International Journal of Molecular Sciences

24 pages, 532 KiB

Open AccessReview

EGFR-Ras-Raf Signaling in Epidermal Stem Cells: Roles in Hair Follicle Development, Regeneration, Tissue Remodeling and Epidermal Cancers

by Eszter Doma^†, Christian Rupp^† and Manuela Baccarini^*

¹ Max. F. Perutz Laboratories, Department of Microbiology, Immunology and Genetics, University of Vienna, Doktor-Bohr-Gasse 9, 1030 Vienna, Austria

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2013, 14(10), 19361-19384; https://doi.org/10.3390/ijms141019361 - 25 Sep 2013

Cited by 40 | Viewed by 14341

Abstract

The mammalian skin is the largest organ of the body and its outermost layer, the epidermis, undergoes dynamic lifetime renewal through the activity of somatic stem cell populations. The EGFR-Ras-Raf pathway has a well-described role in skin development and tumor formation. While research [...] Read more.

The mammalian skin is the largest organ of the body and its outermost layer, the epidermis, undergoes dynamic lifetime renewal through the activity of somatic stem cell populations. The EGFR-Ras-Raf pathway has a well-described role in skin development and tumor formation. While research mainly focuses on its role in cutaneous tumor initiation and maintenance, much less is known about Ras signaling in the epidermal stem cells, which are the main targets of skin carcinogenesis. In this review, we briefly discuss the properties of the epidermal stem cells and review the role of EGFR-Ras-Raf signaling in keratinocyte stem cells during homeostatic and pathological conditions. Full article

(This article belongs to the Special Issue Molecular Research of Epidermal Stem Cells)

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14 pages, 445 KiB

Open AccessReview

Keratin K15 as a Biomarker of Epidermal Stem Cells

by Amrita Bose, Muy-Teck Teh, Ian C. Mackenzie and Ahmad Waseem^*

Centre for Clinical and Diagnostic Oral Sciences, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, Turner Street, London E1 2AD, UK

Int. J. Mol. Sci. 2013, 14(10), 19385-19398; https://doi.org/10.3390/ijms141019385 - 25 Sep 2013

Cited by 96 | Viewed by 10290

Abstract

Keratin 15 (K15) is type I keratin protein co-expressed with the K5/K14 pair present in the basal keratinocytes of all stratified epithelia. Although it is a minor component of the cytoskeleton with a variable expression pattern, nonetheless its expression has been reported as [...] Read more.

Keratin 15 (K15) is type I keratin protein co-expressed with the K5/K14 pair present in the basal keratinocytes of all stratified epithelia. Although it is a minor component of the cytoskeleton with a variable expression pattern, nonetheless its expression has been reported as a stem cell marker in the bulge of hair follicles. Conversely, suprabasal expression of K15 has also been reported in both normal and diseased tissues, which is inconsistent with its role as a stem cell marker. Our recently published work has given evidence of the molecular pathways that seem to control the expression of K15 in undifferentiated and differentiated cells. In this article, we have critically reviewed the published work to establish the reliability of K15 as an epidermal stem cell marker. Full article

(This article belongs to the Special Issue Molecular Research of Epidermal Stem Cells)

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17 pages, 457 KiB

Open AccessArticle

Inhibition of Oxidative Stress by Low-Molecular-Weight Polysaccharides with Various Functional Groups in Skin Fibroblasts

by Szu-Kai Chen¹, Chu-Hsi Hsu^1,2, Min-Lang Tsai^1,*, Rong-Huei Chen^1,* and Gregor P. C. Drummen³

¹ Department of Food Science, National Taiwan Ocean University, 2 Pei-Ning Road, Keelung 20224, Taiwan

² Department of Food and Beverage Management, Yuanpei University, 306, Yuanpei Street, Hsinchu 30015, Taiwan

³ Cellular Stress and Ageing Program, Bionanoscience and Bio-Imaging Program, Bio & Nano-Solutions, Helmutstr. 3A, Düsseldorf 40472, Germany

Int. J. Mol. Sci. 2013, 14(10), 19399-19415; https://doi.org/10.3390/ijms141019399 - 25 Sep 2013

Cited by 40 | Viewed by 8416

Abstract

The aim of this study was to evaluate the in cellulo inhibition of hydrogen-peroxide-induced oxidative stress in skin fibroblasts using different low-molecular-weight polysaccharides (LMPS) prepared from agar (LMAG), chitosan (LMCH) and starch (LMST), which contain various different functional groups (i.e., sulfate, [...] Read more.

The aim of this study was to evaluate the in cellulo inhibition of hydrogen-peroxide-induced oxidative stress in skin fibroblasts using different low-molecular-weight polysaccharides (LMPS) prepared from agar (LMAG), chitosan (LMCH) and starch (LMST), which contain various different functional groups (i.e., sulfate, amine, and hydroxyl groups). The following parameters were evaluated: cell viability, intracellular oxidant production, lipid peroxidation, and DNA damage. Trolox was used as a positive control in order to allow comparison of the antioxidant efficacies of the various LMPS. The experimentally determined attenuation of oxidative stress by LMPS in skin fibroblasts was: LMCH > LMAG > LMST. The different protection levels of these LMPS may be due to the physic-chemical properties of the LMPS’ functional groups, including electron transfer ability, metal ion chelating capacities, radical stabilizing capacity, and the hydrophobicity of the constituent sugars. The results suggest that LMCH might constitute a novel and potential dermal therapeutic and sun-protective agent. Full article

(This article belongs to the Special Issue Oxidative Stress and Ageing)

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18 pages, 465 KiB

Open AccessReview

Mechanisms of Chemical Carcinogenesis in the Kidneys

by Robert Radford^1,2, Helena Frain^1,2, Michael P. Ryan^1,2, Craig Slattery^1,2 and Tara McMorrow^1,2,*

¹ UCD School of Biomolecular and Biomedical Research, Conway Institute, University College Dublin, Dublin, Dublin 4, Ireland

² Renal Disease Research Group, School of Biomolecular and Biomedical Science, Conway Institute of Biomolecular & Biomedical Research, University College Dublin, Dublin 4, Ireland

Int. J. Mol. Sci. 2013, 14(10), 19416-19433; https://doi.org/10.3390/ijms141019416 - 25 Sep 2013

Cited by 20 | Viewed by 9544

Abstract

Chemical carcinogens are substances which induce malignant tumours, increase their incidence or decrease the time taken for tumour formation. Often, exposure to chemical carcinogens results in tissue specific patterns of tumorigenicity. The very same anatomical, biochemical and physiological specialisations which permit the kidney [...] Read more.

Chemical carcinogens are substances which induce malignant tumours, increase their incidence or decrease the time taken for tumour formation. Often, exposure to chemical carcinogens results in tissue specific patterns of tumorigenicity. The very same anatomical, biochemical and physiological specialisations which permit the kidney to perform its vital roles in maintaining tissue homeostasis may in fact increase the risk of carcinogen exposure and contribute to the organ specific carcinogenicity observed with numerous kidney carcinogens. This review will address the numerous mechanisms which play a role in the concentration, bioactivation, and uptake of substances from both the urine and blood which significantly increase the risk of cancer in the kidney. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Organ-Specific Toxicity)

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18 pages, 478 KiB

Open AccessArticle

Systematic Exploration of Natural and Synthetic Flavonoids for the Inhibition of Staphylococcus aureus Biofilms

by Suvi Manner¹, Malena Skogman¹, Darla Goeres², Pia Vuorela^1,3 and Adyary Fallarero^1,*

¹ Pharmaceutical Sciences, Department of Biosciences, Abo Akademi University, Artillerigatan 6A, 3rd Floor, Biocity, Turku FI-20520, Finland

² Center for Biofilm Engineering, Montana State University, Bozeman, MT 59717, USA

³ Division of Pharmaceutical Biology, Faculty of Pharmacy, University of Helsinki, Viikinkaari 5E, P.O. Box 56, Helsinki FI-00014, Finland

Int. J. Mol. Sci. 2013, 14(10), 19434-19451; https://doi.org/10.3390/ijms141019434 - 25 Sep 2013

Cited by 99 | Viewed by 13073

Abstract

When single-cell (or suspended) bacteria switch into the biofilm lifestyle, they become less susceptible to antimicrobials, imposing the need for anti-biofilms research. Flavonoids are among the most extensively studied natural compounds with an unprecedented amount of bioactivity claims. Most studies focus on the [...] Read more.

When single-cell (or suspended) bacteria switch into the biofilm lifestyle, they become less susceptible to antimicrobials, imposing the need for anti-biofilms research. Flavonoids are among the most extensively studied natural compounds with an unprecedented amount of bioactivity claims. Most studies focus on the antibacterial effects against suspended cells; fewer reports have researched their anti-biofilm properties. Here, a high throughput phenotypic platform was utilized to screen for the inhibitory activity of 500 flavonoids, including natural and synthetic derivatives, against Staphylococcus aureus biofilms. Since discrepancies among results from earlier antibacterial studies on flavonoids had been noted, the current study aimed to minimize sources of variations. After the first screen, flavonoids were classified as inactive (443), moderately active (47) or highly active (10). Further, exclusion criteria combining bioactivity and selectivity identified two synthetic flavans as the most promising. The body of data reported here serves three main purposes. First, it offers an improved methodological workflow for anti-biofilm screens of chemical libraries taking into account the (many times ignored) connections between anti-biofilm and antibacterial properties. This is particularly relevant for the study of flavonoids and other natural products. Second, it provides a large and freely available anti-biofilm bioactivity dataset that expands the knowledge on flavonoids and paves the way for future structure-activity relationship studies and structural optimizations. Finally, it identifies two new flavans that can successfully act on biofilms, as well as on suspended bacteria and represent more feasible antibacterial candidates. Full article

(This article belongs to the Special Issue Biofilms: Extracellular Bastions of Bacteria)

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22 pages, 5028 KiB

Open AccessArticle

Mixtures of l-Amino Acids as Reaction Medium for Formation of Iron Nanoparticles: The Order of Addition into a Ferrous Salt Solution Matters

by Karolína M. Šišková^1,*, Libor Machala^2,†, Jiři Tuček^2,†, Josef Kašlík², Peter Mojzeš³ and Radek Zbořil¹

¹ Department of Physical Chemistry, Regional Centre of Advanced Technologies and Materials, Palacký University in Olomouc, 783 71 Olomouc, Czech Republic

² Department of Experimental Physics, Regional Centre of Advanced Technologies and Materials, Palacký University in Olomouc, 783 71 Olomouc, Czech Republic

³ Institute of Physics, Faculty of Mathematics and Physics, Charles University in Prague, Prague, Ke Karlovu 5, 121 16 Prague 2, Czech Republic

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2013, 14(10), 19452-19473; https://doi.org/10.3390/ijms141019452 - 25 Sep 2013

Cited by 11 | Viewed by 8248

Abstract

Owing to Mössbauer spectroscopy, an advanced characterization technique for iron-containing materials, the present study reveals previously unknown possibilities using l-amino acids for the generation of magnetic particles. Based on our results, a simple choice of the order of l-amino acids addition into a [...] Read more.

Owing to Mössbauer spectroscopy, an advanced characterization technique for iron-containing materials, the present study reveals previously unknown possibilities using l-amino acids for the generation of magnetic particles. Based on our results, a simple choice of the order of l-amino acids addition into a reaction mixture containing ferrous ions leads to either superparamagnetic ferric oxide/oxyhydroxide particles, or magnetically strong Fe⁰-Fe₂O₃/FeOOH core-shell particles after chemical reduction. Conversely, when ferric salts are employed with the addition of selected l-amino acids, only Fe⁰-Fe₂O₃/FeOOH core-shell particles are observed, regardless of the addition order. We explain this phenomenon by a specific transient/intermediate complex formation between Fe²⁺ and l-glutamic acid. This type of complexation prevents ferrous ions from spontaneous oxidation in solutions with full air access. Moreover, due to surface-enhanced Raman scattering spectroscopy we show that the functional groups of l-amino acids are not destroyed during the borohydride-induced reduction. These functionalities can be further exploited for (i) attachment of l-amino acids to the as-prepared magnetic particles, and (ii) for targeted bio- and/or environmental applications where the surface chemistry needs to be tailored and directed toward biocompatible species. Full article

(This article belongs to the Special Issue Magnetic Nanoparticles 2013)

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Graphical abstract

10 pages, 348 KiB

Open AccessArticle

Parts Per Trillion Detection of 7-Aminonitrazepam by Nano-Enhanced ELISA

by Chifang Peng^1,*

, Xiaohui Duan¹, Shanshan Song¹ and Feng Xue²

¹ State Key Lab of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi 214122, China

² Animal, Plant & Food Inspection Center, Jiangsu Entry-Exit Inspection and Quarantine Bureau, Nanjing 200001, China

Int. J. Mol. Sci. 2013, 14(10), 19474-19483; https://doi.org/10.3390/ijms141019474 - 25 Sep 2013

Cited by 9 | Viewed by 7631

Abstract

It is challenging to detect 7-aminonitrazepam (7-ANZP) residue in animal tissues simply and sensitively by the enzyme-linked sorbent immunoassay (ELISA) method. This paper demonstrates that utilizing a bioconjugate of gold nanoparticles and enzyme-labeled antibody as a signal probe increases the sensitivity of a [...] Read more.

It is challenging to detect 7-aminonitrazepam (7-ANZP) residue in animal tissues simply and sensitively by the enzyme-linked sorbent immunoassay (ELISA) method. This paper demonstrates that utilizing a bioconjugate of gold nanoparticles and enzyme-labeled antibody as a signal probe increases the sensitivity of a traditional ELISA for 7-ANZP by nearly 20 times. The sensitivity of this ELISA for 7-ANZP was 5.6 pg/mL in buffer, and the limit of detection (LOD) of 0.18 µg/kg for 7-ANZP in urine could be achieved after the urine samples were simply hydrolyzed and diluted by buffer. This simple and sensitive method has potential application for improving the sensitivity of ELISA methods against various small molecules. Full article

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

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Graphical abstract

10 pages, 467 KiB

Open AccessArticle

Semisynthesis and Antifeedant Activity of New Derivatives of a Dihydro-β-Agarofuran from Parnassia wightiana

by Jiang-Jiang Tang^1,†, Fei-Yu Zhang^1,†, Dong-Mei Wang², Jun-Mian Tian¹, Shuai Dong¹ and Jin-Ming Gao^1,*

¹ Shaanxi Engineering Center of Bioresource Chemistry & Sustainable Utilization, College of Science, Northwest A&F University, Yangling 712100, Shaanxi, China

² College of Forestry, Northwest A&F University, Yangling 712100, Shaanxi, China

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2013, 14(10), 19484-19493; https://doi.org/10.3390/ijms141019484 - 26 Sep 2013

Cited by 21 | Viewed by 5953

Abstract

Five new derivatives (2–6) were semi-synthesized using compound 1, a dihydro-β-agarofuran sesquiterpene with C-2 ketone obtained from Parnassia wightiana, as the starting material by acylation, oxidation, reduction, esterification, and amination, respectively. Structures of 2–6 were [...] Read more.

Five new derivatives (2–6) were semi-synthesized using compound 1, a dihydro-β-agarofuran sesquiterpene with C-2 ketone obtained from Parnassia wightiana, as the starting material by acylation, oxidation, reduction, esterification, and amination, respectively. Structures of 2–6 were confirmed by 1D- and 2D-NMR and HR-ESI-MS spectra. In addition, antifeedant activities of these compounds (1–6) were tested against the 3rd-instar larvae of Mythimna separata. Antifeedant effects of compounds 2 and 4 were greater than the parent compound 1 whereas other compounds exhibited low to no feeding deterrent effects against third instar M. separata larvae in lab bioassays. Therefore, our results suggest that acylated and reduced derivatives at C-8 and C-2, respectively, of 1 may improve the antifeeding effect. This preliminary information will be useful in designing new insect control agents against M. separata and other important pests. Full article

(This article belongs to the Section Biochemistry)

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12 pages, 293 KiB

Open AccessReview

Molecular Research in Penile Cancer—Lessons Learned from the Past and Bright Horizons of the Future?

by Chris Protzel¹ and Philippe E. Spiess^2,*

¹ Department of Urology, University of Rostock, Rostock 18055, Germany

² Department of Genitourinary Oncology, Moffitt Cancer Center, Tampa, FL 33612, USA

Int. J. Mol. Sci. 2013, 14(10), 19494-19505; https://doi.org/10.3390/ijms141019494 - 26 Sep 2013

Cited by 15 | Viewed by 7217

Abstract

Penile cancer is a rare tumor. There is a limited understanding of the biological mediators of prognostic and therapeutic importance in penile cancer. However, there exists some fundamental understanding of the major pathways involved in the development of penile pre-neoplastic lesions and neoplasms. [...] Read more.

Penile cancer is a rare tumor. There is a limited understanding of the biological mediators of prognostic and therapeutic importance in penile cancer. However, there exists some fundamental understanding of the major pathways involved in the development of penile pre-neoplastic lesions and neoplasms. The aim of the present review is to highlight our current state of molecular knowledge in penile cancer to foster the necessary tools for researchers to pave major advancements in our current treatment paradigms and cancer specific outcomes. Full article

(This article belongs to the Special Issue Molecular Research in Urology)

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20 pages, 2724 KiB

Open AccessReview

Single Molecule Studies on Dynamics in Liquid Crystals

by Daniela Täuber^* and Christian Von Borczyskowski

Institute of Physics and nanoMA, Technische Universität Chemnitz, Chemnitz D-09107, Germany

Int. J. Mol. Sci. 2013, 14(10), 19506-19525; https://doi.org/10.3390/ijms141019506 - 26 Sep 2013

Cited by 11 | Viewed by 8551

Abstract

Single molecule (SM) methods are able to resolve structure related dynamics of guest molecules in liquid crystals (LC). Highly diluted small dye molecules on the one hand explore structure formation and LC dynamics, on the other hand they report about a distortion caused [...] Read more.

Single molecule (SM) methods are able to resolve structure related dynamics of guest molecules in liquid crystals (LC). Highly diluted small dye molecules on the one hand explore structure formation and LC dynamics, on the other hand they report about a distortion caused by the guest molecules. The anisotropic structure of LC materials is used to retrieve specific conformation related properties of larger guest molecules like conjugated polymers. This in particular sheds light on organization mechanisms within biological cells, where large molecules are found in nematic LC surroundings. This review gives a short overview related to the application of highly sensitive SM detection schemes in LC. Full article

(This article belongs to the Special Issue Experimental and Theoretical Studies of Liquid Crystalline Materials: Where Do We Stand after 120 Years?)

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14 pages, 283 KiB

Open AccessArticle

Synthesis and Activity of Novel Acylthiourea with Hydantoin

by Jintao Han¹, Hongbo Dong¹, Zhihong Xu^1,2, Jinmin Wang¹ and Mingan Wang^1,*

¹ Department of Applied Chemistry, China Agricultural University, Beijing 100193, China

² College of Agricuture, Yangtze University, Jingzhou 434025, Hubei, China

Int. J. Mol. Sci. 2013, 14(10), 19526-19539; https://doi.org/10.3390/ijms141019526 - 26 Sep 2013

Cited by 20 | Viewed by 5631

Abstract

The 41 novel acylthiourea derivatives with hydantoin were synthesized in moderate to excellent yields by using 5-(4-aminophenyl)- and 5-(4-aminobenzyl)-hydantoin or 5-(4-aminobenzyl)-thiohydantoin as raw materials and characterized by IR, ¹H NMR spectra and elementary analysis. The preliminary bioassay showed that these compounds exhibit [...] Read more.

The 41 novel acylthiourea derivatives with hydantoin were synthesized in moderate to excellent yields by using 5-(4-aminophenyl)- and 5-(4-aminobenzyl)-hydantoin or 5-(4-aminobenzyl)-thiohydantoin as raw materials and characterized by IR, ¹H NMR spectra and elementary analysis. The preliminary bioassay showed that these compounds exhibit certain selectively herbicidal activities with the 91%, 94% and 87% inhibition rates of 7l, 8o and 8p against B. campestris, 100%, 100% and 95% efficacy against B. campestris in a greenhouse test, respectively. 7a, 7b, 7c and 7d exhibited 74%, 79%, 79% and 71% inhibition rates against F. oxysporum, respectively. Full article

(This article belongs to the Section Materials Science)

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16 pages, 3513 KiB

Open AccessArticle

Isolation and Characterization of Squamous Cell Carcinoma-Derived Stem-like Cells: Role in Tumor Formation

by Katiuscia Dallaglio^1,†, Tiziana Petrachi^1,†, Alessandra Marconi¹

, Francesca Truzzi¹, Roberta Lotti¹, Annalisa Saltari¹, Paolo Morandi¹, Mario Puviani², Antonino Maiorana³, Dennis R. Roop⁴ and Carlo Pincelli^1,*

¹ Department of Dermatology, University of Modena and Reggio Emilia, Via del Pozzo 71, 41124 Modena, Italy

² Ospedale Civile di Sassuolo, Via Francesco Ruini, 2, 41049 Sassuolo (MO), Italy

³ Department of Laboratories and Pathologic Anatomy, University of Modena and Reggio Emilia, Via del Pozzo 71, 41124 Modena, Italy

⁴ Charles C. Gates Center for Regenerative Medicine and Stem Cell Biology, Department of Dermatology, University of Colorado, Denver, CO 80045, USA

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2013, 14(10), 19540-19555; https://doi.org/10.3390/ijms141019540 - 26 Sep 2013

Cited by 8 | Viewed by 7415

Abstract

In human epidermis, keratinocyte stem cells (KSC) are characterized by high levels of β₁-integrin, resulting in the rapid adhesion to type IV collagen. Since epithelial tumors originate from KSC, we evaluated the features of rapidly adhering (RAD) keratinocytes derived from primary [...] Read more.

In human epidermis, keratinocyte stem cells (KSC) are characterized by high levels of β₁-integrin, resulting in the rapid adhesion to type IV collagen. Since epithelial tumors originate from KSC, we evaluated the features of rapidly adhering (RAD) keratinocytes derived from primary human squamous cell carcinoma of the skin (cSCC). RAD cells expressed higher levels of survivin, a KSC marker, as compared to non-rapidly adhering (NRAD) cells. Moreover, RAD cells proliferated to a greater extent and were more efficient in forming colonies than NRAD cells. RAD cells also migrated significantly better than NRAD cells. When seeded in a silicone chamber and grafted onto the back skin of NOD SCID mice, RAD cells formed tumors 2–4 fold bigger than those derived from NRAD cells. In tumors derived from RAD cells, the mitotic index was significantly higher than in those derived from NRAD cells, while Ki-67 and survivin expression were more pronounced in RAD tumors. This study suggests that SCC RAD stem cells play a critical role in the formation and development of epithelial tumors. Full article

(This article belongs to the Section Biochemistry)

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31 pages, 5891 KiB

Open AccessArticle

Investigations of the Binding of [Pt₂(DTBPA)Cl₂](II) and [Pt₂(TPXA)Cl₂](II) to DNA via Various Cross-Linking Modes

by Hongwei Yue, Bo Yang, Yan Wang^* and Guangju Chen^*

College of Chemistry, Beijing Normal University, Beijing 100875, China

Int. J. Mol. Sci. 2013, 14(10), 19556-19586; https://doi.org/10.3390/ijms141019556 - 26 Sep 2013

Cited by 5 | Viewed by 8524

Abstract

We have constructed models for a series of platinum-DNA adducts that represent the binding of two agents, [Pt₂(DTBPA)Cl₂](II) and [Pt₂(TPXA)Cl₂](II), to DNA via inter- and intra-strand cross-linking, and carried out molecular dynamics simulations and DNA [...] Read more.

We have constructed models for a series of platinum-DNA adducts that represent the binding of two agents, [Pt₂(DTBPA)Cl₂](II) and [Pt₂(TPXA)Cl₂](II), to DNA via inter- and intra-strand cross-linking, and carried out molecular dynamics simulations and DNA conformational dynamics calculations. The effects of trans- and cis-configurations of the centers of these di-nuclear platinum agents, and of different bridging linkers, have been investigated on the conformational distortions of platinum-DNA adducts formed via inter- and intra-strand cross-links. The results demonstrate that the DNA conformational distortions for the various platinum-DNA adducts with differing cross-linking modes are greatly influenced by the difference between the platinum-platinum distance for the platinum agent and the platinum-bound N7–N7 distance for the DNA molecule, and by the flexibility of the bridging linkers in the platinum agent. However, the effects of trans/cis-configurations of the platinum-centers on the DNA conformational distortions in the platinum-DNA adducts depend on the inter- and intra-strand cross-linking modes. In addition, we discuss the relevance of DNA base motions, including opening, shift and roll, to the changes in the parameters of the DNA major and minor grooves caused by binding of the platinum agent. Full article

(This article belongs to the Special Issue Proteins and Protein-Ligand Interactions)

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18 pages, 824 KiB

Open AccessArticle

Regulation of MIR Genes in Response to Abiotic Stress in Hevea brasiliensis

by Virginie Gébelin^1,†, Julie Leclercq^1,†, Songnian Hu²

, Chaorong Tang³ and Pascal Montoro^1,*

¹ Centre de Coopération Internationale en Recherche Agronomique Pour le Développement, Unité Mixte de Recherche Amélioration Génétique et Adaptation des Plantes Méditerranéennes et Tropicales, Avenue Agropolis, Montpellier F-34398, France

² Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100029, China

³ Rubber Research Institute, Chinese Academy of Tropical Agricultural Sciences, Danzhou 531737, China

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2013, 14(10), 19587-19604; https://doi.org/10.3390/ijms141019587 - 27 Sep 2013

Cited by 27 | Viewed by 7949

Abstract

Increasing demand for natural rubber (NR) calls for an increase in latex yield and also an extension of rubber plantations in marginal zones. Both harvesting and abiotic stresses lead to tapping panel dryness through the production of reactive oxygen species. Many microRNAs regulated [...] Read more.

Increasing demand for natural rubber (NR) calls for an increase in latex yield and also an extension of rubber plantations in marginal zones. Both harvesting and abiotic stresses lead to tapping panel dryness through the production of reactive oxygen species. Many microRNAs regulated during abiotic stress modulate growth and development. The objective of this paper was to study the regulation of microRNAs in response to different types of abiotic stress and hormone treatments in Hevea. Regulation of MIR genes differs depending on the tissue and abiotic stress applied. A negative co-regulation between HbMIR398b with its chloroplastic HbCuZnSOD target messenger is observed in response to salinity. The involvement of MIR gene regulation during latex harvesting and tapping panel dryness (TPD) occurrence is further discussed. Full article

(This article belongs to the Special Issue Regulation by non-coding RNAs 2013)

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13 pages, 664 KiB

Open AccessArticle

Histone Deacetylase Inhibition Downregulates Collagen 3A1 in Fibrotic Lung Fibroblasts

by Xiangyu Zhang^†, Hui Liu, Thomas Hock, Victor J. Thannickal and Yan Y. Sanders^*

¹ Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA

^† Current address: Department of Geriatrics, 2nd Xiangya Hospital of Central South University, Changsha, Hunan 41001, China.

Int. J. Mol. Sci. 2013, 14(10), 19605-19617; https://doi.org/10.3390/ijms141019605 - 27 Sep 2013

Cited by 58 | Viewed by 8412

Abstract

Idiopathic pulmonary fibrosis (IPF) is a deadly disease characterized by chronic inflammation and excessive collagen accumulation in the lung. Myofibroblasts are the primary collagen-producing cells in pulmonary fibrosis. Histone deacetylase inhibitor (HDACi) can affect gene expression, and some, such as suberoylanilide hydroxamic acid [...] Read more.

