International Journal of Molecular Sciences

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Open AccessArticle

Biomarkers for Refractory Lupus Nephritis: A Microarray Study of Kidney Tissue

by Thitima Benjachat, Pumipat Tongyoo, Pornpen Tantivitayakul, Poorichaya Somparn, Nattiya Hirankarn, Santitham Prom-On, Prapaporn Pisitkun, Asada Leelahavanichkul, Yingyos Avihingsanon and Natavudh Townamchai

Int. J. Mol. Sci. 2015, 16(6), 14276-14290; https://doi.org/10.3390/ijms160614276 - 23 Jun 2015

Cited by 20 | Viewed by 8256

Abstract

The prognosis of severe lupus nephritis (LN) is very different among individual patients. None of the current biomarkers can be used to predict the development of refractory LN. Because kidney histology is the gold standard for diagnosing LN, the authors hypothesize that molecular [...] Read more.

The prognosis of severe lupus nephritis (LN) is very different among individual patients. None of the current biomarkers can be used to predict the development of refractory LN. Because kidney histology is the gold standard for diagnosing LN, the authors hypothesize that molecular signatures detected in kidney biopsy tissue may have predictive value in determining the therapeutic response. Sixty-seven patients with biopsy-proven severely active LN by International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification III/IV were recruited. Twenty-three kidney tissue samples were used for RNA microarray analysis, while the remaining 44 samples were used for validation by real-time polymerase chain reaction (PCR) gene expression analysis. From hundreds of differential gene expressions in refractory LN, 12 candidates were selected for validation based on gene expression levels as well as relevant functions. The candidate biomarkers were members of the innate immune response molecules, adhesion molecules, calcium-binding receptors, and paracellular tight junction proteins. S100A8, ANXA13, CLDN19 and FAM46B were identified as the best kidney biomarkers for refractory LN, and COL8A1 was identified as the best marker for early loss of kidney function. These new molecular markers can be used to predict refractory LN and may eventually lead to novel molecular targets for therapy. Full article

(This article belongs to the Special Issue Molecular and Cellular Mechanisms in the Pathogenesis of Systemic Lupus Erythematosus)

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809 KiB

Open AccessArticle

Effect of Dose and Administration Period of Seed Cake of Genetically Modified and Non-Modified Flax on Selected Antioxidative Activities in Rats

by Magdalena Matusiewicz, Iwona Kosieradzka, Magdalena Zuk and Jan Szopa

Int. J. Mol. Sci. 2015, 16(6), 14259-14275; https://doi.org/10.3390/ijms160614259 - 23 Jun 2015

Cited by 17 | Viewed by 7338

Abstract

Flaxseed cake containing antioxidants is a valuable dietary component. Its nutritional effect may be diminished by the presence of anti-nutrients. The work was aimed at determining the effect of different contents of flaxseed cake in diets and their administration period on the development [...] Read more.

Flaxseed cake containing antioxidants is a valuable dietary component. Its nutritional effect may be diminished by the presence of anti-nutrients. The work was aimed at determining the effect of different contents of flaxseed cake in diets and their administration period on the development of rats and selected parameters of their health status. Diets with 15% and 30% addition of genetically modified (GM) flax seed cake with enhanced synthesis of polyphenols, as well as Linola non-GM flax were administered in short-term (33 days) and long-term (90 days) experiments. The 30% addition of flaxseed cake reduced digestibility of dietary nutrients, GM flaxseed cake lowered body weight gains. The relative weight of selected organs, hematological blood markers and serum activities of aspartate and alanine aminotransferases (AST, ALT) were not affected. Flaxseed cake consumption reduced serum concentration of albumins and increased globulins. Administration of 30% flaxseed cake improved plasma total antioxidant status and 30% GM flaxseed cake lowered liver thiobarbituric acid reactive substances. The activities of superoxide dismutase in erythrocytes, glutathione peroxidase in plasma and the liver concentration of 8-oxo-2′-deoxyguanosine were not changed. Most morphometric parameters of the small intestine did not differ between feeding groups. The administration of diets with 30% addition of flaxseed cake for 90 days improved the antioxidant status in rats. Full article

(This article belongs to the Special Issue Gene-Nutrient Interactions)

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Open AccessArticle

Biomineral/Agarose Composite Gels Enhance Proliferation of Mesenchymal Stem Cells with Osteogenic Capability

by Yoshika Suzawa, Norihiko Kubo, Soichi Iwai, Yoshiaki Yura, Hajime Ohgushi and Mitsuru Akashi

Int. J. Mol. Sci. 2015, 16(6), 14245-14258; https://doi.org/10.3390/ijms160614245 - 23 Jun 2015

Cited by 23 | Viewed by 6805

Abstract

Hydroxyapatite (HA) or calcium carbonate (CaCO₃) formed on an organic polymer of agarose gel is a biomaterial that can be used for bone tissue regeneration. However, in critical bone defects, the regeneration capability of these materials is limited. Mesenchymal stem cells [...] Read more.

Hydroxyapatite (HA) or calcium carbonate (CaCO₃) formed on an organic polymer of agarose gel is a biomaterial that can be used for bone tissue regeneration. However, in critical bone defects, the regeneration capability of these materials is limited. Mesenchymal stem cells (MSCs) are multipotent cells that can differentiate into bone forming osteoblasts. In this study, we loaded MSCs on HA- or CaCO₃-formed agarose gel and cultured them with dexamethasone, which triggers the osteogenic differentiation of MSCs. High alkaline phosphatase activity was detected on both the HA- and CaCO₃-formed agarose gels; however, basal activity was only detected on bare agarose gel. Bone-specific osteocalcin content was detected on CaCO₃-formed agarose gel on Day 14 of culture, and levels subsequently increased over time. Similar osteocalcin content was detected on HA-formed agarose on Day 21 and levels increased on Day 28. In contrast, only small amounts of osteocalcin were found on bare agarose gel. Consequently, osteogenic capability of MSCs was enhanced on CaCO₃-formed agarose at an early stage, and both HA- and CaCO₃-formed agarose gels well supported the capability at a later stage. Therefore, MSCs loaded on either HA- or CaCO₃-formed agarose could potentially be employed for the repair of critical bone defects. Full article

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

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Open AccessReview

Transcriptional Factors Mediating Retinoic Acid Signals in the Control of Energy Metabolism

by Rui Zhang, Yueqiao Wang, Rui Li and Guoxun Chen

Int. J. Mol. Sci. 2015, 16(6), 14210-14244; https://doi.org/10.3390/ijms160614210 - 23 Jun 2015

Cited by 63 | Viewed by 11447

Abstract

Retinoic acid (RA), an active metabolite of vitamin A (VA), is important for many physiological processes including energy metabolism. This is mainly achieved through RA-regulated gene expression in metabolically active cells. RA regulates gene expression mainly through the activation of two subfamilies in [...] Read more.

