International Journal of Molecular Sciences

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Open AccessReview

New Advances in Urea Transporter UT-A1 Membrane Trafficking

by Guangping Chen

Int. J. Mol. Sci. 2013, 14(5), 10674-10682; https://doi.org/10.3390/ijms140510674 - 21 May 2013

Cited by 5 | Viewed by 6770

The vasopressin-regulated urea transporter UT-A1, expressed in kidney inner medullary collecting duct (IMCD) epithelial cells, plays a critical role in the urinary concentrating mechanisms. As a membrane protein, the function of UT-A1 transport activity relies on its presence in the plasma membrane. Therefore, [...] Read more.

The vasopressin-regulated urea transporter UT-A1, expressed in kidney inner medullary collecting duct (IMCD) epithelial cells, plays a critical role in the urinary concentrating mechanisms. As a membrane protein, the function of UT-A1 transport activity relies on its presence in the plasma membrane. Therefore, UT-A1 successfully trafficking to the apical membrane of the polarized epithelial cells is crucial for the regulation of urea transport. This review summarizes the research progress of UT-A1 regulation over the past few years, specifically on the regulation of UT-A1 membrane trafficking by lipid rafts, N-linked glycosylation and a group of accessory proteins. Full article

(This article belongs to the Special Issue Regulation of Membrane Trafficking and Its Potential Implications)

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Open AccessArticle

Evaluation of the Effect of Different Doses of Low Energy Shock Wave Therapy on the Erectile Function of Streptozotocin (STZ)-Induced Diabetic Rats

by Jing Liu, Feng Zhou, Guang-Yong Li, Lin Wang, Hui-Xi Li, Guang-Yi Bai, Rui-Li Guan, Yong-De Xu, Ze-Zhu Gao, Wen-Jie Tian and Zhong-Cheng Xin

Int. J. Mol. Sci. 2013, 14(5), 10661-10673; https://doi.org/10.3390/ijms140510661 - 21 May 2013

Cited by 73 | Viewed by 10136

Abstract

To investigate the therapeutic effect of different doses of low energy shock wave therapy (LESWT) on the erectile dysfunction (ED) in streptozotocin (STZ) induced diabetic rats. SD rats (n = 75) were randomly divided into 5 groups (normal control, diabetic control, 3 [...] Read more.

To investigate the therapeutic effect of different doses of low energy shock wave therapy (LESWT) on the erectile dysfunction (ED) in streptozotocin (STZ) induced diabetic rats. SD rats (n = 75) were randomly divided into 5 groups (normal control, diabetic control, 3 different dose LESWT treated diabetic groups). Diabetic rats were induced by intra-peritoneal injection of STZ (60 mg/kg) and rats with fasting blood glucose ≥ 300 mg/dL were selected as diabetic models. Twelve weeks later, different doses of LESWT (100, 200 and 300 shocks each time) treatment on penises were used to treat ED (7.33 MPa, 2 shocks/s) three times a week for two weeks. The erectile function was evaluated by intracavernous pressure (ICP) after 1 week washout period. Then the penises were harvested for histological study. The results showed LESWT could significantly improve the erectile function of diabetic rats, increase smooth muscle and endothelial contents, up-regulate the expression of α-SMA, vWF, nNOS and VEGF, and down- regulate the expression of RAGE in corpus cavernosum. The therapeutic effect might relate to treatment dose positively, and the maximal therapeutic effect was noted in the LESWT300 group. Consequently, 300 shocks each time might be the ideal LESWT dose for diabetic ED treatment. Full article

(This article belongs to the Section Biochemistry)

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Open AccessArticle

Transcriptional Profiling of Swine Lung Tissue after Experimental Infection with Actinobacillus pleuropneumoniae

by Zhicai Zuo, Hengmin Cui, Mingzhou Li, Xi Peng, Ling Zhu, Ming Zhang, Jideng Ma, Zhiwen Xu, Meng Gan, Junliang Deng, Xuewei Li and Jing Fang

Int. J. Mol. Sci. 2013, 14(5), 10626-10660; https://doi.org/10.3390/ijms140510626 - 21 May 2013

Cited by 17 | Viewed by 10379

Abstract

Porcine pleuropneumonia is a highly contagious respiratory disease that causes great economic losses worldwide. In this study, we aimed to explore the underlying relationship between infection and injury by investigation of the whole porcine genome expression profiles of swine lung tissues post-inoculated with [...] Read more.

Porcine pleuropneumonia is a highly contagious respiratory disease that causes great economic losses worldwide. In this study, we aimed to explore the underlying relationship between infection and injury by investigation of the whole porcine genome expression profiles of swine lung tissues post-inoculated with experimentally Actinobacillus pleuropneumoniae. Expression profiling experiments of the control group and the treatment group were conducted using a commercially available Agilent Porcine Genechip including 43,603 probe sets. Microarray analysis was conducted on profiles of lung from challenged versus non-challenged swine. We found 11,929 transcripts, identified as differentially expressed at the p ≤0.01 level. There were 1188 genes annotated as swine genes in the GenBank Data Base. GO term analysis identified a total of 89 biological process categories, 82 cellular components and 182 molecular functions that were significantly affected, and at least 27 biological process categories that were related to the host immune response. Gene set enrichment analysis identified 13 pathways that were significantly associated with host response. Many proinflammatory-inflammatory cytokines were activated and involved in the regulation of the host defense response at the site of inflammation; while the cytokines involved in regulation of the host immune response were suppressed. All changes of genes and pathways of induced or repressed expression not only led to a decrease in antigenic peptides presented to T lymphocytes by APCs via the MHC and alleviated immune response injury induced by infection, but also stimulated stem cells to produce granulocytes (neutrophils, eosinophils, and basophils) and monocyte, and promote neutrophils and macrophages to phagocytose bacterial and foreign antigen at the site of inflammation. The defense function of swine infection with Actinobacillus pleuropneumoniae was improved, while its immune function was decreased. Full article

(This article belongs to the Section Biochemistry)

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Open AccessArticle

Effect of Plant Derived Antimicrobials on Salmonella Enteritidis Adhesion to and Invasion of Primary Chicken Oviduct Epithelial Cells in vitro and Virulence Gene Expression

by Indu Upadhyaya, Abhinav Upadhyay, Anup Kollanoor-Johny, Michael J. Darre and Kumar Venkitanarayanan

Int. J. Mol. Sci. 2013, 14(5), 10608-10625; https://doi.org/10.3390/ijms140510608 - 21 May 2013

Cited by 48 | Viewed by 8325

Abstract

Salmonella Enteritidis (SE) is a major foodborne pathogen in the United States and one of the most frequently reported Salmonella serotypes globally. Eggs are the most common food product associated with SE infections in humans. The pathogen colonizes the intestinal tract in layers, [...] Read more.