Idiopathic pulmonary fibrosis (IPF) is a deadly disease characterized by chronic inflammation and excessive collagen accumulation in the lung. Myofibroblasts are the primary collagen-producing cells in pulmonary fibrosis. Histone deacetylase inhibitor (HDACi) can affect gene expression, and some, such as suberoylanilide hydroxamic acid (SAHA), are US FDA approved for cancer treatment. In this study, we investigated SAHA’s effects on the expression of collagen III alpha 1 (COL3A1) in primary human IPF fibroblasts and in a murine model of pulmonary fibrosis. We observed that increased COL3A1 expression in IPF fibroblasts can be substantially reduced by SAHA treatment at the level of transcription as detected by RT-PCR; collagen III protein level was also reduced, as detected by Western blots and immunofluorescence. The deacetylation inhibitor effect of SAHA was verified by observing higher acetylation levels of both histone H3 and H4 in treated IPF cells. Chromatin immunoprecipitation (ChIP) experiments demonstrated that the reduced expression of COL3A1 by SAHA is with increased association of the repressive chromatin marker, H3K27Me3, and decreased association of the active chromatin marker, H3K9Ac. In our murine model of bleomycin-induced pulmonary fibrosis, the SAHA treated group demonstrated significantly less collagen III, as detected by immunohistochemistry. Our data indicate that the HDACi SAHA alters the chromatin associated with COL3A1, resulting in its decreased expression. Full article

(This article belongs to the Section Biochemistry)

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18 pages, 2141 KiB

Open AccessArticle

A Combination of Pre- and Post-Exposure Ascorbic Acid Rescues Mice from Radiation-Induced Lethal Gastrointestinal Damage

by Yasutoshi Ito¹, Manabu Kinoshita^2,*, Tetsuo Yamamoto¹, Tomohito Sato¹, Takeyuki Obara¹, Daizoh Saitoh³, Shuhji Seki² and Yukihiro Takahashi¹

¹ Military Medicine Research Unit, Test and Evaluation Command, Ground Self-Defense Force, 1-2-24 Ikejiri, Setagaya, Tokyo 154-8566, Japan

² Department of Immunology and Microbiology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8613, Japan

³ Division of Traumatology, Research Institute, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8613, Japan

Int. J. Mol. Sci. 2013, 14(10), 19618-19635; https://doi.org/10.3390/ijms141019618 - 27 Sep 2013

Cited by 27 | Viewed by 9858

Abstract

The development of an effective therapy for radiation-induced gastrointestinal damage is important, because it is currently a major complication of treatment and there are few effective therapies available. Although we have recently demonstrated that pretreatment with ascorbic acid attenuates lethal gastrointestinal damage in [...] Read more.

The development of an effective therapy for radiation-induced gastrointestinal damage is important, because it is currently a major complication of treatment and there are few effective therapies available. Although we have recently demonstrated that pretreatment with ascorbic acid attenuates lethal gastrointestinal damage in irradiated mice, more than half of mice eventually died, thus indicating that better approach was needed. We then investigated a more effective therapy for radiation-induced gastrointestinal damage. Mice receiving abdominal radiation at 13 Gy were orally administered ascorbic acid (250 mg/kg/day) for three days before radiation (pretreatment), one shot of engulfment (250 mg/kg) at 8 h before radiation, or were administered the agent for seven days after radiation (post-treatment). None of the control mice survived the abdominal radiation at 13 Gy due to severe gastrointestinal damage (without bone marrow damage). Neither pretreatment with ascorbic acid (20% survival), engulfment (20%), nor post-treatment (0%) was effective in irradiated mice. However, combination therapy using ascorbic acid, including pretreatment, engulfment and post-treatment, rescued all of the mice from lethal abdominal radiation, and was accompanied by remarkable improvements in the gastrointestinal damage (100% survival). Omitting post-treatment from the combination therapy with ascorbic acid markedly reduced the mouse survival (20% survival), suggesting the importance of post-treatment with ascorbic acid. Combination therapy with ascorbic acid may be a potent therapeutic tool for radiation-induced gastrointestinal damage. Full article

(This article belongs to the Collection Radiation Toxicity in Cells)

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15 pages, 535 KiB

Open AccessArticle

Chitosan-Coated Magnetic Nanoparticles Prepared in One Step by Reverse Microemulsion Precipitation

by Raúl G. López^*, María G. Pineda^†, Gilberto Hurtado, Ramón Díaz de León, Salvador Fernández^†, Hened Saade^† and Darío Bueno

¹ Centro de Investigación en Química Aplicada, Blvd. Enrique Reyna 140, Saltillo 25294, Coahuila, Mexico

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2013, 14(10), 19636-19650; https://doi.org/10.3390/ijms141019636 - 27 Sep 2013

Cited by 68 | Viewed by 9947

Abstract

Chitosan-coated magnetic nanoparticles (CMNP) were obtained at 70 °C and 80 °C in a one-step method, which comprises precipitation in reverse microemulsion in the presence of low chitosan concentration in the aqueous phase. X-ray diffractometry showed that CMNP obtained at both temperatures contain [...] Read more.

Chitosan-coated magnetic nanoparticles (CMNP) were obtained at 70 °C and 80 °C in a one-step method, which comprises precipitation in reverse microemulsion in the presence of low chitosan concentration in the aqueous phase. X-ray diffractometry showed that CMNP obtained at both temperatures contain a mixture of magnetite and maghemite nanoparticles with ≈4.5 nm in average diameter, determined by electron microscopy, which suggests that precipitation temperature does not affect the particle size. The chitosan coating on nanoparticles was inferred from Fourier transform infrared spectrometry measurements; furthermore, the carbon concentration in the nanoparticles allowed an estimation of chitosan content in CMNP of 6%–7%. CMNP exhibit a superparamagnetic behavior with relatively high final magnetization values (≈49–53 emu/g) at 20 kOe and room temperature, probably due to a higher magnetite content in the mixture of magnetic nanoparticles. In addition, a slight direct effect of precipitation temperature on magnetization was identified, which was ascribed to a possible higher degree of nanoparticles crystallinity as temperature at which they are obtained increases. Tested for Pb²⁺ removal from a Pb(NO₃)₂ aqueous solution, CMNP showed a recovery efficacy of 100%, which makes them attractive for using in heavy metals ion removal from waste water. Full article

(This article belongs to the Special Issue Magnetic Nanoparticles 2013)

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19 pages, 319 KiB

Open AccessReview

Advanced Knowledge of Three Important Classes of Grape Phenolics: Anthocyanins, Stilbenes and Flavonols

by Riccardo Flamini^1,*, Fulvio Mattivi², Mirko De Rosso¹, Panagiotis Arapitsas²

and Luigi Bavaresco¹

¹ Consiglio per la Ricerca e la Sperimentazione in Agricoltura-Centro di Ricerca per la Viticoltura (CRA-VIT), Viale XXVIII aprile, Conegliano 26-31015, TV, Italy

² IASMA Research and Innovation Centre, Fondazione Edmund Mach, San Michele all'Adige 38010, TN, Italy

Int. J. Mol. Sci. 2013, 14(10), 19651-19669; https://doi.org/10.3390/ijms141019651 - 27 Sep 2013

Cited by 333 | Viewed by 21381

Abstract

Grape is qualitatively and quantitatively very rich in polyphenols. In particular, anthocyanins, flavonols and stilbene derivatives play very important roles in plant metabolism, thanks to their peculiar characteristics. Anthocyanins are responsible for the color of red grapes and wines and confer organoleptic characteristics [...] Read more.

Grape is qualitatively and quantitatively very rich in polyphenols. In particular, anthocyanins, flavonols and stilbene derivatives play very important roles in plant metabolism, thanks to their peculiar characteristics. Anthocyanins are responsible for the color of red grapes and wines and confer organoleptic characteristics on the wine. They are used for chemotaxonomic studies and to evaluate the polyphenolic ripening stage of grape. They are natural colorants, have antioxidant, antimicrobial and anticarcinogenic activity, exert protective effects on the human cardiovascular system, and are used in the food and pharmaceutical industries. Stilbenes are vine phytoalexins present in grape berries and associated with the beneficial effects of drinking wine. The principal stilbene, resveratrol, is characterized by anticancer, antioxidant, anti-inflammatory and cardioprotective activity. Resveratrol dimers and oligomers also occur in grape, and are synthetized by the vine as active defenses against exogenous attack, or produced by extracellular enzymes released from pathogens in an attempt to eliminate undesirable toxic compounds. Flavonols are a ubiquitous class of flavonoids with photo-protection and copigmentation (together with anthocyanins) functions. The lack of expression of the enzyme flavonoid 3',5'-hydroxylase in white grapes restricts the presence of these compounds to quercetin, kaempferol and isorhamnetin derivatives, whereas red grapes usually also contain myricetin, laricitrin and syringetin derivatives. In the last ten years, the technological development of analytical instrumentation, particularly mass spectrometry, has led to great improvements and further knowledge of the chemistry of these compounds. In this review, the biosynthesis and biological role of these grape polyphenols are briefly introduced, together with the latest knowledge of their chemistry. Full article

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

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11 pages, 1265 KiB

Open AccessArticle

BTG1 Expression Correlates with the Pathogenesis and Progression of Ovarian Carcinomas

by Yang Zhao¹, Wen-Feng Gou², Shuo Chen¹, Yasuo Takano³, Yin-Ling Xiu¹ and Hua-Chuan Zheng^2,*

¹ Department of Gynecology, the First Affiliated Hospital of China Medical University, Shenyang 110001, China

² Department of Biochemistry and Molecular Biology, Institute of Pathology and Pathophysiology, College of Basic Medicine, China Medical University, Shenyang 110001, China

³ Clinical Cancer Institute, Kanagawa Cancer Center, Yokohama 241-0815, Japan

Int. J. Mol. Sci. 2013, 14(10), 19670-19680; https://doi.org/10.3390/ijms141019670 - 27 Sep 2013

Cited by 28 | Viewed by 7038

Abstract

BTG (B-cell translocation gene) can inhibit cell proliferation, metastasis, and angiogenesis and regulate cell cycle progression and differentiation in a variety of cell types. We aimed to clarify the role of BTG1 in ovarian carcinogenesis and progression. A BTG1-expressing plasmid was transfected [...] Read more.

BTG (B-cell translocation gene) can inhibit cell proliferation, metastasis, and angiogenesis and regulate cell cycle progression and differentiation in a variety of cell types. We aimed to clarify the role of BTG1 in ovarian carcinogenesis and progression. A BTG1-expressing plasmid was transfected into ovarian carcinoma cells and their phenotypes and related proteins were examined. BTG1 mRNA expression was detected in ovarian normal tissue (n = 17), ovarian benign tumors (n = 12), and ovarian carcinoma (n = 64) using real-time RT-PCR. Ectopic BTG1 expression resulted in lower growth rate, high cisplatin sensitivity, G₁ arrest, apoptosis, and decreased migration and invasion. Phosphoinositide 3-kinase, protein kinase B, Bcl-xL, survivin, vascular endothelial growth factor, and matrix metalloproteinase-2 mRNA and protein expression was reduced in transfectants as compared to control cells. There was higher expression of BTG1 mRNA in normal tissue than in carcinoma tissue (p = 0.001) and in benign tumors than in carcinoma tissue (p = 0.027). BTG1 mRNA expression in International Federation of Gynecology and Obstetrics (FIGO) stage I/II ovarian carcinomas was higher than that in FIGO stage III/IV ovarian carcinomas (p = 0.038). Altered BTG1 expression might play a role in the pathogenesis and progression of ovarian carcinoma by modulating proliferation, migration, invasion, the cell cycle, and apoptosis. Full article

(This article belongs to the Special Issue Advances in Cancer Diagnosis)

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24 pages, 287 KiB

Open AccessReview

Non-Coding RNAs in Muscle Dystrophies

by Daniela Erriquez¹, Giovanni Perini^1,2,* and Alessandra Ferlini^3,*

¹ Department of Pharmacy and Biotechnology, University of Bologna, Bologna 40126, Italy

² Health Sciences and Technologies–Interdepartmental Center for Industrial Research, University of Bologna, Bologna 40064, Italy

³ Section of Microbiology and Medical Genetics, Department of Medical Sciences, University of Ferrara, Ferrara 44100, Italy

Int. J. Mol. Sci. 2013, 14(10), 19681-19704; https://doi.org/10.3390/ijms141019681 - 30 Sep 2013

Cited by 21 | Viewed by 9970

Abstract

ncRNAs are the most recently identified class of regulatory RNAs with vital functions in gene expression regulation and cell development. Among the variety of roles they play, their involvement in human diseases has opened new avenues of research towards the discovery and development [...] Read more.

ncRNAs are the most recently identified class of regulatory RNAs with vital functions in gene expression regulation and cell development. Among the variety of roles they play, their involvement in human diseases has opened new avenues of research towards the discovery and development of novel therapeutic approaches. Important data come from the field of hereditary muscle dystrophies, like Duchenne muscle dystrophy and Myotonic dystrophies, rare diseases affecting 1 in 7000–15,000 newborns and is characterized by severe to mild muscle weakness associated with cardiac involvement. Novel therapeutic approaches are now ongoing for these diseases, also based on splicing modulation. In this review we provide an overview about ncRNAs and their behavior in muscular dystrophy and explore their links with diagnosis, prognosis and treatments, highlighting the role of regulatory RNAs in these pathologies. Full article

(This article belongs to the Special Issue Regulation by non-coding RNAs 2013)

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11 pages, 589 KiB

Open AccessArticle

The COX-2 Selective Blocker Etodolac Inhibits TNFα-Induced Apoptosis in Isolated Rabbit Articular Chondrocytes

by Kousuke Kumagai^1,2,*, Mitsuhiko Kubo¹, Shinji Imai¹, Futoshi Toyoda², Tsutomu Maeda^1,2, Noriaki Okumura¹, Hiroshi Matsuura² and Yoshitaka Matsusue¹

¹ Department of Orthopaedic Surgery, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan

² Department of Physiology, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan

Int. J. Mol. Sci. 2013, 14(10), 19705-19715; https://doi.org/10.3390/ijms141019705 - 30 Sep 2013

Cited by 15 | Viewed by 6657

Abstract

Chondrocyte apoptosis contributes to the disruption of cartilage integrity in osteoarthritis (OA). Recently, we reported that activation of volume-sensitive Cl⁻ current (I_Cl,vol) mediates cell shrinkage, triggering apoptosis in rabbit articular chondrocytes. A cyclooxygenase (COX) blocker is frequently used for [...] Read more.

Chondrocyte apoptosis contributes to the disruption of cartilage integrity in osteoarthritis (OA). Recently, we reported that activation of volume-sensitive Cl⁻ current (I_Cl,vol) mediates cell shrinkage, triggering apoptosis in rabbit articular chondrocytes. A cyclooxygenase (COX) blocker is frequently used for the treatment of OA. In the present study, we examined in vitro effects of selective blockers of COX on the TNFα-induced activation of I_Cl,vol in rabbit chondrocytes using the patch-clamp technique. Exposure of isolated chondrocytes to TNFα resulted in an obvious increase in membrane Cl⁻ conductance. The TNFα-evoked Cl⁻ current exhibited electrophysiological and pharmacological properties similar to those of I_Cl,vol. Pretreatment of cells with selective COX-2 blocker etodolac markedly inhibited I_Cl,vol activation by TNFα as well as subsequent apoptotic events such as apoptotic cell volume decrease (AVD) and elevation of caspase-3/7 activity. In contrast, a COX-1 blocker had no effect on the decrease in cell volume or the increase in caspase-3/7 activity induced by TNFα. Thus, the COX-2-selective blocker had an inhibitory effect on TNFα-induced apoptotic events, which suggests that this drug would have efficacy for the treatment of OA. Full article

(This article belongs to the Special Issue The Chondrocyte Phenotype in Cartilage Biology)

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15 pages, 2106 KiB

Open AccessTechnical Note

A Computational Drug Metabolite Detection Using the Stable Isotopic Mass-Shift Filtering with High Resolution Mass Spectrometry in Pioglitazone and Flurbiprofen

by Masashi Uchida¹, Mitsuhiro Kanazawa², Atsushi Ogiwara², Hiroshi Sezaki³, Akihiro Ando¹ and Yohei Miyamoto^1,*

¹ Toxicology and Pharmacokinetics Laboratories, Pharmaceutical Research Laboratories, Toray Industries, Inc., 6-10-1 Tebiro, Kamakura, Kanagawa 248-8555, Japan

² Reifycs Inc., AIOS Toranomon 10F, 1-6-12 Nishishinbashi, Minato-ku, Tokyo 105-0003, Japan

³ Measurement Assistance Center, Agilent Technologies Japan, Ltd., 9-1 Takakura, Hachioji, Tokyo 192-8510, Japan

Int. J. Mol. Sci. 2013, 14(10), 19716-19730; https://doi.org/10.3390/ijms141019716 - 30 Sep 2013

Cited by 3 | Viewed by 7493

Abstract

The identification of metabolites in drug discovery is important. At present, radioisotopes and mass spectrometry are both widely used. However, rapid and comprehensive identification is still laborious and difficult. In this study, we developed new analytical software and employed a stable isotope as [...] Read more.

The identification of metabolites in drug discovery is important. At present, radioisotopes and mass spectrometry are both widely used. However, rapid and comprehensive identification is still laborious and difficult. In this study, we developed new analytical software and employed a stable isotope as a tool to identify drug metabolites using mass spectrometry. A deuterium-labeled compound and non-labeled compound were both metabolized in human liver microsomes and analyzed by liquid chromatography/time-of-flight mass spectrometry (LC-TOF-MS). We computationally aligned two different MS data sets and filtered ions having a specific mass-shift equal to masses of labeled isotopes between those data using our own software. For pioglitazone and flurbiprofen, eight and four metabolites, respectively, were identified with calculations of mass and formulas and chemical structural fragmentation analysis. With high resolution MS, the approach became more accurate. The approach detected two unexpected metabolites in pioglitazone, i.e., the hydroxypropanamide form and the aldehyde hydrolysis form, which other approaches such as metabolite-biotransformation list matching and mass defect filtering could not detect. We demonstrated that the approach using computational alignment and stable isotopic mass-shift filtering has the ability to identify drug metabolites and is useful in drug discovery. Full article

(This article belongs to the Special Issue Xenobiotic Metabolism)

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32 pages, 565 KiB

Open AccessReview

Carcinogenesis of Pancreatic Adenocarcinoma: Precursor Lesions

by Antonio Gnoni¹, Antonella Licchetta¹, Aldo Scarpa²

, Amalia Azzariti³, Anna Elisabetta Brunetti⁴, Gianni Simone⁵, Patrizia Nardulli⁶, Daniele Santini⁷, Michele Aieta⁸, Sabina Delcuratolo⁴ and Nicola Silvestris^9,*

¹ Medical Oncology Unit, Hospital Vito Fazzi, Lecce 73100, Italy

² Department of Pathology and Diagnostics, University of Verona, Verona 37121, Italy

³ Clinical and Preclinical Pharmacology Laboratory, National Cancer Research Centre Istituto Tumori "Giovanni Paolo II", Bari 70124, Italy

⁴ Scientific Direction, National Cancer Research Centre Istituto Tumori "Giovanni Paolo II", Bari 70124, Italy

⁵ Histopathology Unit, National Cancer Research Centre Istituto Tumori "Giovanni Paolo II", Bari 70124, Italy

⁶ Hospital Pharmacy Unit - National Cancer Research Centre Istituto Tumori "Giovanni Paolo II", Bari 70124, Italy

⁷ Medical Oncology Department, University Campus Bio-Medico, Rome 00199, Italy

⁸ Medical Oncology Unit - CROB-IRCCS, 85028, Rionero in Vulture, Potenza 85100, Italy

⁹ Medical Oncology Unit, National Cancer Research Centre Istituto Tumori "Giovanni Paolo II", Viale Orazio Flacco 65, Bari 70124, Italy

Int. J. Mol. Sci. 2013, 14(10), 19731-19762; https://doi.org/10.3390/ijms141019731 - 30 Sep 2013

Cited by 53 | Viewed by 11690

Abstract

Pancreatic adenocarcinoma displays a variety of molecular changes that evolve exponentially with time and lead cancer cells not only to survive, but also to invade the surrounding tissues and metastasise to distant sites. These changes include: genetic alterations in oncogenes and cancer suppressor [...] Read more.

Pancreatic adenocarcinoma displays a variety of molecular changes that evolve exponentially with time and lead cancer cells not only to survive, but also to invade the surrounding tissues and metastasise to distant sites. These changes include: genetic alterations in oncogenes and cancer suppressor genes; changes in the cell cycle and pathways leading to apoptosis; and also changes in epithelial to mesenchymal transition. The most common alterations involve the epidermal growth factor receptor (EGFR) gene, the HER2 gene, and the K-ras gene. In particular, the loss of function of tumor-suppressor genes has been documented in this tumor, especially in CDKN2a, p53, DPC4 and BRCA2 genes. However, other molecular events involved in pancreatic adenocarcinoma pathogenesis contribute to its development and maintenance, specifically epigenetic events. In fact, key tumor suppressors that are well established to play a role in pancreatic adenocarcinoma may be altered through hypermethylation, and oncogenes can be upregulated secondary to permissive histone modifications. Indeed, factors involved in tumor invasiveness can be aberrantly expressed through dysregulated microRNAs. This review summarizes current knowledge of pancreatic carcinogenesis from its initiation within a normal cell until the time that it has disseminated to distant organs. In this scenario, highlighting these molecular alterations could provide new clinical tools for early diagnosis and new effective therapies for this malignancy. Full article

(This article belongs to the Special Issue Molecular Bases of Cancer Research)

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11 pages, 136 KiB

Open AccessArticle

Preparation and Characterization of Nanoliposomes Entrapping Medium-Chain Fatty Acids and Vitamin C by Lyophilization

by Shuibing Yang^1,2, Chengmei Liu³, Wei Liu³, Haixia Yu², Huijuan Zheng³, Wei Zhou³ and Yaqin Hu^1,*

¹ Department of Food Science and Nutrition, Zhejiang Key Laboratory for Agro-Food Processing, Fuli Institute of Food Science, Zhejiang University, Hangzhou 310058, China

² Ocean Research Center of Zhoushan, Zhejiang University, Zhoushan 316021, China

³ State Key Laboratory of Food Science and Technology, Department of Life Science and Food Engineering, Nanchang University, Nanchang 330047, China

Int. J. Mol. Sci. 2013, 14(10), 19763-19773; https://doi.org/10.3390/ijms141019763 - 30 Sep 2013

Cited by 64 | Viewed by 8664

Abstract

The complex nanoliposomes encapsulating both a hydrophilic drug vitamin C (vit C) and hydrophobic drug medium-chain fatty acids (MCFAs) was prepared by combining double emulsion method with dynamic high pressure microfluidization. The complex nanoliposomes was further freeze-dried under −86 °C for 48 h [...] Read more.

The complex nanoliposomes encapsulating both a hydrophilic drug vitamin C (vit C) and hydrophobic drug medium-chain fatty acids (MCFAs) was prepared by combining double emulsion method with dynamic high pressure microfluidization. The complex nanoliposomes was further freeze-dried under −86 °C for 48 h with sucrose at the sucrose/lipids ratio of 2:1(w/w) in order to enhance its stability. The freeze-dried complex nanoliposomes under the suitable conditions exhibited high entrapment efficiency of MCFAs (44.26 ± 3.34)%, relatively high entrapment efficiency of vit C (62.25 ± 3.43)%, low average size diameter (110.4 ± 7.28) nm and good storage stability at 4 °C for 60 days with slight changes in mean particle diameter and drug entrapment efficiencies. The results of transmission electron microscopy of freeze-dried complex nanoliposomes also showed that the freeze-dried samples with sucrose were stable without great increase in their particle sizes and without destroying their spherical shape. The results indicated that sucrose presented well protection effects in MCFAs-vit C complex nanoliposomes, suggesting the possibility of further usage in commercial liposomes. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles 2013)

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8 pages, 519 KiB

Open AccessCommunication

Generation of an ICF Syndrome Model by Efficient Genome Editing of Human Induced Pluripotent Stem Cells Using the CRISPR System

by Takuro Horii, Daiki Tamura, Sumiyo Morita, Mika Kimura and Izuho Hatada^*

Laboratory of Genome Science, Biosignal Genome Resource Center, Institute for Molecular and Cellular Regulation, Gunma University, Gunma 371-8512, Japan

Int. J. Mol. Sci. 2013, 14(10), 19774-19781; https://doi.org/10.3390/ijms141019774 - 30 Sep 2013

Cited by 90 | Viewed by 12393

Abstract

Genome manipulation of human induced pluripotent stem (iPS) cells is essential to achieve their full potential as tools for regenerative medicine. To date, however, gene targeting in human pluripotent stem cells (hPSCs) has proven to be extremely difficult. Recently, an efficient genome manipulation [...] Read more.

Genome manipulation of human induced pluripotent stem (iPS) cells is essential to achieve their full potential as tools for regenerative medicine. To date, however, gene targeting in human pluripotent stem cells (hPSCs) has proven to be extremely difficult. Recently, an efficient genome manipulation technology using the RNA-guided DNase Cas9, the clustered regularly interspaced short palindromic repeats (CRISPR) system, has been developed. Here we report the efficient generation of an iPS cell model for immunodeficiency, centromeric region instability, facial anomalies syndrome (ICF) syndrome using the CRISPR system. We obtained iPS cells with mutations in both alleles of DNA methyltransferase 3B (DNMT3B) in 63% of transfected clones. Our data suggest that the CRISPR system is highly efficient and useful for genome engineering of human iPS cells. Full article

(This article belongs to the Section Biochemistry)

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10 pages, 201 KiB

Open AccessArticle

Relationship between Serum Osteocalcin Levels and Non-Alcoholic Fatty Liver Disease in Adult Males, South China

by Jun-Jie Liu¹, Yuan-Yuan Chen¹, Zeng-Nan Mo^2,3, Gui-Xiang Tian¹, Ai-Hua Tan⁴, Yong Gao², Xiao-Bo Yang⁵, Hai-Ying Zhang⁵ and Zhi-Xian Li^1,*

¹ Department of Ultrasound, First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China

² Center for Personalized and Genomic Medicine, Guangxi Medical University, Nanning 530021, China

³ Institute of Urology and Nephrology, First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China

⁴ Center for Metabolic Disease and Diabetes, First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China

⁵ Department of occupational health and environmental health, school of public health of Guangxi Medical University, Nanning 530021, China

Int. J. Mol. Sci. 2013, 14(10), 19782-19791; https://doi.org/10.3390/ijms141019782 - 30 Sep 2013

Cited by 27 | Viewed by 6695

Abstract

AIM: To determine serum osteocalcin levels in South Chinese males with non-alcoholic fatty liver disease (NAFLD) and to examine the relation between serum osteocalcin and NAFLD. METHODS: Data were collected from 1683 men attending the Fangchenggang Area Male Healthy and Examination Survey (FAMHES) [...] Read more.

AIM: To determine serum osteocalcin levels in South Chinese males with non-alcoholic fatty liver disease (NAFLD) and to examine the relation between serum osteocalcin and NAFLD. METHODS: Data were collected from 1683 men attending the Fangchenggang Area Male Healthy and Examination Survey (FAMHES) from September 2009 to December 2009. Serum osteocalcin was measured with electrochemiluminescence immunoassay. An abdominal ultrasonographic examination for all individuals was performed by two experienced ultrasonographers. The associations of serum osteocalcin with NAFLD were evaluated. RESULTS: The levels of serum osteocalcin were lower in 364 NAFLD participants than in 1319 non-NAFLD participants (24.51 ± 1.38 ng/mL vs. 20.81 ± 1.33 ng/mL, p < 0.001). Serum osteocalin level was associated with the scale of NAFLD (r = −0.150, p < 0.01). Serum osteocalin level tended to decrease with the scale of NAFLD. Binary logistic regression analysis showed that decreased ORs for NAFLD were observed from the first to the fourth osteocalcin quartiles. CONCLUSIONS: Our findings suggest that a lower serum osteocalcin level is associated with the presence of NAFLD. Full article

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

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13 pages, 768 KiB

Open AccessArticle

Achyranthes bidentata Polypeptides Reduces Oxidative Stress and Exerts Protective Effects against Myocardial Ischemic/Reperfusion Injury in Rats

by Ru Tie^1,†, Lele Ji^1,†, Ying Nan², Wenqing Wang³, Xiangyan Liang¹, Fei Tian¹, Wenjuan Xing⁴, Miaozhang Zhu^4,*, Rong Li^5,* and Haifeng Zhang^1,*

¹ Experiment Teaching Center, Fourth Military Medical University, Xi'an 710032, China

² Department of Physiology, Xi'an Medical University, Xi'an 710021, China

³ Department of Hematology, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China

⁴ Department of Physiology, Fourth Military Medical University, Xi'an 710032, China

⁵ Department of Geratology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2013, 14(10), 19792-19804; https://doi.org/10.3390/ijms141019792 - 30 Sep 2013

Cited by 25 | Viewed by 7729

Abstract

Achyranthes bidentata, a Chinese medicinal herb, is reported to be neuroprotective. However, its role in cardioprotection remains largely unknown. Our present study aimed to investigate the effects of Achyranthes bidentata polypeptides (ABPP) preconditioning on myocardial ischemia/reperfusion (MI/R) injury and to test the [...] Read more.

