimethylacrylate) trithiocarbonate (BDATC) and s-(2-cyanoprop-2-yl)-s-dodecyltrithiocarbonate (CPTCD). The results indicated that the structure of the end-group of RAFT agents had significant effects on the ability to control polymerization. Compared with the above-mentioned RAFT agents, CPTCD provides better control over the molecular weight and molecular weight distribution. The polydispersity index (PDI) was determined to be within the scope of 1.26 to 1.36. The yields, molecular weight, and distribution of the star polymers can be tuned by changing the molar ratio of DVB/PDMAEMA-CPTCD. The chemical composition and structure of the linear and star polymers were characterized by GPC, FTIR, 1H NMR, XRD analysis. For the pure Chitosan membrane, a great improvement was observed for both CO2 permeation rate and ideal selectivity of the blending composite membrane upon increasing the content of SPDMAEMA-8. At a feed gas pressure of 37.5 cmHg and 30 °C, the blinding composite membrane (Cs: SPDMAEMA-8 = 4:4) has a CO2 permeation rate of 8.54 × 10−4 cm3 (STP) cm−2∙s−1∙cm∙Hg−1 and a N2 permeation rate of 6.76 × 10−5 cm3 (STP) cm−2∙s−1∙cm∙Hg−1, and an ideal CO2/N2 selectivity of 35.2. Full article
(This article belongs to the Special Issue Supramolecular Polymers and Their Assemblies)
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22 pages, 4546 KiB  
Article
Identification and Characterization of a PRDM14 Homolog in Japanese Flounder (Paralichthys olivaceus)
by Lin Fan, Jiajun Jiang, Jinning Gao, Huayu Song, Jinxiang Liu, Likun Yang, Zan Li, Yan Chen, Quanqi Zhang and Xubo Wang
Int. J. Mol. Sci. 2015, 16(5), 9097-9118; https://doi.org/10.3390/ijms16059097 - 23 Apr 2015
Cited by 6 | Viewed by 7342
Abstract
PRDM14 is a PR (PRDI-BF1-RIZ1 homologous) domain protein with six zinc fingers and essential roles in genome-wide epigenetic reprogramming. This protein is required for the establishment of germ cells and the maintenance of the embryonic stem cell ground state. In this study, we [...] Read more.
PRDM14 is a PR (PRDI-BF1-RIZ1 homologous) domain protein with six zinc fingers and essential roles in genome-wide epigenetic reprogramming. This protein is required for the establishment of germ cells and the maintenance of the embryonic stem cell ground state. In this study, we cloned the full-length cDNA and genomic DNA of the Paralichthys olivaceus prdm14 (Po-prdm14) gene and isolated the 5' regulatory region of Po-prdm14 by whole-genome sequencing. Peptide sequence alignment, gene structure analysis, and phylogenetic analysis revealed that Po-PRDM14 was homologous to mammalian PRDM14. Results of real-time quantitative polymerase chain reaction amplification (RT-qPCR) and in situ hybridization (ISH) in embryos demonstrated that Po-prdm14 was highly expressed between the morula and late gastrula stages, with its expression peaking in the early gastrula stage. Relatively low expression of Po-prdm14 was observed in the other developmental stages. ISH of gonadal tissues revealed that the transcripts were located in the nucleus of the oocytes in the ovaries but only in the spermatogonia and not the spermatocytes in the testes. We also presume that the Po-prdm14 transcription factor binding sites and their conserved binding region among vertebrates. The combined results suggest that Po-PRDM14 has a conserved function in teleosts and mammals. Full article
(This article belongs to the Special Issue Fish Molecular Biology)
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15 pages, 815 KiB  
Article
Further Study on Chemical Constituents of Parnassia wightiana Wall: Four New Dihydro-β-agarofuran Sesquiterpene Polyesters
by Zhao-Feng Gao, Bo-Hang Zhou, Jie-Yu Zhao, Fang-Jun Cao, Le Zhou and Hui-Ling Geng
Int. J. Mol. Sci. 2015, 16(5), 9119-9133; https://doi.org/10.3390/ijms16059119 - 23 Apr 2015
Cited by 3 | Viewed by 4842
Abstract
Four new (1–4), along with six known (5–10) dihydro-β-agarofuran sesquiterpene polyesters were isolated from the whole plants of Parnassia wightiana. The new compounds were structurally elucidated through spectroscopic analysis including UV (Ultraviolet Spectrum), IR [...] Read more.
Four new (1–4), along with six known (5–10) dihydro-β-agarofuran sesquiterpene polyesters were isolated from the whole plants of Parnassia wightiana. The new compounds were structurally elucidated through spectroscopic analysis including UV (Ultraviolet Spectrum), IR (Infrared Spectrum), 1H-NMR (1Hydrogen-Nuclear Magnetic Resonance), 13C-NMR (13Carbon-Nuclear Magnetic Resonance), DEPT (Distortionless Enhancement by Polarization Transfer), 1H-1H COSY (1H-1H Correlation Spectroscopy), HSQC (Heteronuclear Single Quantum Coherence), HMBC (Heteronuclear Multiple Bond Correlation), NOESY (Nuclear Overhauser Enhancement Spectroscopy) and HR-MS (High Resolution Mass Specttrum) and their absolute configurations were proposed by comparison of NOESY spectra and specific optical rotations with those of known compounds and biosynthesis grounds. Compound 2 is the first sesquiterpene alkaloid isolated from this plant. New compounds 1–4 exhibited some cytotoxic activities against NB4, MKN-45 and MCF-7 cells at 20 μM and of which 4 showed the highest activity against NB4 and MKN-45 cells with inhibition rates of 85.6% and 30.5%, respectively. Full article
(This article belongs to the Section Biochemistry)
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18 pages, 4478 KiB  
Article
PRRT2 Mutant Leads to Dysfunction of Glutamate Signaling
by Ming Li, Fenghe Niu, Xilin Zhu, Xiaopan Wu, Ning Shen, Xiaozhong Peng and Ying Liu
Int. J. Mol. Sci. 2015, 16(5), 9134-9151; https://doi.org/10.3390/ijms16059134 - 23 Apr 2015
Cited by 64 | Viewed by 9257
Abstract
Paroxysmal kinesigenic choreoathetosis (PKC) is an inherited disease of the nervous system. We previously identified PRRT2 as the causative gene of PKC. However, as little is known about the function of PRRT2, elucidating its function will benefit not only PKC studies, but also [...] Read more.
Paroxysmal kinesigenic choreoathetosis (PKC) is an inherited disease of the nervous system. We previously identified PRRT2 as the causative gene of PKC. However, as little is known about the function of PRRT2, elucidating its function will benefit not only PKC studies, but also many other related disorders. Here, we reveal higher levels of glutamate in the plasma of PKC patients and the culture medium of neurons following knock-out Prrt2 expression. Using double immunostaining assays we confirm Prrt2 is located at the glutamatergic neurons in accordance with its function. Our co-immunoprecipitation assays reveal mutant PRRT2 interferes with SNAP25 and GRIA1 interactions, respectively. Furthermore, using live-labeling techniques, we confirmed co-transfection with mutant PRRT2 caused an increase in GRIA1 distribution on the cell surface. Therefore, our results suggest that mutant PRRT2, probably through its weakened interaction with SNAP25, affects glutamate signaling and glutamate receptor activity, resulting in the increase of glutamate release and subsequent neuronal hyperexcitability. Full article
(This article belongs to the Special Issue Pharmacogenetics and Personalized Medicine)
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15 pages, 900 KiB  
Article
Expression Profiling Reveals Genes Involved in the Regulation of Wool Follicle Bulb Regression and Regeneration in Sheep
by Guangbin Liu, Ruize Liu, Xiaohui Tang, Jianhua Cao, Shuhong Zhao and Mei Yu
Int. J. Mol. Sci. 2015, 16(5), 9152-9166; https://doi.org/10.3390/ijms16059152 - 23 Apr 2015
Cited by 26 | Viewed by 5783
Abstract
Wool is an important material in textile manufacturing. In order to investigate the intrinsic factors that regulate wool follicle cycling and wool fiber properties, Illumina sequencing was performed on wool follicle bulb samples from the middle anagen, catagen and late telogen/early anagen phases. [...] Read more.
Wool is an important material in textile manufacturing. In order to investigate the intrinsic factors that regulate wool follicle cycling and wool fiber properties, Illumina sequencing was performed on wool follicle bulb samples from the middle anagen, catagen and late telogen/early anagen phases. In total, 13,898 genes were identified. KRTs and KRTAPs are the most highly expressed gene families in wool follicle bulb. In addition, 438 and 203 genes were identified to be differentially expressed in wool follicle bulb samples from the middle anagen phase compared to the catagen phase and the samples from the catagen phase compared to the late telogen/early anagen phase, respectively. Finally, our data revealed that two groups of genes presenting distinct expression patterns during the phase transformation may have important roles for wool follicle bulb regression and regeneration. In conclusion, our results demonstrated the gene expression patterns in the wool follicle bulb and add new data towards an understanding of the mechanisms involved in wool fiber growth in sheep. Full article
(This article belongs to the Section Biochemistry)
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29 pages, 1244 KiB  
Article
Proteomic Insights into Sulfur Metabolism in the Hydrogen-Producing Hyperthermophilic Archaeon Thermococcus onnurineus NA1
by Yoon-Jung Moon, Joseph Kwon, Sung-Ho Yun, Hye Li Lim, Jonghyun Kim, Soo Jung Kim, Sung Gyun Kang, Jung-Hyun Lee, Seung Il Kim and Young-Ho Chung
Int. J. Mol. Sci. 2015, 16(5), 9167-9195; https://doi.org/10.3390/ijms16059167 - 23 Apr 2015
Cited by 11 | Viewed by 8081
Abstract
The hyperthermophilic archaeon Thermococcus onnurineus NA1 has been shown to produce H2 when using CO, formate, or starch as a growth substrate. This strain can also utilize elemental sulfur as a terminal electron acceptor for heterotrophic growth. To gain insight into sulfur [...] Read more.
The hyperthermophilic archaeon Thermococcus onnurineus NA1 has been shown to produce H2 when using CO, formate, or starch as a growth substrate. This strain can also utilize elemental sulfur as a terminal electron acceptor for heterotrophic growth. To gain insight into sulfur metabolism, the proteome of T. onnurineus NA1 cells grown under sulfur culture conditions was quantified and compared with those grown under H2-evolving substrate culture conditions. Using label-free nano-UPLC-MSE-based comparative proteomic analysis, approximately 38.4% of the total identified proteome (589 proteins) was found to be significantly up-regulated (≥1.5-fold) under sulfur culture conditions. Many of these proteins were functionally associated with carbon fixation, Fe–S cluster biogenesis, ATP synthesis, sulfur reduction, protein glycosylation, protein translocation, and formate oxidation. Based on the abundances of the identified proteins in this and other genomic studies, the pathways associated with reductive sulfur metabolism, H2-metabolism, and oxidative stress defense were proposed. The results also revealed markedly lower expression levels of enzymes involved in the sulfur assimilation pathway, as well as cysteine desulfurase, under sulfur culture condition. The present results provide the first global atlas of proteome changes triggered by sulfur, and may facilitate an understanding of how hyperthermophilic archaea adapt to sulfur-rich, extreme environments. Full article
(This article belongs to the Special Issue Advances in Proteomic Research)
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21 pages, 5568 KiB  
Article
A Polymer Visualization System with Accurate Heating and Cooling Control and High-Speed Imaging
by Anson Wong, Yanting Guo, Chul B. Park and Nan Q. Zhou
Int. J. Mol. Sci. 2015, 16(5), 9196-9216; https://doi.org/10.3390/ijms16059196 - 23 Apr 2015
Cited by 11 | Viewed by 5757
Abstract
A visualization system to observe crystal and bubble formation in polymers under high temperature and pressure has been developed. Using this system, polymer can be subjected to a programmable thermal treatment to simulate the process in high pressure differential scanning calorimetry (HPDSC). With [...] Read more.
A visualization system to observe crystal and bubble formation in polymers under high temperature and pressure has been developed. Using this system, polymer can be subjected to a programmable thermal treatment to simulate the process in high pressure differential scanning calorimetry (HPDSC). With a high-temperature/high-pressure view-cell unit, this system enables in situ observation of crystal formation in semi-crystalline polymers to complement thermal analyses with HPDSC. The high-speed recording capability of the camera not only allows detailed recording of crystal formation, it also enables in situ capture of plastic foaming processes with a high temporal resolution. To demonstrate the system’s capability, crystal formation and foaming processes of polypropylene/carbon dioxide systems were examined. It was observed that crystals nucleated and grew into spherulites, and they grew at faster rates as temperature decreased. This observation agrees with the crystallinity measurement obtained with the HPDSC. Cell nucleation first occurred at crystals’ boundaries due to CO2 exclusion from crystal growth fronts. Subsequently, cells were nucleated around the existing ones due to tensile stresses generated in the constrained amorphous regions between networks of crystals. Full article
(This article belongs to the Section Materials Science)
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19 pages, 1486 KiB  
Article
Cellular Anti-Melanogenic Effects of a Euryale ferox Seed Extract Ethyl Acetate Fraction via the Lysosomal Degradation Machinery
by Seung-Hwa Baek, In-Jeong Nam, Hyeong Seob Kwak, Ki-Chan Kim and Sang-Han Lee
Int. J. Mol. Sci. 2015, 16(5), 9217-9235; https://doi.org/10.3390/ijms16059217 - 23 Apr 2015
Cited by 31 | Viewed by 7927
Abstract
The aim of this study was to investigate the effect of ethyl acetate fraction of Euryale ferox seed extracts (Efse-EA) on melanogenesis in immortalized mouse melanocyte cell line, melan-a. Efse-EA showed strong dose-dependent mushroom tyrosinase inhibitory activity. Treatment of melan-a cells with 30 [...] Read more.
The aim of this study was to investigate the effect of ethyl acetate fraction of Euryale ferox seed extracts (Efse-EA) on melanogenesis in immortalized mouse melanocyte cell line, melan-a. Efse-EA showed strong dose-dependent mushroom tyrosinase inhibitory activity. Treatment of melan-a cells with 30 μg/mL Efse-EA produced strong inhibition of cellular tyrosinase and melanin synthesis. Efse-EA significantly reduced the levels of melanogenesis-related proteins, such as tyrosinase, tyrosinase-related proteins 1 and 2, and microphthalmia-associated transcription factor. Because Efse-EA treatment reduced tyrosinase protein levels without changing its mRNA expression, we investigated whether this decrease was related to proteasomal or lysosomal degradation of tyrosinase. We found that chloroquine, a lysosomal proteolysis inhibitor, almost completely abolished both the down-regulation of tyrosinase and the inhibition of melanin synthesis induced by Efse-EA. These results suggested that Efse-EA may contribute to the inhibition of melanogenesis by altering lysosomal degradation of tyrosinase, and that this extract may provide a new cosmetic skin-whitening agent. Full article
(This article belongs to the Special Issue Inhibitors of Melanogenesis Related Processes: Application to Food, Agricultural and Cosmetic Industry-2014)
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47 pages, 1256 KiB  
Review
In Vitro and in Vivo Antitumoral Effects of Combinations of Polyphenols, or Polyphenols and Anticancer Drugs: Perspectives on Cancer Treatment
by Massimo Fantini, Monica Benvenuto, Laura Masuelli, Giovanni Vanni Frajese, Ilaria Tresoldi, Andrea Modesti and Roberto Bei
Int. J. Mol. Sci. 2015, 16(5), 9236-9282; https://doi.org/10.3390/ijms16059236 - 24 Apr 2015
Cited by 297 | Viewed by 16001
Abstract
Carcinogenesis is a multistep process triggered by genetic alterations that activate different signal transduction pathways and cause the progressive transformation of a normal cell into a cancer cell. Polyphenols, compounds ubiquitously expressed in plants, have anti-inflammatory, antimicrobial, antiviral, anticancer, and immunomodulatory properties, all [...] Read more.
Carcinogenesis is a multistep process triggered by genetic alterations that activate different signal transduction pathways and cause the progressive transformation of a normal cell into a cancer cell. Polyphenols, compounds ubiquitously expressed in plants, have anti-inflammatory, antimicrobial, antiviral, anticancer, and immunomodulatory properties, all of which are beneficial to human health. Due to their ability to modulate the activity of multiple targets involved in carcinogenesis through direct interaction or modulation of gene expression, polyphenols can be employed to inhibit the growth of cancer cells. However, the main problem related to the use of polyphenols as anticancer agents is their poor bioavailability, which might hinder the in vivo effects of the single compound. In fact, polyphenols have a poor absorption and biodistribution, but also a fast metabolism and excretion in the human body. The poor bioavailability of a polyphenol will affect the effective dose delivered to cancer cells. One way to counteract this drawback could be combination treatment with different polyphenols or with polyphenols and other anti-cancer drugs, which can lead to more effective antitumor effects than treatment using only one of the compounds. This report reviews current knowledge on the anticancer effects of combinations of polyphenols or polyphenols and anticancer drugs, with a focus on their ability to modulate multiple signaling transduction pathways involved in cancer. Full article
(This article belongs to the Special Issue Bioactive Phytochemicals in Functional Foods for Cancer Prevention)
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20 pages, 1077 KiB  
Review
Mesenchymal Stem Cells and Induced Pluripotent Stem Cells as Therapies for Multiple Sclerosis
by Juan Xiao, Rongbing Yang, Sangita Biswas, Xin Qin, Min Zhang and Wenbin Deng
Int. J. Mol. Sci. 2015, 16(5), 9283-9302; https://doi.org/10.3390/ijms16059283 - 24 Apr 2015
Cited by 51 | Viewed by 16415
Abstract
Multiple sclerosis (MS) is a chronic, autoimmune, inflammatory demyelinating disorder of the central nervous system that leads to permanent neurological deficits. Current MS treatment regimens are insufficient to treat the irreversible neurological disabilities. Tremendous progress in the experimental and clinical applications of cell-based [...] Read more.
Multiple sclerosis (MS) is a chronic, autoimmune, inflammatory demyelinating disorder of the central nervous system that leads to permanent neurological deficits. Current MS treatment regimens are insufficient to treat the irreversible neurological disabilities. Tremendous progress in the experimental and clinical applications of cell-based therapies has recognized stem cells as potential candidates for regenerative therapy for many neurodegenerative disorders including MS. Mesenchymal stem cells (MSC) and induced pluripotent stem cell (iPSCs) derived precursor cells can modulate the autoimmune response in the central nervous system (CNS) and promote endogenous remyelination and repair process in animal models. This review highlights studies involving the immunomodulatory and regenerative effects of mesenchymal stem cells and iPSCs derived cells in animal models, and their translation into immunomodulatory and neuroregenerative treatment strategies for MS. 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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11 pages, 1243 KiB  
Review
The Role of Food Peptides in Lipid Metabolism during Dyslipidemia and Associated Health Conditions
by Chibuike C. Udenigwe and Kirsti Rouvinen-Watt
Int. J. Mol. Sci. 2015, 16(5), 9303-9313; https://doi.org/10.3390/ijms16059303 - 24 Apr 2015
Cited by 74 | Viewed by 10082
Abstract
Animal and human clinical studies have demonstrated the ability of dietary food proteins to modulate endogenous lipid levels during abnormal lipid metabolism (dyslipidemia). Considering the susceptibility of proteins to gastric proteolytic activities, the hypolipidemic functions of proteins are possibly due, in part, to [...] Read more.
Animal and human clinical studies have demonstrated the ability of dietary food proteins to modulate endogenous lipid levels during abnormal lipid metabolism (dyslipidemia). Considering the susceptibility of proteins to gastric proteolytic activities, the hypolipidemic functions of proteins are possibly due, in part, to their peptide fragments. Food-derived peptides may directly modulate abnormal lipid metabolism in cell cultures and animal models of dyslipidemia. The peptides are thought to act by perturbing intestinal absorption of dietary cholesterol and enterohepatic bile acid circulation, and by inhibiting lipogenic enzymatic activities and gene expression in hepatocytes and adipocytes. Recent evidence indicates that the hypolipidemic activities of some peptides are due to activation of hepatic lipogenic transcription factors. However, detailed molecular mechanisms and structural requirements of peptides for these activities are yet to be elucidated. As hypolipidemic peptides can be released during enzymatic food processing, future studies can explore the prospects of combating metabolic syndrome and associated complications using peptide-rich functional food and nutraceutical products. Full article
(This article belongs to the Special Issue Bioactive Proteins and Peptides Derived from Food)
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27 pages, 8897 KiB  
Review
Insights on Structural Characteristics and Ligand Binding Mechanisms of CDK2
by Yan Li, Jingxiao Zhang, Weimin Gao, Lilei Zhang, Yanqiu Pan, Shuwei Zhang and Yonghua Wang
Int. J. Mol. Sci. 2015, 16(5), 9314-9340; https://doi.org/10.3390/ijms16059314 - 24 Apr 2015
Cited by 71 | Viewed by 12208
Abstract
Cyclin-dependent kinase 2 (CDK2) is a crucial regulator of the eukaryotic cell cycle. However it is well established that monomeric CDK2 lacks regulatory activity, which needs to be aroused by its positive regulators, cyclins E and A, or be phosphorylated on the catalytic [...] Read more.
Cyclin-dependent kinase 2 (CDK2) is a crucial regulator of the eukaryotic cell cycle. However it is well established that monomeric CDK2 lacks regulatory activity, which needs to be aroused by its positive regulators, cyclins E and A, or be phosphorylated on the catalytic segment. Interestingly, these activation steps bring some dynamic changes on the 3D-structure of the kinase, especially the activation segment. Until now, in the monomeric CDK2 structure, three binding sites have been reported, including the adenosine triphosphate (ATP) binding site (Site I) and two non-competitive binding sites (Site II and III). In addition, when the kinase is subjected to the cyclin binding process, the resulting structural changes give rise to a variation of the ATP binding site, thus generating an allosteric binding site (Site IV). All the four sites are demonstrated as being targeted by corresponding inhibitors, as is illustrated by the allosteric binding one which is targeted by inhibitor ANS (fluorophore 8-anilino-1-naphthalene sulfonate). In the present work, the binding mechanisms and their fluctuations during the activation process attract our attention. Therefore, we carry out corresponding studies on the structural characterization of CDK2, which are expected to facilitate the understanding of the molecular mechanisms of kinase proteins. Besides, the binding mechanisms of CDK2 with its relevant inhibitors, as well as the changes of binding mechanisms following conformational variations of CDK2, are summarized and compared. The summary of the conformational characteristics and ligand binding mechanisms of CDK2 in the present work will improve our understanding of the molecular mechanisms regulating the bioactivities of CDK2. Full article
(This article belongs to the Section Biochemistry)
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13 pages, 1289 KiB  
Article
Single Cell Confocal Raman Spectroscopy of Human Osteoarthritic Chondrocytes: A Preliminary Study
by Rajesh Kumar, Gajendra P. Singh, Kirsten M. Grønhaug, Nils K. Afseth, Catharina De Lange Davies, Jon O. Drogset and Magnus B. Lilledahl
Int. J. Mol. Sci. 2015, 16(5), 9341-9353; https://doi.org/10.3390/ijms16059341 - 24 Apr 2015
Cited by 26 | Viewed by 10054
Abstract
A great deal of effort has been focused on exploring the underlying molecular mechanism of osteoarthritis (OA) especially at the cellular level. We report a confocal Raman spectroscopic investigation on human osteoarthritic chondrocytes. The objective of this investigation is to identify molecular features [...] Read more.
A great deal of effort has been focused on exploring the underlying molecular mechanism of osteoarthritis (OA) especially at the cellular level. We report a confocal Raman spectroscopic investigation on human osteoarthritic chondrocytes. The objective of this investigation is to identify molecular features and the stage of OA based on the spectral signatures corresponding to bio-molecular changes at the cellular level in chondrocytes. In this study, we isolated chondrocytes from human osteoarthritic cartilage and acquired Raman spectra from single cells. Major spectral differences between the cells obtained from different International Cartilage Repair Society (ICRS) grades of osteoarthritic cartilage were identified. During progression of OA, a decrease in protein content and an increase in cell death were observed from the vibrational spectra. Principal component analysis and subsequent cross-validation was able to associate osteoarthritic chondrocytes to ICRS Grade I, II and III with specificity 100.0%, 98.1%, and 90.7% respectively, while, sensitivity was 98.6%, 82.8%, and 97.5% respectively. The overall predictive efficiency was 92.2%. Our pilot study encourages further use of Raman spectroscopy as a noninvasive and label free technique for revealing molecular features associated with osteoarthritic chondrocytes. Full article
(This article belongs to the Section Biochemistry)
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14 pages, 3592 KiB  
Article
A Moonlighting Human Protein Is Involved in Mitochondrial Import of tRNA
by Maria Baleva, Ali Gowher, Piotr Kamenski, Ivan Tarassov, Nina Entelis and Benoît Masquida
Int. J. Mol. Sci. 2015, 16(5), 9354-9367; https://doi.org/10.3390/ijms16059354 - 24 Apr 2015
Cited by 19 | Viewed by 7502
Abstract
In yeast Saccharomyces cerevisiae, ~3% of the lysine transfer RNA acceptor 1 (tRK1) pool is imported into mitochondria while the second isoacceptor, tRK2, fully remains in the cytosol. The mitochondrial function of tRK1 is suggested to boost mitochondrial translation under stress conditions. [...] Read more.
In yeast Saccharomyces cerevisiae, ~3% of the lysine transfer RNA acceptor 1 (tRK1) pool is imported into mitochondria while the second isoacceptor, tRK2, fully remains in the cytosol. The mitochondrial function of tRK1 is suggested to boost mitochondrial translation under stress conditions. Strikingly, yeast tRK1 can also be imported into human mitochondria in vivo, and can thus be potentially used as a vector to address RNAs with therapeutic anti-replicative capacity into mitochondria of sick cells. Better understanding of the targeting mechanism in yeast and human is thus critical. Mitochondrial import of tRK1 in yeast proceeds first through a drastic conformational rearrangement of tRK1 induced by enolase 2, which carries this freight to the mitochondrial pre-lysyl-tRNA synthetase (preMSK). The latter may cross the mitochondrial membranes to reach the matrix where imported tRK1 could be used by the mitochondrial translation apparatus. This work focuses on the characterization of the complex that tRK1 forms with human enolases and their role on the interaction between tRK1 and human pre-lysyl-tRNA synthetase (preKARS2). Full article
(This article belongs to the Special Issue Functions of Transfer RNAs)
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17 pages, 3220 KiB  
Article
Different Storage Conditions Influence Biocompatibility and Physicochemical Properties of Iron Oxide Nanoparticles
by Jan Zaloga, Christina Janko, Rohit Agarwal, Johannes Nowak, Robert Müller, Aldo R. Boccaccini, Geoffrey Lee, Stefan Odenbach, Stefan Lyer and Christoph Alexiou
Int. J. Mol. Sci. 2015, 16(5), 9368-9384; https://doi.org/10.3390/ijms16059368 - 24 Apr 2015
Cited by 51 | Viewed by 7692
Abstract
Superparamagnetic iron oxide nanoparticles (SPIONs) have attracted increasing attention in many biomedical fields. In magnetic drug targeting SPIONs are injected into a tumour supplying artery and accumulated inside the tumour with a magnet. The effectiveness of this therapy is thus dependent on magnetic [...] Read more.
Superparamagnetic iron oxide nanoparticles (SPIONs) have attracted increasing attention in many biomedical fields. In magnetic drug targeting SPIONs are injected into a tumour supplying artery and accumulated inside the tumour with a magnet. The effectiveness of this therapy is thus dependent on magnetic properties, stability and biocompatibility of the particles. A good knowledge of the effect of storage conditions on those parameters is of utmost importance for the translation of the therapy concept into the clinic and for reproducibility in preclinical studies. Here, core shell SPIONs with a hybrid coating consisting of lauric acid and albumin were stored at different temperatures from 4 to 45 °C over twelve weeks and periodically tested for their physicochemical properties over time. Surprisingly, even at the highest storage temperature we did not observe denaturation of the protein or colloidal instability. However, the saturation magnetisation decreased by maximally 28.8% with clear correlation to time and storage temperature. Furthermore, the biocompatibility was clearly affected, as cellular uptake of the SPIONs into human T-lymphoma cells was crucially dependent on the storage conditions. Taken together, the results show that the particle properties undergo significant changes over time depending on the way they are stored. Full article
(This article belongs to the Special Issue Magnetic Nanoparticles 2015)
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21 pages, 886 KiB  
Review
New Biofuel Alternatives: Integrating Waste Management and Single Cell Oil Production
by Elia Judith Martínez, Vijaya Raghavan, Fernando González-Andrés and Xiomar Gómez
Int. J. Mol. Sci. 2015, 16(5), 9385-9405; https://doi.org/10.3390/ijms16059385 - 24 Apr 2015
Cited by 62 | Viewed by 11577
Abstract
Concerns about greenhouse gas emissions have increased research efforts into alternatives in bio-based processes. With regard to transport fuel, bioethanol and biodiesel are still the main biofuels used. It is expected that future production of these biofuels will be based on processes using [...] Read more.
Concerns about greenhouse gas emissions have increased research efforts into alternatives in bio-based processes. With regard to transport fuel, bioethanol and biodiesel are still the main biofuels used. It is expected that future production of these biofuels will be based on processes using either non-food competing biomasses, or characterised by low CO2 emissions. Many microorganisms, such as microalgae, yeast, bacteria and fungi, have the ability to accumulate oils under special culture conditions. Microbial oils might become one of the potential feed-stocks for biodiesel production in the near future. The use of these oils is currently under extensive research in order to reduce production costs associated with the fermentation process, which is a crucial factor to increase economic feasibility. An important way to reduce processing costs is the use of wastes as carbon sources. The aim of the present review is to describe the main aspects related to the use of different oleaginous microorganisms for lipid production and their performance when using bio-wastes. The possibilities for combining hydrogen (H2) and lipid production are also explored in an attempt for improving the economic feasibility of the process. Full article
(This article belongs to the Special Issue Green Chemistry and the Biorefinery)
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14 pages, 5167 KiB  
Article
Effects of Mechanical Stretching on the Morphology and Cytoskeleton of Vaginal Fibroblasts from Women with Pelvic Organ Prolapse
by Sumei Wang, Zhenyu Zhang, Dongyuan Lü and Qiuxiang Xu
Int. J. Mol. Sci. 2015, 16(5), 9406-9419; https://doi.org/10.3390/ijms16059406 - 27 Apr 2015
Cited by 30 | Viewed by 10481
Abstract
Mechanical load and postmenopausal hypoestrogen are risk factors for pelvic organ prolapse (POP). In this study, we applied a 0.1-Hz uniaxial cyclic mechanical stretching (CS) with 10% elongation and 10−8 M 17-β-estradiol to vaginal fibroblasts isolated from postmenopausal women with or without [...] Read more.
Mechanical load and postmenopausal hypoestrogen are risk factors for pelvic organ prolapse (POP). In this study, we applied a 0.1-Hz uniaxial cyclic mechanical stretching (CS) with 10% elongation and 10−8 M 17-β-estradiol to vaginal fibroblasts isolated from postmenopausal women with or without POP to investigate the effects of CS and estrogen on cell morphology and cytoskeletons of normal and POP fibroblasts. Under static culture condition, POP fibroblasts exhibited lower cell circularity and higher relative fluorescence intensities (RFIs) of F-actin, α-tubulin and vimentin. When cultured with CS, all fibroblasts grew perpendicular to the force and exhibited a decreased cell projection area, cell circularity and increased cell length/width ratio; normal fibroblasts exhibited increased RFIs of all three types of cytoskeleton, and POP fibroblasts exhibited a decreased RFI of F-actin and no significant differences of α-tubulin and vimentin. After being cultured with 17-β-estradiol and CS, normal fibroblasts no longer exhibited significant changes in the cell projection area and the RFIs of F-actin and α-tubulin; POP fibroblasts exhibited no significant changes in cell circularity, length/width ratio and F-actin even with the increased RFIs of α-tubulin and vimentin. These findings suggest that POP fibroblasts have greater sensitivity to and lower tolerance for mechanical stretching, and estrogen can improve the prognosis. Full article
(This article belongs to the Section Biochemistry)
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11 pages, 354 KiB  
Article
Induction of Nickel Accumulation in Response to Zinc Deficiency in Arabidopsis thaliana
by Sho Nishida, Aki Kato, Chisato Tsuzuki, Junko Yoshida and Takafumi Mizuno
Int. J. Mol. Sci. 2015, 16(5), 9420-9430; https://doi.org/10.3390/ijms16059420 - 27 Apr 2015
Cited by 42 | Viewed by 5829
Abstract
Excessive accumulation of nickel (Ni) can be toxic to plants. In Arabidopsis thaliana, the Fe2+ transporter, iron (Fe)-regulated transporter1 (IRT1), mediates Fe uptake and also implicates in Ni2+ uptake at roots; however, the underlying mechanism of Ni2+ uptake and [...] Read more.
Excessive accumulation of nickel (Ni) can be toxic to plants. In Arabidopsis thaliana, the Fe2+ transporter, iron (Fe)-regulated transporter1 (IRT1), mediates Fe uptake and also implicates in Ni2+ uptake at roots; however, the underlying mechanism of Ni2+ uptake and accumulation remains unelucidated. In the present study, we found that zinc (Zn) deficient conditions resulted in increased accumulation of Ni in plants, particularly in roots, in A. thaliana. In order to elucidate the underlying mechanisms of Ni uptake correlating zinc condition, we traced 63Ni isotope in response to Zn and found that (i) Zn deficiency induces short-term Ni2+ absorption and (ii) Zn2+ inhibits Ni2+ uptake, suggesting competitive uptake between Ni and Zn. Furthermore, the Zrt/Irt-like protein 3 (ZIP3)-defective mutant with an elevated Zn-deficient response exhibited higher Ni accumulation than the wild type, further supporting that the response to Zn deficiency induces Ni accumulation. Previously, expression profile study demonstrated that IRT1 expression is not inducible by Zn deficiency. In the present study, we found increased Ni accumulation in IRT1-null mutant under Zn deficiency in agar culture. These suggest that Zn deficiency induces Ni accumulation in an IRT1-independen manner. The present study revealed that Ni accumulation is inducible in response to Zn deficiency, which may be attributable to a Zn uptake transporter induced by Zn deficiency. Full article
(This article belongs to the Section Biochemistry)
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19 pages, 873 KiB  
Review
Nucleotide Salvage Deficiencies, DNA Damage and Neurodegeneration
by Michael Fasullo and Lauren Endres
Int. J. Mol. Sci. 2015, 16(5), 9431-9449; https://doi.org/10.3390/ijms16059431 - 27 Apr 2015
Cited by 79 | Viewed by 18145
Abstract
Nucleotide balance is critically important not only in replicating cells but also in quiescent cells. This is especially true in the nervous system, where there is a high demand for adenosine triphosphate (ATP) produced from mitochondria. Mitochondria are particularly prone to oxidative stress-associated [...] Read more.
Nucleotide balance is critically important not only in replicating cells but also in quiescent cells. This is especially true in the nervous system, where there is a high demand for adenosine triphosphate (ATP) produced from mitochondria. Mitochondria are particularly prone to oxidative stress-associated DNA damage because nucleotide imbalance can lead to mitochondrial depletion due to low replication fidelity. Failure to maintain nucleotide balance due to genetic defects can result in infantile death; however there is great variability in clinical presentation for particular diseases. This review compares genetic diseases that result from defects in specific nucleotide salvage enzymes and a signaling kinase that activates nucleotide salvage after DNA damage exposure. These diseases include Lesch-Nyhan syndrome, mitochondrial depletion syndromes, and ataxia telangiectasia. Although treatment options are available to palliate symptoms of these diseases, there is no cure. The conclusions drawn from this review include the critical role of guanine nucleotides in preventing neurodegeneration, the limitations of animals as disease models, and the need to further understand nucleotide imbalances in treatment regimens. Such knowledge will hopefully guide future studies into clinical therapies for genetic diseases. Full article
(This article belongs to the Special Issue DNA Damage and Repair in Degenerative Diseases 2014)
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19 pages, 499 KiB  
Article
A Quantum Chemical and Statistical Study of Cytotoxic Activity of Compounds Isolated from Curcuma zedoaria
by Omer Abdalla Ahmed Hamdi, El Hassane Anouar, Jamil A. Shilpi, Zuhra Bashir Khalifa Al Trabolsy, Sharifuddin Bin Md Zain, Nur Shahidatul Shida Zakaria, Mohd Zulkefeli, Jean-Frédéric F. Weber, Sri Nurestri A. Malek, Syarifah Nur Syed Abdul Rahman and Khalijah Awang
Int. J. Mol. Sci. 2015, 16(5), 9450-9468; https://doi.org/10.3390/ijms16059450 - 27 Apr 2015
Cited by 13 | Viewed by 5955
Abstract
A series of 21 compounds isolated from Curcuma zedoaria was subjected to cytotoxicity test against MCF7; Ca Ski; PC3 and HT-29 cancer cell lines; and a normal HUVEC cell line. To rationalize the structure–activity relationships of the isolated compounds; a set of electronic; [...] Read more.