Salmonella Enteritidis (SE) is a major foodborne pathogen in the United States and one of the most frequently reported Salmonella serotypes globally. Eggs are the most common food product associated with SE infections in humans. The pathogen colonizes the intestinal tract in layers, and migrates to reproductive organs systemically. Since adhesion to and invasion of chicken oviduct epithelial cells (COEC) is critical for SE colonization in reproductive tract, reducing these virulence factors could potentially decrease egg yolk contamination. This study investigated the efficacy of sub-inhibitory concentrations of three plant-derived antimicrobials (PDAs), namely carvacrol, thymol and eugenol in reducing SE adhesion to and invasion of COEC, and survival in chicken macrophages. In addition, the effect of PDAs on SE genes critical for oviduct colonization and macrophage survival was determined using real-time quantitative PCR (RT-qPCR). All PDAs significantly reduced SE adhesion to and invasion of COEC (p < 0.001). The PDAs, except thymol consistently decreased SE survival in macrophages (p < 0.001). RT-qPCR results revealed down-regulation in the expression of genes involved in SE colonization and macrophage survival (p < 0.001). The results indicate that PDAs could potentially be used to control SE colonization in chicken reproductive tract; however, in vivo studies validating these results are warranted. Full article

(This article belongs to the Section Biochemistry)

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Open AccessReview

Nanoparticle-Based Systems for T₁-Weighted Magnetic Resonance Imaging Contrast Agents

by Derong Zhu, Fuyao Liu, Lina Ma, Dianjun Liu and Zhenxin Wang

Int. J. Mol. Sci. 2013, 14(5), 10591-10607; https://doi.org/10.3390/ijms140510591 - 21 May 2013

Cited by 82 | Viewed by 11593

Abstract

Because magnetic resonance imaging (MRI) contrast agents play a vital role in diagnosing diseases, demand for new MRI contrast agents, with an enhanced sensitivity and advanced functionalities, is very high. During the past decade, various inorganic nanoparticles have been used as MRI contrast [...] Read more.

Because magnetic resonance imaging (MRI) contrast agents play a vital role in diagnosing diseases, demand for new MRI contrast agents, with an enhanced sensitivity and advanced functionalities, is very high. During the past decade, various inorganic nanoparticles have been used as MRI contrast agents due to their unique properties, such as large surface area, easy surface functionalization, excellent contrasting effect, and other size-dependent properties. This review provides an overview of recent progress in the development of nanoparticle-based T₁-weighted MRI contrast agents. The chemical synthesis of the nanoparticle-based contrast agents and their potential applications were discussed and summarized. In addition, the recent development in nanoparticle-based multimodal contrast agents including T₁-weighted MRI/computed X-ray tomography (CT) and T₁-weighted MRI/optical were also described, since nanoparticles may curtail the shortcomings of single mode contrast agents in diagnostic and clinical settings by synergistically incorporating functionality. Full article

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

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Graphical abstract

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Open AccessArticle

Bacterial Growth Kinetics under a Novel Flexible Methacrylate Dressing Serving as a Drug Delivery Vehicle for Antiseptics

by Christina Forstner, Johannes Leitgeb, Rupert Schuster, Verena Dosch, Axel Kramer, Keith F. Cutting, David J. Leaper and Ojan Assadian

Int. J. Mol. Sci. 2013, 14(5), 10582-10590; https://doi.org/10.3390/ijms140510582 - 21 May 2013

Cited by 12 | Viewed by 9792

Abstract

A flexible methacrylate powder dressing (Altrazeal^®) transforms into a wound contour conforming matrix once in contact with wound exudate. We hypothesised that it may also serve as a drug delivery vehicle for antiseptics. The antimicrobial efficacy and influence on bacterial growth [...] Read more.

A flexible methacrylate powder dressing (Altrazeal^®) transforms into a wound contour conforming matrix once in contact with wound exudate. We hypothesised that it may also serve as a drug delivery vehicle for antiseptics. The antimicrobial efficacy and influence on bacterial growth kinetics in combination with three antiseptics was investigated in an in vitro porcine wound model. Standardized in vitro wounds were contaminated with Staphylococcus aureus (MRSA; ATCC 33591) and divided into six groups: no dressing (negative control), methacrylate dressing alone, and combinations with application of 0.02% Polyhexamethylene Biguanide (PHMB), 0.4% PHMB, 0.1% PHMB + 0.1% betaine, 7.7 mg/mL Povidone-iodine (PVP-iodine), and 0.1% Octenidine-dihydrochloride (OCT) + 2% phenoxyethanol. Bacterial load per gram tissue was measured over five days. The highest reduction was observed with PVP-iodine at 24 h to log₁₀ 1.43 cfu/g, followed by OCT at 48 h to log₁₀ 2.41 cfu/g. Whilst 0.02% PHMB resulted in a stable bacterial load over 120 h to log₁₀ 4.00 cfu/g over 120 h, 0.1% PHMB + 0.1% betaine inhibited growth during the first 48 h, with slightly increasing bacterial numbers up to log₁₀ 5.38 cfu/g at 120 h. These results indicate that this flexible methacrylate dressing can be loaded with various antiseptics serving as drug delivery system. Depending on the selected combination, an individually shaped and controlled antibacterial effect may be achieved using the same type of wound dressing. Full article

(This article belongs to the Special Issue Antimicrobial Polymers)

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Open AccessArticle

Intra-Species Bacterial Quorum Sensing Studied at Single Cell Level in a Double Droplet Trapping System

by Yunpeng Bai, Santoshkumar N. Patil, Steven D. Bowden, Simon Poulter, Jie Pan, George P. C. Salmond, Martin Welch, Wilhelm T. S. Huck and Chris Abell

Int. J. Mol. Sci. 2013, 14(5), 10570-10581; https://doi.org/10.3390/ijms140510570 - 21 May 2013

Cited by 22 | Viewed by 9736

Abstract

In this paper, we investigated the intra-species bacterial quorum sensing at the single cell level using a double droplet trapping system. Escherichia coli transformed to express the quorum sensing receptor protein, LasR, were encapsulated in microdroplets that were positioned adjacent to microdroplets containing [...] Read more.

In this paper, we investigated the intra-species bacterial quorum sensing at the single cell level using a double droplet trapping system. Escherichia coli transformed to express the quorum sensing receptor protein, LasR, were encapsulated in microdroplets that were positioned adjacent to microdroplets containing the autoinducer, N-(3-oxododecanoyl)-L-homoserine lactone (OdDHL). Functional activation of the LasR protein by diffusion of the OdDHL across the droplet interface was measured by monitoring the expression of green fluorescent protein (GFP) from a LasR-dependent promoter. A threshold concentration of OdDHL was found to induce production of quorum-sensing associated GFP by E. coli. Additionally, we demonstrated that LasR-dependent activation of GFP expression was also initiated when the adjacent droplets contained single E. coli transformed with the OdDHL synthase gene, LasI, representing a simple quorum sensing circuit between two droplets. Full article

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

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Open AccessArticle

Analysis of Conformational Motions and Residue Fluctuations for Escherichia coli Ribose-Binding Protein Revealed with Elastic Network Models

by Hai Yan Li, Zan Xia Cao, Li Ling Zhao and Ji Hua Wang

Int. J. Mol. Sci. 2013, 14(5), 10552-10569; https://doi.org/10.3390/ijms140510552 - 21 May 2013

Cited by 9 | Viewed by 7109

Abstract

The ribose-binding protein (RBP) is a sugar-binding bacterial periplasmic protein whose function is associated with a large allosteric conformational change from an open to a closed conformation upon binding to ribose. The open (ligand-free) and closed (ligand-bound) forms of RBP have been found. [...] Read more.