Retinoic acid (RA), an active metabolite of vitamin A (VA), is important for many physiological processes including energy metabolism. This is mainly achieved through RA-regulated gene expression in metabolically active cells. RA regulates gene expression mainly through the activation of two subfamilies in the nuclear receptor superfamily, retinoic acid receptors (RARs) and retinoid X receptors (RXRs). RAR/RXR heterodimers or RXR/RXR homodimers bind to RA response element in the promoters of RA target genes and regulate their expressions upon ligand binding. The development of metabolic diseases such as obesity and type 2 diabetes is often associated with profound changes in the expressions of genes involved in glucose and lipid metabolism in metabolically active cells. RA regulates some of these gene expressions. Recently, in vivo and in vitro studies have demonstrated that status and metabolism of VA regulate macronutrient metabolism. Some studies have shown that, in addition to RARs and RXRs, hepatocyte nuclear factor 4α, chicken ovalbumin upstream promoter-transcription factor II, and peroxisome proliferator activated receptor β/δ may function as transcriptional factors mediating RA response. Herein, we summarize current progresses regarding the VA metabolism and the role of nuclear receptors in mediating RA signals, with an emphasis on their implication in energy metabolism. Full article

(This article belongs to the Special Issue Gene-Nutrient Interactions)

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Open AccessArticle

Bioactive Phytochemicals from Wild Arbutus unedo L. Berries from Different Locations in Portugal: Quantification of Lipophilic Components

by Daniela F. S. Fonseca, Ângelo C. Salvador, Sónia A. O. Santos, Carla Vilela, Carmen S. R. Freire, Armando J. D. Silvestre and Sílvia M. Rocha

Int. J. Mol. Sci. 2015, 16(6), 14194-14209; https://doi.org/10.3390/ijms160614194 - 23 Jun 2015

Cited by 23 | Viewed by 8072

Abstract

The lipophilic composition of wild Arbutus unedo L. berries, collected from six locations in Penacova (center of Portugal), as well as some general chemical parameters, namely total soluble solids, pH, titratable acidity, total phenolic content and antioxidant activity was studied in detail to [...] Read more.

The lipophilic composition of wild Arbutus unedo L. berries, collected from six locations in Penacova (center of Portugal), as well as some general chemical parameters, namely total soluble solids, pH, titratable acidity, total phenolic content and antioxidant activity was studied in detail to better understand its potential as a source of bioactive compounds. The chemical composition of the lipophilic extracts, focused on the fatty acids, triterpenoids, sterols, long chain aliphatic alcohols and tocopherols, was investigated by gas chromatography–mass spectrometry (GC–MS) analysis of the dichloromethane extracts. The lipophilic extractives of the ripe A. unedo berries ranged from 0.72% to 1.66% (w/w of dry weight), and consisted mainly of triterpenoids, fatty acids and sterols. Minor amounts of long chain aliphatic alcohols and tocopherols were also identified. Forty-one compounds were identified and among these, ursolic acid, lupeol, α-amyrin, linoleic and α-linolenic acids, and β-sitosterol were highlighted as the major components. To the best of our knowledge the current research study provides the most detailed phytochemical repository for the lipophilic composition of A. unedo, and offers valuable information for future valuation and exploitation of these berries. Full article

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

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Open AccessArticle

Molecular Mechanisms Underlying Hull-Caryopsis Adhesion/Separation Revealed by Comparative Transcriptomic Analysis of Covered/Naked Barley (Hordeum vulgare L.)

by Ruijun Duan, Huiyan Xiong, Aidong Wang and Guoxiong Chen

Int. J. Mol. Sci. 2015, 16(6), 14181-14193; https://doi.org/10.3390/ijms160614181 - 23 Jun 2015

Cited by 19 | Viewed by 6003

Abstract

The covered/naked caryopsis trait of barley is an important agronomic trait because it is directly linked to dietary use. The formation of covered/naked caryopsis is controlled by an NUD transcription factor, which is involved in pericarp cuticle development. However, the molecular mechanism underlying [...] Read more.

The covered/naked caryopsis trait of barley is an important agronomic trait because it is directly linked to dietary use. The formation of covered/naked caryopsis is controlled by an NUD transcription factor, which is involved in pericarp cuticle development. However, the molecular mechanism underlying this trait remains so far largely unknown. In this study, comparative transcriptomes of grains three weeks after anthesis of Tibetan Hulless barley landrace Dulihuang and covered barley Morex were analyzed using RNA-seq technique. A total of 4031 differentially expressed genes (DEGs) were identified. The Nud gene was overexpressed in Morex, with trace expression in Dulihuang. Among seventeen cuticle related DEGs, sixteen were down regulated and one up regulated in Morex. These results suggest that the Nud gene in covered caryopsis might down regulate cuticle related genes, which may cause a permeable cuticle over pericarp, leading to a hull-caryopsis organ fusion. A functional cuticle covering the pericarp of naked caryopsis might be the result of deletion or low expression level of the Nud gene. The functional cuticle defines a perfect boundary to separate the caryopsis from the hull in naked barley. Full article

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

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Open AccessArticle

Memantine Attenuates Delayed Vasospasm after Experimental Subarachnoid Hemorrhage via Modulating Endothelial Nitric Oxide Synthase

by Chih-Yuan Huang, Liang-Chao Wang, Yan-Shen Shan, Chia-Hsin Pan and Kuen-Jer Tsai

Int. J. Mol. Sci. 2015, 16(6), 14171-14180; https://doi.org/10.3390/ijms160614171 - 23 Jun 2015

Cited by 18 | Viewed by 6368

Abstract

Delayed cerebral vasospasm is an important pathological feature of subarachnoid hemorrhage (SAH). The cause of vasospasm is multifactorial. Impairs nitric oxide availability and endothelial nitric oxide synthase (eNOS) dysfunction has been reported to underlie vasospasm. Memantine, a low-affinity uncompetitive N-methyl-d-aspartate (NMDA) blocker [...] Read more.

Delayed cerebral vasospasm is an important pathological feature of subarachnoid hemorrhage (SAH). The cause of vasospasm is multifactorial. Impairs nitric oxide availability and endothelial nitric oxide synthase (eNOS) dysfunction has been reported to underlie vasospasm. Memantine, a low-affinity uncompetitive N-methyl-d-aspartate (NMDA) blocker has been proven to reduce early brain injury after SAH. This study investigated the effect of memantine on attenuation of vasospasm and restoring eNOS functionality. Male Sprague-Dawley rats weighing 350–450 g were randomly divided into three weight-matched groups, sham surgery, SAH + vehicle, and SAH + memantine groups. The effects of memantine on SAH were evaluated by assessing the severity of vasospasm and the expression of eNOS. Memantine effectively ameliorated cerebral vasospasm by restoring eNOS functionality. Memantine can prevent vasospasm in experimental SAH. Treatment strategies may help combat SAH-induced vasospasm in the future. Full article

(This article belongs to the Special Issue Neurological Injuries’ Monitoring, Tracking and Treatment)

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Open AccessReview

A Plasmacytoid Dendritic Cells-Type I Interferon Axis Is Critically Implicated in the Pathogenesis of Systemic Lupus Erythematosus

by Ji-Min Kim, Sung-Hwan Park, Ho-Youn Kim and Seung-Ki Kwok

Int. J. Mol. Sci. 2015, 16(6), 14158-14170; https://doi.org/10.3390/ijms160614158 - 23 Jun 2015

Cited by 47 | Viewed by 16302

Abstract

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease that is characterized by the generation of immune responses to various nuclear components. Impaired clearance of apoptotic cells and loss of tolerance to self-antigens are involved both in the initiation and in the propagation [...] Read more.

