International Journal of Molecular Sciences

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Open AccessArticle

Identification of Proteins of Altered Abundance in Oil Palm Infected with Ganoderma boninense

by Jameel R. Al-Obaidi, Yusmin Mohd-Yusuf, Nurhanani Razali, Jaime Jacqueline Jayapalan, Chin-Chong Tey, Normahnani Md-Noh, Sarni Mat Junit, Rofina Yasmin Othman and Onn Haji Hashim

Int. J. Mol. Sci. 2014, 15(3), 5175-5192; https://doi.org/10.3390/ijms15035175 - 24 Mar 2014

Cited by 28 | Viewed by 9161

Abstract

Basal stem rot is a common disease that affects oil palm, causing loss of yield and finally killing the trees. The disease, caused by fungus Ganoderma boninense, devastates thousands of hectares of oil palm plantings in Southeast Asia every year. In the [...] Read more.

Basal stem rot is a common disease that affects oil palm, causing loss of yield and finally killing the trees. The disease, caused by fungus Ganoderma boninense, devastates thousands of hectares of oil palm plantings in Southeast Asia every year. In the present study, root proteins of healthy oil palm seedlings, and those infected with G. boninense, were analyzed by 2-dimensional gel electrophoresis (2-DE). When the 2-DE profiles were analyzed for proteins, which exhibit consistent significant change of abundance upon infection with G. boninense, 21 passed our screening criteria. Subsequent analyses by mass spectrometry and database search identified caffeoyl-CoA O-methyltransferase, caffeic acid O-methyltransferase, enolase, fructokinase, cysteine synthase, malate dehydrogenase, and ATP synthase as among proteins of which abundances were markedly altered. Full article

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

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843 KiB

Open AccessArticle

Albumin Suppresses Human Hepatocellular Carcinoma Proliferation and the Cell Cycle

by Shunsuke Nojiri and Takashi Joh

Int. J. Mol. Sci. 2014, 15(3), 5163-5174; https://doi.org/10.3390/ijms15035163 - 24 Mar 2014

Cited by 81 | Viewed by 8963

Abstract

Many investigations have revealed that a low recurrence rate of hepatocellular carcinoma (HCC) is associated with high serum albumin levels in patients; therefore, high levels of serum albumin are a major indicator of a favorable prognosis. However, the mechanism inhibiting the proliferation of [...] Read more.

Many investigations have revealed that a low recurrence rate of hepatocellular carcinoma (HCC) is associated with high serum albumin levels in patients; therefore, high levels of serum albumin are a major indicator of a favorable prognosis. However, the mechanism inhibiting the proliferation of HCC has not yet been elucidated, so we investigated the effect of serum albumin on HCC cell proliferation. Hep3B was cultured in MEM with no serum or containing 5 g/dL human albumin. As control samples, Prionex was added to generate the same osmotic pressure as albumin. After 24-h incubation, the expressions of α-fetoprotein (AFP), p53, p21, and p57 were evaluated with real-time PCR using total RNA extracted from the liver. Protein expressions and the phosphorylation of Rb (retinoblastoma) were determined by Western blot analysis using total protein extracted from the liver. For flow cytometric analysis of the cell cycle, FACS analysis was performed. The percentages of cell cycle distribution were evaluated by PI staining, and all samples were analyzed employing FACScalibur (BD) with appropriate software (ModFit LT; BD). The cell proliferation assay was performed by counting cells with using a Scepter handy automated cell counter (Millipore). The mRNA levels of AFP relative to Alb(−): Alb(−), Alb(+), and Prionex, were 1, 0.7 ± 0.2 (p < 0.001 for Alb(−)), and 1 ± 0.3, respectively. The mRNA levels of p21 were 1, 1.58 ± 0.4 (p = 0.007 for Alb(−) and p = 0.004 for Prionex), and 0.8 ± 0.2, respectively. The mRNA levels of p57 were 1, 4.4 ± 1.4 (p = 0.002 for Alb(−) and Prionex), and 1.0 ± 0.1, respectively. The protein expression levels of Rb were similar in all culture media. The phosphorylation of P807/811 and P780 of Rb protein was reduced in Alb(+). More cells in the G0/G1 phase and fewer cells in S and G2/M phases were obtained in Alb(+) than in Alb(−) (G0/G1: 60.9%, 67.7%, 61.5%; G2/M: 16.5%, 13.1%, 15.6%; S: 22.6%, 19.2%, 23.0%, Alb(−), Alb(+), Prionex, respectively). The same results were obtained in HepG2. Cell proliferation was inhibited in 5 g/dL albumin medium in both HepG2 cells and Hep3B cells in 24 h culture by counting cell numbers. The presence of albumin in serum reduces the phosphorylation of Rb proteins and enhances the expression of p21 and p57, following an increase in the G0/G1 cell population, and suppresses cell proliferation. These results suggest that albumin itself suppresses the proliferation of hepatocellular carcinoma. Full article

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

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Open AccessArticle

Structure and Antitumor and Immunomodulatory Activities of a Water-Soluble Polysaccharide from Dimocarpus longan Pulp

by Fa-Yan Meng, Yuan-Ling Ning, Jia Qi, Zhou He, Jiang Jie, Juan-Juan Lin, Yan-Jun Huang, Fu-Sen Li and Xue-Hua Li

Int. J. Mol. Sci. 2014, 15(3), 5140-5162; https://doi.org/10.3390/ijms15035140 - 24 Mar 2014

Cited by 53 | Viewed by 8786

Abstract

A new water-soluble polysaccharide (longan polysaccharide 1 (LP1)) was extracted and successfully purified from Dimocarpus longan pulp via diethylaminoethyl (DEAE)-cellulose anion-exchange and Sephacryl S-300 HR gel chromatography. The chemical structure was determined using Infrared (IR), gas chromatography (GC) and nuclear magnetic resonance (NMR) [...] Read more.

A new water-soluble polysaccharide (longan polysaccharide 1 (LP1)) was extracted and successfully purified from Dimocarpus longan pulp via diethylaminoethyl (DEAE)-cellulose anion-exchange and Sephacryl S-300 HR gel chromatography. The chemical structure was determined using Infrared (IR), gas chromatography (GC) and nuclear magnetic resonance (NMR) analysis. The results indicated that the molecular weight of the sample was 1.1 × 10⁵ Da. Monosaccharide composition analysis revealed that LP1 was composed of Glc, GalA, Ara and Gal in a molar ratio of 5.39:1.04:0.74:0.21. Structural analysis indicated that LP1 consisted of a backbone of →4)-α-d-Glcp-(1→4)-α-d-GalpA-(1→4)-α-d-Glcp-(1→4)-β-d-Glcp-(1→ units with poly saccharide side chains composed of →2)-β-d-Fruf-(1→2)-l-sorbose-(1→ attached to the O-6 position of the α-d-Glcp residues. In vitro experiments indicated that LP1 had significantly high antitumor activity against SKOV3 and HO8910 tumor cells, with inhibition percentages of 40% and 50%, respectively. In addition, LP1 significantly stimulated the production of the cytokine interferon-γ (IFN-γ), increased the activity of murine macrophages and enhanced B- and T-lymphocyte proliferation. The results of this study demonstrate that LP1 has potential applications as a natural antitumor agent with immunomodulatory activity. Full article

(This article belongs to the Section Materials Science)

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Open AccessArticle

Application of Computational Methods for the Design of BACE-1 Inhibitors: Validation of in Silico Modelling

by Marek Bajda, Jakub Jończyk, Barbara Malawska and Sławomir Filipek

Int. J. Mol. Sci. 2014, 15(3), 5128-5139; https://doi.org/10.3390/ijms15035128 - 24 Mar 2014

Cited by 18 | Viewed by 7897

Abstract

β-Secretase (BACE-1) constitutes an important target for search of anti-Alzheimer’s drugs. The first inhibitors of this enzyme were peptidic compounds with high molecular weight and low bioavailability. Therefore, the search for new efficient non-peptidic inhibitors has been undertaken by many scientific groups. We [...] Read more.