A series of 21 compounds isolated from Curcuma zedoaria was subjected to cytotoxicity test against MCF7; Ca Ski; PC3 and HT-29 cancer cell lines; and a normal HUVEC cell line. To rationalize the structure–activity relationships of the isolated compounds; a set of electronic; steric and hydrophobic descriptors were calculated using density functional theory (DFT) method. Statistical analyses were carried out using simple and multiple linear regressions (SLR; MLR); principal component analysis (PCA); and hierarchical cluster analysis (HCA). SLR analyses showed that the cytotoxicity of the isolated compounds against a given cell line depend on certain descriptors; and the corresponding correlation coefficients (R2) vary from 0%–55%. MLR results revealed that the best models can be achieved with a limited number of specific descriptors applicable for compounds having a similar basic skeleton. Based on PCA; HCA and MLR analyses; active compounds were classified into subgroups; which was in agreement with the cell based cytotoxicity assay. Full article
(This article belongs to the Section Physical Chemistry, Theoretical and Computational Chemistry)
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15 pages, 1103 KiB  
Article
Relationship between Proinflammatory and Antioxidant Proteins with the Severity of Cardiovascular Disease in Type 2 Diabetes Mellitus
by Beatriz García-Fontana, Sonia Morales-Santana, Victoria Longobardo, Rebeca Reyes-García, Pedro Rozas-Moreno, José Antonio García-Salcedo and Manuel Muñoz-Torres
Int. J. Mol. Sci. 2015, 16(5), 9469-9483; https://doi.org/10.3390/ijms16059469 - 27 Apr 2015
Cited by 17 | Viewed by 6346
Abstract
Type 2 diabetes mellitus patients are at significant risk of cardiovascular disease, however, the pathophysiology of these complications is complex and incompletely known in this population. The aim of this study was to compare the serum proteome of patients with type 2 diabetes [...] Read more.
Type 2 diabetes mellitus patients are at significant risk of cardiovascular disease, however, the pathophysiology of these complications is complex and incompletely known in this population. The aim of this study was to compare the serum proteome of patients with type 2 diabetes mellitus presenting or not presenting cardiovascular disease with non-diabetic subjects to find essential proteins related to these cardiovascular complications. This cross-sectional study compares the serum proteome by a combination of protein depletion with 2D-DIGE (2-dimension Difference Gel Electrophoresis) methodology. The proteins differentially expressed were identified by MALDI TOF/TOF (Matrix-assisted laser desorption/ionization and Time-Of-Flight ion detector) or LC-MS/MS (Liquid Chromatography coupled to Mass-Mass Spectrometry). Type 2 diabetes mellitus patients with cardiovascular disease showed higher expression of plasma retinol binding protein and glutathione peroxidase-3 compared to those without cardiovascular disease and non-diabetic controls. These results show that proteins related to the inflammatory and redox state appear to play an important role in the pathogenesis of the cardiovascular disease in the type 2 diabetes mellitus patients. Full article
(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease 2015)
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20 pages, 952 KiB  
Article
In Ovo Administration of Silver Nanoparticles and/or Amino Acids Influence Metabolism and Immune Gene Expression in Chicken Embryos
by Subrat K. Bhanja, Anna Hotowy, Manish Mehra, Ewa Sawosz, Lane Pineda, Krishna Prasad Vadalasetty, Natalia Kurantowicz and André Chwalibog
Int. J. Mol. Sci. 2015, 16(5), 9484-9503; https://doi.org/10.3390/ijms16059484 - 27 Apr 2015
Cited by 53 | Viewed by 8277
Abstract
Due to their physicochemical and biological properties, silver nanoparticles (NanoAg) have a wide range of applications. In the present study, their roles as a carrier of nutrients and an immunomodulator were tested in chicken embryos. Cysteine (Cys)+NanoAg injected embryos had smaller livers but [...] Read more.
Due to their physicochemical and biological properties, silver nanoparticles (NanoAg) have a wide range of applications. In the present study, their roles as a carrier of nutrients and an immunomodulator were tested in chicken embryos. Cysteine (Cys)+NanoAg injected embryos had smaller livers but heavier breasts on the 19th day of embryogenesis. Cys injected embryos had lower oxygen consumption compared to threonine (Thr) or NanoAg injected embryos. The energy expenditure in Thr+NanoAg, or NanoAg injected embryos was higher than Cys or Cys+NanoAg but was not different from uninjected control embryos. Relative expression of the hepatic insulin-like growth factor-I (IGF-I) gene was higher in Cys or NanoAg injected embryos after lipopolysaccharide (LPS) induction. The gene expression of hepatic tumour necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) did not differ among amino acids, NanoAg and uninjected controls in the non-LPS groups, but increased by many folds in the LPS treated NanoAg, Cys and Cys+NanoAg groups. In LPS treated spleens, TNF-α expression was also up-regulated by NanoAg, amino acids and their combinations, but interleukin-10 (IL-10) expression was down-regulated in Thr, Cys or Thr+NanoAg injected embryos. Toll like receptor-2 (TLR2) expression did not differ in NanoAg or amino acids injected embryos; however, toll like receptor-4 (TLR4) expression was higher in all treated embryos, except for Cys+NanoAg, than in uninjected control embryos. We concluded that NanoAg either alone or in combination with amino acids did not affect embryonic growth but improved immunocompetence, indicating that NanoAg and amino acid complexes can act as potential agents for the enhancement of innate and adaptive immunity in chicken. Full article
(This article belongs to the Special Issue Bioactive Nanoparticles 2014)
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16 pages, 1550 KiB  
Article
An Exploratory Pilot Study of Genetic Marker for IgE-Mediated Allergic Diseases with Expressions of FcεR1α and Cε
by En-Chih Liao, Ching-Yun Chang, Chia-Wei Hsieh, Sheng-Jie Yu, Sui-Chu Yin and Jaw-Ji Tsai
Int. J. Mol. Sci. 2015, 16(5), 9504-9519; https://doi.org/10.3390/ijms16059504 - 27 Apr 2015
Cited by 8 | Viewed by 5634
Abstract
The high affinity immunoglobulin E (IgE) receptor-FcεR1 is mainly expressed on the surface of effector cells. Cross-linking of IgE Abs bound to FcεR1 by multi-valent antigens can induce the activation of these cells and the secretion of inflammatory mediators. Since FcεR1 plays a [...] Read more.
The high affinity immunoglobulin E (IgE) receptor-FcεR1 is mainly expressed on the surface of effector cells. Cross-linking of IgE Abs bound to FcεR1 by multi-valent antigens can induce the activation of these cells and the secretion of inflammatory mediators. Since FcεR1 plays a central role in the induction and maintenance of allergic responses, this study aimed to investigate the association of FcεR1 with the allergic phenotype of Cε expression and cytokine and histamine release from peripheral leukocytes. Peripheral leukocytes from 67 allergic and 50 non-allergic subjects were used for genotyping analysis. Peripheral mononuclear cells (PBMCs) were used for Cε expression and ELISpot analysis, while polymorphonuclear cells (PMNs) were used for histamine release. The association between genotype polymorphism of the FcεR1α promoter region (rs2427827 and rs2251746) and allergic features of Cε expression and histamine were analyzed, and their effects on leukocytes function were compared with wild type. The genotype polymorphisms of FcεR1α promoter region with CT and TT in rs2427827 and TC in rs2251746 were significantly higher in allergic patients than in non-allergic controls. Patients with single nucleotide polymorphism (SNP) of FcεR1α promoter region had high levels of total IgE, mite-specific Der p 2 (Group 2 allergen of Dermatophagoides pteronyssinus)-specific IgE and IgE secretion B cells. The mRNA expression of FcεR1α was significantly increased after Der p2 stimulation in PBMCs with SNPs of the FcεR1α promoter region. Despite the increased Cε mRNA expression in PBMCs and histamine release from PMNs and the up-regulated mRNA expression of interleukin (IL)-6 and IL-8 secretions after Der p2 stimulation, there was no statistically significant difference between SNPs of the FcεR1α promoter region and the wild type. SNPs of FcεR1α promoter region were associated with IgE expression, IgE producing B cells, and increased Der p2-induced FcεR1α mRNA expression. These SNPs may be used as a disease marker for IgE-mediated allergic inflammation caused by Dermatophagoides pteronyssinus. Full article
(This article belongs to the Special Issue Emerging Classes of Biomarkers for Molecular Diagnostics)
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20 pages, 3123 KiB  
Article
Structural, Magnetic and Luminescent Properties of Lanthanide Complexes with N-Salicylideneglycine
by Ján Vančo, Zdeněk Trávníček, Ondřej Kozák and Roman Boča
Int. J. Mol. Sci. 2015, 16(5), 9520-9539; https://doi.org/10.3390/ijms16059520 - 28 Apr 2015
Cited by 20 | Viewed by 7260
Abstract
A series of anionic heavy lanthanide complexes, involving the N-salicylideneglycinato(2-) Schiff base ligand (salgly) and having the general formula K[Ln(salgly)2(H2O)2]∙H2O (1–6), where Ln stands for Gd, Tb, Dy, Ho, Er [...] Read more.
A series of anionic heavy lanthanide complexes, involving the N-salicylideneglycinato(2-) Schiff base ligand (salgly) and having the general formula K[Ln(salgly)2(H2O)2]∙H2O (1–6), where Ln stands for Gd, Tb, Dy, Ho, Er and Tm, was prepared using the one-pot template synthesis. The complexes were thoroughly characterized by elemental and Thermogravimetric/Differential Thermal Analyses (TG/DTA), Fourier Transform Infrared Spectroscopy (FT-IR), and photoluminescence spectroscopies, electrospray-ionization mass spectrometry, and their magnetic properties were studied by temperature-dependent dc magnetic measurements using the superconducting quantum interference device (SQUID). The X-ray structure of the terbium(III) complex (2), representing the unique structure between the lanthanide complexes of N-salicylideneamino acids, was determined. The results of spectral and structural studies revealed the isostructural nature of the prepared complexes, in which the lanthanide ion is octacoordinated by two O,N,O-donor salgly ligands and two aqua ligands. The analysis of magnetic data confirmed that the complexes behave as paramagnets obeying the Curie law. The results of photoluminescence spectral studies of the complexes showed the different origin in their luminescent properties between the solid state and solution. An antenna effect of the Schiff base ligand was observed in a powder form of the complex only, while it acts as a fluorophore in a solution. Full article
(This article belongs to the Special Issue Advances in Anisotropic and Smart Materials)
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17 pages, 968 KiB  
Article
Single-Stage Operation of Hybrid Dark-Photo Fermentation to Enhance Biohydrogen Production through Regulation of System Redox Condition: Evaluation with Real-Field Wastewater
by Rashmi Chandra, G. N. Nikhil and S. Venkata Mohan
Int. J. Mol. Sci. 2015, 16(5), 9540-9556; https://doi.org/10.3390/ijms16059540 - 28 Apr 2015
Cited by 42 | Viewed by 8083
Abstract
Harnessing hydrogen competently through wastewater treatment using a particular class of biocatalyst is indeed a challenging issue. Therefore, biohydrogen potential of real-field wastewater was evaluated by hybrid fermentative process in a single-stage process. The cumulative hydrogen production (CHP) was observed to be higher [...] Read more.
Harnessing hydrogen competently through wastewater treatment using a particular class of biocatalyst is indeed a challenging issue. Therefore, biohydrogen potential of real-field wastewater was evaluated by hybrid fermentative process in a single-stage process. The cumulative hydrogen production (CHP) was observed to be higher with distillery wastewater (271 mL) than with dairy wastewater (248 mL). Besides H2 production, the hybrid process was found to be effective in wastewater treatment. The chemical oxygen demand (COD) removal efficiency was found higher in distillery wastewater (56%) than in dairy wastewater (45%). Co-culturing photo-bacterial flora assisted in removal of volatile fatty acids (VFA) wherein 63% in distillery wastewater and 68% in case of dairy wastewater. Voltammograms illustrated dominant reduction current and low cathodic Tafel slopes supported H2 production. Overall, the augmented dark-photo fermentation system (ADPFS) showed better performance than the control dark fermentation system (DFS). This kind of holistic approach is explicitly viable for practical scale-up operation. Full article
(This article belongs to the Special Issue Photosynthesis and Biological Hydrogen Production)
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16 pages, 677 KiB  
Review
miRNAs in the Pathogenesis of Systemic Lupus Erythematosus
by Bo Qu and Nan Shen
Int. J. Mol. Sci. 2015, 16(5), 9557-9572; https://doi.org/10.3390/ijms16059557 - 28 Apr 2015
Cited by 55 | Viewed by 7669
Abstract
MicroRNAs (miRNAs) were first discovered as regulatory RNAs that controlled the timing of the larval development of Caenorhabditis elegans. Since then, nearly 30,000 mature miRNA products have been found in many species, including plants, warms, flies and mammals. Currently, miRNAs are well [...] Read more.
MicroRNAs (miRNAs) were first discovered as regulatory RNAs that controlled the timing of the larval development of Caenorhabditis elegans. Since then, nearly 30,000 mature miRNA products have been found in many species, including plants, warms, flies and mammals. Currently, miRNAs are well established as endogenous small (~22 nt) noncoding RNAs, which have functions in regulating mRNA stability and translation. Owing to intensive investigations during the last decade, miRNAs were found to play essential roles in regulating many physiological and pathological processes. Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by elevated autoantibodies against nuclear antigens and excessive inflammatory responses affecting multiple organs. Although efforts were taken and theories were produced to elucidate the pathogenesis of SLE, we still lack sufficient knowledge about the disease for developing effective therapies for lupus patients. Recent advances indicate that miRNAs are involved in the development of SLE, which gives us new insights into the pathogenesis of SLE and might lead to the finding of new therapeutic targets. Here, we will review recent discoveries about how miRNAs are involved in the pathogenesis of SLE and how it can promote the development of new therapy. Full article
(This article belongs to the Special Issue Molecular and Cellular Mechanisms in the Pathogenesis of Systemic Lupus Erythematosus)
15 pages, 2741 KiB  
Article
In Vivo Molecular MRI Imaging of Prostate Cancer by Targeting PSMA with Polypeptide-Labeled Superparamagnetic Iron Oxide Nanoparticles
by Yunkai Zhu, Ying Sun, Yaqing Chen, Weiyong Liu, Jun Jiang, Wenbin Guan, Zhongyang Zhang and Yourong Duan
Int. J. Mol. Sci. 2015, 16(5), 9573-9587; https://doi.org/10.3390/ijms16059573 - 28 Apr 2015
Cited by 55 | Viewed by 8102
Abstract
The prostate specific membrane antigen (PSMA) is broadly overexpressed on prostate cancer (PCa) cell surfaces. In this study, we report the synthesis, characterization, in vitro binding assay, and in vivo magnetic resonance imaging (MRI) evaluation of PSMA targeting superparamagnetic iron oxide nanoparticles (SPIONs). [...] Read more.
The prostate specific membrane antigen (PSMA) is broadly overexpressed on prostate cancer (PCa) cell surfaces. In this study, we report the synthesis, characterization, in vitro binding assay, and in vivo magnetic resonance imaging (MRI) evaluation of PSMA targeting superparamagnetic iron oxide nanoparticles (SPIONs). PSMA-targeting polypeptide CQKHHNYLC was conjugated to SPIONs to form PSMA-targeting molecular MRI contrast agents. In vitro studies demonstrated specific uptake of polypeptide-SPIONs by PSMA expressing cells. In vivo MRI studies found that MRI signals in PSMA-expressing tumors could be specifically enhanced with polypeptide-SPION, and further Prussian blue staining showed heterogeneous deposition of SPIONs in the tumor tissues. Taken altogether, we have developed PSMA-targeting polypeptide-SPIONs that could specifically enhance MRI signal in tumor-bearing mice, which might provide a new strategy for the molecular imaging of PCa. Full article
(This article belongs to the Special Issue Magnetic Nanoparticles 2015)
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12 pages, 1262 KiB  
Article
Carotenoid Profile of Tomato Sauces: Effect of Cooking Time and Content of Extra Virgin Olive Oil
by Anna Vallverdú-Queralt, Jorge Regueiro, José Fernando Rinaldi De Alvarenga, Xavier Torrado and Rosa M. Lamuela-Raventos
Int. J. Mol. Sci. 2015, 16(5), 9588-9599; https://doi.org/10.3390/ijms16059588 - 28 Apr 2015
Cited by 37 | Viewed by 8688
Abstract
The consumption of carotenoid-rich vegetables such as tomatoes and tomato sauces is associated with reduced risk of several chronic diseases. The predominant carotenoids in tomato products are in the (all-E) configuration, but (Z) isomers can be formed [...] Read more.
The consumption of carotenoid-rich vegetables such as tomatoes and tomato sauces is associated with reduced risk of several chronic diseases. The predominant carotenoids in tomato products are in the (all-E) configuration, but (Z) isomers can be formed during thermal processing. The effect of cooking time (15, 30, 45 and 60 min) and the addition of extra virgin olive oil (5% and 10%) on the carotenoid extractability of tomato sauces was monitored using liquid chromatography-tandem mass spectrometry (LC-ESI-MS/MS) and LC-ultraviolet detection (LC-UV). The thermal treatment and the addition of extra virgin olive oil increased the levels of antioxidant activity, total carotenoids, Z-lycopene isomers, α-carotene and β-carotene. These results are of particular nutritional benefit since higher lycopene intake has been associated with a reduced risk of lethal prostate and a reduction of prostate-specific antigen (PSA) levels. Moreover, β-carotene has been reported to suppress the up-regulation of heme oxygenase-1 gene expression in a dose dependent manner and to suppress UVA-induced HO-1 gene expression in cultured FEK4. Full article
(This article belongs to the Special Issue Antioxidant 2.0——Redox Modulation by Food and Drugs)
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12 pages, 10923 KiB  
Communication
High Density Infill in Cracks and Protrusions from the Articular Calcified Cartilage in Osteoarthritis in Standardbred Horse Carpal Bones
by Sheila Laverty, Mathieu Lacourt, Chan Gao, Janet E. Henderson and Alan Boyde
Int. J. Mol. Sci. 2015, 16(5), 9600-9611; https://doi.org/10.3390/ijms16059600 - 28 Apr 2015
Cited by 21 | Viewed by 6193
Abstract
We studied changes in articular calcified cartilage (ACC) and subchondral bone (SCB) in the third carpal bones (C3) of Standardbred racehorses with naturally-occurring repetitive loading-induced osteoarthritis (OA). Two osteochondral cores were harvested from dorsal sites from each of 15 post-mortem C3 and classified [...] Read more.
We studied changes in articular calcified cartilage (ACC) and subchondral bone (SCB) in the third carpal bones (C3) of Standardbred racehorses with naturally-occurring repetitive loading-induced osteoarthritis (OA). Two osteochondral cores were harvested from dorsal sites from each of 15 post-mortem C3 and classified as control or as showing early or advanced OA changes from visual inspection. We re-examined X-ray micro-computed tomography (µCT) image sets for the presence of high-density mineral infill (HDMI) in ACC cracks and possible high-density mineralized protrusions (HDMP) from the ACC mineralizing (tidemark) front (MF) into hyaline articular cartilage (HAC). We hypothesized and we show that 20-µm µCT resolution in 10-mm diameter samples is sufficient to detect HDMI and HDMP: these are lost upon tissue decalcification for routine paraffin wax histology owing to their predominant mineral content. The findings show that µCT is sufficient to discover HDMI and HDMP, which were seen in 2/10 controls, 6/9 early OA and 8/10 advanced OA cases. This is the first report of HDMI and HDMP in the equine carpus and in the Standardbred breed and the first to rely solely on µCT. HDMP are a candidate cause for mechanical tissue destruction in OA. Full article
(This article belongs to the Section Biochemistry)
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13 pages, 710 KiB  
Article
Skeletal Muscle Depletion Predicts the Prognosis of Patients with Hepatocellular Carcinoma Treated with Sorafenib
by Kenji Imai, Koji Takai, Tatsunori Hanai, Takayasu Ideta, Tsuneyuki Miyazaki, Takahiro Kochi, Atsushi Suetsugu, Makoto Shiraki and Masahito Shimizu
Int. J. Mol. Sci. 2015, 16(5), 9612-9624; https://doi.org/10.3390/ijms16059612 - 28 Apr 2015
Cited by 59 | Viewed by 6365
Abstract
The aim of this study was to determine whether skeletal muscle depletion predicts the prognosis of patients with hepatocellular carcinoma (HCC) that is being treated with sorafenib. We evaluated 40 consecutive HCC patients who received sorafenib treatment. The skeletal muscle cross-sectional area was [...] Read more.
The aim of this study was to determine whether skeletal muscle depletion predicts the prognosis of patients with hepatocellular carcinoma (HCC) that is being treated with sorafenib. We evaluated 40 consecutive HCC patients who received sorafenib treatment. The skeletal muscle cross-sectional area was measured by computed tomography at the third lumbar vertebra (L3), from which the L3 skeletal muscle index (L3 SMI) was obtained. The factors contributing to overall survival, sorafenib dose reduction, and discontinuation of sorafenib were analyzed using the Cox proportional hazards model. L3 SMI (p = 0.020) and log (α-fetoprotein (AFP)) (p = 0.010) were identified as independent prognostic factors in HCC patients treated with sorafenib. The initial dose of sorafenib (p = 0.008) was an independent risk factor for sorafenib dose reduction, and log (AFP) (p = 0.008) was the only significant risk factor for the discontinuation of this drug. L3 SMI was not a risk factor for either dose reduction (p = 0.423) or the discontinuation (p = 0.132) of sorafenib. A multiple linear regression analysis determined the following relationship between skeletal muscle mass (assessed as L3 SMI) and the explanatory factors: L3 SMI = −0.1896 × (Age) − 10.3441 × (Child-Pugh score) − 9.3922 × (log (AFP)) + 1.6139 × (log (AFP)) × (Child-Pugh score) + 112.9166. Skeletal muscle depletion is inversely associated with age, Child-Pugh score, and log (AFP). Moreover, it is an independent prognostic factor for HCC patients treated with sorafenib. Full article
(This article belongs to the Special Issue Viral Hepatitis Research)
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10 pages, 990 KiB  
Article
A Fusion Protein of RGD4C and β-Lactamase Has a Favorable Targeting Effect in Its Use in Antibody Directed Enzyme Prodrug Therapy
by Hao Wang, Xiao-Liang Zhou, Wei Long, Jin-Jian Liu and Fei-Yue Fan
Int. J. Mol. Sci. 2015, 16(5), 9625-9634; https://doi.org/10.3390/ijms16059625 - 28 Apr 2015
Cited by 10 | Viewed by 5634
Abstract
Antibody directed enzyme prodrug therapy (ADEPT) utilizing β-lactamase is a promising treatment strategy to enhance the therapeutic effect and safety of cytotoxic agents. In this method, a conjugate (antibody-β-lactamase fusion protein) is employed to precisely activate nontoxic cephalosporin prodrugs at the tumor site. [...] Read more.
Antibody directed enzyme prodrug therapy (ADEPT) utilizing β-lactamase is a promising treatment strategy to enhance the therapeutic effect and safety of cytotoxic agents. In this method, a conjugate (antibody-β-lactamase fusion protein) is employed to precisely activate nontoxic cephalosporin prodrugs at the tumor site. A major obstacle to the clinical translation of this method, however, is the low catalytic activity and high immunogenicity of the wild-type enzymes. To overcome this challenge, we fused a cyclic decapeptide (RGD4C) targeting to the integrin with a β-lactamase variant with reduced immunogenicity which retains acceptable catalytic activity for prodrug hydrolysis. Here, we made a further investigation on its targeting effect and pharmacokinetic properties, the results demonstrated that the fusion protein retains a targeting effect on integrin positive cells and has acceptable pharmacokinetic characteristics, which benefits its use in ADEPT. Full article
(This article belongs to the Section Biochemistry)
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19 pages, 2876 KiB  
Article
The miRNA Transcriptome Directly Reflects the Physiological and Biochemical Differences between Red, White, and Intermediate Muscle Fiber Types
by Jideng Ma, Hongmei Wang, Rui Liu, Long Jin, Qianzi Tang, Xun Wang, Anan Jiang, Yaodong Hu, Zongwen Li, Li Zhu, Ruiqiang Li, Mingzhou Li and Xuewei Li
Int. J. Mol. Sci. 2015, 16(5), 9635-9653; https://doi.org/10.3390/ijms16059635 - 29 Apr 2015
Cited by 21 | Viewed by 10529
Abstract
MicroRNAs (miRNAs) are small non-coding RNAs that can regulate their target genes at the post-transcriptional level. Skeletal muscle comprises different fiber types that can be broadly classified as red, intermediate, and white. Recently, a set of miRNAs was found expressed in a fiber [...] Read more.
MicroRNAs (miRNAs) are small non-coding RNAs that can regulate their target genes at the post-transcriptional level. Skeletal muscle comprises different fiber types that can be broadly classified as red, intermediate, and white. Recently, a set of miRNAs was found expressed in a fiber type-specific manner in red and white fiber types. However, an in-depth analysis of the miRNA transcriptome differences between all three fiber types has not been undertaken. Herein, we collected 15 porcine skeletal muscles from different anatomical locations, which were then clearly divided into red, white, and intermediate fiber type based on the ratios of myosin heavy chain isoforms. We further illustrated that three muscles, which typically represented each muscle fiber type (i.e., red: peroneal longus (PL), intermediate: psoas major muscle (PMM), white: longissimus dorsi muscle (LDM)), have distinct metabolic patterns of mitochondrial and glycolytic enzyme levels. Furthermore, we constructed small RNA libraries for PL, PMM, and LDM using a deep sequencing approach. Results showed that the differentially expressed miRNAs were mainly enriched in PL and played a vital role in myogenesis and energy metabolism. Overall, this comprehensive analysis will contribute to a better understanding of the miRNA regulatory mechanism that achieves the phenotypic diversity of skeletal muscles. Full article
(This article belongs to the Collection Regulation by Non-coding RNAs)
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39 pages, 7243 KiB  
Review
Structural Basis for Carbapenem-Hydrolyzing Mechanisms of Carbapenemases Conferring Antibiotic Resistance
by Jeong Ho Jeon, Jung Hun Lee, Jae Jin Lee, Kwang Seung Park, Asad Mustafa Karim, Chang-Ro Lee, Byeong Chul Jeong and Sang Hee Lee
Int. J. Mol. Sci. 2015, 16(5), 9654-9692; https://doi.org/10.3390/ijms16059654 - 29 Apr 2015
Cited by 154 | Viewed by 19133
Abstract
Carbapenems (imipenem, meropenem, biapenem, ertapenem, and doripenem) are β-lactam antimicrobial agents. Because carbapenems have the broadest spectra among all β-lactams and are primarily used to treat infections by multi-resistant Gram-negative bacteria, the emergence and spread of carbapenemases became a major public health concern. [...] Read more.
Carbapenems (imipenem, meropenem, biapenem, ertapenem, and doripenem) are β-lactam antimicrobial agents. Because carbapenems have the broadest spectra among all β-lactams and are primarily used to treat infections by multi-resistant Gram-negative bacteria, the emergence and spread of carbapenemases became a major public health concern. Carbapenemases are the most versatile family of β-lactamases that are able to hydrolyze carbapenems and many other β-lactams. According to the dependency of divalent cations for enzyme activation, carbapenemases can be divided into metallo-carbapenemases (zinc-dependent class B) and non-metallo-carbapenemases (zinc-independent classes A, C, and D). Many studies have provided various carbapenemase structures. Here we present a comprehensive and systematic review of three-dimensional structures of carbapenemase-carbapenem complexes as well as those of carbapenemases. We update recent studies in understanding the enzymatic mechanism of each class of carbapenemase, and summarize structural insights about regions and residues that are important in acquiring the carbapenemase activity. Full article
(This article belongs to the Special Issue Protein Crystallography in Molecular Biology 2015)
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26 pages, 4367 KiB  
Article
MicroRNA Expression Profile of Neural Progenitor-Like Cells Derived from Rat Bone Marrow Mesenchymal Stem Cells under the Influence of IGF-1, bFGF and EGF
by Tee Jong Huat, Amir Ali Khan, Jafri Malin Abdullah, Fauziah Mohamad Idris and Hasnan Jaafar
Int. J. Mol. Sci. 2015, 16(5), 9693-9718; https://doi.org/10.3390/ijms16059693 - 29 Apr 2015
Cited by 33 | Viewed by 8934
Abstract
Insulin-like growth factor 1 (IGF-1) enhances cellular proliferation and reduces apoptosis during the early differentiation of bone marrow derived mesenchymal stem cells (BMSCs) into neural progenitor-like cells (NPCs) in the presence of epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF). BMSCs [...] Read more.
Insulin-like growth factor 1 (IGF-1) enhances cellular proliferation and reduces apoptosis during the early differentiation of bone marrow derived mesenchymal stem cells (BMSCs) into neural progenitor-like cells (NPCs) in the presence of epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF). BMSCs were differentiated in three groups of growth factors: (A) EGF + bFGF, (B) EGF + bFGF + IGF-1, and (C) without growth factor. To unravel the molecular mechanisms of the NPCs derivation, microarray analysis using GeneChip® miRNA arrays was performed. The profiles were compared among the groups. Annotated microRNA fingerprints (GSE60060) delineated 46 microRNAs temporally up-regulated or down-regulated compared to group C. The expressions of selected microRNAs were validated by real-time PCR. Among the 46 microRNAs, 30 were consistently expressed for minimum of two consecutive time intervals. In Group B, only miR-496 was up-regulated and 12 microRNAs, including the let-7 family, miR-1224, miR-125a-3p, miR-214, miR-22, miR-320, miR-708, and miR-93, were down-regulated. Bioinformatics analysis reveals that some of these microRNAs (miR-22, miR-214, miR-125a-3p, miR-320 and let-7 family) are associated with reduction of apoptosis. Here, we summarize the roles of key microRNAs associated with IGF-1 in the differentiation of BMSCs into NPCs. These findings may provide clues to further our understanding of the mechanisms and roles of microRNAs as key regulators of BMSC-derived NPC maintenance. Full article
(This article belongs to the Special Issue Stem Cell Activation in Adult Organism)
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13 pages, 746 KiB  
Article
New Coumarin Derivatives and Other Constituents from the Stem Bark of Zanthoxylum avicennae: Effects on Neutrophil Pro-Inflammatory Responses
by Jih-Jung Chen, Chieh-Kai Yang, Yueh-Hsiung Kuo, Tsong-Long Hwang, Wen-Lung Kuo, Yun-Ping Lim, Ping-Jyun Sung, Tsung-Hsien Chang and Ming-Jen Cheng
Int. J. Mol. Sci. 2015, 16(5), 9719-9731; https://doi.org/10.3390/ijms16059719 - 29 Apr 2015
Cited by 24 | Viewed by 6730
Abstract
Three new coumarin derivatives, 8-formylalloxanthoxyletin (1), avicennone (2), and (Z)-avicennone (3), have been isolated from the stem bark of Zanthoxylum avicennae (Z. avicennae), together with 15 known compounds (4–18). [...] Read more.
Three new coumarin derivatives, 8-formylalloxanthoxyletin (1), avicennone (2), and (Z)-avicennone (3), have been isolated from the stem bark of Zanthoxylum avicennae (Z. avicennae), together with 15 known compounds (4–18). The structures of these new compounds were determined through spectroscopic and MS analyses. Compounds 1, 4, 9, 12, and 15 exhibited inhibition (half maximal inhibitory concentration (IC50) values ≤7.65 µg/mL) of superoxide anion generation by human neutrophils in response to formyl-l-methionyl-l-leucyl-l-phenylalanine/cytochalasin B (fMLP/CB). Compounds 1, 2, 4, 8 and 9 inhibited fMLP/CB-induced elastase release with IC50 values ≤8.17 µg/mL. This investigation reveals bioactive isolates (especially 1, 2, 4, 8, 9, 12 and 15) could be further developed as potential candidates for the treatment or prevention of various inflammatory diseases. Full article
(This article belongs to the Special Issue Plant Molecular Biology)
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17 pages, 2647 KiB  
Article
De Novo Transcriptome Sequencing of Low Temperature-Treated Phlox subulata and Analysis of the Genes Involved in Cold Stress
by Yanting Qu, Aimin Zhou, Xing Zhang, Huanwei Tang, Ming Liang, Hui Han and Yuhu Zuo
Int. J. Mol. Sci. 2015, 16(5), 9732-9748; https://doi.org/10.3390/ijms16059732 - 29 Apr 2015
Cited by 17 | Viewed by 7448
Abstract
Phlox subulata, a perennial herbaceous flower, can survive during the winter of northeast China, where the temperature can drop to −30 °C, suggesting that P. subulata is an ideal model for studying the molecular mechanisms of cold acclimation in plants. However, little [...] Read more.
Phlox subulata, a perennial herbaceous flower, can survive during the winter of northeast China, where the temperature can drop to −30 °C, suggesting that P. subulata is an ideal model for studying the molecular mechanisms of cold acclimation in plants. However, little is known about the gene expression profile of P. subulata under cold stress. Here, we examined changes in cold stress-related genes in P. subulata. We sequenced three cold-treated (CT) and control (CK) samples of P. subulata. After de novo assembly and quantitative assessment of the obtained reads, 99,174 unigenes were generated. Based on similarity searches with known proteins in public protein databases, 59,994 unigenes were functionally annotated. Among all differentially expressed genes (DEGs), 8302, 10,638 and 11,021 up-regulated genes and 9898, 17,876, and 12,358 down-regulated genes were identified after treatment at 4, 0, and −10 °C, respectively. Furthermore, 3417 up-regulated unigenes were expressed only in CT samples. Twenty major cold-related genes, including transcription factors, antioxidant enzymes, osmoregulation proteins, and Ca2+ and ABA signaling components, were identified, and their expression levels were estimated. Overall, this is the first transcriptome sequencing of this plant species under cold stress. Studies of DEGs involved in cold-related metabolic pathways may facilitate the discovery of cold-resistance genes. Full article
(This article belongs to the Special Issue Abiotic Stress and Gene Networks in Plants)
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21 pages, 3351 KiB  
Review
Ultrasound Imaging for Risk Assessment in Atherosclerosis
by David C. Steinl and Beat A. Kaufmann
Int. J. Mol. Sci. 2015, 16(5), 9749-9769; https://doi.org/10.3390/ijms16059749 - 29 Apr 2015
Cited by 75 | Viewed by 21037
Abstract
Atherosclerosis and its consequences like acute myocardial infarction or stroke are highly prevalent in western countries, and the incidence of atherosclerosis is rapidly rising in developing countries. Atherosclerosis is a disease that progresses silently over several decades before it results in the aforementioned [...] Read more.
Atherosclerosis and its consequences like acute myocardial infarction or stroke are highly prevalent in western countries, and the incidence of atherosclerosis is rapidly rising in developing countries. Atherosclerosis is a disease that progresses silently over several decades before it results in the aforementioned clinical consequences. Therefore, there is a clinical need for imaging methods to detect the early stages of atherosclerosis and to better risk stratify patients. In this review, we will discuss how ultrasound imaging can contribute to the detection and risk stratification of atherosclerosis by (a) detecting advanced and early plaques; (b) evaluating the biomechanical consequences of atherosclerosis in the vessel wall; (c) assessing plaque neovascularization and (d) imaging the expression of disease-relevant molecules using molecular imaging. Full article
(This article belongs to the Special Issue Atherosclerosis and Vascular Imaging)
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2 pages, 605 KiB  
Comment
Clouded Issues for PHACTR1
by Philipp G. Sand
Int. J. Mol. Sci. 2015, 16(5), 9770-9771; https://doi.org/10.3390/ijms16059770 - 29 Apr 2015
Cited by 1 | Viewed by 3628
Abstract
I have read with interest the recent paper by Han and coworkers [1] on the putative effects of a PHACTR1 variant in the context of coronary artery disease. The authors conclude to a significant risk-enhancing role of rs12526453 on the grounds of 19 [...] Read more.
I have read with interest the recent paper by Han and coworkers [1] on the putative effects of a PHACTR1 variant in the context of coronary artery disease. The authors conclude to a significant risk-enhancing role of rs12526453 on the grounds of 19 earlier case-control studies. [...] Full article
(This article belongs to the Section Biochemistry)
22 pages, 1139 KiB  
Review
Changing the Face of Kynurenines and Neurotoxicity: Therapeutic Considerations
by Zsuzsanna Bohár, József Toldi, Ferenc Fülöp and László Vécsei
Int. J. Mol. Sci. 2015, 16(5), 9772-9793; https://doi.org/10.3390/ijms16059772 - 29 Apr 2015
Cited by 70 | Viewed by 10401
Abstract
Kynurenines are the products of tryptophan metabolism. Among them, kynurenine and kynurenic acid are generally thought to have neuroprotective properties, while 3-hydroxykynurenine, 3-hydroxyanthranilic acid and quinolinic acid are considered neurotoxic. They participate in immunoregulation and inflammation and possess pro- or anti-excitotoxic properties, and [...] Read more.
Kynurenines are the products of tryptophan metabolism. Among them, kynurenine and kynurenic acid are generally thought to have neuroprotective properties, while 3-hydroxykynurenine, 3-hydroxyanthranilic acid and quinolinic acid are considered neurotoxic. They participate in immunoregulation and inflammation and possess pro- or anti-excitotoxic properties, and their involvement in oxidative stress has also been suggested. Consequently, it is not surprising that kynurenines have been closely related to neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis and multiple sclerosis. More information about the less-known metabolites, picolinic and cinnabarinic acid, evaluation of new receptorial targets, such as aryl-hydrocarbon receptors, and intensive research on the field of the immunomodulatory function of kynurenines delineated the high importance of this pathway in general homeostasis. Emerging knowledge about the kynurenine pathway provides new target points for the development of therapeutical solutions against neurodegenerative diseases. Full article
(This article belongs to the Special Issue Neuroprotective Strategies 2015)
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10 pages, 677 KiB  
Article
Association between PDCD1 Gene Polymorphisms and Risk of Systemic Lupus Erythematosus in Three Main Ethnic Groups of the Malaysian Population
by Kek Heng Chua, Lay Hoong Lian, Xiu Jia Sim, Tien Eang Cheah and Tze Pheng Lau
Int. J. Mol. Sci. 2015, 16(5), 9794-9803; https://doi.org/10.3390/ijms16059794 - 29 Apr 2015
Cited by 22 | Viewed by 5656
Abstract
The programmed cell death 1 (PDCD1) gene encodes for the PD-1 (programmed death 1) molecule, which negatively regulates self-reactive T- and B-cells in the maintenance of peripheral tolerance. A previous report had shown the development of lupus-like phenotypes in PD-1-deficient C57BL/6 [...] Read more.