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease that is characterized by the generation of immune responses to various nuclear components. Impaired clearance of apoptotic cells and loss of tolerance to self-antigens are involved both in the initiation and in the propagation of the disease. Dendritic cells (DCs) are key factors in the balance between autoimmunity and tolerance and play a role linking innate and adaptive immunity. DCs, particularly plasmacytoid DCs (pDCs), are the main source of type I interferon (IFN) cytokines, which contribute to the immunopathogenesis of SLE. There is accumulating evidence that pDCs and type I IFN cytokines take the leading part in the development of SLE. In this review, we discuss recent data regarding the role of pDCs and type I IFN cytokines in the pathogenesis of SLE and the potential for employing therapies targeting against aberrant regulation of the pDC-type I IFN axis for treating SLE. Full article

(This article belongs to the Special Issue Molecular and Cellular Mechanisms in the Pathogenesis of Systemic Lupus Erythematosus)

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Open AccessArticle

Local Controlled Release of Polyphenol Conjugated with Gelatin Facilitates Bone Formation

by Yoshitomo Honda, Tomonari Tanaka, Tomoko Tokuda, Takahiro Kashiwagi, Koji Kaida, Ayato Hieda, Yasuyuki Umezaki, Yoshiya Hashimoto, Koichi Imai, Naoyuki Matsumoto, Shunsuke Baba and Kimishige Shimizutani

Int. J. Mol. Sci. 2015, 16(6), 14143-14157; https://doi.org/10.3390/ijms160614143 - 23 Jun 2015

Cited by 29 | Viewed by 7509

Abstract

Catechins are extensively used in health care treatments. Nevertheless, there is scarce information about the feasibility of local administration with polyphenols for bone regeneration therapy, possibly due to lack of effective delivery systems. Here we demonstrated that the epigallocatechin-3-gallate-conjugated gelatin (EGCG/Gel) prepared by [...] Read more.

Catechins are extensively used in health care treatments. Nevertheless, there is scarce information about the feasibility of local administration with polyphenols for bone regeneration therapy, possibly due to lack of effective delivery systems. Here we demonstrated that the epigallocatechin-3-gallate-conjugated gelatin (EGCG/Gel) prepared by an aqueous chemical synthesis using 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-morpholinium chloride (DMT-MM) gradually disintegrated with time and facilitated bone formation in a critical size defect of a mouse calvaria. Conjugation of EGCG with the Gel generated cross-linking between the two molecules, thereby leading to a retardation of the degradation of the EGCG/Gel and to a delayed release of EGCG. The prepared EGCG/Gels represented significant osteogenic capability compared with that of the uncross-linked Gel and the cross-linked Gel with uncombined-EGCG. In vitro experiments disclosed that the EGCG/Gel induced osteoblastogenesis of a mouse mesenchymal stem cell line (D1 cells) within 14 days. Using fluorescently-labeled EGCG/Gel, we found that the fraction of EGCG/Gel adsorbed onto the cell membrane of the D1 cells possibly via a Gel-cell interaction. The interaction might confer the long-term effects of EGCG on the cells, resulting in a potent osteogenic capability of the EGCG/Gel in vivo. These results should provide insight into local controlled release of polyphenols for bone therapy. Full article

(This article belongs to the Special Issue Phenolics and Polyphenolics 2015)

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Open AccessReview

Circulating Cell-Free Tumour DNA in the Management of Cancer

by Glenn Francis and Sandra Stein

Int. J. Mol. Sci. 2015, 16(6), 14122-14142; https://doi.org/10.3390/ijms160614122 - 19 Jun 2015

Cited by 95 | Viewed by 11287

Abstract

With the development of new sensitive molecular techniques, circulating cell-free tumour DNA containing mutations can be identified in the plasma of cancer patients. The applications of this technology may result in significant changes to the care and management of cancer patients. Whilst, currently, [...] Read more.

With the development of new sensitive molecular techniques, circulating cell-free tumour DNA containing mutations can be identified in the plasma of cancer patients. The applications of this technology may result in significant changes to the care and management of cancer patients. Whilst, currently, these “liquid biopsies” are used to supplement the histological diagnosis of cancer and metastatic disease, in the future these assays may replace the need for invasive procedures. Applications include the monitoring of tumour burden, the monitoring of minimal residual disease, monitoring of tumour heterogeneity, monitoring of molecular resistance and early diagnosis of tumours and metastatic disease. Full article

(This article belongs to the Special Issue Emerging Classes of Biomarkers for Molecular Diagnostics)

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Open AccessReview

Novel Therapeutic GPCRs for Psychiatric Disorders

by Hidetoshi Komatsu

Int. J. Mol. Sci. 2015, 16(6), 14109-14121; https://doi.org/10.3390/ijms160614109 - 19 Jun 2015

Cited by 50 | Viewed by 12922

Abstract

G protein-coupled receptors (GPCRs) are the most common targets of the neuropharmacological drugs in the central nervous system (CNS). GPCRs are activated by manifold neurotransmitters, and their activation in turn evokes slow synaptic transmission. They are deeply involved in multiple neurological and psychiatric [...] Read more.

G protein-coupled receptors (GPCRs) are the most common targets of the neuropharmacological drugs in the central nervous system (CNS). GPCRs are activated by manifold neurotransmitters, and their activation in turn evokes slow synaptic transmission. They are deeply involved in multiple neurological and psychiatric disorders such as Parkinson’s disease and schizophrenia. In the brain, the striatum is strongly innervated by the ventral tegmental area (VTA) and plays a central role in manifestation of psychiatric disorders. Recently, anatomical and comprehensive transcriptome analysis of the non-odorant GPCR superfamily revealed that the orphan GPCRs GPR88, GPR6, and GPR52, as well as dopamine D1 and D2 receptors and the adenosine A2a receptor, are the most highly enriched in the rodent striatum. Genetically engineered animal models and molecular biological studies have suggested that these striatally enriched GPCRs have a potential to be therapeutic psychiatric receptors. This review summarizes the current understanding of the therapeutic GPCR candidates for psychiatric disorders. Full article

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

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Open AccessCommunication

Expression Profiling of Circulating MicroRNAs in Canine Myxomatous Mitral Valve Disease

by Qinghong Li, Lisa M. Freeman, John E. Rush and Dorothy P. Laflamme

Int. J. Mol. Sci. 2015, 16(6), 14098-14108; https://doi.org/10.3390/ijms160614098 - 19 Jun 2015

Cited by 21 | Viewed by 6435

Abstract

MicroRNAs (miRNAs) are small non-coding RNAs that have shown promise as noninvasive biomarkers in cardiac disease. This study was undertaken to investigate the miRNA expression profile in dogs with myxomatous mitral valve disease (MMVD). 277 miRNAs were quantified using RT-qPCR from six normal [...] Read more.

MicroRNAs (miRNAs) are small non-coding RNAs that have shown promise as noninvasive biomarkers in cardiac disease. This study was undertaken to investigate the miRNA expression profile in dogs with myxomatous mitral valve disease (MMVD). 277 miRNAs were quantified using RT-qPCR from six normal dogs (American College of Veterinary Internal Medicine Stage A), six dogs with MMVD mild to moderate cardiac enlargement (ACVIM Stage B1/B2) and six dogs with MMVD and congestive heart failure (ACVIM Stage C/D). Eleven miRNAs were differentially expressed (False Discovery Rate < 0.05). Dogs in Stage B1/B2 or C/D had four upregulated miRNAs, including three cfa-let-7/cfa-miR-98 family members, while seven others were downregulated, compared to Stage A. Expression of six of the 11 miRNAs also were significantly different between dogs in Stage C/D and those in Stage B1/B2. The expression changes were greater as disease severity increased. These miRNAs may be candidates for novel biomarkers and may provide insights into genetic regulatory pathways in canine MMVD. Full article

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

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Open AccessReview

Hepatoma-Derived Growth Factor: Its Possible Involvement in the Progression of Hepatocellular Carcinoma

by Hirayuki Enomoto, Hideji Nakamura, Weidong Liu and Shuhei Nishiguchi

Int. J. Mol. Sci. 2015, 16(6), 14086-14097; https://doi.org/10.3390/ijms160614086 - 19 Jun 2015

Cited by 37 | Viewed by 7336

Abstract

The development of hepatocellular carcinoma (HCC) is an important complication of viral infection induced by hepatitis virus C, and our major research theme is to identify a new growth factor related to the progression of HCC. HDGF (hepatoma-derived growth factor) is a novel [...] Read more.