β-Secretase (BACE-1) constitutes an important target for search of anti-Alzheimer’s drugs. The first inhibitors of this enzyme were peptidic compounds with high molecular weight and low bioavailability. Therefore, the search for new efficient non-peptidic inhibitors has been undertaken by many scientific groups. We started our work from the development of in silico methodology for the design of novel BACE-1 ligands. It was validated on the basis of crystal structures of complexes with inhibitors, redocking, cross-docking and training/test sets of reference ligands. The presented procedure of assessment of the novel compounds as β-secretase inhibitors could be widely used in the design process. Full article

(This article belongs to the Collection Computational, Structural and Spectroscopic Studies of Enzyme Mechanisms, Inhibition and Dynamics)

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Open AccessArticle

Synthesis and Biological Evaluation of 2-Aminobenzamide Derivatives as Antimicrobial Agents: Opening/Closing Pharmacophore Site

by Yahia N. Mabkhot, Abdullah M. Al-Majid, Assem Barakat, Salim S. Al-Showiman, Munirah S. Al-Har, Smaail Radi, Muhammad Moazzam Naseer and Taibi B. Hadda

Int. J. Mol. Sci. 2014, 15(3), 5115-5127; https://doi.org/10.3390/ijms15035115 - 21 Mar 2014

Cited by 31 | Viewed by 7767

Abstract

A series of new 2-aminobenzamide derivatives (1–10) has been synthesized in good to excellent yields by adopting both conventional and/or a time-efficient microwave assisted methodologies starting from isatoic anhydride (ISA) and characterized on the basis of their physical, spectral [...] Read more.

A series of new 2-aminobenzamide derivatives (1–10) has been synthesized in good to excellent yields by adopting both conventional and/or a time-efficient microwave assisted methodologies starting from isatoic anhydride (ISA) and characterized on the basis of their physical, spectral and microanalytical data. Selected compounds of this series were then tested against various bacterial (Bacillus subtilis (RCMB 000107) and Staphylococcus aureus (RCMB 000106). Pseudomonas aeruginosa (RCMB 000102) and Escherichia coli (RCMB 000103) and fungal strains (Saccharomyces cerevisiae (RCMB 006002), Aspergillus fumigatus (RCMB 002003) and Candida albicans (RCMB 005002) to explore their potential as antimicrobial agents. Compound 5 was found to be the most active compound among those tested, which showed excellent antifungal activity against Aspergillus fumigatus (RCMB 002003) more potent than standard Clotrimazole, and moderate to good antibacterial and antifungal activity against most of the other strains of bacteria and fungi. Furthermore, potential pharmacophore sites were identified and their activity was related with the structures in the solution. Full article

(This article belongs to the Section Biochemistry)

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Open AccessReview

No Stress! Relax! Mechanisms Governing Growth and Shape in Plant Cells

by Gea Guerriero, Jean-Francois Hausman and Giampiero Cai

Int. J. Mol. Sci. 2014, 15(3), 5094-5114; https://doi.org/10.3390/ijms15035094 - 21 Mar 2014

Cited by 52 | Viewed by 14385

Abstract

The mechanisms through which plant cells control growth and shape are the result of the coordinated action of many events, notably cell wall stress relaxation and turgor-driven expansion. The scalar nature of turgor pressure would drive plant cells to assume spherical shapes; however, [...] Read more.

The mechanisms through which plant cells control growth and shape are the result of the coordinated action of many events, notably cell wall stress relaxation and turgor-driven expansion. The scalar nature of turgor pressure would drive plant cells to assume spherical shapes; however, this is not the case, as plant cells show an amazing variety of morphologies. Plant cell walls are dynamic structures that can display alterations in matrix polysaccharide composition and concentration, which ultimately affect the wall deformation rate. The wide varieties of plant cell shapes, spanning from elongated cylinders (as pollen tubes) and jigsaw puzzle-like epidermal cells, to very long fibres and branched stellate leaf trichomes, can be understood if the underlying mechanisms regulating wall biosynthesis and cytoskeletal dynamics are addressed. This review aims at gathering the available knowledge on the fundamental mechanisms regulating expansion, growth and shape in plant cells by putting a special emphasis on the cell wall-cytoskeleton system continuum. In particular, we discuss from a molecular point of view the growth mechanisms characterizing cell types with strikingly different geometries and describe their relationship with primary walls. The purpose, here, is to provide the reader with a comprehensive overview of the multitude of events through which plant cells manage to expand and control their final shapes. Full article

(This article belongs to the Special Issue Plant Cell Compartmentation and Volume Control)

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Open AccessArticle

Differential Transcriptome Analysis between Paulownia fortunei and Its Synthesized Autopolyploid

by Xiaoshen Zhang, Minjie Deng and Guoqiang Fan

Int. J. Mol. Sci. 2014, 15(3), 5079-5093; https://doi.org/10.3390/ijms15035079 - 21 Mar 2014

Cited by 32 | Viewed by 7525

Abstract

Paulownia fortunei is an ecologically and economically important tree species that is widely used as timber and chemical pulp. Its autotetraploid, which carries a number of valuable traits, was successfully induced with colchicine. To identify differences in gene expression between P. fortunei and [...] Read more.

Paulownia fortunei is an ecologically and economically important tree species that is widely used as timber and chemical pulp. Its autotetraploid, which carries a number of valuable traits, was successfully induced with colchicine. To identify differences in gene expression between P. fortunei and its synthesized autotetraploid, we performed transcriptome sequencing using an Illumina Genome Analyzer IIx (GAIIx). About 94.8 million reads were generated and assembled into 383,056 transcripts, including 18,984 transcripts with a complete open reading frame. A conducted Basic Local Alignment Search Tool (BLAST) search indicated that 16,004 complete transcripts had significant hits in the National Center for Biotechnology Information (NCBI) non-redundant database. The complete transcripts were given functional assignments using three public protein databases. One thousand one hundred fifty eight differentially expressed complete transcripts were screened through a digital abundance analysis, including transcripts involved in energy metabolism and epigenetic regulation. Finally, the expression levels of several transcripts were confirmed by quantitative real-time PCR. Our results suggested that polyploidization caused epigenetic-related changes, which subsequently resulted in gene expression variation between diploid and autotetraploid P. fortunei. This might be the main mechanism affected by the polyploidization. Our results represent an extensive survey of the P. fortunei transcriptome and will facilitate subsequent functional genomics research in P. fortunei. Moreover, the gene expression profiles of P. fortunei and its autopolyploid will provide a valuable resource for the study of polyploidization. Full article