Achyranthes bidentata, a Chinese medicinal herb, is reported to be neuroprotective. However, its role in cardioprotection remains largely unknown. Our present study aimed to investigate the effects of Achyranthes bidentata polypeptides (ABPP) preconditioning on myocardial ischemia/reperfusion (MI/R) injury and to test the possible mechanisms. Rats were treated with ABPP (10 mg/kg/d, i.p.) or saline once daily for one week. Afterward, all the animals were subjected to 30 min of myocardial ischemia followed by 4 h of reperfusion. ABPP preconditioning for one week significantly improved cardiac function following MI/R. Meanwhile, ABPP reduced infarct size, plasma creatine kinase (CK)/lactate dehydrogenase (LDH) activities and myocardial apoptosis at the end of reperfusion in rat hearts. Moreover, ABPP preconditioning significantly inhibited superoxide generation, gp91^ph^ox expression, malonaldialdehyde formation and enhanced superoxide dismutase activity in I/R hearts. Furthermore, ABPP treatment inhibited PTEN expression and increased Akt phosphorylation in I/R rat heart. PI3K inhibitor wortmannin blocked Akt activation, and abolished ABPP-stimulated anti-oxidant effect and cardioprotection. Our study demonstrated for the first time that ABPP reduces oxidative stress and exerts cardioprotection against MI/R injury in rats. Inhibition of PTEN and activation of Akt may contribute to the anti-oxidant capacity and cardioprotection of ABPP. Full article

(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease)

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26 pages, 492 KiB

Open AccessReview

Interplay between Cartilage and Subchondral Bone Contributing to Pathogenesis of Osteoarthritis

by Ashish R. Sharma

, Supriya Jagga, Sang-Soo Lee and Ju-Suk Nam^*

Infectious Diseases Medical Research Center/Institute for Skeletal Aging, College of Medicine, Hallym University, Chuncheon 200702, Korea

Int. J. Mol. Sci. 2013, 14(10), 19805-19830; https://doi.org/10.3390/ijms141019805 - 30 Sep 2013

Cited by 243 | Viewed by 19598

Abstract

Osteoarthritis (OA) is a common debilitating joint disorder, affecting large sections of the population with significant disability and impaired quality of life. During OA, functional units of joints comprising cartilage and subchondral bone undergo uncontrolled catabolic and anabolic remodeling processes to adapt to [...] Read more.

Osteoarthritis (OA) is a common debilitating joint disorder, affecting large sections of the population with significant disability and impaired quality of life. During OA, functional units of joints comprising cartilage and subchondral bone undergo uncontrolled catabolic and anabolic remodeling processes to adapt to local biochemical and biological signals. Changes in cartilage and subchondral bone are not merely secondary manifestations of OA but are active components of the disease, contributing to its severity. Increased vascularization and formation of microcracks in joints during OA have suggested the facilitation of molecules from cartilage to bone and vice versa. Observations from recent studies support the view that both cartilage and subchondral bone can communicate with each other through regulation of signaling pathways for joint homeostasis under pathological conditions. In this review we have tried to summarize the current knowledge on the major signaling pathways that could control the cartilage-bone biochemical unit in joints and participate in intercellular communication between cartilage and subchondral bone during the process of OA. An understanding of molecular communication that regulates the functional behavior of chondrocytes and osteoblasts in both physiological and pathological conditions may lead to development of more effective strategies for treating OA patients. Full article

(This article belongs to the Special Issue The Chondrocyte Phenotype in Cartilage Biology)

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15 pages, 4702 KiB

Open AccessArticle

Cytokines, Chaperones and Neuroinflammatory Responses in Heroin-Related Death: What Can We Learn from Different Patterns of Cellular Expression?

by Margherita Neri¹, Laura Panata², Mauro Bacci², Carmela Fiore¹, Irene Riezzo¹, Emanuela Turillazzi¹ and Vittorio Fineschi^1,*

¹ Department of Forensic Pathology, University of Foggia, Ospedale Colonnello D'Avanzo, Viale degli Aviatori 1, Foggia 71100, Italy

² Department of Forensic Pathology, University of Perugia, Via del Giochetto, Perugia 06100, Italy

Int. J. Mol. Sci. 2013, 14(10), 19831-19845; https://doi.org/10.3390/ijms141019831 - 30 Sep 2013

Cited by 20 | Viewed by 7486

Abstract

Heroin (3,6-diacetylmorphine) has various effects on the central nervous system with several neuropathological alterations including hypoxic-ischemic brain damage from respiratory depressing effects and neuroinflammatory response. Both of these mechanisms induce the release of cytokines, chemokines and other inflammatory mediators by the activation of [...] Read more.

Heroin (3,6-diacetylmorphine) has various effects on the central nervous system with several neuropathological alterations including hypoxic-ischemic brain damage from respiratory depressing effects and neuroinflammatory response. Both of these mechanisms induce the release of cytokines, chemokines and other inflammatory mediators by the activation of many cell types such as leucocytes and endothelial and glial cells, especially microglia, the predominant immunocompetent cell type within the central nervous system. The aim of this study is to clarify the correlation between intravenous heroin administration in heroin related death and the neuroinflammatory response. We selected 45 cases among autopsies executed for heroin-related death (358 total cases); immunohistochemical studies and Western blotting analyses were used to investigate the expression of brain markers such as tumor necrosis factor-α, oxygen-regulated protein 150, (interleukins) IL-1β, IL-6, IL-8, IL-10, IL-15, cyclooxygenase-2, heat shock protein 70, and CD68 (MAC387). Findings demonstrated that morphine induces inflammatory response and cytokine release. In particular, oxygen-regulated protein 150, cyclooxygenase-2, heat shock protein 70, IL-6 and IL-15 cytokines were over-expressed with different patterns of cellular expression. Full article

(This article belongs to the Special Issue Molecular Research in Neurotoxicology)

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21 pages, 724 KiB

Open AccessReview

Development of Nonalcoholic Hepatopathy: Contributions of Oxidative Stress and Advanced Glycation End Products

by Juliana Célia de F. Santos^1,†, Iara B. Valentim^1,2, Orlando R. P. De Araújo^1,†, Terezinha Da R. Ataide³ and Marília O. F. Goulart^1,4,*

¹ Institute of Chemistry and Biotechnology, Federal University of Alagoas (IQB/UFAL), Maceio, Alagoas 57072-900, Brazil

² Federal Institute for Education, Science and Technology of Alagoas, Maceio, Alagoas 57020-600, Brazil

³ Faculty of Nutrition, Federal University of Alagoas (FANUT/UFAL), Maceio, Alagoas 57072-970, Brazil

⁴ Northeast Biotechnology Network (RENORBIO), Federal University of Alagoas (UFAL), Maceio, Alagoas 57072-900, Brazil

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2013, 14(10), 19846-19866; https://doi.org/10.3390/ijms141019846 - 1 Oct 2013

Cited by 62 | Viewed by 12356

Abstract

Advanced glycation end products (AGEs) are generated spontaneously in cells; however, under conditions of hyperglycemia and lipid peroxidation, their levels are higher than usual, which contribute to the development of diseases such as the nonalcoholic fatty liver disease (NAFLD). NAFLD is associated with [...] Read more.

Advanced glycation end products (AGEs) are generated spontaneously in cells; however, under conditions of hyperglycemia and lipid peroxidation, their levels are higher than usual, which contribute to the development of diseases such as the nonalcoholic fatty liver disease (NAFLD). NAFLD is associated with oxidative stress (OS), which is linked to the transition of steatosis to steatohepatitis due to lipid peroxidation. The AGE-receptor interaction in hepatic stellate cells leads to an increase in reactive oxygen species and enhances the proliferation and activation of these cells, worsening liver fibrosis and disease progression. In this vicious cycle, there is production of (carboxymethyl)lysine, a biomarker for products of advanced glycation and lipid peroxidation, being a shared component between the two pathways. In this review, we aim to compile evidence to support the basic molecular mechanisms of AGEs and OS generation and their influence, independently or combined, on the evolution of NAFLD. The deeper understanding of the interrelations of AGEs + OS may help to elucidate the pathogenic pathways of NAFLD and to devise rational therapeutic interventions for this disease, with an expected positive impact on quality of life of patients. Full article

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

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24 pages, 569 KiB

Open AccessReview

Immunological Mechanisms in the Pathophysiology of Non-Alcoholic Steatohepatitis

by Luisa Vonghia^1,2,*, Peter Michielsen¹ and Sven Francque¹

¹ Department of Gastroenterology and Hepatology, University Hospital Antwerp, Wilrijkstraat 10, Edegem 2650, Belgium

² Department of Basic Medical Sciences, Neuroscience and Sensory Organs, University of Bari, Policlinico, Piazza Giulio Cesare, Bari 70100, Italy

Int. J. Mol. Sci. 2013, 14(10), 19867-19890; https://doi.org/10.3390/ijms141019867 - 1 Oct 2013

Cited by 57 | Viewed by 10453

Abstract

Non-alcoholic steatohepatitis (NASH) is characterized by the presence of steatosis, inflammation and hepatocyte injury and constitutes hepatic manifestation of the metabolic syndrome. The pathogenesis of NASH is complex and implicates cross-talk between different metabolically active sites, such as liver and adipose tissue. Obesity [...] Read more.

Non-alcoholic steatohepatitis (NASH) is characterized by the presence of steatosis, inflammation and hepatocyte injury and constitutes hepatic manifestation of the metabolic syndrome. The pathogenesis of NASH is complex and implicates cross-talk between different metabolically active sites, such as liver and adipose tissue. Obesity is considered a chronic low-grade inflammatory state and the liver has been recognized as being an “immunological organ”. The complex role of the immune system in the pathogenesis of NASH is currently raising great interest, also in view of the possible therapeutic potential of immunotherapy in NASH. This review focuses on the disturbances of the cells constituting the innate and adaptive immune system in the liver and in adipose tissue. Full article

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

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20 pages, 457 KiB

Open AccessReview

Radical Roles for RAGE in the Pathogenesis of Oxidative Stress in Cardiovascular Diseases and Beyond

by Gurdip Daffu, Carmen Hurtado Del Pozo, Karen M. O'Shea, Radha Ananthakrishnan, Ravichandran Ramasamy and Ann Marie Schmidt^*

Diabetes Research Program, Division of Endocrinology, Department of Medicine, New York University Langone Medical Center, 550 First Avenue, Smilow 901C, New York, NY 10016, USA

Int. J. Mol. Sci. 2013, 14(10), 19891-19910; https://doi.org/10.3390/ijms141019891 - 1 Oct 2013

Cited by 191 | Viewed by 13955

Abstract

Oxidative stress is a central mechanism by which the receptor for advanced glycation endproducts (RAGE) mediates its pathological effects. Multiple experimental inquiries in RAGE-expressing cultured cells have demonstrated that ligand-RAGE interaction mediates generation of reactive oxygen species (ROS) and consequent downstream signal transduction [...] Read more.

Oxidative stress is a central mechanism by which the receptor for advanced glycation endproducts (RAGE) mediates its pathological effects. Multiple experimental inquiries in RAGE-expressing cultured cells have demonstrated that ligand-RAGE interaction mediates generation of reactive oxygen species (ROS) and consequent downstream signal transduction and regulation of gene expression. The primary mechanism by which RAGE generates oxidative stress is via activation of NADPH oxidase; amplification mechanisms in the mitochondria may further drive ROS production. Recent studies indicating that the cytoplasmic domain of RAGE binds to the formin mDia1 provide further support for the critical roles of this pathway in oxidative stress; mDia1 was required for activation of rac1 and NADPH oxidase in primary murine aortic smooth muscle cells treated with RAGE ligand S100B. In vivo, in multiple distinct disease models in animals, RAGE action generates oxidative stress and modulates cellular/tissue fate in range of disorders, such as in myocardial ischemia, atherosclerosis, and aneurysm formation. Blockade or genetic deletion of RAGE was shown to be protective in these settings. Indeed, beyond cardiovascular disease, evidence is accruing in human subjects linking levels of RAGE ligands and soluble RAGE to oxidative stress in disorders such as doxorubicin toxicity, acetaminophen toxicity, neurodegeneration, hyperlipidemia, diabetes, preeclampsia, rheumatoid arthritis and pulmonary fibrosis. Blockade of RAGE signal transduction may be a key strategy for the prevention of the deleterious consequences of oxidative stress, particularly in chronic disease. Full article

(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease)

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12 pages, 340 KiB

Open AccessArticle

Inhibiting Invasion into Human Bladder Carcinoma 5637 Cells with Diallyl Trisulfide by Inhibiting Matrix Metalloproteinase Activities and Tightening Tight Junctions

by Dong Yeok Shin¹, Hee-Jae Cha²

, Gi-Young Kim³, Wun-Jae Kim⁴ and Yung Hyun Choi^5,6,*

¹ Dongnam Institute of Radiological & Medicine Sciences, Busan 619-953, Korea

² Departments of Parasitology and Genetics, College of Medicine, Kosin University, Busan 602-702, Korea

³ Laboratory of Immunobiology, Department of Marine Life Sciences, Jeju National University, Jeju 690-756, Korea

⁴ Department of Urology, College of Medicine, Chungbuk National University, Cheongju 361-763, Korea

⁵ Anti-Aging Research Center & Blue-Bio Industry RIC, Dongeui University, Busan 614-714, Korea

⁶ Department of Biochemistry, College of Oriental Medicine, Dongeui University, Busan 614-052, Korea

Int. J. Mol. Sci. 2013, 14(10), 19911-19922; https://doi.org/10.3390/ijms141019911 - 1 Oct 2013

Cited by 18 | Viewed by 6844

Abstract

Diallyl trisulfide (DATS), an organosulfur compound in garlic, possesses pronounced anti-cancer potential. However, the anti-invasive mechanism of this compound in human bladder carcinoma is not fully understood. In this study, we evaluated the anti-invasive effects of DATS on a human bladder carcinoma (5637) [...] Read more.

Diallyl trisulfide (DATS), an organosulfur compound in garlic, possesses pronounced anti-cancer potential. However, the anti-invasive mechanism of this compound in human bladder carcinoma is not fully understood. In this study, we evaluated the anti-invasive effects of DATS on a human bladder carcinoma (5637) cell line and investigated the underlying mechanism. The results indicated that DATS suppressed migration and invasion of 5637 cells by reducing the activities and expression of matrix metalloproteinase (MMP)-2 and MMP-9 at both the protein and mRNA levels. DATS treatment up-regulated expression of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 in 5637 cells. The inhibitory effects of DATS on invasiveness were associated with an increase in transepithelial electrical resistance and repression of the levels of claudin family members. Although further studies are needed, our data demonstrate that DATS exhibits anti-invasive effects in 5637 cells by down-regulating the activity of tight junctions and MMPs. DATS may have future utility in clinical applications for treating bladder cancer. Full article

(This article belongs to the Section Biochemistry)

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9 pages, 193 KiB

Open AccessArticle

Using Next-Generation Sequencing and Cross-Species Amplification in the Genus Pseudopungtungia

by Young-Eun Yun¹, Jeong-Nam Yu¹, Sang Ki Kim², Ui Wook Hwang^2,3 and Myounghai Kwak^1,*

¹ National Institute of Biological Resources, Incheon 404-708, Korea

² School of Life Science, Kyungpook National University, Daegu 702-701, Korea

³ Department of Biology, Teachers College & Institute for Phylogenomics and Evolution, Kyungpook National University, Daegu 702-701, Korea

Int. J. Mol. Sci. 2013, 14(10), 19923-19931; https://doi.org/10.3390/ijms141019923 - 1 Oct 2013

Cited by 2 | Viewed by 5697

Abstract

Nuclear microsatellite markers for Pungtungia herzi were developed using a combination of next-generation sequencing and Sanger sequencing. One hundred primer sets in the flanking region of dinucleotide and trinucleotide repeat motifs were designed and tested for efficiency in polymerase chain reaction amplification. Of [...] Read more.

Nuclear microsatellite markers for Pungtungia herzi were developed using a combination of next-generation sequencing and Sanger sequencing. One hundred primer sets in the flanking region of dinucleotide and trinucleotide repeat motifs were designed and tested for efficiency in polymerase chain reaction amplification. Of these primer sets, 16 new markers (16%) were successfully amplified with unambiguous polymorphic alleles in 16 individuals of Pungtungia herzi. Cross-species amplification with these markers was then examined in two related species, Pseudopungtungia nigra and Pseudopungtungia tenuicorpa. Fifteen and 11 primer pairs resulted in successful amplification in Pseudopungtungia nigra and Pseudopungtungia tenuicorpa, respectively, with various polymorphisms, ranging from one allele (monomorphic) to 11 alleles per marker. These results indicated that developing microsatellite markers for cross-amplification from a species that is abundant and phylogenetically close to the species of interest is a good alternative when tissue samples of an endangered species are insufficient to develop microsatellites. Full article

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

19 pages, 4099 KiB

Open AccessReview

Nematicons and Their Electro-Optic Control: Light Localization and Signal Readdressing via Reorientation in Liquid Crystals

by Armando Piccardi, Alessandro Alberucci and Gaetano Assanto^*

Nonlinear Optics and OptoElectronics Lab (NooEL), University of Rome "Roma Tre", Via della Vasca Navale 84, Rome 00146, Italy

Int. J. Mol. Sci. 2013, 14(10), 19932-19950; https://doi.org/10.3390/ijms141019932 - 8 Oct 2013

Cited by 8 | Viewed by 6501

Abstract

Liquid crystals in the nematic phase exhibit substantial reorientation when the molecules are driven by electric fields of any frequencies. Exploiting such a response at optical frequencies, self-focusing supports transverse localization of light and the propagation of self-confined beams and waveguides, namely “nematicons”. [...] Read more.

Liquid crystals in the nematic phase exhibit substantial reorientation when the molecules are driven by electric fields of any frequencies. Exploiting such a response at optical frequencies, self-focusing supports transverse localization of light and the propagation of self-confined beams and waveguides, namely “nematicons”. Nematicons can guide other light signals and interact with inhomogeneities and other beams. Moreover, they can be effectively deviated by using the electro-optic response of the medium, leading to several strategies for voltage-controlled reconfiguration of light-induced guided-wave circuits and signal readdressing. Hereby, we outline the main features of nematicons and review the outstanding progress achieved in the last twelve years on beam self-trapping and electro-optic readdressing. Full article

(This article belongs to the Special Issue Experimental and Theoretical Studies of Liquid Crystalline Materials: Where Do We Stand after 120 Years?)

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20 pages, 1181 KiB

Open AccessArticle

CD8⁺ T Cell-Induced Expression of Tissue Inhibitor of Metalloproteinses-1 Exacerbated Osteoarthritis

by Jeng-Long Hsieh¹, Ai-Li Shiau²

, Che-Hsin Lee³, Shiu-Ju Yang⁴, Bih-O Lee⁵, I-Ming Jou⁶, Chao-Liang Wu⁷

, Shun-Hua Chen² and Po-Chuan Shen^8,*

¹ Department of Nursing, Chung Hwa University of Medical Technology, Tainan 717, Taiwan

² Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan

³ Department of Microbiology, School of Medicine, China Medical University, Taichung 404, Taiwan

⁴ Institute of Basic Medical Science, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan

⁵ Department of Nursing, Chang Gung University of Technology, Puzih, Chiayi County 613, Taiwan

⁶ Department of Orthopedics, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan

⁷ Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan

⁸ Department of Orthopedic Surgery, Tainan Hospital, Department of Health, Executive Yuan, Tainan 700, Taiwan

Int. J. Mol. Sci. 2013, 14(10), 19951-19970; https://doi.org/10.3390/ijms141019951 - 8 Oct 2013

Cited by 61 | Viewed by 7907

Abstract

Despites the fact that T cells are involved in the pathogenesis of osteoarthritis (OA) little is known about the roles of CD8⁺ T cells in this disease. We investigated the effects of CD8⁺ T cells and the expression of tissue inhibitor [...] Read more.

Despites the fact that T cells are involved in the pathogenesis of osteoarthritis (OA) little is known about the roles of CD8⁺ T cells in this disease. We investigated the effects of CD8⁺ T cells and the expression of tissue inhibitor of metalloproteinases 1 (TIMP-1) on joint pathology. Using anterior cruciate ligament-transection (ACLT), OA was induced in mice. The knee joints were histologically assessed for manifestations of OA. The CD8⁺ T cells from splenocytes and synovium were flow-cytometrically and immunochemically evaluated, respectively. Local expression of TIMP-1, matrix metalloproteinase (MMP)-13, and VEGF were examined. Cartilage degeneration was slower in CD8⁺ T cell knockout mice than in control mice. CD8⁺ T cells were activated once OA was initiated and expanded during OA progression. More CD8⁺ T cells from splenocytes expressed TIMP-1 in ACLT-group mice than in Sham-group mice. The number of TIMP-1-expressing CD8⁺ T cells in OA mice correlated with the disease severity. TIMP-1 expression in cartilage was co-localized with that of MMP-13 and VEGF. TIMP-1 protein was detected in synovium in which angiogenesis occurred. During the pathogenesis of OA, the expression of TIMP-1, VEGF and MMP-13 accompanying with CD8⁺ T cells activation were increased. Furthermore, inhibiting the expression of TIMP-1 in joints could retard the progression of OA. Full article

(This article belongs to the Section Biochemistry)

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5 pages, 169 KiB

Open AccessShort Note

Eleven Novel Polymorphic Microsatellite Loci for Oval Squid Sepioteuthis Lessoniana (Shiro-Ika Type)

by Satoshi Tomano¹, Kamarudin Ahmad-Syazni¹, Yukio Ueta², Kenichi Ohara³ and Tetsuya Umino^1,*

¹ Graduate School of Biosphere Science, Hiroshima University, Higashi-Hiroshima, Hiroshima 739-8528, Japan

² Tokushima Agriculture, Forestry and Fisheries Technology Support Center, Naruto, Tokushima 771-0361, Japan

³ Gifu Prefectural Research Institute for Freshwater Fish and Aquatic Environments, Gero, Gifu 509-2592, Japan

Int. J. Mol. Sci. 2013, 14(10), 19971-19975; https://doi.org/10.3390/ijms141019971 - 8 Oct 2013

Cited by 6 | Viewed by 5512

Abstract

The oval squid Sepioteuthis lessoniana is one of the most economically important squid species in Japan; however, its population structure is poorly understood due to the lack of hypervariable markers. Such information is critical for managing sustainable fisheries, as well as for ensuring [...] Read more.

The oval squid Sepioteuthis lessoniana is one of the most economically important squid species in Japan; however, its population structure is poorly understood due to the lack of hypervariable markers. Such information is critical for managing sustainable fisheries, as well as for ensuring the existence of wild S. lessoniana stocks. Eleven candidate microsatellite loci were isolated from a small insert genomic DNA library. Polymorphisms in these 11 loci were screened in 24 wild individuals. The number of alleles per locus was found to range from 5 to 19 alleles, and the observed heterozygosity ranged from 0.292 to 0.958. No evidence for linkage disequilibrium was detected among all the loci. The genotypic proportions conformed to Hardy-Weinberg equilibrium, except at one locus. In conclusion, these polymorphic microsatellite loci may be used to develop a genetic framework to manage S. lessoniana in the future. Full article

11 pages, 336 KiB

Open AccessArticle

N,N’-alkylated Imidazolium-Derivatives Act as Quorum-Sensing Inhibitors Targeting the Pectobacterium atrosepticum-Induced Symptoms on Potato Tubers

by Yannick Raoul Des Essarts^1,2, Mohamad Sabbah³, Arnaud Comte⁴

, Laurent Soulère³, Yves Queneau³, Yves Dessaux¹, Valérie Hélias^2,5 and Denis Faure^1,*

¹ Centre National de la Recherche Scientifique, Institut des Sciences du Végétal, UPR 2355, Gif-sur-Yvette 91198, France

² FN3PT/RD3PT, Fédération Nationale des Producteurs de Plants de Pomme de terre, 43-45 Rue de Naples, Paris F-75008, France

³ INSA Lyon, ICBMS, UMR 5246, CNRS, Université Lyon 1, INSA-Lyon, CPE-Lyon, Bât J. Verne, 20 av A. Einstein, 69621 Villeurbanne Cedex, France

⁴ Service de Chimiothèque, ICBMS, UMR 5246, CNRS, Université Lyon 1, INSA-Lyon, CPE-Lyon, Bât Curien, 43 bd du 11 Novembre 1918, 69622 Villeurbanne Cedex, France

⁵ Institut National de la Recherche Agronomique, UMR 1349IGEPP, Le Rheu F-35653, France

Int. J. Mol. Sci. 2013, 14(10), 19976-19986; https://doi.org/10.3390/ijms141019976 - 8 Oct 2013

Cited by 15 | Viewed by 7346

Abstract

Bacteria belonging to the Pectobacterium genus are the causative agents of the blackleg and soft-rot diseases that affect potato plants and tubers worldwide. In Pectobacterium, the expression of the virulence genes is controlled by quorum-sensing (QS) and N-acylhomoserine lactones (AHLs). In [...] Read more.

Bacteria belonging to the Pectobacterium genus are the causative agents of the blackleg and soft-rot diseases that affect potato plants and tubers worldwide. In Pectobacterium, the expression of the virulence genes is controlled by quorum-sensing (QS) and N-acylhomoserine lactones (AHLs). In this work, we screened a chemical library of QS-inhibitors (QSIs) and AHL-analogs to find novel QSIs targeting the virulence of Pectobacterium. Four N,N’-bisalkylated imidazolium salts were identified as QSIs; they were active at the µM range. In potato tuber assays, two of them were able to decrease the severity of the symptoms provoked by P. atrosepticum. This work extends the range of the QSIs acting on the Pectobacterium-induced soft-rot disease. Full article

(This article belongs to the Special Issue Quorum Sensing Research in Microbial Systems)

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32 pages, 1299 KiB

Open AccessReview

Non-Coding RNAs: The “Dark Matter” of Cardiovascular Pathophysiology

by Claudio Iaconetti, Clarice Gareri, Alberto Polimeni and Ciro Indolfi^*

Division of Cardiology, Magna Graecia University, URT Consiglio Nazionale delle Ricerche (CNR), Catanzaro 88100, Italy

Int. J. Mol. Sci. 2013, 14(10), 19987-20018; https://doi.org/10.3390/ijms141019987 - 9 Oct 2013

Cited by 55 | Viewed by 11315

Abstract

Large-scale analyses of mammalian transcriptomes have identified a significant number of different RNA molecules that are not translated into protein. In fact, the use of new sequencing technologies has identified that most of the genome is transcribed, producing a heterogeneous population of RNAs [...] Read more.

Large-scale analyses of mammalian transcriptomes have identified a significant number of different RNA molecules that are not translated into protein. In fact, the use of new sequencing technologies has identified that most of the genome is transcribed, producing a heterogeneous population of RNAs which do not encode for proteins (ncRNAs). Emerging data suggest that these transcripts influence the development of cardiovascular disease. The best characterized non-coding RNA family is represented by short highly conserved RNA molecules, termed microRNAs (miRNAs), which mediate a process of mRNA silencing through transcript degradation or translational repression. These microRNAs (miRNAs) are expressed in cardiovascular tissues and play key roles in many cardiovascular pathologies, such as coronary artery disease (CAD) and heart failure (HF). Potential links between other ncRNAs, like long non-coding RNA, and cardiovascular disease are intriguing but the functions of these transcripts are largely unknown. Thus, the functional characterization of ncRNAs is essential to improve the overall understanding of cellular processes involved in cardiovascular diseases in order to define new therapeutic strategies. This review outlines the current knowledge of the different ncRNA classes and summarizes their role in cardiovascular development and disease. Full article

(This article belongs to the Special Issue Regulation by non-coding RNAs 2013)

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18 pages, 513 KiB

Open AccessReview

Genetic Correction of Stem Cells in the Treatment of Inherited Diseases and Focus on Xeroderma Pigmentosum

by Sophie Rouanet^1,†, Emilie Warrick^2,†, Yannick Gache¹, Sabine Scarzello¹, Marie-Françoise Avril³, Françoise Bernerd² and Thierry Magnaldo^1,*

¹ Genetics and Physiopathology of Epithelial Cancers, INSERM U 1081-CNRS UMR 7284-UNS, Institute for Research on Cancer and Aging, Nice, Medical school, 28 Avenue de Valombrose, 06107 Nice Cedex 2, France

² Oréal Research and Innovation, 92217 Clichy, France

³ Hopital Cochin, Pavillon Tarnier, APHP, Université Paris 6, 75006 Paris, France

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2013, 14(10), 20019-20036; https://doi.org/10.3390/ijms141020019 - 9 Oct 2013

Cited by 7 | Viewed by 8929

Abstract

Somatic stem cells ensure tissue renewal along life and healing of injuries. Their safe isolation, genetic manipulation ex vivo and reinfusion in patients suffering from life threatening immune deficiencies (for example, severe combined immunodeficiency (SCID)) have demonstrated the efficacy of ex vivo gene [...] Read more.