The development of hepatocellular carcinoma (HCC) is an important complication of viral infection induced by hepatitis virus C, and our major research theme is to identify a new growth factor related to the progression of HCC. HDGF (hepatoma-derived growth factor) is a novel growth factor that belongs to a new gene family. HDGF was initially purified from the conditioned medium of a hepatoma cell line. HDGF promotes cellular proliferation as a DNA binding nuclear factor and a secreted protein acting via a receptor-mediated pathway. HDGF is a unique multi-functional protein that can function as a growth factor, angiogenic factor and anti-apoptotic factor and it participates in the development and progression of various malignant diseases. The expression level of HDGF may be an independent prognostic factor for predicting the disease-free and overall survival in patients with various malignancies, including HCC. Furthermore, the overexpression of HDGF promotes the proliferation of HCC cells, while a reduction in the HDGF expression inhibits the proliferation of HCC cells. This article provides an overview of the characteristics of HDGF and describes the potential role of HDGF as a growth-promoting factor for HCC. Full article

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

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Open AccessCase Report

Successful and Safe Long-Term Standard Antiviral Therapy in a Patient with “Explosive” Immune Response in Course of HCV-Related Liver Cirrhosis

by Paolo Conca, Giovanni Cafaro, Amalia De Renzo, Antonio Coppola, Ernesto Cimino and Giovanni Tarantino

Int. J. Mol. Sci. 2015, 16(6), 14075-14085; https://doi.org/10.3390/ijms160614075 - 19 Jun 2015

Cited by 5 | Viewed by 6448

Abstract

Hepatitis C virus (HCV) has been recognized to be both a hepato- and lymphotropic virus. HCV lymphotropism represents an essential detail in the pathogenesis of virus-related autoimmune and lymphoproliferative disorders, ranging from clonal expansion of B-cells with organ and non-organ-specific autoantibody production up [...] Read more.

Hepatitis C virus (HCV) has been recognized to be both a hepato- and lymphotropic virus. HCV lymphotropism represents an essential detail in the pathogenesis of virus-related autoimmune and lymphoproliferative disorders, ranging from clonal expansion of B-cells with organ and non-organ-specific autoantibody production up to overt non-Hodgkin’s lymphoma along a continuous step-by-step model of B-cell lymphomagenesis, where the intermediated mixed cryoglobulinemia could be considered as a stage of suppressible antigen-driven lymphoproliferation. The HCV long-lasting extrahepatic replicative state generates an abnormal systemic immunological response, including rheumatoid factor (RF) and cryo- and non-cryoprecipitable immune complexes, as well as clinical manifestations, comprising dermatitis, polyarthralgias and arthritis, pulmonary disease, aplastic anemia, glomerulonephritis and vasculitis. The mechanism of these extra-hepatic disorders is thought of as linked to immune complex disease, but their pathogenesis is poorly clarified. Immune-suppressive treatment could induce high-level hepatitis C viremia and impair hepatic disease. We report a female patient, whose chronic HCV-related liver cirrhosis with associated explosive, but oligosymptomatic lymphoproliferative immune response, i.e., RF beyond three thousand times the upper of normal range (unr), type II cryoglobulinemia with cryocrit 40% and monoclonal gammopathy IgM-k, has been successfully and safely treated by long-lasting (sixty-six months) combined antiviral therapy (pegylated interferon alfa and ribavirin), at moderate and tapering dose regimen, prolonged for nearly 24 months after the first viral suppression. At the last follow-up (fifty-one months), the patient was showing very-long term antiviral response, progressive decline of secondary immune activation and absence of significant side-effects. Further research is required to fully verify the real impact on therapeutic choice/regimen. Full article

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

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Open AccessReview

Is Correction of Iron Deficiency a New Addition to the Treatment of the Heart Failure?

by Donald S. Silverberg, Dov Wexler and Doron Schwartz

Int. J. Mol. Sci. 2015, 16(6), 14056-14074; https://doi.org/10.3390/ijms160614056 - 18 Jun 2015

Cited by 23 | Viewed by 6699

Abstract

Anemia is present in about 40% of heart failure (HF) patients. Iron deficiency (ID) is present in about 60% of the patients with anemia (about 24% of all HF patients) and in about 40% of patients without anemia (about 24% of all HF [...] Read more.

Anemia is present in about 40% of heart failure (HF) patients. Iron deficiency (ID) is present in about 60% of the patients with anemia (about 24% of all HF patients) and in about 40% of patients without anemia (about 24% of all HF patients). Thus ID is present in about half the patients with HF. The ID in HF is associated with reduced iron stores in the bone marrow and the heart. ID is an independent risk factor for severity and worsening of the HF. Correction of ID with intravenous (IV) iron usually corrects both the anemia and the ID. Currently used IV iron preparations are very safe and effective in treating the ID in HF whereas little information is available on the effectiveness of oral iron. In HF IV iron correction of ID is associated with improvement in functional status, exercise capacity, quality of life and, in some studies, improvement in rate of hospitalization for HF, cardiac structure and function, and renal function. Large long-term adequately-controlled intervention studies are needed to clarify the effect of IV iron in HF. Several heart associations suggest that ID should be routinely sought for in all HF patients and corrected if present. In this paper we present our approach to diagnosis and treatment of iron deficiency in heart failure. Full article

(This article belongs to the Special Issue Pathogenesis of Cardiac Arrhythmias and Heart Failure)

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Open AccessArticle

Fungal Community Successions in Rhizosphere Sediment of Seagrasses Enhalus acoroides under PAHs Stress

by Juan Ling, Yanying Zhang, Meilin Wu, Youshao Wang, Junde Dong, Yufeng Jiang, Qingsong Yang and Siquan Zeng

Int. J. Mol. Sci. 2015, 16(6), 14039-14055; https://doi.org/10.3390/ijms160614039 - 18 Jun 2015

Cited by 17 | Viewed by 6597

Abstract

Seagrass meadows represent one of the highest productive marine ecosystems and are of great ecological and economic values. Recently, they have been confronted with worldwide decline. Fungi play important roles in sustaining the ecosystem health as degraders of polycyclic aromatic hydrocarbons (PAHs), but [...] Read more.