The ribose-binding protein (RBP) is a sugar-binding bacterial periplasmic protein whose function is associated with a large allosteric conformational change from an open to a closed conformation upon binding to ribose. The open (ligand-free) and closed (ligand-bound) forms of RBP have been found. Here we investigate the conformational motions and residue fluctuations of the RBP by analyzing the modes of motion with two coarse-grained elastic network models, the Gaussian Network Model (GNM) and Anisotropic Network Model (ANM). The calculated B-factors in both the calculated models are in good agreement with the experimentally determined B-factors in X-ray crystal structures. The slowest mode analysis by GNM shows that both forms have the same motion hinge axes around residues Ser103, Gln235, Asp264 and the two domains of both structures have similar fluctuation range. The superposition of the first three dominant modes of ANM, consisting of the rotating, bending and twisting motions of the two forms, accounts for large rearrangement of domains from the ligand-free (open) to ligand-bound (closed) conformation and thus constitutes a critical component of the RBP’s functions. By analyzing cross-correlations between residue fluctuation and the difference-distance plot, it is revealed that the conformational change can be described as a rigid rotation of the two domains with respect to each other, whereas the internal structure of the two domains remains largely intact. The results directly indicate that the dominant dynamic characteristics of protein structures can be captured from their static native state using coarse-grained models. Full article

(This article belongs to the Section Biochemistry)

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Open AccessArticle

NS5ATP9 Contributes to Inhibition of Cell Proliferation by Hepatitis C Virus (HCV) Nonstructural Protein 5A (NS5A) via MEK/Extracellular Signal Regulated Kinase (ERK) Pathway

by Qi Wang, Yongsheng Wang, Yue Li, Xuesong Gao, Shunai Liu and Jun Cheng

Int. J. Mol. Sci. 2013, 14(5), 10539-10551; https://doi.org/10.3390/ijms140510539 - 21 May 2013

Cited by 8 | Viewed by 7788

Abstract

Hepatitis C virus (HCV) nonstructural protein 5A (NS5A) is a remarkable protein as it clearly plays multiple roles in mediating viral replication, host-cell interactions and viral pathogenesis. However, on the impact of cell growth, there have been different study results. NS5ATP9, also known [...] Read more.

Hepatitis C virus (HCV) nonstructural protein 5A (NS5A) is a remarkable protein as it clearly plays multiple roles in mediating viral replication, host-cell interactions and viral pathogenesis. However, on the impact of cell growth, there have been different study results. NS5ATP9, also known as KIAA0101, p15PAF, L5, and OEACT-1, was first identified as a proliferating cell nuclear antigen-binding protein. Earlier studies have shown that NS5ATP9 might play an important role in HCV infection. The aim of this study is to investigate the function of NS5ATP9 on hepatocellular carcinoma (HCC) cell lines proliferation under HCV NS5A expression. The results showed that overexpression of NS5ATP9 inhibited the proliferation of Bel7402 cells, whereas knockdown of NS5ATP9 by interfering RNA promoted the growth of HepG2 cells. Under HCV NS5A expression, RNA interference (RNAi) targeting of NS5ATP9 could reverse the inhibition of HepG2 cell proliferation, suggesting that NS5ATP9 might be an anti-proliferation gene that plays an important role in the suppression of cell growth mediated by HCV NS5A via MEK/ERK signaling pathway. These findings might provide new insights into HCV NS5A and NS5ATP9. Full article

(This article belongs to the Special Issue Signalling Molecules and Signal Transduction in Cells)

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Open AccessReview

Obesity-Associated Oxidative Stress: Strategies Finalized to Improve Redox State

by Isabella Savini, Maria Valeria Catani, Daniela Evangelista, Valeria Gasperi and Luciana Avigliano

Int. J. Mol. Sci. 2013, 14(5), 10497-10538; https://doi.org/10.3390/ijms140510497 - 21 May 2013

Cited by 383 | Viewed by 21911

Abstract

Obesity represents a major risk factor for a plethora of severe diseases, including diabetes, cardiovascular disease, non-alcoholic fatty liver disease, and cancer. It is often accompanied by an increased risk of mortality and, in the case of non-fatal health problems, the quality of [...] Read more.

Obesity represents a major risk factor for a plethora of severe diseases, including diabetes, cardiovascular disease, non-alcoholic fatty liver disease, and cancer. It is often accompanied by an increased risk of mortality and, in the case of non-fatal health problems, the quality of life is impaired because of associated conditions, including sleep apnea, respiratory problems, osteoarthritis, and infertility. Recent evidence suggests that oxidative stress may be the mechanistic link between obesity and related complications. In obese patients, antioxidant defenses are lower than normal weight counterparts and their levels inversely correlate with central adiposity; obesity is also characterized by enhanced levels of reactive oxygen or nitrogen species. Inadequacy of antioxidant defenses probably relies on different factors: obese individuals may have a lower intake of antioxidant- and phytochemical-rich foods, such as fruits, vegetables, and legumes; otherwise, consumption of antioxidant nutrients is normal, but obese individuals may have an increased utilization of these molecules, likewise to that reported in diabetic patients and smokers. Also inadequate physical activity may account for a decreased antioxidant state. In this review, we describe current concepts in the meaning of obesity as a state of chronic oxidative stress and the potential interventions to improve redox balance. Full article

(This article belongs to the Special Issue Redox Signaling in Biology and Patho-Biology)

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Open AccessArticle

Inhibition of CCL2 Signaling in Combination with Docetaxel Treatment Has Profound Inhibitory Effects on Prostate Cancer Growth in Bone

by Peter S. Kirk, Theodore Koreckij, Holly M. Nguyen, Lisha G. Brown, Linda A. Snyder, Robert L. Vessella and Eva Corey

Int. J. Mol. Sci. 2013, 14(5), 10483-10496; https://doi.org/10.3390/ijms140510483 - 21 May 2013

Cited by 35 | Viewed by 6674

Abstract

The C-C chemokine ligand 2 (CCL2) stimulates migration, proliferation, and invasion of prostate cancer (PCa) cells, and its signaling also plays a role in the activation of osteoclasts. Therefore targeting CCL2 signaling in regulation of tumor progression in bone metastases is an area [...] Read more.

The C-C chemokine ligand 2 (CCL2) stimulates migration, proliferation, and invasion of prostate cancer (PCa) cells, and its signaling also plays a role in the activation of osteoclasts. Therefore targeting CCL2 signaling in regulation of tumor progression in bone metastases is an area of intense research. The objective of our study was to investigate the efficacy of CCL2 blockade by neutralizing antibodies to inhibit the growth of PCa in bone. We used a preclinical model of cancer growth in the bone in which PCa C4-2B cells were injected directly into murine tibiae. Animals were treated for ten weeks with neutralizing anti-CCL2 antibodies, docetaxel, or a combination of both, and then followed an additional nine weeks. CCL2 blockade inhibited the growth of PCa in bone, with even more pronounced inhibition in combination with docetaxel. CCL2 blockade also resulted in increases in bone mineral density. Furthermore, our results showed that the tumor inhibition lasted even after discontinuation of the treatment. Our data provide compelling evidence that CCL2 blockade slows PCa growth in bone, both alone and in combination with docetaxel. These results support the continued investigations of CCL2 blockade as a treatment for advanced metastatic PCa. Full article

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

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Open AccessArticle

The Role of Sulfur Dioxide in the Regulation of Mitochondrion-Related Cardiomyocyte Apoptosis in Rats with Isopropylarterenol-Induced Myocardial Injury

by Hongfang Jin, Angie Dong Liu, Lukas Holmberg, Manman Zhao, Siyao Chen, Jinyan Yang, Yan Sun, Shanshan Chen, Chaoshu Tang and Junbao Du

Int. J. Mol. Sci. 2013, 14(5), 10465-10482; https://doi.org/10.3390/ijms140510465 - 21 May 2013

Cited by 63 | Viewed by 7843

Abstract

The authors investigated the regulatory effects of sulfur dioxide (SO₂) on myocardial injury induced by isopropylarterenol (ISO) hydrochloride and its mechanisms. Wistar rats were divided into four groups: control group, ISO group, ISO plus SO₂ group, and SO₂ only [...] Read more.