Somatic stem cells ensure tissue renewal along life and healing of injuries. Their safe isolation, genetic manipulation ex vivo and reinfusion in patients suffering from life threatening immune deficiencies (for example, severe combined immunodeficiency (SCID)) have demonstrated the efficacy of ex vivo gene therapy. Similarly, adult epidermal stem cells have the capacity to renew epidermis, the fully differentiated, protective envelope of our body. Stable skin replacement of severely burned patients have proven life saving. Xeroderma pigmentosum (XP) is a devastating disease due to severe defects in the repair of mutagenic DNA lesions introduced upon exposure to solar radiations. Most patients die from the consequences of budding hundreds of skin cancers in the absence of photoprotection. We have developed a safe procedure of genetic correction of epidermal stem cells isolated from XP patients. Preclinical and safety assessments indicate successful correction of XP epidermal stem cells in the long term and their capacity to regenerate a normal skin with full capacities of DNA repair. Full article

(This article belongs to the Special Issue Molecular Research of Epidermal Stem Cells)

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11 pages, 156 KiB

Open AccessReview

New Insights in the Pathogenesis of Multiple Sclerosis—Role of Acrolein in Neuronal and Myelin Damage

by Melissa Tully^1,2 and Riyi Shi^1,3,*

¹ Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA

² Indiana University School of Medicine, Indianapolis, IN 46202, USA

³ Department of Basic Medical Sciences, College of Veterinary Medicine, Purdue University, West Lafayette, IN 47907, USA

Int. J. Mol. Sci. 2013, 14(10), 20037-20047; https://doi.org/10.3390/ijms141020037 - 9 Oct 2013

Cited by 54 | Viewed by 7924

Abstract

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) characterized by an inappropriate inflammatory reaction resulting in widespread myelin injury along white matter tracts. Neurological impairment as a result of the disease can be attributed to immune-mediated injury to [...] Read more.

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) characterized by an inappropriate inflammatory reaction resulting in widespread myelin injury along white matter tracts. Neurological impairment as a result of the disease can be attributed to immune-mediated injury to myelin, axons and mitochondria, but the molecular mechanisms underlying the neuropathy remain incompletely understood. Incomplete mechanistic knowledge hinders the development of therapies capable of alleviating symptoms and slowing disease progression in the long-term. Recently, oxidative stress has been implicated as a key component of neural tissue damage prompting investigation of reactive oxygen species (ROS) scavengers as a potential therapeutic option. Despite the establishment of oxidative stress as a crucial process in MS development and progression, ROS scavengers have had limited success in animal studies which has prompted pursuit of an alternative target capable of curtailing oxidative stress. Acrolein, a toxic β-unsaturated aldehyde capable of initiating and perpetuating oxidative stress, has been suggested as a viable point of intervention to guide the development of new treatments. Sequestering acrolein using an FDA-approved compound, hydralazine, offers neuroprotection resulting in dampened symptom severity and slowed disease progression in experimental autoimmune encephalomyelitis (EAE) mice. These results provide promise for therapeutic development, indicating the possible utility of neutralizing acrolein to preserve and improve neurological function in MS patients. Full article

(This article belongs to the Special Issue Pathology and Treatment of Central Nervous System Diseases)

16 pages, 841 KiB

Open AccessArticle

Transcriptional Regulation of a Chitinase Gene by 20-Hydroxyecdysone and Starvation in the Oriental Fruit Fly, Bactrocera dorsalis

by Wen-Jia Yang, Kang-Kang Xu, Rui-Ying Zhang, Wei Dou and Jin-Jun Wang^*

Key Laboratory of Entomology and Pest Control Engineering, College of Plant Protection, Southwest University, Chongqing 400716, China

Int. J. Mol. Sci. 2013, 14(10), 20048-20063; https://doi.org/10.3390/ijms141020048 - 9 Oct 2013

Cited by 27 | Viewed by 6362

Abstract

Insect chitinases are hydrolytic enzymes that are required for the degradation of glycosidic bonds of chitin. In this study, we identified and characterized a full-length cDNA of the chitinase gene (BdCht2) in the oriental fruit fly, Bactrocera dorsalis. The cDNA [...] Read more.

Insect chitinases are hydrolytic enzymes that are required for the degradation of glycosidic bonds of chitin. In this study, we identified and characterized a full-length cDNA of the chitinase gene (BdCht2) in the oriental fruit fly, Bactrocera dorsalis. The cDNA contains an open reading frame (ORF) of 1449 bp that encodes 483 amino acid residues and 126- and 296-bp non-coding regions at the 5'- and 3'-ends, respectively. The BdCht2 genome has four exons and three introns. The predicted molecular mass of the deduced BdCht2 is approximately 54.3 kDa, with an isoelectric point of 5.97. The 977 bp 5' flanking region was identified and the transcription factor binding sites were predicted. Bioinformatic analyses showed that the deduced amino acid sequence of BdCht2 had 34%–66% identity to that of chitinases identified in other insect species. Quantitative real-time PCR (qPCR) analyses indicated that BdCht2 was mainly expressed during the larval-pupal and pupal-adult transitions. The tissue-specific expression showed that the highest expression was in the integument, followed by the fat body and other tissues. Moreover, the expression of BdCht2 was upregulated significantly upon 20-hydroxyecdysone (20E) at different dose injections after 8 h compared to that of the control. Starvation also increased the expression of BdCht2 in the third-instar larvae and was suppressed again by re-feeding the insects. These results suggest that BdCht2 plays an important role in the molting process of B. dorsalis larvae and can be regulated by 20E. Full article

(This article belongs to the Section Biochemistry)

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15 pages, 3656 KiB

Open AccessReview

Marine Polysaccharide Networks and Diatoms at the Nanometric Scale

by Vesna Svetličić^*, Vera Žutić, Galja Pletikapić and Tea Mišić Radić

Division for Marine and Environmental Research, Ruđer Bošković Institute, Bijenička 54, 10000 Zagreb, Croatia

Int. J. Mol. Sci. 2013, 14(10), 20064-20078; https://doi.org/10.3390/ijms141020064 - 9 Oct 2013

Cited by 30 | Viewed by 9589

Abstract

Despite many advances in research on photosynthetic carbon fixation in marine diatoms, the biophysical and biochemical mechanisms of extracellular polysaccharide production remain significant challenges to be resolved at the molecular scale in order to proceed toward an understanding of their functions at the [...] Read more.

Despite many advances in research on photosynthetic carbon fixation in marine diatoms, the biophysical and biochemical mechanisms of extracellular polysaccharide production remain significant challenges to be resolved at the molecular scale in order to proceed toward an understanding of their functions at the cellular level, as well as their interactions and fate in the ocean. This review covers studies of diatom extracellular polysaccharides using atomic force microscopy (AFM) imaging and the quantification of physical forces. Following a brief summary of the basic principle of the AFM experiment and the first AFM studies of diatom extracellular polymeric substance (EPS), we focus on the detection of supramolecular structures in polysaccharide systems produced by marine diatoms. Extracellular polysaccharide fibrils, attached to the diatom cell wall or released into the surrounding seawater, form distinct supramolecular assemblies best described as gel networks. AFM makes characterization of the diatom polysaccharide networks at the micro and nanometric scales and a clear distinction between the self-assembly and self-organization of these complex systems in marine environments possible. Full article

(This article belongs to the Special Issue Biofilms: Extracellular Bastions of Bacteria)

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33 pages, 792 KiB

Open AccessReview

Disease Animal Models of TDP-43 Proteinopathy and Their Pre-Clinical Applications

by Yu-Chih Liu^1,2, Po-Min Chiang^1,2 and Kuen-Jer Tsai^1,2,*

¹ Institute of Clinical Medicine, National Cheng Kung University, Tainan 704, Taiwan

² Institute of Basic Medical Science, National Cheng Kung University, Tainan 704, Taiwan

Int. J. Mol. Sci. 2013, 14(10), 20079-20111; https://doi.org/10.3390/ijms141020079 - 9 Oct 2013

Cited by 35 | Viewed by 13498

Abstract

Frontotemperal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) are two common neurodegenerative diseases. TDP-43 is considered to be a major disease protein in FTLD/ALS, but it’s exact role in the pathogenesis and the effective treatments remains unknown. To address this question and [...] Read more.

Frontotemperal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) are two common neurodegenerative diseases. TDP-43 is considered to be a major disease protein in FTLD/ALS, but it’s exact role in the pathogenesis and the effective treatments remains unknown. To address this question and to determine a potential treatment for FTLD/ALS, the disease animal models of TDP-43 proteinopathy have been established. TDP-43 proteinopathy is the histologic feature of FTLD/ALS and is associated with disease progression. Studies on the disease animal models with TDP-43 proteinopathy and their pre-clinical applications are reviewed and summarized. Through these disease animal models, parts of TDP-43 functions in physiological and pathological conditions will be better understood and possible treatments for FTLD/ALS with TDP-43 proteinopathy may be identified for possible clinical applications in the future. Full article

(This article belongs to the Special Issue Post-Transcriptional Gene Regulation by Ribonucleoprotein Complexes)

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19 pages, 1007 KiB

Open AccessReview

Role of Hepatic Progenitor Cells in Nonalcoholic Fatty Liver Disease Development: Cellular Cross-Talks and Molecular Networks

by Guido Carpino^1,2,*, Anastasia Renzi¹, Paolo Onori¹

and Eugenio Gaudio¹

¹ Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome, Rome 00161, Italy

² Department of Movement, Human and Health Sciences, University of Rome "Foro Italico", Piazza Lauro De Bosis 6, Rome 00135, Italy

Int. J. Mol. Sci. 2013, 14(10), 20112-20130; https://doi.org/10.3390/ijms141020112 - 9 Oct 2013

Cited by 49 | Viewed by 13079

Abstract

Nonalcoholic fatty liver disease (NAFLD) includes a spectrum of diseases ranging from simple fatty liver to nonalcoholic steatohepatitis, (NASH) which may progress to cirrhosis and hepatocellular carcinoma. NASH has been independently correlated with atherosclerosis progression and cardiovascular risk. NASH development is characterized by [...] Read more.

Nonalcoholic fatty liver disease (NAFLD) includes a spectrum of diseases ranging from simple fatty liver to nonalcoholic steatohepatitis, (NASH) which may progress to cirrhosis and hepatocellular carcinoma. NASH has been independently correlated with atherosclerosis progression and cardiovascular risk. NASH development is characterized by intricate interactions between resident and recruited cells that enable liver damage progression. The increasing general agreement is that the cross-talk between hepatocytes, hepatic stellate cells (HSCs) and macrophages in NAFLD has a main role in the derangement of lipid homeostasis, insulin resistance, danger recognition, immune tolerance response and fibrogenesis. Moreover, several evidences have suggested that hepatic stem/progenitor cell (HPCs) activation is a component of the adaptive response of the liver to oxidative stress in NAFLD. HPC activation determines the appearance of a ductular reaction. In NASH, ductular reaction is independently correlated with progressive portal fibrosis raising the possibility of a periportal fibrogenetic pathway for fibrogenesis that is parallel to the deposition of subsinusoidal collagen in zone 3 by HSCs. Recent evidences indicated that adipokines, a class of circulating factors, have a key role in the cross-talk among HSCs, HPCs and liver macrophages. This review will be focused on cellular cross-talk and the relative molecular networks which are at the base of NASH progression and fibrosis. Full article

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

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Graphical abstract

8 pages, 208 KiB

Open AccessTechnical Note

Determination of Homoarginine, Arginine, NMMA, ADMA, and SDMA in Biological Samples by HPLC-ESI-Mass Spectrometry

by Luigi Servillo¹, Alfonso Giovane¹, Nunzia D'Onofrio¹, Rosario Casale¹, Domenico Cautela², Domenico Castaldo² and Maria Luisa Balestrieri^1,*

¹ Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, 80138 Naples, Italy

² Stazione Sperimentale per le Industrie delle Essenze e dei derivati dagli Agrumi (SSEA), Azienda Speciale della Camera di Commercio di Reggio Calabria, 89125 Reggio Calabria, Italy

Int. J. Mol. Sci. 2013, 14(10), 20131-20138; https://doi.org/10.3390/ijms141020131 - 9 Oct 2013

Cited by 15 | Viewed by 7634

Abstract

N^G,N^G-dimethyl-L-arginine (ADMA) and N^G-methyl-L-arginine (NMMA) are endogenous inhibitors of nitric oxide synthase (NOS). In contrast, N^G,N'^G-dimethyl-L-arginine (SDMA) possesses only a weak inhibitory potency towards neuronal NOS and it is known [...] Read more.

N^G,N^G-dimethyl-L-arginine (ADMA) and N^G-methyl-L-arginine (NMMA) are endogenous inhibitors of nitric oxide synthase (NOS). In contrast, N^G,N'^G-dimethyl-L-arginine (SDMA) possesses only a weak inhibitory potency towards neuronal NOS and it is known to limit nitric oxide (NO) production by competing with L-arginine for cellular uptake. The inhibition of NOS is associated with endothelial dysfunction in cardiovascular diseases as well in chronic renal failure. L-Homoarginine (HArg), a structural analog of L-arginine (Arg), is an alternative but less efficient substrate for NOS. Besides, it inhibits arginase, leading to an increased availability of L-arginine for NOS to produce NO. However, its relation with cardiovascular disease remains unclear. To date, several analytical methods for the quantitative determination of Arg, HArg, NMMA, AMDA, and SDMA in biological samples have been described. Here, we present a simple, fast, and accurate HPLC-ESI-MS/MS method which allows both the simultaneous determination and quantification of these compounds without needing derivatization, and the possibility to easily modulate the chromatographic separation between HArg and NMMA (or between SDMA and ADMA). Data on biological samples revealed the feasibility of the method, the minimal sample preparation, and the fast run time which make this method very suitable and accurate for analysis in the basic and clinical settings. Full article

(This article belongs to the Special Issue ADMA and Nitrergic System)

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18 pages, 1117 KiB

Open AccessArticle

Characterization of Apoptosis Induced by Emodin and Related Regulatory Mechanisms in Human Neuroblastoma Cells

by Fu-Jen Huang^1,2, Yan-Der Hsuuw³ and Wen-Hsiung Chan^4,5,*

¹ Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan

² Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan

³ Department of Life Science, National Pingtung University of Science and Technology, Pingtung 91201, Taiwan

⁴ Department of Bioscience Technology and Center for Nanotechnology, Chung Yuan Christian University, Chung Li 32023, Taiwan

⁵ Institute of Biomedical Technology, Chung Yuan Christian University, Chung Li 32023, Taiwan

Int. J. Mol. Sci. 2013, 14(10), 20139-20156; https://doi.org/10.3390/ijms141020139 - 9 Oct 2013

Cited by 25 | Viewed by 7644

Abstract

Emodin (1,3,8-trihydroxy-6-methylanthraquinone), a major constituent of rhubarb, has a wide range of therapeutic applications. Recent studies have shown that emodin can induce or prevent cell apoptosis, although the precise molecular mechanisms underlying these effects are unknown. Experiments from the current study revealed that [...] Read more.

Emodin (1,3,8-trihydroxy-6-methylanthraquinone), a major constituent of rhubarb, has a wide range of therapeutic applications. Recent studies have shown that emodin can induce or prevent cell apoptosis, although the precise molecular mechanisms underlying these effects are unknown. Experiments from the current study revealed that emodin (10–20 μM) induces apoptotic processes in the human neuroblastoma cell line, IMR-32, but exerts no injury effects at treatment doses below 10 μM. Treatment with emodin at concentrations of 10–20 μM led to a direct increase in the reactive oxygen species (ROS) content in IMR-32 cells, along with significant elevation of cytoplasmic free calcium and nitric oxide (NO) levels, loss of mitochondrial membrane potential (MMP), activation of caspases-9 and -3, and cell death. Pretreatment with nitric oxide (NO) scavengers suppressed the apoptotic biochemical changes induced by 20 μM emodin, and attenuated emodin-induced p53 and p21 expression involved in apoptotic signaling. Our results collectively indicate that emodin at concentrations of 10–20 μM triggers apoptosis of IMR-32 cells via a mechanism involving both ROS and NO. Based on the collective results, we propose a model for an emodin-triggered apoptotic signaling cascade that sequentially involves ROS, Ca²⁺, NO, p53, caspase-9 and caspase-3. Full article

(This article belongs to the Collection Programmed Cell Death and Apoptosis)

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14 pages, 956 KiB

Open AccessArticle

Microscale Diffusion Measurements and Simulation of a Scaffold with a Permeable Strut

by Seung Youl Lee^1,†, Byung Ryong Lee^2,†, Jongwan Lee¹, Seongjun Kim³, Jung Kyung Kim⁴

, Young Hun Jeong² and Songwan Jin^2,*

¹ Department of Mechanical System Engineering, Graduate School of Knowledge-Based Technology and Energy, Korea Polytechnic University, Jeongwang-dong, Siheung-si, Gyeonggi-do 429-793, Korea

² Department of Mechanical Engineering, Korea Polytechnic University, Jeongwang-dong, Siheung-si, Gyeonggi-do 429-793, Korea

³ Department of Mechanical Engineering, Graduate School, Kookmin University, Jeongneung-ro 77, Seongbuk-gu, Seoul 136-702, Korea

⁴ School of Mechanical Systems Engineering, Kookmin University, Jeongneung-ro 77, Seongbuk-gu, Seoul 136-702, Korea

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2013, 14(10), 20157-20170; https://doi.org/10.3390/ijms141020157 - 10 Oct 2013

Cited by 10 | Viewed by 7652

Abstract

Electrospun nanofibrous structures provide good performance to scaffolds in tissue engineering. We measured the local diffusion coefficients of 3-kDa FITC-dextran in line patterns of electrospun nanofibrous structures fabricated by the direct-write electrospinning (DWES) technique using the fluorescence recovery after photobleaching (FRAP) method. No [...] Read more.

Electrospun nanofibrous structures provide good performance to scaffolds in tissue engineering. We measured the local diffusion coefficients of 3-kDa FITC-dextran in line patterns of electrospun nanofibrous structures fabricated by the direct-write electrospinning (DWES) technique using the fluorescence recovery after photobleaching (FRAP) method. No significant differences were detected between DWES line patterns fabricated with polymer supplied at flow rates of 0.1 and 0.5 mL/h. The oxygen diffusion coefficients of samples were estimated to be ~92%–94% of the oxygen diffusion coefficient in water based on the measured diffusion coefficient of 3-kDa FITC-dextran. We also simulated cell growth and distribution within spatially patterned scaffolds with struts consisting of either oxygen-permeable or non-permeable material. The permeable strut scaffolds exhibited enhanced cell growth. Saturated depths at which cells could grow to confluence were 15% deeper for the permeable strut scaffolds than for the non-permeable strut scaffold. Full article

(This article belongs to the Special Issue Frontiers of Micro-Spectroscopy in Biological Applications)

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18 pages, 1236 KiB

Open AccessArticle

Understanding the Electronic Structures and Absorption Properties of Porphyrin Sensitizers YD2 and YD2-o-C8 for Dye-Sensitized Solar Cells

by Li-Heng Han¹, Cai-Rong Zhang^1,2,*

, Jian-Wu Zhe³, Neng-Zhi Jin³, Yu-Lin Shen³, Wei Wang¹, Ji-Jun Gong¹, Yu-Hong Chen^1,2 and Zi-Jiang Liu⁴

¹ Department of Applied Physics, Lanzhou University of Technology, Lanzhou 730050, Gansu, China

² State Key Laboratory of Gansu Advanced Non-ferrous Metal Materials, Lanzhou University of Technology, Lanzhou 730050, Gansu, China

³ Gansu Computing Center, Lanzhou, Gansu 730030, China

⁴ Department of Physics, Lanzhou City University, Lanzhou 730070, Gansu, China

Int. J. Mol. Sci. 2013, 14(10), 20171-20188; https://doi.org/10.3390/ijms141020171 - 10 Oct 2013

Cited by 56 | Viewed by 8908

Abstract

The electronic structures and excitation properties of dye sensitizers determine the photon-to-current conversion efficiency of dye sensitized solar cells (DSSCs). In order to understand the different performance of porphyrin dye sensitizers YD2 and YD2-o-C8 in DSSC, their geometries and electronic structures have been [...] Read more.

The electronic structures and excitation properties of dye sensitizers determine the photon-to-current conversion efficiency of dye sensitized solar cells (DSSCs). In order to understand the different performance of porphyrin dye sensitizers YD2 and YD2-o-C8 in DSSC, their geometries and electronic structures have been studied using density functional theory (DFT), and the electronic absorption properties have been investigated via time-dependent DFT (TDDFT) with polarizable continuum model for solvent effects. The geometrical parameters indicate that YD2 and YD2-o-C8 have similar conjugate length and charge transfer (CT) distance. According to the experimental spectra, the HSE06 functional in TDDFT is the most suitable functional for describing the Q and B absorption bands of porphyrins. The transition configurations and molecular orbital analysis suggest that the diarylamino groups are major chromophores for effective CT excitations (ECTE), and therefore act as electron donor in photon-induced electron injection in DSSCs. The analysis of excited states properties and the free energy changes for electron injection support that the better performance of YD2-o-C8 in DSSCs result from the more excited states with ECTE character and the larger absolute value of free energy change for electron injection. Full article

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

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15 pages, 950 KiB

Open AccessArticle

Effect of Chain-Extenders on the Properties and Hydrolytic Degradation Behavior of the Poly(lactide)/ Poly(butylene adipate-co-terephthalate) Blends

by Weifu Dong, Benshu Zou, Yangyang Yan, Piming Ma^* and Mingqing Chen^*

The Key Laboratory of Food Colloids and Biotechnology, Ministry of Education, School of Chemical and Material Engineering, Jiangnan University, 1800 Lihu Road, Wuxi 214122, China

Int. J. Mol. Sci. 2013, 14(10), 20189-20203; https://doi.org/10.3390/ijms141020189 - 10 Oct 2013

Cited by 123 | Viewed by 12192

Abstract

Biodegradable poly(lactide)/poly(butylene adipate-co-terephthalate) (PLA/PBAT) blends were prepared by reactive blending in the presence of chain-extenders. Two chain-extenders with multi-epoxy groups were studied. The effect of chain-extenders on the morphology, mechanical properties, thermal behavior, and hydrolytic degradation of the blends was investigated. [...] Read more.

Biodegradable poly(lactide)/poly(butylene adipate-co-terephthalate) (PLA/PBAT) blends were prepared by reactive blending in the presence of chain-extenders. Two chain-extenders with multi-epoxy groups were studied. The effect of chain-extenders on the morphology, mechanical properties, thermal behavior, and hydrolytic degradation of the blends was investigated. The compatibility between the PLA and PBAT was significantly improved by in situ formation of PLA-co-PBAT copolymers in the presence of the chain-extenders, results in an enhanced ductility of the blends, e.g., the elongation at break was increased to 500% without any decrease in the tensile strength. The differential scanning calorimeter (DSC) results reveal that cold crystallization of PLA was enhanced due to heterogeneous nucleation effect of the in situ compatibilized PBAT domains. As known before, PLA is sensitive to hydrolysis and in the presence of PBAT and the chain-extenders, the hydrolytic degradation of the blend was evident. A three-stage hydrolysis mechanism for the system is proposed based on a study of weight loss and molecular weight reduction of the samples and the pH variation of the degradation medium. Full article

(This article belongs to the Section Materials Science)

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16 pages, 2129 KiB

Open AccessArticle

OsPOP5, A Prolyl Oligopeptidase Family Gene from Rice Confers Abiotic Stress Tolerance in Escherichia coli

by Cun-Mei Tan^†, Rong-Jun Chen^†, Jian-Hua Zhang^†, Xiao-Ling Gao, Li-Hua Li, Ping-Rong Wang, Xiao-Jian Deng and Zheng-Jun Xu^*

¹ Rice Institute, Sichuan Agriculture of University, Chengdu 611130, China

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2013, 14(10), 20204-20219; https://doi.org/10.3390/ijms141020204 - 10 Oct 2013

Cited by 24 | Viewed by 7439

Abstract

The prolyl oligopeptidase family, which is a group of serine peptidases, can hydrolyze peptides smaller than 30 residues. The prolyl oligopeptidase family in plants includes four members, which are prolyl oligopeptidase (POP, EC3.4.21.26), dipeptidyl peptidase IV (DPPIV, EC3.4.14.5), oligopeptidase B (OPB, EC3.4.21.83), and [...] Read more.

The prolyl oligopeptidase family, which is a group of serine peptidases, can hydrolyze peptides smaller than 30 residues. The prolyl oligopeptidase family in plants includes four members, which are prolyl oligopeptidase (POP, EC3.4.21.26), dipeptidyl peptidase IV (DPPIV, EC3.4.14.5), oligopeptidase B (OPB, EC3.4.21.83), and acylaminoacyl peptidase (ACPH, EC3.4.19.1). POP is found in human and rat, and plays important roles in multiple biological processes, such as protein secretion, maturation and degradation of peptide hormones, and neuropathies, signal transduction and memory and learning. However, the function of POP is unclear in plants. In order to study POP function in plants, we cloned the cDNA of the OsPOP5 gene from rice by nested-PCR. Sequence analysis showed that the cDNA encodes a protein of 596 amino acid residues with M_w ≈ 67.29 kD. In order to analyze the protein function under different abiotic stresses, OsPOP5 was expressed in Escherichia coli. OsPOP5 protein enhanced the tolerance of E. coli to high salinity, high temperature and simulated drought. The results indicate that OsPOP5 is a stress-related gene in rice and it may play an important role in plant tolerance to abiotic stress. Full article

(This article belongs to the Section Biochemistry)

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16 pages, 3072 KiB

Open AccessArticle

Proteomic Analysis Identifies an NADPH Oxidase 1 (Nox1)-Mediated Role for Actin-Related Protein 2/3 Complex Subunit 2 (ARPC2) in Promoting Smooth Muscle Cell Migration

by Imad Al Ghouleh^1,2, Andrés Rodríguez^1,2,†, Patrick J. Pagano^1,2,* and Gábor Csányi^1,2,*

¹ Vascular Medicine Institute, 12th Floor BST, 200 Lothrop Street, University of Pittsburgh, PA 15261, USA

² Department of Pharmacology & Chemical Biology, 13th Floor BST, 200 Lothrop Street, University of Pittsburgh, PA 15261, USA

^† Current address: Instituto do Coração, Hospital Das Clinicas Faculdade De Medicina Da USP, Av. Eneas Carvalho Aguiar, 44. Vascular Biology Laboratory - 9th Floor, Anexo 2 Sao Paulo, Brazil.

Int. J. Mol. Sci. 2013, 14(10), 20220-20235; https://doi.org/10.3390/ijms141020220 - 11 Oct 2013

Cited by 16 | Viewed by 6849

Abstract

A variety of vascular pathologies, including hypertension, restenosis and atherosclerosis, are characterized by vascular smooth muscle cell (VSMC) hypertrophy and migration. NADPH oxidase 1 (Nox1) plays a pivotal role in these phenotypes via distinct downstream signaling. However, the mediators differentiating these distinct phenotypes [...] Read more.

A variety of vascular pathologies, including hypertension, restenosis and atherosclerosis, are characterized by vascular smooth muscle cell (VSMC) hypertrophy and migration. NADPH oxidase 1 (Nox1) plays a pivotal role in these phenotypes via distinct downstream signaling. However, the mediators differentiating these distinct phenotypes and their precise role in vascular disease are still not clear. The present study was designed to identify novel targets of VSMC Nox1 signaling using 2D Differential In-Gel Electrophoresis and Mass Spectrometry (2D-DIGE/MS). VSMC treatment with scrambled (Scrmb) or Nox1 siRNA and incubation with the oxidant hydrogen peroxide (H₂O₂; 50 µM, 3 h) followed by 2D-DIGE/MS on cell lysates identified 10 target proteins. Among these proteins, actin-related protein 2/3 complex subunit 2 (ARPC2) with no previous link to Nox isozymes, H₂O₂, or other reactive oxygen species (ROS), was identified and postulated to play an intermediary role in VSMC migration. Western blot confirmed that Nox1 mediates H₂O₂-induced ARPC2 expression in VSMC. Treatment with a p38 MAPK inhibitor (SB203580) resulted in reduced ARPC2 expression in H₂O₂-treated VSMC. Additionally, wound-healing “scratch” assay confirmed that H₂O₂ stimulates VSMC migration via Nox1. Importantly, gene silencing of ARPC2 suppressed H₂O₂-stimulated VSMC migration. These results demonstrate for the first time that Nox1-mediated VSMC migration involves ARPC2 as a downstream signaling target. Full article

(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease)

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20 pages, 1585 KiB

Open AccessArticle

Acidosis Decreases c-Myc Oncogene Expression in Human Lymphoma Cells: A Role for the Proton-Sensing G Protein-Coupled Receptor TDAG8

by Zhigang Li¹, Lixue Dong¹, Eric Dean^1,† and Li V. Yang^1,2,3,4,*

¹ Department of Oncology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA

² Department of Internal Medicine, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA

³ Department of Anatomy and Cell Biology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA

⁴ Lineberger Comprehensive Cancer Center, UNC at Chapel Hill, NC 27599, USA

^† Eric Dean was a summer research student from University of North Carolina at Chapel Hill.