The programmed cell death 1 (PDCD1) gene encodes for the PD-1 (programmed death 1) molecule, which negatively regulates self-reactive T- and B-cells in the maintenance of peripheral tolerance. A previous report had shown the development of lupus-like phenotypes in PD-1-deficient C57BL/6 mice, was suggestive to the role of PDCD1 in predisposing to systemic lupus erythematosus (SLE). Hence, we aimed to investigate the association between PDCD1 and SLE susceptibility in the Malaysian population. A TaqMan-based real-time PCR was employed to screen for PD1.1, PD1.3, PD1.5 and PD1.6 in both SLE and healthy control groups of 200 samples each. The observed frequency for PD1.5C/C genotype was significantly higher in Indian SLE patients and Malay controls (p < 0.01). On the other hand, the PD1.5C/T genotype might predispose the Malays to SLE, but confer a protective effect among the Indians (p < 0.01). The PD1.1, PD1.3 and PD1.6 were, however, not correlated to genetic predisposition of SLE in our Malaysian population. In conclusion, PD1.5 variant was significantly associated to SLE susceptibility in our Malaysian cohort. Our failure in replicating the association between other investigated PDCD1 variants and risk of getting SLE might due to ethnic and geographic variations in the distribution of these genetic variants. Full article
(This article belongs to the Special Issue Molecular and Cellular Mechanisms in the Pathogenesis of Systemic Lupus Erythematosus)
27 pages, 3550 KiB  
Review
Microfluidic Impedance Flow Cytometry Enabling High-Throughput Single-Cell Electrical Property Characterization
by Jian Chen, Chengcheng Xue, Yang Zhao, Deyong Chen, Min-Hsien Wu and Junbo Wang
Int. J. Mol. Sci. 2015, 16(5), 9804-9830; https://doi.org/10.3390/ijms16059804 - 29 Apr 2015
Cited by 137 | Viewed by 15779
Abstract
This article reviews recent developments in microfluidic impedance flow cytometry for high-throughput electrical property characterization of single cells. Four major perspectives of microfluidic impedance flow cytometry for single-cell characterization are included in this review: (1) early developments of microfluidic impedance flow cytometry for [...] Read more.
This article reviews recent developments in microfluidic impedance flow cytometry for high-throughput electrical property characterization of single cells. Four major perspectives of microfluidic impedance flow cytometry for single-cell characterization are included in this review: (1) early developments of microfluidic impedance flow cytometry for single-cell electrical property characterization; (2) microfluidic impedance flow cytometry with enhanced sensitivity; (3) microfluidic impedance and optical flow cytometry for single-cell analysis and (4) integrated point of care system based on microfluidic impedance flow cytometry. We examine the advantages and limitations of each technique and discuss future research opportunities from the perspectives of both technical innovation and clinical applications. Full article
(This article belongs to the Special Issue Single Cell Analysis in Biotechnology and Systems Biology)
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19 pages, 1892 KiB  
Article
Abnormal Mitochondrial Function and Impaired Granulosa Cell Differentiation in Androgen Receptor Knockout Mice
by Ruey-Sheng Wang, Heng-Yu Chang, Shu-Huei Kao, Cheng-Heng Kao, Yi-Chen Wu, Shuyuan Yeh, Chii-Reuy Tzeng and Chawnshang Chang
Int. J. Mol. Sci. 2015, 16(5), 9831-9849; https://doi.org/10.3390/ijms16059831 - 30 Apr 2015
Cited by 34 | Viewed by 10282
Abstract
In the ovary, the paracrine interactions between the oocyte and surrounded granulosa cells are critical for optimal oocyte quality and embryonic development. Mice lacking the androgen receptor (AR−/−) were noted to have reduced fertility with abnormal ovarian function that might [...] Read more.
In the ovary, the paracrine interactions between the oocyte and surrounded granulosa cells are critical for optimal oocyte quality and embryonic development. Mice lacking the androgen receptor (AR−/−) were noted to have reduced fertility with abnormal ovarian function that might involve the promotion of preantral follicle growth and prevention of follicular atresia. However, the detailed mechanism of how AR in granulosa cells exerts its effects on oocyte quality is poorly understood. Comparing in vitro maturation rate of oocytes, we found oocytes collected from AR−/− mice have a significantly poor maturating rate with 60% reached metaphase II and 30% remained in germinal vesicle breakdown stage, whereas 95% of wild-type AR (AR+/+) oocytes had reached metaphase II. Interestingly, we found these AR−/− female mice also had an increased frequency of morphological alterations in the mitochondria of granulosa cells with reduced ATP generation (0.18 ± 0.02 vs. 0.29 ± 0.02 µM/mg protein; p < 0.05) and aberrant mitochondrial biogenesis. Mechanism dissection found loss of AR led to a significant decrease in the expression of peroxisome proliferator-activated receptor γ (PPARγ) co-activator 1-β (PGC1-β) and its sequential downstream genes, nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factor A (TFAM), in controlling mitochondrial biogenesis. These results indicate that AR may contribute to maintain oocyte quality and fertility via controlling the signals of PGC1-β-mediated mitochondrial biogenesis in granulosa cells. Full article
(This article belongs to the Special Issue Mitochondrial Dysfunction in Ageing and Diseases)
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16 pages, 4184 KiB  
Article
Generation of Rho Zero Cells: Visualization and Quantification of the mtDNA Depletion Process
by Susanna Schubert, Sandra Heller, Birgit Löffler, Ingo Schäfer, Martina Seibel, Gaetano Villani and Peter Seibel
Int. J. Mol. Sci. 2015, 16(5), 9850-9865; https://doi.org/10.3390/ijms16059850 - 30 Apr 2015
Cited by 20 | Viewed by 12902
Abstract
Human mitochondrial DNA (mtDNA) is located in discrete DNA-protein complexes, so called nucleoids. These structures can be easily visualized in living cells by utilizing the fluorescent stain PicoGreen®. In contrary, cells devoid of endogenous mitochondrial genomes (ρ0 cells) display no [...] Read more.
Human mitochondrial DNA (mtDNA) is located in discrete DNA-protein complexes, so called nucleoids. These structures can be easily visualized in living cells by utilizing the fluorescent stain PicoGreen®. In contrary, cells devoid of endogenous mitochondrial genomes (ρ0 cells) display no mitochondrial staining in the cytoplasm. A modified restriction enzyme can be targeted to mitochondria to cleave the mtDNA molecules in more than two fragments, thereby activating endogenous nucleases. By applying this novel enzymatic approach to generate mtDNA-depleted cells the destruction of mitochondrial nucleoids in cultured cells could be detected in a time course. It is clear from these experiments that mtDNA-depleted cells can be seen as early as 48 h post-transfection using the depletion system. To prove that mtDNA is degraded during this process, mtDNA of transfected cells was quantified by real-time PCR. A significant decline could be observed 24 h post-transfection. Combination of both results showed that mtDNA of transfected cells is completely degraded and, therefore, ρ0 cells were generated within 48 h. Thus, the application of a mitochondrially-targeted restriction endonuclease proves to be a first and fast, but essential step towards a therapy for mtDNA disorders. Full article
(This article belongs to the Section Biochemistry)
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30 pages, 11963 KiB  
Review
Structural Insights into tRNA Dynamics on the Ribosome
by Xabier Agirrezabala and Mikel Valle
Int. J. Mol. Sci. 2015, 16(5), 9866-9895; https://doi.org/10.3390/ijms16059866 - 30 Apr 2015
Cited by 13 | Viewed by 8844
Abstract
High-resolution structures at different stages, as well as biochemical, single molecule and computational approaches have highlighted the elasticity of tRNA molecules when bound to the ribosome. It is well acknowledged that the inherent structural flexibility of the tRNA lies at the heart of [...] Read more.
High-resolution structures at different stages, as well as biochemical, single molecule and computational approaches have highlighted the elasticity of tRNA molecules when bound to the ribosome. It is well acknowledged that the inherent structural flexibility of the tRNA lies at the heart of the protein synthesis process. Here, we review the recent advances and describe considerations that the conformational changes of the tRNA molecules offer about the mechanisms grounded in translation. Full article
(This article belongs to the Special Issue Functions of Transfer RNAs)
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14 pages, 1876 KiB  
Article
Escherichia coli Maltose-Binding Protein Induces M1 Polarity of RAW264.7 Macrophage Cells via a TLR2- and TLR4-Dependent Manner
by Wan Wang, Hong-Yan Yuan, Guo-Mu Liu, Wei-Hua Ni, Fang Wang and Gui-Xiang Tai
Int. J. Mol. Sci. 2015, 16(5), 9896-9909; https://doi.org/10.3390/ijms16059896 - 30 Apr 2015
Cited by 17 | Viewed by 7335
Abstract
Maltose-binding protein (MBP) is a critical player of the maltose/maltodextrin transport system in Escherichia coli. Our previous studies have revealed that MBP nonspecifically induces T helper type 1 (Th1) cell activation and activates peritoneal macrophages obtained from mouse. In the present study, [...] Read more.
Maltose-binding protein (MBP) is a critical player of the maltose/maltodextrin transport system in Escherichia coli. Our previous studies have revealed that MBP nonspecifically induces T helper type 1 (Th1) cell activation and activates peritoneal macrophages obtained from mouse. In the present study, we reported a direct stimulatory effect of MBP on RAW264.7 cells, a murine macrophage cell line. When stimulated with MBP, the production of nitric oxide (NO), IL-1β, IL-6 and IL-12p70, and the expressions of CD80, MHC class II and inducible nitric oxide synthase (iNOS) were all increased in RAW264.7 cells, indicating the activation and polarization of RAW264.7 cells into M1 macrophages induced by MBP. Further study showed that MBP stimulation upregulated the expression of TLR2 and TLR4 on RAW264.7 cells, which was accompanied by subsequent phosphorylation of IκB-α and p38 MAPK. Pretreatment with anti-TLR2 or anti-TLR4 antibodies largely inhibited the phosphorylation of IκB-α and p38 MAPK, and greatly reduced MBP-induced NO and IL-12p70 production, suggesting that the MBP-induced macrophage activation and polarization were mediated by TLR2 and TLR4 signaling pathways. The observed results were independent of lipopolysaccharide contamination. Our study provides a new insight into a mechanism by which MBP enhances immune responses and warrants the potential application of MBP as an immune adjuvant in immune therapies. Full article
(This article belongs to the Special Issue Mechanism of Action and Applications of Cytokines in Immunotherapy)
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12 pages, 903 KiB  
Review
Effects of Dietary Vitamin E on Fertility Functions in Poultry Species
by Deivendran Rengaraj and Yeong Ho Hong
Int. J. Mol. Sci. 2015, 16(5), 9910-9921; https://doi.org/10.3390/ijms16059910 - 30 Apr 2015
Cited by 66 | Viewed by 16345
Abstract
Vitamin E is found in high quantities in vegetable oils. Although vitamin E has multiple functions in humans and animals, its key function is protecting cells from oxidative damage. Since its discovery, several studies have demonstrated that vitamin E deficiency causes impaired fertility [...] Read more.
Vitamin E is found in high quantities in vegetable oils. Although vitamin E has multiple functions in humans and animals, its key function is protecting cells from oxidative damage. Since its discovery, several studies have demonstrated that vitamin E deficiency causes impaired fertility in humans and lab animals. However, the effects of vitamin E deficiency or of its supplementation on the fertility of farm animals, particularly on poultry, are less well studied. Therefore, a comprehensive review of the effects of dietary vitamin E on the fertility of poultry species is needed in order to understand the beneficial role of vitamin E in the maintenance of sperm and egg qualities. Based on the observations reviewed here, we found that a moderate amount of vitamin E in poultry diet significantly protects semen/sperm qualities in male birds and egg qualities in female birds via decreasing the lipid peroxidation in semen/sperms and eggs. This review provides an overall understanding of the effects of dietary vitamin E on fertility functions in poultry species. Full article
(This article belongs to the Special Issue Advances in Reproductive Biology)
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14 pages, 2083 KiB  
Article
Quantitative Real-Time PCR Analysis of YKL-40 and Its Comparison with Mammalian Chitinase mRNAs in Normal Human Tissues Using a Single Standard DNA
by Misa Ohno, Peter O. Bauer, Yuta Kida, Masayoshi Sakaguchi, Yasusato Sugahara and Fumitaka Oyama
Int. J. Mol. Sci. 2015, 16(5), 9922-9935; https://doi.org/10.3390/ijms16059922 - 30 Apr 2015
Cited by 9 | Viewed by 7457
Abstract
YKL-40 (YKL for the first three N-terminal residues of a 40 kDa protein) belongs to a group of human chitinase-like proteins (CLPs), which are similar to chitinases but lack chitinolytic activity. YKL-40 mRNA and its protein levels have been reported elevated in [...] Read more.
YKL-40 (YKL for the first three N-terminal residues of a 40 kDa protein) belongs to a group of human chitinase-like proteins (CLPs), which are similar to chitinases but lack chitinolytic activity. YKL-40 mRNA and its protein levels have been reported elevated in multiple disorders including asthma, cystic fibrosis, rheumatoid arthritis and malignant tumors. Here, we quantified the YKL-40 mRNA levels and compared them with chitinases and housekeeping genes in normal human tissues. To establish the quantitative real-time PCR (qPCR) system for evaluation of relative YKL-40 mRNA levels, we constructed a human standard DNA molecule by ligating cDNAs of YKL-40, two mammalian chitinases and two housekeeping genes in a one-to-one ratio. We generated cDNAs from various normal human tissues and analyzed the YKL-40 mRNA expression levels using a qPCR system with the standard DNA. We found that YKL-40 mRNA is present widely in human tissues while its expression patterns exhibit clear tissue specificity. Highest YKL-40 mRNA levels were detected in the liver, followed by kidney, trachea and lung. The levels of YKL-40 mRNA in the kidney and liver were more than 100-times higher than those of chitotriosidase mRNA. Our study provides for the first time a comprehensive analysis of the relative expression levels of YKL-40 mRNA versus mammalian chitinases in normal human tissues. Full article
(This article belongs to the Section Biochemistry)
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13 pages, 1464 KiB  
Article
Aminolevulinic Acid-Mediated Photodynamic Therapy of Human Meningioma: An in Vitro Study on Primary Cell Lines
by Mustafa El-Khatib, Carolin Tepe, Brigitte Senger, Maxine Dibué-Adjei, Markus Johannes Riemenschneider, Walter Stummer, Hans Jakob Steiger and Jan Frédérick Cornelius
Int. J. Mol. Sci. 2015, 16(5), 9936-9948; https://doi.org/10.3390/ijms16059936 - 30 Apr 2015
Cited by 29 | Viewed by 7070
Abstract
Objective: Five-aminolevulinic acid (5-ALA)-induced porphyrins in malignant gliomas are potent photosensitizers. Promising results of ALA-PDT (photodynamic therapy) in recurrent glioblastomas have been published. Recently, 5-ALA-induced fluorescence was studied in meningioma surgery. Here, we present an experimental study of ALA-PDT in an in vitro [...] Read more.
Objective: Five-aminolevulinic acid (5-ALA)-induced porphyrins in malignant gliomas are potent photosensitizers. Promising results of ALA-PDT (photodynamic therapy) in recurrent glioblastomas have been published. Recently, 5-ALA-induced fluorescence was studied in meningioma surgery. Here, we present an experimental study of ALA-PDT in an in vitro model of primary meningioma cell lines. Methods: We processed native tumor material obtained intra-operatively within 24 h for cell culture. Epithelial membrane antigen (EMA) immunohistochemistry was performed after the first passage to confirm that cells were meningioma cells. For 5-ALA-PDT treatment, about 5000 cells per well were seeded in 20 wells of a blank 96-well plate. Each block of 4 wells was inoculated with 150 µL of 0, 25, 50 and 100 µg/mL 5-ALA solutions; one block was used as negative control without 5-ALA and without PDT. Following incubation for 3 h PDT was performed using a laser (635 nm, 18.75 J/cm2). The therapeutic response was analyzed by the water soluble tetrazolium salt (WST-1) cell viability assay 90 min after PDT. Results: 5-ALA-PDT was performed in 14 primary meningioma cell lines. EMA expression was verified in 10 primary cell cultures. The remaining 4 were EMA negative and PDT was without any effect in these cultures. All 10 EMA-positive cell lines showed a significant and dose-dependent decrease in viability rate (p < 0.001). Cell survival at 5-ALA concentrations of 12.5, 25, 50 and 100 μg/mL was 96.5% ± 7.6%, 67.9% ± 29.9%, 24.0% ± 16.7% and 13.8% ± 7.5%, respectively. For the negative controls (no 5-ALA/PDT and ALA/no PDT), the viability rates were 101.72% ± 3.5% and 100.17% ± 3.6%, respectively. The LD50 for 5-ALA was estimated between 25 and 50 µg/mL. Conclusion: This study reveals dose-dependent cytotoxic effects of 5-ALA-PDT on primary cell lines of meningiomas. Either 5-ALA or PDT alone did not affect cell survival. Further efforts are necessary to study the potential therapeutic effects of 5-ALA-PDT in vivo. Full article
(This article belongs to the Special Issue Advances in Photodynamic Therapy)
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27 pages, 1800 KiB  
Review
Pathogenesis of Brain Edema and Investigation into Anti-Edema Drugs
by Shotaro Michinaga and Yutaka Koyama
Int. J. Mol. Sci. 2015, 16(5), 9949-9975; https://doi.org/10.3390/ijms16059949 - 30 Apr 2015
Cited by 264 | Viewed by 36082
Abstract
Brain edema is a potentially fatal pathological state that occurs after brain injuries such as stroke and head trauma. In the edematous brain, excess accumulation of extracellular fluid results in elevation of intracranial pressure, leading to impaired nerve function. Despite the seriousness of [...] Read more.
Brain edema is a potentially fatal pathological state that occurs after brain injuries such as stroke and head trauma. In the edematous brain, excess accumulation of extracellular fluid results in elevation of intracranial pressure, leading to impaired nerve function. Despite the seriousness of brain edema, only symptomatic treatments to remove edema fluid are currently available. Thus, the development of novel anti-edema drugs is required. The pathogenesis of brain edema is classified as vasogenic or cytotoxic edema. Vasogenic edema is defined as extracellular accumulation of fluid resulting from disruption of the blood-brain barrier (BBB) and extravasations of serum proteins, while cytotoxic edema is characterized by cell swelling caused by intracellular accumulation of fluid. Various experimental animal models are often used to investigate mechanisms underlying brain edema. Many soluble factors and functional molecules have been confirmed to induce BBB disruption or cell swelling and drugs targeted to these factors are expected to have anti-edema effects. In this review, we discuss the mechanisms and involvement of factors that induce brain edema formation, and the possibility of anti-edema drugs targeting them. Full article
(This article belongs to the Special Issue Neurological Injuries’ Monitoring, Tracking and Treatment)
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22 pages, 2887 KiB  
Article
Sasa quelpaertensis Leaf Extract Inhibits Colon Cancer by Regulating Cancer Cell Stemness in Vitro and in Vivo
by Soo Jin Min, Ji Ye Lim, Haeng Ran Kim, Se-Jae Kim and Yuri Kim
Int. J. Mol. Sci. 2015, 16(5), 9976-9997; https://doi.org/10.3390/ijms16059976 - 30 Apr 2015
Cited by 46 | Viewed by 11531
Abstract
A rare subpopulation of cancer cells, termed cancer stem cells (CSCs), may be responsible for tumor relapse and resistance to conventional chemotherapy. The development of a non-toxic, natural treatment for the elimination of CSCs is considered a strategy for cancer treatment with minimal [...] Read more.
A rare subpopulation of cancer cells, termed cancer stem cells (CSCs), may be responsible for tumor relapse and resistance to conventional chemotherapy. The development of a non-toxic, natural treatment for the elimination of CSCs is considered a strategy for cancer treatment with minimal side effects. In the present study, the potential for Sasa quelpaertensis leaf extract (SQE) and its two bioactive compounds, tricin and p-coumaric acid, to exert anti-CSC effects by suppressing cancer stemness characteristics were evaluated in colon cancer cells. CD133+CD44+ cells were isolated from HT29 and HCT116 cell lines using flow-activated cell sorting (FACs). SQE treatment was found to significantly suppress the self-renewal capacity of both cell lines. SQE treatment was also associated with the down-regulation of β-catenin and phosphorylated GSK3β, while significantly enhancing cell differentiation by up-regulating CK20 expression and blocking the expression of several stem cell markers, including DLK1, Notch1, and Sox-2. In vivo, SQE supplementation suppressed tumor growth in a xenograft model by down-regulating stem cell markers and β-catenin as well as HIF-1α signaling. Compared with two bioactive compounds of SQE, SQE exhibited the most effective anti-CSC properties. Taken together, these results provide evidence that SQE inhibits colon cancer by regulating the characteristics of CSCs. Full article
(This article belongs to the Special Issue Bioactive Phytochemicals in Functional Foods for Cancer Prevention)
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18 pages, 1303 KiB  
Article
Evaluation and Selection of Appropriate Reference Genes for Real-Time Quantitative PCR Analysis of Gene Expression in Nile Tilapia (Oreochromis niloticus) during Vaccination and Infection
by Erlong Wang, Kaiyu Wang, Defang Chen, Jun Wang, Yang He, Bo Long, Lei Yang, Qian Yang, Yi Geng, Xiaoli Huang, Ping Ouyang and Weimin Lai
Int. J. Mol. Sci. 2015, 16(5), 9998-10015; https://doi.org/10.3390/ijms16059998 - 30 Apr 2015
Cited by 57 | Viewed by 9493
Abstract
qPCR as a powerful and attractive methodology has been widely applied to aquaculture researches for gene expression analyses. However, the suitable reference selection is critical for normalizing target genes expression in qPCR. In the present study, six commonly used endogenous controls were selected [...] Read more.
qPCR as a powerful and attractive methodology has been widely applied to aquaculture researches for gene expression analyses. However, the suitable reference selection is critical for normalizing target genes expression in qPCR. In the present study, six commonly used endogenous controls were selected as candidate reference genes to evaluate and analyze their expression levels, stabilities and normalization to immune-related gene IgM expression during vaccination and infection in spleen of tilapia with RefFinder and GeNorm programs. The results showed that all of these candidate reference genes exhibited transcriptional variations to some extent at different periods. Among them, EF1A was the most stable reference with RefFinder, followed by 18S rRNA, ACTB, UBCE, TUBA and GAPDH respectively and the optimal number of reference genes for IgM normalization under different experiment sets was two with GeNorm. Meanwhile, combination the Cq (quantification cycle) value and the recommended comprehensive ranking of reference genes, EF1A and ACTB, the two optimal reference genes, were used together as reference genes for accurate analysis of immune-related gene expression during vaccination and infection in Nile tilapia with qPCR. Moreover, the highest IgM expression level was at two weeks post-vaccination when normalized to EF1A, 18S rRNA, ACTB, and EF1A together with ACTB compared to one week post-vaccination before normalizing, which was also consistent with the IgM antibody titers detection by ELISA. Full article
(This article belongs to the Special Issue Fish Molecular Biology)
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22 pages, 4571 KiB  
Article
Instrumentation on Multi-Scaled Scattering of Bio-Macromolecular Solutions
by Benjamin Chu, Dufei Fang and Yimin Mao
Int. J. Mol. Sci. 2015, 16(5), 10016-10037; https://doi.org/10.3390/ijms160510016 - 4 May 2015
Cited by 4 | Viewed by 7339
Abstract
The design, construction and initial tests on a combined laser light scattering and synchrotron X-ray scattering instrument can cover studies of length scales from atomic sizes in Angstroms to microns and dynamics from microseconds to seconds are presented. In addition to static light [...] Read more.
The design, construction and initial tests on a combined laser light scattering and synchrotron X-ray scattering instrument can cover studies of length scales from atomic sizes in Angstroms to microns and dynamics from microseconds to seconds are presented. In addition to static light scattering (SLS), dynamic light scattering (DLS), small angle X-ray scattering (SAXS) and wide angle X-ray diffraction (WAXD), the light scattering instrument is being developed to carry out studies in mildly turbid solutions, in the presence of multiple scattering. Three-dimensional photon cross correlation function (3D-PCCF) measurements have been introduced to couple with synchrotron X-ray scattering to study the structure, size and dynamics of macromolecules in solution. Full article
(This article belongs to the Special Issue Laser Application in Life Sciences)
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23 pages, 1976 KiB  
Article
Nitrogen Removal Characteristics of a Newly Isolated Indigenous Aerobic Denitrifier from Oligotrophic Drinking Water Reservoir, Zoogloea sp. N299
by Ting-Lin Huang, Shi-Lei Zhou, Hai-Han Zhang, Shi-Yuan Bai, Xiu-Xiu He and Xiao Yang
Int. J. Mol. Sci. 2015, 16(5), 10038-10060; https://doi.org/10.3390/ijms160510038 - 4 May 2015
Cited by 99 | Viewed by 8252
Abstract
Nitrogen is considered to be one of the most widespread pollutants leading to eutrophication of freshwater ecosystems, especially in drinking water reservoirs. In this study, an oligotrophic aerobic denitrifier was isolated from drinking water reservoir sediment. Nitrogen removal performance was explored. The strain [...] Read more.
Nitrogen is considered to be one of the most widespread pollutants leading to eutrophication of freshwater ecosystems, especially in drinking water reservoirs. In this study, an oligotrophic aerobic denitrifier was isolated from drinking water reservoir sediment. Nitrogen removal performance was explored. The strain was identified by 16S rRNA gene sequence analysis as Zoogloea sp. N299. This species exhibits a periplasmic nitrate reductase gene (napA). Its specific growth rate was 0.22 h−1. Obvious denitrification and perfect nitrogen removal performances occurred when cultured in nitrate and nitrite mediums, at rates of 75.53% ± 1.69% and 58.65% ± 0.61%, respectively. The ammonia removal rate reached 44.12% ± 1.61% in ammonia medium. Zoogloea sp. N299 was inoculated into sterilized and unsterilized reservoir source waters with a dissolved oxygen level of 5–9 mg/L, pH 8–9, and C/N 1.14:1. The total nitrogen removal rate reached 46.41% ± 3.17% (sterilized) and 44.88% ± 4.31% (unsterilized). The cell optical density suggested the strain could survive in oligotrophic drinking water reservoir water conditions and perform nitrogen removal. Sodium acetate was the most favorable carbon source for nitrogen removal by strain N299 (p < 0.05). High C/N was beneficial for nitrate reduction (p < 0.05). The nitrate removal efficiencies showed no significant differences among the tested inoculums dosage (p > 0.05). Furthermore, strain N299 could efficiently remove nitrate at neutral and slightly alkaline and low temperature conditions. These results, therefore, demonstrate that Zoogloea sp. N299 has high removal characteristics, and can be used as a nitrogen removal microbial inoculum with simultaneous aerobic nitrification and denitrification in a micro-polluted reservoir water ecosystem. Full article
(This article belongs to the Section Biochemistry)
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16 pages, 1030 KiB  
Article
Autistic Children Exhibit Decreased Levels of Essential Fatty Acids in Red Blood Cells
by Sarah A. Brigandi, Hong Shao, Steven Y. Qian, Yiping Shen, Bai-Lin Wu and Jing X. Kang
Int. J. Mol. Sci. 2015, 16(5), 10061-10076; https://doi.org/10.3390/ijms160510061 - 4 May 2015
Cited by 82 | Viewed by 13427
Abstract
Omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids (PUFA) are essential nutrients for brain development and function. However, whether or not the levels of these fatty acids are altered in individuals with autism remains debatable. In this study, we compared the fatty acid [...] Read more.
Omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids (PUFA) are essential nutrients for brain development and function. However, whether or not the levels of these fatty acids are altered in individuals with autism remains debatable. In this study, we compared the fatty acid contents between 121 autistic patients and 110 non-autistic, non-developmentally delayed controls, aged 3–17. Analysis of the fatty acid composition of red blood cell (RBC) membrane phospholipids showed that the percentage of total PUFA was lower in autistic patients than in controls; levels of n-6 arachidonic acid (AA) and n-3 docosahexaenoic acid (DHA) were particularly decreased (p < 0.001). In addition, plasma levels of the pro-inflammatory AA metabolite prostaglandin E2 (PGE2) were higher in a subset of the autistic participants (n = 20) compared to controls. Our study demonstrates an alteration in the PUFA profile and increased production of a PUFA-derived metabolite in autistic patients, supporting the hypothesis that abnormal lipid metabolism is implicated in autism. Full article
(This article belongs to the Special Issue Bioactive Lipids and Lipidomics)
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18 pages, 773 KiB  
Article
Peripheral Blood Lymphocyte Subsets (CD4+, CD8+ T Cells, NK Cells) in Patients with Cardiovascular and Neurological Complications after Carotid Endarterectomy
by Katarzyna Kotfis, Jowita Biernawska, Małgorzata Zegan-Barańska and Maciej Żukowski
Int. J. Mol. Sci. 2015, 16(5), 10077-10094; https://doi.org/10.3390/ijms160510077 - 4 May 2015
Cited by 23 | Viewed by 6616
Abstract
Background: The aim of the study was to evaluate the differences in the circulating immune cells’ subgroups after the atherosclerotic plaque removal in patients presenting with postoperative complications as compared to the patients without complications after carotid endarterectomy (CEA). Methods: Patients with significant [...] Read more.
Background: The aim of the study was to evaluate the differences in the circulating immune cells’ subgroups after the atherosclerotic plaque removal in patients presenting with postoperative complications as compared to the patients without complications after carotid endarterectomy (CEA). Methods: Patients with significant carotid atherosclerosis (n = 124, age range: 44 to 87 years) who underwent CEA were enrolled in a prospective study. The immunology study using flow cytometry was performed to determine the percentages of peripheral blood T cells (CD4+, CD8+, Treg—CD4+/CD25+) and NK (natural killer) cells before and after the procedure. The data were expressed as the percentage of total lymphocytes ± the standard error of mean. Results: The mean percentage of lymphocytes (61.54% ± 17.50% vs. 71.82% ± 9.68%, p = 0.030) and CD4 T lymphocytes (T helper, 38.13% ± 13.78% vs. 48.39% ± 10.24%, p = 0.027) was significantly lower six hours after CEA in patients with postoperative 30-day cardiovascular and neurological complications as compared to the group without complications. On the other hand the mean NK level in the group with complications was significantly higher (21.61% ± 9.00% vs. 15.80% ± 9.31%, p = 0.048). Conclusions: The results of this study suggest that after carotid endarterectomy the percentages of circulating immune cells subsets differ in patients with and without postoperative complications. Full article
(This article belongs to the Section Biochemistry)
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10 pages, 739 KiB  
Article
Histomorphometric Evaluation of the Small Coronary Arteries in Rats Exposed to Industrial Noise
by Ana Lousinha, Eduardo Antunes, Gonçalo Borrecho, Maria João Oliveira, José Brito and José Martins dos Santos
Int. J. Mol. Sci. 2015, 16(5), 10095-10104; https://doi.org/10.3390/ijms160510095 - 4 May 2015
Cited by 7 | Viewed by 4702
Abstract
Morphological changes induced by industrial noise (IN) have been experimentally observed in several organs. Histological observations of the coronary arteries showed prominent perivascular tissue and fibrosis among IN-exposed rats. The effects on the small arteries are unknown. Objective: To evaluate the histomorphometric changes [...] Read more.
Morphological changes induced by industrial noise (IN) have been experimentally observed in several organs. Histological observations of the coronary arteries showed prominent perivascular tissue and fibrosis among IN-exposed rats. The effects on the small arteries are unknown. Objective: To evaluate the histomorphometric changes induced by IN on rat heart small arteries. Methods: Twenty Wistar rats exposed to IN during a maximum period of seven months and 20 age-matched controls were studied. Hearts were transversely sectioned from ventricular apex to atria and a mid-ventricular fragment was selected for analysis. The histological images were obtained with an optical microscope using 400× magnifications. A total of 634 arterial vessels (298 IN-exposed and 336 controls) were selected. The mean lumen-to-vessel wall (L/W) and mean vessel wall-to-perivascular tissue (W/P) ratios were calculated using image J software. Results: There were no differences between exposed and control animals in their L/W ratios (p = 0.687) and time variations in this ratio were non-significant (p = 0.110). In contrast, exposed animals showed lower W/P ratios than control animals (p < 0.001), with significant time variations (p = 0.004). Conclusions: Industrial noise induced an increase in the perivascular tissue of rat small coronary arteries, with significant development of periarterial fibrosis. Full article
(This article belongs to the Section Biochemistry)
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16 pages, 1789 KiB  
Article
Effect of γ-Cyclodextrin Inclusion Complex on the Absorption of R-α-Lipoic Acid in Rats
by Ryota Uchida, Kosuke Iwamoto, Suetada Nagayama, Atsushi Miyajima, Hinako Okamoto, Naoko Ikuta, Hiroshi Fukumi, Keiji Terao and Takashi Hirota
Int. J. Mol. Sci. 2015, 16(5), 10105-10120; https://doi.org/10.3390/ijms160510105 - 4 May 2015
Cited by 16 | Viewed by 6767
Abstract
R-α-lipoic acid (RLA) is an endogenous organic acid, and works as a cofactor for mitochondrial enzymes and as a kind of antioxidant. Inclusion complexes of RLA with α-, β- or γ-cyclodextrins (CD) were prepared and orally administered as a suspension to rats. Among [...] Read more.
R-α-lipoic acid (RLA) is an endogenous organic acid, and works as a cofactor for mitochondrial enzymes and as a kind of antioxidant. Inclusion complexes of RLA with α-, β- or γ-cyclodextrins (CD) were prepared and orally administered as a suspension to rats. Among them, RLA/γ-CD showed the highest plasma exposure, and its area under the plasma concentration-time curve (AUC) of RLA was 2.2 times higher than that after oral administration of non-inclusion RLA. On the other hand, the AUC after oral administration of non-inclusion RLA and RLA/γ-CD to pylorus-ligated rats did not differ. However, the AUC after intraduodenal administration of RLA/γ-CD was 5.1 times higher than that of non-inclusion RLA, and was almost comparable to the AUC after intraduodenal administration of RLA-Na solution. Furthermore, the AUC after intraduodenal administration of RLA/γ-CD was not affected by biliary ligation or co-administration of an amylase inhibitor. These findings demonstrated that RLA was absorbed from the small intestine effectively when orally administered as a γ-CD inclusion complex, which could be easily dissolved in the lumen of the intestine. In conclusion, γ-CD inclusion complex is an appropriate formulation for supplying RLA as a drug or nutritional supplement with respect to absorption. Full article
(This article belongs to the Section Biochemistry)
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13 pages, 939 KiB  
Review
Ultrasound Tissue Characterization of Vulnerable Atherosclerotic Plaque
by Eugenio Picano and Marco Paterni
Int. J. Mol. Sci. 2015, 16(5), 10121-10133; https://doi.org/10.3390/ijms160510121 - 5 May 2015
Cited by 66 | Viewed by 7840
Abstract
A thrombotic occlusion of the vessel fed by ruptured coronary atherosclerotic plaque may result in unstable angina, myocardial infarction or death, whereas embolization from a plaque in carotid arteries may result in transient ischemic attack or stroke. The atherosclerotic plaque prone to such [...] Read more.
A thrombotic occlusion of the vessel fed by ruptured coronary atherosclerotic plaque may result in unstable angina, myocardial infarction or death, whereas embolization from a plaque in carotid arteries may result in transient ischemic attack or stroke. The atherosclerotic plaque prone to such clinical events is termed high-risk or vulnerable plaque, and its identification in humans before it becomes symptomatic has been elusive to date. Ultrasonic tissue characterization of the atherosclerotic plaque is possible with different techniques—such as vascular, transesophageal, and intravascular ultrasound—on a variety of arterial segments, including carotid, aorta, and coronary districts. The image analysis can be based on visual, video-densitometric or radiofrequency methods and identifies three distinct textural patterns: hypo-echoic (corresponding to lipid- and hemorrhage-rich plaque), iso- or moderately hyper-echoic (fibrotic or fibro-fatty plaque), and markedly hyperechoic with shadowing (calcific plaque). Hypoechoic or dishomogeneous plaques, with spotty microcalcification and large plaque burden, with plaque neovascularization and surface irregularities by contrast-enhanced ultrasound, are more prone to clinical complications than hyperechoic, extensively calcified, homogeneous plaques with limited plaque burden, smooth luminal plaque surface and absence of neovascularization. Plaque ultrasound morphology is important, along with plaque geometry, in determining the atherosclerotic prognostic burden in the individual patient. New quantitative methods beyond backscatter (to include speed of sound, attenuation, strain, temperature, and high order statistics) are under development to evaluate vascular tissues. Although not yet ready for widespread clinical use, tissue characterization is listed by the American Society of Echocardiography roadmap to 2020 as one of the most promising fields of application in cardiovascular ultrasound imaging, offering unique opportunities for the early detection and treatment of atherosclerotic disease. Full article
(This article belongs to the Special Issue Atherosclerosis and Vascular Imaging)
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24 pages, 1375 KiB  
Article
Evolutionary Analysis of the B56 Gene Family of PP2A Regulatory Subunits
by Lauren M. Sommer, Hyuk Cho, Madhusudan Choudhary and Joni M. Seeling
Int. J. Mol. Sci. 2015, 16(5), 10134-10157; https://doi.org/10.3390/ijms160510134 - 5 May 2015
Cited by 15 | Viewed by 6690
Abstract
Protein phosphatase 2A (PP2A) is an abundant serine/threonine phosphatase that functions as a tumor suppressor in numerous cell-cell signaling pathways, including Wnt, myc, and ras. The B56 subunit of PP2A regulates its activity, and is encoded by five genes in humans. B56 proteins [...] Read more.