(This article belongs to the Section Biochemistry)

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Open AccessArticle

A Chrysanthemum Heat Shock Protein Confers Tolerance to Abiotic Stress

by Aiping Song, Xirong Zhu, Fadi Chen, Haishun Gao, Jiafu Jiang and Sumei Chen

Int. J. Mol. Sci. 2014, 15(3), 5063-5078; https://doi.org/10.3390/ijms15035063 - 21 Mar 2014

Cited by 88 | Viewed by 9051

Abstract

Heat shock proteins are associated with protection against various abiotic stresses. Here, the isolation of a chrysanthemum cDNA belonging to the HSP70 family is reported. The cDNA, designated CgHSP70, encodes a 647-residue polypeptide, of estimated molecular mass 70.90 kDa and pI 5.12. [...] Read more.

Heat shock proteins are associated with protection against various abiotic stresses. Here, the isolation of a chrysanthemum cDNA belonging to the HSP70 family is reported. The cDNA, designated CgHSP70, encodes a 647-residue polypeptide, of estimated molecular mass 70.90 kDa and pI 5.12. A sub-cellular localization assay indicated that the cDNA product is deposited in the cytoplasm and nucleus. The performance of Arabidopsis thaliana plants constitutively expressing CgHSP70 demonstrated that the gene enhances tolerance to heat, drought and salinity. When CgHSP70 was stably over-expressed in chrysanthemum, the plants showed an increased peroxidase (POD) activity, higher proline content and inhibited malondialdehyde (MDA) content. After heat stress, drought or salinity the transgenic plants were better able to recover, demonstrating CgHSP70 positive effect. Full article

(This article belongs to the Special Issue Plant Cell Compartmentation and Volume Control)

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Open AccessArticle

A Caspase-Dependent Pathway Is Involved in Wnt/β-Catenin Signaling Promoted Apoptosis in Bacillus Calmette-Guerin Infected RAW264.7 Macrophages

by Xiaoling Wu, Guangcun Deng, Xiujing Hao, Yong Li, Jin Zeng, Chunyan Ma, Yulong He, Xiaoming Liu and Yujiong Wang

Int. J. Mol. Sci. 2014, 15(3), 5045-5062; https://doi.org/10.3390/ijms15035045 - 21 Mar 2014

Cited by 62 | Viewed by 9747

Abstract

Apoptosis of alveolar macrophages following Mycobacterium tuberculosis infection have been demonstrated to play a central role in the pathogenesis of tuberculosis. In the present study, we found that Wnt/β-catenin signaling possesses the potential to promote macrophage apoptosis in response to mycobacterial infection. In [...] Read more.

Apoptosis of alveolar macrophages following Mycobacterium tuberculosis infection have been demonstrated to play a central role in the pathogenesis of tuberculosis. In the present study, we found that Wnt/β-catenin signaling possesses the potential to promote macrophage apoptosis in response to mycobacterial infection. In agreement with other findings, an activation Wnt/β-catenin signaling was observed in murine macrophage RAW264.7 cells upon Mycobacterium bovis Bacillus Calmette-Guerin (BCG) infection at a multiple-of-infection of 10, which was accompanied with up-regulation of pro-inflammatory cytokines TNF-α and IL-6 production. However, the BCG-induced TNF-α and IL-6 secretion could be significantly reduced when the cells were exposed to a canonical Wnt signaling ligand, Wnt3a. Importantly, the activation of Wnt/β-catenin signaling was able to further promote apoptosis in BCG-infected RAW264.7 cells in part by a mitochondria-dependent apoptosis pathway. Immunoblotting analysis further demonstrated that Wnt/β-catenin signaling-induced cell apoptosis partly through a caspase-dependent apoptosis mechanism by down-regulation of anti-apoptotic protein Mcl-1, and up-regulation of pro-apoptotic proteins Bax and cleaved-caspase-3, as well as enhancement of caspase-3 activity in BCG-infected RAW264.7 cells. These data may imply an underlying mechanism of alveolar macrophages in response to mycobacterial infection, by which the pathogen induces Wnt/β-catenin signaling activation, which in turn represses mycobacterium-trigged inflammatory responses and promotes mycobacteria-infected cell apoptosis. Full article

(This article belongs to the Section Biochemistry)

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Open AccessArticle

Atmospheric Oxidation Mechanism and Kinetic Studies for OH and NO₃ Radical-Initiated Reaction of Methyl Methacrylate

by Rui Gao, Ledong Zhu, Qingzhu Zhang and Wenxing Wang

Int. J. Mol. Sci. 2014, 15(3), 5032-5044; https://doi.org/10.3390/ijms15035032 - 20 Mar 2014

Cited by 14 | Viewed by 8266

Abstract

The mechanism for OH and NO₃ radical-initiated oxidation reactions of methyl methacrylate (MMA) was investigated by using density functional theory (DFT) molecular orbital theory. Geometrical parameters of the reactants, intermediates, transition states, and products were fully optimized at the B3LYP/6-31G(d,p) level. Detailed [...] Read more.

The mechanism for OH and NO₃ radical-initiated oxidation reactions of methyl methacrylate (MMA) was investigated by using density functional theory (DFT) molecular orbital theory. Geometrical parameters of the reactants, intermediates, transition states, and products were fully optimized at the B3LYP/6-31G(d,p) level. Detailed oxidation pathways were presented and discussed. The rate constants were deduced by the canonical variational transition-state (CVT) theory with the small-curvature tunneling (SCT) correction and the multichannel Rice-Ramspergere-Kassele-Marcus (RRKM) theory, based on the potential energy surface profiles over the general atmospheric temperature range of 180–370 K. The calculated results were in reasonable agreement with experimental measurement. Full article

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

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Open AccessArticle

Bovine Induced Pluripotent Stem Cells Are More Resistant to Apoptosis than Testicular Cells in Response to Mono-(2-ethylhexyl) Phthalate

by Ying-Chu Lin, Kung-Kai Kuo, Kenly Wuputra, Shih-Han Lin, Chia-Chen Ku, Ya-Han Yang, Shin-Wei Wang, Sheng-Wen Wang, Deng-Chyang Wu, Chun-Chien Wu, Chee-Yin Chai, Cheng-Lung Lin, Chang-Shen Lin, Masayuki Kajitani, Hiroyuki Miyoshi, Yukio Nakamura, Shinichi Hashimoto, Kouji Matsushima, Chunyuan Jin, Shau-Ku Huang, Shigeo Saito and Kazunari K. Yokoyama Show full author list Hide full author list

Int. J. Mol. Sci. 2014, 15(3), 5011-5031; https://doi.org/10.3390/ijms15035011 - 20 Mar 2014

Cited by 21 | Viewed by 8308

Abstract

Although the androgen receptor (AR) has been implicated in the promotion of apoptosis in testicular cells (TSCs), the molecular pathway underlying AR-mediated apoptosis and its sensitivity to environmental hormones in TSCs and induced pluripotent stem cells (iPSCs) remain unclear. We generated the iPSCs [...] Read more.