The authors investigated the regulatory effects of sulfur dioxide (SO₂) on myocardial injury induced by isopropylarterenol (ISO) hydrochloride and its mechanisms. Wistar rats were divided into four groups: control group, ISO group, ISO plus SO₂ group, and SO₂ only group. Cardiac function was measured and cardiomyocyte apoptosis was detected. Bcl-2, bax and cytochrome c (cytc) expressions, and caspase-9 and caspase-3 activities in the left ventricular tissues were examined in the rats. The opening status of myocardial mitochondrial permeability transition pore (MPTP) and membrane potential were analyzed. The results showed that ISO-treated rats developed heart dysfunction and cardiac injury. Furthermore, cardiomyocyte apoptosis in the left ventricular tissues was augmented, left ventricular tissue bcl-2 expression was down-regulated, bax expression was up-regulated, mitochondrial membrane potential was significantly reduced, MPTP opened, cytc release from mitochondrion into cytoplasm was significantly increased, and both caspase-9 and caspase-3 activities were increased. Administration of an SO₂ donor, however, markedly improved heart function and relieved myocardial injury of the ISO-treated rats; it lessened cardiomyocyte apoptosis, up-regulated myocardial bcl-2, down-regulated bax expression, stimulated mitochondrial membrane potential, closed MPTP, and reduced cytc release as well as caspase-9 and caspase-3 activities in the left ventricular tissue. Hence, SO₂ attenuated myocardial injury in association with the inhibition of apoptosis in myocardial tissues, and the bcl-2/cytc/caspase-9/caspase-3 pathway was possibly involved in this process. Full article

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

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Open AccessReview

Human Prostatic Acid Phosphatase: Structure, Function and Regulation

by Sakthivel Muniyan, Nagendra K. Chaturvedi, Jennifer G. Dwyer, Chad A. LaGrange, William G. Chaney and Ming-Fong Lin

Int. J. Mol. Sci. 2013, 14(5), 10438-10464; https://doi.org/10.3390/ijms140510438 - 21 May 2013

Cited by 67 | Viewed by 14057

Abstract

Human prostatic acid phosphatase (PAcP) is a 100 kDa glycoprotein composed of two subunits. Recent advances demonstrate that cellular PAcP (cPAcP) functions as a protein tyrosine phosphatase by dephosphorylating ErbB-2/Neu/HER-2 at the phosphotyrosine residues in prostate cancer (PCa) cells, which results in reduced [...] Read more.

Human prostatic acid phosphatase (PAcP) is a 100 kDa glycoprotein composed of two subunits. Recent advances demonstrate that cellular PAcP (cPAcP) functions as a protein tyrosine phosphatase by dephosphorylating ErbB-2/Neu/HER-2 at the phosphotyrosine residues in prostate cancer (PCa) cells, which results in reduced tumorigenicity. Further, the interaction of cPAcP and ErbB-2 regulates androgen sensitivity of PCa cells. Knockdown of cPAcP expression allows androgen-sensitive PCa cells to develop the castration-resistant phenotype, where cells proliferate under an androgen-reduced condition. Thus, cPAcP has a significant influence on PCa cell growth. Interestingly, promoter analysis suggests that PAcP expression can be regulated by NF-κB, via a novel binding sequence in an androgen-independent manner. Further understanding of PAcP function and regulation of expression will have a significant impact on understanding PCa progression and therapy. Full article

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

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Open AccessReview

Claudins Overexpression in Ovarian Cancer: Potential Targets for Clostridium Perfringens Enterotoxin (CPE) Based Diagnosis and Therapy

by Diana P. English and Alessandro D. Santin

Int. J. Mol. Sci. 2013, 14(5), 10412-10437; https://doi.org/10.3390/ijms140510412 - 17 May 2013

Cited by 49 | Viewed by 11526

Abstract

Claudins are a family of tight junction proteins regulating paracellular permeability and cell polarity with different patterns of expression in benign and malignant human tissues. There are approximately 27 members of the claudin family identified to date with varying cell and tissue-specific expression. [...] Read more.

Claudins are a family of tight junction proteins regulating paracellular permeability and cell polarity with different patterns of expression in benign and malignant human tissues. There are approximately 27 members of the claudin family identified to date with varying cell and tissue-specific expression. Claudins-3, -4 and -7 represent the most highly differentially expressed claudins in ovarian cancer. While their exact role in ovarian tumors is still being elucidated, these proteins are thought to be critical for ovarian cancer cell invasion/dissemination and resistance to chemotherapy. Claudin-3 and claudin-4 are the natural receptors for the Clostridium perfringens enterotoxin (CPE), a potent cytolytic toxin. These surface proteins may therefore represent attractive targets for the detection and treatment of chemotherapy-resistant ovarian cancer and other aggressive solid tumors overexpressing claudin-3 and -4 using CPE-based theranostic agents. Full article

(This article belongs to the Special Issue Genes and Pathways in the Pathogenesis of Ovarian Cancer)

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Open AccessArticle

An Ultrasensitive Electrochemiluminescence Immunoassay for Carbohydrate Antigen 19-9 in Serum Based on Antibody Labeled Fe₃O₄ Nanoparticles as Capture Probes and Graphene/CdTe Quantum Dot Bionanoconjugates as Signal Amplifiers

by Ning Gan, Jing Zhou, Ping Xiong, Tianhua Li, Shan Jiang, Yuting Cao and Qianli Jiang

Int. J. Mol. Sci. 2013, 14(5), 10397-10411; https://doi.org/10.3390/ijms140510397 - 17 May 2013

Cited by 18 | Viewed by 10234

Abstract

The CdTe quantum dots (QDs), graphene nanocomposite (CdTe-G) and dextran–Fe₃O₄ magnetic nanoparticles have been synthesized for developing an ultrasensitive electrochemiluminescence (ECL) immunoassay for Carcinoembryonic antigen 19-9 (CA 19-9) in serums. Firstly, the capture probes (CA 19-9 Ab1/Fe₃O₄ [...] Read more.