Protein phosphatase 2A (PP2A) is an abundant serine/threonine phosphatase that functions as a tumor suppressor in numerous cell-cell signaling pathways, including Wnt, myc, and ras. The B56 subunit of PP2A regulates its activity, and is encoded by five genes in humans. B56 proteins share a central core domain, but have divergent amino- and carboxy-termini, which are thought to provide isoform specificity. We performed phylogenetic analyses to better understand the evolution of the B56 gene family. We found that B56 was present as a single gene in eukaryotes prior to the divergence of animals, fungi, protists, and plants, and that B56 gene duplication prior to the divergence of protostomes and deuterostomes led to the origin of two B56 subfamilies, B56αβε and B56γδ. Further duplications led to three B56αβε genes and two B56γδ in vertebrates. Several nonvertebrate B56 gene names are based on distinct vertebrate isoform names, and would best be renamed. B56 subfamily genes lack significant divergence within primitive chordates, but each became distinct in complex vertebrates. Two vertebrate lineages have undergone B56 gene loss, Xenopus and Aves. In Xenopus, B56δ function may be compensated for by an alternatively spliced transcript, B56δ/γ, encoding a B56δ-like amino-terminal region and a B56γ core. Full article
(This article belongs to the Section Biochemistry)
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15 pages, 4327 KiB  
Article
The Heart Protection Effect of Alcalase Potato Protein Hydrolysate Is through IGF1R-PI3K-Akt Compensatory Reactivation in Aging Rats on High Fat Diets
by Wei-Syun Hu, Wei-Jen Ting, Wen-Dee Chiang, Peiying Pai, Yu-Lan Yeh, Chung-Ho Chang, Wan-Teng Lin and Chih-Yang Huang
Int. J. Mol. Sci. 2015, 16(5), 10158-10172; https://doi.org/10.3390/ijms160510158 - 5 May 2015
Cited by 28 | Viewed by 6273
Abstract
The prevalence of obesity is high in older adults. Alcalase potato protein hydrolysate (APPH), a nutraceutical food, might have greater benefits and be more economical than hypolipidemic drugs. In this study, serum lipid profiles and heart protective effects were evaluated in high fat [...] Read more.
The prevalence of obesity is high in older adults. Alcalase potato protein hydrolysate (APPH), a nutraceutical food, might have greater benefits and be more economical than hypolipidemic drugs. In this study, serum lipid profiles and heart protective effects were evaluated in high fat diet (HFD) induced hyperlipidemia in aging rats treated with APPH (15, 45 and 75 mg/kg/day) and probucol (500 mg/kg/day). APPH treatments reduced serum triacylglycerol (TG), total cholesterol (TC), and low density lipoprotein (LDL) levels to the normal levels expressed in the control group. Additionally, the IGF1R-PI3K-Akt survival pathway was reactivated, and Fas-FADD (Fas-associated death domain) induced apoptosis was inhibited by APPH treatments (15 and 45 mg/kg/day) in HFD aging rat hearts. APPH (75 mg/kg/day) rather than probucol (500 mg/kg/day) treatment could reduce serum lipids without affecting HDL expression. The heart protective effect of APPH in aging rats with hyperlipidemia was through lowering serum lipids and enhancing the activation of the compensatory IGF1R-PI3K-Akt survival pathway. Full article
(This article belongs to the Section Biochemistry)
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12 pages, 1089 KiB  
Article
Design, Synthesis and Biological Evaluation of 1,4-Disubstituted-3,4-dihydroisoquinoline Compounds as New Tubulin Polymerization Inhibitors
by Ling Zhang, Yunlong Song, Jingjing Huang, Jia Liu, Wenwen Zhu, Youjun Zhou, Jiaguo Lv, Canhui Zheng and Ju Zhu
Int. J. Mol. Sci. 2015, 16(5), 10173-10184; https://doi.org/10.3390/ijms160510173 - 5 May 2015
Cited by 4 | Viewed by 5449
Abstract
A series of 1,4-disubstituted-3,4-dihydroisoquinoline derivatives designed as tubulin polymerization inhibitors were synthesized. Their cytotoxic activities against the CEM leukemia cell line were evaluated. Most of them displayed moderate cytotoxic activities, and compounds 21 and 32 showed good activities with IC50 of 4.10 [...] Read more.
A series of 1,4-disubstituted-3,4-dihydroisoquinoline derivatives designed as tubulin polymerization inhibitors were synthesized. Their cytotoxic activities against the CEM leukemia cell line were evaluated. Most of them displayed moderate cytotoxic activities, and compounds 21 and 32 showed good activities with IC50 of 4.10 and 0.64 μM, respectively. The most potent compound 32 was further confirmed to be able to inhibit tubulin polymerization, and its hypothetical binding mode with tubulin was obtained by molecular docking. Full article
(This article belongs to the Section Materials Science)
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16 pages, 2232 KiB  
Article
Resistance of Lung Cancer Cells Grown as Multicellular Tumour Spheroids to Zinc Sulfophthalocyanine Photosensitization
by Sello Lebohang Manoto, Nicolette Nadene Houreld and Heidi Abrahamse
Int. J. Mol. Sci. 2015, 16(5), 10185-10200; https://doi.org/10.3390/ijms160510185 - 5 May 2015
Cited by 22 | Viewed by 5569
Abstract
Photodynamic therapy (PDT) is phototherapeutic modality used in the treatment of neoplastic and non-neoplastic diseases. The photochemical interaction of light, photosensitizer (PS) and molecular oxygen produces singlet oxygen which induces cell death. Zinc sulfophthalocyanine (ZnPcSmix) has been shown to be effective [...] Read more.
Photodynamic therapy (PDT) is phototherapeutic modality used in the treatment of neoplastic and non-neoplastic diseases. The photochemical interaction of light, photosensitizer (PS) and molecular oxygen produces singlet oxygen which induces cell death. Zinc sulfophthalocyanine (ZnPcSmix) has been shown to be effective in A549 monolayers, multicellular tumor spheroids (MCTSs) (250 µm) and not on MCTSs with a size of 500 µm. A549 cells used in this study were grown as MCTSs to a size of 500 µm in order to determine their susceptibility to PDT. ZnPcSmix distribution in MCTSs and nuclear morphology was determined using a fluorescent microscope. Changes in cellular responses were evaluated using cell morphology, viability, proliferation, cytotoxicity, cell death analysis and mitochondrial membrane potential. Untreated MCTSs, showed no changes in cellular morphology, proliferation, cytotoxicity and nuclear morphology. Photoactivated ZnPcSmix also showed no changes in cellular morphology and nuclear morphology. However, photoactivated ZnPcSmix resulted in a significant dose dependant decrease in viability and proliferation as well as an increase in cell membrane damage in MCTSs over time. ZnPcSmix photosensitization induces apoptotic cell death in MCTSs with a size of 500 µm and more resistantance when compared to monolayer cells and MCTSs with a size of 250 µm. Full article
(This article belongs to the Special Issue Advances in Photodynamic Therapy)
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13 pages, 1574 KiB  
Article
Hierarchically Ordered Supramolecular Protein-Polymer Composites with Thermoresponsive Properties
by Salla Välimäki, Joona Mikkilä, Ville Liljeström, Henna Rosilo, Ari Ora and Mauri A. Kostiainen
Int. J. Mol. Sci. 2015, 16(5), 10201-10213; https://doi.org/10.3390/ijms160510201 - 5 May 2015
Cited by 14 | Viewed by 8861
Abstract
Synthetic macromolecules that can bind and co-assemble with proteins are important for the future development of biohybrid materials. Active systems are further required to create materials that can respond and change their behavior in response to external stimuli. Here we report that stimuli-responsive [...] Read more.
Synthetic macromolecules that can bind and co-assemble with proteins are important for the future development of biohybrid materials. Active systems are further required to create materials that can respond and change their behavior in response to external stimuli. Here we report that stimuli-responsive linear-branched diblock copolymers consisting of a cationic multivalent dendron with a linear thermoresponsive polymer tail at the focal point, can bind and complex Pyrococcus furiosus ferritin protein cages into crystalline arrays. The multivalent dendron structure utilizes cationic spermine units to bind electrostatically on the surface of the negatively charged ferritin cage and the in situ polymerized poly(di(ethylene glycol) methyl ether methacrylate) linear block enables control with temperature. Cloud point of the final product was determined with dynamic light scattering (DLS), and it was shown to be approximately 31 °C at a concentration of 150 mg/L. Complexation of the polymer binder and apoferritin was studied with DLS, small-angle X-ray scattering, and transmission electron microscopy, which showed the presence of crystalline arrays of ferritin cages with a face-centered cubic (fcc, \( Fm\overline{3}m \)) Bravais lattice where lattice parameter a = 18.6 nm. The complexation process was not temperature dependent but the final complexes had thermoresponsive characteristics with negative thermal expansion. Full article
(This article belongs to the Special Issue Supramolecular Interactions)
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14 pages, 705 KiB  
Article
Response of Different Genotypes of Faba Bean Plant to Drought Stress
by Manzer H. Siddiqui, Mutahhar Y. Al-Khaishany, Mohammed A. Al-Qutami, Mohamed H. Al-Whaibi, Anil Grover, Hayssam M. Ali, Mona S. Al-Wahibi and Najat A. Bukhari
Int. J. Mol. Sci. 2015, 16(5), 10214-10227; https://doi.org/10.3390/ijms160510214 - 5 May 2015
Cited by 161 | Viewed by 10488
Abstract
Drought stress is one of the major abiotic stresses that are a threat to crop production worldwide. Drought stress impairs the plants growth and yield. Therefore, the aim of the present experiment was to select the tolerant genotype/s on the basis of moprpho-physiological [...] Read more.
Drought stress is one of the major abiotic stresses that are a threat to crop production worldwide. Drought stress impairs the plants growth and yield. Therefore, the aim of the present experiment was to select the tolerant genotype/s on the basis of moprpho-physiological and biochemical characteristics of 10 Vicia faba genotypes (Zafar 1, Zafar 2, Shebam, Makamora, Espan, Giza Blanka, Giza 3, C4, C5 and G853) under drought stress. We studied the effect of different levels of drought stress i.e., (i) normal irrigation (ii) mild stress (iii) moderate stress, and (iv) severe stress on plant height (PH) plant−1, fresh weight (FW) and dry weight (DW) plant−1, area leaf−1, leaf relative water content (RWC), proline (Pro) content, total chlorophyll (Total Chl) content, electrolyte leakage (EL), malondialdehyde (MDA), hydrogen peroxide (H2O2) content, and activities of catalase (CAT), peroxidase (POD) and superoxide dismutase (SOD) of genotypes of faba bean. Drought stress reduced all growth parameters and Total Chl content of all genotypes. However, the deteriorating effect of drought stress on the growth performance of genotypes “C5” and “Zafar 1” were relatively low due to its better antioxidant enzymes activities (CAT, POD and SOD), and accumulation of Pro and Total Chl, and leaf RWC. In the study, genotype “C5” and “Zafar 1” were found to be relatively tolerant to drought stress and genotypes “G853” and “C4” were sensitive to drought stress. Full article
(This article belongs to the Special Issue Molecular Research in Plant Secondary Metabolism 2015)
14 pages, 1219 KiB  
Review
Cell Death Pathways and Phthalocyanine as an Efficient Agent for Photodynamic Cancer Therapy
by Ivan Mfouo-Tynga and Heidi Abrahamse
Int. J. Mol. Sci. 2015, 16(5), 10228-10241; https://doi.org/10.3390/ijms160510228 - 6 May 2015
Cited by 64 | Viewed by 9478
Abstract
The mechanisms of cell death can be predetermined (programmed) or not and categorized into apoptotic, autophagic and necrotic pathways. The process of Hayflick limits completes the execution of death-related mechanisms. Reactive oxygen species (ROS) are associated with oxidative stress and subsequent cytodamage by [...] Read more.
The mechanisms of cell death can be predetermined (programmed) or not and categorized into apoptotic, autophagic and necrotic pathways. The process of Hayflick limits completes the execution of death-related mechanisms. Reactive oxygen species (ROS) are associated with oxidative stress and subsequent cytodamage by oxidizing and degrading cell components. ROS are also involved in immune responses, where they stabilize and activate both hypoxia-inducible factors and phagocytic effectors. ROS production and presence enhance cytodamage and photodynamic-induced cell death. Photodynamic cancer therapy (PDT) uses non-toxic chemotherapeutic agents, photosensitizer (PS), to initiate a light-dependent and ROS-related cell death. Phthalocyanines (PCs) are third generation and stable PSs with improved photochemical abilities. They are effective inducers of cell death in various neoplastic models. The metallated PCs localize in critical cellular organelles and are better inducers of cell death than other previous generation PSs as they favor mainly apoptotic cell death events. Full article
(This article belongs to the Special Issue Advances in Photodynamic Therapy)
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25 pages, 2336 KiB  
Article
The Drosophila Retinoblastoma Binding Protein 6 Family Member Has Two Isoforms and Is Potentially Involved in Embryonic Patterning
by Rodney Hull, Brent Oosthuysen, Umar-Faruq Cajee, Lehlogonolo Mokgohloa, Ekene Nweke, Ricardo Jorge Antunes, Theresa H. T. Coetzer and Monde Ntwasa
Int. J. Mol. Sci. 2015, 16(5), 10242-10266; https://doi.org/10.3390/ijms160510242 - 6 May 2015
Cited by 6 | Viewed by 5814
Abstract
The human retinoblastoma binding protein 6 (RBBP6) is implicated in esophageal, lung, hepatocellular and colon cancers. Furthermore, RBBP6 was identified as a strong marker for colon cancer prognosis and as a predisposing factor in familial myeloproliferative neoplasms. Functionally, the mammalian protein interacts with [...] Read more.
The human retinoblastoma binding protein 6 (RBBP6) is implicated in esophageal, lung, hepatocellular and colon cancers. Furthermore, RBBP6 was identified as a strong marker for colon cancer prognosis and as a predisposing factor in familial myeloproliferative neoplasms. Functionally, the mammalian protein interacts with p53 and enhances the activity of Mdm2, the prototypical negative regulator of p53. However, since RBBP6 (known as PACT in mice) exists in multiple isoforms and pact−/− mice exhibit a more severe phenotype than mdm2−/− mutants, it must possess some Mdm2-independent functions. The function of the invertebrate homologue is poorly understood. This is complicated by the absence of the Mdm2 gene in both Drosophila and Caenorhabditis elegans. We have experimentally identified the promoter region of Snama, the Drosophila homologue, analyzed potential transcription factor binding sites and confirmed the existence of an additional isoform. Using band shift and co-immunoprecipitation assays combined with mass spectrometry, we found evidence that this gene may be regulated by, amongst others, DREF, which regulates hundreds of genes related to cell proliferation. The potential transcription factors for Snama fall into distinct functional groups, including anteroposterior embryonic patterning and nucleic acid metabolism. Significantly, previous work in mice shows that pact−/− induces an anteroposterior phenotype in embryos when rescued by simultaneous deletion of p53. Taken together, these observations indicate the significance of RBBP6 proteins in carcinogenesis and in developmental defects. Full article
(This article belongs to the Section Biochemistry)
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14 pages, 1030 KiB  
Review
Mechanism of Action of IL-7 and Its Potential Applications and Limitations in Cancer Immunotherapy
by Jianbao Gao, Lintao Zhao, Yisong Y. Wan and Bo Zhu
Int. J. Mol. Sci. 2015, 16(5), 10267-10280; https://doi.org/10.3390/ijms160510267 - 6 May 2015
Cited by 99 | Viewed by 15100
Abstract
Interleukin-7 (IL-7) is a non-hematopoietic cell-derived cytokine with a central role in the adaptive immune system. It promotes lymphocyte development in the thymus and maintains survival of naive and memory T cell homeostasis in the periphery. Moreover, it is important for the organogenesis [...] Read more.
Interleukin-7 (IL-7) is a non-hematopoietic cell-derived cytokine with a central role in the adaptive immune system. It promotes lymphocyte development in the thymus and maintains survival of naive and memory T cell homeostasis in the periphery. Moreover, it is important for the organogenesis of lymph nodes (LN) and for the maintenance of activated T cells recruited into the secondary lymphoid organs (SLOs). The immune capacity of cancer patients is suppressed that is characterized by lower T cell counts, less effector immune cells infiltration, higher levels of exhausted effector cells and higher levels of immunosuppressive cytokines, such as transforming growth factor β (TGF-β). Recombinant human IL-7 (rhIL-7) is an ideal solution for the immune reconstitution of lymphopenia patients by promoting peripheral T cell expansion. Furthermore, it can antagonize the immunosuppressive network. In animal models, IL-7 has been proven to prolong the survival of tumor-bearing hosts. In this review, we will focus on the mechanism of action and applications of IL-7 in cancer immunotherapy and the potential restrictions for its usage. Full article
(This article belongs to the Special Issue Mechanism of Action and Applications of Cytokines in Immunotherapy)
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20 pages, 1188 KiB  
Review
Anti-NR2A/B Antibodies and Other Major Molecular Mechanisms in the Pathogenesis of Cognitive Dysfunction in Systemic Lupus Erythematosus
by Sen Hee Tay and Anselm Mak
Int. J. Mol. Sci. 2015, 16(5), 10281-10300; https://doi.org/10.3390/ijms160510281 - 6 May 2015
Cited by 32 | Viewed by 8932
Abstract
Systemic lupus erythematosus (SLE) is an autoimmune disease that affects approximately 1–45.3 per 100,000 people worldwide. Although deaths as a result of active and renal diseases have been substantially declining amongst SLE patients, disease involving the central nervous system (CNS), collectively termed neuropsychiatric [...] Read more.
Systemic lupus erythematosus (SLE) is an autoimmune disease that affects approximately 1–45.3 per 100,000 people worldwide. Although deaths as a result of active and renal diseases have been substantially declining amongst SLE patients, disease involving the central nervous system (CNS), collectively termed neuropsychiatric systemic lupus erythematosus (NPSLE), remains one of the important causes of death in these patients. Cognitive dysfunction is one of the most common manifestations of NPSLE, which comprises deficits in information-processing speed, attention and executive function, in conjunction with preservation of speech. Albeit a prevalent manifestation of NPSLE, the pathogenetic mechanisms of cognitive dysfunction remain unclear. Recent advances in genetic studies, molecular techniques, neuropathology, neuroimaging and cognitive science have gleaned valuable insights into the pathophysiology of lupus-related cognitive dysfunction. In recent years, a role for autoantibodies, molecular and cellular mechanisms in cognitive dysfunction, has been emerging, challenging our previous concept of the brain as an immune privileged site. This review will focus on the potential pathogenic factors involved in NPSLE, including anti-N-methyl-d-aspartate receptor subunit NR2A/B (anti-NR2A/B) antibodies, matrix metalloproteinase-9, neutrophil extracellular traps and pro-inflammatory mediators. Better understanding of these mechanistic processes will enhance identification of new therapeutic modalities to halt the progression of cognitive decline in SLE patients. Full article
(This article belongs to the Special Issue Molecular and Cellular Mechanisms in the Pathogenesis of Systemic Lupus Erythematosus)
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23 pages, 5506 KiB  
Article
Gene Overexpression and RNA Silencing Tools for the Genetic Manipulation of the S-(+)-Abscisic Acid Producing Ascomycete Botrytis cinerea
by Zhong-Tao Ding, Zhi Zhang, Di Luo, Jin-Yan Zhou, Juan Zhong, Jie Yang, Liang Xiao, Dan Shu and Hong Tan
Int. J. Mol. Sci. 2015, 16(5), 10301-10323; https://doi.org/10.3390/ijms160510301 - 6 May 2015
Cited by 16 | Viewed by 7846
Abstract
The phytopathogenic ascomycete Botrytis cinerea produces several secondary metabolites that have biotechnical significance and has been particularly used for S-(+)-abscisic acid production at the industrial scale. To manipulate the expression levels of specific secondary metabolite biosynthetic genes of B. cinerea with Agrobacterium [...] Read more.
The phytopathogenic ascomycete Botrytis cinerea produces several secondary metabolites that have biotechnical significance and has been particularly used for S-(+)-abscisic acid production at the industrial scale. To manipulate the expression levels of specific secondary metabolite biosynthetic genes of B. cinerea with Agrobacterium tumefaciens-mediated transformation system, two expression vectors (pCBh1 and pCBg1 with different selection markers) and one RNA silencing vector, pCBSilent1, were developed with the In-Fusion assembly method. Both expression vectors were highly effective in constitutively expressing eGFP, and pCBSilent1 effectively silenced the eGFP gene in B. cinerea. Bcaba4, a gene suggested to participate in ABA biosynthesis in B. cinerea, was then targeted for gene overexpression and RNA silencing with these reverse genetic tools. The overexpression of bcaba4 dramatically induced ABA formation in the B. cinerea wild type strain Bc-6, and the gene silencing of bcaba4 significantly reduced ABA-production in an ABA-producing B. cinerea strain. Full article
(This article belongs to the Section Biochemistry)
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13 pages, 7861 KiB  
Article
Cell Adhesion and in Vivo Osseointegration of Sandblasted/Acid Etched/Anodized Dental Implants
by Mu-Hyon Kim, Kyeongsoon Park, Kyung-Hee Choi, Soo-Hong Kim, Se Eun Kim, Chang-Mo Jeong and Jung-Bo Huh
Int. J. Mol. Sci. 2015, 16(5), 10324-10336; https://doi.org/10.3390/ijms160510324 - 6 May 2015
Cited by 66 | Viewed by 10411
Abstract
The authors describe a new type of titanium (Ti) implant as a Modi-anodized (ANO) Ti implant, the surface of which was treated by sandblasting, acid etching (SLA), and anodized techniques. The aim of the present study was to evaluate the adhesion of MG-63 [...] Read more.
The authors describe a new type of titanium (Ti) implant as a Modi-anodized (ANO) Ti implant, the surface of which was treated by sandblasting, acid etching (SLA), and anodized techniques. The aim of the present study was to evaluate the adhesion of MG-63 cells to Modi-ANO surface treated Ti in vitro and to investigate its osseointegration characteristics in vivo. Four different types of Ti implants were examined, that is, machined Ti (control), SLA, anodized, and Modi-ANO Ti. In the cell adhesion study, Modi-ANO Ti showed higher initial MG-63 cell adhesion and induced greater filopodia growth than other groups. In vivo study in a beagle model revealed the bone-to-implant contact (BIC) of Modi-ANO Ti (74.20% ± 10.89%) was much greater than those of machined (33.58% ± 8.63%), SLA (58.47% ± 12.89), or ANO Ti (59.62% ± 18.30%). In conclusion, this study demonstrates that Modi-ANO Ti implants produced by sandblasting, acid etching, and anodizing improve cell adhesion and bone ongrowth as compared with machined, SLA, or ANO Ti implants. These findings suggest that the application of Modi-ANO surface treatment could improve the osseointegration of dental implant. Full article
(This article belongs to the Special Issue Biomaterials for Tissue Engineering)
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17 pages, 1190 KiB  
Article
Effect of Melatonin on the Extracellular-Regulated Kinase Signal Pathway Activation and Human Osteoblastic Cell Line hFOB 1.19 Proliferation
by Xiao-Chuan Xiong, Yue Zhu, Rui Ge, Li-Feng Liu and Wei Yuan
Int. J. Mol. Sci. 2015, 16(5), 10337-10353; https://doi.org/10.3390/ijms160510337 - 7 May 2015
Cited by 24 | Viewed by 5980
Abstract
It has been shown that melatonin may affect bone metabolism. However, it is controversial whether melatonin could promote osteoblast proliferation, and the precise molecular mechanism of melatonin on osteoblast proliferation is still obscure. In this study, the results of the CCK-8 assay showed [...] Read more.
It has been shown that melatonin may affect bone metabolism. However, it is controversial whether melatonin could promote osteoblast proliferation, and the precise molecular mechanism of melatonin on osteoblast proliferation is still obscure. In this study, the results of the CCK-8 assay showed that melatonin significantly promoted human osteoblastic cell line hFOB 1.19 cell proliferation at 1, 2.5, 5, 10, 25, 50 and 100 µM concentrations for 24 h, but there were no significant differences among the groups. Western blot demonstrated that 10 µM melatonin significantly promoted ERK1/2 phosphorylation. Furthermore, we also detected the phosphorylation of c-Raf, MEK1/2, p90RSK and MSK1, and all of them increased with 10 µM melatonin. U0126 (a selective inhibitor of MEK that disrupts downstream activation of ERK1/2) downregulated the phosphorylation of ERK1/2, p90RSK and MSK1. U0126 also attenuated the proliferation of osteoblasts stimulated by melatonin. In conclusion, this study for the first time indicates that melatonin (10 nM–100 µM) promotes the proliferation of a human osteoblastic cell line hFOB 1.19 through activation of c-Raf, MEK1/2, ERK1/2, p90RSK and MSK1. Full article
(This article belongs to the Special Issue Molecular Machinery of Cell Growth Regulation)
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22 pages, 167 KiB  
Article
Optimal Decision Rules for Biomarker-Based Subgroup Selection for a Targeted Therapy in Oncology
by Johannes Krisam and Meinhard Kieser
Int. J. Mol. Sci. 2015, 16(5), 10354-10375; https://doi.org/10.3390/ijms160510354 - 7 May 2015
Cited by 10 | Viewed by 5191
Abstract
Throughout recent years, there has been a rapidly increasing interest regarding the evaluation of so-called targeted therapies. These therapies are assumed to show a greater benefit in a pre-specified subgroup of patients—commonly identified by a predictive biomarker—as compared to the total patient population [...] Read more.
Throughout recent years, there has been a rapidly increasing interest regarding the evaluation of so-called targeted therapies. These therapies are assumed to show a greater benefit in a pre-specified subgroup of patients—commonly identified by a predictive biomarker—as compared to the total patient population of interest. This situation has led to the necessity to develop biostatistical methods allowing an efficient evaluation of such treatments. Among others, adaptive enrichment designs have been proposed as a solution. These designs allow the selection of the most promising patient population based on an efficacy analysis at interim and restricting recruitment to these patients afterwards. As has recently been shown, the performance of the applied interim decision rule in such a design plays a crucial role in ensuring a successful trial. In this work, we investigate the situation when the primary outcome of the trial is a binary variable. Optimal decision rules are derived which incorporate the uncertainty about the treatment effects. These optimal decision rules are evaluated with respect to their performance in an adaptive enrichment design in terms of correct selection probability and power, and are compared to proposed ad hoc decision rules. Our methods are illustrated by means of a clinical trial example. Full article
(This article belongs to the Special Issue Emerging Classes of Biomarkers for Molecular Diagnostics)
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13 pages, 1761 KiB  
Article
Identification and Validation of Evolutionarily Conserved Unusually Short Pre-mRNA Introns in the Human Genome
by Makoto K. Shimada, Noriko Sasaki-Haraguchi and Akila Mayeda
Int. J. Mol. Sci. 2015, 16(5), 10376-10388; https://doi.org/10.3390/ijms160510376 - 7 May 2015
Cited by 12 | Viewed by 7236
Abstract
According to the length distribution of human introns, there is a large population of short introns with a threshold of 65 nucleotides (nt) and a peak at 85 nt. Using human genome and transcriptome databases, we investigated the introns shorter than 66 nt, [...] Read more.
According to the length distribution of human introns, there is a large population of short introns with a threshold of 65 nucleotides (nt) and a peak at 85 nt. Using human genome and transcriptome databases, we investigated the introns shorter than 66 nt, termed ultra-short introns, the identities of which are scarcely known. Here, we provide for the first time a list of bona fide human ultra-short introns, which have never been characterized elsewhere. By conducting BLAST searches of the databases, we screened 22 introns (37–65 nt) with conserved lengths and sequences among closely related species. We then provide experimental and bioinformatic evidence for the splicing of 15 introns, of which 12 introns were remarkably G-rich and 9 introns contained completely inefficient splice sites and/or branch sites. These unorthodox characteristics of ultra-short introns suggest that there are unknown splicing mechanisms that differ from the well-established mechanism. Full article
(This article belongs to the Special Issue Pre-mRNA Splicing 2015)
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22 pages, 8268 KiB  
Article
Subcellular Sequestration and Impact of Heavy Metals on the Ultrastructure and Physiology of the Multicellular Freshwater Alga Desmidium swartzii
by Ancuela Andosch, Margit Höftberger, Cornelius Lütz and Ursula Lütz-Meindl
Int. J. Mol. Sci. 2015, 16(5), 10389-10410; https://doi.org/10.3390/ijms160510389 - 7 May 2015
Cited by 39 | Viewed by 7455 | Correction
Abstract
Due to modern life with increasing traffic, industrial production and agricultural practices, high amounts of heavy metals enter ecosystems and pollute soil and water. As a result, metals can be accumulated in plants and particularly in algae inhabiting peat bogs of low pH [...] Read more.
Due to modern life with increasing traffic, industrial production and agricultural practices, high amounts of heavy metals enter ecosystems and pollute soil and water. As a result, metals can be accumulated in plants and particularly in algae inhabiting peat bogs of low pH and high air humidity. In the present study, we investigated the impact and intracellular targets of aluminum, copper, cadmium, chromium VI and zinc on the filamentous green alga Desmidium swartzii, which is an important biomass producer in acid peat bogs. By means of transmission electron microscopy (TEM) and electron energy loss spectroscopy (EELS) it is shown that all metals examined are taken up into Desmidium readily, where they are sequestered in cell walls and/or intracellular compartments. They cause effects on cell ultrastructure to different degrees and additionally disturb photosynthetic activity and biomass production. Our study shows a clear correlation between toxicity of a metal and the ability of the algae to compartmentalize it intracellularly. Cadmium and chromium, which are not compartmentalized, exert the most toxic effects. In addition, this study shows that the filamentous alga Desmidium reacts more sensitively to aluminum and zinc when compared to its unicellular relative Micrasterias, indicating a severe threat to the ecosystem. Full article
(This article belongs to the Special Issue Effects of Herbicides and Heavy Metals to the Structure and Function of Plant Cells)
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15 pages, 1190 KiB  
Article
TCF4 Is a Molecular Target of Resveratrol in the Prevention of Colorectal Cancer
by Jin Boo Jeong, Jihye Lee and Seong-Ho Lee
Int. J. Mol. Sci. 2015, 16(5), 10411-10425; https://doi.org/10.3390/ijms160510411 - 7 May 2015
Cited by 28 | Viewed by 8473
Abstract
The Wnt/β-catenin pathway plays an essential role in the tumorigenesis of colorectal cancer. T-cell factor-4 (TCF4) is a member of the TCF/LEF (lymphoid enhancer factor) family of transcription factors, and dysregulation of β-catenin is decisive for the initiation and progression of colorectal cancer. [...] Read more.
The Wnt/β-catenin pathway plays an essential role in the tumorigenesis of colorectal cancer. T-cell factor-4 (TCF4) is a member of the TCF/LEF (lymphoid enhancer factor) family of transcription factors, and dysregulation of β-catenin is decisive for the initiation and progression of colorectal cancer. However, the role of TCF4 in the transcriptional regulation of its target gene remained poorly understood. Resveratrol is a dietary phytoalexin and present in many plants, including grape skin, nuts and fruits. Although resveratrol has been widely implicated in anti-tumorigenic and pro-apoptotic properties in several cancer models, the underlying cellular mechanisms are only partially understood. The current study was performed to elucidate the molecular mechanism of the anti-cancer activity of resveratrol in human colorectal cancer cells. The treatment of resveratrol and other phytochemicals decreased the expression of TCF4. Resveratrol decreases cellular accumulation of exogenously-introduced TCF4 protein, but did not change the TCF4 transcription. The inhibition of proteasomal degradation using MG132 (carbobenzoxy-Leu-Leu-leucinal) and lactacystin ameliorates resveratrol-stimulated down-regulation of TCF4. The half-life of TCF4 was decreased in the cells exposed to resveratrol. Resveratrol increased phosphorylation of TCF4 at serine/threonine residues through ERK (extracellular signal-regulated kinases) and p38-dependent pathways. The TCF4 knockdown decreased TCF/β-catenin-mediated transcriptional activity and sensitized resveratrol-induced apoptosis. The current study provides a new mechanistic link between resveratrol and TCF4 down-regulation and significant benefits for further preclinical and clinical practice. Full article
(This article belongs to the Collection Programmed Cell Death and Apoptosis)
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17 pages, 3753 KiB  
Article
Humic Acid Increases Amyloid β-Induced Cytotoxicity by Induction of ER Stress in Human SK-N-MC Neuronal Cells
by Hsin-Hua Li, Fung-Jou Lu, Hui-Chih Hung, Guang-Yaw Liu, Te-Jen Lai and Chih-Li Lin
Int. J. Mol. Sci. 2015, 16(5), 10426-10442; https://doi.org/10.3390/ijms160510426 - 7 May 2015
Cited by 12 | Viewed by 8239
Abstract
Humic acid (HA) is a possible etiological factor associated with for several vascular diseases. It is known that vascular risk factors can directly increase the susceptibility to Alzheimer’s disease (AD), which is a neurodegenerative disorder due to accumulation of amyloid β (Aβ) peptide [...] Read more.
Humic acid (HA) is a possible etiological factor associated with for several vascular diseases. It is known that vascular risk factors can directly increase the susceptibility to Alzheimer’s disease (AD), which is a neurodegenerative disorder due to accumulation of amyloid β (Aβ) peptide in the brain. However, the role that HA contributes to Aβ-induced cytotoxicity has not been demonstrated. In the present study, we demonstrate that HA exhibits a synergistic effect enhancing Aβ-induced cytotoxicity in cultured human SK-N-MC neuronal cells. Furthermore, this deterioration was mediated through the activation of endoplasmic reticulum (ER) stress by stimulating PERK and eIF2α phosphorylation. We also observed HA and Aβ-induced cytotoxicity is associated with mitochondrial dysfunction caused by down-regulation of the Sirt1/PGC1α pathway, while in contrast, treating the cells with the ER stress inhibitor Salubrinal, or over-expression of Sirt1 significantly reduced loss of cell viability by HA and Aβ. Our findings suggest a new mechanism by which HA can deteriorate Aβ-induced cytotoxicity through modulation of ER stress, which may provide significant insights into the pathogenesis of AD co-occurring with vascular injury. Full article
(This article belongs to the Special Issue Molecular Research in Neurotoxicology)
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14 pages, 4375 KiB  
Article
5-ALA Fluorescence Image Guided Resection of Glioblastoma Multiforme: A Meta-Analysis of the Literature
by Samy Eljamel
Int. J. Mol. Sci. 2015, 16(5), 10443-10456; https://doi.org/10.3390/ijms160510443 - 7 May 2015
Cited by 99 | Viewed by 9385
Abstract
Background: Glioblastoma multiforme (GBM) is one of the most deadly cancers in humans. Despite recent advances in anti-cancer therapies, most patients with GBM die from local disease progression. Fluorescence image guided surgical resection (FIGR) was recently advocated to enhance local control of GBM. [...] Read more.
Background: Glioblastoma multiforme (GBM) is one of the most deadly cancers in humans. Despite recent advances in anti-cancer therapies, most patients with GBM die from local disease progression. Fluorescence image guided surgical resection (FIGR) was recently advocated to enhance local control of GBM. This is meta-analyses of 5-aminolevulinic (5-ALA) induced FIGR. Materials: Review of the literature produced 503 potential publications; only 20 of these fulfilled the inclusion criteria of this analysis, including a total of 565 patients treated with 5-ALA-FIGR reporting on its outcomes and 800 histological samples reporting 5-ALA-FIGR sensitivity and specificity. Results: The mean gross total resection (GTR) rate was 75.4% (95% CI: 67.4–83.5, p < 0.001). The mean time to tumor progression (TTP) was 8.1 months (95% CI: 4.7–12, p < 0.001). The mean overall survival gain reported was 6.2 months (95% CI: −1–13, p < 0.001). The specificity was 88.9% (95% CI: 83.9–93.9, p < 0.001) and the sensitivity was 82.6% (95% CI: 73.9–91.9, p < 0.001). Conclusion: 5-ALA-FIGR in GBM is highly sensitive and specific, and imparts significant benefits to patients in terms of improved GTR and TTP. Full article
(This article belongs to the Special Issue Advances in Photodynamic Therapy)
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13 pages, 5522 KiB  
Article
4,4'-Diisothiocyanostilbene-2,2'-disulfonic Acid (DIDS) Ameliorates Ischemia-Hypoxia-Induced White Matter Damage in Neonatal Rats through Inhibition of the Voltage-Gated Chloride Channel ClC-2
by Baixiong Zhao, Hongyu Quan, Teng Ma, Yanping Tian, Qiyan Cai and Hongli Li
Int. J. Mol. Sci. 2015, 16(5), 10457-10469; https://doi.org/10.3390/ijms160510457 - 7 May 2015
Cited by 12 | Viewed by 5717
Abstract
Chronic cerebral hypoperfusion is believed to cause white matter lesions (WMLs), leading to cognitive impairment. Previous studies have shown that inflammation and apoptosis of oligodendrocytes (OLs) are involved in the pathogenesis of WMLs, but effective treatments have not been studied. In this study, [...] Read more.