Seagrass meadows represent one of the highest productive marine ecosystems and are of great ecological and economic values. Recently, they have been confronted with worldwide decline. Fungi play important roles in sustaining the ecosystem health as degraders of polycyclic aromatic hydrocarbons (PAHs), but fewer studies have been conducted in seagrass ecosystems. Hence, we investigated the dynamic variations of the fungal community succession under PAH stress in rhizosphere sediment of seagrasses Enhalus acoroides in this study. Polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE), quantitative PCR (qPCR) and a clone library have been employed to analyze the fungal community’s shifts. Sequencing results of DGGE and the clone library showed that the predominant species belong to phyla Ascomycota and Basidiomycota. The abundance of three groups decreased sharply over the incubation period, whereas they demonstrated different fungal diversity patterns. Both the exposure time and the PAH concentrations affected the microbial diversity as assessed by PCR-DGGE analysis. Redundancy analysis (RDA) indicated that significant factors driving community shifts were ammonium and pH (p < 0.05). Significant amounts of the variations (31.1%) were explained by pH and ammonium, illustrating that those two parameters were the most likely ones to influence or be influenced by the fungal communities’ changes. Investigation results also indicated that fungal communities in seagrass meadow were very sensitive to PAH-induced stress and may be used as potential indicators for the PAH contamination. Full article

(This article belongs to the Special Issue Microbial Metabolism of Toxic Organic Pollutants and Transformation of Metals/Metalloids and Ecotoxicity Assessment)

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Open AccessArticle

A Comparative Proteomic Analysis of the Buds and the Young Expanding Leaves of the Tea Plant (Camellia sinensis L.)

by Qin Li, Juan Li, Shuoqian Liu, Jianan Huang, Haiyan Lin, Kunbo Wang, Xiaomei Cheng and Zhonghua Liu

Int. J. Mol. Sci. 2015, 16(6), 14007-14038; https://doi.org/10.3390/ijms160614007 - 18 Jun 2015

Cited by 27 | Viewed by 9467

Abstract

Tea (Camellia sinensis L.) is a perennial woody plant that is widely cultivated to produce a popular non-alcoholic beverage; this beverage has received much attention due to its pleasant flavor and bioactive ingredients, particularly several important secondary metabolites. Due to the significant [...] Read more.

Tea (Camellia sinensis L.) is a perennial woody plant that is widely cultivated to produce a popular non-alcoholic beverage; this beverage has received much attention due to its pleasant flavor and bioactive ingredients, particularly several important secondary metabolites. Due to the significant changes in the metabolite contents of the buds and the young expanding leaves of tea plants, high-performance liquid chromatography (HPLC) analysis and isobaric tags for relative and absolute quantitation (iTRAQ) analysis were performed. A total of 233 differentially expressed proteins were identified. Among these, 116 proteins were up-regulated and 117 proteins were down-regulated in the young expanding leaves compared with the buds. A large array of diverse functions was revealed, including roles in energy and carbohydrate metabolism, secondary metabolite metabolism, nucleic acid and protein metabolism, and photosynthesis- and defense-related processes. These results suggest that polyphenol biosynthesis- and photosynthesis-related proteins regulate the secondary metabolite content of tea plants. The energy and antioxidant metabolism-related proteins may promote tea leaf development. However, reverse transcription quantitative real-time PCR (RT-qPCR) showed that the protein expression levels were not well correlated with the gene expression levels. These findings improve our understanding of the molecular mechanism of the changes in the metabolite content of the buds and the young expanding leaves of tea plants. Full article

(This article belongs to the Special Issue Plant Proteomic Research)

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Open AccessArticle

Leaf Age-Dependent Photoprotective and Antioxidative Response Mechanisms to Paraquat-Induced Oxidative Stress in Arabidopsis thaliana

by Julietta Moustaka, Georgia Tanou, Ioannis-Dimosthenis Adamakis, Eleftherios P. Eleftheriou and Michael Moustakas

Int. J. Mol. Sci. 2015, 16(6), 13989-14006; https://doi.org/10.3390/ijms160613989 - 18 Jun 2015

Cited by 85 | Viewed by 9589

Abstract

Exposure of Arabidopsis thaliana young and mature leaves to the herbicide paraquat (Pq) resulted in a localized increase of hydrogen peroxide (H₂O₂) in the leaf veins and the neighboring mesophyll cells, but this increase was not similar in the [...] Read more.

Exposure of Arabidopsis thaliana young and mature leaves to the herbicide paraquat (Pq) resulted in a localized increase of hydrogen peroxide (H₂O₂) in the leaf veins and the neighboring mesophyll cells, but this increase was not similar in the two leaf types. Increased H₂O₂ production was concomitant with closed reaction centers (q_P). Thirty min after Pq exposure despite the induction of the photoprotective mechanism of non-photochemical quenching (NPQ) in mature leaves, H₂O₂ production was lower in young leaves mainly due to the higher increase activity of ascorbate peroxidase (APX). Later, 60 min after Pq exposure, the total antioxidant capacity of young leaves was not sufficient to scavenge the excess reactive oxygen species (ROS) that were formed, and thus, a higher H₂O₂ accumulation in young leaves occurred. The energy allocation of absorbed light in photosystem II (PSII) suggests the existence of a differential photoprotective regulatory mechanism in the two leaf types to the time-course Pq exposure accompanied by differential antioxidant protection mechanisms. It is concluded that tolerance to Pq-induced oxidative stress is related to the redox state of quinone A (Q_A). Full article

(This article belongs to the Special Issue Effects of Herbicides and Heavy Metals to the Structure and Function of Plant Cells)

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Open AccessReview

Adsorption of Silver Nanoparticles onto Different Surface Structures of Chitin/Chitosan and Correlations with Antimicrobial Activities

by Masayuki Ishihara, Vinh Quang Nguyen, Yasutaka Mori, Shingo Nakamura and Hidemi Hattori

Int. J. Mol. Sci. 2015, 16(6), 13973-13988; https://doi.org/10.3390/ijms160613973 - 18 Jun 2015

Cited by 78 | Viewed by 9708

Abstract

Size-controlled spherical silver nanoparticles (Ag NPs) can be simply prepared by autoclaving mixtures of glass powder containing silver with glucose. Moreover, chitins with varying degrees of deacetylation (DDAc < 30%) and chitosan powders and sheets (DDAc > 75%) with varying surface structure properties [...] Read more.

Size-controlled spherical silver nanoparticles (Ag NPs) can be simply prepared by autoclaving mixtures of glass powder containing silver with glucose. Moreover, chitins with varying degrees of deacetylation (DDAc < 30%) and chitosan powders and sheets (DDAc > 75%) with varying surface structure properties have been evaluated as Ag NP carriers. Chitin/chitosan-Ag NP composites in powder or sheet form were prepared by mixing Ag NP suspensions with each of the chitin/chitosan-based material at pH 7.3, leading to homogenous dispersion and stable adsorption of Ag NPs onto chitin carriers with nanoscale fiber-like surface structures, and chitosan carriers with nanoscale porous surface structures. Although these chitins exhibited mild antiviral, bactericidal, and antifungal activities, chitin powders with flat/smooth film-like surface structures had limited antimicrobial activities and Ag NP adsorption. The antimicrobial activities of chitin/chitosan-Ag NP composites increased with increasing amounts of adsorbed Ag NPs, suggesting that the surface structures of chitin/chitosan carriers strongly influence adsorption of Ag NPs and antimicrobial activities. These observations indicate that chitin/chitosan-Ag NPs with nanoscale surface structures have potential as antimicrobial biomaterials and anti-infectious wound dressings. Full article

(This article belongs to the Special Issue Chitins 2015)

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Open AccessArticle

Transcriptional Profiling Reveals Differential Gene Expression of Amur Ide (Leuciscus waleckii) during Spawning Migration

by Jun Cui, Jian Xu, Songhao Zhang, Kai Wang, Yanliang Jiang, Shahid Mahboob, Khalid A. Al-Ghanim and Peng Xu

Int. J. Mol. Sci. 2015, 16(6), 13959-13972; https://doi.org/10.3390/ijms160613959 - 18 Jun 2015

Cited by 15 | Viewed by 6309

Abstract

Amur ide (Leuciscus waleckii), an important aquaculture species, inhabits neutral freshwater but can tolerate high salinity or alkalinity. As an extreme example, the population in Dali Nor lake inhabits alkalized soda water permanently, and migrates from alkaline water to neutral freshwater [...] Read more.

