International Journal of Molecular Sciences

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Open AccessArticle

Multivalent Protein Assembly Using Monovalent Self-Assembling Building Blocks

by Katja Petkau-Milroy, Michael H. Sonntag, Alexander Colditz and Luc Brunsveld

Int. J. Mol. Sci. 2013, 14(10), 21189-21201; https://doi.org/10.3390/ijms141021189 - 22 Oct 2013

Cited by 7 | Viewed by 7700

Discotic molecules, which self-assemble in water into columnar supramolecular polymers, emerged as an alternative platform for the organization of proteins. Here, a monovalent discotic decorated with one single biotin was synthesized to study the self-assembling multivalency of this system in regard to streptavidin. [...] Read more.

Discotic molecules, which self-assemble in water into columnar supramolecular polymers, emerged as an alternative platform for the organization of proteins. Here, a monovalent discotic decorated with one single biotin was synthesized to study the self-assembling multivalency of this system in regard to streptavidin. Next to tetravalent streptavidin, monovalent streptavidin was used to study the protein assembly along the supramolecular polymer in detail without the interference of cross-linking. Upon self-assembly of the monovalent biotinylated discotics, multivalent proteins can be assembled along the supramolecular polymer. The concentration of discotics, which influences the length of the final polymers at the same time dictates the amount of assembled proteins. Full article

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

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Open AccessReview

Dietary Polyunsaturated Fatty Acids and Inflammation: The Role of Phospholipid Biosynthesis

by William Raphael and Lorraine M. Sordillo

Int. J. Mol. Sci. 2013, 14(10), 21167-21188; https://doi.org/10.3390/ijms141021167 - 22 Oct 2013

Cited by 131 | Viewed by 16004

Abstract

The composition of fatty acids in the diets of both human and domestic animal species can regulate inflammation through the biosynthesis of potent lipid mediators. The substrates for lipid mediator biosynthesis are derived primarily from membrane phospholipids and reflect dietary fatty acid intake. [...] Read more.

The composition of fatty acids in the diets of both human and domestic animal species can regulate inflammation through the biosynthesis of potent lipid mediators. The substrates for lipid mediator biosynthesis are derived primarily from membrane phospholipids and reflect dietary fatty acid intake. Inflammation can be exacerbated with intake of certain dietary fatty acids, such as some ω-6 polyunsaturated fatty acids (PUFA), and subsequent incorporation into membrane phospholipids. Inflammation, however, can be resolved with ingestion of other fatty acids, such as ω-3 PUFA. The influence of dietary PUFA on phospholipid composition is influenced by factors that control phospholipid biosynthesis within cellular membranes, such as preferential incorporation of some fatty acids, competition between newly ingested PUFA and fatty acids released from stores such as adipose, and the impacts of carbohydrate metabolism and physiological state. The objective of this review is to explain these factors as potential obstacles to manipulating PUFA composition of tissue phospholipids by specific dietary fatty acids. A better understanding of the factors that influence how dietary fatty acids can be incorporated into phospholipids may lead to nutritional intervention strategies that optimize health. Full article

(This article belongs to the Special Issue Phospholipids: Molecular Sciences 2012)

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Open AccessArticle

Identification of Combined Genetic Determinants of Liver Stiffness within the SREBP1c-PNPLA3 Pathway

by Marcin Krawczyk, Frank Grünhage and Frank Lammert

Int. J. Mol. Sci. 2013, 14(10), 21153-21166; https://doi.org/10.3390/ijms141021153 - 22 Oct 2013

Cited by 14 | Viewed by 7515

Abstract

The common PNPLA3 (adiponutrin) variant, p.I148M, was identified as a genetic determinant of liver fibrosis. Since the expression of PNPLA3 is induced by sterol regulatory element binding protein 1c (SREBP1c), we investigate two common SREBP1c variants (rs2297508 and rs11868035) for their association with [...] Read more.