Chronic cerebral hypoperfusion is believed to cause white matter lesions (WMLs), leading to cognitive impairment. Previous studies have shown that inflammation and apoptosis of oligodendrocytes (OLs) are involved in the pathogenesis of WMLs, but effective treatments have not been studied. In this study, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), a chloride (Cl−) channel blocker, was injected into chronic cerebral ischemia-hypoxia rat models at different time points. Our results showed that DIDS significantly reduced the elevated mRNA levels and protein expression of chloride channel 2 (ClC-2) in neonatal rats induced by ischemia-hypoxia. Meanwhile, DIDS application significantly decreased the concentrations of reactive oxygen species (ROS); and the mRNA levels of inducible nitric oxide synthase (iNOS) and tumor necrosis factor-alpha TNF-α in neonatal rats with hypoxic-ischemic damage. Myelin staining was weaker in neonatal rats with hypoxic-ischemic damage compared to normal controls in corpus callosum and other white matter, which was ameliorated by DIDS. Furthermore, the elevated number of caspase-3 and neural/glial antigen 2 (NG-2) double-labeled positive cells was attenuated by DIDS after ischemia anoxic injury. Administration of DIDS soon after injury alleviated damage to OLs much more effectively in white matter. In conclusion, our study suggests that early application of DIDS after ischemia-hypoxia injury may partially protect developing OLs. Full article
(This article belongs to the Section Biochemistry)
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21 pages, 2855 KiB  
Article
Investigation of the Anti-Melanogenic and Antioxidant Characteristics of Eucalyptus camaldulensis Flower Essential Oil and Determination of Its Chemical Composition
by Huey-Chun Huang, Ya-Chi Ho, Jia-Min Lim, Tzu-Yun Chang, Chen-Lung Ho and Tsong-Min Chang
Int. J. Mol. Sci. 2015, 16(5), 10470-10490; https://doi.org/10.3390/ijms160510470 - 7 May 2015
Cited by 65 | Viewed by 10308
Abstract
The effects of essential oil from Eucalyptus camaldulensis flowers oil on melanogenesis and the oil’s antioxidant characteristics were investigated. Assays of mushroom and cellular tyrosinase activities and melanin content of mouse melanoma cells were performed spectrophotometrically, and the expression of melanogenesis-related proteins was [...] Read more.
The effects of essential oil from Eucalyptus camaldulensis flowers oil on melanogenesis and the oil’s antioxidant characteristics were investigated. Assays of mushroom and cellular tyrosinase activities and melanin content of mouse melanoma cells were performed spectrophotometrically, and the expression of melanogenesis-related proteins was determined by Western blotting. The possible signaling pathways involved in essential oil-mediated depigmentation were also investigated using specific protein kinase inhibitors. The results revealed that E. camaldulensis flower essential oil effectively suppresses intracellular tyrosinase activity and decreases melanin amount in B16F10 mouse melanoma cells. The essential oil also exhibits antioxidant properties and effectively decreases intracellular reactive oxygen species (ROS) levels. The volatile chemical composition of the essential oil was analyzed with gas chromatography–mass spectrometry (GC/MS). The chemical constituents in the essential oil are predominately oxygenated monoterpenes (34.9%), followed by oxygenated sesquiterpenes (31.8%), monoterpene hydrocarbons (29.0%) and sesquiterpene hydrocarbons (4.3%). Our results indicated that E. camaldulensis flower essential oil inhibits melanogenesis through its antioxidant properties and by down-regulating both mitogen-activated protein kinases (MAPK) and protein kinase A (PKA) signaling pathways. The present study indicates that the essential oil has the potential to be developed into a skin care product. Full article
(This article belongs to the Section Biochemistry)
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16 pages, 4265 KiB  
Article
Regulative Effect of Mir-205 on Osteogenic Differentiation of Bone Mesenchymal Stem Cells (BMSCs): Possible Role of SATB2/Runx2 and ERK/MAPK Pathway
by Nan Hu, Chunzhen Feng, Yi Jiang, Qing Miao and Hongchen Liu
Int. J. Mol. Sci. 2015, 16(5), 10491-10506; https://doi.org/10.3390/ijms160510491 - 7 May 2015
Cited by 103 | Viewed by 8729
Abstract
Bone mesenchymal stem cells (BMSCs) have multiple potentials to differentiate into osteoblasts and adipocytes, and methods to enhance their osteogenic differentiation are gaining increasing attention. MicroRNAs are critical regulation factors during the process of the osteogenic induction in BMSCs, and mir-205 has been [...] Read more.
Bone mesenchymal stem cells (BMSCs) have multiple potentials to differentiate into osteoblasts and adipocytes, and methods to enhance their osteogenic differentiation are gaining increasing attention. MicroRNAs are critical regulation factors during the process of the osteogenic induction in BMSCs, and mir-205 has been substantiated to be involved in the osteogenic process, but the underlying mechanisms remain unclear. The purpose of this article is to investigate the role of mir-205 in the osteogenic differentiation of BMSCs. We found that mir-205 expression was down-regulated in a time-dependent manner during BMSC osteo-induction. Inhibition of mir-205 enhanced osteogenic abilities by up-regulating bone sialoprotein (BSP) and osteopontin (OPN) protein levels and increasing alkaline phosphatase (ALP) activity and osteocalcin secretion. Furthermore, we found that mir-205 could regulate protein expression of special AT-rich sequence-binding protein 2 (SATB2) and runt-related transcription factor 2 (Runx2), and over-expression of SATB2 activated Runx2 and reversed the negative effects of mir-205 on osteoblastic differentiation. Furthermore, we examined the extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (p38 MAPK) pathways during osteogenic induction and our data indicates that mir-205 might exert negative functions on the osteogenic differentiation in BMSCs at least partly via altering phosphorylation of ERK and p38 MAPK. These results shed new light on the molecular mechanisms of microRNAs in governing differentiation of BMSCs. Full article
(This article belongs to the Collection Regulation by Non-coding RNAs)
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19 pages, 3434 KiB  
Article
Dihydroaustrasulfone Alcohol (WA-25) Impedes Macrophage Foam Cell Formation by Regulating the Transforming Growth Factor-β1 Pathway
by Yi-Chen Wang, Han-Chun Hung, Chien-Wei Feng, Shi-Ying Huang, Chun-Hong Chen, Yen-You Lin, Yao-Chang Chen, San-Nan Yang, Jui-Hsin Su, Jyh-Horng Sheu and Zhi-Hong Wen
Int. J. Mol. Sci. 2015, 16(5), 10507-10525; https://doi.org/10.3390/ijms160510507 - 7 May 2015
Cited by 14 | Viewed by 7597
Abstract
Atherosclerosis is considered an inflammatory disease. However, clinically used anti-atherosclerotic drugs, such as simvastatin, have many side effects. Recently, several unique marine compounds have been isolated that possess a variety of bioactivities. In a previous study, we found a synthetic precursor of the [...] Read more.
Atherosclerosis is considered an inflammatory disease. However, clinically used anti-atherosclerotic drugs, such as simvastatin, have many side effects. Recently, several unique marine compounds have been isolated that possess a variety of bioactivities. In a previous study, we found a synthetic precursor of the marine compound (austrasulfone), which is dihydroaustrasulfone alcohol (WA-25), has anti-atherosclerotic effects in vivo. However, the detailed mechanisms remain unclear. Therefore, to clarify the mechanisms through which WA-25 exerts anti-atherosclerotic activity, we used RAW 264.7 macrophages as an in vitro model to evaluate the effects of WA-25. In lipopolysaccharide (LPS)-stimulated RAW 264.7 cells, WA-25 significantly inhibited expression of the pro-inflammatory proteins, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). In contrast, simvastatin increased the COX-2 expression compared to WA-25. In addition, WA-25 impedes foam cell formation and up-regulated the lysosomal and cyclic adenosine monophosphate (cAMP) signaling pathway. We also observed that transforming growth factor β1 (TGF-β1) was up-regulated by WA-25 and simvastatin in LPS-induced RAW 264.7 cells, and the promising anti-atherosclerosis effects of WA-25 were disrupted by blockade of TGF-β1 signaling. Besides, WA-25 might act through increasing lipolysis than through alteration of lipid export. Taken together, these data demonstrate that WA-25 may have potential as an anti-atherosclerotic drug with anti-inflammatory effects. Full article
(This article belongs to the Special Issue Bioactivity of Marine Natural Products)
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11 pages, 2321 KiB  
Article
Chitosan Oligosaccharides Inhibit/Disaggregate Fibrils and Attenuate Amyloid β-Mediated Neurotoxicity
by Xueling Dai, Wanqi Hou, Yaxuan Sun, Zhaolan Gao, Shigong Zhu and Zhaofeng Jiang
Int. J. Mol. Sci. 2015, 16(5), 10526-10536; https://doi.org/10.3390/ijms160510526 - 8 May 2015
Cited by 54 | Viewed by 8744
Abstract
Alzheimer’s disease (AD) is characterized by a large number of amyloid-β (Aβ) deposits in the brain. Therefore, inhibiting Aβ aggregation or destabilizing preformed aggregates could be a promising therapeutic target for halting/slowing the progression of AD. Chitosan oligosaccharides (COS) have previously been reported [...] Read more.
Alzheimer’s disease (AD) is characterized by a large number of amyloid-β (Aβ) deposits in the brain. Therefore, inhibiting Aβ aggregation or destabilizing preformed aggregates could be a promising therapeutic target for halting/slowing the progression of AD. Chitosan oligosaccharides (COS) have previously been reported to exhibit antioxidant and neuroprotective effects. Recent study shows that COS could markedly decrease oligomeric Aβ-induced neurotoxicity and oxidative stress in rat hippocampal neurons. However, the potential mechanism that COS reduce Aβ-mediated neurotoxicity remains unclear. In the present study, our findings from circular dichroism spectroscopy, transmission electron microscope and thioflavin T fluorescence assay suggested that COS act as an inhibitor of Aβ aggregation and this effect shows dose-dependency. Moreover, data from thioflavin T assay indicated that COS could significantly inhibit fibrils formation and disrupt preformed fibrils in a dose-dependent manner. Furthermore, the addition of COS attenuated Aβ1-42-induced neurotoxicity in rat cortical neurons. Taken together, our results demonstrated for the first time that COS could inhibit Aβ1-42 fibrils formation and disaggregate preformed fibrils, suggesting that COS may have anti-Aβ fibrillogenesis and fibril-destabilizing properties. These findings highlight the potential role of COS as novel therapeutic agents for the prevention and treatment of AD. Full article
(This article belongs to the Special Issue Bioactivity of Marine Natural Products)
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25 pages, 1202 KiB  
Review
Cyanobacterial Hydrogenases and Hydrogen Metabolism Revisited: Recent Progress and Future Prospects
by Namita Khanna and Peter Lindblad
Int. J. Mol. Sci. 2015, 16(5), 10537-10561; https://doi.org/10.3390/ijms160510537 - 8 May 2015
Cited by 74 | Viewed by 13679
Abstract
Cyanobacteria have garnered interest as potential cell factories for hydrogen production. In conjunction with photosynthesis, these organisms can utilize inexpensive inorganic substrates and solar energy for simultaneous biosynthesis and hydrogen evolution. However, the hydrogen yield associated with these organisms remains far too low [...] Read more.
Cyanobacteria have garnered interest as potential cell factories for hydrogen production. In conjunction with photosynthesis, these organisms can utilize inexpensive inorganic substrates and solar energy for simultaneous biosynthesis and hydrogen evolution. However, the hydrogen yield associated with these organisms remains far too low to compete with the existing chemical processes. Our limited understanding of the cellular hydrogen production pathway is a primary setback in the potential scale-up of this process. In this regard, the present review discusses the recent insight around ferredoxin/flavodoxin as the likely electron donor to the bidirectional Hox hydrogenase instead of the generally accepted NAD(P)H. This may have far reaching implications in powering solar driven hydrogen production. However, it is evident that a successful hydrogen-producing candidate would likely integrate enzymatic traits from different species. Engineering the [NiFe] hydrogenases for optimal catalytic efficiency or expression of a high turnover [FeFe] hydrogenase in these photo-autotrophs may facilitate the development of strains to reach target levels of biohydrogen production in cyanobacteria. The fundamental advancements achieved in these fields are also summarized in this review. Full article
(This article belongs to the Special Issue Photosynthesis and Biological Hydrogen Production)
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16 pages, 1314 KiB  
Article
Removal of Toxic Mercury from Petroleum Oil by Newly Synthesized Molecularly-Imprinted Polymer
by Nor Ain Shahera Khairi, Nor Azah Yusof, Abdul Halim Abdullah and Faruq Mohammad
Int. J. Mol. Sci. 2015, 16(5), 10562-10577; https://doi.org/10.3390/ijms160510562 - 8 May 2015
Cited by 32 | Viewed by 7108
Abstract
In recent years, molecularly-imprinted polymers (MIPs) have attracted the attention of several researchers due to their capability for molecular recognition, easiness of preparation, stability and cost-effective production. By taking advantage of these facts, Hg(II) imprinted and non-imprinted copolymers were prepared by polymerizing mercury [...] Read more.
In recent years, molecularly-imprinted polymers (MIPs) have attracted the attention of several researchers due to their capability for molecular recognition, easiness of preparation, stability and cost-effective production. By taking advantage of these facts, Hg(II) imprinted and non-imprinted copolymers were prepared by polymerizing mercury nitrate stock solution (or without it) with methacrylic acid (MAA), 2-hydroxyl ethyl methacrylate (HEMA), methanol and ethylene glycol dimethacrylate (EGDMA) as the monomer, co-monomer solvent (porogen) and cross-linker, respectively. Thus, the formed Hg(II) imprinted polymer was characterized by using Fourier transform infrared spectroscopy (FTIR), field emission scanning electron microscopy (FESEM), Brunauer, Emmett and Teller (BET) and thermal gravimetric analysis (TGA). The separation and preconcentration characteristics of Hg(II) imprinted polymer were investigated by solid phase extraction (SPE) procedures, and an optimal pH of 7 was investigated as ideal. The specific surface area of the Hg(II) imprinted polymer was found to be 19.45 m2/g with a size range from 100 to 140 µm in diameter. The maximum adsorption capacity was observed to be 1.11 mg/g of Hg(II) imprinted beads with 87.54% removal of Hg(II) ions within the first 5 min. The results of the study therefore confirm that the Hg(II) imprinted polymer can be used multiple times without significantly losing its adsorption capacity. Full article
(This article belongs to the Section Materials Science)
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23 pages, 1519 KiB  
Review
Encapsulated Cellular Implants for Recombinant Protein Delivery and Therapeutic Modulation of the Immune System
by Aurélien Lathuilière, Nicolas Mach and Bernard L. Schneider
Int. J. Mol. Sci. 2015, 16(5), 10578-10600; https://doi.org/10.3390/ijms160510578 - 8 May 2015
Cited by 32 | Viewed by 9465
Abstract
Ex vivo gene therapy using retrievable encapsulated cellular implants is an effective strategy for the local and/or chronic delivery of therapeutic proteins. In particular, it is considered an innovative approach to modulate the activity of the immune system. Two recently proposed therapeutic schemes [...] Read more.
Ex vivo gene therapy using retrievable encapsulated cellular implants is an effective strategy for the local and/or chronic delivery of therapeutic proteins. In particular, it is considered an innovative approach to modulate the activity of the immune system. Two recently proposed therapeutic schemes using genetically engineered encapsulated cells are discussed here: the chronic administration of monoclonal antibodies for passive immunization against neurodegenerative diseases and the local delivery of a cytokine as an adjuvant for anti-cancer vaccines. Full article
(This article belongs to the Special Issue Artificial Organs)
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23 pages, 1460 KiB  
Article
Calculated Third Order Rate Constants for Interpreting the Mechanisms of Hydrolyses of Chloroformates, Carboxylic Acid Halides, Sulfonyl Chlorides and Phosphorochloridates
by T. William Bentley
Int. J. Mol. Sci. 2015, 16(5), 10601-10623; https://doi.org/10.3390/ijms160510601 - 8 May 2015
Cited by 9 | Viewed by 7588
Abstract
Hydrolyses of acid derivatives (e.g., carboxylic acid chlorides and fluorides, fluoro- and chloroformates, sulfonyl chlorides, phosphorochloridates, anhydrides) exhibit pseudo-first order kinetics. Reaction mechanisms vary from those involving a cationic intermediate (SN1) to concerted SN2 processes, and further to third [...] Read more.
Hydrolyses of acid derivatives (e.g., carboxylic acid chlorides and fluorides, fluoro- and chloroformates, sulfonyl chlorides, phosphorochloridates, anhydrides) exhibit pseudo-first order kinetics. Reaction mechanisms vary from those involving a cationic intermediate (SN1) to concerted SN2 processes, and further to third order reactions, in which one solvent molecule acts as the attacking nucleophile and a second molecule acts as a general base catalyst. A unified framework is discussed, in which there are two reaction channels—an SN1-SN2 spectrum and an SN2-SN3 spectrum. Third order rate constants (k3) are calculated for solvolytic reactions in a wide range of compositions of acetone-water mixtures, and are shown to be either approximately constant or correlated with the Grunwald-Winstein Y parameter. These data and kinetic solvent isotope effects, provide the experimental evidence for the SN2-SN3 spectrum (e.g., for chloro- and fluoroformates, chloroacetyl chloride, p-nitrobenzoyl p-toluenesulfonate, sulfonyl chlorides). Deviations from linearity lead to U- or V-shaped plots, which assist in the identification of the point at which the reaction channel changes from SN2-SN3 to SN1-SN2 (e.g., for benzoyl chloride). Full article
(This article belongs to the Special Issue Solution Chemical Kinetics)
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12 pages, 696 KiB  
Review
Potential Role of Thymosin Beta 4 in Liver Fibrosis
by Jieun Kim and Youngmi Jung
Int. J. Mol. Sci. 2015, 16(5), 10624-10635; https://doi.org/10.3390/ijms160510624 - 8 May 2015
Cited by 21 | Viewed by 9212
Abstract
Liver fibrosis, the main characteristic of chronic liver diseases, is strongly associated with the activation of hepatic stellate cells (HSCs), which are responsible for extracellular matrix production. As such, investigating the effective regulators controlling HSC activation provides important clues for developing therapeutics to [...] Read more.
Liver fibrosis, the main characteristic of chronic liver diseases, is strongly associated with the activation of hepatic stellate cells (HSCs), which are responsible for extracellular matrix production. As such, investigating the effective regulators controlling HSC activation provides important clues for developing therapeutics to inhibit liver fibrosis. Thymosin beta 4 (Tβ4), a major actin-sequestering protein, is known to be involved in various cellular responses. A growing body of evidence suggests that Tβ4 has a potential role in the pathogenesis of liver fibrosis and that it is especially associated with the activation of HSCs. However, it remains unclear whether Tβ4 promotes or suppresses the activation of HSCs. Herein, we review the potential role of Tβ4 in liver fibrosis by describing the effects of exogenous and endogenous Tβ4, and we discuss the possible signaling pathway regulated by Tβ4. Exogenous Tβ4 reduces liver fibrosis by inhibiting the proliferation and migration of HSCs. Tβ4 is expressed endogenously in the activated HSCs, but this endogenous Tβ4 displays opposite effects in HSC activation, either as an activator or an inhibitor. Although the role of Tβ4 has not been established, it is apparent that Tβ4 influences HSC activation, suggesting that Tβ4 is a potential therapeutic target for treating liver diseases. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Human Liver Diseases)
14 pages, 1935 KiB  
Article
Frequent Epigenetic Suppression of Tumor Suppressor Gene Glutathione Peroxidase 3 by Promoter Hypermethylation and Its Clinical Implication in Clear Cell Renal Cell Carcinoma
by Qianling Liu, Jie Jin, Jianming Ying, Mengkui Sun, Yun Cui, Lian Zhang, Ben Xu, Yu Fan and Qian Zhang
Int. J. Mol. Sci. 2015, 16(5), 10636-10649; https://doi.org/10.3390/ijms160510636 - 11 May 2015
Cited by 29 | Viewed by 6333
Abstract
The goal of this study is to identify novel tumor suppressor genes silenced by promoter methylation in clear cell renal cell carcinoma (ccRCC) and discover new epigenetic biomarkers for early cancer detection. Reactive oxygen species (ROS) is a major cause of DNA damage [...] Read more.
The goal of this study is to identify novel tumor suppressor genes silenced by promoter methylation in clear cell renal cell carcinoma (ccRCC) and discover new epigenetic biomarkers for early cancer detection. Reactive oxygen species (ROS) is a major cause of DNA damage that correlates with cancer initiation and progression. Glutathione peroxidase 3 (GPX3), the only known extracellular glycosylated enzyme of GPXs, is a major scavenger of ROS. GPX3 has been identified as a tumor suppressor in many cancers. However, the role of GPX3 in ccRCC remains unclear. This study aimed to investigate its epigenetic alteration in ccRCC and possible clinicopathological association. In our study, GPX3 methylation and down-regulation were detected in 5 out of 6 ccRCC cell lines and the GPX3 mRNA and protein expression level in ccRCC tumors was significantly lower than in adjacent non-malignant renal tissues (p < 0.0001). Treatment with 5-Aza-2'-deoxycytidine restored GPX3 expression in ccRCC cells. Aberrant methylation was further detected in 77.1% (162/210) of RCC primary tumors, but only 14.6% (7/48) in adjacent non-malignant renal tissues. GPX3 methylation status was significantly associated with higher tumor nuclear grade (p = 0.014). Thus, our results showing frequent GPX3 inactivation by promoter hypermethylation in ccRCC may reveal the failure in the cellular antioxidant system in ccRCC and may be associated with renal tumorigenesis. GPX3 tumor specific methylation may serve as a biomarker for early detection and prognosis prediction of ccRCC. Full article
(This article belongs to the Special Issue Molecular Classification of Human Cancer: Diagnosis and Treatment)
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15 pages, 709 KiB  
Article
Biohydrogen and Bioethanol Production from Biodiesel-Based Glycerol by Enterobacter aerogenes in a Continuous Stir Tank Reactor
by Rujira Jitrwung and Viviane Yargeau
Int. J. Mol. Sci. 2015, 16(5), 10650-10664; https://doi.org/10.3390/ijms160510650 - 11 May 2015
Cited by 26 | Viewed by 7745
Abstract
Crude glycerol from the biodiesel manufacturing process is being produced in increasing quantities due to the expanding number of biodiesel plants. It has been previously shown that, in batch mode, semi-anaerobic fermentation of crude glycerol by Enterobacter aerogenes can produce biohydrogen and bioethanol [...] Read more.
Crude glycerol from the biodiesel manufacturing process is being produced in increasing quantities due to the expanding number of biodiesel plants. It has been previously shown that, in batch mode, semi-anaerobic fermentation of crude glycerol by Enterobacter aerogenes can produce biohydrogen and bioethanol simultaneously. The present study demonstrated the possible scaling-up of this process from small batches performed in small bottles to a 3.6-L continuous stir tank reactor (CSTR). Fresh feed rate, liquid recycling, pH, mixing speed, glycerol concentration, and waste recycling were optimized for biohydrogen and bioethanol production. Results confirmed that E. aerogenes uses small amounts of oxygen under semi-anaerobic conditions for growth before using oxygen from decomposable salts, mainly NH4NO3, under anaerobic condition to produce hydrogen and ethanol. The optimal conditions were determined to be 500 rpm, pH 6.4, 18.5 g/L crude glycerol (15 g/L glycerol) and 33% liquid recycling for a fresh feed rate of 0.44 mL/min. Using these optimized conditions, the process ran at a lower media cost than previous studies, was stable after 7 days without further inoculation and resulted in yields of 0.86 mol H2/mol glycerol and 0.75 mol ethanol/mole glycerol. Full article
(This article belongs to the Special Issue Photosynthesis and Biological Hydrogen Production)
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9 pages, 677 KiB  
Article
Consumption of Bilberries Controls Gingival Inflammation
by Cecilia Widén, Michael Coleman, Sladjana Critén, Pernilla Karlgren-Andersson, Stefan Renvert and G. Rutger Persson
Int. J. Mol. Sci. 2015, 16(5), 10665-10673; https://doi.org/10.3390/ijms160510665 - 11 May 2015
Cited by 25 | Viewed by 9706
Abstract
Bioactive molecules in berries may be helpful in reducing the risk of oral diseases. The aim of this study was to determine the effect of bilberry consumption on the outcome of a routine dental clinical parameter of inflammation, bleeding on probing (BOP), as [...] Read more.
Bioactive molecules in berries may be helpful in reducing the risk of oral diseases. The aim of this study was to determine the effect of bilberry consumption on the outcome of a routine dental clinical parameter of inflammation, bleeding on probing (BOP), as well as the impact on selected biomarkers of inflammation, such as cytokines, in gingival crevicular fluid (GCF) in individuals with gingivitis. Study individuals who did not receive standard of care treatment were allocated to either a placebo group or to groups that consumed either 250 or 500 g bilberries daily over seven days. The placebo group consumed an inactive product (starch). A study group, receiving standard of care (debridement only) was also included to provide a reference to standard of care treatment outcome. Cytokine levels were assayed using the Luminex MagPix system. The mean reduction in BOP before and after consumption of test product over 1 week was 41% and 59% in the groups that consumed either 250 or 500 g of bilberries/day respectively, and was 31% in the placebo group, and 58% in the standard of care reference group. The analysis only showed a significant reduction in cytokine levels in the group that consumed 500 g of bilberries/day. A statistically significant reduction was observed for IL-1b (p = 0.025), IL-6 (p = 0.012) and VEGF (p = 0.017) in GCF samples in the group that consumed 500 g of bilberries daily. It appears that berry intake has an ameliorating effect on some markers of gingival inflammation reducing gingivitis to a similar extent compared to standard of care. Full article
(This article belongs to the Special Issue Antioxidant 2.0——Redox Modulation by Food and Drugs)
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12 pages, 1125 KiB  
Review
Skeletal Muscle Mitochondrial Energetic Efficiency and Aging
by Raffaella Crescenzo, Francesca Bianco, Arianna Mazzoli, Antonia Giacco, Giovanna Liverini and Susanna Iossa
Int. J. Mol. Sci. 2015, 16(5), 10674-10685; https://doi.org/10.3390/ijms160510674 - 11 May 2015
Cited by 28 | Viewed by 9138
Abstract
Aging is associated with a progressive loss of maximal cell functionality, and mitochondria are considered a key factor in aging process, since they determine the ATP availability in the cells. Mitochondrial performance during aging in skeletal muscle is reported to be either decreased [...] Read more.
Aging is associated with a progressive loss of maximal cell functionality, and mitochondria are considered a key factor in aging process, since they determine the ATP availability in the cells. Mitochondrial performance during aging in skeletal muscle is reported to be either decreased or unchanged. This heterogeneity of results could partly be due to the method used to assess mitochondrial performance. In addition, in skeletal muscle the mitochondrial population is heterogeneous, composed of subsarcolemmal and intermyofibrillar mitochondria. Therefore, the purpose of the present review is to summarize the results obtained on the functionality of the above mitochondrial populations during aging, taking into account that the mitochondrial performance depends on organelle number, organelle activity, and energetic efficiency of the mitochondrial machinery in synthesizing ATP from the oxidation of fuels. Full article
(This article belongs to the Special Issue Mitochondrial Dysfunction in Ageing and Diseases)
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18 pages, 1177 KiB  
Article
Identification of MicroRNA for Intermuscular Bone Development in Blunt Snout Bream (Megalobrama amblycephala)
by Shi-Ming Wan, Shao-Kui Yi, Jia Zhong, Chun-Hong Nie, Ning-Nan Guan, Bo-Xiang Chen and Ze-Xia Gao
Int. J. Mol. Sci. 2015, 16(5), 10686-10703; https://doi.org/10.3390/ijms160510686 - 11 May 2015
Cited by 39 | Viewed by 7440
Abstract
Intermuscular bone (IB), which occurs only in the myosepta of the lower teleosts, is attracting more attention of researchers due to its particular development and lack of genetic information. MicroRNAs (miRNAs) are emerging as important regulators for biological processes. In the present study, [...] Read more.
Intermuscular bone (IB), which occurs only in the myosepta of the lower teleosts, is attracting more attention of researchers due to its particular development and lack of genetic information. MicroRNAs (miRNAs) are emerging as important regulators for biological processes. In the present study, miRNAs from IBs and connective tissue (CT; encircled IBs) from six-month-old Megalobrama amblycephala were characterized and compared. The results revealed the sequences and expression levels of 218 known miRNA genes (belonging to 97 families). Of these miRNAs, 44 known microRNA sequences exhibited significant expression differences between the two libraries, with 24 and 20 differentially-expressed miRNAs exhibiting higher expression in the CT and IBs libraries, respectively. The expressions of 11 miRNAs were selected to validate in nine tissues. Among the high-ranked predicted gene targets, differentiation, cell cycle, metabolism, signal transduction and transcriptional regulation were implicated. The pathway analysis of differentially-expressed miRNAs indicated that they were abundantly involved in regulating the development and differentiation of IBs and CT. This study characterized the miRNA for IBs of teleosts for the first time, which provides an opportunity for further understanding of miRNA function in the regulation of IB development. Full article
(This article belongs to the Special Issue Fish Molecular Biology)
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11 pages, 4621 KiB  
Article
One-Pot Exfoliation of Graphite and Synthesis of Nanographene/Dimesitylporphyrin Hybrids
by M. Mar Bernal and Emilio M. Pérez
Int. J. Mol. Sci. 2015, 16(5), 10704-10714; https://doi.org/10.3390/ijms160510704 - 12 May 2015
Cited by 20 | Viewed by 6909
Abstract
A simple one-pot process to exfoliate graphite and synthesize nanographene-dimesitylporphyrin hybrids has been developed. Despite the bulky mesityl groups, which are expected to hinder the efficient π–π stacking between the porphyrin core and graphene, the liquid-phase exfoliation of graphite is significantly favored by [...] Read more.
A simple one-pot process to exfoliate graphite and synthesize nanographene-dimesitylporphyrin hybrids has been developed. Despite the bulky mesityl groups, which are expected to hinder the efficient π–π stacking between the porphyrin core and graphene, the liquid-phase exfoliation of graphite is significantly favored by the presence of the porphyrins. Metallation of the porphyrin further enhances this effect. The resulting graphene/porphyrin hybrids were characterized by spectroscopy (UV-visible, fluorescence, and Raman) and microscopy (STEM, scanning transmission electron microscopy). Full article
(This article belongs to the Special Issue Supramolecular Interactions)
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19 pages, 865 KiB  
Article
The Multi-Biomarker Approach for Heart Failure in Patients with Hypertension
by Agata Bielecka-Dabrowa, Anna Gluba-Brzózka, Marta Michalska-Kasiczak, Małgorzata Misztal, Jacek Rysz and Maciej Banach
Int. J. Mol. Sci. 2015, 16(5), 10715-10733; https://doi.org/10.3390/ijms160510715 - 12 May 2015
Cited by 33 | Viewed by 6704
Abstract
We assessed the predictive ability of selected biomarkers using N-terminal pro-brain natriuretic peptide (NT-proBNP) as the benchmark and tried to establish a multi-biomarker approach to heart failure (HF) in hypertensive patients. In 120 hypertensive patients with or without overt heart failure, the [...] Read more.
We assessed the predictive ability of selected biomarkers using N-terminal pro-brain natriuretic peptide (NT-proBNP) as the benchmark and tried to establish a multi-biomarker approach to heart failure (HF) in hypertensive patients. In 120 hypertensive patients with or without overt heart failure, the incremental predictive value of the following biomarkers was investigated: Collagen III N-terminal propeptide (PIIINP), cystatin C (CysC), lipocalin-2/NGAL, syndecan-4, tumor necrosis factor-α (TNF-α), interleukin 1 receptor type I (IL1R1), galectin-3, cardiotrophin-1 (CT-1), transforming growth factor β (TGF-β) and N-terminal pro-brain natriuretic peptide (NT-proBNP). The highest discriminative value for HF was observed for NT-proBNP (area under the receiver operating characteristic curve (AUC) = 0.873) and TGF-β (AUC = 0.878). On the basis of ROC curve analysis we found that CT-1 > 152 pg/mL, TGF-β < 7.7 ng/mL, syndecan > 2.3 ng/mL, NT-proBNP > 332.5 pg/mL, CysC > 1 mg/L and NGAL > 39.9 ng/mL were significant predictors of overt HF. There was only a small improvement in predictive ability of the multi-biomarker panel including the four biomarkers with the best performance in the detection of HF—NT-proBNP, TGF-β, CT-1, CysC—compared to the panel with NT-proBNP, TGF-β and CT-1 only. Biomarkers with different pathophysiological backgrounds (NT-proBNP, TGF-β, CT-1, CysC) give additive prognostic value for incident HF in hypertensive patients compared to NT-proBNP alone. Full article
(This article belongs to the Special Issue Improvement of Cardiac Function in Heart Failure)
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14 pages, 809 KiB  
Article
Ultrasound Assessment of Carotid Plaque Echogenicity Response to Statin Therapy: A Systematic Review and Meta-Analysis
by Pranvera Ibrahimi, Fisnik Jashari, Gani Bajraktari, Per Wester and Michael Y. Henein
Int. J. Mol. Sci. 2015, 16(5), 10734-10747; https://doi.org/10.3390/ijms160510734 - 12 May 2015
Cited by 44 | Viewed by 8355
Abstract
Objective: To evaluate in a systematic review and meta-analysis model the effect of statin therapy on carotid plaque echogenicity assessed by ultrasound. Methods: We have systematically searched electronic databases (PubMed, MEDLINE, EMBASE and Cochrane Center Register) up to April, 2015, for studies evaluating [...] Read more.
Objective: To evaluate in a systematic review and meta-analysis model the effect of statin therapy on carotid plaque echogenicity assessed by ultrasound. Methods: We have systematically searched electronic databases (PubMed, MEDLINE, EMBASE and Cochrane Center Register) up to April, 2015, for studies evaluating the effect of statins on plaque echogenicity. Two researchers independently determined the eligibility of studies evaluating the effect of statin therapy on carotid plaque echogenicity that used ultrasound and grey scale median (GSM) or integrated back scatter (IBS). Results: Nine out of 580 identified studies including 566 patients’ carotid artery data were meta-analyzed for a mean follow up of 7.2 months. A consistent increase in the echogenicity of carotid artery plaques, after statin therapy, was reported. Pooled weighted mean difference % (WMD) on plaque echogenicity after statin therapy was 29% (95% CI 22%–36%), p < 0.001, I2 = 92.1%. In a meta-regression analysis using % mean changes of LDL, HDL and hsCRP as moderators, it was shown that the effects of statins on plaque echogenicity were related to changes in hsCRP, but not to LDL and HDL changes from the baseline. The effect of statins on the plaque was progressive; it showed significance after the first month of treatment, and the echogenicity continued to increase in the following six and 12 months. Conclusions: Statin therapy is associated with a favorable increase of carotid plaque echogenicity. This effect seems to be dependent on the period of treatment and hsCRP change from the baseline, independent of changes in LDL and HDL. Full article
(This article belongs to the Special Issue Atherosclerosis and Vascular Imaging)
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19 pages, 1101 KiB  
Review
Caffeic Acid Phenethyl Ester Is a Potential Therapeutic Agent for Oral Cancer
by Ying-Yu Kuo, Wai-Tim Jim, Liang-Cheng Su, Chi-Jung Chung, Ching-Yu Lin, Chieh Huo, Jen-Chih Tseng, Shih-Han Huang, Chih-Jen Lai, Bo-Chih Chen, Bi-Juan Wang, Tzu-Min Chan, Hui-Ping Lin, Wun-Shaing Wayne Chang, Chuang-Rung Chang and Chih-Pin Chuu
Int. J. Mol. Sci. 2015, 16(5), 10748-10766; https://doi.org/10.3390/ijms160510748 - 12 May 2015
Cited by 89 | Viewed by 10439
Abstract
Head and neck cancers, which affect 650,000 people and cause 350,000 deaths per year, is the sixth leading cancer by cancer incidence and eighth by cancer-related death worldwide. Oral cancer is the most common type of head and neck cancer. More than 90% [...] Read more.
Head and neck cancers, which affect 650,000 people and cause 350,000 deaths per year, is the sixth leading cancer by cancer incidence and eighth by cancer-related death worldwide. Oral cancer is the most common type of head and neck cancer. More than 90% of oral cancers are oral and oropharyngeal squamous cell carcinoma (OSCC). The overall five-year survival rate of OSCC patients is approximately 63%, which is due to the low response rate to current therapeutic drugs. In this review we discuss the possibility of using caffeic acid phenethyl ester (CAPE) as an alternative treatment for oral cancer. CAPE is a strong antioxidant extracted from honeybee hive propolis. Recent studies indicate that CAPE treatment can effectively suppress the proliferation, survival, and metastasis of oral cancer cells. CAPE treatment inhibits Akt signaling, cell cycle regulatory proteins, NF-κB function, as well as activity of matrix metalloproteinase (MMPs), epidermal growth factor receptor (EGFR), and Cyclooxygenase-2 (COX-2). Therefore, CAPE treatment induces cell cycle arrest and apoptosis in oral cancer cells. According to the evidence that aberrations in the EGFR/phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling, NF-κB function, COX-2 activity, and MMPs activity are frequently found in oral cancers, and that the phosphorylation of Akt, EGFR, and COX-2 correlates to oral cancer patient survival and clinical progression, we believe that CAPE treatment will be useful for treatment of advanced oral cancer patients. Full article
(This article belongs to the Special Issue Molecular Classification of Human Cancer: Diagnosis and Treatment)
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30 pages, 830 KiB  
Article
Theoretical in-Solution Conformational/Tautomeric Analyses for Chain Systems with Conjugated Double Bonds Involving Nitrogen(s)
by Peter I. Nagy
Int. J. Mol. Sci. 2015, 16(5), 10767-10796; https://doi.org/10.3390/ijms160510767 - 13 May 2015
Cited by 3 | Viewed by 6996
Abstract
Conformational/tautomeric transformations for X=CH–CH=Y structures (X = CH2, O, NH and Y = NH) have been studied in the gas phase, in dichloromethane and in aqueous solutions. The paper is a continuation of a former study where s-cis/s-trans conformational [...] Read more.