Amur ide (Leuciscus waleckii), an important aquaculture species, inhabits neutral freshwater but can tolerate high salinity or alkalinity. As an extreme example, the population in Dali Nor lake inhabits alkalized soda water permanently, and migrates from alkaline water to neutral freshwater to spawn. In this study, we performed comparative transcriptome profiling study on the livers of Amur ide to interrogate the expression differences between the population that permanently inhabit freshwater in Ganggeng Nor lake (FW) and the spawning population that recently migrated from alkaline water into freshwater (SM). A total of 637,234,880 reads were generated, resulting in 53,440 assembled contigs that were used as reference sequences. Comparisons of these transcriptome files revealed 444 unigenes with significant differential expression (p-value ≤ 0.01, fold-change ≥ 2), including 246 genes that were up-regulated in SM and 198 genes that were up-regulated in FW. The gene ontology (GO) enrichment analysis and KEGG pathway analysis indicated that the mTOR signaling pathway, Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway, and oxidative phosphorylation were highly likely to affect physiological changes during spawning migration. Overall, this study demonstrates that transcriptome changes played a role in Amur ide spawning migration. These results provide a foundation for further analyses on the physiological and molecular mechanisms underlying Amur ide spawning migration. Full article

(This article belongs to the Section Biochemistry)

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Open AccessArticle

Transcriptome-Wide Identification of miRNA Targets under Nitrogen Deficiency in Populus tomentosa Using Degradome Sequencing

by Min Chen, Hai Bao, Qiuming Wu and Yanwei Wang

Int. J. Mol. Sci. 2015, 16(6), 13937-13958; https://doi.org/10.3390/ijms160613937 - 18 Jun 2015

Cited by 23 | Viewed by 6496

Abstract

miRNAs are endogenous non-coding small RNAs with important regulatory roles in stress responses. Nitrogen (N) is an indispensable macronutrient required for plant growth and development. Previous studies have identified a variety of known and novel miRNAs responsive to low N stress in plants, [...] Read more.

miRNAs are endogenous non-coding small RNAs with important regulatory roles in stress responses. Nitrogen (N) is an indispensable macronutrient required for plant growth and development. Previous studies have identified a variety of known and novel miRNAs responsive to low N stress in plants, including Populus. However, miRNAs involved in the cleavage of target genes and the corresponding regulatory networks in response to N stress in Populus remain largely unknown. Consequently, degradome sequencing was employed for global detection and validation of N-responsive miRNAs and their targets. A total of 60 unique miRNAs (39 conserved, 13 non-conserved, and eight novel) were experimentally identified to target 64 mRNA transcripts and 21 precursors. Among them, we further verified the cleavage of 11 N-responsive miRNAs identified previously and provided empirical evidence for the cleavage mode of these miRNAs on their target mRNAs. Furthermore, five miRNA stars (miRNA*s) were shown to have cleavage function. The specificity and diversity of cleavage sites on the targets and miRNA precursors in P. tomentosa were further detected. Identification and annotation of miRNA-mediated cleavage of target genes in Populus can increase our understanding of miRNA-mediated molecular mechanisms of woody plants adapted to low N environments. Full article

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

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Open AccessArticle

Characterization of Behaviour and Remote Degeneration Following Thalamic Stroke in the Rat

by Nina Weishaupt, Patricia Riccio, Taylor Dobbs, Vladimir C. Hachinski and Shawn N. Whitehead

Int. J. Mol. Sci. 2015, 16(6), 13921-13936; https://doi.org/10.3390/ijms160613921 - 17 Jun 2015

Cited by 10 | Viewed by 6324

Abstract

Subcortical ischemic strokes are among the leading causes of cognitive impairment. Selective atrophy of remote brain regions connected to the infarct is thought to contribute to deterioration of cognitive functions. The mechanisms underlying this secondary degenerative process are incompletely understood, but are thought [...] Read more.

Subcortical ischemic strokes are among the leading causes of cognitive impairment. Selective atrophy of remote brain regions connected to the infarct is thought to contribute to deterioration of cognitive functions. The mechanisms underlying this secondary degenerative process are incompletely understood, but are thought to include inflammation. We induce ischemia by unilateral injection of endothelin-I into the rat dorsomedial thalamic nucleus, which has defined reciprocal connections to the frontal cortex. We use a comprehensive test battery to probe for changes in behaviour, including executive functions. After a four-week recovery period, brain sections are stained with markers for degeneration, microglia, astrocytes and myelin. Degenerative processes are localized within the stroke core and along the full thalamocortical projection, which does not translate into measurable behavioural deficits. Significant microglia recruitment, astrogliosis or myelin loss along the axonal projection or within the frontal cortex cannot be detected. These findings indicate that critical effects of stroke-induced axonal degeneration may only be measurable beyond a threshold of stroke severity and/or follow a different time course. Further investigations are needed to clarify the impact of inflammation accompanying axonal degeneration on delayed remote atrophy after stroke. Full article

(This article belongs to the Special Issue The Immune System and Inflammation in Cerebral Ischemia)

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Open AccessArticle

In Vitro Proliferation and Anti-Apoptosis of the Papain-Generated Casein and Soy Protein Hydrolysates towards Osteoblastic Cells (hFOB1.19)

by Xiao-Wen Pan and Xin-Huai Zhao

Int. J. Mol. Sci. 2015, 16(6), 13908-13920; https://doi.org/10.3390/ijms160613908 - 17 Jun 2015

Cited by 22 | Viewed by 5457

Abstract

Casein and soy protein were digested by papain to three degrees of hydrolysis (DH) 7.3%–13.3%, to obtain respective six casein and soy protein hydrolysates, aiming to clarify their in vitro proliferation and anti-apoptosis towards a human osteoblastic cell line (hFOB1.19 cells). Six casein [...] Read more.

Casein and soy protein were digested by papain to three degrees of hydrolysis (DH) 7.3%–13.3%, to obtain respective six casein and soy protein hydrolysates, aiming to clarify their in vitro proliferation and anti-apoptosis towards a human osteoblastic cell line (hFOB1.19 cells). Six casein and soy protein hydrolysates at five levels (0.01–0.2 mg/mL) mostly showed proliferation as positive 17β-estradiol did, because they conferred the osteoblasts with cell viability of 100%–114% and 104%–123%, respectively. The hydrolysates of higher DH values had stronger proliferation. Casein and soy protein hydrolysates of the highest DH values altered cell cycle progression, and enhanced cell proportion of S-phase from 50.5% to 56.5% and 60.5%. The two also antagonized etoposide- and NaF-induced osteoblast apoptosis. In apoptotic prevention, apoptotic cells were decreased from 31.6% to 22.6% and 15.6% (etoposide treatment), or from 19.5% to 17.7% and 12.4% (NaF treatment), respectively. In apoptotic reversal, soy protein hydrolysate decreased apoptotic cells from 13.3% to 11.7% (etoposide treatment), or from 14.5% to 11.0% (NaF treatment), but casein hydrolysate showed no reversal effect. It is concluded that the hydrolysates of two kinds had estradiol-like action on the osteoblasts, and soy protein hydrolysates had stronger proliferation and anti-apoptosis on the osteoblasts than casein hydrolysates. Full article

(This article belongs to the Section Biochemistry)

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Open AccessArticle

Dimethyl Fumarate Protects Neural Stem/Progenitor Cells and Neurons from Oxidative Damage through Nrf2-ERK1/2 MAPK Pathway

by Qin Wang, Sergei Chuikov, Sophina Taitano, Qi Wu, Arjun Rastogi, Samuel J. Tuck, Joseph M. Corey, Steven K. Lundy and Yang Mao-Draayer

Int. J. Mol. Sci. 2015, 16(6), 13885-13907; https://doi.org/10.3390/ijms160613885 - 17 Jun 2015

Cited by 110 | Viewed by 10545

Abstract

Multiple sclerosis (MS) is the most common multifocal inflammatory demyelinating disease of the central nervous system (CNS). Due to the progressive neurodegenerative nature of MS, developing treatments that exhibit direct neuroprotective effects are needed. Tecfidera™ (BG-12) is an oral formulation of the fumaric [...] Read more.