Although the androgen receptor (AR) has been implicated in the promotion of apoptosis in testicular cells (TSCs), the molecular pathway underlying AR-mediated apoptosis and its sensitivity to environmental hormones in TSCs and induced pluripotent stem cells (iPSCs) remain unclear. We generated the iPSCs from bovine TSCs via the electroporation of OCT4. The established iPSCs were supplemented with leukemia inhibitory factor and bone morphogenetic protein 4 to maintain and stabilize the expression of stemness genes and their pluripotency. Apoptosis signaling was assessed after exposure to mono-(2-ethylhexyl) phthalate (MEHP), the active metabolite of di-(2-ethylhexyl) phthalate. Here, we report that iPSCs were more resistant to MEHP-induced apoptosis than were original TSCs. MEHP also repressed the expression of AR and inactivated WNT signaling, and then led to the commitment of cells to apoptosis via the cyclin dependent kinase inhibitor p21^CIP1. The loss of the frizzed receptor 7 and the gain of p21^CIP were responsible for the stimulatory effect of MEHP on AR-mediated apoptosis. Our results suggest that testicular iPSCs can be used to study the signaling pathways involved in the response to environmental disruptors, and to assess the toxicity of environmental endocrine disruptors in terms of the maintenance of stemness and pluripotency. Full article

(This article belongs to the Section Biochemistry)

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Open AccessArticle

Investigation into Variation of Endogenous Metabolites in Bone Marrow Cells and Plasma in C3H/He Mice Exposed to Benzene

by Rongli Sun, Juan Zhang, Lihong Yin and Yuepu Pu

Int. J. Mol. Sci. 2014, 15(3), 4994-5010; https://doi.org/10.3390/ijms15034994 - 20 Mar 2014

Cited by 29 | Viewed by 6849

Abstract

Benzene is identified as a carcinogen. Continued exposure of benzene may eventually lead to damage to the bone marrow, accompanied by pancytopenia, aplastic anemia or leukemia. This paper explores the variations of endogenous metabolites to provide possible clues for the molecular mechanism of [...] Read more.

Benzene is identified as a carcinogen. Continued exposure of benzene may eventually lead to damage to the bone marrow, accompanied by pancytopenia, aplastic anemia or leukemia. This paper explores the variations of endogenous metabolites to provide possible clues for the molecular mechanism of benzene-induced hematotoxicity. Liquid chromatography coupled with time of flight-mass spectrometry (LC-TOF-MS) and principal component analysis (PCA) was applied to investigate the variation of endogenous metabolites in bone marrow cells and plasma of male C3H/He mice. The mice were injected subcutaneously with benzene (0, 300, 600 mg/day) once daily for seven days. The body weights, relative organ weights, blood parameters and bone marrow smears were also analyzed. The results indicated that benzene caused disturbances in the metabolism of oxidation of fatty acids and essential amino acids (lysine, phenylalanine and tyrosine) in bone marrow cells. Moreover, fatty acid oxidation was also disturbed in plasma and thus might be a common disturbed metabolic pathway induced by benzene in multiple organs. This study aims to investigate the underlying molecular mechanisms involved in benzene hematotoxicity, especially in bone marrow cells. Full article

(This article belongs to the Special Issue Mass Spectrometry Application in Biology)

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Open AccessReview

The Multiple Mechanisms of Cell Death Triggered by Resveratrol in Lymphoma and Leukemia

by Raffaele Frazzi and Marco Tigano

Int. J. Mol. Sci. 2014, 15(3), 4977-4993; https://doi.org/10.3390/ijms15034977 - 20 Mar 2014

Cited by 28 | Viewed by 9190

Abstract

Lymphoma and leukemia represent a serious threat to human health and life expectancy. Resveratrol is, among the natural-derived chemopreventive molecules, one of the most effective and better studied. In this paper the main mechanisms of cell death triggered by- or linked to- resveratrol [...] Read more.

Lymphoma and leukemia represent a serious threat to human health and life expectancy. Resveratrol is, among the natural-derived chemopreventive molecules, one of the most effective and better studied. In this paper the main mechanisms of cell death triggered by- or linked to- resveratrol are reviewed and discussed. The main focus is on lymphoma and leukemia experimental models where resveratrol has been tested and investigated at the cellular, molecular or physiological levels. The most relevant in vivo challenges involving resveratrol are also reported and analyzed in order to define the key features of this polyphenol and the potential for the treatment of hematologic tumors. Full article

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

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Open AccessReview

P-Glycoprotein and Drug Resistance in Systemic Autoimmune Diseases

by Andrea Picchianti-Diamanti, Maria Manuela Rosado, Marco Scarsella, Bruno Laganà and Raffaele D'Amelio

Int. J. Mol. Sci. 2014, 15(3), 4965-4976; https://doi.org/10.3390/ijms15034965 - 20 Mar 2014

Cited by 43 | Viewed by 7557

Abstract

Autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are chronic inflammatory disorders of unknown etiology characterized by a wide range of abnormalities of the immune system that may compromise the function of several organs, such as [...] Read more.

Autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are chronic inflammatory disorders of unknown etiology characterized by a wide range of abnormalities of the immune system that may compromise the function of several organs, such as kidney, heart, joints, brain and skin. Corticosteroids (CCS), synthetic and biologic immunosuppressive agents have demonstrated the capacity to improve the course of autoimmune diseases. However, a significant number of patients do not respond or develop resistance to these therapies over time. P-glycoprotein (P-gp) is a transmembrane protein that pumps several drugs out of the cell, including CCS and immunosuppressants; thus, its over-expression or hyper-function has been proposed as a possible mechanism of drug resistance in patients with autoimmune disorders. Recently, different authors have demonstrated that P-gp inhibitors, such as cyclosporine A (CsA) and its analogue Tacrolimus, are able to reduce P-gp expression and or function in SLE, RA and PsA patients. These observations suggest that P-gp antagonists could be adopted to revert drug resistance and improve disease outcome. The complex inter-relationship among drug resistance, P-gp expression and autoimmunity still remains elusive. Full article

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

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Open AccessArticle

Exogenous Asymmetric Dimethylarginine (ADMA) in Pathogenesis of Ischemia-Reperfusion-Induced Gastric Lesions: Interaction with Protective Nitric Oxide (NO) and Calcitonin Gene-Related Peptide (CGRP)

by Marcin Magierowski, Katarzyna Jasnos, Zbigniew Sliwowski, Marcin Surmiak, Gracjana Krzysiek-Maczka, Agata Ptak-Belowska, Slawomir Kwiecien and Tomasz Brzozowski

Int. J. Mol. Sci. 2014, 15(3), 4946-4964; https://doi.org/10.3390/ijms15034946 - 20 Mar 2014

Cited by 23 | Viewed by 6945

Abstract

Asymmetric dimethylarginine (ADMA) is an endogenous nitric oxide (NO) synthesis inhibitor and pro-inflammatory factor. We investigated the role of ADMA in rat gastric mucosa compromised through 30 min of gastric ischemia (I) and 3 h of reperfusion (R). These I/R animals were pretreated [...] Read more.