The CdTe quantum dots (QDs), graphene nanocomposite (CdTe-G) and dextran–Fe₃O₄ magnetic nanoparticles have been synthesized for developing an ultrasensitive electrochemiluminescence (ECL) immunoassay for Carcinoembryonic antigen 19-9 (CA 19-9) in serums. Firstly, the capture probes (CA 19-9 Ab1/Fe₃O₄) for enriching CA 19-9 were synthesized by immobilizing the CA 19-9’s first antibody (CA 19-9 Ab1) on magnetic nanoparticles (dextran-Fe₃O₄). Secondly, the signal probes (CA 19-9 Ab2/CdTe-G), which can emit an ECL signal, were formed by attaching the secondary CA 19-9 antibody (CA 19-9 Ab2) to the surface of the CdTe-G. Thirdly, the above two probes were used for conjugating with a serial of CA 19-9 concentrations. Graphene can immobilize dozens of CdTe QDs on their surface, which can emit stronger ECL intensity than CdTe QDs. Based on the amplified signal, ultrasensitive antigen detection can be realized. Under the optimal conditions, the ECL signal depended linearly on the logarithm of CA 19-9 concentration from 0.005 to 100 pg/mL, and the detection limit was 0.002 pg/mL. Finally, five samples of human serum were tested, and the results were compared with a time-resolved fluorescence assay (TRFA). The novel immunoassay provides a stable, specific and highly sensitive immunoassay protocol for tumor marker detection at very low levels, which can be applied in early diagnosis of tumor. Full article

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

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Open AccessArticle

Influence of Growth Conditions on Magnetite Nanoparticles Electro-Crystallized in the Presence of Organic Molecules

by Saba Mosivand, Lorena M. A. Monzon, Iraj Kazeminezhad and J. Michael D. Coey

Int. J. Mol. Sci. 2013, 14(5), 10383-10396; https://doi.org/10.3390/ijms140510383 - 17 May 2013

Cited by 24 | Viewed by 7245

Abstract

Magnetite nanoparticles were synthesized by electrocrystallization in the presence of thiourea or sodium butanoate as an organic stabilizer. The synthesis was performed in a thermostatic electrochemical cell containing two iron electrodes with an aqueous solution of sodium sulfate as electrolyte. The effects of [...] Read more.

Magnetite nanoparticles were synthesized by electrocrystallization in the presence of thiourea or sodium butanoate as an organic stabilizer. The synthesis was performed in a thermostatic electrochemical cell containing two iron electrodes with an aqueous solution of sodium sulfate as electrolyte. The effects of organic concentration, applied potential and growth temperature on particle size, morphology, structure and magnetic properties were investigated. The magnetite nanoparticles were characterized by X-ray diffraction, electron microscopy, magnetometry and Mössbauer spectrometry. When the synthesis is performed in the presence of sodium butanoate at 60 °C, a paramagnetic ferric salt is obtained as a second phase; it is possible to avoid formation of this phase, increase the specific magnetization and improve the structure of the oxide particles by tuning the growth conditions. Room-temperature magnetization values range from 45 to 90 Am²kg⁻¹, depending on the particle size, type of surfactant and synthesis conditions. Mössbauer spectra, which were recorded at 290 K for all the samples, are typical of nonstoichiometric Fe_3−δO₄, with a small excess of Fe³⁺, 0.05 ≤ δ ≤ 0.15. Full article

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

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Open AccessArticle

The Role of Peritoneal Alternatively Activated Macrophages in the Process of Peritoneal Fibrosis Related to Peritoneal Dialysis

by Jie Wang, Zong-Pei Jiang, Ning Su, Jin-Jin Fan, Yi-Ping Ruan, Wen-Xing Peng, Ya-Fang Li and Xue-Qing Yu

Int. J. Mol. Sci. 2013, 14(5), 10369-10382; https://doi.org/10.3390/ijms140510369 - 17 May 2013

Cited by 32 | Viewed by 8379

Abstract

It has been confirmed that alternatively activated macrophages (M2) participate in tissue remodeling and fibrosis occurrence, but the effect of M2 on peritoneal fibrosis related to peritoneal dialysis (PD) hasn’t been elucidated. This study was therefore conducted to assess the association between M2 [...] Read more.

It has been confirmed that alternatively activated macrophages (M2) participate in tissue remodeling and fibrosis occurrence, but the effect of M2 on peritoneal fibrosis related to peritoneal dialysis (PD) hasn’t been elucidated. This study was therefore conducted to assess the association between M2 and peritoneal fibrosis related to PD. In this study, peritoneal fibrosis was induced by intraperitoneal (i.p.) injection of Lactate-4.25% dialysate (100 mL/kg) to C57BL/6J mice for 28 days, and liposome-encapsulated clodronate (LC, the specific scavenger of macrophages) was used to treat the peritoneal fibrosis mice model by i.p. injection at day 18 and day 21. All animals were sacrificed at day 29. Parietal peritonea were stained with Masson’s trichrome, and the expression of type I collagen (Col-I), fibronectin, mannose receptor (CD206), transforming growth factor beta (TGF-β), chemokine receptor 7 (CCR7), chitinase 3-like 3 (Ym-1) and arginase-1 (Arg-1) was determined by Western blotting, immunofluorescence and quantitative real-time PCR. Our results revealed that peritoneal thickness, Col-I, fibronectin, CD206, TGF-β, Ym-1 and Arg-1 were upregulated in the peritoneal fibrosis mice model, and all of these indexes were downregulated in those treated with LC. Additionally, there was no difference in the level of CCR7 between the model and treatment group. Our study indicated that peritoneal M2 played an important role in the process of peritoneal fibrosis related to PD and might be a potential target for intervention therapy of peritoneal fibrosis. Full article

(This article belongs to the Section Biochemistry)

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Open AccessArticle

Ultraviolet (UV) and Hydrogen Peroxide Activate Ceramide-ER Stress-AMPK Signaling Axis to Promote Retinal Pigment Epithelium (RPE) Cell Apoptosis

by Jin Yao, Hui-E Bi, Yi Sheng, Li-Bo Cheng, Ri-Le Wendu, Cheng-Hu Wang, Guo-Fan Cao and Qin Jiang

Int. J. Mol. Sci. 2013, 14(5), 10355-10368; https://doi.org/10.3390/ijms140510355 - 17 May 2013

Cited by 68 | Viewed by 11311

Abstract

Ultraviolet (UV) radiation and reactive oxygen species (ROS) impair the physiological functions of retinal pigment epithelium (RPE) cells by inducing cell apoptosis, which is the main cause of age-related macular degeneration (AMD). The mechanism by which UV/ROS induces RPE cell death is not [...] Read more.

Ultraviolet (UV) radiation and reactive oxygen species (ROS) impair the physiological functions of retinal pigment epithelium (RPE) cells by inducing cell apoptosis, which is the main cause of age-related macular degeneration (AMD). The mechanism by which UV/ROS induces RPE cell death is not fully addressed. Here, we observed the activation of a ceramide-endoplasmic reticulum (ER) stress-AMP activated protein kinase (AMPK) signaling axis in UV and hydrogen peroxide (H₂O₂)-treated RPE cells. UV and H₂O₂ induced an early ceramide production, profound ER stress and AMPK activation. Pharmacological inhibitors against ER stress (salubrinal), ceramide production (fumonisin B1) and AMPK activation (compound C) suppressed UV- and H₂O₂-induced RPE cell apoptosis. Conversely, cell permeable short-chain C6 ceramide and AMPK activator AICAR (5-amino-1-β-D-ribofuranosyl-imidazole-4-carboxamide) mimicked UV and H₂O₂’s effects and promoted RPE cell apoptosis. Together, these results suggest that UV/H₂O₂ activates the ceramide-ER stress-AMPK signaling axis to promote RPE cell apoptosis. Full article

(This article belongs to the Special Issue UV-Induced Cell Death 2012)

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Open AccessArticle

Ischemic Preconditioning Protects against Spinal Cord Ischemia-Reperfusion Injury in Rabbits by Attenuating Blood Spinal Cord Barrier Disruption

by Bo Fang, Xiao-Man Li, Xi-Jia Sun, Na-Ren Bao, Xiao-Yan Ren, Huang-Wei Lv and Hong Ma

Int. J. Mol. Sci. 2013, 14(5), 10343-10354; https://doi.org/10.3390/ijms140510343 - 17 May 2013

Cited by 42 | Viewed by 8505

Abstract

Ischemic preconditioning has been reported to protect against spinal cord ischemia-reperfusion (I-R) injury, but the underlying mechanisms are not fully understood. To investigate this, Japanese white rabbits underwent I-R (30 min aortic occlusion followed by reperfusion), ischemic preconditioning (three cycles of 5 min [...] Read more.