Conformational/tautomeric transformations for X=CH–CH=Y structures (X = CH2, O, NH and Y = NH) have been studied in the gas phase, in dichloromethane and in aqueous solutions. The paper is a continuation of a former study where s-cis/s-trans conformational equilibria were predicted for analogues. The s-trans conformation is preferred for the present molecules in the gas phase on the basis of its lowest internal free energy as calculated at the B97D/aug-cc-pvqz and CCSD(T)CBS (coupled-cluster singles and doubles with non-iterative triples extrapolated to the complete basis set) levels. Transition state barriers are of 29–36 kJ/mol for rotations about the central C–C bonds. In solution, an s-trans form is still favored on the basis of its considerably lower internal free energy compared with the s-cis forms as calculated by IEF-PCM (integral-equation formalism of the polarizable continuum dielectric solvent model) at the theoretical levels indicated. A tetrahydrate model in the supermolecule/continuum approach helped explore the 2solute-solvent hydrogen bond pattern. The calculated transition state barrier for rotation about the C–C bond decreased to 27 kJ/mol for the tetrahydrate. Considering explicit solvent models, relative solvation free energies were calculated by means of the free energy perturbation method through Monte Carlo simulations. These calculated values differ remarkably from those by the PCM approach in aqueous solution, nonetheless the same prevalent conformation was predicted by the two methods. Aqueous solution structure-characteristics were determined by Monte Carlo. Equilibration of conformers/tautomers through water-assisted double proton-relay is discussed. This mechanism is not viable, however, in non-protic solvents where the calculated potential of mean force curve does not predict remarkable solute dimerization and subsequent favorable orientation. Full article
(This article belongs to the Special Issue Solution Chemical Kinetics)
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24 pages, 2312 KiB  
Review
Chemical Reactions Directed Peptide Self-Assembly
by Dnyaneshwar B. Rasale and Apurba K. Das
Int. J. Mol. Sci. 2015, 16(5), 10797-10820; https://doi.org/10.3390/ijms160510797 - 13 May 2015
Cited by 20 | Viewed by 10301
Abstract
Fabrication of self-assembled nanostructures is one of the important aspects in nanoscience and nanotechnology. The study of self-assembled soft materials remains an area of interest due to their potential applications in biomedicine. The versatile properties of soft materials can be tuned using a [...] Read more.
Fabrication of self-assembled nanostructures is one of the important aspects in nanoscience and nanotechnology. The study of self-assembled soft materials remains an area of interest due to their potential applications in biomedicine. The versatile properties of soft materials can be tuned using a bottom up approach of small molecules. Peptide based self-assembly has significant impact in biology because of its unique features such as biocompatibility, straight peptide chain and the presence of different side chain functionality. These unique features explore peptides in various self-assembly process. In this review, we briefly introduce chemical reaction-mediated peptide self-assembly. Herein, we have emphasised enzymes, native chemical ligation and photochemical reactions in the exploration of peptide self-assembly. Full article
(This article belongs to the Special Issue Supramolecular Interactions)
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13 pages, 1641 KiB  
Article
Preparation and in Vivo Evaluation of a Dutasteride-Loaded Solid-Supersaturatable Self-Microemulsifying Drug Delivery System
by Min-Soo Kim, Eun-Sol Ha, Gwang-Ho Choo and In-Hwan Baek
Int. J. Mol. Sci. 2015, 16(5), 10821-10833; https://doi.org/10.3390/ijms160510821 - 13 May 2015
Cited by 40 | Viewed by 9575
Abstract
The purpose of this study was to prepare a dutasteride-loaded solid-supersaturatable self-microemulsifying drug delivery system (SMEDDS) using hydrophilic additives with high oral bioavailability, and to determine if there was a correlation between the in vitro dissolution data and the in vivo pharmacokinetic parameters [...] Read more.
The purpose of this study was to prepare a dutasteride-loaded solid-supersaturatable self-microemulsifying drug delivery system (SMEDDS) using hydrophilic additives with high oral bioavailability, and to determine if there was a correlation between the in vitro dissolution data and the in vivo pharmacokinetic parameters of this delivery system in rats. A dutasteride-loaded solid-supersaturatable SMEDDS was generated by adsorption of liquid SMEDDS onto Aerosil 200 colloidal silica using a spray drying process. The dissolution and oral absorption of dutasteride from solid SMEDDS significantly increased after the addition of hydroxypropylmethyl cellulose (HPMC) or Soluplus. Solid SMEDDS/Aerosil 200/Soluplus microparticles had higher oral bioavailability with 6.8- and 5.0-fold higher peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) values, respectively, than that of the equivalent physical mixture. A linear correlation between in vitro dissolution efficiency and in vivo pharmacokinetic parameters was demonstrated for both AUC and Cmax values. Therefore, the preparation of a solid-supersaturatable SMEDDS with HPMC or Soluplus could be a promising formulation strategy to develop novel solid dosage forms of dutasteride. Full article
(This article belongs to the Section Materials Science)
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21 pages, 3659 KiB  
Review
Optimization of Catheter Ablation of Atrial Fibrillation: Insights Gained from Clinically-Derived Computer Models
by Jichao Zhao, Sanjay R. Kharche, Brian J. Hansen, Thomas A. Csepe, Yufeng Wang, Martin K. Stiles and Vadim V. Fedorov
Int. J. Mol. Sci. 2015, 16(5), 10834-10854; https://doi.org/10.3390/ijms160510834 - 13 May 2015
Cited by 20 | Viewed by 8594
Abstract
Atrial fibrillation (AF) is the most common heart rhythm disturbance, and its treatment is an increasing economic burden on the health care system. Despite recent intense clinical, experimental and basic research activity, the treatment of AF with current antiarrhythmic drugs and catheter/surgical therapies [...] Read more.
Atrial fibrillation (AF) is the most common heart rhythm disturbance, and its treatment is an increasing economic burden on the health care system. Despite recent intense clinical, experimental and basic research activity, the treatment of AF with current antiarrhythmic drugs and catheter/surgical therapies remains limited. Radiofrequency catheter ablation (RFCA) is widely used to treat patients with AF. Current clinical ablation strategies are largely based on atrial anatomy and/or substrate detected using different approaches, and they vary from one clinical center to another. The nature of clinical ablation leads to ambiguity regarding the optimal patient personalization of the therapy partly due to the fact that each empirical configuration of ablation lines made in a patient is irreversible during one ablation procedure. To investigate optimized ablation lesion line sets, in silico experimentation is an ideal solution. 3D computer models give us a unique advantage to plan and assess the effectiveness of different ablation strategies before and during RFCA. Reliability of in silico assessment is ensured by inclusion of accurate 3D atrial geometry, realistic fiber orientation, accurate fibrosis distribution and cellular kinetics; however, most of this detailed information in the current computer models is extrapolated from animal models and not from the human heart. The predictive power of computer models will increase as they are validated with human experimental and clinical data. To make the most from a computer model, one needs to develop 3D computer models based on the same functionally and structurally mapped intact human atria with high spatial resolution. The purpose of this review paper is to summarize recent developments in clinically-derived computer models and the clinical insights they provide for catheter ablation. Full article
(This article belongs to the Special Issue Improvement of Cardiac Function in Heart Failure)
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15 pages, 726 KiB  
Article
Prediction of Protein–Protein Interactions with Clustered Amino Acids and Weighted Sparse Representation
by Qiaoying Huang, Zhuhong You, Xiaofeng Zhang and Yong Zhou
Int. J. Mol. Sci. 2015, 16(5), 10855-10869; https://doi.org/10.3390/ijms160510855 - 13 May 2015
Cited by 28 | Viewed by 6455
Abstract
With the completion of the Human Genome Project, bioscience has entered into the era of the genome and proteome. Therefore, protein–protein interactions (PPIs) research is becoming more and more important. Life activities and the protein–protein interactions are inseparable, such as DNA synthesis, gene [...] Read more.
With the completion of the Human Genome Project, bioscience has entered into the era of the genome and proteome. Therefore, protein–protein interactions (PPIs) research is becoming more and more important. Life activities and the protein–protein interactions are inseparable, such as DNA synthesis, gene transcription activation, protein translation, etc. Though many methods based on biological experiments and machine learning have been proposed, they all spent a long time to learn and obtained an imprecise accuracy. How to efficiently and accurately predict PPIs is still a big challenge. To take up such a challenge, we developed a new predictor by incorporating the reduced amino acid alphabet (RAAA) information into the general form of pseudo-amino acid composition (PseAAC) and with the weighted sparse representation-based classification (WSRC). The remarkable advantages of introducing the reduced amino acid alphabet is being able to avoid the notorious dimensionality disaster or overfitting problem in statistical prediction. Additionally, experiments have proven that our method achieved good performance in both a low- and high-dimensional feature space. Among all of the experiments performed on the PPIs data of Saccharomyces cerevisiae, the best one achieved 90.91% accuracy, 94.17% sensitivity, 87.22% precision and a 83.43% Matthews correlation coefficient (MCC) value. In order to evaluate the prediction ability of our method, extensive experiments are performed to compare with the state-of-the-art technique, support vector machine (SVM). The achieved results show that the proposed approach is very promising for predicting PPIs, and it can be a helpful supplement for PPIs prediction. Full article
(This article belongs to the Special Issue Proteins and Protein-Ligand Interactions)
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18 pages, 1023 KiB  
Review
Borrowing Nuclear DNA Helicases to Protect Mitochondrial DNA
by Lin Ding and Yilun Liu
Int. J. Mol. Sci. 2015, 16(5), 10870-10887; https://doi.org/10.3390/ijms160510870 - 13 May 2015
Cited by 30 | Viewed by 10835
Abstract
In normal cells, mitochondria are the primary organelles that generate energy, which is critical for cellular metabolism. Mitochondrial dysfunction, caused by mitochondrial DNA (mtDNA) mutations or an abnormal mtDNA copy number, is linked to a range of human diseases, including Alzheimer’s disease, premature [...] Read more.
In normal cells, mitochondria are the primary organelles that generate energy, which is critical for cellular metabolism. Mitochondrial dysfunction, caused by mitochondrial DNA (mtDNA) mutations or an abnormal mtDNA copy number, is linked to a range of human diseases, including Alzheimer’s disease, premature aging‎ and cancer. mtDNA resides in the mitochondrial lumen, and its duplication requires the mtDNA replicative helicase, Twinkle. In addition to Twinkle, many DNA helicases, which are encoded by the nuclear genome and are crucial for nuclear genome integrity, are transported into the mitochondrion to also function in mtDNA replication and repair. To date, these helicases include RecQ-like helicase 4 (RECQ4), petite integration frequency 1 (PIF1), DNA replication helicase/nuclease 2 (DNA2) and suppressor of var1 3-like protein 1 (SUV3). Although the nuclear functions of some of these DNA helicases have been extensively studied, the regulation of their mitochondrial transport and the mechanisms by which they contribute to mtDNA synthesis and maintenance remain largely unknown. In this review, we attempt to summarize recent research progress on the role of mammalian DNA helicases in mitochondrial genome maintenance and the effects on mitochondria-associated diseases. Full article
(This article belongs to the Special Issue Mitochondrial Dysfunction in Ageing and Diseases)
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19 pages, 1208 KiB  
Review
Potential Anti-Cancer Activities and Mechanisms of Costunolide and Dehydrocostuslactone
by Xuejing Lin, Zhangxiao Peng and Changqing Su
Int. J. Mol. Sci. 2015, 16(5), 10888-10906; https://doi.org/10.3390/ijms160510888 - 13 May 2015
Cited by 117 | Viewed by 10568
Abstract
Costunolide (CE) and dehydrocostuslactone (DE) are derived from many species of medicinal plants, such as Saussurea lappa Decne and Laurus nobilis L. They have been reported for their wide spectrum of biological effects, including anti-inflammatory, anticancer, antiviral, antimicrobial, antifungal, antioxidant, antidiabetic, antiulcer, and [...] Read more.
Costunolide (CE) and dehydrocostuslactone (DE) are derived from many species of medicinal plants, such as Saussurea lappa Decne and Laurus nobilis L. They have been reported for their wide spectrum of biological effects, including anti-inflammatory, anticancer, antiviral, antimicrobial, antifungal, antioxidant, antidiabetic, antiulcer, and anthelmintic activities. In recent years, they have caused extensive interest in researchers due to their potential anti-cancer activities for various types of cancer, and their anti-cancer mechanisms, including causing cell cycle arrest, inducing apoptosis and differentiation, promoting the aggregation of microtubule protein, inhibiting the activity of telomerase, inhibiting metastasis and invasion, reversing multidrug resistance, restraining angiogenesis has been studied. This review will summarize anti-cancer activities and associated molecular mechanisms of these two compounds for the purpose of promoting their research and application. Full article
(This article belongs to the Section Biochemistry)
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14 pages, 855 KiB  
Review
Possibility of Breast Cancer Prevention: Use of Soy Isoflavones and Fermented Soy Beverage Produced Using Probiotics
by Akimitsu Takagi, Mitsuyoshi Kano and Chiaki Kaga
Int. J. Mol. Sci. 2015, 16(5), 10907-10920; https://doi.org/10.3390/ijms160510907 - 13 May 2015
Cited by 93 | Viewed by 15579
Abstract
The various beneficial effects of soybeans, which are rich in phytochemicals, have received much attention because of increasing health awareness. Soy milk that has been fermented using lactic acid bacteria has been used to prepare cheese-like products, tofu (bean-curd), and yogurt-type products. However, [...] Read more.
The various beneficial effects of soybeans, which are rich in phytochemicals, have received much attention because of increasing health awareness. Soy milk that has been fermented using lactic acid bacteria has been used to prepare cheese-like products, tofu (bean-curd), and yogurt-type products. However, the distinct odor of soybeans has limited the acceptance of such foods, particularly in Western countries. In Japan, while tofu and soy milk have long been habitually consumed, the development of novel, palatable food products has not been easy. The unpleasant odor of soy milk and the absorption efficiency for isoflavones can be improved using a recently developed fermented soy milk beverage. Cancer has been the leading cause of death, and breast cancer is the most common malignancy among women. The most common type of breast cancer is estrogen-dependent, and the anti-estrogenic effects of isoflavones are known. The present review focuses on the characteristics of soy milk fermented using probiotics, an epidemiological study examining the incidence of breast cancer and soy isoflavone consumption, and a non-clinical study examining breast cancer prevention using fermented soy milk beverage. Full article
(This article belongs to the Special Issue Bioactive Phytochemicals in Functional Foods for Cancer Prevention)
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13 pages, 1208 KiB  
Article
MicroRNA-27a-3p Inhibits Melanogenesis in Mouse Skin Melanocytes by Targeting Wnt3a
by Yuanyuan Zhao, Pengchao Wang, Jinzhu Meng, Yuankai Ji, Dongmei Xu, Tianzhi Chen, Ruiwen Fan, Xiuju Yu, Jianbo Yao and Changsheng Dong
Int. J. Mol. Sci. 2015, 16(5), 10921-10933; https://doi.org/10.3390/ijms160510921 - 14 May 2015
Cited by 37 | Viewed by 5978
Abstract
MicroRNAs (miRNAs) play an essential role in the regulation of almost all the biological processes, including melanogenesis. MiR-27a-3p is nearly six times higher in white alpaca skin compared to brown skin, which indicates that miR-27a-3p may be a candidate regulator for melanogenesis. Wnt3a [...] Read more.
MicroRNAs (miRNAs) play an essential role in the regulation of almost all the biological processes, including melanogenesis. MiR-27a-3p is nearly six times higher in white alpaca skin compared to brown skin, which indicates that miR-27a-3p may be a candidate regulator for melanogenesis. Wnt3a plays an important role in promoting melanoblasts to differentiate into melanocytes and melanogenesis. To confirm the function of miR-27a-3p to melanogenesis in mammals, miR-27a-3p mimic, inhibitor and their negative control were transfected into mouse melanocytes. As a result, miR-27a-3p inhibits melanogenesis by repressing Wnt3a at post-transcriptional level. A significant decrease in Wnt3a luciferase activity was observed in 293T cells co-transfected with the matched luciferase reporter vector and pre-miR-27a. Furthermore, the presence of exogenous miR-27a-3p significantly decreased Wnt3a protein expression rather than mRNA and reduced β-catenin mRNA levels in melanocytes. The over-expression of miR-27a-3p significantly increased the melanin content of melanocytes. However, miR-27a-3p inhibitor performs an opposite effect on melanogenesis. Wnt3a is one target of miR-27a-3p. MiR-27a-3p could inhibit Wnt3a protein amount by post-transcriptional regulation and melanogenesis in mouse melanocytes. Previous studies reported that Wnt3a promoted melanogenensis in mouse melanocytes. Thus, miR-27-3p inhibits melanogenesis by repressing Wnt3a protein expression. Full article
(This article belongs to the Section Biochemistry)
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18 pages, 3986 KiB  
Article
Characterization and Evaluation of Neuronal Trans-Differentiation with Electrophysiological Properties of Mesenchymal Stem Cells Isolated from Porcine Endometrium
by Raghavendra Baregundi Subbarao, Imran Ullah, Eun-Jin Kim, Si-Jung Jang, Won-Jae Lee, Ryoung Hoon Jeon, Dawon Kang, Sung-Lim Lee, Bong-Wook Park and Gyu-Jin Rho
Int. J. Mol. Sci. 2015, 16(5), 10934-10951; https://doi.org/10.3390/ijms160510934 - 14 May 2015
Cited by 23 | Viewed by 7072
Abstract
Endometrial stromal cells (EMSCs) obtained from porcine uterus (n = 6) were positive for mesenchymal stem cell markers (CD29, CD44 and CD90), and negative for epithelial marker CD9 and hematopoietic markers CD34, CD45 analyzed by flow cytometry. Further the cells were positive [...] Read more.
Endometrial stromal cells (EMSCs) obtained from porcine uterus (n = 6) were positive for mesenchymal stem cell markers (CD29, CD44 and CD90), and negative for epithelial marker CD9 and hematopoietic markers CD34, CD45 analyzed by flow cytometry. Further the cells were positive for expression of mesenchymal markers, CD105, CD140b, and CD144 by PCR. Pluripotent markers OCT4, SOX2, and NANOG were positively expressed in EMSCs analyzed by Western blotting and PCR. Further, differentiation into adipocytes and osteocytes was confirmed by cytochemical staining and lineage specific gene expression by quantitative realtime-PCR. Adipocyte (FABP, LPL, AP2) and osteocyte specific genes (ON, BG, RUNX2) in differentiated EMSCs showed significant (p < 0.05) increase in expression compared to undifferentiated control cells. Neurogenic transdifferentiation of EMSCs exhibited distinctive dendritic morphology with axon projections and neuronal specific genes, NFM, NGF, MBP, NES, B3T and MAP2 and proteins, B3T, NFM, NGF, and TRKA were positively expressed in neuronal differentiated cells. Functional analysis of neuronal differentiated EMSCs displayed voltage-dependence and kinetics for transient outward K+ currents (Ito), at holding potential of −80 mV, Na+ currents and during current clamp, neuronal differentiated EMSCs was more negative than that of control EMSCs. Porcine EMSCs is a suitable model for studying molecular mechanism of transdifferentiation, assessment of electrophysiological properties and their efficiency during in vivo transplantation. Full article
(This article belongs to the Section Biochemistry)
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34 pages, 1954 KiB  
Review
Mass Spectrometry-Based Proteomics for Pre-Eclampsia and Preterm Birth
by Kai P. Law, Ting-Li Han, Chao Tong and Philip N. Baker
Int. J. Mol. Sci. 2015, 16(5), 10952-10985; https://doi.org/10.3390/ijms160510952 - 14 May 2015
Cited by 43 | Viewed by 11914
Abstract
Pregnancy-related complications such as pre-eclampsia and preterm birth now represent a notable burden of adverse health. Pre-eclampsia is a hypertensive disorder unique to pregnancy. It is an important cause of maternal death worldwide and a leading cause of fetal growth restriction and iatrogenic [...] Read more.
Pregnancy-related complications such as pre-eclampsia and preterm birth now represent a notable burden of adverse health. Pre-eclampsia is a hypertensive disorder unique to pregnancy. It is an important cause of maternal death worldwide and a leading cause of fetal growth restriction and iatrogenic prematurity. Fifteen million infants are born preterm each year globally, but more than one million of those do not survive their first month of life. Currently there are no predictive tests available for diagnosis of these pregnancy-related complications and the biological mechanisms of the diseases have not been fully elucidated. Mass spectrometry-based proteomics have all the necessary attributes to provide the needed breakthrough in understanding the pathophysiology of complex human diseases thorough the discovery of biomarkers. The mass spectrometry methodologies employed in the studies for pregnancy-related complications are evaluated in this article. Top-down proteomic and peptidomic profiling by laser mass spectrometry, liquid chromatography or capillary electrophoresis coupled to mass spectrometry, and bottom-up quantitative proteomics and targeted proteomics by liquid chromatography mass spectrometry have been applied to elucidate protein biomarkers and biological mechanism of pregnancy-related complications. The proteomes of serum, urine, amniotic fluid, cervical-vaginal fluid, placental tissue, and cytotrophoblastic cells have all been investigated. Numerous biomarkers or biomarker candidates that could distinguish complicated pregnancies from healthy controls have been proposed. Nevertheless, questions as to the clinically utility and the capacity to elucidate the pathogenesis of the pre-eclampsia and preterm birth remain to be answered. Full article
(This article belongs to the Special Issue Prediction, Diagnostics and Prevention of Pregnancy Complications)
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11 pages, 1634 KiB  
Article
Prenatal Exposure to Lipopolysaccharide Results in Myocardial Fibrosis in Rat Offspring
by Xin Chen, Yujie Tang, Meng Gao, Shugang Qin, Jianzhi Zhou and Xiaohui Li
Int. J. Mol. Sci. 2015, 16(5), 10986-10996; https://doi.org/10.3390/ijms160510986 - 14 May 2015
Cited by 23 | Viewed by 6015
Abstract
The epigenetic plasticity hypothesis indicates that exposure during pregnancy may cause adult-onset disorders, including hypertension, myocardial infarction and heart failure. Moreover, myocardial fibrosis coincides with hypertension, myocardial infarction and heart failure. This study was designed to investigate the effects of prenatal exposure to [...] Read more.
The epigenetic plasticity hypothesis indicates that exposure during pregnancy may cause adult-onset disorders, including hypertension, myocardial infarction and heart failure. Moreover, myocardial fibrosis coincides with hypertension, myocardial infarction and heart failure. This study was designed to investigate the effects of prenatal exposure to lipopolysaccharide (LPS) on myocardial fibrosis. The result showed that at six and 16 weeks of age, the LPS-treated offspring exhibited increased collagen synthesis, an elevated cardiac index (CI), higher mRNA levels of TIMP-2 and TGFβ and a reduced mRNA level of MMP2. The protein levels corresponded to the mRNA levels. The offspring that were prenatally treated with pyrrolidine dithiocarbamic acid (PDTC), an inhibitor of NF-κB, displayed improvements in the CI and in collagen synthesis. Moreover, PDTC ameliorated the expression of cytokines and proteins associated with myocardial fibrosis. The results showed that maternal inflammation can induce myocardial fibrosis in offspring during aging accompanied by an imbalance of TIMP-2/MMP2 and TGFβ expression. Full article
(This article belongs to the Special Issue Improvement of Cardiac Function in Heart Failure)
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16 pages, 2085 KiB  
Article
Molecular Cloning and Functional Characterization of Mannose Receptor in Zebra Fish (Danio rerio) during Infection with Aeromonas sobria
by Feifei Zheng, Muhammad Asim, Jiangfeng Lan, Lijuan Zhao, Shun Wei, Nan Chen, Xiaoling Liu, Yang Zhou and Li Lin
Int. J. Mol. Sci. 2015, 16(5), 10997-11012; https://doi.org/10.3390/ijms160510997 - 15 May 2015
Cited by 36 | Viewed by 7600
Abstract
Mannose receptor (MR) is a member of pattern-recognition receptors (PRRs), which plays a significant role in immunity responses. Much work on MR has been done in mammals and birds while little in fish. In this report, a MR gene (designated as zfMR) was [...] Read more.
Mannose receptor (MR) is a member of pattern-recognition receptors (PRRs), which plays a significant role in immunity responses. Much work on MR has been done in mammals and birds while little in fish. In this report, a MR gene (designated as zfMR) was cloned from zebra fish (Danio rerio), which is an attractive model for the studies of animal diseases. The full-length cDNA of zfMR contains 6248 bp encoding a putative protein of 1428 amino acids. The predicted amino acid sequences showed that zfMR contained a cysteine-rich domain, a single fibronectin type II (FN II) domain, eight C-type lectin-like domains (CTLDs), a transmembrane domain and a short C-terminal cytoplasmic domain, sharing highly conserved structures with MRs from the other species. The MR mRNA could be detected in all examined tissues with highest level in kidney. The temporal expression patterns of MR, IL-1β and TNF-α mRNAs were analyzed in the liver, spleen, kidney and intestine post of infection with Aeromonas sobria. By immunohistochemistry assay, slight enhancement of MR protein was also observed in the spleen and intestine of the infected zebra fish. The established zebra fish-A. sobria infection model will be valuable for elucidating the role of MR in fish immune responses to infection. Full article
(This article belongs to the Special Issue Fish Molecular Biology)
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21 pages, 1929 KiB  
Review
The Real Culprit in Systemic Lupus Erythematosus: Abnormal Epigenetic Regulation
by Haijing Wu, Ming Zhao, Christopher Chang and Qianjin Lu
Int. J. Mol. Sci. 2015, 16(5), 11013-11033; https://doi.org/10.3390/ijms160511013 - 15 May 2015
Cited by 32 | Viewed by 9854
Abstract
Systemic lupus erythematosus (SLE) is an autoimmune disease involving multiple organs and the presence of anti-nuclear antibodies. The pathogenesis of SLE has been intensively studied but remains far from clear. B and T lymphocyte abnormalities, dysregulation of apoptosis, defects in the clearance of [...] Read more.
Systemic lupus erythematosus (SLE) is an autoimmune disease involving multiple organs and the presence of anti-nuclear antibodies. The pathogenesis of SLE has been intensively studied but remains far from clear. B and T lymphocyte abnormalities, dysregulation of apoptosis, defects in the clearance of apoptotic materials, and various genetic and epigenetic factors are attributed to the development of SLE. The latest research findings point to the association between abnormal epigenetic regulation and SLE, which has attracted considerable interest worldwide. It is the purpose of this review to present and discuss the relationship between aberrant epigenetic regulation and SLE, including DNA methylation, histone modifications and microRNAs in patients with SLE, the possible mechanisms of immune dysfunction caused by epigenetic changes, and to better understand the roles of aberrant epigenetic regulation in the initiation and development of SLE and to provide an insight into the related therapeutic options in SLE. Full article
(This article belongs to the Special Issue Molecular and Cellular Mechanisms in the Pathogenesis of Systemic Lupus Erythematosus)
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21 pages, 1416 KiB  
Article
Synthesis, Characterization and Biological Evaluation of Transition Metal Complexes Derived from N, S Bidentate Ligands
by Enis Nadia Md Yusof, Thahira Begum S. A. Ravoof, Edward R. T. Tiekink, Abhimanyu Veerakumarasivam, Karen Anne Crouse, Mohamed Ibrahim Mohamed Tahir and Haslina Ahmad
Int. J. Mol. Sci. 2015, 16(5), 11034-11054; https://doi.org/10.3390/ijms160511034 - 15 May 2015
Cited by 69 | Viewed by 8754
Abstract
Two bidentate NS ligands were synthesized by the condensation reaction of S-2-methylbenzyldithiocarbazate (S2MBDTC) with 2-methoxybenzaldehyde (2MB) and 3-methoxybenzaldehyde (3MB). The ligands were reacted separately with acetates of Cu(II), Ni(II) and Zn(II) yielding 1:2 (metal:ligand) complexes. The metal complexes formed were expected to have [...] Read more.
Two bidentate NS ligands were synthesized by the condensation reaction of S-2-methylbenzyldithiocarbazate (S2MBDTC) with 2-methoxybenzaldehyde (2MB) and 3-methoxybenzaldehyde (3MB). The ligands were reacted separately with acetates of Cu(II), Ni(II) and Zn(II) yielding 1:2 (metal:ligand) complexes. The metal complexes formed were expected to have a general formula of [M(NS)2] where M = Cu2+, Ni2+, and Zn2+. These compounds were characterized by elemental analysis, molar conductivity, magnetic susceptibility and various spectroscopic techniques. The magnetic susceptibility measurements and spectral results supported the predicted coordination geometry in which the Schiff bases behaved as bidentate NS donor ligands coordinating via the azomethine nitrogen and thiolate sulfur. The molecular structures of the isomeric S2M2MBH (1) and S2M3MBH (2) were established by X-ray crystallography to have very similar l-shaped structures. The Schiff bases and their metal complexes were evaluated for their biological activities against estrogen receptor-positive (MCF-7) and estrogen receptor-negative (MDA-MB-231) breast cancer cell lines. Only the Cu(II) complexes showed marked cytotoxicity against the cancer cell lines. Both Schiff bases and other metal complexes were found to be inactive. In concordance with the cytotoxicity studies, the DNA binding studies indicated that Cu(II) complexes have a strong DNA binding affinity. Full article
(This article belongs to the Section Materials Science)
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32 pages, 996 KiB  
Review
Molecular Connections between Cancer Cell Metabolism and the Tumor Microenvironment
by Calvin R. Justus, Edward J. Sanderlin and Li V. Yang
Int. J. Mol. Sci. 2015, 16(5), 11055-11086; https://doi.org/10.3390/ijms160511055 - 15 May 2015
Cited by 116 | Viewed by 14253
Abstract
Cancer cells preferentially utilize glycolysis, instead of oxidative phosphorylation, for metabolism even in the presence of oxygen. This phenomenon of aerobic glycolysis, referred to as the “Warburg effect”, commonly exists in a variety of tumors. Recent studies further demonstrate that both genetic factors [...] Read more.
Cancer cells preferentially utilize glycolysis, instead of oxidative phosphorylation, for metabolism even in the presence of oxygen. This phenomenon of aerobic glycolysis, referred to as the “Warburg effect”, commonly exists in a variety of tumors. Recent studies further demonstrate that both genetic factors such as oncogenes and tumor suppressors and microenvironmental factors such as spatial hypoxia and acidosis can regulate the glycolytic metabolism of cancer cells. Reciprocally, altered cancer cell metabolism can modulate the tumor microenvironment which plays important roles in cancer cell somatic evolution, metastasis, and therapeutic response. In this article, we review the progression of current understandings on the molecular interaction between cancer cell metabolism and the tumor microenvironment. In addition, we discuss the implications of these interactions in cancer therapy and chemoprevention. Full article
(This article belongs to the Special Issue Advances in Molecular Oncology)
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14 pages, 964 KiB  
Article
Mitochondria-Derived Reactive Oxygen Species Play an Important Role in Doxorubicin-Induced Platelet Apoptosis
by Zhicheng Wang, Jie Wang, Rufeng Xie, Ruilai Liu and Yuan Lu
Int. J. Mol. Sci. 2015, 16(5), 11087-11100; https://doi.org/10.3390/ijms160511087 - 15 May 2015
Cited by 86 | Viewed by 8198
Abstract
Doxorubicin (DOX) is an effective chemotherapeutic agent; however; its use is limited by some side effects; such as cardiotoxicity and thrombocytopenia. DOX-induced cardiotoxicity has been intensively investigated; however; DOX-induced thrombocytopenia has not been clearly elucidated. Here we show that DOX-induced mitochondria-mediated intrinsic apoptosis [...] Read more.
Doxorubicin (DOX) is an effective chemotherapeutic agent; however; its use is limited by some side effects; such as cardiotoxicity and thrombocytopenia. DOX-induced cardiotoxicity has been intensively investigated; however; DOX-induced thrombocytopenia has not been clearly elucidated. Here we show that DOX-induced mitochondria-mediated intrinsic apoptosis and glycoprotein (GP)Ibα shedding in platelets. DOX did not induce platelet activation; whereas; DOX obviously reduced adenosine diphosphate (ADP)- and thrombin-induced platelet aggregation; and impaired platelet adhesion on the von Willebrand factor (vWF) surface. In addition; we also show that DOX induced intracellular reactive oxygen species (ROS) production and mitochondrial ROS generation in a dose-dependent manner. The mitochondria-targeted ROS scavenger Mito-TEMPO blocked intracellular ROS and mitochondrial ROS generation. Furthermore; Mito-TEMPO reduced DOX-induced platelet apoptosis and GPIbα shedding. These data indicate that DOX induces platelet apoptosis; and impairs platelet function. Mitochondrial ROS play a pivotal role in DOX-induced platelet apoptosis and GPIbα shedding. Therefore; DOX-induced platelet apoptosis might contribute to DOX-triggered thrombocytopenia; and mitochondria-targeted ROS scavenger would have potential clinical utility in platelet-associated disorders involving mitochondrial oxidative damage. Full article
(This article belongs to the Special Issue Mitochondrial Dysfunction in Ageing and Diseases)
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24 pages, 1113 KiB  
Article
Serum Amyloid A Receptor Blockade and Incorporation into High-Density Lipoprotein Modulates Its Pro-Inflammatory and Pro-Thrombotic Activities on Vascular Endothelial Cells
by Belal Chami, Nicola Barrie, Xiaoping Cai, Xiaosuo Wang, Moumita Paul, Rebecca Morton-Chandra, Alexandra Sharland, Joanne M. Dennis, Saul B. Freedman and Paul K. Witting
Int. J. Mol. Sci. 2015, 16(5), 11101-11124; https://doi.org/10.3390/ijms160511101 - 15 May 2015
Cited by 24 | Viewed by 9079
Abstract
The acute phase protein serum amyloid A (SAA), a marker of inflammation, induces expression of pro-inflammatory and pro-thrombotic mediators including ICAM-1, VCAM-1, IL-6, IL-8, MCP-1 and tissue factor (TF) in both monocytes/macrophages and endothelial cells, and induces endothelial dysfunction—a precursor to atherosclerosis. In [...] Read more.
The acute phase protein serum amyloid A (SAA), a marker of inflammation, induces expression of pro-inflammatory and pro-thrombotic mediators including ICAM-1, VCAM-1, IL-6, IL-8, MCP-1 and tissue factor (TF) in both monocytes/macrophages and endothelial cells, and induces endothelial dysfunction—a precursor to atherosclerosis. In this study, we determined the effect of pharmacological inhibition of known SAA receptors on pro-inflammatory and pro-thrombotic activities of SAA in human carotid artery endothelial cells (HCtAEC). HCtAEC were pre-treated with inhibitors of formyl peptide receptor-like-1 (FPRL-1), WRW4; receptor for advanced glycation-endproducts (RAGE), (endogenous secretory RAGE; esRAGE) and toll-like receptors-2/4 (TLR2/4) (OxPapC), before stimulation by added SAA. Inhibitor activity was also compared to high-density lipoprotein (HDL), a known inhibitor of SAA-induced effects on endothelial cells. SAA significantly increased gene expression of TF, NFκB and TNF and protein levels of TF and VEGF in HCtAEC. These effects were inhibited to variable extents by WRW4, esRAGE and OxPapC either alone or in combination, suggesting involvement of endothelial cell SAA receptors in pro-atherogenic gene expression. In contrast, HDL consistently showed the greatest inhibitory action, and often abrogated SAA-mediated responses. Increasing HDL levels relative to circulating free SAA may prevent SAA-mediated endothelial dysfunction and ameliorate atherogenesis. Full article
(This article belongs to the Section Biochemistry)
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6 pages, 616 KiB  
Editorial
The Need for Translational Research to Advance Peripheral Artery Disease Management
by Joseph V. Moxon and Jonathan Golledge
Int. J. Mol. Sci. 2015, 16(5), 11125-11130; https://doi.org/10.3390/ijms160511125 - 18 May 2015
Viewed by 4271
Abstract
Peripheral artery disease (PAD) is a broad term encompassing a range of atherosclerotic and aneurysmal conditions of the extra-coronary arteries [1]. [...] Full article
(This article belongs to the Special Issue Advances in Peripheral Artery Disease)
47 pages, 8182 KiB  
Review
Imaging of Small Animal Peripheral Artery Disease Models: Recent Advancements and Translational Potential
by Jenny B. Lin, Evan H. Phillips, Ti'Air E. Riggins, Gurneet S. Sangha, Sreyashi Chakraborty, Janice Y. Lee, Roy J. Lycke, Clarissa L. Hernandez, Arvin H. Soepriatna, Bradford R. H. Thorne, Alexa A. Yrineo and Craig J. Goergen
Int. J. Mol. Sci. 2015, 16(5), 11131-11177; https://doi.org/10.3390/ijms160511131 - 18 May 2015
Cited by 42 | Viewed by 13035
Abstract
Peripheral artery disease (PAD) is a broad disorder encompassing multiple forms of arterial disease outside of the heart. As such, PAD development is a multifactorial process with a variety of manifestations. For example, aneurysms are pathological expansions of an artery that can lead [...] Read more.