Asymmetric dimethylarginine (ADMA) is an endogenous nitric oxide (NO) synthesis inhibitor and pro-inflammatory factor. We investigated the role of ADMA in rat gastric mucosa compromised through 30 min of gastric ischemia (I) and 3 h of reperfusion (R). These I/R animals were pretreated with ADMA with or without the combination of l-arginine, calcitonin gene-related peptide (CGRP) or a small dose of capsaicin, all of which are known to afford protection against gastric lesions, or with a farnesoid X receptor (FXR) agonist, GW 4064, to increase the metabolism of ADMA. In the second series, ADMA was administered to capsaicin-denervated rats. The area of gastric damage was measured with planimetry, gastric blood flow (GBF) was determined by H₂-gas clearance, and plasma ADMA and CGRP levels were determined using ELISA and RIA. ADMA significantly increased I/R-induced gastric injury while significantly decreasing GBF, the luminal NO content, and the plasma level of CGRP. This effect of ADMA was significantly attenuated by pretreatment with CGRP, l-arginine, capsaicin, or a PGE₂ analogue. In GW4064 pretreated animals, the I/R injury was significantly reduced and this effect was abolished by co-treatment with ADMA. I/R damage potentiated by ADMA was exacerbated in capsaicin-denervated animals with a further reduction of CGRP. Plasma levels of IL-10 were significantly decreased while malonylodialdehyde (MDA) and plasma TNF-α contents were significantly increased by ADMA. In conclusion, ADMA aggravates I/R-induced gastric lesions due to a decrease of GBF, which is mediated by a fall in NO and CGRP release, and the enhancement of lipid peroxidation and its pro-inflammatory properties. Full article

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

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Open AccessComment

Calcium and Vitamin D in the Regulation of Energy Balance: Where Do We Stand?

by Mario J. Soares, Kaveri Pathak and Emily K. Calton

Int. J. Mol. Sci. 2014, 15(3), 4938-4945; https://doi.org/10.3390/ijms15034938 - 20 Mar 2014

Cited by 40 | Viewed by 9071

Abstract

There is a pandemic of obesity and associated chronic diseases. Dietary calcium and vitamin D have many extra-skeletal roles in human health. In this review we have summarized the current understanding of their influence on human energy balance by examining the epidemiological, clinical, [...] Read more.

There is a pandemic of obesity and associated chronic diseases. Dietary calcium and vitamin D have many extra-skeletal roles in human health. In this review we have summarized the current understanding of their influence on human energy balance by examining the epidemiological, clinical, animal, cellular and molecular evidence. We opine that while calcium and vitamin D are functional nutrients in the battle against obesity, there is a need for prospective human trials to tilt the balance of evidence in favour of these nutrients. Full article

(This article belongs to the Special Issue Nutritional Control of Metabolism)

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Open AccessArticle

iNR-Drug: Predicting the Interaction of Drugs with Nuclear Receptors in Cellular Networking

by Yue-Nong Fan, Xuan Xiao, Jian-Liang Min and Kuo-Chen Chou

Int. J. Mol. Sci. 2014, 15(3), 4915-4937; https://doi.org/10.3390/ijms15034915 - 19 Mar 2014

Cited by 84 | Viewed by 9522

Abstract

Nuclear receptors (NRs) are closely associated with various major diseases such as cancer, diabetes, inflammatory disease, and osteoporosis. Therefore, NRs have become a frequent target for drug development. During the process of developing drugs against these diseases by targeting NRs, we are often [...] Read more.

Nuclear receptors (NRs) are closely associated with various major diseases such as cancer, diabetes, inflammatory disease, and osteoporosis. Therefore, NRs have become a frequent target for drug development. During the process of developing drugs against these diseases by targeting NRs, we are often facing a problem: Given a NR and chemical compound, can we identify whether they are really in interaction with each other in a cell? To address this problem, a predictor called “iNR-Drug” was developed. In the predictor, the drug compound concerned was formulated by a 256-D (dimensional) vector derived from its molecular fingerprint, and the NR by a 500-D vector formed by incorporating its sequential evolution information and physicochemical features into the general form of pseudo amino acid composition, and the prediction engine was operated by the SVM (support vector machine) algorithm. Compared with the existing prediction methods in this area, iNR-Drug not only can yield a higher success rate, but is also featured by a user-friendly web-server established at http://www.jci-bioinfo.cn/iNR-Drug/, which is particularly useful for most experimental scientists to obtain their desired data in a timely manner. It is anticipated that the iNR-Drug server may become a useful high throughput tool for both basic research and drug development, and that the current approach may be easily extended to study the interactions of drug with other targets as well. Full article

(This article belongs to the Special Issue Molecular Science for Drug Development and Biomedicine)

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Open AccessArticle

Phosphosite Mapping of HIP-55 Protein in Mammalian Cells

by Ning Liu, Ningning Sun, Xiang Gao and Zijian Li

Int. J. Mol. Sci. 2014, 15(3), 4903-4914; https://doi.org/10.3390/ijms15034903 - 19 Mar 2014

Cited by 5 | Viewed by 6590

Abstract

In the present study, hematopoietic progenitor kinase 1 (HPK1)-interacting protein of 55 kDa (HIP-55) protein was over-expressed in HEK293 cells, which was genetically attached with 6x His tag. The protein was purified by nickel-charged resin and was then subjected to [...] Read more.

In the present study, hematopoietic progenitor kinase 1 (HPK1)-interacting protein of 55 kDa (HIP-55) protein was over-expressed in HEK293 cells, which was genetically attached with 6x His tag. The protein was purified by nickel-charged resin and was then subjected to tryptic digestion. The phosphorylated peptides within the HIP-55 protein were enriched by TiO₂ affinity chromatography, followed by mass spectrometry analysis. Fourteen phosphorylation sites along the primary structure of HIP-55 protein were identified, most of which had not been previously reported. Our results indicate that bio-mass spectrometry coupled with manual interpretation can be used to successfully identify the phosphorylation modification in HIP-55 protein in HEK293 cells. Full article

(This article belongs to the Special Issue Mass Spectrometry Application in Biology)

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Open AccessArticle

Comparative Molecular Dynamics Simulations of Mitogen-Activated Protein Kinase-Activated Protein Kinase 5

by Inger Lindin, Yimingjiang Wuxiuer, Aina Westrheim Ravna, Ugo Moens and Ingebrigt Sylte

Int. J. Mol. Sci. 2014, 15(3), 4878-4902; https://doi.org/10.3390/ijms15034878 - 19 Mar 2014

Cited by 7 | Viewed by 11582

Abstract

The mitogen-activated protein kinase-activated protein kinase MK5 is a substrate of the mitogen-activated protein kinases p38, ERK3 and ERK4. Cell culture and animal studies have demonstrated that MK5 is involved in tumour suppression and promotion, embryogenesis, anxiety, cell motility and cell cycle regulation [...] Read more.