Ischemic preconditioning has been reported to protect against spinal cord ischemia-reperfusion (I-R) injury, but the underlying mechanisms are not fully understood. To investigate this, Japanese white rabbits underwent I-R (30 min aortic occlusion followed by reperfusion), ischemic preconditioning (three cycles of 5 min aortic occlusion plus 5 min reperfusion) followed by I-R, or sham surgery. At 4 and 24 h following reperfusion, neurological function was assessed using Tarlov scores, blood spinal cord barrier permeability was measured by Evan’s Blue extravasation, spinal cord edema was evaluated using the wet-dry method, and spinal cord expression of zonula occluden-1 (ZO-1), matrix metalloproteinase-9 (MMP-9), and tumor necrosis factor-α (TNF-α) were measured by Western blot and a real-time polymerase chain reaction. ZO-1 was also assessed using immunofluorescence. Spinal cord I-R injury reduced neurologic scores, and ischemic preconditioning treatment ameliorated this effect. Ischemic preconditioning inhibited I-R-induced increases in blood spinal cord barrier permeability and water content, increased ZO-1 mRNA and protein expression, and reduced MMP-9 and TNF-α mRNA and protein expression. These findings suggest that ischemic preconditioning attenuates the increase in blood spinal cord barrier permeability due to spinal cord I-R injury by preservation of tight junction protein ZO-1 and reducing MMP-9 and TNF-α expression. Full article

(This article belongs to the Special Issue Neuroprotective Strategies 2014)

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Open AccessArticle

Peripheral Blood miR-328 Expression as a Potential Biomarker for the Early Diagnosis of NSCLC

by Paola Ulivi, Giovanni Foschi, Marta Mengozzi, Emanuela Scarpi, Rosella Silvestrini, Dino Amadori and Wainer Zoli

Int. J. Mol. Sci. 2013, 14(5), 10332-10342; https://doi.org/10.3390/ijms140510332 - 16 May 2013

Cited by 70 | Viewed by 8323

Abstract

Lung cancer is often diagnosed at an advanced stage, with subsequently poor prognosis. There are no biomarkers available to facilitate early diagnosis or to discriminate between benign and malignant nodules. MicroRNAs (miRNAs) are stable molecules that can be found and measured in peripheral [...] Read more.

Lung cancer is often diagnosed at an advanced stage, with subsequently poor prognosis. There are no biomarkers available to facilitate early diagnosis or to discriminate between benign and malignant nodules. MicroRNAs (miRNAs) are stable molecules that can be found and measured in peripheral blood, thus representing potential diagnostic biomarkers. We evaluated 100 individuals comprising 86 patients with predominantly early-stage non-small cell lung cancer (NSCLC) and 24 healthy donors. RNA was extracted from peripheral blood samples and the expression of a panel of miRNAs was analyzed by Real-Time PCR method. Expression levels of miR-328, miR-18a, miR-339 and miR-140 were significantly higher in NSCLC patients than in healthy donors (p < 0.05). In particular, miR-328 showed good diagnostic accuracy in discriminating between patients with early NSCLC and healthy donors (AUC ROC 0.82, 95% CI 0.72–0.92), with 70% sensitivity and 83% specificity at the best relative expression cut-off of 300. Moreover, miR-339 was a good discriminant between healthy donors and late-stage NSCLC patients (AUC ROC 0.79, 95% CI 0.68–0.91). In conclusion, miR-328 represents a potential diagnostic biomarker of NSCLC, especially for the identification of early-stage tumors. Its role in discriminating between benign and malignant nodules detected by spiral CT warrants further investigation. Full article

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

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Open AccessReview

Methylated DNA and microRNA in Body Fluids as Biomarkers for Cancer Detection

by Yanning Ma, Xian Wang and Hongchuan Jin

Int. J. Mol. Sci. 2013, 14(5), 10307-10331; https://doi.org/10.3390/ijms140510307 - 16 May 2013

Cited by 35 | Viewed by 7492

Abstract

Epigenetic alterations including DNA methylation and microRNAs (miRNAs) play important roles in the initiation and progression of human cancers. As the extensively studied epigenetic changes in tumors, DNA methylation and miRNAs are the most potential epigenetic biomarkers for cancer diagnosis. After the identification [...] Read more.

Epigenetic alterations including DNA methylation and microRNAs (miRNAs) play important roles in the initiation and progression of human cancers. As the extensively studied epigenetic changes in tumors, DNA methylation and miRNAs are the most potential epigenetic biomarkers for cancer diagnosis. After the identification of circulating cell-free nuclear acids, increasing evidence demonstrated great potential of cell-free epigenetic biomarkers in the blood or other body fluids for cancer detection. Full article

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

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Open AccessArticle

An Exonuclease III Protection-Based Electrochemical Method for Estrogen Receptor Assay

by Sha Zhu, Ya Cao, Yuanyuan Xu, Yongmei Yin and Genxi Li

Int. J. Mol. Sci. 2013, 14(5), 10298-10306; https://doi.org/10.3390/ijms140510298 - 16 May 2013

Cited by 13 | Viewed by 7405

Abstract

Estrogen receptor (ER), expressed in approximately 80% of primary breast cancer cells, has proven to be a valuable predictive factor of the disease. Herein, by making use of the specific binding of ER to its DNA response elements, we propose an Exonuclease III [...] Read more.

Estrogen receptor (ER), expressed in approximately 80% of primary breast cancer cells, has proven to be a valuable predictive factor of the disease. Herein, by making use of the specific binding of ER to its DNA response elements, we propose an Exonuclease III (Exo III) protection-based electrochemical method for detecting ER proteins. In this assay, the presence of ER can protect the duplex DNA molecules immobilized on an electrode surface from Exo III-catalyzed digestion, resulting in an increased electrochemical signal. Experimental results have revealed that the proposed method can allow the quantification of ER in the range of 0.5 to 100 nM with a satisfactory detection limit of 0.38 nM. Furthermore, since this approach can also be employed to detect ER directly in nuclear extracts, it may be of great use in biomedical applications in the future. Full article

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

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Open AccessReview

Plant Defense against Insect Herbivores

by Joel Fürstenberg-Hägg, Mika Zagrobelny and Søren Bak

Int. J. Mol. Sci. 2013, 14(5), 10242-10297; https://doi.org/10.3390/ijms140510242 - 16 May 2013

Cited by 628 | Viewed by 41801

Abstract

Plants have been interacting with insects for several hundred million years, leading to complex defense approaches against various insect feeding strategies. Some defenses are constitutive while others are induced, although the insecticidal defense compound or protein classes are often similar. Insect herbivory induce [...] Read more.