Multiple sclerosis (MS) is the most common multifocal inflammatory demyelinating disease of the central nervous system (CNS). Due to the progressive neurodegenerative nature of MS, developing treatments that exhibit direct neuroprotective effects are needed. Tecfidera™ (BG-12) is an oral formulation of the fumaric acid esters (FAE), containing the active metabolite dimethyl fumarate (DMF). Although BG-12 showed remarkable efficacy in lowering relapse rates in clinical trials, its mechanism of action in MS is not yet well understood. In this study, we reported the potential neuroprotective effects of dimethyl fumarate (DMF) on mouse and rat neural stem/progenitor cells (NPCs) and neurons. We found that DMF increased the frequency of the multipotent neurospheres and the survival of NPCs following oxidative stress with hydrogen peroxide (H₂O₂) treatment. In addition, utilizing the reactive oxygen species (ROS) assay, we showed that DMF reduced ROS production induced by H₂O₂. DMF also decreased oxidative stress-induced apoptosis. Using motor neuron survival assay, DMF significantly promoted survival of motor neurons under oxidative stress. We further analyzed the expression of oxidative stress-induced genes in the NPC cultures and showed that DMF increased the expression of transcription factor nuclear factor-erythroid 2-related factor 2 (Nrf2) at both levels of RNA and protein. Furthermore, we demonstrated the involvement of Nrf2-ERK1/2 MAPK pathway in DMF-mediated neuroprotection. Finally, we utilized SuperArray gene screen technology to identify additional anti-oxidative stress genes (Gstp1, Sod2, Nqo1, Srxn1, Fth1). Our data suggests that analysis of anti-oxidative stress mechanisms may yield further insights into new targets for treatment of multiple sclerosis (MS). Full article

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

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Open AccessReview

Lipidomics by Supercritical Fluid Chromatography

by Laurent Laboureur, Mario Ollero and David Touboul

Int. J. Mol. Sci. 2015, 16(6), 13868-13884; https://doi.org/10.3390/ijms160613868 - 17 Jun 2015

Cited by 95 | Viewed by 12516

Abstract

This review enlightens the role of supercritical fluid chromatography (SFC) in the field of lipid analysis. SFC has been popular in the late 1980s and 1990s before almost disappearing due to the commercial success of liquid chromatography (LC). It is only 20 years [...] Read more.

This review enlightens the role of supercritical fluid chromatography (SFC) in the field of lipid analysis. SFC has been popular in the late 1980s and 1990s before almost disappearing due to the commercial success of liquid chromatography (LC). It is only 20 years later that a regain of interest appeared when new commercial instruments were introduced. As SFC is fully compatible with the injection of extracts in pure organic solvent, this technique is perfectly suitable for lipid analysis and can be coupled with either highly universal (UV or evaporative light scattering) or highly specific (mass spectrometry) detection methods. A short history of the use of supercritical fluids as mobile phase for the separation oflipids will be introduced first. Then, the advantages and drawbacks of SFC are discussed for each class of lipids (fatty acyls, glycerolipids, glycerophospholipids, sphingolipids, sterols, prenols, polyketides) defined by the LIPID MAPS consortium. Full article

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

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Open AccessArticle

Metabolomics Analysis Reveals Specific Novel Tetrapeptide and Potential Anti-Inflammatory Metabolites in Pathogenic Aspergillus species

by Kim-Chung Lee, Emily W. T. Tam, Ka-Ching Lo, Alan K. L. Tsang, Candy C. Y. Lau, Kelvin K. W. To, Jasper F. W. Chan, Ching-Wan Lam, Kwok-Yung Yuen, Susanna K. P. Lau and Patrick C. Y. Woo

Int. J. Mol. Sci. 2015, 16(6), 13850-13867; https://doi.org/10.3390/ijms160613850 - 17 Jun 2015

Cited by 10 | Viewed by 6413

Abstract

Infections related to Aspergillus species have emerged to become an important focus in infectious diseases, as a result of the increasing use of immunosuppressive agents and high fatality associated with invasive aspergillosis. However, laboratory diagnosis of Aspergillus infections remains difficult. In this study, [...] Read more.

Infections related to Aspergillus species have emerged to become an important focus in infectious diseases, as a result of the increasing use of immunosuppressive agents and high fatality associated with invasive aspergillosis. However, laboratory diagnosis of Aspergillus infections remains difficult. In this study, by comparing the metabolomic profiles of the culture supernatants of 30 strains of six pathogenic Aspergillus species (A. fumigatus, A. flavus, A. niger, A. terreus, A. nomius and A. tamarii) and 31 strains of 10 non-Aspergillus fungi, eight compounds present in all strains of the six Aspergillus species but not in any strain of the non-Aspergillus fungi were observed. One of the eight compounds, Leu–Glu–Leu–Glu, is a novel tetrapeptide and represents the first linear tetrapeptide observed in Aspergillus species, which we propose to be named aspergitide. Two other closely related Aspergillus-specific compounds, hydroxy-(sulfooxy)benzoic acid and (sulfooxy)benzoic acid, may possess anti-inflammatory properties, as 2-(sulfooxy)benzoic acid possesses a structure similar to those of aspirin [2-(acetoxy)benzoic acid] and salicylic acid (2-hydroxybenzoic acid). Further studies to examine the potentials of these Aspergillus-specific compounds for laboratory diagnosis of aspergillosis are warranted and further experiments will reveal whether Leu–Glu–Leu–Glu, hydroxy-(sulfooxy)benzoic acid and (sulfooxy)benzoic acid are virulent factors of the pathogenic Aspergillus species. Full article

(This article belongs to the Special Issue Microbial Genomics and Metabolomics)

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Open AccessArticle

by Aidan Petrovich, Adam Borne, Vladimir N. Uversky and Bin Xue

Int. J. Mol. Sci. 2015, 16(6), 13829-13849; https://doi.org/10.3390/ijms160613829 - 16 Jun 2015

Cited by 7 | Viewed by 6249

Abstract

Computational methods are prevailing in identifying protein intrinsic disorder. The results from predictors are often given as per-residue disorder scores. The scores describe the disorder propensity of amino acids of a protein and can be further represented as a disorder curve. Many proteins [...] Read more.