The common PNPLA3 (adiponutrin) variant, p.I148M, was identified as a genetic determinant of liver fibrosis. Since the expression of PNPLA3 is induced by sterol regulatory element binding protein 1c (SREBP1c), we investigate two common SREBP1c variants (rs2297508 and rs11868035) for their association with liver stiffness. In 899 individuals (aged 17–83 years, 547 males) with chronic liver diseases, hepatic fibrosis was non-invasively phenotyped by transient elastography (TE). The SREBP1c single nucleotide polymorphisms (SNPs) were genotyped using PCR-based assays with 5'-nuclease and fluorescence detection. The SREBP1c rs11868035 variant affected liver fibrosis significantly (p = 0.029): median TE levels were 7.2, 6.6 and 6.0 kPa in carriers of (TT) (n = 421), (CT) (n = 384) and (CC) (n = 87) genotypes, respectively. Overall, the SREBP1c SNP was associated with low TE levels (5.0–8.0 kPa). Carriers of both PNPLA3 and SREBP1c risk genotypes displayed significantly (p = 0.005) higher median liver stiffness, as compared to patients carrying none of these variants. The common SREBP1c variant may affect early stages of liver fibrosis. Our study supports a role of the SREBP1c-PNPLA3 pathway as a “disease module” that promotes hepatic fibrogenesis. Full article

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

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Open AccessArticle

The Effect on Proliferation and Differentiation of Cementoblast by Using Sclerostin as Inhibitor

by Xingfu Bao, Yuyan Liu, Guanghong Han, Zhigang Zuo and Min Hu

Int. J. Mol. Sci. 2013, 14(10), 21140-21152; https://doi.org/10.3390/ijms141021140 - 21 Oct 2013

Cited by 25 | Viewed by 11738 | Correction

Abstract

Cementogenesis is of great importance for normal teeth root development and is involved in the repair process of root resorption caused by orthodontic treatment. As highly differentiated mesenchymal cells, cementoblasts are responsible for this process under the regulation of many endogenous agents. Among [...] Read more.

Cementogenesis is of great importance for normal teeth root development and is involved in the repair process of root resorption caused by orthodontic treatment. As highly differentiated mesenchymal cells, cementoblasts are responsible for this process under the regulation of many endogenous agents. Among these molecules, sclerostin has been much investigated recently for its distinct antagonism effect on bone metabolism. Encoded by the sost gene, sclerostin is expressed in osteocytes and cementocytes of cellular cementum. it is still unclear. In the current study, we investigated the effects of sclerostin on the processes of proliferation and differentiation; a series of experiments including MTT, apoptosis examination, alkaline phosphatase (ALP) activity, gene analysis, and alizarin red staining were carried out to evaluate the proliferation and differentiation of cementoblasts. Protein expression including osteoprotegerin (OPG) and receptor activator of nuclear factor kappa B ligand (RANKL) were also checked to analyze changes in osteoclastogenesis. Results show that sclerostin inhibits cementoblasts proliferation and differentiation, and promotes osteoclastogenesis. Interestingly, the monoclonal antibody for sclerostin has shown positive effects on osteoporosis, indicating that it may facilitate cementogenesis and benefit the treatment of cementum related diseases. Full article

(This article belongs to the Section Biochemistry)

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Open AccessArticle

Crosstalk between Delta Opioid Receptor and Nerve Growth Factor Signaling Modulates Neuroprotection and Differentiation in Rodent Cell Models

by Dwaipayan Sen, Michael Huchital and Yulong L. Chen

Int. J. Mol. Sci. 2013, 14(10), 21114-21139; https://doi.org/10.3390/ijms141021114 - 21 Oct 2013

Cited by 23 | Viewed by 7936

Abstract

Both opioid signaling and neurotrophic factor signaling have played an important role in neuroprotection and differentiation in the nervous system. Little is known about whether the crosstalk between these two signaling pathways will affect neuroprotection and differentiation. Previously, we found that nerve growth [...] Read more.

Both opioid signaling and neurotrophic factor signaling have played an important role in neuroprotection and differentiation in the nervous system. Little is known about whether the crosstalk between these two signaling pathways will affect neuroprotection and differentiation. Previously, we found that nerve growth factor (NGF) could induce expression of the delta opioid receptor gene (Oprd1, dor), mainly through PI3K/Akt/NF-κB signaling in PC12h cells. In this study, using two NGF-responsive rodent cell model systems, PC12h cells and F11 cells, we found the delta opioid neuropeptide [D-Ala², D-Leu⁵] enkephalin (DADLE)-mediated neuroprotective effect could be blocked by pharmacological reagents: the delta opioid antagonist naltrindole, PI3K inhibitor LY294002, MAPK inhibitor PD98059, and Trk inhibitor K252a, respectively. Western blot analysis revealed that DADLE activated both the PI3K/Akt and MAPK pathways in the two cell lines. siRNA Oprd1 gene knockdown experiment showed that the upregulation of NGF mRNA level was inhibited with concomitant inhibition of the survival effects of DADLE in the both cell models. siRNA Oprd1 gene knockdown also attenuated the DADLE-mediated neurite outgrowth in PC12h cells as well as phosphorylation of MAPK and Akt in PC12h and F11 cells, respectively. These data together strongly suggest that delta opioid peptide DADLE acts through the NGF-induced functional G protein-coupled Oprd1 to provide its neuroprotective and differentiating effects at least in part by regulating survival and differentiating MAPK and PI3K/Akt signaling pathways in NGF-responsive rodent neuronal cells. Full article