Plants have been interacting with insects for several hundred million years, leading to complex defense approaches against various insect feeding strategies. Some defenses are constitutive while others are induced, although the insecticidal defense compound or protein classes are often similar. Insect herbivory induce several internal signals from the wounded tissues, including calcium ion fluxes, phosphorylation cascades and systemic- and jasmonate signaling. These are perceived in undamaged tissues, which thereafter reinforce their defense by producing different, mostly low molecular weight, defense compounds. These bioactive specialized plant defense compounds may repel or intoxicate insects, while defense proteins often interfere with their digestion. Volatiles are released upon herbivory to repel herbivores, attract predators or for communication between leaves or plants, and to induce defense responses. Plants also apply morphological features like waxes, trichomes and latices to make the feeding more difficult for the insects. Extrafloral nectar, food bodies and nesting or refuge sites are produced to accommodate and feed the predators of the herbivores. Meanwhile, herbivorous insects have adapted to resist plant defenses, and in some cases even sequester the compounds and reuse them in their own defense. Both plant defense and insect adaptation involve metabolic costs, so most plant-insect interactions reach a stand-off, where both host and herbivore survive although their development is suboptimal. Full article

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

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Open AccessArticle

Molecular Cloning and Characterization of the First Caspase in the Striped Stem Borer, Chilo suppressalis

by Ming-Xing Lu, Yu-Zhou Du, Shuang-Shuang Cao, Pingyang Liu and Jianyong Li

Int. J. Mol. Sci. 2013, 14(5), 10229-10241; https://doi.org/10.3390/ijms140510229 - 15 May 2013

Cited by 12 | Viewed by 6029

Abstract

Apoptosis is executed through the activity of the caspases that are aspartyl-specific proteases. In this study, we isolated the caspase gene (Cscaspase-1) of Chilo suppressalis (one of the leading pests responsible for destruction of rice crops). It possesses the open reading [...] Read more.

Apoptosis is executed through the activity of the caspases that are aspartyl-specific proteases. In this study, we isolated the caspase gene (Cscaspase-1) of Chilo suppressalis (one of the leading pests responsible for destruction of rice crops). It possesses the open reading frame (ORF) of 295 amino acids including prodomain, large subunit and small subunits, and two cleavage sites (Asp²³ and Asp¹⁹⁴) were found to be located among them. In addition to these profiles, Cscaspase-1 contains two active sites (His¹³⁴ and Cys¹⁷⁶). Genomic analysis demonstrated there was no intron in the genome of Cscaspase-1. The Cscaspase-1 transcripts were found in all tissues of the fifth instar larvae, and higher levels were found in the midgut, hindgut and Malpighian tubules. Examination of Cscaspase-1 expression in different developmental stages indicated low constitutive levels in the eggs and early larvae stages, and higher abundances were exhibited in the last larvae and pupae stages. The relative mRNA levels of Cscaspase-1 were induced by heat and cold temperatures. For example, the highest increase of Cscaspase-1 transcription was at −3 °C and 36 °C respectively. In a word, Cscaspase-1 plays a role of effector in the apoptosis of C. suppressalis. It also correlates with development, metamorphosis and thermotolerance of C. suppreassalis. Full article

(This article belongs to the Section Biochemistry)

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Open AccessReview

Bioavailability of Heavy Metals in Soil: Impact on Microbial Biodegradation of Organic Compounds and Possible Improvement Strategies

by Ademola O. Olaniran, Adhika Balgobind and Balakrishna Pillay

Int. J. Mol. Sci. 2013, 14(5), 10197-10228; https://doi.org/10.3390/ijms140510197 - 15 May 2013

Cited by 471 | Viewed by 22799

Abstract

Co-contamination of the environment with toxic chlorinated organic and heavy metal pollutants is one of the major problems facing industrialized nations today. Heavy metals may inhibit biodegradation of chlorinated organics by interacting with enzymes directly involved in biodegradation or those involved in general [...] Read more.

Co-contamination of the environment with toxic chlorinated organic and heavy metal pollutants is one of the major problems facing industrialized nations today. Heavy metals may inhibit biodegradation of chlorinated organics by interacting with enzymes directly involved in biodegradation or those involved in general metabolism. Predictions of metal toxicity effects on organic pollutant biodegradation in co-contaminated soil and water environments is difficult since heavy metals may be present in a variety of chemical and physical forms. Recent advances in bioremediation of co-contaminated environments have focussed on the use of metal-resistant bacteria (cell and gene bioaugmentation), treatment amendments, clay minerals and chelating agents to reduce bioavailable heavy metal concentrations. Phytoremediation has also shown promise as an emerging alternative clean-up technology for co-contaminated environments. However, despite various investigations, in both aerobic and anaerobic systems, demonstrating that metal toxicity hampers the biodegradation of the organic component, a paucity of information exists in this area of research. Therefore, in this review, we discuss the problems associated with the degradation of chlorinated organics in co-contaminated environments, owing to metal toxicity and shed light on possible improvement strategies for effective bioremediation of sites co-contaminated with chlorinated organic compounds and heavy metals. Full article

(This article belongs to the Special Issue Green Biocides)

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Open AccessArticle

Oxidative and Molecular Responses in Capsicum annuum L. after Hydrogen Peroxide, Salicylic Acid and Chitosan Foliar Applications

by Laura Mejía-Teniente, Flor de Dalia Durán-Flores, Angela María Chapa-Oliver, Irineo Torres-Pacheco, Andrés Cruz-Hernández, Mario M. González-Chavira, Rosalía V. Ocampo-Velázquez and Ramón G. Guevara-González

Int. J. Mol. Sci. 2013, 14(5), 10178-10196; https://doi.org/10.3390/ijms140510178 - 15 May 2013

Cited by 92 | Viewed by 11288

Abstract

Hydrogen peroxide (H₂O₂) is an important ROS molecule (Reactive oxygen species) that serves as a signal of oxidative stress and activation of signaling cascades as a result of the early response of the plant to biotic stress. This response [...] Read more.

Hydrogen peroxide (H₂O₂) is an important ROS molecule (Reactive oxygen species) that serves as a signal of oxidative stress and activation of signaling cascades as a result of the early response of the plant to biotic stress. This response can also be generated with the application of elicitors, stable molecules that induce the activation of transduction cascades and hormonal pathways, which trigger induced resistance to environmental stress. In this work, we evaluated the endogenous H₂O₂ production caused by salicylic acid (SA), chitosan (QN), and H₂O₂ elicitors in Capsicum annuum L. Hydrogen peroxide production after elicitation, catalase (CAT) and phenylalanine ammonia lyase (PAL) activities, as well as gene expression analysis of cat1, pal, and pathogenesis-related protein 1 (pr1) were determined. Our results displayed that 6.7 and 10 mM SA concentrations, and, 14 and 18 mM H₂O₂ concentrations, induced an endogenous H₂O₂ and gene expression. QN treatments induced the same responses in lesser proportion than the other two elicitors. Endogenous H₂O₂ production monitored during several days, showed results that could be an indicator for determining application opportunity uses in agriculture for maintaining plant alert systems against a stress. Full article

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

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Open AccessArticle

Frequency-Dependent Magnetic Susceptibility of Magnetite and Cobalt Ferrite Nanoparticles Embedded in PAA Hydrogel

by Susanne Van Berkum, Joris T. Dee, Albert P. Philipse and Ben H. Erné

Int. J. Mol. Sci. 2013, 14(5), 10162-10177; https://doi.org/10.3390/ijms140510162 - 14 May 2013

Cited by 62 | Viewed by 13296

Abstract

Chemically responsive hydrogels with embedded magnetic nanoparticles are of interest for biosensors that magnetically detect chemical changes. A crucial point is the irreversible linkage of nanoparticles to the hydrogel network, preventing loss of nanoparticles upon repeated swelling and shrinking of the gel. Here, [...] Read more.