Int. J. Mol. Sci. 2013, 14(10), 20236-20255; https://doi.org/10.3390/ijms141020236 - 11 Oct 2013

Cited by 37 | Viewed by 10329

Abstract

Acidosis is a biochemical hallmark of the tumor microenvironment. Here, we report that acute acidosis decreases c-Myc oncogene expression in U937 human lymphoma cells. The level of c-Myc transcripts, but not mRNA or protein stability, contributes to c-Myc protein reduction under acidosis. The [...] Read more.

Acidosis is a biochemical hallmark of the tumor microenvironment. Here, we report that acute acidosis decreases c-Myc oncogene expression in U937 human lymphoma cells. The level of c-Myc transcripts, but not mRNA or protein stability, contributes to c-Myc protein reduction under acidosis. The pH-sensing receptor TDAG8 (GPR65) is involved in acidosis-induced c-Myc downregulation. TDAG8 is expressed in U937 lymphoma cells, and the overexpression or knockdown of TDAG8 further decreases or partially rescues c-Myc expression, respectively. Acidic pH alone is insufficient to reduce c-Myc expression, as it does not decrease c-Myc in H1299 lung cancer cells expressing very low levels of pH-sensing G protein-coupled receptors (GPCRs). Instead, c-Myc is slightly increased by acidosis in H1299 cells, but this increase is completely inhibited by ectopic overexpression of TDAG8. Interestingly, TDAG8 expression is decreased by more than 50% in human lymphoma samples in comparison to non-tumorous lymph nodes and spleens, suggesting a potential tumor suppressor function of TDAG8 in lymphoma. Collectively, our results identify a novel mechanism of c-Myc regulation by acidosis in the tumor microenvironment and indicate that modulation of TDAG8 and related pH-sensing receptor pathways may be exploited as a new approach to inhibit Myc expression. Full article

(This article belongs to the Collection G Protein-Coupled Receptor Signaling and Regulation)

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26 pages, 562 KiB

Open AccessArticle

HuR-Regulated mRNAs Associated with Nuclear hnRNP A1-RNP Complexes

by Olga Papadodima¹, Aristotelis Chatziioannou¹

, Meropi Patrinou-Georgoula¹, Fragiskos N. Kolisis², Vasiliki Pletsa^1,* and Apostolia Guialis^1,*

¹ Division of Biological Research and Biotechnology, Institute of Biology, Medicinal Chemistry and Biotechnology, National Hellenic Research Foundation, 48 Vas. Constantinou Avenue, Athens 11635, Greece

² Laboratory of Biotechnology, School of Chemical Engineering, National Technical University of Athens, Athens 15780, Greece

Int. J. Mol. Sci. 2013, 14(10), 20256-20281; https://doi.org/10.3390/ijms141020256 - 11 Oct 2013

Cited by 3 | Viewed by 9030

Abstract

Post-transcriptional regulatory networks are dependent on the interplay of many RNA-binding proteins having a major role in mRNA processing events in mammals. We have been interested in the concerted action of the two RNA-binding proteins hnRNP A1 and HuR, both stable components of [...] Read more.

Post-transcriptional regulatory networks are dependent on the interplay of many RNA-binding proteins having a major role in mRNA processing events in mammals. We have been interested in the concerted action of the two RNA-binding proteins hnRNP A1 and HuR, both stable components of immunoselected hnRNP complexes and having a major nuclear localization. Specifically, we present here the application of the RNA-immunoprecipitation (RIP)-Chip technology to identify a population of nuclear transcripts associated with hnRNP A1-RNPs as isolated from the nuclear extract of either HuR WT or HuR-depleted (KO) mouse embryonic fibroblast (MEF) cells. The outcome of this analysis was a list of target genes regulated via HuR for their association (either increased or reduced) with the nuclear hnRNP A1-RNP complexes. Real time PCR analysis was applied to validate a selected number of nuclear mRNA transcripts, as well as to identify pre-spliced transcripts (in addition to their mature mRNA counterpart) within the isolated nuclear hnRNP A1-RNPs. The differentially enriched mRNAs were found to belong to GO categories relevant to biological processes anticipated for hnRNP A1 and HuR (such as transport, transcription, translation, apoptosis and cell cycle) indicating their concerted function in mRNA metabolism. Full article

(This article belongs to the Special Issue Post-Transcriptional Gene Regulation by Ribonucleoprotein Complexes)

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Graphical abstract

17 pages, 1209 KiB

Open AccessArticle

Targeting of Rho Kinase Ameliorates Impairment of Diabetic Endothelial Function in Intrarenal Artery

by Hongping Yin^1,†, Hailong Ru^2,†, Liping Yu³, Yanhua Kang², Guohua Lin², Chuanfei Liu², Lixian Sun⁴, Liyun Shi², Qinghua Sun⁵ and Cuiqing Liu^2,*

¹ Laboratory Center for Medical Science, Hangzhou Normal University, Hangzhou 310036, China

² College of Medicine, Hangzhou Normal University, Hangzhou 310036, China

³ Experimental Animal Center, Hangzhou Normal University, Hangzhou 310036, China

⁴ Department of Cardiology, Chengde Medical College, Chengde 067000, China

⁵ College of Public Health, the Ohio State University, Columbus, OH 43210, USA

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2013, 14(10), 20282-20298; https://doi.org/10.3390/ijms141020282 - 14 Oct 2013

Cited by 11 | Viewed by 6202

Abstract

Endothelial dysfunction in kidney vasculature is the initial and key element for nephropathy in diabetes mellitus. Accumulating evidence suggests the protective role of Rho kinase inhibitors in endothelial dysfunction via modulating eNOS activity and NO production. However, the role of Rho kinase in [...] Read more.

Endothelial dysfunction in kidney vasculature is the initial and key element for nephropathy in diabetes mellitus. Accumulating evidence suggests the protective role of Rho kinase inhibitors in endothelial dysfunction via modulating eNOS activity and NO production. However, the role of Rho kinase in diabetes-related endothelial dysfunction in kidney vasculature and the relevant mechanisms remain unknown. We assessed whether pharmacological inhibition of Rho kinase attenuates endothelial dysfunction in intrarenal arteries from type 1 diabetic rats. Fasudil, a Rho kinase inhibitor effectively decreased the phosphorylated level of MYPT1 without affecting the expression of ROCKs in the kidney. Fasudil treatment showed no improvement in diabetes-related abnormality in metabolic indices, but it significantly ameliorated endothelial dysfunction in intrarenal arteries and lessened the mesangial matrix expansion in the kidney cortex. Mechanistically, superoxide production in the intrarenal artery and NOX4 member of NADPH oxidase in the renal cortex that contribute to diabetic nephropathy were also prevented by the Rho kinase inhibitor. In conclusion, the present results indicate that Rho kinase is involved in endothelial dysfunction in type 1 diabetes via enhancement of oxidative stress and provides new evidence for Rho kinase inhibitors as potential therapeutic agents for the treatment of diabetic nephropathy. Full article

(This article belongs to the Section Biochemistry)

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27 pages, 2063 KiB

Open AccessArticle

Physiological and Proteomic Responses of Diploid and Tetraploid Black Locust (Robinia pseudoacacia L.) Subjected to Salt Stress

by Zhiming Wang^1,†, Mingyue Wang^1,†, Likun Liu² and Fanjuan Meng^1,*

¹ College of Life Science, Northeast Forestry University, Harbin 150040, China

² Department of Medical Biotechnology, College of Biomedical Science, Kangwon National University, Chuncheon, Gangwon-do 200-701, Korea

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2013, 14(10), 20299-20325; https://doi.org/10.3390/ijms141020299 - 14 Oct 2013

Cited by 111 | Viewed by 9161

Abstract

Tetraploid black locust (Robinia pseudoacacia L.) is adaptable to salt stress. Here, we compared morphological, physiological, ultrastructural, and proteomic traits of leaves in tetraploid black locust and its diploid relatives under salt stress. The results showed that diploid (2×) plants suffered from [...] Read more.

Tetraploid black locust (Robinia pseudoacacia L.) is adaptable to salt stress. Here, we compared morphological, physiological, ultrastructural, and proteomic traits of leaves in tetraploid black locust and its diploid relatives under salt stress. The results showed that diploid (2×) plants suffered from greater negative effects than those of tetraploid (4×) plants. After salt treatment, plant growth was inhibited, photosynthesis was reduced, reactive oxygen species, malondialdehyde content, and relative electrolyte leakage increased, and defense-related enzyme activities decreased in 2× compared to those in 4×. In addition, salt stress resulted in distorted chloroplasts, swollen thylakoid membranes, accumulation of plastoglobules, and increased starch grains in 2× compared to those in 4×. However, 4× developed diverse responses under salt stress. A comparative proteomic analysis revealed that 41 and 37 proteins were differentially expressed in 2× and 4×, respectively. These proteins were mainly involved in photosynthesis, stress and defense, energy, metabolism, transcription/translation, and transportation. Distinct patterns of protein changes between 2× and 4× were analyzed. Collectively, our results suggest that the plants showed significantly different responses to salt stress based on ploidy level of the plant. The 4× possessed a better salt protection mechanism than that of 2×, suggesting salt tolerance in the polyploid plant. Full article

(This article belongs to the Section Biochemistry)

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14 pages, 724 KiB

Open AccessArticle

MicroRNA Expression Profiling of the Porcine Developing Hypothalamus and Pituitary Tissue

by Lifan Zhang^1,†, Zhaowei Cai^2,†, Shengjuan Wei^3,†, Huiyun Zhou¹, Hongmei Zhou¹, Xiaoling Jiang¹ and Ningying Xu^1,*

¹ College of Animal Science, Zhejiang University, Hangzhou 310058, China

² Laboratory Animal Research Center, Zhejiang Chinese Medical University, Hangzhou 310053, China

³ Department of Animal Sciences, Washington State University, Pullman, WA 99164, USA

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2013, 14(10), 20326-20339; https://doi.org/10.3390/ijms141020326 - 14 Oct 2013

Cited by 21 | Viewed by 7485

Abstract

MicroRNAs (miRNAs), a class of small non-coding RNA molecules, play important roles in gene expressions at transcriptional and post-transcriptional stages in mammalian brain. So far, a growing number of porcine miRNAs and their function have been identified, but little is known regarding the [...] Read more.

MicroRNAs (miRNAs), a class of small non-coding RNA molecules, play important roles in gene expressions at transcriptional and post-transcriptional stages in mammalian brain. So far, a growing number of porcine miRNAs and their function have been identified, but little is known regarding the porcine developing hypothalamus and pituitary. In the present study, Solexa sequencing analysis showed 14,129,397 yielded reads, 6,680,678 of which were related to 674 unique miRNAs. After a microarray assay, we detected 175 unique miRNAs in the hypothalamus, including 136 previously known miRNAs and 39 novel candidates, while a total of 140 miRNAs, including 104 known and 36 new candidate miRNAs, were discovered in pituitary. More importantly, 37 and 30 differentially expressed miRNAs from several developmental stages of hypothalamus and pituitary were revealed, respectively. The 37 differentially expressed miRNAs in hypothalamus represented 6 different expression patterns, while the 30 differentially expressed miRNAs in pituitary represented 7 different expression patterns. To clarify potential target genes and specific functions of these differentially expressed miRNAs in hypothalamus and pituitary, TargetScan and Gorilla prediction tools were then applied. The current functional analysis showed that the differentially expressed miRNAs in hypothalamus and pituitary shared many biological processes, with the main differences being found in tissue-specific processes including: CDP-diacylglycerol biosynthetic/metabolic process; phosphatidic acid biosynthetic/metabolic process; energy reserve metabolic process for hypothalamus; adult behavior; sterol transport/homeostasis; and cholesterol/reverse cholesterol transport for pituitary. Overall, this study identified miRNA profiles and differentially expressed miRNAs among various developmental stages in hypothalamus and pituitary and indicated miRNA profiles change with age and brain location, enhancing our knowledge about spatial and temporal expressions of miRNAs in the porcine developing brain. Full article

(This article belongs to the Section Biochemistry)

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19 pages, 834 KiB

Open AccessArticle

Strengths and Weaknesses of Recently Engineered Red Fluorescent Proteins Evaluated in Live Cells Using Fluorescence Correlation Spectroscopy

by Amanda P. Siegel¹, Michelle A. Baird², Michael W. Davidson² and Richard N. Day^1,*

¹ Department of Cellular and Integrative Physiology, Indiana University School of Medicine, 635 Barnhill Dr., MS 333, Indianapolis, IN 46202, USA

² National High Magnetic Field Laboratory and Department of Biological Science, 1800 E. Paul Dirac Dr., Florida State University, Tallahassee, FL 32310, USA

Int. J. Mol. Sci. 2013, 14(10), 20340-20358; https://doi.org/10.3390/ijms141020340 - 14 Oct 2013

Cited by 24 | Viewed by 8661

Abstract

The scientific community is still looking for a bright, stable red fluorescent protein (FP) as functional as the current best derivatives of green fluorescent protein (GFP). The red FPs exploit the reduced background of cells imaged in the red region of the visible [...] Read more.

The scientific community is still looking for a bright, stable red fluorescent protein (FP) as functional as the current best derivatives of green fluorescent protein (GFP). The red FPs exploit the reduced background of cells imaged in the red region of the visible spectrum, but photophysical short comings have limited their use for some spectroscopic approaches. Introduced nearly a decade ago, mCherry remains the most often used red FP for fluorescence correlation spectroscopy (FCS) and other single molecule techniques, despite the advent of many newer red FPs. All red FPs suffer from complex photophysics involving reversible conversions to a dark state (flickering), a property that results in fairly low red FP quantum yields and potential interference with spectroscopic analyses including FCS. The current report describes assays developed to determine the best working conditions for, and to uncover the shortcoming of, four recently engineered red FPs for use in FCS and other diffusion and spectroscopic studies. All five red FPs assayed had potential shortcomings leading to the conclusion that the current best red FP for FCS is still mCherry. The assays developed here aim to enable the rapid evaluation of new red FPs and their smooth adaptation to live cell spectroscopic microscopy and nanoscopy. Full article

(This article belongs to the Special Issue Frontiers of Micro-Spectroscopy in Biological Applications)

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27 pages, 1335 KiB

Open AccessReview

HKT Transporters—State of the Art

by Pedro Almeida^1,*, Diana Katschnig² and Albertus H. De Boer¹

¹ Vrije Universiteit Amsterdam, Faculty Earth and Life Sciences, Department of Structural Biology, Amsterdam NL-1081 HV, The Netherlands

² Vrije Universiteit Amsterdam, Faculty Earth and Life Sciences, Systems Ecology, Department of Ecological Science, Amsterdam NL-1081 HV, The Netherlands

Int. J. Mol. Sci. 2013, 14(10), 20359-20385; https://doi.org/10.3390/ijms141020359 - 14 Oct 2013

Cited by 114 | Viewed by 10007

Abstract

The increase in soil salinity poses a serious threat to agricultural yields. Under salinity stress, several Na⁺ transporters play an essential role in Na⁺ tolerance in plants. Amongst all Na⁺ transporters, HKT has been shown to have a crucial role [...] Read more.

The increase in soil salinity poses a serious threat to agricultural yields. Under salinity stress, several Na⁺ transporters play an essential role in Na⁺ tolerance in plants. Amongst all Na⁺ transporters, HKT has been shown to have a crucial role in both mono and dicotyledonous plants in the tolerance to salinity stress. Here we present an overview of the physiological role of HKT transporters in plant Na⁺ homeostasis. HKT regulation and amino acids important to the correct function of HKT transporters are reviewed. The functions of the most recently characterized HKT members from both HKT1 and HKT2 subfamilies are also discussed. Topics that still need to be studied in future research (e.g., HKT regulation) as well as research suggestions (e.g., generation of HKT mutants) are addressed. Full article

(This article belongs to the Section Biochemistry)

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13 pages, 2239 KiB

Open AccessArticle

Molecular Study of a Hoxa2 Gain-of-Function in Chondrogenesis: A Model of Idiopathic Proportionate Short Stature

by Pierre M. L. Deprez¹, Miloud G. Nichane², Benoît G. Lengelé³, René Rezsöhazy² and Catherine Nyssen-Behets^3,*

¹ Ecole de Kinésiologie et Récréologie, Faculté des Sciences de la Santé et Services Communautaires, Université de Moncton, Moncton, NB E1A 3E9, Canada

² Embryologie Moléculaire et Cellulaire Animale, Institut des Sciences de la Vie, Université catholique de Louvain, Louvain-la-Neuve 1348, Belgium

³ Morphologie, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Brussels 1200, Belgium

Int. J. Mol. Sci. 2013, 14(10), 20386-20398; https://doi.org/10.3390/ijms141020386 - 14 Oct 2013

Cited by 6 | Viewed by 8293

Abstract

In a previous study using transgenic mice ectopically expressing Hoxa2 during chondrogenesis, we associated the animal phenotype to human idiopathic proportionate short stature. Our analysis showed that this overall size reduction was correlated with a negative influence of Hoxa2 at the first step [...] Read more.

In a previous study using transgenic mice ectopically expressing Hoxa2 during chondrogenesis, we associated the animal phenotype to human idiopathic proportionate short stature. Our analysis showed that this overall size reduction was correlated with a negative influence of Hoxa2 at the first step of endochondral ossification. However, the molecular pathways leading to such phenotype are still unknown. Using protein immunodetection and histological techniques comparing transgenic mice to controls, we show here that the persistent expression of Hoxa2 in chondrogenic territories provokes a general down-regulation of the main factors controlling the differentiation cascade, such as Bapx1, Bmp7, Bmpr1a, Ihh, Msx1, Pax9, Sox6, Sox9 and Wnt5a. These data confirm the impairment of chondrogenic differentiation by Hoxa2 overexpression. They also show a selective effect of Hoxa2 on endochondral ossification processes since Gdf5 and Gdf10, and Bmp4 or PthrP were up-regulated and unmodified, respectively. Since Hoxa2 deregulation in mice induces a proportionate short stature phenotype mimicking human idiopathic conditions, our results give an insight into understanding proportionate short stature pathogenesis by highlighting molecular factors whose combined deregulation may be involved in such a disease. Full article

(This article belongs to the Special Issue The Chondrocyte Phenotype in Cartilage Biology)

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15 pages, 337 KiB

Open AccessArticle

Genetic Diversity and Population Differentiation of Calanthe tsoongiana, a Rare and Endemic Orchid in China

by Xin Qian, Cai-xia Wang and Min Tian^*

Research Institution of Subtropical Forestry, Chinese Academy of Forestry, 73, Daqiao Road, Fuyang 311400, Zhejiang, China

Int. J. Mol. Sci. 2013, 14(10), 20399-20413; https://doi.org/10.3390/ijms141020399 - 14 Oct 2013

Cited by 34 | Viewed by 7745

Abstract

Calanthe tsoongiana is a rare terrestrial orchid endemic to China, and this species has experienced severe habitat loss and fragmentation. Inter-simple sequence repeat (ISSR) markers were employed to assess the genetic diversity and differentiation of six populations of C. tsoongiana. Based on [...] Read more.

Calanthe tsoongiana is a rare terrestrial orchid endemic to China, and this species has experienced severe habitat loss and fragmentation. Inter-simple sequence repeat (ISSR) markers were employed to assess the genetic diversity and differentiation of six populations of C. tsoongiana. Based on 124 discernible fragments yielded by eleven selected primers, high genetic diversity was revealed at the species level; however, genetic diversity at the population level was relatively low. High-level genetic differentiation among populations was detected based on analysis of molecular variance (AMOVA), indicating potential limited gene flow. No significant relationship was observed between genetic and geographic distances among the sampled populations. These results suggested that restricted gene flow might be due to habitat fragmentation and reduced population size as a result of human activities. Based on the findings, several conservation strategies were proposed for the preservation of this threatened species. Full article

(This article belongs to the Section Biochemistry)

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13 pages, 622 KiB

Open AccessArticle

Characterization of 42 Microsatellite Markers from Poison Ivy, Toxicodendron radicans (Anacardiaceae)

by Tsai-Wen Hsu¹, Huei-Chuan Shih², Chia-Chi Kuo², Tzen-Yuh Chiang^3,* and Yu-Chung Chiang^4,*

¹ Endemic Species Research Institute, Nantou 552, Taiwan

² Department of Nursing, Meiho University, Pingtung 912, Taiwan

³ Department of Life Sciences, National Cheng Kung University, Tainan 701, Taiwan

⁴ Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung 804, Taiwan

Int. J. Mol. Sci. 2013, 14(10), 20414-20426; https://doi.org/10.3390/ijms141020414 - 14 Oct 2013

Cited by 17 | Viewed by 6265

Abstract

Poison ivy, Toxicodendron radicans, and poison oaks, T. diversilobum and T. pubescens, are perennial woody species of the Anacardiaceae and are poisonous, containing strong allergens named urushiols that cause allergic contact dermatitis. Poison ivy is a species distributed from [...] Read more.

Poison ivy, Toxicodendron radicans, and poison oaks, T. diversilobum and T. pubescens, are perennial woody species of the Anacardiaceae and are poisonous, containing strong allergens named urushiols that cause allergic contact dermatitis. Poison ivy is a species distributed from North America to East Asia, while T. diversilobum and T. pubescens are distributed in western and eastern North America, respectively. Phylogreography and population structure of these species remain unclear. Here, we developed microsatellite markers, via constructing a magnetic enriched microsatellite library, from poison ivy. We designed 51 primer pairs, 42 of which successfully yielded products that were subsequently tested for polymorphism in poison oak, and three subspecies of poison ivy. Among the 42 loci, 38 are polymorphic, while 4 are monomorphic. The number of alleles and the expected heterozygosity ranged from 1 to 12 and from 0.10 to 0.87, respectively, in poison ivy, while varied from 2 to 8 and, from 0.26 to 0.83, respectively in poison oak. Genetic analysis revealed distinct differentiation between poison ivy and poison oak, whereas slight genetic differentiation was detected among three subspecies of poison ivy. These highly polymorphic microsatellite fingerprints enable biologists to explore the population genetics, phylogeography, and speciation in Toxicodendron. Full article

(This article belongs to the Section Biochemistry)

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16 pages, 284 KiB

Open AccessReview

An Emerging Role for Long Non-Coding RNA Dysregulation in Neurological Disorders

by Chiara Fenoglio^*, Elisa Ridolfi, Daniela Galimberti and Elio Scarpini

Department of Pathophysiology and Transplantation, University of Milan, "Dino Ferrari" Center, IRCCS Cà Granda Foundation Ospedale Maggiore Policlinico, Via F.Sforza 35, Milan 20122, Italy

Int. J. Mol. Sci. 2013, 14(10), 20427-20442; https://doi.org/10.3390/ijms141020427 - 14 Oct 2013

Cited by 61 | Viewed by 10751

Abstract

A novel class of transcripts, long non coding RNAs (lncRNAs), has recently emerged as key players in several biological processes, including dosage compensation, genomic imprinting, chromatin regulation, embryonic development and segmentation, stem cell pluripotency, cell fate determination and potentially many other biological processes, [...] Read more.

A novel class of transcripts, long non coding RNAs (lncRNAs), has recently emerged as key players in several biological processes, including dosage compensation, genomic imprinting, chromatin regulation, embryonic development and segmentation, stem cell pluripotency, cell fate determination and potentially many other biological processes, which still are to be elucidated. LncRNAs are pervasively transcribed in the genome and several lines of evidence correlate dysregulation of different lncRNAs to human diseases including neurological disorders. Although their mechanisms of action are yet to be fully elucidated, evidence suggests lncRNA contributions to the pathogenesis of a number of diseases. In this review, the current state of knowledge linking lncRNAs to different neurological disorders is discussed and potential future directions are considered. Full article

(This article belongs to the Special Issue Regulation by non-coding RNAs 2013)

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16 pages, 760 KiB

Open AccessArticle

Inhibition of Melanogenesis by Gallic Acid: Possible Involvement of the PI3K/Akt, MEK/ERK and Wnt/β-Catenin Signaling Pathways in B16F10 Cells

by Tzu-Rong Su^1,†, Jen-Jie Lin^2,†, Chi-Chu Tsai³, Tsu-Kei Huang¹, Zih-Yan Yang⁴, Ming-O Wu^5,6, Yu-Qing Zheng⁵, Ching-Chyuan Su¹ and Yu-Jen Wu^5,*

¹ Antai Medical Care Cooperation Antai Tian-Sheng Memorial Hospital, Pingtung 92842, Taiwan

² Graduate Institute of Veterinary Medicine, National Pingtung University of Science and Technology, Pingtung 91202, Taiwan

³ Kaohsiung District Agricultural Improvement Station, Pingtung 900, Taiwan

⁴ Graduate Institute of Food Science, National Pingtung University of Science and Technology, Pingtung 91202, Taiwan

⁵ Department of Beauty Science, Meiho University, Pingtung 91202, Taiwan

⁶ Graduate Institute of Applied Health and Biotechnology, Meiho University, Pingtung 91202, Taiwan

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2013, 14(10), 20443-20458; https://doi.org/10.3390/ijms141020443 - 14 Oct 2013

Cited by 150 | Viewed by 12590

Abstract

Gallic acid is one of the major flavonoids found in plants. It acts as an antioxidant, and seems to have anti-inflammatory, anti-viral, and anti-cancer properties. In this study, we investigated the effects of gallic acid on melanogenesis, including the activation of melanogenesis signaling [...] Read more.

Gallic acid is one of the major flavonoids found in plants. It acts as an antioxidant, and seems to have anti-inflammatory, anti-viral, and anti-cancer properties. In this study, we investigated the effects of gallic acid on melanogenesis, including the activation of melanogenesis signaling pathways. Gallic acid significantly inhibited both melanin synthesis and tyrosinase activity in a dose- and time-dependent manner, and decreased the expression of melanogenesis-related proteins, such as microphthalmia-associated transcription factor (MITF), tyrosinase, tyrosinase-related protein-1 (TRP1), and dopachrome tautomerase (Dct). In addition, gallic acid also acts by phosphorylating and activating melanogenesis inhibitory proteins such as Akt and mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK). Using inhibitors against PI3K/Akt (LY294002) or MEK/ERK-specific (PD98059), the hypopigmentation effect was suppressed, and the gallic acid-initiated activation of MEK/ERK and PI3K/Akt was also revoked. Gallic acid also increased GSK3β and p-β-catenin expression but down-regulated p-GSK3β. Moreover, GSK3β-specific inhibitor (SB216763) restored gallic acid-induced melanin reduction. These results suggest that activation of the MEK/ERK, PI3K/Akt, and inhibition of Wnt/β-catenin signaling pathways is involved in the melanogenesis signaling cascade, and that activation by gallic acid reduces melanin synthesis via down-regulation of MITF and its downstream signaling pathway. In conclusion, gallic acid may be a potentially agent for the treatment of certain skin conditions. Full article

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19 pages, 3436 KiB

Open AccessArticle

Twist and miR-34a Are Involved in the Generation of Tumor-Educated Myeloid-Derived Suppressor Cells

by Xin Wang^1,2,†, Xusheng Chang^3,†, Guangzuan Zhuo^4,†, Mingjuan Sun^5,* and Kai Yin^1,*

¹ Department of General Surgery, Changhai Hospital, the Second Military Medical University, Shanghai 200433, China

² Department of Gynaecology and Obstetrics, the 306 Hospital of PLA, Beijing 100037, China

³ Department of General Surgery, Yancheng City First People's Hospital, Yancheng City 224000, Jiangsu, China

⁴ Department of Colorectal Surgery, the Second Artillery General Hospital of PLA, Beijing 10008, China

⁵ Department of Biochemistry and Molecular Biology, Second Military Medical University, Shanghai 200433, China

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2013, 14(10), 20459-20477; https://doi.org/10.3390/ijms141020459 - 14 Oct 2013

Cited by 13 | Viewed by 6175

Abstract

Tumors can induce the generation and accumulation of immunosuppressive cells such as myeloid-derived suppressor cells in the tumor microenvironment, contributing to tumor immunological escapes. Many studies have demonstrated that multiple factors could induce myeloid precursor cells into myeloid-derived suppressor cells, not dendritic cells. [...] Read more.