Peripheral artery disease (PAD) is a broad disorder encompassing multiple forms of arterial disease outside of the heart. As such, PAD development is a multifactorial process with a variety of manifestations. For example, aneurysms are pathological expansions of an artery that can lead to rupture, while ischemic atherosclerosis reduces blood flow, increasing the risk of claudication, poor wound healing, limb amputation, and stroke. Current PAD treatment is often ineffective or associated with serious risks, largely because these disorders are commonly undiagnosed or misdiagnosed. Active areas of research are focused on detecting and characterizing deleterious arterial changes at early stages using non-invasive imaging strategies, such as ultrasound, as well as emerging technologies like photoacoustic imaging. Earlier disease detection and characterization could improve interventional strategies, leading to better prognosis in PAD patients. While rodents are being used to investigate PAD pathophysiology, imaging of these animal models has been underutilized. This review focuses on structural and molecular information and disease progression revealed by recent imaging efforts of aortic, cerebral, and peripheral vascular disease models in mice, rats, and rabbits. Effective translation to humans involves better understanding of underlying PAD pathophysiology to develop novel therapeutics and apply non-invasive imaging techniques in the clinic. Full article
(This article belongs to the Special Issue Advances in Peripheral Artery Disease)
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18 pages, 721 KiB  
Review
Clonal Expansion of T Cells in Abdominal Aortic Aneurysm: A Role for Doxycycline as Drug of Choice?
by Albert M. Kroon and Jan-Willem Taanman
Int. J. Mol. Sci. 2015, 16(5), 11178-11195; https://doi.org/10.3390/ijms160511178 - 18 May 2015
Cited by 15 | Viewed by 6362
Abstract
Most reported studies with animal models of abdominal aortic aneurysm (AAA) and several studies with patients have suggested that doxycycline favourably modifies AAA; however, a recent large long-term clinical trial found that doxycycline did not limit aneurysm growth. Thus, there is currently no [...] Read more.
Most reported studies with animal models of abdominal aortic aneurysm (AAA) and several studies with patients have suggested that doxycycline favourably modifies AAA; however, a recent large long-term clinical trial found that doxycycline did not limit aneurysm growth. Thus, there is currently no convincing evidence that doxycycline reduces AAA expansion. Here, we critically review the available experimental and clinical information about the effects of doxycycline when used as a pharmacological treatment for AAA. The view that AAA can be considered an autoimmune disease and the observation that AAA tissue shows clonal expansion of T cells is placed in the light of the well-known inhibition of mitochondrial protein synthesis by doxycycline. In T cell leukaemia animal models, this inhibitory effect of the antibiotic has been shown to impede T cell proliferation, resulting in complete tumour eradication. We suggest that the available evidence of doxycycline action on AAA is erroneously ascribed to its inhibition of matrix metalloproteinases (MMPs) by competitive binding of the zinc ion co-factor. Although competitive binding may explain the inhibition of proteolytic activity, it does not explain the observed decreases of MMP mRNA levels. We propose that the observed effects of doxycycline are secondary to inhibition of mitochondrial protein synthesis. Provided that serum doxycycline levels are kept at adequate levels, the inhibition will result in a proliferation arrest, especially of clonally expanding T cells. This, in turn, leads to the decrease of proinflammatory cytokines that are normally generated by these cells. The drastic change in cell type composition may explain the changes in MMP mRNA and protein levels in the tissue samples. Full article
(This article belongs to the Special Issue Advances in Peripheral Artery Disease)
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17 pages, 6141 KiB  
Article
Immunohistochemical Analysis of the Natural Killer Cell Cytotoxicity Pathway in Human Abdominal Aortic Aneurysms
by Irene Hinterseher, Charles M. Schworer, John H. Lillvis, Elizabeth Stahl, Robert Erdman, Zoran Gatalica, Gerard Tromp and Helena Kuivaniemi
Int. J. Mol. Sci. 2015, 16(5), 11196-11212; https://doi.org/10.3390/ijms160511196 - 18 May 2015
Cited by 32 | Viewed by 6834
Abstract
Our previous analysis using genome-wide microarray expression data revealed extreme overrepresentation of immune related genes belonging the Natural Killer (NK) Cell Mediated Cytotoxicity pathway (hsa04650) in human abdominal aortic aneurysm (AAA). We followed up the microarray studies by immunohistochemical analyses using antibodies against [...] Read more.
Our previous analysis using genome-wide microarray expression data revealed extreme overrepresentation of immune related genes belonging the Natural Killer (NK) Cell Mediated Cytotoxicity pathway (hsa04650) in human abdominal aortic aneurysm (AAA). We followed up the microarray studies by immunohistochemical analyses using antibodies against nine members of the NK pathway (VAV1, VAV3, PLCG1, PLCG2, HCST, TYROBP, PTK2B, TNFA, and GZMB) and aortic tissue samples from AAA repair operations (n = 6) and control aortae (n = 8) from age-, sex- and ethnicity-matched donors from autopsies. The results confirmed the microarray results. Two different members of the NK pathway, HCST and GRZB, which act at different steps in the NK-pathway, were actively transcribed and translated into proteins in the same cells in the AAA tissue demonstrated by double staining. Furthermore, double staining with antibodies against CD68 or CD8 together with HCST, TYROBP, PTK2B or PLCG2 revealed that CD68 and CD8 positive cells expressed proteins of the NK-pathway but were not the only inflammatory cells involved in the NK-pathway in the AAA tissue. The results provide strong evidence that the NK Cell Mediated Cytotoxicity Pathway is activated in human AAA and valuable insight for future studies to dissect the pathogenesis of human AAA. Full article
(This article belongs to the Special Issue Advances in Peripheral Artery Disease)
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16 pages, 2247 KiB  
Article
Inhibitory Effect of Statins on Inflammation-Related Pathways in Human Abdominal Aortic Aneurysm Tissue
by Koichi Yoshimura, Ayako Nagasawa, Junichi Kudo, Masahiko Onoda, Noriyasu Morikage, Akira Furutani, Hiroki Aoki and Kimikazu Hamano
Int. J. Mol. Sci. 2015, 16(5), 11213-11228; https://doi.org/10.3390/ijms160511213 - 18 May 2015
Cited by 56 | Viewed by 6814
Abstract
HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase inhibitors (statins) have been suggested to attenuate abdominal aortic aneurysm (AAA) growth. However, the effects of statins in human AAA tissues are not fully elucidated. The aim of this study was to investigate the direct effects of statins on [...] Read more.
HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase inhibitors (statins) have been suggested to attenuate abdominal aortic aneurysm (AAA) growth. However, the effects of statins in human AAA tissues are not fully elucidated. The aim of this study was to investigate the direct effects of statins on proinflammatory molecules in human AAA walls in ex vivo culture. Simvastatin strongly inhibited the activation of nuclear factor (NF)-κB induced by tumor necrosis factor (TNF)-α in human AAA walls, but showed little effect on c-jun N-terminal kinase (JNK) activation. Simvastatin, as well as pitavastatin significantly reduced the secretion of matrix metalloproteinase (MMP)-9, monocyte chemoattractant protein (MCP)-2 and epithelial neutrophil-activating peptide (CXCL5) under both basal and TNF-α-stimulated conditions. Similar to statins, the Rac1 inhibitor NSC23766 significantly inhibited the activation of NF-κB, accompanied by a decreased secretion of MMP-9, MCP-2 and CXCL5. Moreover, the effect of simvastatin and the JNK inhibitor SP600125 was additive in inhibiting the secretion of MMP-9, MCP-2 and CXCL5. These findings indicate that statins preferentially inhibit the Rac1/NF-κB pathway to suppress MMP-9 and chemokine secretion in human AAA, suggesting a mechanism for the potential effect of statins in attenuating AAA progression. Full article
(This article belongs to the Special Issue Advances in Peripheral Artery Disease)
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30 pages, 8226 KiB  
Article
Transcriptional (ChIP-Chip) Analysis of ELF1, ETS2, RUNX1 and STAT5 in Human Abdominal Aortic Aneurysm
by Matthew C. Pahl, Robert Erdman, Helena Kuivaniemi, John H. Lillvis, James R. Elmore and Gerard Tromp
Int. J. Mol. Sci. 2015, 16(5), 11229-11258; https://doi.org/10.3390/ijms160511229 - 18 May 2015
Cited by 19 | Viewed by 7465
Abstract
We investigated transcriptional control of gene expression in human abdominal aortic aneurysm (AAA). We previously identified 3274 differentially expressed genes in human AAA tissue compared to non-aneurysmal controls. Four expressed transcription factors (ELF1, ETS2, STAT5 and RUNX1) were selected for genome-wide chromatin immunoprecipitation. [...] Read more.
We investigated transcriptional control of gene expression in human abdominal aortic aneurysm (AAA). We previously identified 3274 differentially expressed genes in human AAA tissue compared to non-aneurysmal controls. Four expressed transcription factors (ELF1, ETS2, STAT5 and RUNX1) were selected for genome-wide chromatin immunoprecipitation. Transcription factor binding was enriched in 4760 distinct genes (FDR < 0.05), of which 713 were differentially expressed in AAA. Functional classification using Gene Ontology (GO), KEGG, and Network Analysis revealed enrichment in several biological processes including “leukocyte migration” (FDR = 3.09 × 10−05) and “intracellular protein kinase cascade” (FDR = 6.48 × 10−05). In the control aorta, the most significant GO categories differed from those in the AAA samples and included “cytoskeleton organization” (FDR = 1.24 × 10−06) and “small GTPase mediated signal transduction” (FDR = 1.24 × 10−06). Genes up-regulated in AAA tissue showed a highly significant enrichment for GO categories “leukocyte migration” (FDR = 1.62 × 10−11), “activation of immune response” (FDR = 8.44 × 10−11), “T cell activation” (FDR = 4.14 × 10−10) and “regulation of lymphocyte activation” (FDR = 2.45 × 10−09), whereas the down-regulated genes were enriched in GO categories “cytoskeleton organization” (FDR = 7.84 × 10−05), “muscle cell development” (FDR = 1.00 × 10−04), and “organ morphogenesis” (FDR = 3.00 × 10−04). Quantitative PCR assays confirmed a sub-set of the transcription factor binding sites including those in MTMR11, DUSP10, ITGAM, MARCH1, HDAC8, MMP14, MAGI1, THBD and SPOCK1. Full article
(This article belongs to the Special Issue Advances in Peripheral Artery Disease)
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17 pages, 3189 KiB  
Article
The Potential Role of DNA Methylation in Abdominal Aortic Aneurysms
by Evan J. Ryer, Kaitryn E. Ronning, Robert Erdman, Charles M. Schworer, James R. Elmore, Thomas C. Peeler, Christopher D. Nevius, John H. Lillvis, Robert P. Garvin, David P. Franklin, Helena Kuivaniemi and Gerard Tromp
Int. J. Mol. Sci. 2015, 16(5), 11259-11275; https://doi.org/10.3390/ijms160511259 - 18 May 2015
Cited by 34 | Viewed by 6538
Abstract
Abdominal aortic aneurysm (AAA) is a complex disorder that has a significant impact on the aging population. While both genetic and environmental risk factors have been implicated in AAA formation, the precise genetic markers involved and the factors influencing their expression remain an [...] Read more.
Abdominal aortic aneurysm (AAA) is a complex disorder that has a significant impact on the aging population. While both genetic and environmental risk factors have been implicated in AAA formation, the precise genetic markers involved and the factors influencing their expression remain an area of ongoing investigation. DNA methylation has been previously used to study gene silencing in other inflammatory disorders and since AAA has an extensive inflammatory component, we sought to examine the genome-wide DNA methylation profiles in mononuclear blood cells of AAA cases and matched non-AAA controls. To this end, we collected blood samples and isolated mononuclear cells for DNA and RNA extraction from four all male groups: AAA smokers (n = 11), AAA non-smokers (n = 9), control smokers (n = 10) and control non-smokers (n = 11). Methylation data were obtained using the Illumina 450k Human Methylation Bead Chip and analyzed using the R language and multiple Bioconductor packages. Principal component analysis and linear analysis of CpG island subsets identified four regions with significant differences in methylation with respect to AAA: kelch-like family member 35 (KLHL35), calponin 2 (CNN2), serpin peptidase inhibitor clade B (ovalbumin) member 9 (SERPINB9), and adenylate cyclase 10 pseudogene 1 (ADCY10P1). Follow-up studies included RT-PCR and immunostaining for CNN2 and SERPINB9. These findings are novel and suggest DNA methylation may play a role in AAA pathobiology. Full article
(This article belongs to the Special Issue Advances in Peripheral Artery Disease)
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18 pages, 1283 KiB  
Article
Adventitial Tertiary Lymphoid Organs as Potential Source of MicroRNA Biomarkers for Abdominal Aortic Aneurysm
by Rafaelle Spear, Ludovic Boytard, Renaud Blervaque, Maggy Chwastyniak, David Hot, Jonathan Vanhoutte, Bart Staels, Yves Lemoine, Nicolas Lamblin, François-René Pruvot, Stephan Haulon, Philippe Amouyel and Florence Pinet
Int. J. Mol. Sci. 2015, 16(5), 11276-11293; https://doi.org/10.3390/ijms160511276 - 18 May 2015
Cited by 34 | Viewed by 5932
Abstract
Abdominal aortic aneurysm (AAA) is an inflammatory disease associated with marked changes in the cellular composition of the aortic wall. This study aims to identify microRNA (miRNA) expression in aneurysmal inflammatory cells isolated by laser microdissection from human tissue samples. The distribution of [...] Read more.
Abdominal aortic aneurysm (AAA) is an inflammatory disease associated with marked changes in the cellular composition of the aortic wall. This study aims to identify microRNA (miRNA) expression in aneurysmal inflammatory cells isolated by laser microdissection from human tissue samples. The distribution of inflammatory cells (neutrophils, B and T lymphocytes, mast cells) was evaluated in human AAA biopsies. We observed in half of the samples that adventitial tertiary lymphoid organs (ATLOs) with a thickness from 0.5 to 2 mm were located exclusively in the adventitia. Out of the 850 miRNA that were screened by microarray in isolated ATLOs (n = 2), 164 miRNAs were detected in ATLOs. The three miRNAs (miR-15a-3p, miR-30a-5p and miR-489-3p) with the highest expression levels were chosen and their expression quantified by RT-PCR in isolated ATLOs (n = 4), M1 (n = 2) and M2 macrophages (n = 2) and entire aneurysmal biopsies (n = 3). Except for the miR-30a-5p, a similar modulation was found in ATLOs and the two subtypes of macrophages. The modulated miRNAs were then evaluated in the plasma of AAA patients for their potential as AAA biomarkers. Our data emphasize the potential of miR-15a-3p and miR-30a-5p as biomarkers of AAA but also as triggers of ATLO evolution. Further investigations will be required to evaluate their targets in order to better understand AAA pathophysiology. Full article
(This article belongs to the Special Issue Advances in Peripheral Artery Disease)
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29 pages, 981 KiB  
Review
A Review of the Pathophysiology and Potential Biomarkers for Peripheral Artery Disease
by Smriti Murali Krishna, Joseph V. Moxon and Jonathan Golledge
Int. J. Mol. Sci. 2015, 16(5), 11294-11322; https://doi.org/10.3390/ijms160511294 - 18 May 2015
Cited by 139 | Viewed by 26399
Abstract
Peripheral artery disease (PAD) is due to the blockage of the arteries supplying blood to the lower limbs usually secondary to atherosclerosis. The most severe clinical manifestation of PAD is critical limb ischemia (CLI), which is associated with a risk of limb loss [...] Read more.
Peripheral artery disease (PAD) is due to the blockage of the arteries supplying blood to the lower limbs usually secondary to atherosclerosis. The most severe clinical manifestation of PAD is critical limb ischemia (CLI), which is associated with a risk of limb loss and mortality due to cardiovascular events. Currently CLI is mainly treated by surgical or endovascular revascularization, with few other treatments in routine clinical practice. There are a number of problems with current PAD management strategies, such as the difficulty in selecting the appropriate treatments for individual patients. Many patients undergo repeated attempts at revascularization surgery, but ultimately require an amputation. There is great interest in developing new methods to identify patients who are unlikely to benefit from revascularization and to improve management of patients unsuitable for surgery. Circulating biomarkers that predict the progression of PAD and the response to therapies could assist in the management of patients. This review provides an overview of the pathophysiology of PAD and examines the association between circulating biomarkers and PAD presence, severity and prognosis. While some currently identified circulating markers show promise, further larger studies focused on the clinical value of the biomarkers over existing risk predictors are needed. Full article
(This article belongs to the Special Issue Advances in Peripheral Artery Disease)
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16 pages, 4948 KiB  
Article
Immunohistochemical Analysis of Paraoxonases and Chemokines in Arteries of Patients with Peripheral Artery Disease
by Anna Hernández-Aguilera, Julio Sepúlveda, Esther Rodríguez-Gallego, Maria Guirro, Anabel García-Heredia, Noemí Cabré, Fedra Luciano-Mateo, Isabel Fort-Gallifa, Vicente Martín-Paredero, Jorge Joven and Jordi Camps
Int. J. Mol. Sci. 2015, 16(5), 11323-11338; https://doi.org/10.3390/ijms160511323 - 18 May 2015
Cited by 23 | Viewed by 5867
Abstract
Oxidative damage to lipids and lipoproteins is implicated in the development of atherosclerotic vascular diseases, including peripheral artery disease (PAD). The paraoxonases (PON) are a group of antioxidant enzymes, termed PON1, PON2, and PON3 that protect lipoproteins and cells from peroxidation and, as [...] Read more.
Oxidative damage to lipids and lipoproteins is implicated in the development of atherosclerotic vascular diseases, including peripheral artery disease (PAD). The paraoxonases (PON) are a group of antioxidant enzymes, termed PON1, PON2, and PON3 that protect lipoproteins and cells from peroxidation and, as such, may be involved in protection against the atherosclerosis process. PON1 inhibits the production of chemokine (C–C motif) ligand 2 (CCL2) in endothelial cells incubated with oxidized lipoproteins. PON1 and CCL2 are ubiquitously distributed in tissues, and this suggests a joint localization and combined systemic effect. The aim of the present study has been to analyze the quantitative immunohistochemical localization of PON1, PON3, CCL2 and CCL2 receptors in a series of patients with severe PAD. Portions of femoral and/or popliteal arteries from 66 patients with PAD were obtained during surgical procedures for infra-inguinal limb revascularization. We used eight normal arteries from donors as controls. PON1 and PON3, CCL2 and the chemokine-binding protein 2, and Duffy antigen/chemokine receptor, were increased in PAD patients. There were no significant changes in C–C chemokine receptor type 2. Our findings suggest that paraoxonases and chemokines play an important role in the development and progression of atherosclerosis in peripheral artery disease. Full article
(This article belongs to the Special Issue Advances in Peripheral Artery Disease)
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16 pages, 699 KiB  
Article
Influence of Regular Exercise on Body Fat and Eating Patterns of Patients with Intermittent Claudication
by Anthony Leicht, Robert Crowther and Jonathan Golledge
Int. J. Mol. Sci. 2015, 16(5), 11339-11354; https://doi.org/10.3390/ijms160511339 - 18 May 2015
Cited by 7 | Viewed by 5539
Abstract
This study examined the impact of regular supervised exercise on body fat, assessed via anthropometry, and eating patterns of peripheral arterial disease patients with intermittent claudication (IC). Body fat, eating patterns and walking ability were assessed in 11 healthy adults (Control) and age- [...] Read more.
This study examined the impact of regular supervised exercise on body fat, assessed via anthropometry, and eating patterns of peripheral arterial disease patients with intermittent claudication (IC). Body fat, eating patterns and walking ability were assessed in 11 healthy adults (Control) and age- and mass-matched IC patients undertaking usual care (n = 10; IC-Con) or supervised exercise (12-months; n = 10; IC-Ex). At entry, all groups exhibited similar body fat and eating patterns. Maximal walking ability was greatest for Control participants and similar for IC-Ex and IC-Con patients. Supervised exercise resulted in significantly greater improvements in maximal walking ability (IC-Ex 148%–170% vs. IC-Con 29%–52%) and smaller increases in body fat (IC-Ex −2.1%–1.4% vs. IC-Con 8.4%–10%). IC-Con patients exhibited significantly greater increases in body fat compared with Control at follow-up (8.4%–10% vs. −0.6%–1.4%). Eating patterns were similar for all groups at follow-up. The current study demonstrated that regular, supervised exercise significantly improved maximal walking ability and minimised increase in body fat amongst IC patients without changes in eating patterns. The study supports the use of supervised exercise to minimize cardiovascular risk amongst IC patients. Further studies are needed to examine the additional value of other lifestyle interventions such as diet modification. Full article
(This article belongs to the Special Issue Advances in Peripheral Artery Disease)
14 pages, 993 KiB  
Article
Correlation between Patient-Reported Symptoms and Ankle-Brachial Index after Revascularization for Peripheral Arterial Disease
by Hyung Gon Je, Bo Hyun Kim, Kyoung Im Cho, Jae Sik Jang, Yong Hyun Park and John Spertus
Int. J. Mol. Sci. 2015, 16(5), 11355-11368; https://doi.org/10.3390/ijms160511355 - 18 May 2015
Cited by 16 | Viewed by 5948
Abstract
Improvement in quality of life (QoL) is a primary treatment goal for patients with peripheral arterial disease (PAD). The current study aimed to quantify improvement in the health status of PAD patients following peripheral revascularization using the peripheral artery questionnaire (PAQ) and ankle-brachial [...] Read more.
Improvement in quality of life (QoL) is a primary treatment goal for patients with peripheral arterial disease (PAD). The current study aimed to quantify improvement in the health status of PAD patients following peripheral revascularization using the peripheral artery questionnaire (PAQ) and ankle-brachial index (ABI), and to evaluate possible correlation between the two methods. The PAQ and ABI were assessed in 149 symptomatic PAD patients before, and three months after peripheral revascularization. Mean PAQ summary scores improved significantly three months after revascularization (+49.3 ± 15 points, p < 0.001). PAQ scores relating to patient symptoms showed the largest improvement following revascularization. The smallest increases were seen in reported treatment satisfaction (all p’s < 0.001). As expected the ABI of treated limbs showed significant improvement post-revascularization (p < 0.001). ABI after revascularization correlated with patient-reported changes in the physical function and QoL domains of the PAQ. Twenty-two percent of PAD patients were identified as having a poor response to revascularization (increase in ABI < 0.15). Interestingly, poor responders reported improvement in symptoms on the PAQ, although this was less marked than in patients with an increase in ABI > 0.15 following revascularization. In conclusion, data from the current study suggest a significant correlation between improvement in patient-reported outcomes assessed by PAQ and ABI in symptomatic PAD patients undergoing peripheral revascularization. Full article
(This article belongs to the Special Issue Advances in Peripheral Artery Disease)
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16 pages, 767 KiB  
Article
Statin, Calcium Channel Blocker and Beta Blocker Therapy May Decrease the Incidence of Tuberculosis Infection in Elderly Taiwanese Patients with Type 2 Diabetes
by Mei-Yueh Lee, Kun-Der Lin, Wei-Hao Hsu, Hsiu-Ling Chang, Yi-Hsin Yang, Pi-Jung Hsiao and Shyi-Jang Shin
Int. J. Mol. Sci. 2015, 16(5), 11369-11384; https://doi.org/10.3390/ijms160511369 - 18 May 2015
Cited by 33 | Viewed by 7335
Abstract
Background: It is well known that diabetes mellitus impairs immunity and therefore is an independent risk factor for tuberculosis. However, the influence of associated metabolic factors, such as hypertension, dyslipidemia and gout has yet to be confirmed. This study aimed to investigate whether [...] Read more.
Background: It is well known that diabetes mellitus impairs immunity and therefore is an independent risk factor for tuberculosis. However, the influence of associated metabolic factors, such as hypertension, dyslipidemia and gout has yet to be confirmed. This study aimed to investigate whether the strong association between tuberculosis and diabetes mellitus is independent from the influence of hypertension and dyslipidemia, and its treatment in elderly Taiwanese patients. Methods: A total of 27,958 patients aged more than 65 years were identified from the National Health Insurance Research Database (NIHRD) in 1997 and were followed from 1998 to 2009. The demographic characteristics between the patients with and without diabetes were analyzed using the χ2 test. A total of 13,981 patients with type 2 diabetes were included in this study. Cox proportional hazard regression models were used to determine the independent effects of diabetes on the risk of tuberculosis. Results: After adjusting for age, sex, other co-morbidities and medications, calcium channel blocker, beta blocker and statin users had a lower independent association, with risk ratios of 0.76 (95% CI, 0.58–0.98), 0.72 (95% CI, 0.58–0.91) and 0.76 (95% CI, 0.60–0.97), respectively. Conclusion: Calcium channel blocker, beta blocker and statin therapy may decrease the incidence of tuberculosis infection in elderly Taiwanese patients with type 2 diabetes. Full article
(This article belongs to the Section Biochemistry)
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13 pages, 1104 KiB  
Article
Polymorphisms of the Ovine BMPR-IB, BMP-15 and FSHR and Their Associations with Litter Size in Two Chinese Indigenous Sheep Breeds
by Weimin Wang, Shijia Liu, Fadi Li, Xiangyu Pan, Chong Li, Xiaoxue Zhang, Youji Ma, Yongfu La, Rui Xi and Tingfu Li
Int. J. Mol. Sci. 2015, 16(5), 11385-11397; https://doi.org/10.3390/ijms160511385 - 18 May 2015
Cited by 51 | Viewed by 7933
Abstract
The Small Tailed Han sheep and Hu sheep are two prolific local sheep in China. In this study, the polymorphisms of BMPR-IB (Bone morphogenetic protein receptor IB), BMP-15 (Bone morphogenetic protein 15) and FSHR (follicle stimulating hormone receptor) were investigated to check whether [...] Read more.
The Small Tailed Han sheep and Hu sheep are two prolific local sheep in China. In this study, the polymorphisms of BMPR-IB (Bone morphogenetic protein receptor IB), BMP-15 (Bone morphogenetic protein 15) and FSHR (follicle stimulating hormone receptor) were investigated to check whether they are associated with litter size in Small Tailed Han sheep and Hu sheep. Consequently, three polymorphisms, FecB mutation in BMPR-IB (c.746A>G), FecG mutation in BMP-15 (c.718C>T) and the mutation (g. 47C>T) in FSHR were found in the above two sheep breeds with a total number of 1630 individuals. The single marker association analysis showed that the three mutations were significantly associated with litter size. The ewes with genotype FecBB/FecBB and FecBB/FecB+ had 0.78 and 0.58 more lambs (p < 0.01) than those with genotype FecB+/FecB+, respectively. The heterozygous Han and Hu ewes with FecXG/FecX+ genotype showed 0.30 (p = 0.05) more lambs than those with the FecX+/FecX+ genotype. For FSHR gene, the ewes with genotype CC had 0.52 (p < 0.01) and 0.75 (p < 0.01) more lambs than those with genotypes TC and TT, respectively. Combined effect analyses indicated an extremely significant interaction (p < 0.01) between the random combinations of BMPR-IB, BMP-15 and FSHR genes on litter size. In addition, the Han and Hu ewes with BB/G+/CC genotype harbor the highest litter size among ewes analyzed in current study. In conclusion, BMPR-IB, BMP-15 and FSHR polymorphisms could be used as genetic markers in multi-gene pyramiding for improving litter size in sheep husbandry. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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19 pages, 1132 KiB  
Article
Comparative Analysis of Anther Transcriptome Profiles of Two Different Rice Male Sterile Lines Genotypes under Cold Stress
by Bin Bai, Jun Wu, Wen-Tao Sheng, Bo Zhou, Li-Jie Zhou, Wen Zhuang, Dong-Ping Yao and Qi-Yun Deng
Int. J. Mol. Sci. 2015, 16(5), 11398-11416; https://doi.org/10.3390/ijms160511398 - 18 May 2015
Cited by 74 | Viewed by 11319
Abstract
Rice is highly sensitive to cold stress during reproductive developmental stages, and little is known about the mechanisms of cold responses in rice anther. Using the HiSeq™ 2000 sequencing platform, the anther transcriptome of photo thermo sensitive genic male sterile lines (PTGMS) rice [...] Read more.
Rice is highly sensitive to cold stress during reproductive developmental stages, and little is known about the mechanisms of cold responses in rice anther. Using the HiSeq™ 2000 sequencing platform, the anther transcriptome of photo thermo sensitive genic male sterile lines (PTGMS) rice Y58S and P64S (Pei’ai64S) were analyzed at the fertility sensitive stage under cold stress. Approximately 243 million clean reads were obtained from four libraries and aligned against the oryza indica genome and 1497 and 5652 differentially expressed genes (DEGs) were identified in P64S and Y58S, respectively. Both gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted for these DEGs. Functional classification of DEGs was also carried out. The DEGs common to both genotypes were mainly involved in signal transduction, metabolism, transport, and transcriptional regulation. Most of the DEGs were unique for each comparison group. We observed that there were more differentially expressed MYB (Myeloblastosis) and zinc finger family transcription factors and signal transduction components such as calmodulin/calcium dependent protein kinases in the Y58S comparison group. It was also found that ribosome-related DEGs may play key roles in cold stress signal transduction. These results presented here would be particularly useful for further studies on investigating the molecular mechanisms of rice responses to cold stress. Full article
(This article belongs to the Special Issue Abiotic Stress and Gene Networks in Plants)
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22 pages, 1532 KiB  
Article
Identification and Expression Analysis of Candidate Genes Associated with Defense Responses to Phytophthora capsici in Pepper Line “PI 201234”
by Pingyong Wang, Xiaodan Liu, Jinju Guo, Chen Liu, Nan Fu and Huolin Shen
Int. J. Mol. Sci. 2015, 16(5), 11417-11438; https://doi.org/10.3390/ijms160511417 - 18 May 2015
Cited by 21 | Viewed by 6800
Abstract
Phytophthora capsici (Leonian), classified as an oomycete, seriously threatens the production of pepper (Capsicum annuum). Current understanding of the defense responses in pepper to P. capsici is limited. In this study, RNA-sequencing analysis was utilized to identify differentially expressed genes in [...] Read more.
Phytophthora capsici (Leonian), classified as an oomycete, seriously threatens the production of pepper (Capsicum annuum). Current understanding of the defense responses in pepper to P. capsici is limited. In this study, RNA-sequencing analysis was utilized to identify differentially expressed genes in the resistant line “PI 201234”, with 1220 differentially expressed genes detected. Of those genes, 480 were up-regulated and 740 were down-regulated, with 211 candidate genes found to be involved in defense responses based on the gene annotations. Furthermore, the expression patterns of 12 candidate genes were further validated via quantitative real-time PCR (qPCR). These genes were found to be significantly up-regulated at different time points post-inoculation (6 hpi, 24 hpi, and 5 dpi) in the resistant line “PI 201234” and susceptible line “Qiemen”. Seven genes were found to be involved in cell wall modification, phytoalexin biosynthesis, symptom development, and phytohormone signaling pathways, thus possibly playing important roles in combating exogenous pathogens. The genes identified herein will provide a basis for further gene cloning and functional verification studies and will aid in an understanding of the regulatory mechanism of pepper resistance to P. capsici. Full article
(This article belongs to the Special Issue Plant Molecular Biology)
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13 pages, 4169 KiB  
Article
Visfatin Mediates SCLC Cells Migration across Brain Endothelial Cells through Upregulation of CCL2
by Tingting Liu, Ziwei Miao, Jiusheng Jiang, Shuai Yuan, Wengang Fang, Bo Li and Yuhua Chen
Int. J. Mol. Sci. 2015, 16(5), 11439-11451; https://doi.org/10.3390/ijms160511439 - 18 May 2015
Cited by 29 | Viewed by 6216
Abstract
Small-cell lung cancer (SCLC) is characterized as an aggressive tumor with brain metastasis. Although preventing SCLC metastasis to the brain is immensely important for survival, the molecular mechanisms of SCLC cells penetrating the blood–brain barrier (BBB) are largely unknown. Recently, visfatin has been [...] Read more.
Small-cell lung cancer (SCLC) is characterized as an aggressive tumor with brain metastasis. Although preventing SCLC metastasis to the brain is immensely important for survival, the molecular mechanisms of SCLC cells penetrating the blood–brain barrier (BBB) are largely unknown. Recently, visfatin has been considered as a novel pro-inflammatory adipocytokine involved in various cancers. Herein, we present evidence that elevated levels of visfatin in the serum of SCLC patients were associated with brain metastasis, and visfain was increased in NCI-H446 cells, a SCLC cell line, during interacting with human brain microvascular endothelial cells (HBMEC). Using in vitro BBB model, we found that visfatin could promote NCI-H446 cells migration across HBMEC monolayer, while the effect was inhibited by knockdown of visfatin. Furthermore, our findings indicated that CC chemokine ligand 2 (CCL2) was involved in visfatin-mediated NCI-H446 cells transendothelial migtation. Results also showed that the upregulation of CCL2 in the co-culture system was reversed by blockade of visfatin. In particular, visfatin-induced CCL2 was attenuated by specific inhibitor of PI3K/Akt signaling in NCI-H446 cells. Taken together, we demonstrated that visfatin was a prospective target for SCLC metastasis to brain, and understanding the molecular mediators would lead to effective strategies for inhibition of SCLC brain metastasis. Full article
(This article belongs to the Section Biochemistry)
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13 pages, 872 KiB  
Article
A Solid-State NMR Study of Selenium Substitution into Nanocrystalline Hydroxyapatite
by Joanna Kolmas, Marzena Kuras, Ewa Oledzka and Marcin Sobczak
Int. J. Mol. Sci. 2015, 16(5), 11452-11464; https://doi.org/10.3390/ijms160511452 - 19 May 2015
Cited by 24 | Viewed by 6708
Abstract
The substitution of selenium oxyanions in the hydroxyapatite structure was examined using multinuclear solid-state resonance spectroscopy (ssNMR). The study was supported by powder X-ray diffractometry (PXRD) and wavelength dispersion X-ray fluorescence (WD-XRF). Samples of pure hydroxyapatite (HA300) and selenate (HA300 [...] Read more.
The substitution of selenium oxyanions in the hydroxyapatite structure was examined using multinuclear solid-state resonance spectroscopy (ssNMR). The study was supported by powder X-ray diffractometry (PXRD) and wavelength dispersion X-ray fluorescence (WD-XRF). Samples of pure hydroxyapatite (HA300) and selenate (HA300-1.2SeO4) or selenite (HA300-1.2SeO3) substituted hydroxyapatites were synthesized using the standard wet method and heated at 300 °C to remove loosely bonded water. PXRD data showed that all samples are single-phase, nanocrystalline hydroxyapatite. The incorporation of selenite and selenate ions affected the lattice constants. In selenium-containing samples the concentration of Se was very similar and amounted to 9.55% and 9.64%, for HA300-1.2SeO4 and HA300-1.2SeO3, respectively. PXRD and ssNMR data showed that the selenite doping significantly decreases the crystallite size and crystallinity degree. 31P and 1H NMR experiments demonstrated the developed surface hydrated layer in all samples, especially in HA300-1.2SeO3. 1H NMR studies showed the dehydroxylation of HA during the selenium oxyanions substitution and the existence of hydrogen bonding in structural hydroxyl group channels. 1H→77Se cross polarization NMR experiments indicated that selenites and selenates are located in the crystal lattice and on the crystal surface. Full article
(This article belongs to the Special Issue Biomaterials for Tissue Engineering)
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17 pages, 821 KiB  
Article
Gene Expression Signature in Endemic Osteoarthritis by Microarray Analysis
by Xi Wang, Yujie Ning, Feng Zhang, Fangfang Yu, Wuhong Tan, Yanxia Lei, Cuiyan Wu, Jingjing Zheng, Sen Wang, Hanjie Yu, Zheng Li, Mikko J. Lammi and Xiong Guo
Int. J. Mol. Sci. 2015, 16(5), 11465-11481; https://doi.org/10.3390/ijms160511465 - 19 May 2015
Cited by 4 | Viewed by 7388
Abstract
Kashin-Beck Disease (KBD) is an endemic osteochondropathy with an unknown pathogenesis. Diagnosis of KBD is effective only in advanced cases, which eliminates the possibility of early treatment and leads to an inevitable exacerbation of symptoms. Therefore, we aim to identify an accurate blood-based [...] Read more.
Kashin-Beck Disease (KBD) is an endemic osteochondropathy with an unknown pathogenesis. Diagnosis of KBD is effective only in advanced cases, which eliminates the possibility of early treatment and leads to an inevitable exacerbation of symptoms. Therefore, we aim to identify an accurate blood-based gene signature for the detection of KBD. Previously published gene expression profile data on cartilage and peripheral blood mononuclear cells (PBMCs) from adults with KBD were compared to select potential target genes. Microarray analysis was conducted to evaluate the expression of the target genes in a cohort of 100 KBD patients and 100 healthy controls. A gene expression signature was identified using a training set, which was subsequently validated using an independent test set with a minimum redundancy maximum relevance (mRMR) algorithm and support vector machine (SVM) algorithm. Fifty unique genes were differentially expressed between KBD patients and healthy controls. A 20-gene signature was identified that distinguished between KBD patients and controls with 90% accuracy, 85% sensitivity, and 95% specificity. This study identified a 20-gene signature that accurately distinguishes between patients with KBD and controls using peripheral blood samples. These results promote the further development of blood-based genetic biomarkers for detection of KBD. Full article
(This article belongs to the Special Issue Emerging Classes of Biomarkers for Molecular Diagnostics)
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18 pages, 1126 KiB  
Article
Anti-Fibrotic Effects of Class I HDAC Inhibitor, Mocetinostat Is Associated with IL-6/Stat3 Signaling in Ischemic Heart Failure
by Hikmet Nural-Guvener, Liudmila Zakharova, Lorraine Feehery, Snjezana Sljukic and Mohamed Gaballa
Int. J. Mol. Sci. 2015, 16(5), 11482-11499; https://doi.org/10.3390/ijms160511482 - 19 May 2015
Cited by 79 | Viewed by 8863
Abstract
Background: Recent studies have linked histone deacetylases (HDAC) to remodeling of the heart and cardiac fibrosis in heart failure. However, the molecular mechanisms linking chromatin remodeling events with observed anti-fibrotic effects are unknown. Here, we investigated the molecular players involved in anti-fibrotic effects [...] Read more.