Chemically responsive hydrogels with embedded magnetic nanoparticles are of interest for biosensors that magnetically detect chemical changes. A crucial point is the irreversible linkage of nanoparticles to the hydrogel network, preventing loss of nanoparticles upon repeated swelling and shrinking of the gel. Here, acrylic acid monomers are adsorbed onto ferrite nanoparticles, which subsequently participate in polymerization during synthesis of poly(acrylic acid)-based hydrogels (PAA). To demonstrate the fixation of the nanoparticles to the polymer, our original approach is to measure low-field AC magnetic susceptibility spectra in the 0.1 Hz to 1 MHz range. In the hydrogel, the magnetization dynamics of small iron oxide nanoparticles are comparable to those of the particles dispersed in a liquid, due to fast Néel relaxation inside the particles; this renders the ferrogel useful for chemical sensing at frequencies of several kHz. However, ferrogels holding thermally blocked iron oxide or cobalt ferrite nanoparticles show significant decrease of the magnetic susceptibility resulting from a frozen magnetic structure. This confirms that the nanoparticles are unable to rotate thermally inside the hydrogel, in agreement with their irreversible fixation to the polymer network. Full article

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

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Graphical abstract

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Open AccessReview

MAPKs and Signal Transduction in the Control of Gastrointestinal Epithelial Cell Proliferation and Differentiation

by Luciana H. Osaki and Patrícia Gama

Int. J. Mol. Sci. 2013, 14(5), 10143-10161; https://doi.org/10.3390/ijms140510143 - 13 May 2013

Cited by 119 | Viewed by 12005

Abstract

Mitogen-activated protein kinase (MAPK) pathways are activated by several stimuli and transduce the signal inside cells, generating diverse responses including cell proliferation, differentiation, migration and apoptosis. Each MAPK cascade comprises a series of molecules, and regulation takes place at different levels. They communicate [...] Read more.

Mitogen-activated protein kinase (MAPK) pathways are activated by several stimuli and transduce the signal inside cells, generating diverse responses including cell proliferation, differentiation, migration and apoptosis. Each MAPK cascade comprises a series of molecules, and regulation takes place at different levels. They communicate with each other and with additional pathways, creating a signaling network that is important for cell fate determination. In this review, we focus on ERK, JNK, p38 and ERK5, the major MAPKs, and their interactions with PI3K-Akt, TGFβ/Smad and Wnt/β-catenin pathways. More importantly, we describe how MAPKs regulate cell proliferation and differentiation in the rapidly renewing epithelia that lines the gastrointestinal tract and, finally, we highlight the recent findings on nutritional aspects that affect MAPK transduction cascades. Full article

(This article belongs to the Special Issue Signalling Molecules and Signal Transduction in Cells)

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Open AccessReview

TrkB Receptor Signalling: Implications in Neurodegenerative, Psychiatric and Proliferative Disorders

by Vivek K. Gupta, Yuyi You, Veer Bala Gupta, Alexander Klistorner and Stuart L. Graham

Int. J. Mol. Sci. 2013, 14(5), 10122-10142; https://doi.org/10.3390/ijms140510122 - 13 May 2013

Cited by 185 | Viewed by 19187

Abstract

The Trk family of receptors play a wide variety of roles in physiological and disease processes in both neuronal and non-neuronal tissues. Amongst these the TrkB receptor in particular has attracted major attention due to its critical role in signalling for brain derived [...] Read more.

The Trk family of receptors play a wide variety of roles in physiological and disease processes in both neuronal and non-neuronal tissues. Amongst these the TrkB receptor in particular has attracted major attention due to its critical role in signalling for brain derived neurotrophic factor (BDNF), neurotrophin-3 (NT3) and neurotrophin-4 (NT4). TrkB signalling is indispensable for the survival, development and synaptic plasticity of several subtypes of neurons in the nervous system. Substantial evidence has emerged over the last decade about the involvement of aberrant TrkB signalling and its compromise in various neuropsychiatric and degenerative conditions. Unusual changes in TrkB signalling pathway have also been observed and implicated in a range of cancers. Variations in TrkB pathway have been observed in obesity and hyperphagia related disorders as well. Both BDNF and TrkB have been shown to play critical roles in the survival of retinal ganglion cells in the retina. The ability to specifically modulate TrkB signalling can be critical in various pathological scenarios associated with this pathway. In this review, we discuss the mechanisms underlying TrkB signalling, disease implications and explore plausible ameliorative or preventive approaches. Full article

(This article belongs to the Section Biochemistry)

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Open AccessArticle

Native High Density Lipoproteins (HDL) Interfere with Platelet Activation Induced by Oxidized Low Density Lipoproteins (OxLDL)

by Sigrun Badrnya, Alice Assinger and Ivo Volf

Int. J. Mol. Sci. 2013, 14(5), 10107-10121; https://doi.org/10.3390/ijms140510107 - 10 May 2013

Cited by 20 | Viewed by 7256

Abstract

Platelets and lipoproteins play a crucial role in atherogenesis, in part by their ability to modulate inflammation and oxidative stress. While oxidized low density lipoproteins (OxLDL) play a central role in the development of this disease, high density lipoproteins (HDL) represent an atheroprotective [...] Read more.

Platelets and lipoproteins play a crucial role in atherogenesis, in part by their ability to modulate inflammation and oxidative stress. While oxidized low density lipoproteins (OxLDL) play a central role in the development of this disease, high density lipoproteins (HDL) represent an atheroprotective factor of utmost importance. As platelet function is remarkably sensitive to the influence of plasma lipoproteins, it was the aim of this study to clarify if HDL are able to counteract the stimulating effects of OxLDL with special emphasis on aspects of platelet function that are relevant to inflammation. Therefore, HDL were tested for their ability to interfere with pro-thrombotic and pro-inflammatory aspects of platelet function. We are able to show that HDL significantly impaired OxLDL-induced platelet aggregation and adhesion. In gel-filtered platelets, HDL decreased both the formation of reactive oxygen species and CD40L expression. Furthermore, HDL strongly interfered with OxLDL-induced formation of platelet-neutrophil aggregates in whole blood, suggesting that platelets represent a relevant and sensitive target for HDL. The finding that HDL effectively competed with the binding of OxLDL to the platelet surface might contribute to their atheroprotective and antithrombotic properties. Full article

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

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Int. J. Mol. Sci., Volume 14, Issue 5 (May 2013) – 111 articles , Pages 8684-10682

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