The mitogen-activated protein kinase-activated protein kinase MK5 is a substrate of the mitogen-activated protein kinases p38, ERK3 and ERK4. Cell culture and animal studies have demonstrated that MK5 is involved in tumour suppression and promotion, embryogenesis, anxiety, cell motility and cell cycle regulation. In the present study, homology models of MK5 were used for molecular dynamics (MD) simulations of: (1) MK5 alone; (2) MK5 in complex with an inhibitor; and (3) MK5 in complex with the interaction partner p38α. The calculations showed that the inhibitor occupied the active site and disrupted the intramolecular network of amino acids. However, intramolecular interactions consistent with an inactive protein kinase fold were not formed. MD with p38α showed that not only the p38 docking region, but also amino acids in the activation segment, αH helix, P-loop, regulatory phosphorylation region and the C-terminal of MK5 may be involved in forming a very stable MK5-p38α complex, and that p38α binding decreases the residual fluctuation of the MK5 model. Electrostatic Potential Surface (EPS) calculations of MK5 and p38α showed that electrostatic interactions are important for recognition and binding. Full article

(This article belongs to the Collection Computational, Structural and Spectroscopic Studies of Enzyme Mechanisms, Inhibition and Dynamics)

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Graphical abstract

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Open AccessArticle

Dimers of G-Protein Coupled Receptors as Versatile Storage and Response Units

by Michael S. Parker, Renu Sah, Ambikaipakan Balasubramaniam, Edwards A. Park, Floyd R. Sallee and Steven L. Parker

Int. J. Mol. Sci. 2014, 15(3), 4856-4877; https://doi.org/10.3390/ijms15034856 - 19 Mar 2014

Cited by 2 | Viewed by 6652

Abstract

The status and use of transmembrane, extracellular and intracellular domains in oligomerization of heptahelical G-protein coupled receptors (GPCRs) are reviewed and for transmembrane assemblies also supplemented by new experimental evidence. The transmembrane-linked GPCR oligomers typically have as the minimal unit an asymmetric ~180 [...] Read more.

The status and use of transmembrane, extracellular and intracellular domains in oligomerization of heptahelical G-protein coupled receptors (GPCRs) are reviewed and for transmembrane assemblies also supplemented by new experimental evidence. The transmembrane-linked GPCR oligomers typically have as the minimal unit an asymmetric ~180 kDa pentamer consisting of receptor homodimer or heterodimer and a G-protein αβγ subunit heterotrimer. With neuropeptide Y (NPY) receptors, this assembly is converted to ~90 kDa receptor monomer-Gα complex by receptor and Gα agonists, and dimers/heteropentamers are depleted by neutralization of Gαi subunits by pertussis toxin. Employing gradient centrifugation, quantification and other characterization of GPCR dimers at the level of physically isolated and identified heteropentamers is feasible with labeled agonists that do not dissociate upon solubilization. This is demonstrated with three neuropeptide Y (NPY) receptors and could apply to many receptors that use large peptidic agonists. Full article

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

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Open AccessReview

The Growth Hormone Secretagogue Receptor: Its Intracellular Signaling and Regulation

by Yue Yin, Yin Li and Weizhen Zhang

Int. J. Mol. Sci. 2014, 15(3), 4837-4855; https://doi.org/10.3390/ijms15034837 - 19 Mar 2014

Cited by 110 | Viewed by 13061

Abstract

The growth hormone secretagogue receptor (GHSR), also known as the ghrelin receptor, is involved in mediating a wide variety of biological effects of ghrelin, including: stimulation of growth hormone release, increase of food intake and body weight, modulation of glucose and lipid metabolism, [...] Read more.

The growth hormone secretagogue receptor (GHSR), also known as the ghrelin receptor, is involved in mediating a wide variety of biological effects of ghrelin, including: stimulation of growth hormone release, increase of food intake and body weight, modulation of glucose and lipid metabolism, regulation of gastrointestinal motility and secretion, protection of neuronal and cardiovascular cells, and regulation of immune function. Dependent on the tissues and cells, activation of GHSR may trigger a diversity of signaling mechanisms and subsequent distinct physiological responses. Distinct regulation of GHSR occurs at levels of transcription, receptor interaction and internalization. Here we review the current understanding on the intracellular signaling pathways of GHSR and its modulation. An overview of the molecular structure of GHSR is presented first, followed by the discussion on its signaling mechanisms. Finally, potential mechanisms regulating GHSR are reviewed. Full article

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

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Open AccessArticle

Identification of the Novel Interacting Partners of the Mammalian Target of Rapamycin Complex 1 in Human CCRF-CEM and HEK293 Cells

by Hazir Rahman, Muhammad Qasim, Michael Oellerich and Abdul R. Asif

Int. J. Mol. Sci. 2014, 15(3), 4823-4836; https://doi.org/10.3390/ijms15034823 - 18 Mar 2014

Cited by 8 | Viewed by 8500

Abstract

The present study was undertaken to identify proteins that interact with the mammalian target of rapamycin complex 1 (mTORC1) to enable it to carry out its crucial cell signaling functions. Endogenous and myc-tag mTORC1 was purified, in-gel tryptic digested and then identified by [...] Read more.

The present study was undertaken to identify proteins that interact with the mammalian target of rapamycin complex 1 (mTORC1) to enable it to carry out its crucial cell signaling functions. Endogenous and myc-tag mTORC1 was purified, in-gel tryptic digested and then identified by nano-LC ESI Q-TOF MS/MS analysis. A total of nine novel interacting proteins were identified in both endogenous and myc-tag mTORC1 purifications. These new mTORC1 interacting partners include heterogeneous nuclear ribonucleoproteins A2/B1, enhancer of mRNA decapping protein 4, 60S acidic ribosomal protein, P0, nucleolin, dynamin 2, glyceraldehyde 3 phosphate dehydrogenase, 2-oxoglutarate dehydrogenase, glycosyl transferase 25 family member 1 and prohibitin 2. Furthermore hnRNP A2/B1 and dynamin 2 interaction with mTORC1 was confirmed on immunoblotting. The present study has for the first time identified novel interacting partners of mTORC1 in human T lymphoblasts (CCRF-CEM) and human embryonic kidney (HEK293) cells. These new interacting proteins may offer new targets for therapeutic interventions in human diseases caused by perturbed mTORC1 signaling. Full article

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

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Open AccessReview

Toxicological Assessment of Inhaled Nanoparticles: Role of in Vivo, ex Vivo, in Vitro, and in Silico Studies

by Eleonore Fröhlich and Sharareh Salar-Behzadi

Int. J. Mol. Sci. 2014, 15(3), 4795-4822; https://doi.org/10.3390/ijms15034795 - 18 Mar 2014

Cited by 192 | Viewed by 18208

Abstract

The alveolar epithelium of the lung is by far the most permeable epithelial barrier of the human body. The risk for adverse effects by inhaled nanoparticles (NPs) depends on their hazard (negative action on cells and organism) and on exposure (concentration in the [...] Read more.