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

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Open AccessReview

Cancer Development, Progression, and Therapy: An Epigenetic Overview

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

Int. J. Mol. Sci. 2013, 14(10), 21087-21113; https://doi.org/10.3390/ijms141021087 - 21 Oct 2013

Cited by 255 | Viewed by 23856

Abstract

Carcinogenesis involves uncontrolled cell growth, which follows the activation of oncogenes and/or the deactivation of tumor suppression genes. Metastasis requires down-regulation of cell adhesion receptors necessary for tissue-specific, cell–cell attachment, as well as up-regulation of receptors that enhance cell motility. Epigenetic changes, including [...] Read more.

Carcinogenesis involves uncontrolled cell growth, which follows the activation of oncogenes and/or the deactivation of tumor suppression genes. Metastasis requires down-regulation of cell adhesion receptors necessary for tissue-specific, cell–cell attachment, as well as up-regulation of receptors that enhance cell motility. Epigenetic changes, including histone modifications, DNA methylation, and DNA hydroxymethylation, can modify these characteristics. Targets for these epigenetic changes include signaling pathways that regulate apoptosis and autophagy, as well as microRNA. We propose that predisposed normal cells convert to cancer progenitor cells that, after growing, undergo an epithelial-mesenchymal transition. This process, which is partially under epigenetic control, can create a metastatic form of both progenitor and full-fledged cancer cells, after which metastasis to a distant location may occur. Identification of epigenetic regulatory mechanisms has provided potential therapeutic avenues. In particular, epigenetic drugs appear to potentiate the action of traditional therapeutics, often by demethylating and re-expressing tumor suppressor genes to inhibit tumorigenesis. Epigenetic drugs may inhibit both the formation and growth of cancer progenitor cells, thus reducing the recurrence of cancer. Adopting epigenetic alteration as a new hallmark of cancer is a logical and necessary step that will further encourage the development of novel epigenetic biomarkers and therapeutics. Full article

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

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Open AccessReview

Angiotensin-Converting Enzymes Play a Dominant Role in Fertility

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

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

Cited by 88 | Viewed by 9848

Abstract

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

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

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Open AccessArticle

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

by Qingtian Li, Jia Liu, Dunxian Tan, Andrew C. Allan, Yuzhuang Jiang, Xuefeng Xu, Zhenhai Han and Jin Kong

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

Cited by 25 | Viewed by 7240

Abstract

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

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

(This article belongs to the Section Biochemistry)

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Open AccessArticle

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

by Yaxing Wang, Cheng Li, Xiaojing Guo and Guozhong Wu

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

Cited by 18 | Viewed by 7213

Abstract

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

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

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

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Open AccessReview

Impaired Glutathione Synthesis in Neurodegeneration

by Koji Aoyama and Toshio Nakaki

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

Cited by 174 | Viewed by 16738

Abstract

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

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

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

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Open AccessArticle

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

by Xia Hu, Chunyan Wang, Hui Chen and Junning Ma

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

Cited by 43 | Viewed by 8013

Abstract

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

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

(This article belongs to the Section Biochemistry)

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Open AccessReview

Biofilm Matrix and Its Regulation in Pseudomonas aeruginosa

by Qing Wei and Luyan Z. Ma

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

Cited by 255 | Viewed by 22113

Abstract

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

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

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

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Open AccessArticle

DNA Damage Induced MutS Homologue hMSH4 Acetylation

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

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

Cited by 1 | Viewed by 6011

Abstract

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

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

(This article belongs to the Section Biochemistry)