Tumors can induce the generation and accumulation of immunosuppressive cells such as myeloid-derived suppressor cells in the tumor microenvironment, contributing to tumor immunological escapes. Many studies have demonstrated that multiple factors could induce myeloid precursor cells into myeloid-derived suppressor cells, not dendritic cells. In our study, we found that tumor supernatants could induce the generation of myeloid-derived suppressor cells by disturbing the development of dendritic cells. Twist and miR-34a may regulate the effect of tumor cells inducing myeloid-derived suppressor cells via TGF-β and/or IL-10. Full article

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14 pages, 271 KiB

Open AccessArticle

Transcriptome Comparative Profiling of Barley eibi1 Mutant Reveals Pleiotropic Effects of HvABCG31 Gene on Cuticle Biogenesis and Stress Responsive Pathways

by Zujun Yang^1,*

, Tao Zhang¹, Tao Lang¹, Guangrong Li¹, Guoxiong Chen² and Eviatar Nevo³

¹ School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, Sichuan, China

² Extreme Stress Resistance and Biotechnology Laboratory, Cold and Arid Regions Environmental and Engineering Institute, Chinese Academy of Sciences, Lanzhou 730000, Gansu, China

³ Institute of Evolution, University of Haifa, Mount Carmel, Haifa 31905, Israel

Int. J. Mol. Sci. 2013, 14(10), 20478-20491; https://doi.org/10.3390/ijms141020478 - 14 Oct 2013

Cited by 13 | Viewed by 7155

Abstract

Wild barley eibi1 mutant with HvABCG31 gene mutation has low capacity to retain leaf water, a phenotype associated with reduced cutin deposition and a thin cuticle. To better understand how such a mutant plant survives, we performed a genome-wide gene expression analysis. The [...] Read more.

Wild barley eibi1 mutant with HvABCG31 gene mutation has low capacity to retain leaf water, a phenotype associated with reduced cutin deposition and a thin cuticle. To better understand how such a mutant plant survives, we performed a genome-wide gene expression analysis. The leaf transcriptomes between the near-isogenic lines eibi1 and the wild type were compared using the 22-k Barley1 Affymetrix microarray. We found that the pleiotropic effect of the single gene HvABCG31 mutation was linked to the co-regulation of metabolic processes and stress-related system. The cuticle development involved cytochrome P450 family members and fatty acid metabolism pathways were significantly up-regulated by the HvABCG31 mutation, which might be anticipated to reduce the levels of cutin monomers or wax and display conspicuous cuticle defects. The candidate genes for responses to stress were induced by eibi1 mutant through activating the jasmonate pathway. The down-regulation of co-expressed enzyme genes responsible for DNA methylation and histone deacetylation also suggested that HvABCG31 mutation may affect the epigenetic regulation for barley development. Comparison of transcriptomic profiling of barley under biotic and abiotic stresses revealed that the functions of HvABCG31 gene to high-water loss rate might be different from other osmotic stresses of gene mutations in barley. The transcriptional profiling of the HvABCG31 mutation provided candidate genes for further investigation of the physiological and developmental changes caused by the mutant. Full article

(This article belongs to the Section Biochemistry)

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16 pages, 870 KiB

Open AccessArticle

Significant Overexpression of DVL1 in Taiwanese Colorectal Cancer Patients with Liver Metastasis

by Ming-Yii Huang^1,2,3, Li-Chen Yen⁴, Hsueh-Chiao Liu⁵, Po-Ping Liu⁶, Fu-Yen Chung⁴, Tsu-Nai Wang⁷, Jaw-Yuan Wang^3,8,9,10,*

and Shiu-Ru Lin^4,11,*

¹ Department of Radiation Oncology, Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan

² Department of Radiation Oncology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan

³ Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan

⁴ Division of Medical Research, Fooyin University Hospital, Pingtung 928, Taiwan

⁵ Personalized Medical Service Center, Division of Laboratory Medicine, Fooyin University Hospital, Pingtung 928, Taiwan

⁶ Department of Surgery, Fooyin University Hospital, Pingtung 928, Taiwan

⁷ Department of Public Health, College of Health Science, Kaohsiung Medical University, Kaohsiung 807, Taiwan

⁸ Division of Gastrointestinal and General Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan

⁹ Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan

¹⁰ Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan

¹¹ School of Medical and Health Sciences, Fooyin University, Kaohsiung 831, Taiwan

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Int. J. Mol. Sci. 2013, 14(10), 20492-20507; https://doi.org/10.3390/ijms141020492 - 14 Oct 2013

Cited by 17 | Viewed by 6881

Abstract

Undetected micrometastasis plays a key role in the metastasis of cancer in colorectal cancer (CRC) patients. The aim of this study is to identify a biomarker of CRC patients with liver metastasis through the detection of circulating tumor cells (CTCs). Microarray and bioinformatics [...] Read more.

Undetected micrometastasis plays a key role in the metastasis of cancer in colorectal cancer (CRC) patients. The aim of this study is to identify a biomarker of CRC patients with liver metastasis through the detection of circulating tumor cells (CTCs). Microarray and bioinformatics analysis of 10 CRC cancer tissue specimens compared with normal adjacent tissues revealed that 31 genes were up-regulated (gene expression ratio of cancer tissue to paired normal tissue > 2) in the cancer patients. We used a weighted enzymatic chip array (WEnCA) including 31 prognosis-related genes to investigate CTCs in 214 postoperative stage I–III CRC patients and to analyze the correlation between gene expression and clinico-pathological parameters. We employed the immunohistochemistry (IHC) method with polyclonal mouse antibody against DVL1 to detect DVL1 expression in 60 CRC patients. CRC liver metastasis occurred in 19.16% (41/214) of the patients. Using univariate analysis and multivariate proportional hazards regression analysis, we found that DVL1 mRNA overexpression had a significant, independent predictive value for liver metastasis in CRC patients (OR: 5.764; 95% CI: 2.588–12.837; p < 0.0001 on univariate analysis; OR: 3.768; 95% CI: 1.469–9.665; p = 0.006 on multivariate analysis). IHC staining of the immunoreactivity of DVL1 showed that DVL1 was localized in the cytoplasm of CRC cells. High expression of DVL1 was observed in 55% (33/60) of CRC tumor specimens and was associated significantly with tumor depth, perineural invasion and liver metastasis status (all p < 0.05). Our experimental results demonstrated that DVL1 is significantly overexpressed in CRC patients with liver metastasis, leading us to conclude that DVL1 could be a potential prognostic and predictive marker for CRC patients. Full article

(This article belongs to the Special Issue Pathogenesis and Prevention of Colorectal Cancer)

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35 pages, 301 KiB

Open AccessReview

Advances in the Research of Melatonin in Autism Spectrum Disorders: Literature Review and New Perspectives

by Sylvie Tordjman^1,2,*, Imen Najjar¹, Eric Bellissant^3,4, George M. Anderson^5,6, Marianne Barburoth², David Cohen⁷, Nemat Jaafari⁸, Olivier Schischmanoff^9,10, Rémi Fagard^9,10, Enas Lagdas¹, Solenn Kermarrec¹, Sophie Ribardiere¹, Michel Botbol¹¹, Claire Fougerou^3,4, Guillaume Bronsard¹² and Julie Vernay-Leconte¹

¹ Hospital-University Department of Child and Adolescent Psychiatry, Guillaume Régnier Hospital, Rennes 1 University, Rennes 35000, France

² Laboratory of Psychology of Perception, CNRS UMR 8158, Paris 75270, France

³ Inserm CIC 0203 Clinical Investigation Centre, University Hospital, Rennes 1 University, Rennes 35033, France

⁴ Department of Clinical Pharmacology, University Hospital, Rennes 1 University, Rennes 35033, France

⁵ Laboratory of Developmental Neurochemistry, Yale Child Study Center, New Haven, CT 06519, USA

⁶ Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT 06519, USA

⁷ Hospital-University Department of Child and Adolescent Psychiatry, Pitié-SalpétrièreHospital, Paris 6 University, Paris 75013, France

⁸ CIC INSERM U 802, CHU de Poitiers, Unité de recherche clinique intersectorielle en psychiatrie du Centre Hospitalier Henri Laborit, Poitiers 86022, France

⁹ INSERM UMR U978, University of Paris 13, Bobigny 93009, France

¹⁰ Laboratoire de Biochimie et Biologie Moléculaire, Hôpital Avicenne, APHP, Bobigny 93009, France

¹¹ Service Hospitalo-Universitaire de Psychiatrie de l'Enfant et de l'Adolescent de Brest, UBO, Brest 29238, France

¹² Maison Départementale de l’Adolescent et Centre Médico-Psycho-Pédagogique, Conseil Général des Bouches-du-Rhône, Laboratoire de Santé Publique EA3279, Faculté de Médecine de la Timone, Marseille 13256, France

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Int. J. Mol. Sci. 2013, 14(10), 20508-20542; https://doi.org/10.3390/ijms141020508 - 14 Oct 2013

Cited by 102 | Viewed by 17944

Abstract

Abnormalities in melatonin physiology may be involved or closely linked to the pathophysiology and behavioral expression of autistic disorder, given its role in neurodevelopment and reports of sleep-wake rhythm disturbances, decreased nocturnal melatonin production, and beneficial therapeutic effects of melatonin in individuals with [...] Read more.

Abnormalities in melatonin physiology may be involved or closely linked to the pathophysiology and behavioral expression of autistic disorder, given its role in neurodevelopment and reports of sleep-wake rhythm disturbances, decreased nocturnal melatonin production, and beneficial therapeutic effects of melatonin in individuals with autism. In addition, melatonin, as a pineal gland hormone produced from serotonin, is of special interest in autistic disorder given reported alterations in central and peripheral serotonin neurobiology. More specifically, the role of melatonin in the ontogenetic establishment of circadian rhythms and the synchronization of peripheral oscillators opens interesting perspectives to ascertain better the mechanisms underlying the significant relationship found between lower nocturnal melatonin excretion and increased severity of autistic social communication impairments, especially for verbal communication and social imitative play. In this article, first we review the studies on melatonin levels and the treatment studies of melatonin in autistic disorder. Then, we discuss the relationships between melatonin and autistic behavioral impairments with regard to social communication (verbal and non-verbal communication, social interaction), and repetitive behaviors or interests with difficulties adapting to change. In conclusion, we emphasize that randomized clinical trials in autism spectrum disorders are warranted to establish potential therapeutic efficacy of melatonin for social communication impairments and stereotyped behaviors or interests. Full article

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

12 pages, 469 KiB

Open AccessArticle

Combined Taurine, Epigallocatechin Gallate and Genistein Therapy Reduces HSC-T6 Cell Proliferation and Modulates the Expression of Fibrogenic Factors

by Yan Li¹, Ying Luo², Xuerong Zhang², Xing Lin², Min He² and Ming Liao^2,*

¹ Guangxi University Library, Guangxi University, Nanning 530004, Guangxi, China

² Key Laboratory Joint Established by Ministry of Education and Guangxi, Medical Scientific Research Center of Guangxi Medical University, Nanning 530021, Guangxi, China

Int. J. Mol. Sci. 2013, 14(10), 20543-20554; https://doi.org/10.3390/ijms141020543 - 14 Oct 2013

Cited by 20 | Viewed by 6922 | Correction

Abstract

Hepatic fibrogenesis involves the activation of hepatic stellate cells (HSCs), which synthesize excess extracellular matrix and contribute to the development of liver fibrosis. In a prior study we tested the effect of combined treatment with taurine, epigallocatechin gallate and genistein on the development [...] Read more.

Hepatic fibrogenesis involves the activation of hepatic stellate cells (HSCs), which synthesize excess extracellular matrix and contribute to the development of liver fibrosis. In a prior study we tested the effect of combined treatment with taurine, epigallocatechin gallate and genistein on the development of alcohol-induced liver fibrosis in vitro. In this study, the biological activity of the combination of these molecules was assessed by measuring its effect on cell proliferation, fibrosis-related gene expression, and proteomic expression profiling in the activated HSC cell line, HSC-T6. HSC-T6 cells were incubated with different concentrations of the drug combination taurine, epigallocatechin gallate and genistein. Cell proliferation was evaluated by MTT assay. Transforming growth factor β1 (TGF-β1), collagen type I (Col-I), matrix metalloproteinase-2 (MMP-2), and tissue inhibitor of metalloproteinases 1 and 2 (TIMP-1 and TIMP-2) mRNA were analyzed by semi-quantitative reverse-transcription PCR. Proteomic profiling of HSC-T6 cells was also performed by SELDI-TOF-MS. Combined drug treatment significantly inhibited cell proliferation and TGF-β1, Col-I, TIMP-1 and TIMP-2 mRNA expression in activated HSC-T6 cells, while the expression of MMP-2 mRNA increased. A total of 176 protein m/z peaks were identified. The intensities of 10 protein peaks were downregulated and two protein peaks were upregulated in HSC-T6 cells after combined drug treatment. In conclusion, combined drug treatment with taurine, epigallocatechin gallate and genistein can inhibit HSC proliferation, and impact fibrosis-related gene and protein expression. The antifibrotic effects of this drug combination may be due to its effects on the expression of fibrogenic genes. Full article

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

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9 pages, 490 KiB

Open AccessArticle

The Key Enzyme of the Sialic Acid Metabolism Is Involved in Embryoid Body Formation and Expression of Marker Genes of Germ Layer Formation

by Wenke Weidemann, Jessica Hering, Dorit Bennmann, Annett Thate and Rüdiger Horstkorte^*

Institut für Physiologische Chemie, Martin-Luther-Universität Halle-Wittenberg, Hollystr.1, Halle D-06114, Germany

Int. J. Mol. Sci. 2013, 14(10), 20555-20563; https://doi.org/10.3390/ijms141020555 - 14 Oct 2013

Cited by 6 | Viewed by 7102

Abstract

The bi-functional enzyme UDP-N-acetyl-2-epimerase/N-acetylmannosamine kinase (GNE) is the key enzyme of the sialic acid biosynthesis. Sialic acids are negatively charged nine carbon amino sugars and are found on most glycoproteins and many glycolipids in terminal positions, where they are [...] Read more.

The bi-functional enzyme UDP-N-acetyl-2-epimerase/N-acetylmannosamine kinase (GNE) is the key enzyme of the sialic acid biosynthesis. Sialic acids are negatively charged nine carbon amino sugars and are found on most glycoproteins and many glycolipids in terminal positions, where they are involved in a variety of biological important molecular interactions. Inactivation of the GNE by homologous recombination results in early embryonic lethality in mice. Here, we report that GNE-deficient embryonic stem cells express less differentiation markers compared to wild-type embryonic stem cells. As a result, GNE-deficient embryonic stem cells fail to form proper embryoid bodies (EB) within the first day of culture. However, when culturing these cells in the presence of sialic acids for three days, also GNE-deficient embryonic stem cells form normal EBs. In contrast, when culturing these cells in sialic acid reduced medium, GNE-deficient embryonic stem cells proliferate faster and form larger EBs without any change in the expression of markers of the germ layers. Full article

(This article belongs to the Special Issue Glycosylation and Glycoproteins)

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14 pages, 324 KiB

Open AccessArticle

Erucin Exerts Anti-Inflammatory Properties in Murine Macrophages and Mouse Skin: Possible Mediation through the Inhibition of NFκB Signaling

by Han Jin Cho^1,2, Ki Won Lee^2,3,4 and Jung Han Yoon Park^1,3,*

¹ Department of Food and Nutrition, Hallym University, Chuncheon 200-702, Korea

² Institute of Green Bio Science & Technology Seoul National University, Pyeongchang 232-916, Korea

³ Advanced Institutes of Convergence Technology, Seoul National University, Suwon, Gyonggi-do 443-270, Korea

⁴ WCU Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul 151-921, Korea

Int. J. Mol. Sci. 2013, 14(10), 20564-20577; https://doi.org/10.3390/ijms141020564 - 15 Oct 2013

Cited by 33 | Viewed by 6958

Abstract

Erucin, an isothiocyanate, is a hydrolysis product of glucoerucin found in arugula and has recently been reported to have anti-cancer properties in various cancer cells. In this study, we assessed the anti-inflammatory effects of erucin and the underlying mechanisms, using lipopolysaccharide (LPS)-stimulated RAW [...] Read more.

Erucin, an isothiocyanate, is a hydrolysis product of glucoerucin found in arugula and has recently been reported to have anti-cancer properties in various cancer cells. In this study, we assessed the anti-inflammatory effects of erucin and the underlying mechanisms, using lipopolysaccharide (LPS)-stimulated RAW 264.7 murine macrophages and 12-O-tetradecanoylphorbol-13-acetate-treated mouse skin. In RAW 264.7 cells, erucin (2.5, 5 μmol/L) inhibited LPS-induced production of nitric oxide and prostaglandin E₂. Erucin inhibited LPS-induced degradation of the inhibitor of κBα and translocation of p65 to the nucleus and, subsequently, reduced LPS-induced nuclear factor κB (NFκB) DNA binding activities, as well as the transcriptional activity of NFκB, leading to the decreased expression of NFκB-target genes, including tumor necrosis factor-α, interleukin (IL)-6, IL-1β, inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, as well as transcriptional activity of iNOS and COX-2. In mice, erucin (100, 300 nmoles) treatment significantly inhibited phorbol ester-induced formation of ear edema and expression of iNOS and COX-2 proteins. These results indicate that erucin exerts a potent anti-inflammatory activity by inhibiting the pro-inflammatory enzymes and cytokines, which may be mediated, at least in part, via the inhibition of NFκB signaling. Full article

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19 pages, 2311 KiB

Open AccessArticle

Structural Insights into a Novel Interkingdom Signaling Circuit by Cartography of the Ligand-Binding Sites of the Homologous Quorum Sensing LuxR-Family

by Sonia Covaceuszach¹, Giuliano Degrassi^2,3, Vittorio Venturi^2,* and Doriano Lamba^1,*

¹ Institute of Crystallography, National Research Council, Trieste Outstation, Area Science Park-Basovizza, S.S. n° 14 Km 163.5, I-34149 Trieste, Italy

² International Centre for Genetic Engineering and Biotechnology, Padriciano 99, I-34149 Trieste, Italy

³ IBIOBA-CONICET-ICGEB, International Centre for Genetic Engineering and Biotechnology, Scientific and Technological Center, Godoy Cruz 2390, C1425FQD, Buenos Aires, Argentina

Int. J. Mol. Sci. 2013, 14(10), 20578-20596; https://doi.org/10.3390/ijms141020578 - 15 Oct 2013

Cited by 19 | Viewed by 7438

Abstract

Recent studies have identified a novel interkingdom signaling circuit, via plant signaling molecules, and a bacterial sub-family of LuxR proteins, bridging eukaryotes and prokaryotes. Indeed pivotal plant-bacteria interactions are regulated by the so called Plant Associated Bacteria (PAB) LuxR solo regulators that, although [...] Read more.

Recent studies have identified a novel interkingdom signaling circuit, via plant signaling molecules, and a bacterial sub-family of LuxR proteins, bridging eukaryotes and prokaryotes. Indeed pivotal plant-bacteria interactions are regulated by the so called Plant Associated Bacteria (PAB) LuxR solo regulators that, although closely related to the quorum sensing (QS) LuxR family, do not bind or respond to canonical quorum sensing N-acyl homoserine lactones (AHLs), but only to specific host plant signal molecules. The large body of structural data available for several members of the QS LuxR family complexed with different classes of ligands (AHLs and other compounds), has been exploited to dissect the cartography of their regulatory domains through structure-based multiple sequence alignments, structural superimposition and a comparative analysis of the contact residues involved in ligand binding. In the absence of experimentally determined structures of members of the PAB LuxR solos subfamily, an homology model of its prototype OryR is presented, aiming to elucidate the architecture of its ligand-binding site. The obtained model, in combination with the cartography of the regulatory domains of the homologous QS LuxRs, provides novel insights into the 3D structure of its ligand-binding site and unveils the probable molecular determinants responsible for differences in selectivity towards specific host plant signal molecules, rather than to canonical QS compounds. Full article

(This article belongs to the Special Issue Quorum Sensing Research in Microbial Systems)

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17 pages, 635 KiB

Open AccessReview

The Epidermal Growth Factor Receptor and Its Ligands in Cardiovascular Disease

by Nader Makki¹, Kristina W. Thiel¹ and Francis J. Miller, Jr.^1,2,*

¹ Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA

² Veterans Affairs Medical Center, Iowa City, IA 52242, USA

Int. J. Mol. Sci. 2013, 14(10), 20597-20613; https://doi.org/10.3390/ijms141020597 - 15 Oct 2013

Cited by 127 | Viewed by 11640

Abstract

The epidermal growth factor receptor (EGFR) family and its ligands serve as a switchboard for the regulation of multiple cellular processes. While it is clear that EGFR activity is essential for normal cardiac development, its function in the vasculature and its role in [...] Read more.

The epidermal growth factor receptor (EGFR) family and its ligands serve as a switchboard for the regulation of multiple cellular processes. While it is clear that EGFR activity is essential for normal cardiac development, its function in the vasculature and its role in cardiovascular disease are only beginning to be elucidated. In the blood vessel, endothelial cells and smooth muscle cells are both a source and a target of EGF-like ligands. Activation of EGFR has been implicated in blood pressure regulation, endothelial dysfunction, neointimal hyperplasia, atherogenesis, and cardiac remodeling. Furthermore, increased circulating EGF-like ligands may mediate accelerated vascular disease associated with chronic inflammation. Although EGFR inhibitors are currently being used clinically for the treatment of cancer, additional studies are necessary to determine whether abrogation of EGFR signaling is a potential strategy for the treatment of cardiovascular disease. Full article

(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease)

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21 pages, 1193 KiB

Open AccessArticle

A Comparative Proteomic Analysis of Pinellia ternata Leaves Exposed to Heat Stress

by Yunhao Zhu¹, Guosheng Zhu², Qiaosheng Guo^1,*, Zaibiao Zhu¹, Changlin Wang¹ and Zuoyi Liu^3,*

¹ Institute of Chinese Medicinal Materials, Nanjing Agricultural University, Nanjing 210095, China

² Institute of Morden Chinese Medical Materials, Guizhou Academy of Agricaltural Sciences, Guiyang 550006, China

³ Key Laboratory of Agricultural Biotechnology, Guizhou Academy of Agricultural Sciences, Guiyang 550006, China

Int. J. Mol. Sci. 2013, 14(10), 20614-20634; https://doi.org/10.3390/ijms141020614 - 15 Oct 2013

Cited by 50 | Viewed by 7665

Abstract

Pinellia ternata is an important traditional Chinese medicinal plant. The growth of P. ternata is sensitive to high temperatures. To gain a better understanding of heat stress responses in P. ternata, we performed a comparative proteomic analysis. P. ternata seedlings were subjected [...] Read more.

Pinellia ternata is an important traditional Chinese medicinal plant. The growth of P. ternata is sensitive to high temperatures. To gain a better understanding of heat stress responses in P. ternata, we performed a comparative proteomic analysis. P. ternata seedlings were subjected to a temperature of 38 °C and samples were collected 24 h after treatment. Increased relative ion leakage and lipid peroxidation suggested that oxidative stress was frequently generated in rice leaves exposed to high temperature. Two-dimensional electrophoresis (2-DE) was used to analyze heat-responsive proteins. More than 600 protein spots were reproducibly detected on each gel; of these spots, 20 were up-regulated, and 7 were down-regulated. A total of 24 proteins and protein species were successfully identified by MALDI-TOF/TOF MS. These proteins and protein species were found to be primarily small heat shock proteins (58%) as well as proteins involved in RNA processing (17%), photosynthesis (13%), chlorophyll biosynthetic processes (4%), protein degradation (4%) and defense (4%). Using 2-DE Western blot analysis, we confirmed the identities of the cytosolic class II small heat shock protein (sHSPs-CII) identified by MS. The expression levels of four different proteins [cytosolic class I small heat shock protein (sHSPs-CI), sHSPs-CII, mitochondrial small heat shock protein (sHSPs-MIT), glycine-rich RNA-binding protein (GRP)] were analyzed at the transcriptional level by quantitative real-time PCR. The mRNA levels of three sHSPs correlated with the corresponding protein levels. However, GRP was down-regulated at the beginning of heat stress but then increased substantially to reach a peak after 24 h of heat stress. Our study provides valuable new insight into the responses of P. ternata to heat stress. Full article

(This article belongs to the Section Biochemistry)

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23 pages, 545 KiB

Open AccessReview

Mass Spectrometry Coupled Experiments and Protein Structure Modeling Methods

by Jaewoo Pi^1,2 and Lee Sael^1,2,*

¹ Department of Computer Science, Stony Brook University, Stony Brook, NY 11794, USA

² Department of Computer Science, State University of New York Korea, Incheon 406-840, Korea

Int. J. Mol. Sci. 2013, 14(10), 20635-20657; https://doi.org/10.3390/ijms141020635 - 15 Oct 2013

Cited by 12 | Viewed by 7914

Abstract

With the accumulation of next generation sequencing data, there is increasing interest in the study of intra-species difference in molecular biology, especially in relation to disease analysis. Furthermore, the dynamics of the protein is being identified as a critical factor in its function. [...] Read more.

With the accumulation of next generation sequencing data, there is increasing interest in the study of intra-species difference in molecular biology, especially in relation to disease analysis. Furthermore, the dynamics of the protein is being identified as a critical factor in its function. Although accuracy of protein structure prediction methods is high, provided there are structural templates, most methods are still insensitive to amino-acid differences at critical points that may change the overall structure. Also, predicted structures are inherently static and do not provide information about structural change over time. It is challenging to address the sensitivity and the dynamics by computational structure predictions alone. However, with the fast development of diverse mass spectrometry coupled experiments, low-resolution but fast and sensitive structural information can be obtained. This information can then be integrated into the structure prediction process to further improve the sensitivity and address the dynamics of the protein structures. For this purpose, this article focuses on reviewing two aspects: the types of mass spectrometry coupled experiments and structural data that are obtainable through those experiments; and the structure prediction methods that can utilize these data as constraints. Also, short review of current efforts in integrating experimental data in the structural modeling is provided. Full article

(This article belongs to the Special Issue Protein Folding)

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24 pages, 493 KiB

Open AccessArticle

Absolute Quantification of Selected Proteins in the Human Osteoarthritic Secretome

by Mandy J. Peffers^1,*, Robert J. Beynon^2,† and Peter D. Clegg^1,†

¹ Department of Musculoskeletal Biology, Institute of Ageing and Chronic Disease, University of Liverpool, Leahurst, Chester High Road, Neston, Cheshire, CH64 7TE, UK

² Protein Function Group, Institute of Integrative Biology, University of Liverpool, Biosciences Building, Crown Street, Liverpool, L69 7ZB, UK

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2013, 14(10), 20658-20681; https://doi.org/10.3390/ijms141020658 - 15 Oct 2013

Cited by 41 | Viewed by 8211

Abstract

Osteoarthritis (OA) is characterized by a loss of extracellular matrix which is driven by catabolic cytokines. Proteomic analysis of the OA cartilage secretome enables the global study of secreted proteins. These are an important class of molecules with roles in numerous pathological mechanisms. [...] Read more.

Osteoarthritis (OA) is characterized by a loss of extracellular matrix which is driven by catabolic cytokines. Proteomic analysis of the OA cartilage secretome enables the global study of secreted proteins. These are an important class of molecules with roles in numerous pathological mechanisms. Although cartilage studies have identified profiles of secreted proteins, quantitative proteomics techniques have been implemented that would enable further biological questions to be addressed. To overcome this limitation, we used the secretome from human OA cartilage explants stimulated with IL-1β and compared proteins released into the media using a label-free LC-MS/MS-based strategy. We employed QconCAT technology to quantify specific proteins using selected reaction monitoring. A total of 252 proteins were identified, nine were differentially expressed by IL-1 β stimulation. Selected protein candidates were quantified in absolute amounts using QconCAT. These findings confirmed a significant reduction in TIMP-1 in the secretome following IL-1β stimulation. Label-free and QconCAT analysis produced equivocal results indicating no effect of cytokine stimulation on aggrecan, cartilage oligomeric matrix protein, fibromodulin, matrix metalloproteinases 1 and 3 or plasminogen release. This study enabled comparative protein profiling and absolute quantification of proteins involved in molecular pathways pertinent to understanding the pathogenesis of OA. Full article

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10 pages, 435 KiB

Open AccessArticle

Thermal Properties and Crystallite Morphology of Nylon 66 Modified with a Novel Biphenyl Aromatic Liquid Crystalline Epoxy Resin

by Zhiqi Cai, Shuang Mei, Yuan Lu, Yuanqi He, Pihui Pi, Jiang Cheng, Yu Qian and Xiufang Wen^*

School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640, China

Int. J. Mol. Sci. 2013, 14(10), 20682-20691; https://doi.org/10.3390/ijms141020682 - 15 Oct 2013

Cited by 15 | Viewed by 8465

Abstract

In order to improve the thermal properties of important engineering plastics, a novel kind of liquid crystalline epoxy resin (LCER), 3,3',5,5' -Tetramethylbiphenyl-4,4' -diyl bis(4-(oxiran-2-ylmethoxy)benzoate) (M1) was introduced to blend with nylon 66 (M2) at high temperature. The effects of M1 [...] Read more.