Background: Recent studies have linked histone deacetylases (HDAC) to remodeling of the heart and cardiac fibrosis in heart failure. However, the molecular mechanisms linking chromatin remodeling events with observed anti-fibrotic effects are unknown. Here, we investigated the molecular players involved in anti-fibrotic effects of HDAC inhibition in congestive heart failure (CHF) myocardium and cardiac fibroblasts in vivo. Methods and Results: MI was created by coronary artery occlusion. Class I HDACs were inhibited in three-week post MI rats by intraperitoneal injection of Mocetinostat (20 mg/kg/day) for duration of three weeks. Cardiac function and heart tissue were analyzed at six week post-MI. CD90+ cardiac fibroblasts were isolated from ventricles through enzymatic digestion of heart. In vivo treatment of CHF animals with Mocetinostat reduced CHF-dependent up-regulation of HDAC1 and HDAC2 in CHF myocardium, improved cardiac function and decreased scar size and total collagen amount. Moreover, expression of pro-fibrotic markers, collagen-1, fibronectin and Connective Tissue Growth Factor (CTGF) were reduced in the left ventricle (LV) of Mocetinostat-treated CHF hearts. Cardiac fibroblasts isolated from Mocetinostat-treated CHF ventricles showed a decrease in expression of collagen I and III, fibronectin and Timp1. In addition, Mocetinostat attenuated CHF-induced elevation of IL-6 levels in CHF myocardium and cardiac fibroblasts. In parallel, levels of pSTAT3 were reduced via Mocetinostat in CHF myocardium. Conclusions: Anti-fibrotic effects of Mocetinostat in CHF are associated with the IL-6/STAT3 signaling pathway. In addition, our study demonstrates in vivo regulation of cardiac fibroblasts via HDAC inhibition. Full article
(This article belongs to the Special Issue Improvement of Cardiac Function in Heart Failure)
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9 pages, 1806 KiB  
Article
Microwave-Assisted Synthesis of Glutathione-Capped CdTe/CdSe Near-Infrared Quantum Dots for Cell Imaging
by Xiaogang Chen, Liang Li, Yongxian Lai, Jianna Yan, Yichen Tang and Xiuli Wang
Int. J. Mol. Sci. 2015, 16(5), 11500-11508; https://doi.org/10.3390/ijms160511500 - 19 May 2015
Cited by 27 | Viewed by 7776
Abstract
These glutathione (GSH)-conjugated CdTe/CdSe core/shell quantum dot (QD) nanoparticles in aqueous solution were synthesized using a microwave-assisted approach. The prepared type II core/shell QD nanoparticles were characterized by UV–Vis absorption, photoluminescence (PL) spectroscopy, X-ray powder diffraction (XRD) and high-resolution transmission electron microscopy (HR-TEM). [...] Read more.
These glutathione (GSH)-conjugated CdTe/CdSe core/shell quantum dot (QD) nanoparticles in aqueous solution were synthesized using a microwave-assisted approach. The prepared type II core/shell QD nanoparticles were characterized by UV–Vis absorption, photoluminescence (PL) spectroscopy, X-ray powder diffraction (XRD) and high-resolution transmission electron microscopy (HR-TEM). Results revealed that the QD nanoparticles exhibited good dispersity, a uniform size distribution and tunable fluorescence emission in the near-infrared (NIR) region. In addition, these nanoparticles exhibited good biocompatibility and photoluminescence in cell imaging. In particular, this type of core/shell NIR QDs may have potential applications in molecular imaging. Full article
(This article belongs to the Special Issue Bioactive Nanoparticles)
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13 pages, 927 KiB  
Article
Periodic CO2 Dosing Strategy for Dunaliella salina Batch Culture
by Kezhen Ying, D. James Gilmour and William B. Zimmerman
Int. J. Mol. Sci. 2015, 16(5), 11509-11521; https://doi.org/10.3390/ijms160511509 - 19 May 2015
Cited by 10 | Viewed by 6606
Abstract
A periodic CO2 dosing strategy for D. salina 19/30 batch culture is proposed. A model of periodic CO2 dosing including dosing time calculation, dosing interval estimation and final chlorophyll yield prediction was established. In experiments, 5% CO2/95% N2 [...] Read more.
A periodic CO2 dosing strategy for D. salina 19/30 batch culture is proposed. A model of periodic CO2 dosing including dosing time calculation, dosing interval estimation and final chlorophyll yield prediction was established. In experiments, 5% CO2/95% N2 gas was periodically dosed into D. salina culture. Two different gas dosing flow rates were tested. The corresponding dosing time for each flow rate was estimated via the model (10 min·d−1 for 0.7 L·min−1 and 36 min·d−1 for 0.3 L·min−1). Daily pH measurements showed that the pH of these cultures dosed periodically was always kept between 7.5 and 9.5, which highlights that periodic gas supply can maintain a suitable range of pH for microalgal growth without expensive buffers. Notably the culture dosed for set daily intervals was seen to have similar growth to the culture supplied constantly, but with much higher CO2 capture efficiency (11%–18%) compared to continuous dosing (0.25%). It shows great potential for using periodic gas supply to reduce cost, wasted gas and energy use. Full article
(This article belongs to the Special Issue Microalgal Biotechnology)
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9 pages, 2011 KiB  
Brief Report
Proteogenomic Analysis Identifies a Novel Human SHANK3 Isoform
by Fahad Benthani, Phuong N. Tran, Nicola Currey, Irvin Ng, Marc Giry-Laterriere, Louise Carey, Maija R. J. Kohonen-Corish and Laurent Pangon
Int. J. Mol. Sci. 2015, 16(5), 11522-11530; https://doi.org/10.3390/ijms160511522 - 19 May 2015
Cited by 3 | Viewed by 7974
Abstract
Mutations of the SHANK3 gene have been associated with autism spectrum disorder. Individuals harboring different SHANK3 mutations display considerable heterogeneity in their cognitive impairment, likely due to the high SHANK3 transcriptional diversity. In this study, we report a novel interaction between the Mutated [...] Read more.
Mutations of the SHANK3 gene have been associated with autism spectrum disorder. Individuals harboring different SHANK3 mutations display considerable heterogeneity in their cognitive impairment, likely due to the high SHANK3 transcriptional diversity. In this study, we report a novel interaction between the Mutated in colorectal cancer (MCC) protein and a newly identified SHANK3 protein isoform in human colon cancer cells and mouse brain tissue. Hence, our proteogenomic analysis identifies a new human long isoform of the key synaptic protein SHANK3 that was not predicted by the human reference genome. Taken together, our findings describe a potential new role for MCC in neurons, a new human SHANK3 long isoform and, importantly, highlight the use of proteomic data towards the re-annotation of GC-rich genomic regions. Full article
(This article belongs to the Section Biochemistry)
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19 pages, 2778 KiB  
Article
Optimal Scanning Protocols for Dual-Energy CT Angiography in Peripheral Arterial Stents: An in Vitro Phantom Study
by Abdulrahman Almutairi, Zhonghua Sun, Zakariya Al Safran, Abduljaleel Poovathumkadavi, Suha Albader and Husam Ifdailat
Int. J. Mol. Sci. 2015, 16(5), 11531-11549; https://doi.org/10.3390/ijms160511531 - 20 May 2015
Cited by 19 | Viewed by 6318
Abstract
Objective: To identify the optimal dual-energy computed tomography (DECT) scanning protocol for peripheral arterial stents while achieving a low radiation dose, while still maintaining diagnostic image quality, as determined by an in vitro phantom study. Methods: Dual-energy scans in monochromatic spectral imaging mode [...] Read more.
Objective: To identify the optimal dual-energy computed tomography (DECT) scanning protocol for peripheral arterial stents while achieving a low radiation dose, while still maintaining diagnostic image quality, as determined by an in vitro phantom study. Methods: Dual-energy scans in monochromatic spectral imaging mode were performed on a peripheral arterial phantom with use of three gemstone spectral imaging (GSI) protocols, three pitch values, and four kiloelectron volts (keV) ranges. A total of 15 stents of different sizes, materials, and designs were deployed in the phantom. Image noise, the signal-to-noise ratio (SNR), different levels of adaptive statistical iterative reconstruction (ASIR), and the four levels of monochromatic energy for DECT imaging of peripheral arterial stents were measured and compared to determine the optimal protocols. Results: A total of 36 scans with 180 datasets were reconstructed from a combination of different protocols. There was a significant reduction of image noise with a higher SNR from monochromatic energy images between 65 and 70 keV in all investigated preset GSI protocols (p < 0.05). In addition, significant effects were found from the main effect analysis for these factors: GSI, pitch, and keV (p = 0.001). In contrast, there was significant interaction on the unstented area between GSI and ASIR (p = 0.015) and a very high significant difference between keV and ASIR (p < 0.001). A radiation dose reduction of 50% was achieved. Conclusions: The optimal scanning protocol and energy level in the phantom study were GSI-48, pitch value 0.984, and 65 keV, which resulted in lower image noise and a lower radiation dose, but with acceptable diagnostic images. Full article
(This article belongs to the Section Biochemistry)
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24 pages, 2238 KiB  
Article
De Novo Assembly and Characterization of the Transcriptome of the Chinese Medicinal Herb, Gentiana rigescens
by Xiaodong Zhang, Andrew C. Allan, Caixia Li, Yuanzhong Wang and Qiuyang Yao
Int. J. Mol. Sci. 2015, 16(5), 11550-11573; https://doi.org/10.3390/ijms160511550 - 20 May 2015
Cited by 43 | Viewed by 10156
Abstract
Gentiana rigescens is an important medicinal herb in China. The main validated medicinal component gentiopicroside is synthesized in shoots, but is mainly found in the plant’s roots. The gentiopicroside biosynthetic pathway and its regulatory control remain to be elucidated. Genome resources of gentian [...] Read more.
Gentiana rigescens is an important medicinal herb in China. The main validated medicinal component gentiopicroside is synthesized in shoots, but is mainly found in the plant’s roots. The gentiopicroside biosynthetic pathway and its regulatory control remain to be elucidated. Genome resources of gentian are limited. Next-generation sequencing (NGS) technologies can aid in supplying global gene expression profiles. In this study we present sequence and transcript abundance data for the root and leaf transcriptome of G. rigescens, obtained using the Illumina Hiseq2000. Over fifty million clean reads were obtained from leaf and root libraries. This yields 76,717 unigenes with an average length of 753 bp. Among these, 33,855 unigenes were identified as putative homologs of annotated sequences in public protein and nucleotide databases. Digital abundance analysis identified 3306 unigenes differentially enriched between leaf and root. Unigenes found in both tissues were categorized according to their putative functional categories. Of the differentially expressed genes, over 130 were annotated as related to terpenoid biosynthesis. This work is the first study of global transcriptome analyses in gentian. These sequences and putative functional data comprise a resource for future investigation of terpenoid biosynthesis in Gentianaceae species and annotation of the gentiopicroside biosynthetic pathway and its regulatory mechanisms. Full article
(This article belongs to the Special Issue Molecular Research in Plant Secondary Metabolism 2015)
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35 pages, 1321 KiB  
Review
Vasa Vasorum in Atherosclerosis and Clinical Significance
by Junyan Xu, Xiaotong Lu and Guo-Ping Shi
Int. J. Mol. Sci. 2015, 16(5), 11574-11608; https://doi.org/10.3390/ijms160511574 - 20 May 2015
Cited by 119 | Viewed by 23954
Abstract
Atherosclerosis is a chronic inflammatory disease that leads to several acute cardiovascular complications with poor prognosis. For decades, the role of the adventitial vasa vasorum (VV) in the initiation and progression of atherosclerosis has received broad attention. The presence of VV neovascularization precedes [...] Read more.
Atherosclerosis is a chronic inflammatory disease that leads to several acute cardiovascular complications with poor prognosis. For decades, the role of the adventitial vasa vasorum (VV) in the initiation and progression of atherosclerosis has received broad attention. The presence of VV neovascularization precedes the apparent symptoms of clinical atherosclerosis. VV also mediates inflammatory cell infiltration, intimal thickening, intraplaque hemorrhage, and subsequent atherothrombosis that results in stroke or myocardial infarction. Intraplaque neovessels originating from VV can be immature and hence susceptible to leakage, and are thus regarded as the leading cause of intraplaque hemorrhage. Evidence supports VV as a new surrogate target of atherosclerosis evaluation and treatment. This review provides an overview into the relationship between VV and atherosclerosis, including the anatomy and function of VV, the stimuli of VV neovascularization, and the available underlying mechanisms that lead to poor prognosis. We also summarize translational researches on VV imaging modalities and potential therapies that target VV neovascularization or its stimuli. Full article
(This article belongs to the Special Issue Atherosclerosis and Vascular Imaging)
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20 pages, 6643 KiB  
Article
Spontaneous γH2AX Foci in Human Solid Tumor-Derived Cell Lines in Relation to p21WAF1 and WIP1 Expression
by Razmik Mirzayans, Bonnie Andrais, April Scott, Ying W. Wang, Robert H. Weiss and David Murray
Int. J. Mol. Sci. 2015, 16(5), 11609-11628; https://doi.org/10.3390/ijms160511609 - 20 May 2015
Cited by 21 | Viewed by 10080
Abstract
Phosphorylation of H2AX on Ser139 (γH2AX) after exposure to ionizing radiation produces nuclear foci that are detectable by immunofluorescence microscopy. These so-called γH2AX foci have been adopted as quantitative markers for DNA double-strand breaks. High numbers of spontaneous γH2AX foci have also been [...] Read more.
Phosphorylation of H2AX on Ser139 (γH2AX) after exposure to ionizing radiation produces nuclear foci that are detectable by immunofluorescence microscopy. These so-called γH2AX foci have been adopted as quantitative markers for DNA double-strand breaks. High numbers of spontaneous γH2AX foci have also been reported for some human solid tumor-derived cell lines, but the molecular mechanism(s) for this response remains elusive. Here we show that cancer cells (e.g., HCT116; MCF7) that constitutively express detectable levels of p21WAF1 (p21) exhibit low numbers of γH2AX foci (<3/nucleus), whereas p21 knockout cells (HCT116p21−/−) and constitutively low p21-expressing cells (e.g., MDA-MB-231) exhibit high numbers of foci (e.g., >50/nucleus), and that these foci are not associated with apoptosis. The majority (>95%) of cells within HCT116p21−/− and MDA-MB-231 cultures contain high levels of phosphorylated p53, which is localized in the nucleus. We further show an inverse relationship between γH2AX foci and nuclear accumulation of WIP1, an oncogenic phosphatase. Our studies suggest that: (i) p21 deficiency might provide a selective pressure for the emergence of apoptosis-resistant progeny exhibiting genomic instability, manifested as spontaneous γH2AX foci coupled with phosphorylation and nuclear accumulation of p53; and (ii) p21 might contribute to positive regulation of WIP1, resulting in dephosphorylation of γH2AX. Full article
(This article belongs to the Special Issue Molecular Classification of Human Cancer: Diagnosis and Treatment)
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19 pages, 2480 KiB  
Article
Optimization of NaOH Molarity, LUSI Mud/Alkaline Activator, and Na2SiO3/NaOH Ratio to Produce Lightweight Aggregate-Based Geopolymer
by Rafiza Abdul Razak, Mohd Mustafa Al Bakri Abdullah, Kamarudin Hussin, Khairul Nizar Ismail, Djwantoro Hardjito and Zarina Yahya
Int. J. Mol. Sci. 2015, 16(5), 11629-11647; https://doi.org/10.3390/ijms160511629 - 21 May 2015
Cited by 40 | Viewed by 9057
Abstract
This paper presents the mechanical function and characterization of an artificial lightweight geopolymer aggregate (ALGA) using LUSI (Sidoarjo mud) and alkaline activator as source materials. LUSI stands for LU-Lumpur and SI-Sidoarjo, meaning mud from Sidoarjo which erupted near the Banjarpanji-1 exploration well in [...] Read more.
This paper presents the mechanical function and characterization of an artificial lightweight geopolymer aggregate (ALGA) using LUSI (Sidoarjo mud) and alkaline activator as source materials. LUSI stands for LU-Lumpur and SI-Sidoarjo, meaning mud from Sidoarjo which erupted near the Banjarpanji-1 exploration well in Sidoarjo, East Java, Indonesia on 27 May 2006. The effect of NaOH molarity, LUSI mud/Alkaline activator (LM/AA) ratio, and Na2SiO3/NaOH ratio to the ALGA are investigated at a sintering temperature of 950 °C. The results show that the optimum NaOH molarity found in this study is 12 M due to the highest strength (lowest AIV value) of 15.79% with lower water absorption and specific gravity. The optimum LUSI mud/Alkaline activator (LM/AA) ratio of 1.7 and the Na2SiO3/NaOH ratio of 0.4 gives the highest strength with AIV value of 15.42% with specific gravity of 1.10 g/cm3 and water absorption of 4.7%. The major synthesized crystalline phases were identified as sodalite, quartz and albite. Scanning Electron Microscope (SEM) image showed more complete geopolymer matrix which contributes to highest strength of ALGA produced. Full article
(This article belongs to the Section Materials Science)
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11 pages, 2427 KiB  
Article
The Influence of PSCA Gene Variation on Its Expression and Gastric Adenocarcinoma Susceptibility in the Northwest Chinese Population
by Wentao Zhang, Ping Liang, Weihua Wang, Peng Dai, Qin Wang, Wei Yan, Jinrong Zhao, Jianbin Sun, Yong Peng, Daxiang Cui and Zhen Yan
Int. J. Mol. Sci. 2015, 16(5), 11648-11658; https://doi.org/10.3390/ijms160511648 - 21 May 2015
Cited by 12 | Viewed by 6516
Abstract
Gastric adenocarcinoma (GAC) imposes a considerable health burden around the world. Gene variation in prostate stem cell antigen gene (PSCA) has been identified to be associated with GAC risk, while the results showed regional variation. To explore the influence of PSCA [...] Read more.
Gastric adenocarcinoma (GAC) imposes a considerable health burden around the world. Gene variation in prostate stem cell antigen gene (PSCA) has been identified to be associated with GAC risk, while the results showed regional variation. To explore the influence of PSCA gene variation on its expression and GAC risk in the Northwest Chinese population, four single nucleotide polymorphisms (SNPs) of PSCA were genotyped in 476 GAC cases and 481 controls using MassARRAY system. Two SNPs of rs2294008 (C>T) and rs2976392 (G>A) were identified to be associated with GAC risk. rs2294008, rs2976392 and rs10216533 made up two statistically significant haplotypes (Hap-CGG and Hap-TAG). Additionally, PSCA expression was analyzed by quantitative real time PCR, immunohistochemistry and tissue microarray. The results showed that PSCA expression was decreased in GAC tissues compared with adjacent normal tissues. For normal tissues, PSCA expression was higher with Hap-TA than that with Hap-CG. For GAC tissues, the differentiation degree of Hap-TA was higher than that of Hap-CG. The expression distribution of PSCA in multiple human organs showed disparity. These results suggest that PSCA gene variation has a potential effect on its expression and GAC risk in the Northwest Chinese population. Full article
(This article belongs to the Special Issue Human Single Nucleotide Polymorphisms and Disease Diagnostics)
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19 pages, 851 KiB  
Article
Acute Toxicity-Supported Chronic Toxicity Prediction: A k-Nearest Neighbor Coupled Read-Across Strategy
by Swapnil Chavan, Ran Friedman and Ian A. Nicholls
Int. J. Mol. Sci. 2015, 16(5), 11659-11677; https://doi.org/10.3390/ijms160511659 - 21 May 2015
Cited by 39 | Viewed by 7813
Abstract
A k-nearest neighbor (k-NN) classification model was constructed for 118 RDT NEDO (Repeated Dose Toxicity New Energy and industrial technology Development Organization; currently known as the Hazard Evaluation Support System (HESS)) database chemicals, employing two acute toxicity (LD50)-based [...] Read more.
A k-nearest neighbor (k-NN) classification model was constructed for 118 RDT NEDO (Repeated Dose Toxicity New Energy and industrial technology Development Organization; currently known as the Hazard Evaluation Support System (HESS)) database chemicals, employing two acute toxicity (LD50)-based classes as a response and using a series of eight PaDEL software-derived fingerprints as predictor variables. A model developed using Estate type fingerprints correctly predicted the LD50 classes for 70 of 94 training set chemicals and 19 of 24 test set chemicals. An individual category was formed for each of the chemicals by extracting its corresponding k-analogs that were identified by k-NN classification. These categories were used to perform the read-across study for prediction of the chronic toxicity, i.e., Lowest Observed Effect Levels (LOEL). We have successfully predicted the LOELs of 54 of 70 training set chemicals (77%) and 14 of 19 test set chemicals (74%) to within an order of magnitude from their experimental LOEL values. Given the success thus far, we conclude that if the k-NN model predicts LD50 classes correctly for a certain chemical, then the k-analogs of such a chemical can be successfully used for data gap filling for the LOEL. This model should support the in silico prediction of repeated dose toxicity. Full article
(This article belongs to the Section Molecular Toxicology)
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11 pages, 1413 KiB  
Article
Genetic Variant rs10757278 on Chromosome 9p21 Contributes to Myocardial Infarction Susceptibility
by Guangyuan Chen, Xiuhua Fu, Guangyu Wang, Guiyou Liu and Xiuping Bai
Int. J. Mol. Sci. 2015, 16(5), 11678-11688; https://doi.org/10.3390/ijms160511678 - 21 May 2015
Cited by 12 | Viewed by 6217
Abstract
Large-scale genome-wide association studies (GWAS) have revealed that rs10757278 polymorphism (or its proxy rs1333049) on chromosome 9p21 is associated with myocardial infarction (MI) susceptibility in individuals of Caucasian ancestry. Following studies in other populations investigated this association. However, some of these studies reported [...] Read more.
Large-scale genome-wide association studies (GWAS) have revealed that rs10757278 polymorphism (or its proxy rs1333049) on chromosome 9p21 is associated with myocardial infarction (MI) susceptibility in individuals of Caucasian ancestry. Following studies in other populations investigated this association. However, some of these studies reported weak or no significant association. Here, we reevaluated this association using large-scale samples by searching PubMed and Google Scholar databases. Our results showed significant association between rs10757278 polymorphism and MI with p = 6.09 × 10−22, odds ratio (OR) = 1.29, 95% confidence interval (CI) 1.22–1.36 in pooled population. We further performed a subgroup analysis, and found significant association between rs10757278 polymorphism and MI in Asian and Caucasian populations. We identified that the association between rs10757278 polymorphism and MI did not vary substantially by excluding any one study. However, the heterogeneity among the selected studies varies substantially by excluding the study from the Pakistan population. We found even more significant association between rs10757278 polymorphism and MI in pooled population, p = 3.55 × 10−53, after excluding the study from the Pakistan population. In summary, previous studies reported weak or no significant association between rs10757278 polymorphism and MI. Interestingly, our analysis suggests that rs10757278 polymorphism is significantly associated with MI susceptibility by analyzing large-scale samples. Full article
(This article belongs to the Section Biochemistry)
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10 pages, 668 KiB  
Article
Oxidized LDL Is Strictly Limited to Hyperthyroidism Irrespective of Fat Feeding in Female Sprague Dawley Rats
by Sieglinde Zelzer, Harald Mangge, Sabine Pailer, Herwig Ainoedhofer, Petra Kieslinger, Tatjana Stojakovic, Hubert Scharnagl, Florian Prüller, Daniel Weghuber, Christian Datz, Johannes Haybaeck, Barbara Obermayer-Pietsch, Christian Trummer, Johanna Gostner and Hans-Jürgen Gruber
Int. J. Mol. Sci. 2015, 16(5), 11689-11698; https://doi.org/10.3390/ijms160511689 - 21 May 2015
Cited by 3 | Viewed by 5711
Abstract
Metabolic dysfunctions might play a crucial role in the pathophysiology of thyroid dysfunctions. This study aimed to investigate the impact of a controlled diet (normal versus high fat feeding) on hypothyroid and hyperthyroid Sprague Dawley rats. Female Sprague Dawley rats (n [...] Read more.
Metabolic dysfunctions might play a crucial role in the pathophysiology of thyroid dysfunctions. This study aimed to investigate the impact of a controlled diet (normal versus high fat feeding) on hypothyroid and hyperthyroid Sprague Dawley rats. Female Sprague Dawley rats (n = 66) were grouped into normal diet (n = 30) and high-fat diet (n = 36) groups and subdivided into controls, hypothyroid and hyperthyroid groups, induced through propylthiouracil or triiodothyronine (T3) treatment, respectively. After 12 weeks of treatment metabolic parameters, such as oxidized LDL (oxLDL), malondialdehyde (MDA), 4-hydroxynonenal (HNE), the lipid profile, body weight and food intake parameters were analyzed. Successfully induced thyroid dysfunctions were shown by T3 levels, both under normal and high fat diet. Thyroid dysfunctions were accompanied by changes in calorie intake and body weight as well as in the lipid profile. In detail, hypothyroid rats showed significantly decreased oxLDL levels, whereas hyperthyroid rats showed significantly increased oxLDL levels. These effects were seen under high fat diet and were less pronounced with normal feeding. Taken together, we showed for the first time in female SD rats that only hyper-, but not hypothyroidism, is associated with high atherogenic oxidized LDL irrespective of normal or high-fat diet in Sprague Dawley rats. Full article
(This article belongs to the Section Biochemistry)
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14 pages, 900 KiB  
Article
MicroRNA-24 Regulates Osteogenic Differentiation via Targeting T-Cell Factor-1
by Weigong Zhao, Caijun Wu, Yanying Dong, Yunfeng Ma, Yaofeng Jin and Yanhong Ji
Int. J. Mol. Sci. 2015, 16(5), 11699-11712; https://doi.org/10.3390/ijms160511699 - 21 May 2015
Cited by 21 | Viewed by 5820
Abstract
MicroRNAs (miRNAs) have been reported to have diverse biological roles in regulating many biological processes, including osteogenic differentiation. In the present study, we identified that miR-24 was a critical regulator during osteogenic differentiation. We found that overexpression of miR-24 significantly inhibited osteogenic differentiation, [...] Read more.
MicroRNAs (miRNAs) have been reported to have diverse biological roles in regulating many biological processes, including osteogenic differentiation. In the present study, we identified that miR-24 was a critical regulator during osteogenic differentiation. We found that overexpression of miR-24 significantly inhibited osteogenic differentiation, which decreased alkaline phosphatase activity, matrix mineralization and the expression of osteogenic differentiation markers. In contrast, inhibition of miR-24 exhibited an opposite effect. Furthermore, we delineated that miR-24 regulates post-transcriptionals of T-cell factor-1 (Tcf-1) via targeting the 3'-untranslated region (UTR) of Tcf-1 mRNA. MiR-24 was further found to regulate the protein expression of Tcf-1 in the murine osteoprogenitors cells and bone mesenchymal stem cells. Additionally, the positive effect of miR-24 suppression on osteoblast differentiation was apparently abrogated by Tcf-1 silencing. Taken together, our data suggest that miR-24 participates in osteogenic differentiation by targeting and regulating Tcf-1 expression in osteoblastic cells. Full article
(This article belongs to the Section Biochemistry)
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15 pages, 3618 KiB  
Article
Intravital FRET: Probing Cellular and Tissue Function in Vivo
by Helena Radbruch, Daniel Bremer, Ronja Mothes, Robert Günther, Jan Leo Rinnenthal, Julian Pohlan, Carolin Ulbricht, Anja E. Hauser and Raluca Niesner
Int. J. Mol. Sci. 2015, 16(5), 11713-11727; https://doi.org/10.3390/ijms160511713 - 21 May 2015
Cited by 22 | Viewed by 7515
Abstract
The development of intravital Förster Resonance Energy Transfer (FRET) is required to probe cellular and tissue function in the natural context: the living organism. Only in this way can biomedicine truly comprehend pathogenesis and develop effective therapeutic strategies. Here we demonstrate and discuss [...] Read more.
The development of intravital Förster Resonance Energy Transfer (FRET) is required to probe cellular and tissue function in the natural context: the living organism. Only in this way can biomedicine truly comprehend pathogenesis and develop effective therapeutic strategies. Here we demonstrate and discuss the advantages and pitfalls of two strategies to quantify FRET in vivo—ratiometrically and time-resolved by fluorescence lifetime imaging—and show their concrete application in the context of neuroinflammation in adult mice. Full article
(This article belongs to the Special Issue Förster Resonance Energy Transfer (FRET) 2015)
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22 pages, 3308 KiB  
Review
Soy and Breast Cancer: Focus on Angiogenesis
by Lenka Varinska, Peter Gal, Gabriela Mojzisova, Ladislav Mirossay and Jan Mojzis
Int. J. Mol. Sci. 2015, 16(5), 11728-11749; https://doi.org/10.3390/ijms160511728 - 22 May 2015
Cited by 162 | Viewed by 16939
Abstract
Epidemiological studies have revealed that high consumption of soy products is associated with low incidences of hormone-dependent cancers, including breast and prostate cancer. Soybeans contain large amounts of isoflavones, such as the genistein and daidzain. Previously, it has been demonstrated that genistein, one [...] Read more.
Epidemiological studies have revealed that high consumption of soy products is associated with low incidences of hormone-dependent cancers, including breast and prostate cancer. Soybeans contain large amounts of isoflavones, such as the genistein and daidzain. Previously, it has been demonstrated that genistein, one of the predominant soy isoflavones, can inhibit several steps involved in carcinogenesis. It is suggested that genistein possesses pleiotropic molecular mechanisms of action including inhibition of tyrosine kinases, DNA topoisomerase II, 5α-reductase, galectin-induced G2/M arrest, protein histidine kinase, and cyclin-dependent kinases, modulation of different signaling pathways associated with the growth of cancer cells (e.g., NF-κB, Akt, MAPK), etc. Moreover, genistein is also a potent inhibitor of angiogenesis. Uncontrolled angiogenesis is considered as a key step in cancer growth, invasion, and metastasis. Genistein was found to inhibit angiogenesis through regulation of multiple pathways, such as regulation of VEGF, MMPs, EGFR expressions and NF-κB, PI3-K/Akt, ERK1/2 signaling pathways, thereby causing strong antiangiogenic effects. This review focuses on the antiangiogenic properties of soy isoflavonoids and examines their possible underlying mechanisms. Full article
(This article belongs to the Special Issue Bioactive Phytochemicals in Functional Foods for Cancer Prevention)
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16 pages, 2331 KiB  
Article
Aminomethylphosphonic Acid and Methoxyacetic Acid Induce Apoptosis in Prostate Cancer Cells
by Keshab R. Parajuli, Qiuyang Zhang, Sen Liu and Zongbing You
Int. J. Mol. Sci. 2015, 16(5), 11750-11765; https://doi.org/10.3390/ijms160511750 - 22 May 2015
Cited by 11 | Viewed by 7239
Abstract
Aminomethylphosphonic acid (AMPA) and its parent compound herbicide glyphosate are analogs to glycine, which have been reported to inhibit proliferation and promote apoptosis of cancer cells, but not normal cells. Methoxyacetic acid (MAA) is the active metabolite of ester phthalates widely used in [...] Read more.
Aminomethylphosphonic acid (AMPA) and its parent compound herbicide glyphosate are analogs to glycine, which have been reported to inhibit proliferation and promote apoptosis of cancer cells, but not normal cells. Methoxyacetic acid (MAA) is the active metabolite of ester phthalates widely used in industry as gelling, viscosity and stabilizer; its exposure is associated with developmental and reproductive toxicities in both rodents and humans. MAA has been reported to suppress prostate cancer cell growth by inducing growth arrest and apoptosis. However, it is unknown whether AMPA and MAA can inhibit cancer cell growth. In this study, we found that AMPA and MAA inhibited cell growth in prostate cancer cell lines (LNCaP, C4-2B, PC-3 and DU-145) through induction of apoptosis and cell cycle arrest at the G1 phase. Importantly, the AMPA-induced apoptosis was potentiated with the addition of MAA, which was due to downregulation of the anti-apoptotic gene baculoviral inhibitor of apoptosis protein repeat containing 2 (BIRC2), leading to activation of caspases 7 and 3. These results demonstrate that the combination of AMPA and MAA can promote the apoptosis of prostate cancer cells, suggesting that they can be used as potential therapeutic drugs in the treatment of prostate cancer. Full article
(This article belongs to the Special Issue Molecular and Cellular Mechanisms of Chemical-Induced Toxicity and Carcinogenesis)
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19 pages, 4040 KiB  
Article
Supramolecular Phase-Selective Gelation by Peptides Bearing Side-Chain Azobenzenes: Effect of Ultrasound and Potential for Dye Removal and Oil Spill Remediation
by Jürgen Bachl, Stefan Oehm, Judith Mayr, Carlos Cativiela, José Juan Marrero-Tellado and David Díaz Díaz
Int. J. Mol. Sci. 2015, 16(5), 11766-11784; https://doi.org/10.3390/ijms160511766 - 22 May 2015
Cited by 42 | Viewed by 8158
Abstract
Phase selective gelation (PSG) of organic phases from their non-miscible mixtures with water was achieved using tetrapeptides bearing a side-chain azobenzene moiety. The presence of the chromophore allowed PSG at the same concentration as the minimum gelation concentration (MGC) necessary to obtain the [...] Read more.
Phase selective gelation (PSG) of organic phases from their non-miscible mixtures with water was achieved using tetrapeptides bearing a side-chain azobenzene moiety. The presence of the chromophore allowed PSG at the same concentration as the minimum gelation concentration (MGC) necessary to obtain the gels in pure organic phases. Remarkably, the presence of the water phase during PSG did not impact the thermal, mechanical, and morphological properties of the corresponding organogels. In the case of miscible oil/water mixtures, the entire mixture was gelled, resulting in the formation of quasi-hydrogels. Importantly, PSG could be triggered at room temperature by ultrasound treatment of the mixture or by adding ultrasound-aided concentrated solution of the peptide in an oil-phase to a mixture of the same oil and water. Moreover, the PSG was not affected by the presence of salts or impurities existing in water from natural sources. The process could be scaled-up, and the oil phases (e.g., aromatic solvents, gasoline, diesel fuel) recovered almost quantitatively after a simple distillation process, which also allowed the recovery and reuse of the gelator. Finally, these peptidic gelators could be used to quantitatively remove toxic dyes from aqueous solutions. Full article
(This article belongs to the Special Issue Supramolecular Interactions)
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19 pages, 3920 KiB  
Review
Biomedical Application of Low Molecular Weight Heparin/Protamine Nano/Micro Particles as Cell- and Growth Factor-Carriers and Coating Matrix
by Masayuki Ishihara, Satoko Kishimoto, Makoto Takikawa, Hidemi Hattori, Shingo Nakamura and Masafumi Shimizu
Int. J. Mol. Sci. 2015, 16(5), 11785-11803; https://doi.org/10.3390/ijms160511785 - 22 May 2015
Cited by 17 | Viewed by 8705
Abstract
Low molecular weight heparin (LMWH)/protamine (P) nano/micro particles (N/MPs) (LMWH/P N/MPs) were applied as carriers for heparin-binding growth factors (GFs) and for adhesive cells including adipose-derived stromal cells (ADSCs) and bone marrow-derived mesenchymal stem cells (BMSCs). A mixture of LMWH and P yields [...] Read more.
Low molecular weight heparin (LMWH)/protamine (P) nano/micro particles (N/MPs) (LMWH/P N/MPs) were applied as carriers for heparin-binding growth factors (GFs) and for adhesive cells including adipose-derived stromal cells (ADSCs) and bone marrow-derived mesenchymal stem cells (BMSCs). A mixture of LMWH and P yields a dispersion of N/MPs (100 nm–3 μm in diameter). LMWH/P N/MPs can be immobilized onto cell surfaces or extracellular matrix, control the release, activate GFs and protect various GFs. Furthermore, LMWH/P N/MPs can also bind to adhesive cell surfaces, inducing cells and LMWH/P N/MPs-aggregate formation. Those aggregates substantially promoted cellular viability, and induced vascularization and fibrous tissue formation in vivo. The LMWH/P N/MPs, in combination with ADSCs or BMSCs, are effective cell-carriers and are potential promising novel therapeutic agents for inducing vascularization and fibrous tissue formation in ischemic disease by transplantation of the ADSCs and LMWH/P N/MPs-aggregates. LMWH/P N/MPs can also bind to tissue culture plates and adsorb exogenous GFs or GFs from those cells. The LMWH/P N/MPs-coated matrix in the presence of GFs may provide novel biomaterials that can control cellular activity such as growth and differentiation. Furthermore, three-dimensional (3D) cultures of cells including ADSCs and BMSCs using plasma-medium gel with LMWH/P N/MPs exhibited efficient cell proliferation. Thus, LMWH/P N/MPs are an adequate carrier both for GFs and for stromal cells such as ADSCs and BMSCs, and are a functional coating matrix for their cultures. Full article
(This article belongs to the Special Issue Biomaterials for Tissue Engineering)
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