Computational methods are prevailing in identifying protein intrinsic disorder. The results from predictors are often given as per-residue disorder scores. The scores describe the disorder propensity of amino acids of a protein and can be further represented as a disorder curve. Many proteins share similar patterns in their disorder curves. The similar patterns are often associated with similar functions and evolutionary origins. Therefore, finding and characterizing specific patterns of disorder curves provides a unique and attractive perspective of studying the function of intrinsically disordered proteins. In this study, we developed a new computational tool named IDalign using dynamic programming. This tool is able to identify similar patterns among disorder curves, as well as to present the distribution of intrinsic disorder in query proteins. The disorder-based information generated by IDalign is significantly different from the information retrieved from classical sequence alignments. This tool can also be used to infer functions of disordered regions and disordered proteins. The web server of IDalign is available at (http://labs.cas.usf.edu/bioinfo/service.html). Full article

(This article belongs to the Special Issue In-Silico Prediction and Characterization of Intrinsic Disorder in Proteins)

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Open AccessArticle

Regulation of Human Trophoblast GLUT3 Glucose Transporter by Mammalian Target of Rapamycin Signaling

by Jie Xu, Chunmei Lu, Jiao Wang, Ruotong Zhang, Xin Qian and Hui Zhu

Int. J. Mol. Sci. 2015, 16(6), 13815-13828; https://doi.org/10.3390/ijms160613815 - 16 Jun 2015

Cited by 12 | Viewed by 6100

Abstract

Glucose transporter isoform-3 (GLUT3), one of the primary placental facilitative glucose transporters responsible for basal glucose transport, has a crucial role in glucose transport and fetal growth during early pregnancy. A GLUT3 mutation in mice has been reported to cause loss of early [...] Read more.

Glucose transporter isoform-3 (GLUT3), one of the primary placental facilitative glucose transporters responsible for basal glucose transport, has a crucial role in glucose transport and fetal growth during early pregnancy. A GLUT3 mutation in mice has been reported to cause loss of early pregnancy or late-gestational fetal growth restriction. However, the underlying mechanisms that regulate the placental GLUT3 transporter in humans are largely unknown. In the present study, we used the JEG-3 human choriocarcinoma cell line, which resembles a first trimester placental model, to study the role of the mammalian target of rapamycin complex 1 (mTORC1) in the regulation of placental GLUT3. We combined rapamycin treatment and small interfering (si) RNA-mediated silencing approaches with mRNA and protein expression/localization studies to investigate the alteration of GLUT3 expression and localization following mTORC1 inhibition in JEG-3 trophoblasts. Inhibition of mTORC1 signaling by silencing raptor decreased GLUT3 mRNA expression (−41%) and protein expression (−50%). Similar effects were obtained in cells in which mTORC1 was inhibited by rapamycin. Immunofluorescence analysis revealed that GLUT3 expression was markedly reduced in the cell surface and cytoplasm of JEG-3 cells in response to mTORC1 silencing. Because placental mTORC1 activity and GLUT3 expression are decreased in human intrauterine growth restriction, our data suggested one possible mechanism for the abnormal fetal growth in this pregnancy complication. Full article

(This article belongs to the Section Biochemistry)

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Reducing the Oxidation Level of Dextran Aldehyde in a Chitosan/Dextran-Based Surgical Hydrogel Increases Biocompatibility and Decreases Antimicrobial Efficacy

by Maggie Chan, Heather J. L. Brooks, Stephen C. Moratti, Lyall R. Hanton and Jaydee D. Cabral

Int. J. Mol. Sci. 2015, 16(6), 13798-13814; https://doi.org/10.3390/ijms160613798 - 16 Jun 2015

Cited by 28 | Viewed by 7100

Abstract

A highly oxidized form of a chitosan/dextran-based hydrogel (CD-100) containing 80% oxidized dextran aldehyde (DA-100) was developed as a post-operative aid, and found to significantly prevent adhesion formation in endoscopic sinus surgery (ESS). However, the CD-100 hydrogel showed moderate in vitro cytotoxicity to [...] Read more.

A highly oxidized form of a chitosan/dextran-based hydrogel (CD-100) containing 80% oxidized dextran aldehyde (DA-100) was developed as a post-operative aid, and found to significantly prevent adhesion formation in endoscopic sinus surgery (ESS). However, the CD-100 hydrogel showed moderate in vitro cytotoxicity to mammalian cell lines, with the DA-100 found to be the cytotoxic component. In order to extend the use of the hydrogel to abdominal surgeries, reformulation using a lower oxidized DA (DA-25) was pursued. The aim of the present study was to compare the antimicrobial efficacy, in vitro biocompatibility and wound healing capacity of the highly oxidized CD-100 hydrogel with the CD-25 hydrogel. Antimicrobial studies were performed against a range of clinically relevant abdominal microorganisms using the micro-broth dilution method. Biocompatibility testing using human dermal fibroblasts was assessed via a tetrazolium reduction assay (MTT) and a wound healing model. In contrast to the original DA-100 formulation, DA-25 was found to be non-cytotoxic, and showed no overall impairment of cell migration, with wound closure occurring at 72 h. However, the lower oxidation level negatively affected the antimicrobial efficacy of the hydrogel (CD-25). Although the CD-25 hydrogel’s antimicrobial efficacy and anti-fibroblast activity is decreased when compared to the original CD-100 hydrogel formulation, previous in vivo studies show that the CD-25 hydrogel remains an effective, biocompatible barrier agent in the prevention of postoperative adhesions. Full article

(This article belongs to the Special Issue Antimicrobial Polymers 2016)

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Transcriptional Profiling of Hydrogen Production Metabolism of Rhodobacter capsulatus under Temperature Stress by Microarray Analysis

by Muazzez Gürgan, Nilüfer Afşar Erkal, Ebru Özgür, Ufuk Gündüz, Inci Eroglu and Meral Yücel

Int. J. Mol. Sci. 2015, 16(6), 13781-13797; https://doi.org/10.3390/ijms160613781 - 16 Jun 2015

Cited by 8 | Viewed by 5666

Abstract

Biohydrogen is a clean and renewable form of hydrogen, which can be produced by photosynthetic bacteria in outdoor large-scale photobioreactors using sunlight. In this study, the transcriptional response of Rhodobacter capsulatus to cold (4 °C) and heat (42 °C) stress was studied using [...] Read more.

Biohydrogen is a clean and renewable form of hydrogen, which can be produced by photosynthetic bacteria in outdoor large-scale photobioreactors using sunlight. In this study, the transcriptional response of Rhodobacter capsulatus to cold (4 °C) and heat (42 °C) stress was studied using microarrays. Bacteria were grown in 30/2 acetate/glutamate medium at 30 °C for 48 h under continuous illumination. Then, cold and heat stresses were applied for two and six hours. Growth and hydrogen production were impaired under both stress conditions. Microarray chips for R. capsulatus were custom designed by Affymetrix (GeneChip^®. TR_RCH2a520699F). The numbers of significantly changed genes were 328 and 293 out of 3685 genes under cold and heat stress, respectively. Our results indicate that temperature stress greatly affects the hydrogen production metabolisms of R. capsulatus. Specifically, the expression of genes that participate in nitrogen metabolism, photosynthesis and the electron transport system were induced by cold stress, while decreased by heat stress. Heat stress also resulted in down regulation of genes related to cell envelope, transporter and binding proteins. Transcriptome analysis and physiological results were consistent with each other. The results presented here may aid clarification of the genetic mechanisms for hydrogen production in purple non-sulfur (PNS) bacteria under temperature stress. Full article

(This article belongs to the Special Issue Photosynthesis and Biological Hydrogen Production)

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Int. J. Mol. Sci., Volume 16, Issue 6 (June 2015) – 136 articles , Pages 11834-14290

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