The alveolar epithelium of the lung is by far the most permeable epithelial barrier of the human body. The risk for adverse effects by inhaled nanoparticles (NPs) depends on their hazard (negative action on cells and organism) and on exposure (concentration in the inhaled air and pattern of deposition in the lung). With the development of advanced in vitro models, not only in vivo, but also cellular studies can be used for toxicological testing. Advanced in vitro studies use combinations of cells cultured in the air-liquid interface. These cultures are useful for particle uptake and mechanistic studies. Whole-body, nose-only, and lung-only exposures of animals could help to determine retention of NPs in the body. Both approaches also have their limitations; cellular studies cannot mimic the entire organism and data obtained by inhalation exposure of rodents have limitations due to differences in the respiratory system from that of humans. Simulation programs for lung deposition in humans could help to determine the relevance of the biological findings. Combination of biological data generated in different biological models and in silico modeling appears suitable for a realistic estimation of potential risks by inhalation exposure to NPs. Full article

(This article belongs to the Special Issue Nanotoxicology and Lung Diseases)

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Open AccessArticle

Over-Expression of Platelet-Derived Growth Factor-D Promotes Tumor Growth and Invasion in Endometrial Cancer

by Yuan Wang, Haifeng Qiu, Weixu Hu, Shaoru Li and Jinjin Yu

Int. J. Mol. Sci. 2014, 15(3), 4780-4794; https://doi.org/10.3390/ijms15034780 - 18 Mar 2014

Cited by 28 | Viewed by 6890

Abstract

The platelet-derived growth factor-D (PDGF-D) was demonstrated to be able to promote tumor growth and invasion in human malignancies. However, little is known about its roles in endometrial cancer. In the present study, we investigated the expression and functions of PDGF-D in human [...] Read more.

The platelet-derived growth factor-D (PDGF-D) was demonstrated to be able to promote tumor growth and invasion in human malignancies. However, little is known about its roles in endometrial cancer. In the present study, we investigated the expression and functions of PDGF-D in human endometrial cancer. Alterations of PDGF-D mRNA and protein were determined by real time PCR, western blot and immunohistochemical staining. Up-regulation of PDGF-D was achieved by stably transfecting the pcDNA3-PDGF-D plasmids into ECC-1 cells; and knockdown of PDGF-D was achieved by transient transfection with siRNA-PDGF-D into Ishikawa cells. The MTT assay, colony formation assay and Transwell assay were used to detect the effects of PDGF-D on cellular proliferation and invasion. The xenograft assay was used to investigate the functions of PDGF-D in vivo. Compared to normal endometrium, more than 50% cancer samples showed over-expression of PDGF-D (p < 0.001), and high level of PDGF-D was correlated with late stage (p = 0.003), deep myometrium invasion (p < 0.001) and lympha vascular space invasion (p = 0.006). In vitro, over-expressing PDGF-D in ECC-1 cells significantly accelerated tumor growth and promoted cellular invasion by increasing the level of MMP2 and MMP9; while silencing PDGF-D in Ishikawa cells impaired cell proliferation and inhibited the invasion, through suppressing the expression of MMP2 and MMP9. Moreover, we also demonstrated that over-expressed PDGF-D could induce EMT and knockdown of PDGF-D blocked the EMT transition. Consistently, in xenografts assay, PDGF-D over-expression significantly promoted tumor growth and tumor weights. We demonstrated that PDGF-D was commonly over-expressed in endometrial cancer, which was associated with late stage deep myometrium invasion and lympha vascular space invasion. Both in vitro and in vivo experiments showed PDGF-D could promote tumor growth and invasion through up-regulating MMP2/9 and inducing EMT. Thus, we propose targeting PDGF-D to be a potent strategy for endometrial cancer treatment. Full article

(This article belongs to the Section Biochemistry)

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Open AccessReview

The Role of Chemokines in Hepatitis C Virus-Mediated Liver Disease

by Anette Brass and Erwin Daniel Brenndörfer

Int. J. Mol. Sci. 2014, 15(3), 4747-4779; https://doi.org/10.3390/ijms15034747 - 18 Mar 2014

Cited by 25 | Viewed by 10120

Abstract

The hepatitis C virus (HCV) is a global health problem affecting more than 170 million people. A chronic HCV infection is associated with liver fibrosis, liver cirrhosis and hepatocellular carcinoma. To enable viral persistence, HCV has developed mechanisms to modulate both innate and [...] Read more.

The hepatitis C virus (HCV) is a global health problem affecting more than 170 million people. A chronic HCV infection is associated with liver fibrosis, liver cirrhosis and hepatocellular carcinoma. To enable viral persistence, HCV has developed mechanisms to modulate both innate and adaptive immunity. The recruitment of antiviral immune cells in the liver is mainly dependent on the release of specific chemokines. Thus, the modulation of their expression could represent an efficient viral escape mechanism to hamper specific immune cell migration to the liver during the acute phase of the infection. HCV-mediated changes in hepatic immune cell chemotaxis during the chronic phase of the infection are significantly affecting antiviral immunity and tissue damage and thus influence survival of both the host and the virus. This review summarizes our current understanding of the HCV-mediated modulation of chemokine expression and of its impact on the development of liver disease. A profound knowledge of the strategies used by HCV to interfere with the host’s immune response and the pro-fibrotic and pro-carcinogenic activities of HCV is essential to be able to design effective immunotherapies against HCV and HCV-mediated liver diseases. Full article

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

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Open AccessArticle

Nitric Oxide Functions as a Signal in Ultraviolet-B-Induced Baicalin Accumulation in Scutellaria baicalensis Suspension Cultures

by Jin-Jie Zhang, Xue-Qin Li, Jun-Wei Sun and Song-Heng Jin

Int. J. Mol. Sci. 2014, 15(3), 4733-4746; https://doi.org/10.3390/ijms15034733 - 18 Mar 2014

Cited by 16 | Viewed by 7286

Abstract

Stress induced by ultraviolet-B (UV-B) irradiation stimulates the accumulation of various secondary metabolites in plants. Nitric oxide (NO) serves as an important secondary messenger in UV-B stress-induced signal transduction pathways. NO can be synthesized in plants by either enzymatic catalysis or an inorganic [...] Read more.

Stress induced by ultraviolet-B (UV-B) irradiation stimulates the accumulation of various secondary metabolites in plants. Nitric oxide (NO) serves as an important secondary messenger in UV-B stress-induced signal transduction pathways. NO can be synthesized in plants by either enzymatic catalysis or an inorganic nitrogen pathway. The effects of UV-B irradiation on the production of baicalin and the associated molecular pathways in plant cells are poorly understood. In this study, nitric oxide synthase (NOS) activity, NO release and the generation of baicalin were investigated in cell suspension cultures of Scutellaria baicalensis exposed to UV-B irradiation. UV-B irradiation significantly increased NOS activity, NO release and baicalin biosynthesis in S. baicalensis cells. Additionally, exogenous NO supplied by the NO donor, sodium nitroprusside (SNP), led to a similar increase in the baicalin content as the UV-B treatment. The NOS inhibitor, N^ω-nitro-l-arginine (LNNA), and NO scavenger, 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO) partially inhibited UV-B-induced NO release and baicalin accumulation. These results suggest that NO is generated by NOS or NOS-like enzymes and plays an important role in baicalin biosynthesis as part of the defense response of S. baicalensis cells to UV-B irradiation. Full article

(This article belongs to the Special Issue Signalling Molecules and Signal Transduction in Cells 2014)

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Open AccessReview

Current Progress in Bioactive Ceramic Scaffolds for Bone Repair and Regeneration

by Chengde Gao, Youwen Deng, Pei Feng, Zhongzheng Mao, Pengjian Li, Bo Yang, Junjie Deng, Yiyuan Cao, Cijun Shuai and Shuping Peng

Int. J. Mol. Sci. 2014, 15(3), 4714-4732; https://doi.org/10.3390/ijms15034714 - 18 Mar 2014

Cited by 245 | Viewed by 16286

Abstract

Bioactive ceramics have received great attention in the past decades owing to their success in stimulating cell proliferation, differentiation and bone tissue regeneration. They can react and form chemical bonds with cells and tissues in human body. This paper provides a comprehensive review [...] Read more.