In order to improve the thermal properties of important engineering plastics, a novel kind of liquid crystalline epoxy resin (LCER), 3,3',5,5' -Tetramethylbiphenyl-4,4' -diyl bis(4-(oxiran-2-ylmethoxy)benzoate) (M1) was introduced to blend with nylon 66 (M2) at high temperature. The effects of M1 on chemical modification and crystallite morphology of M2 were investigated by rheometry, thermo gravimetric analysis (TGA), dynamic differential scanning calorimetry (DSC) and polarized optical microscopy (POM). TGA results showed that the initial decomposition temperature of M2 increased by about 8 °C by adding 7% wt M1, indicating the improvement of thermal stability. DSC results illustrated that the melting point of composites decreased by 12 °C compared to M2 as the content of M1 increased, showing the improvement of processing property. POM measurements confirmed that dimension of nylon-66 spherulites and crystallization region decreased because of the addition of liquid crystalline epoxy M1. Full article

(This article belongs to the Special Issue Experimental and Theoretical Studies of Liquid Crystalline Materials: Where Do We Stand after 120 Years?)

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12 pages, 2035 KiB

Open AccessArticle

Molecular Cloning and Characterization of the Calcineurin Subunit A from Plutella xylostella

by Xi'en Chen and Yalin Zhang^*

Key Laboratory of Plant Protection Resources & Pest Management of Ministry of Education, Northwest A&F University, Yangling 712100, Shaanxi, China

Int. J. Mol. Sci. 2013, 14(10), 20692-20703; https://doi.org/10.3390/ijms141020692 - 15 Oct 2013

Cited by 5 | Viewed by 6053

Abstract

Calcineurin (or PP2B) has been reported to be involved in an array of physiological process in insects, and the calcineurin subunit A (CNA) plays a central role in calcineurin activity. We cloned the CNA gene from Plutella xylostella (PxCNA). This gene [...] Read more.

Calcineurin (or PP2B) has been reported to be involved in an array of physiological process in insects, and the calcineurin subunit A (CNA) plays a central role in calcineurin activity. We cloned the CNA gene from Plutella xylostella (PxCNA). This gene contains an ORF of 1488 bp that encodes a 495 amino acid protein, showing 98%, and 80% identities to the CNA of Bombyx mori, and humans respectively. The full-length of PxCNA and its catalytic domain (CNA_1–341, defined as PxCNα) were both expressed in Escherichia coli. Purified recombinant PxCNA displayed no phosphatase activity, whereas recombinant PxCNα showed high phosphatase activity with a Km of 4.6 mM and a kcat of 0.66 S⁻¹ against pNPP. It could be activated at different degrees by Mn²⁺, Ni²⁺, Mg²⁺, and Ca²⁺. The optimum reaction pH was about 7.5 and the optimum reaction temperature was around 45 °C. An in vitro inhibition assay showed that okadaic acid (OA) and cantharidin (CTD) competitively inhibited recombinant PxCNα activity with the IC₅₀ values of 8.95 μM and 77.64 μM, respectively. However, unlike previous reports, pyrethroid insecticides were unable to inhibit recombinant PxCNα, indicating that the P. xylostella calcineurin appears not to be sensitive to class II pyrethroid insecticides. Full article

(This article belongs to the Section Biochemistry)

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25 pages, 590 KiB

Open AccessReview

Multiple Hits, Including Oxidative Stress, as Pathogenesis and Treatment Target in Non-Alcoholic Steatohepatitis (NASH)

by Akinobu Takaki^*, Daisuke Kawai and Kazuhide Yamamoto

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

Int. J. Mol. Sci. 2013, 14(10), 20704-20728; https://doi.org/10.3390/ijms141020704 - 15 Oct 2013

Cited by 380 | Viewed by 22673

Abstract

Multiple parallel hits, including genetic differences, insulin resistance and intestinal microbiota, account for the progression of non-alcoholic steatohepatitis (NASH). Multiple hits induce adipokine secretion, endoplasmic reticulum (ER) and oxidative stress at the cellular level that subsequently induce hepatic steatosis, inflammation and fibrosis, among [...] Read more.

Multiple parallel hits, including genetic differences, insulin resistance and intestinal microbiota, account for the progression of non-alcoholic steatohepatitis (NASH). Multiple hits induce adipokine secretion, endoplasmic reticulum (ER) and oxidative stress at the cellular level that subsequently induce hepatic steatosis, inflammation and fibrosis, among which oxidative stress is considered a key contributor to progression from simple fatty liver to NASH. Although several clinical trials have shown that anti-oxidative therapy can effectively control hepatitis activities in the short term, the long-term effect remains obscure. Several trials of long-term anti-oxidant protocols aimed at treating cerebrovascular diseases or cancer development have failed to produce a benefit. This might be explained by the non-selective anti-oxidative properties of these drugs. Molecular hydrogen is an effective antioxidant that reduces only cytotoxic reactive oxygen species (ROS) and several diseases associated with oxidative stress are sensitive to hydrogen. The progress of NASH to hepatocellular carcinoma can be controlled using hydrogen-rich water. Thus, targeting mitochondrial oxidative stress might be a good candidate for NASH treatment. Long term clinical intervention is needed to control this complex lifestyle-related disease. Full article

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

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15 pages, 557 KiB

Open AccessArticle

Supramolecular Interactions of Terpyridine-Derived Cores of Metallomesogen Precursors

by Young Hoon Lee¹, Jack M. Harrowfield^2,*, Jong Won Shin³, Mi Seon Won¹, Elisabeth Rukmini⁴, Shinya Hayami⁵, Kil Sik Min³ and Yang Kim^1,*

¹ Department of Chemistry and Advanced Materials, Kosin University, 149-1, Dongsam-dong, Yeongdo-gu, Busan 606-701, Korea

² Institut de Science et de l'Ingénierie Supramoléculaires, Université de Strasbourg, 8, allée Gaspard Monge 67083, Strasbourg, France

³ Department of Chemistry, Graduate School, Kyungpook National University, Daegu 702-701, Korea

⁴ School of Medicine, Atma Jaya Catholic University of Indonesia, Pluit Raya #2, Jakarta 14440, Indonesia

⁵ Department of Chemistry, Graduate School of Science and Technology, Kumamoto University, 2-39-1 Kurokami, Kumamoto 860-8555, Japan

Int. J. Mol. Sci. 2013, 14(10), 20729-20743; https://doi.org/10.3390/ijms141020729 - 15 Oct 2013

Cited by 6 | Viewed by 6944

Abstract

Use of Hirshfeld surfaces calculated from crystal structure determinations on various transition metal ion complexes of three terpyridine ligands carrying trimethoxyphenyl substituents has enabled an assessment of the contribution made by the ligand components to the interactions determining the lattice structures, interactions expected [...] Read more.

Use of Hirshfeld surfaces calculated from crystal structure determinations on various transition metal ion complexes of three terpyridine ligands carrying trimethoxyphenyl substituents has enabled an assessment of the contribution made by the ligand components to the interactions determining the lattice structures, interactions expected also to be present in metallomesogens derived from similar ligands. The form of the link joining the trimethoxyphenyl substituent to the 4' position of 2,2';6',2''-terpyridine is of some importance. In the case of the Co(II) complexes of two of the ligands, their spin-crossover characteristics can be rationalised in terms of the different interactions seen in their lattices. Full article

(This article belongs to the Special Issue Synthesis, Characterization and Application of Supramolecular Systems)

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24 pages, 2863 KiB

Open AccessArticle

Molecular Cloning, Sequence Characterization and Expression Analysis of a CD63 Homologue from the Coleopteran Beetle, Tenebrio molitor

by Bharat Bhusan Patnaik¹

, Seong Min Kang², Gi Won Seo¹, Hyo Jeong Lee¹, Hongray Howrelia Patnaik¹, Yong Hun Jo¹, Hamisi Tindwa¹, Yong Seok Lee³, Bok Luel Lee², Nam Jung Kim⁴, In Seok Bang⁵ and Yeon Soo Han^1,*

¹ Division of Plant Biotechnology, Institute of Environmentally-Friendly Agriculture (IEFA), College of Agriculture and Life Sciences, Chonnam National University, Gwangju 500-757, Korea

² National Research Laboratory of Defense Proteins, College of Pharmacy, Pusan National University, Jangjeon Dong, Kumjeong Ku, Busan 609-735, Korea

³ Department of Life Science and Biotechnology, College of Natural Sciences, Soonchunhyang University, Asan city 336-745, Korea

⁴ Division of Applied Entomology, National Academy of Agricultural Science, Rural Development, 61th, Seodun-dong, Gwonseon-gu, Suwon, Gyeonggi-do 441-853, Korea

⁵ Department of Biological Science and the Research Institute for Basic Sciences, Hoseo University, Asan 336-795, Korea

Int. J. Mol. Sci. 2013, 14(10), 20744-20767; https://doi.org/10.3390/ijms141020744 - 15 Oct 2013

Cited by 16 | Viewed by 10978

Abstract

CD63, a member of the tetraspanin membrane protein family, plays a pivotal role in cell growth, motility, signal transduction, host-pathogen interactions and cancer. In this work, the cDNA encoding CD63 homologue (TmCD63) was cloned from larvae of a coleopteran beetle, Tenebrio molitor. The [...] Read more.

CD63, a member of the tetraspanin membrane protein family, plays a pivotal role in cell growth, motility, signal transduction, host-pathogen interactions and cancer. In this work, the cDNA encoding CD63 homologue (TmCD63) was cloned from larvae of a coleopteran beetle, Tenebrio molitor. The cDNA is comprised of an open reading frame of 705 bp, encoding putative protein of 235 amino acid residues. In silico analysis shows that the protein has four putative transmembrane domains and one large extracellular loop. The characteristic “Cys-Cys-Gly” motif and “Cys188” residues are highly conserved in the large extracellular loop. Phylogenetic analysis of TmCD63 revealed that they belong to the insect cluster with 50%–56% identity. Analysis of spatial expression patterns demonstrated that TmCD63 mRNA is mainly expressed in gut and Malphigian tubules of larvae and the testis of the adult. Developmental expression patterns of CD63 mRNA showed that TmCD63 transcripts are detected in late larval, pupal and adult stages. Interestingly, TmCD63 transcripts are upregulated to the maximum level of 4.5 fold, in response to DAP-type peptidoglycan during the first 6 h, although other immune elicitors also caused significant increase to the transcript level at later time-points. These results suggest that CD63 might contribute to T. molitor immune response against various microbial pathogens. Full article

(This article belongs to the Section Biochemistry)

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25 pages, 1241 KiB

Open AccessArticle

Crosstalk between Beta-Catenin and Snail in the Induction of Epithelial to Mesenchymal Transition in Hepatocarcinoma: Role of the ERK1/2 Pathway

by Nathalie Zucchini-Pascal^†, Ludovic Peyre^*,† and Roger Rahmani

¹ Laboratory of Xenobiotic's Cellular and Molecular Toxicology, INRA, UMR 1331 TOXALIM (Research Centre in Food Toxicology), Sophia Antipolis 06903, France

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2013, 14(10), 20768-20792; https://doi.org/10.3390/ijms141020768 - 16 Oct 2013

Cited by 55 | Viewed by 10773

Abstract

Epithelial to mesenchymal transition (EMT) is an integral process in the progression of many epithelial tumors. It involves a coordinated series of events, leading to the loss of epithelial features and the acquisition of a mesenchymal phenotype, resulting in invasion and metastasis. The [...] Read more.

Epithelial to mesenchymal transition (EMT) is an integral process in the progression of many epithelial tumors. It involves a coordinated series of events, leading to the loss of epithelial features and the acquisition of a mesenchymal phenotype, resulting in invasion and metastasis. The EMT of hepatocellular carcinoma (HCC) cells is thought to be a key event in intrahepatic dissemination and distal metastasis. In this study, we used 12-O-tet-radecanoylphorbol-13-acetate (TPA) to dissect the signaling pathways involved in the EMT of HepG2 hepatocarcinoma cells. The spectacular change in phenotype induced by TPA, leading to a pronounced spindle-shaped fibroblast-like cell morphology, required ERK1/2 activation. This ERK1/2-dependent EMT process was characterized by a loss of E-cadherin function, modification of the cytoskeleton, the acquisition of mesenchymal markers and profound changes to extracellular matrix composition and mobility. Snail was essential for E-cadherin repression, but was not sufficient for full commitment of the TPA-triggered EMT. We found that TPA triggered the formation of a complex between Snail and β-catenin that activated the Wnt pathway. This study thus provides the first evidence for the existence of a complex network governed by the ERK1/2 signaling pathway, converging on the coregulation of Snail and the Wnt/β-catenin pathway and responsible for the onset and the progression of EMT in hepatocellular carcinoma cells. Full article

(This article belongs to the Special Issue Molecular Research of Carcinogenesis)

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16 pages, 822 KiB

Open AccessReview

Lipid Transport and Metabolism in Healthy and Osteoarthritic Cartilage

by Amanda Villalvilla^1,*, Rodolfo Gómez², Raquel Largo¹

and Gabriel Herrero-Beaumont¹

¹ Osteoarticular Pathology Laboratory, IIS Fundación Jiménez Díaz, Madrid 28040, Spain

² Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne NE2 4HH, UK

Int. J. Mol. Sci. 2013, 14(10), 20793-20808; https://doi.org/10.3390/ijms141020793 - 16 Oct 2013

Cited by 88 | Viewed by 10032

Abstract

Cartilage is an avascular tissue and cartilage metabolism depends on molecule diffusion from synovial fluid and subchondral bone. Thus, nutrient availability is limited by matrix permeability according to the size and charge of the molecules. Matrix composition limits the access of molecules to [...] Read more.

Cartilage is an avascular tissue and cartilage metabolism depends on molecule diffusion from synovial fluid and subchondral bone. Thus, nutrient availability is limited by matrix permeability according to the size and charge of the molecules. Matrix composition limits the access of molecules to chondrocytes, determining cell metabolism and cartilage maintenance. Lipids are important nutrients in chondrocyte metabolism and are available for these cells through de novo synthesis but also through diffusion from surrounding tissues. Cartilage status and osteoarthritis development depend on lipid availability. This paper reviews lipid transport and metabolism in cartilage. We also analyze signalling pathways directly mediated by lipids and those that involve mTOR pathways, both in normal and osteoarthritic cartilage. Full article

(This article belongs to the Special Issue The Chondrocyte Phenotype in Cartilage Biology)

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11 pages, 2200 KiB

Open AccessArticle

Ultrastructural Analysis of Nanogold-Labeled Cell Surface Microvilli in Liquid by Atmospheric Scanning Electron Microscopy and Their Relevance in Cell Adhesion

by Toshiyuki Murai^1,*, Mari Sato², Hidetoshi Nishiyama³, Mitsuo Suga³ and Chikara Sato²

¹ Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan

² Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Higashi 1-1-1, Tsukuba, Ibaraki 305-8568, Japan

³ Advanced Technology Division, JEOL Ltd., Akishima, Tokyo 196-8558, Japan

Int. J. Mol. Sci. 2013, 14(10), 20809-20819; https://doi.org/10.3390/ijms141020809 - 16 Oct 2013

Cited by 17 | Viewed by 8390

Abstract

The adhesion of leukocytes circulating in the blood to vascular endothelium is critical for their trafficking in the vasculature, and CD44 is an important cell surface receptor for rolling adhesion. In this study, we demonstrate the correlative observation of CD44 distribution at the [...] Read more.

The adhesion of leukocytes circulating in the blood to vascular endothelium is critical for their trafficking in the vasculature, and CD44 is an important cell surface receptor for rolling adhesion. In this study, we demonstrate the correlative observation of CD44 distribution at the lymphocyte cell surface in liquid by fluorescence optical microscopy and immuno-electron microscopy using an atmospheric scanning electron microscope (ASEM). The ultrastructure of the cell surface was clearly imaged by ASEM using positively charged Nanogold particles. ASEM analysis demonstrated microvilli projections around the cell surface and the localization of CD44 on the microvilli. Treatment of cells with cytochalasin D resulted in a loss of the microvilli projections and concomitantly abrogated CD44-mediated adhesion to its ligand hyaluronan. These results suggest the functional relevance of microvilli in CD44-mediated rolling adhesion under shear flow. Full article

(This article belongs to the Special Issue Frontiers of Micro-Spectroscopy in Biological Applications)

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13 pages, 306 KiB

Open AccessArticle

Identification of Novel MicroRNAs in Primates by Using the Synteny Information and Small RNA Deep Sequencing Data

by Zhidong Yuan^1,2, Hongde Liu², Yumin Nie², Suping Ding¹, Mingli Yan¹, Shuhua Tan¹, Yuanchang Jin¹ and Xiao Sun^2,*

¹ School of Life Sciences, Hunan University of Science and Technology, Xiangtan 411201, China

² State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China

Int. J. Mol. Sci. 2013, 14(10), 20820-20832; https://doi.org/10.3390/ijms141020820 - 16 Oct 2013

Cited by 2 | Viewed by 6388

Abstract

Current technologies that are used for genome-wide microRNA (miRNA) prediction are mainly based on BLAST tool. They often produce a large number of false positives. Here, we describe an effective approach for identifying orthologous pre-miRNAs in several primates based on syntenic information. Some [...] Read more.

Current technologies that are used for genome-wide microRNA (miRNA) prediction are mainly based on BLAST tool. They often produce a large number of false positives. Here, we describe an effective approach for identifying orthologous pre-miRNAs in several primates based on syntenic information. Some of them have been validated by small RNA high throughput sequencing data. This approach uses the synteny information and experimentally validated miRNAs of human, and incorporates currently available algorithms and tools to identify the pre-miRNAs in five other primates. First, we identified 929 potential pre-miRNAs in the marmoset in which miRNAs have not yet been reported. Then, we predicted the miRNAs in other primates, and we successfully re-identified most of the published miRNAs and found 721, 979, 650 and 639 new potential pre-miRNAs in chimpanzee, gorilla, orangutan and rhesus macaque, respectively. Furthermore, the miRNA transcriptome in the four primates have been re-analyzed and some novel predicted miRNAs have been supported by the small RNA sequencing data. Finally, we analyzed the potential functions of those validated miRNAs and explored the regulatory elements and transcription factors of some validated miRNA genes of interest. The results show that our approach can effectively identify novel miRNAs and some miRNAs that supported by small RNA sequencing data maybe play roles in the nervous system. Full article

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

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12 pages, 2493 KiB

Open AccessArticle

Lentivirus-Mediated ERK2 siRNA Reduces Joint Capsule Fibrosis in a Rat Model of Post-Traumatic Joint Contracture

by Fengfeng Li^†, Shen Liu^† and Cunyi Fan^*

¹ Department of Orthopaedics, Sixth Affiliated People's Hospital, Shanghai Jiaotong University, 600 Yishan Road, Shanghai 200233, China

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2013, 14(10), 20833-20844; https://doi.org/10.3390/ijms141020833 - 17 Oct 2013

Cited by 25 | Viewed by 7156

Abstract

Extracellular signal-regulated kinase (ERK)-2 is presumed to play an important role in the development of post-traumatic joint contractures. Using a rat injury model, we investigated whether treatment with ERK2 small interfering RNA (siRNA) could reduce the extent of joint capsule fibrosis after an [...] Read more.

Extracellular signal-regulated kinase (ERK)-2 is presumed to play an important role in the development of post-traumatic joint contractures. Using a rat injury model, we investigated whether treatment with ERK2 small interfering RNA (siRNA) could reduce the extent of joint capsule fibrosis after an induced injury. Rats were separated into three groups (n = 32 each): non-operated control group, operated contracture group and contracture-treatment group. Stable post-traumatic joint contracture was created through surgical intra-articular joint injury followed by eight weeks of immobilization. In the contracture-treatment group, the rats were treated with lentivirus (LV)-mediated ERK2 siRNA at days 3 and 7 post-surgery. The posterior joint capsule was assessed by western blotting, immunohistochemistry and biochemical analysis for changes in ERK2, phosphorylated (p)-ERK2, myofibroblast, total collagen and relative collagen Type III expression level. Biomechanical testing was used to assess the development of flexion contractures. Statistical analysis was performed using an analysis of variance. In the operated contracture group, rats that developed flexion contractures also showed elevated phosphorylated p-ERK2 expression. In the contracture-treatment group, ERK2 siRNA significantly reduced p-ERK2 expression levels, as well as the severity of flexion contracture development (p < 0.01). Myofibroblast numbers and measurements of total collagen content were also significantly reduced following ERK2 siRNA (p < 0.01). Relative collagen type III expression as a proportion of total of Types I and III collagen, however, was significantly increased in response to ERK2 siRNA (p < 0.01). Our findings demonstrate a role for ERK2 in the induction of joint capsule fibrosis after injury. Furthermore, we show that development of flexion contractures and the resultant increase of joint capsule fibrosis can be reduced by LV-mediated ERK2 siRNA treatment. Full article

(This article belongs to the Section Biochemistry)

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32 pages, 586 KiB

Open AccessReview

Protein Glutathionylation in Cardiovascular Diseases

by Anna Pastore¹

and Fiorella Piemonte^2,*

¹ Laboratory of Biochemistry, Bambino Gesù Children's Hospital, IRCCS, 00165 Rome, Italy

² Unit of Neuromuscular and Neurodegenerative Diseases, Bambino Gesù Children's Hospital, IRCCS, 00165 Rome, Italy

Int. J. Mol. Sci. 2013, 14(10), 20845-20876; https://doi.org/10.3390/ijms141020845 - 17 Oct 2013

Cited by 84 | Viewed by 11550

Abstract

The perturbation of thiol-disulfide homeostasis is an important consequence of many diseases, with redox signals implicated in several physio-pathological processes. A prevalent form of cysteine modification is the reversible formation of protein mixed disulfides with glutathione (S-glutathionylation). The abundance of glutathione [...] Read more.

The perturbation of thiol-disulfide homeostasis is an important consequence of many diseases, with redox signals implicated in several physio-pathological processes. A prevalent form of cysteine modification is the reversible formation of protein mixed disulfides with glutathione (S-glutathionylation). The abundance of glutathione in cells and the ready conversion of sulfenic acids to S-glutathione mixed disulfides supports the reversible protein S-glutathionylation as a common feature of redox signal transduction, able to regulate the activities of several redox sensitive proteins. In particular, protein S-glutathionylation is emerging as a critical signaling mechanism in cardiovascular diseases, because it regulates numerous physiological processes involved in cardiovascular homeostasis, including myocyte contraction, oxidative phosphorylation, protein synthesis, vasodilation, glycolytic metabolism and response to insulin. Thus, perturbations in protein glutathionylation status may contribute to the etiology of many cardiovascular diseases, such as myocardial infarction, cardiac hypertrophy and atherosclerosis. Various reports show the importance of oxidative cysteine modifications in modulating cardiovascular function. In this review, we illustrate tools and strategies to monitor protein S-glutathionylation and describe the proteins so far identified as glutathionylated in myocardial contraction, hypertrophy and inflammation. Full article

(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease)

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13 pages, 2278 KiB

Open AccessArticle

Serial Changes of Serum Growth Factor Levels and Liver Regeneration after Partial Hepatectomy in Healthy Humans

by Kazuyuki Matsumoto^1,†, Yasuhiro Miyake^1,*,†, Yuzo Umeda², Hiroshi Matsushita¹, Hiroaki Matsuda², Akinobu Takaki¹, Hiroshi Sadamori², Kazuhiro Nouso¹, Takahito Yagi², Toshiyoshi Fujiwara² and Kazuhide Yamamoto¹

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

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

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2013, 14(10), 20877-20889; https://doi.org/10.3390/ijms141020877 - 17 Oct 2013

Cited by 29 | Viewed by 7191

Abstract

This study aimed to investigate the associations of the serial changes of serum levels of various growth factors with liver regeneration after hepatectomy in healthy liver donors. Sixteen healthy liver donors who underwent conventional liver resection were included. Serum levels of various growth [...] Read more.

This study aimed to investigate the associations of the serial changes of serum levels of various growth factors with liver regeneration after hepatectomy in healthy liver donors. Sixteen healthy liver donors who underwent conventional liver resection were included. Serum levels of various growth factors before hepatectomy and on postoperative day (POD) 1, 3, 5 and 7 were measured. Liver volume data calculated by multi-detector computed tomography using workstation. The ratio of remnant liver volume on POD 0 to liver volume before the operation was 51% ± 20%. The ratio of liver volume on POD 14 to liver volume on POD 0 were inversely correlated with remnant liver volume on POD 0 (r = −0.91). The ratio of liver volume on POD 14 to liver volume on POD 0 were significantly correlated with serum hepatocyte growth factor (HGF) levels on POD 1 (r = 0.54), serum leptin levels on POD 1 (r = 0.54), and serum macrophage colony-stimulating factor (M-CSF) levels on POD 5 (r = 0.76) and POD 7 (r = 0.80). These results suggest that early-phase elevation of serum levels of HGF, leptin and M-CSF may be associated with the acceleration of liver regeneration after hepatectomy in humans. Full article

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

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23 pages, 948 KiB

Open AccessReview

Boronic Acid-Based Approach for Separation and Immobilization of Glycoproteins and Its Application in Sensing

by Xiaojin Wang, Ning Xia^* and Lin Liu

College of Chemistry and Chemical Engineering, Anyang Normal University, Anyang 455000, Henan, China

Int. J. Mol. Sci. 2013, 14(10), 20890-20912; https://doi.org/10.3390/ijms141020890 - 17 Oct 2013

Cited by 99 | Viewed by 17118

Abstract

Glycoproteins influence a broad spectrum of biological processes including cell-cell interaction, host-pathogen interaction, or protection of proteins against proteolytic degradation. The analysis of their glyco-structures and concentration levels are increasingly important in diagnosis and proteomics. Boronic acids can covalently react with cis-diols [...] Read more.

Glycoproteins influence a broad spectrum of biological processes including cell-cell interaction, host-pathogen interaction, or protection of proteins against proteolytic degradation. The analysis of their glyco-structures and concentration levels are increasingly important in diagnosis and proteomics. Boronic acids can covalently react with cis-diols in the oligosaccharide chains of glycoproteins to form five- or six-membered cyclic esters. Based on this interaction, boronic acid-based ligands and materials have attracted much attention in both chemistry and biology as the recognition motif for enrichment and chemo/biosensing of glycoproteins in recent years. In this work, we reviewed the progress in the separation, immobilization and detection of glycoproteins with boronic acid-functionalized materials and addressed its application in sensing. Full article

(This article belongs to the Special Issue Glycosylation and Glycoproteins)

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17 pages, 611 KiB

Open AccessArticle

Overexpression of Ferredoxin, PETF, Enhances Tolerance to Heat Stress in Chlamydomonas reinhardtii

by Yi-Hsien Lin¹

, Kui-You Pan², Ching-Hui Hung³, Hsiang-En Huang⁴, Ching-Lian Chen³, Teng-Yung Feng³ and Li-Fen Huang^2,*

¹ Department of Plant Medicine, National Pingtung University of Science and Technology, Pingtung 912, Taiwan

² Graduate School of Biotechnology and Bioengineering, Yuan Ze University, Taoyuan 320, Taiwan

³ Institute of Plant and Microbial Biology, Academia Sinica, Taipei 115, Taiwan

⁴ Department of Life Science, National Taitung University, Taitung 684, Taiwan

Int. J. Mol. Sci. 2013, 14(10), 20913-20929; https://doi.org/10.3390/ijms141020913 - 17 Oct 2013

Cited by 60 | Viewed by 10964

Abstract

Reactive oxygen species (ROS) produced by plants in adverse environments can cause damage to organelles and trigger cell death. Removal of excess ROS can be achieved through the ascorbate scavenger pathway to prevent plant cell death. The amount of this scavenger can be [...] Read more.

Reactive oxygen species (ROS) produced by plants in adverse environments can cause damage to organelles and trigger cell death. Removal of excess ROS can be achieved through the ascorbate scavenger pathway to prevent plant cell death. The amount of this scavenger can be regulated by ferredoxin (FDX). Chloroplastic FDXs are electron transfer proteins that perform in distributing photosynthetic reducing power. In this study, we demonstrate that overexpression of the endogenous photosynthetic FDX gene, PETF, in Chlamydomonas reinhardtii could raise the level of reduced ascorbate and diminish H₂O₂ levels under normal growth conditions. Furthermore, the overexpressing PETF transgenic Chlamydomonas lines produced low levels of H₂O₂ and exhibited protective effects that were observed through decreased chlorophyll degradation and increased cell survival under heat-stress conditions. The findings of this study suggest that overexpression of PETF can increase the efficiency of ROS scavenging in chloroplasts to confer heat tolerance. The roles of PETF in the downregulation of the ROS level offer a method for potentially improving the tolerance of crops against heat stress. Full article

(This article belongs to the Section Biochemistry)

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24 pages, 402 KiB

Open AccessReview

MicroRNA-Regulated Pathways in Hematological Malignancies: How to Avoid Cells Playing Out of Tune

by Alessandro Fatica^1,*,†

and Francesco Fazi^2,*,†

¹ Department of Biology and Biotechnology "Charles Darwin", Sapienza University of Rome, Rome 00185, Italy

² Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina 04100, Italy

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2013, 14(10), 20930-20953; https://doi.org/10.3390/ijms141020930 - 18 Oct 2013

Cited by 22 | Viewed by 8013

Abstract

The coordinated expression and interplay among lineage specific transcription factors and microRNAs contribute to the regulation of gene expression and determination of cell specificity. In hematopoietic stem cells (HSCs), unique combinations of transcription factors largely control growth and maturation of different blood cell [...] Read more.