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Open AccessArticle

Pesticide Removal from Aqueous Solutions by Adding Salting Out Agents

by Fátima Moscoso, Francisco J. Deive, José M. S. S. Esperança and Ana Rodríguez

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

Cited by 17 | Viewed by 7361

Abstract

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

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

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

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Open AccessReview

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

by Alessandro Fatica and Francesco Fazi

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

Cited by 22 | Viewed by 7647

Abstract

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

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

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

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Open AccessArticle

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

by Yi-Hsien Lin, Kui-You Pan, Ching-Hui Hung, Hsiang-En Huang, Ching-Lian Chen, Teng-Yung Feng and Li-Fen Huang

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

Cited by 54 | Viewed by 10378

Abstract

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

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

(This article belongs to the Section Biochemistry)

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Open AccessReview

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

by Xiaojin Wang, Ning Xia and Lin Liu

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

Cited by 93 | Viewed by 15732

Abstract

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

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

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

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Open AccessArticle

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

by Kazuyuki Matsumoto, Yasuhiro Miyake, Yuzo Umeda, Hiroshi Matsushita, Hiroaki Matsuda, Akinobu Takaki, Hiroshi Sadamori, Kazuhiro Nouso, Takahito Yagi, Toshiyoshi Fujiwara and Kazuhide Yamamoto

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

Cited by 26 | Viewed by 6936

Abstract

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

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

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

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Open AccessReview

Protein Glutathionylation in Cardiovascular Diseases

by Anna Pastore and Fiorella Piemonte

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

Cited by 81 | Viewed by 10949

Abstract

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

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

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

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Open AccessArticle

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

by Fengfeng Li, Shen Liu and Cunyi Fan

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

Cited by 24 | Viewed by 6839

Abstract

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

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

(This article belongs to the Section Biochemistry)

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Open AccessArticle

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

by Zhidong Yuan, Hongde Liu, Yumin Nie, Suping Ding, Mingli Yan, Shuhua Tan, Yuanchang Jin and Xiao Sun

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

Cited by 2 | Viewed by 6180

Abstract

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

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

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

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Open AccessArticle

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

by Toshiyuki Murai, Mari Sato, Hidetoshi Nishiyama, Mitsuo Suga and Chikara Sato

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

Cited by 16 | Viewed by 8030

Abstract

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

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

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

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Open AccessReview

Lipid Transport and Metabolism in Healthy and Osteoarthritic Cartilage

by Amanda Villalvilla, Rodolfo Gómez, Raquel Largo and Gabriel Herrero-Beaumont

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

Cited by 80 | Viewed by 9123

Abstract

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

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

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

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Open AccessArticle

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

by Nathalie Zucchini-Pascal, Ludovic Peyre and Roger Rahmani

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

Cited by 53 | Viewed by 10246

Abstract

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

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

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

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Open AccessArticle

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

by Bharat Bhusan Patnaik, Seong Min Kang, Gi Won Seo, Hyo Jeong Lee, Hongray Howrelia Patnaik, Yong Hun Jo, Hamisi Tindwa, Yong Seok Lee, Bok Luel Lee, Nam Jung Kim, In Seok Bang and Yeon Soo Han

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

Cited by 15 | Viewed by 10550

Abstract

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

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

(This article belongs to the Section Biochemistry)

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Open AccessArticle

Supramolecular Interactions of Terpyridine-Derived Cores of Metallomesogen Precursors

by Young Hoon Lee, Jack M. Harrowfield, Jong Won Shin, Mi Seon Won, Elisabeth Rukmini, Shinya Hayami, Kil Sik Min and Yang Kim

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

Cited by 6 | Viewed by 6697

Abstract

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

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

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

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

by Akinobu Takaki, Daisuke Kawai and Kazuhide Yamamoto

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

Cited by 342 | Viewed by 21088

Abstract

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

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

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

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Open AccessArticle

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

by Xi'en Chen and Yalin Zhang

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

Cited by 5 | Viewed by 5886

Abstract

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

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

(This article belongs to the Section Biochemistry)

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Open AccessArticle

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

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

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

Cited by 13 | Viewed by 8087

Abstract

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

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

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

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Open AccessArticle

Absolute Quantification of Selected Proteins in the Human Osteoarthritic Secretome

by Mandy J. Peffers, Robert J. Beynon and Peter D. Clegg

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

Cited by 40 | Viewed by 7876

Abstract

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

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

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Int. J. Mol. Sci., Volume 14, Issue 10 (October 2013) – 105 articles , Pages 19361-21201

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