Bioactive ceramics have received great attention in the past decades owing to their success in stimulating cell proliferation, differentiation and bone tissue regeneration. They can react and form chemical bonds with cells and tissues in human body. This paper provides a comprehensive review of the application of bioactive ceramics for bone repair and regeneration. The review systematically summarizes the types and characters of bioactive ceramics, the fabrication methods for nanostructure and hierarchically porous structure, typical toughness methods for ceramic scaffold and corresponding mechanisms such as fiber toughness, whisker toughness and particle toughness. Moreover, greater insights into the mechanisms of interaction between ceramics and cells are provided, as well as the development of ceramic-based composite materials. The development and challenges of bioactive ceramics are also discussed from the perspective of bone repair and regeneration. Full article

(This article belongs to the Section Materials Science)

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Open AccessReview

Tau Protein Modifications and Interactions: Their Role in Function and Dysfunction

by Anna Mietelska-Porowska, Urszula Wasik, Marcelina Goras, Anna Filipek and Grazyna Niewiadomska

Int. J. Mol. Sci. 2014, 15(3), 4671-4713; https://doi.org/10.3390/ijms15034671 - 18 Mar 2014

Cited by 279 | Viewed by 18277

Abstract

Tau protein is abundant in the central nervous system and involved in microtubule assembly and stabilization. It is predominantly associated with axonal microtubules and present at lower level in dendrites where it is engaged in signaling functions. Post-translational modifications of tau and its [...] Read more.

Tau protein is abundant in the central nervous system and involved in microtubule assembly and stabilization. It is predominantly associated with axonal microtubules and present at lower level in dendrites where it is engaged in signaling functions. Post-translational modifications of tau and its interaction with several proteins play an important regulatory role in the physiology of tau. As a consequence of abnormal modifications and expression, tau is redistributed from neuronal processes to the soma and forms toxic oligomers or aggregated deposits. The accumulation of tau protein is increasingly recognized as the neuropathological hallmark of a number of dementia disorders known as tauopathies. Dysfunction of tau protein may contribute to collapse of cytoskeleton, thereby causing improper anterograde and retrograde movement of motor proteins and their cargos on microtubules. These disturbances in intraneuronal signaling may compromise synaptic transmission as well as trophic support mechanisms in neurons. Full article

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

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Open AccessArticle

Influence of Green, Red and Blue Light Emitting Diodes on Multiprotein Complex Proteins and Photosynthetic Activity under Different Light Intensities in Lettuce Leaves (Lactuca sativa L.)

by Sowbiya Muneer, Eun Jeong Kim, Jeong Suk Park and Jeong Hyun Lee

Int. J. Mol. Sci. 2014, 15(3), 4657-4670; https://doi.org/10.3390/ijms15034657 - 17 Mar 2014

Cited by 254 | Viewed by 34457

Abstract

The objective of this study was to investigate the response of light emitting diodes (LEDs) at different light intensities (70 and 80 for green LEDs, 88 and 238 for red LEDs and 80 and 238 μmol m⁻² s⁻¹ for blue LEDs) [...] Read more.

The objective of this study was to investigate the response of light emitting diodes (LEDs) at different light intensities (70 and 80 for green LEDs, 88 and 238 for red LEDs and 80 and 238 μmol m⁻² s⁻¹ for blue LEDs) at three wavelengths in lettuce leaves. Lettuce leaves were exposed to (522 nm), red (639 nm) and blue (470 nm) LEDs of different light intensities. Thylakoid multiprotein complex proteins and photosynthetic metabolism were then investigated. Biomass and photosynthetic parameters increased with an increasing light intensity under blue LED illumination and decreased when illuminated with red and green LEDs with decreased light intensity. The expression of multiprotein complex proteins including PSII-core dimer and PSII-core monomer using blue LEDs illumination was higher at higher light intensity (238 μmol m⁻² s⁻¹) and was lowered with decreased light intensity (70–80 μmol m⁻² s⁻¹). The responses of chloroplast sub-compartment proteins, including those active in stomatal opening and closing, and leaf physiological responses at different light intensities, indicated induced growth enhancement upon illumination with blue LEDs. High intensity blue LEDs promote plant growth by controlling the integrity of chloroplast proteins that optimize photosynthetic performance in the natural environment. Full article

(This article belongs to the Section Biochemistry)

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Open AccessArticle

Genome-Wide Analysis of the RNA Helicase Gene Family in Gossypium raimondii

by Jie Chen, Yujuan Zhang, Jubo Liu, Minxuan Xia, Wei Wang and Fafu Shen

Int. J. Mol. Sci. 2014, 15(3), 4635-4656; https://doi.org/10.3390/ijms15034635 - 17 Mar 2014

Cited by 23 | Viewed by 8549

Abstract

The RNA helicases, which help to unwind stable RNA duplexes, and have important roles in RNA metabolism, belong to a class of motor proteins that play important roles in plant development and responses to stress. Although this family of genes has been the [...] Read more.

The RNA helicases, which help to unwind stable RNA duplexes, and have important roles in RNA metabolism, belong to a class of motor proteins that play important roles in plant development and responses to stress. Although this family of genes has been the subject of systematic investigation in Arabidopsis, rice, and tomato, it has not yet been characterized in cotton. In this study, we identified 161 putative RNA helicase genes in the genome of the diploid cotton species Gossypium raimondii. We classified these genes into three subfamilies, based on the presence of either a DEAD-box (51 genes), DEAH-box (52 genes), or DExD/H-box (58 genes) in their coding regions. Chromosome location analysis showed that the genes that encode RNA helicases are distributed across all 13 chromosomes of G. raimondii. Syntenic analysis revealed that 62 of the 161 G. raimondii helicase genes (38.5%) are within the identified syntenic blocks. Sixty-six (40.99%) helicase genes from G. raimondii have one or several putative orthologs in tomato. Additionally, GrDEADs have more conserved gene structures and more simple domains than GrDEAHs and GrDExD/Hs. Transcriptome sequencing data demonstrated that many of these helicases, especially GrDEADs, are highly expressed at the fiber initiation stage and in mature leaves. To our knowledge, this is the first report of a genome-wide analysis of the RNA helicase gene family in cotton. Full article

(This article belongs to the Section Biochemistry)

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Int. J. Mol. Sci., Volume 15, Issue 3 (March 2014) – 106 articles , Pages 3356-5192

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