The coordinated expression and interplay among lineage specific transcription factors and microRNAs contribute to the regulation of gene expression and determination of cell specificity. In hematopoietic stem cells (HSCs), unique combinations of transcription factors largely control growth and maturation of different blood cell lineages through cooperative regulation of specific target genes. MicroRNAs provide an additional level of control beyond transcription factors. By acting as regulators of crucial lineage-specific genetic programs, microRNAs direct early multipotential progenitor cells to adopt a certain cell fate program. Thus, alteration of specific microRNA levels may affect proliferation, differentiation and genetic stability of HSCs, contributing to the onset of myeloproliferative disorders and leukemia. The major aim of this review is to highlight the critical role of microRNA-regulated pathways during the establishment and progression of hematological malignancies, with a particular attention to leukemia, lymphomas and myelodysplastic syndromes. This will give us the opportunity to discuss the potential use of microRNA-based therapeutic approaches in these diseases. MicroRNAs are indeed emerging as relevant tools to improve the efficacy of currently used therapeutic protocols. Full article

(This article belongs to the Special Issue Molecular Bases of Cancer Research)

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12 pages, 432 KiB

Open AccessArticle

Pesticide Removal from Aqueous Solutions by Adding Salting Out Agents

by Fátima Moscoso^1,2, Francisco J. Deive¹, José M. S. S. Esperança² and Ana Rodríguez^1,*

¹ Department of Chemical Engineering, University of Vigo, 36310 Vigo, Spain

² Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa, Av. da República, 2780-157 Oeiras, Portugal

Int. J. Mol. Sci. 2013, 14(10), 20954-20965; https://doi.org/10.3390/ijms141020954 - 18 Oct 2013

Cited by 19 | Viewed by 7665

Abstract

Phase segregation in aqueous biphasic systems (ABS) composed of four hydrophilic ionic liquids (ILs): 1-butyl-3-methylimidazolium methylsulfate and 1-ethyl-3-methylimidazolium methylsulfate (C_nC₁im C₁SO₄, n = 2 and 4), tributylmethyl phosphonium methylsulfate (P₄₄₄₁ C₁SO₄ [...] Read more.

Phase segregation in aqueous biphasic systems (ABS) composed of four hydrophilic ionic liquids (ILs): 1-butyl-3-methylimidazolium methylsulfate and 1-ethyl-3-methylimidazolium methylsulfate (C_nC₁im C₁SO₄, n = 2 and 4), tributylmethyl phosphonium methylsulfate (P₄₄₄₁ C₁SO₄) and methylpyridinium methylsulfate (C₁Py C₁SO₄) and two high charge density potassium inorganic salts (K₂CO₃ and K₂HPO₄) were determined by the cloud point method at 298.15 K. The influence of the addition of the selected inorganic salts to aqueous mixtures of ILs was discussed in the light of the Hofmeister series and in terms of molar Gibbs free energy of hydration. The effect of the alkyl chain length of the cation on the methylsulfate-based ILs has been investigated. All the solubility data were satisfactorily correlated to several empirical equations. A pesticide (pentachlorophenol, PCP) extraction process based on the inorganic salt providing a greater salting out effect was tackled. The viability of the proposed process was analyzed in terms of partition coefficients and extraction efficiencies. Full article

(This article belongs to the Special Issue Ionic Liquids 2014 & Selected Papers from ILMAT 2013)

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17 pages, 857 KiB

Open AccessArticle

DNA Damage Induced MutS Homologue hMSH4 Acetylation

by Yen-Lin Chu, Xiling Wu, Jing Xu, Jennifer L. Watts and Chengtao Her^*

School of Molecular Biosciences, Mail Drop 64-7520, Washington State University, Pullman, WA 99164-7520, USA

Int. J. Mol. Sci. 2013, 14(10), 20966-20982; https://doi.org/10.3390/ijms141020966 - 18 Oct 2013

Cited by 1 | Viewed by 6255

Abstract

Acetylation of non-histone proteins is increasingly recognized as an important post-translational modification for controlling the actions of various cellular processes including DNA repair and damage response. Here, we report that the human MutS homologue hMSH4 undergoes acetylation following DNA damage induced by ionizing [...] Read more.

Acetylation of non-histone proteins is increasingly recognized as an important post-translational modification for controlling the actions of various cellular processes including DNA repair and damage response. Here, we report that the human MutS homologue hMSH4 undergoes acetylation following DNA damage induced by ionizing radiation (IR). To determine which acetyltransferases are responsible for hMSH4 acetylation in response to DNA damage, potential interactions of hMSH4 with hTip60, hGCN5, and hMof were analyzed. The results of these experiments indicate that only hMof interacts with hMSH4 in a DNA damage-dependent manner. Intriguingly, the interplay between hMSH4 and hMof manipulates the outcomes of nonhomologous end joining (NHEJ)-mediated DNA double strand break (DSB) repair and thereby controls cell survival in response to IR. This study also shows that hMSH4 interacts with HDAC3, by which HDAC3 negatively regulates the levels of hMSH4 acetylation. Interestingly, elevated levels of HDAC3 correlate with increased NHEJ-mediated DSB repair, suggesting that hMSH4 acetylation per se may not directly affect the role of hMSH4 in DSB repair. Full article

(This article belongs to the Section Biochemistry)

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23 pages, 683 KiB

Open AccessReview

Biofilm Matrix and Its Regulation in Pseudomonas aeruginosa

by Qing Wei and Luyan Z. Ma^*

State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, No.3, 1st Beichen West Road, Chaoyang District, Beijing 100101, China

Int. J. Mol. Sci. 2013, 14(10), 20983-21005; https://doi.org/10.3390/ijms141020983 - 18 Oct 2013

Cited by 273 | Viewed by 24323

Abstract

Biofilms are communities of microorganisms embedded in extracellular polymeric substances (EPS) matrix. Bacteria in biofilms demonstrate distinct features from their free-living planktonic counterparts, such as different physiology and high resistance to immune system and antibiotics that render biofilm a source of chronic and [...] Read more.

Biofilms are communities of microorganisms embedded in extracellular polymeric substances (EPS) matrix. Bacteria in biofilms demonstrate distinct features from their free-living planktonic counterparts, such as different physiology and high resistance to immune system and antibiotics that render biofilm a source of chronic and persistent infections. A deeper understanding of biofilms will ultimately provide insights into the development of alternative treatment for biofilm infections. The opportunistic pathogen Pseudomonas aeruginosa, a model bacterium for biofilm research, is notorious for its ability to cause chronic infections by its high level of drug resistance involving the formation of biofilms. In this review, we summarize recent advances in biofilm formation, focusing on the biofilm matrix and its regulation in P. aeruginosa, aiming to provide resources for the understanding and control of bacterial biofilms. Full article

(This article belongs to the Special Issue Biofilms: Extracellular Bastions of Bacteria)

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15 pages, 639 KiB

Open AccessArticle

Differences in the Structure of the Gut Bacteria Communities in Development Stages of the Chinese White Pine Beetle (Dendroctonus armandi)

by Xia Hu

, Chunyan Wang, Hui Chen^* and Junning Ma

College of Forestry, Northwest A&F University, Yangling 712100, Shaanxi, China

Int. J. Mol. Sci. 2013, 14(10), 21006-21020; https://doi.org/10.3390/ijms141021006 - 18 Oct 2013

Cited by 46 | Viewed by 8323

Abstract

The Chinese white pine beetle Dendroctonus armandi Tsai and Li, is arguably the most destructive forest insect in the Qinling Mountains in Northern China. Little is known about the structure of the bacterial communities associated with D. armandi even though this wood-boring [...] Read more.

The Chinese white pine beetle Dendroctonus armandi Tsai and Li, is arguably the most destructive forest insect in the Qinling Mountains in Northern China. Little is known about the structure of the bacterial communities associated with D. armandi even though this wood-boring insect plays important roles in ecosystem and biological invasion processes that result in huge economic losses in pine forests. The aim of this study was to investigate the composition of the bacterial communities present in the guts of D. armandi at different developmental stages using a culture-independent method involving PCR-denaturing gradient gel electrophoresis (DGGE). Analysis of PCR-amplified 16S rRNA gene fragments of bacteria from the guts of larvae, pupae, and male and female adults revealed bacterial communities of low complexity that differed according to the developmental stage. Citrobacter spp. and Pantoea spp. predominated in larvae and adults, whereas Methylobacterium was the dominant genus at the pupal stage. The main difference between the guts of male and female adults was the greater dominance of Citrobacter in females. Previous studies suggest that the bacterial community associated with D. armandi guts may influence insect development. The data obtained in this study regarding the phylogenetic relationships and the community structure of intestinal bacteria at different developmental stages of the D. armandi life cycle contribute to our understanding of D. armandi and could aid the development of new pest control strategies. Full article

(This article belongs to the Section Biochemistry)

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24 pages, 665 KiB

Open AccessReview

Impaired Glutathione Synthesis in Neurodegeneration

by Koji Aoyama and Toshio Nakaki^*

Department of Pharmacology, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi, Tokyo 173-8605, Japan

Int. J. Mol. Sci. 2013, 14(10), 21021-21044; https://doi.org/10.3390/ijms141021021 - 18 Oct 2013

Cited by 184 | Viewed by 18175

Abstract

Glutathione (GSH) was discovered in yeast cells in 1888. Studies of GSH in mammalian cells before the 1980s focused exclusively on its function for the detoxication of xenobiotics or for drug metabolism in the liver, in which GSH is present at its highest [...] Read more.

Glutathione (GSH) was discovered in yeast cells in 1888. Studies of GSH in mammalian cells before the 1980s focused exclusively on its function for the detoxication of xenobiotics or for drug metabolism in the liver, in which GSH is present at its highest concentration in the body. Increasing evidence has demonstrated other important roles of GSH in the brain, not only for the detoxication of xenobiotics but also for antioxidant defense and the regulation of intracellular redox homeostasis. GSH also regulates cell signaling, protein function, gene expression, and cell differentiation/proliferation in the brain. Clinically, inborn errors in GSH-related enzymes are very rare, but disorders of GSH metabolism are common in major neurodegenerative diseases showing GSH depletion and increased levels of oxidative stress in the brain. GSH depletion would precipitate oxidative damage in the brain, leading to neurodegenerative diseases. This review focuses on the significance of GSH function, the synthesis of GSH and its metabolism, and clinical disorders of GSH metabolism. A potential approach to increase brain GSH levels against neurodegeneration is also discussed. Full article

(This article belongs to the Special Issue Molecular Research in Neurotoxicology)

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8 pages, 293 KiB

Open AccessArticle

The Influence of Silica Nanoparticles on Ionic Liquid Behavior: A Clear Difference between Adsorption and Confinement

by Yaxing Wang^1,2, Cheng Li¹, Xiaojing Guo¹ and Guozhong Wu^1,*

¹ Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800, China

² Graduate University of Chinese Academy of Sciences, Beijing 100049, China

Int. J. Mol. Sci. 2013, 14(10), 21045-21052; https://doi.org/10.3390/ijms141021045 - 18 Oct 2013

Cited by 19 | Viewed by 7472

Abstract

The phase behaviors of ionic liquids (ILs) confined in nanospace and adsorbed on outer surface of nanoparticles are expected to be different from those of the bulk. Anomalous phase behaviors of room temperature ionic liquid tributylhexadecylphosphonium bromide (P₄₄₄₁₆Br) confined in ordered [...] Read more.

The phase behaviors of ionic liquids (ILs) confined in nanospace and adsorbed on outer surface of nanoparticles are expected to be different from those of the bulk. Anomalous phase behaviors of room temperature ionic liquid tributylhexadecylphosphonium bromide (P₄₄₄₁₆Br) confined in ordered mesoporous silica nanoparticles with average pore size 3.7 nm and adsorbed on outer surface of the same silica nanoparticles were reported. It was revealed that the melting points (T_m) of confined and adsorbed ILs depressed significantly in comparison with the bulk one. The T_m depressions for confined and adsorbed ILs are 8 °C and 14 °C, respectively. For comparison with the phase behavior of confined P₄₄₄₁₆Br, 1-butyl-3-methylimidazolium bromide (BmimBr) was entrapped within silica nanopores, we observed an enhancement of 50 °C in T_m under otherwise similar conditions. The XRD analysis indicates the formation of crystalline-like phase under confinement, in contrast to the amorphous phase in adsorbed IL. It was confirmed that the behavior of IL has clear difference. Moreover, the complex π-π stacking and H-bonding do not exist in the newly proposed phosphonium-based IL in comparison with the widely studied imidazolium-based IL. The opposite change in melting point of P₄₄₄₁₆Br@SiO₂ and BmimBr@SiO₂ indicates that the cationic species plays an important role in the variation of melting point. Full article

(This article belongs to the Special Issue Experimental and Theoretical Studies of Liquid Crystalline Materials: Where Do We Stand after 120 Years?)

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18 pages, 950 KiB

Open AccessArticle

A Genome-Wide Expression Profile of Salt-Responsive Genes in the Apple Rootstock Malus zumi

by Qingtian Li^1,†, Jia Liu^1,2,†, Dunxian Tan³, Andrew C. Allan⁴, Yuzhuang Jiang¹, Xuefeng Xu¹, Zhenhai Han¹ and Jin Kong^1,*

¹ College of Agronomy and Biotechnology, China Agricultural University, Beijing 100193, China

² Horticulture Research Institute, Sichuan Academy of Agricultural Sciences, Chengdu 610066, Sichuan, China

³ Department of Cellular & Structural Biology, the UT Health Science Center, San Antonio, TX 78229-3900, USA

⁴ Plant & Food Research, Private Bag 92169, Auckland, New Zealand

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2013, 14(10), 21053-21070; https://doi.org/10.3390/ijms141021053 - 18 Oct 2013

Cited by 25 | Viewed by 7588

Abstract

In some areas of cultivation, a lack of salt tolerance severely affects plant productivity. Apple, Malus x domestica Borkh., is sensitive to salt, and, as a perennial woody plant the mechanism of salt stress adaption will be different from that of annual herbal [...] Read more.

In some areas of cultivation, a lack of salt tolerance severely affects plant productivity. Apple, Malus x domestica Borkh., is sensitive to salt, and, as a perennial woody plant the mechanism of salt stress adaption will be different from that of annual herbal model plants, such as Arabidopsis. Malus zumi is a salt tolerant apple rootstock, which survives high salinity (up to 0.6% NaCl). To examine the mechanism underlying this tolerance, a genome-wide expression analysis was performed, using a cDNA library constructed from salt-treated seedlings of Malus zumi. A total of 15,000 cDNA clones were selected for microarray analysis. In total a group of 576 cDNAs, of which expression changed more than four-fold, were sequenced and 18 genes were selected to verify their expression pattern under salt stress by semi-quantitative RT-PCR. Our genome-wide expression analysis resulted in the isolation of 50 novel Malus genes and the elucidation of a new apple-specific mechanism of salt tolerance, including the stabilization of photosynthesis under stress, involvement of phenolic compounds, and sorbitol in ROS scavenging and osmoprotection. The promoter regions of 111 genes were analyzed by PlantCARE, suggesting an intensive cross-talking of abiotic stress in Malus zumi. An interaction network of salt responsive genes was constructed and molecular regulatory pathways of apple were deduced. Our research will contribute to gene function analysis and further the understanding of salt-tolerance mechanisms in fruit trees. Full article

(This article belongs to the Section Biochemistry)

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16 pages, 310 KiB

Open AccessReview

Angiotensin-Converting Enzymes Play a Dominant Role in Fertility

by Pei-Pei Pan, Qi-Tao Zhan, Fang Le, Ying-Ming Zheng and Fan Jin^*

Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, 1 Xueshi Road, Hangzhou 310006, China

Int. J. Mol. Sci. 2013, 14(10), 21071-21086; https://doi.org/10.3390/ijms141021071 - 21 Oct 2013

Cited by 94 | Viewed by 10545

Abstract

According to the World Health Organization, infertility, associated with metabolic syndrome, has become a global issue with a 10%–20% incidence worldwide. An accumulating body of evidence has shown that the renin–angiotensin system is involved in the fertility problems observed in some populations. Moreover, [...] Read more.

According to the World Health Organization, infertility, associated with metabolic syndrome, has become a global issue with a 10%–20% incidence worldwide. An accumulating body of evidence has shown that the renin–angiotensin system is involved in the fertility problems observed in some populations. Moreover, alterations in the expression of angiotensin-converting enzyme-1, angiotensin-converting enzyme-2, and angiotensin-converting enzyme-3 might be one of the most important mechanisms underlying both female and male infertility. However, as a pseudogene in humans, further studies are needed to explore whether the abnormal angiotensin-converting enzyme-3 gene could result in the problems of human reproduction. In this review, the relationship between angiotensin-converting enzymes and fertile ability is summarized, and a new procedure for the treatment of infertility is discussed. Full article

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27 pages, 692 KiB

Open AccessReview

Cancer Development, Progression, and Therapy: An Epigenetic Overview

by Sibaji Sarkar^*, Garrick Horn, Kimberly Moulton, Anuja Oza, Shannon Byler, Shannon Kokolus and McKenna Longacre

Cancer Center, L913, Department of Medicine, Boston University School of Medicine, 72 East Concord Street, Boston, MA 02118, USA

Int. J. Mol. Sci. 2013, 14(10), 21087-21113; https://doi.org/10.3390/ijms141021087 - 21 Oct 2013

Cited by 291 | Viewed by 27586

Abstract

Carcinogenesis involves uncontrolled cell growth, which follows the activation of oncogenes and/or the deactivation of tumor suppression genes. Metastasis requires down-regulation of cell adhesion receptors necessary for tissue-specific, cell–cell attachment, as well as up-regulation of receptors that enhance cell motility. Epigenetic changes, including [...] Read more.

Carcinogenesis involves uncontrolled cell growth, which follows the activation of oncogenes and/or the deactivation of tumor suppression genes. Metastasis requires down-regulation of cell adhesion receptors necessary for tissue-specific, cell–cell attachment, as well as up-regulation of receptors that enhance cell motility. Epigenetic changes, including histone modifications, DNA methylation, and DNA hydroxymethylation, can modify these characteristics. Targets for these epigenetic changes include signaling pathways that regulate apoptosis and autophagy, as well as microRNA. We propose that predisposed normal cells convert to cancer progenitor cells that, after growing, undergo an epithelial-mesenchymal transition. This process, which is partially under epigenetic control, can create a metastatic form of both progenitor and full-fledged cancer cells, after which metastasis to a distant location may occur. Identification of epigenetic regulatory mechanisms has provided potential therapeutic avenues. In particular, epigenetic drugs appear to potentiate the action of traditional therapeutics, often by demethylating and re-expressing tumor suppressor genes to inhibit tumorigenesis. Epigenetic drugs may inhibit both the formation and growth of cancer progenitor cells, thus reducing the recurrence of cancer. Adopting epigenetic alteration as a new hallmark of cancer is a logical and necessary step that will further encourage the development of novel epigenetic biomarkers and therapeutics. Full article

(This article belongs to the Special Issue Molecular Research of Carcinogenesis)

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26 pages, 1185 KiB

Open AccessArticle

Crosstalk between Delta Opioid Receptor and Nerve Growth Factor Signaling Modulates Neuroprotection and Differentiation in Rodent Cell Models

by Dwaipayan Sen^1,†, Michael Huchital¹ and Yulong L. Chen^1,2,*

¹ Department of Biological Sciences, Binghamton University, the State University of New York at Binghamton, Binghamton, NY 13902, USA

² The Center for Development and Behavioral Neurosciences, Binghamton University, the State University of New York at Binghamton, Binghamton, NY 13902, USA

^† Current address: Department of Hematology, Christian Medical College, Vellore, Tamil Nadu 632002, India.

Int. J. Mol. Sci. 2013, 14(10), 21114-21139; https://doi.org/10.3390/ijms141021114 - 21 Oct 2013

Cited by 23 | Viewed by 8264

Abstract

Both opioid signaling and neurotrophic factor signaling have played an important role in neuroprotection and differentiation in the nervous system. Little is known about whether the crosstalk between these two signaling pathways will affect neuroprotection and differentiation. Previously, we found that nerve growth [...] Read more.

Both opioid signaling and neurotrophic factor signaling have played an important role in neuroprotection and differentiation in the nervous system. Little is known about whether the crosstalk between these two signaling pathways will affect neuroprotection and differentiation. Previously, we found that nerve growth factor (NGF) could induce expression of the delta opioid receptor gene (Oprd1, dor), mainly through PI3K/Akt/NF-κB signaling in PC12h cells. In this study, using two NGF-responsive rodent cell model systems, PC12h cells and F11 cells, we found the delta opioid neuropeptide [D-Ala², D-Leu⁵] enkephalin (DADLE)-mediated neuroprotective effect could be blocked by pharmacological reagents: the delta opioid antagonist naltrindole, PI3K inhibitor LY294002, MAPK inhibitor PD98059, and Trk inhibitor K252a, respectively. Western blot analysis revealed that DADLE activated both the PI3K/Akt and MAPK pathways in the two cell lines. siRNA Oprd1 gene knockdown experiment showed that the upregulation of NGF mRNA level was inhibited with concomitant inhibition of the survival effects of DADLE in the both cell models. siRNA Oprd1 gene knockdown also attenuated the DADLE-mediated neurite outgrowth in PC12h cells as well as phosphorylation of MAPK and Akt in PC12h and F11 cells, respectively. These data together strongly suggest that delta opioid peptide DADLE acts through the NGF-induced functional G protein-coupled Oprd1 to provide its neuroprotective and differentiating effects at least in part by regulating survival and differentiating MAPK and PI3K/Akt signaling pathways in NGF-responsive rodent neuronal cells. Full article

(This article belongs to the Special Issue Pathology and Treatment of Central Nervous System Diseases)

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13 pages, 9360 KiB

Open AccessArticle

The Effect on Proliferation and Differentiation of Cementoblast by Using Sclerostin as Inhibitor

by Xingfu Bao¹, Yuyan Liu², Guanghong Han², Zhigang Zuo³ and Min Hu^1,*

¹ Department of Orthodontics, School of Stomatology, Jilin University, Changchun 130021, China

² Department of Endodontics, School of Stomatology, Jilin University, Changchun 130021, China

³ Department of Orthodontics, School of Stomatology, Tianjin Medical University, Tianjin 300014, China

Int. J. Mol. Sci. 2013, 14(10), 21140-21152; https://doi.org/10.3390/ijms141021140 - 21 Oct 2013

Cited by 28 | Viewed by 12287 | Correction

Abstract

Cementogenesis is of great importance for normal teeth root development and is involved in the repair process of root resorption caused by orthodontic treatment. As highly differentiated mesenchymal cells, cementoblasts are responsible for this process under the regulation of many endogenous agents. Among [...] Read more.

Cementogenesis is of great importance for normal teeth root development and is involved in the repair process of root resorption caused by orthodontic treatment. As highly differentiated mesenchymal cells, cementoblasts are responsible for this process under the regulation of many endogenous agents. Among these molecules, sclerostin has been much investigated recently for its distinct antagonism effect on bone metabolism. Encoded by the sost gene, sclerostin is expressed in osteocytes and cementocytes of cellular cementum. it is still unclear. In the current study, we investigated the effects of sclerostin on the processes of proliferation and differentiation; a series of experiments including MTT, apoptosis examination, alkaline phosphatase (ALP) activity, gene analysis, and alizarin red staining were carried out to evaluate the proliferation and differentiation of cementoblasts. Protein expression including osteoprotegerin (OPG) and receptor activator of nuclear factor kappa B ligand (RANKL) were also checked to analyze changes in osteoclastogenesis. Results show that sclerostin inhibits cementoblasts proliferation and differentiation, and promotes osteoclastogenesis. Interestingly, the monoclonal antibody for sclerostin has shown positive effects on osteoporosis, indicating that it may facilitate cementogenesis and benefit the treatment of cementum related diseases. Full article

(This article belongs to the Section Biochemistry)

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Graphical abstract

14 pages, 286 KiB

Open AccessArticle

Identification of Combined Genetic Determinants of Liver Stiffness within the SREBP1c-PNPLA3 Pathway

by Marcin Krawczyk^†, Frank Grünhage^† and Frank Lammert^*

¹ Department of Medicine II, Saarland University Medical Center, Homburg 66421, Germany

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2013, 14(10), 21153-21166; https://doi.org/10.3390/ijms141021153 - 22 Oct 2013

Cited by 14 | Viewed by 7805

Abstract

The common PNPLA3 (adiponutrin) variant, p.I148M, was identified as a genetic determinant of liver fibrosis. Since the expression of PNPLA3 is induced by sterol regulatory element binding protein 1c (SREBP1c), we investigate two common SREBP1c variants (rs2297508 and rs11868035) for their association with [...] Read more.

The common PNPLA3 (adiponutrin) variant, p.I148M, was identified as a genetic determinant of liver fibrosis. Since the expression of PNPLA3 is induced by sterol regulatory element binding protein 1c (SREBP1c), we investigate two common SREBP1c variants (rs2297508 and rs11868035) for their association with liver stiffness. In 899 individuals (aged 17–83 years, 547 males) with chronic liver diseases, hepatic fibrosis was non-invasively phenotyped by transient elastography (TE). The SREBP1c single nucleotide polymorphisms (SNPs) were genotyped using PCR-based assays with 5'-nuclease and fluorescence detection. The SREBP1c rs11868035 variant affected liver fibrosis significantly (p = 0.029): median TE levels were 7.2, 6.6 and 6.0 kPa in carriers of (TT) (n = 421), (CT) (n = 384) and (CC) (n = 87) genotypes, respectively. Overall, the SREBP1c SNP was associated with low TE levels (5.0–8.0 kPa). Carriers of both PNPLA3 and SREBP1c risk genotypes displayed significantly (p = 0.005) higher median liver stiffness, as compared to patients carrying none of these variants. The common SREBP1c variant may affect early stages of liver fibrosis. Our study supports a role of the SREBP1c-PNPLA3 pathway as a “disease module” that promotes hepatic fibrogenesis. Full article

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

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22 pages, 935 KiB

Open AccessReview

Dietary Polyunsaturated Fatty Acids and Inflammation: The Role of Phospholipid Biosynthesis

by William Raphael^† and Lorraine M. Sordillo^*,†

¹ Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, 736 Wilson Rd., Room D202, East Lansing, MI 48824, USA

^† These authors contributed equally to this work.

Int. J. Mol. Sci. 2013, 14(10), 21167-21188; https://doi.org/10.3390/ijms141021167 - 22 Oct 2013

Cited by 142 | Viewed by 17212

Abstract

The composition of fatty acids in the diets of both human and domestic animal species can regulate inflammation through the biosynthesis of potent lipid mediators. The substrates for lipid mediator biosynthesis are derived primarily from membrane phospholipids and reflect dietary fatty acid intake. [...] Read more.

The composition of fatty acids in the diets of both human and domestic animal species can regulate inflammation through the biosynthesis of potent lipid mediators. The substrates for lipid mediator biosynthesis are derived primarily from membrane phospholipids and reflect dietary fatty acid intake. Inflammation can be exacerbated with intake of certain dietary fatty acids, such as some ω-6 polyunsaturated fatty acids (PUFA), and subsequent incorporation into membrane phospholipids. Inflammation, however, can be resolved with ingestion of other fatty acids, such as ω-3 PUFA. The influence of dietary PUFA on phospholipid composition is influenced by factors that control phospholipid biosynthesis within cellular membranes, such as preferential incorporation of some fatty acids, competition between newly ingested PUFA and fatty acids released from stores such as adipose, and the impacts of carbohydrate metabolism and physiological state. The objective of this review is to explain these factors as potential obstacles to manipulating PUFA composition of tissue phospholipids by specific dietary fatty acids. A better understanding of the factors that influence how dietary fatty acids can be incorporated into phospholipids may lead to nutritional intervention strategies that optimize health. Full article

(This article belongs to the Special Issue Phospholipids: Molecular Sciences 2012)

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Int. J. Mol. Sci., Volume 14, Issue 10 (October 2013) – 105 articles , Pages 19361-21201

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