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Int. J. Mol. Sci., Volume 15, Issue 7 (July 2014), Pages 11204-13134

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Open AccessArticle PSNO: Predicting Cysteine S-Nitrosylation Sites by Incorporating Various Sequence-Derived Features into the General Form of Chou’s PseAAC
Int. J. Mol. Sci. 2014, 15(7), 11204-11219; doi:10.3390/ijms150711204
Received: 14 April 2014 / Revised: 26 May 2014 / Accepted: 27 May 2014 / Published: 25 June 2014
Cited by 26 | PDF Full-text (1052 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
S-nitrosylation (SNO) is one of the most universal reversible post-translational modifications involved in many biological processes. Malfunction or dysregulation of SNO leads to a series of severe diseases, such as developmental abnormalities and various diseases. Therefore, the identification of SNO sites (SNOs)
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S-nitrosylation (SNO) is one of the most universal reversible post-translational modifications involved in many biological processes. Malfunction or dysregulation of SNO leads to a series of severe diseases, such as developmental abnormalities and various diseases. Therefore, the identification of SNO sites (SNOs) provides insights into disease progression and drug development. In this paper, a new bioinformatics tool, named PSNO, is proposed to identify SNOs from protein sequences. Firstly, we explore various promising sequence-derived discriminative features, including the evolutionary profile, the predicted secondary structure and the physicochemical properties. Secondly, rather than simply combining the features, which may bring about information redundancy and unwanted noise, we use the relative entropy selection and incremental feature selection approach to select the optimal feature subsets. Thirdly, we train our model by the technique of the k-nearest neighbor algorithm. Using both informative features and an elaborate feature selection scheme, our method, PSNO, achieves good prediction performance with a mean Mathews correlation coefficient (MCC) value of about 0.5119 on the training dataset using 10-fold cross-validation. These results indicate that PSNO can be used as a competitive predictor among the state-of-the-art SNOs prediction tools. A web-server, named PSNO, which implements the proposed method, is freely available at http://59.73.198.144:8088/PSNO/. Full article
Open AccessArticle The REST Gene Signature Predicts Drug Sensitivity in Neuroblastoma Cell Lines and Is Significantly Associated with Neuroblastoma Tumor Stage
Int. J. Mol. Sci. 2014, 15(7), 11220-11233; doi:10.3390/ijms150711220
Received: 23 April 2014 / Revised: 30 May 2014 / Accepted: 3 June 2014 / Published: 25 June 2014
Cited by 4 | PDF Full-text (786 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Neuroblastoma is the most common and deadly solid tumor in children, and there is currently no effective treatment available for neuroblastoma patients. The repressor element-1 silencing transcription (REST) factor has been found to play important roles in the regulation of neural differentiation and
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Neuroblastoma is the most common and deadly solid tumor in children, and there is currently no effective treatment available for neuroblastoma patients. The repressor element-1 silencing transcription (REST) factor has been found to play important roles in the regulation of neural differentiation and tumorigenesis. Recently, a REST signature consisting of downstream targets of REST has been reported to have clinical relevance in both breast cancer and glioblastoma. However it remains unclear how the REST signature works in neuroblastoma. Publicly available datasets were mined and bioinformatic approaches were used to investigate the utility of the REST signature in neuroblastoma with both preclinical and real patient data. The REST signature was found to be associated with drug sensitivity in neuroblastoma cell lines. Further, neuroblastoma patients with enhanced REST activity are significantly associated with higher clinical stages. Loss of heterozygosity on chromosome 11q23, which occurs in a large subset of high-risk neuroblastomas, tends to be correlated with high REST activity, with marginal significance. In conclusion, the REST signature has important implications for targeted therapy, and it is a prognostic factor in neuroblastoma patients. Full article
Open AccessArticle Development of Laser Ionization Techniques for Evaluation of the Effect of Cancer Drugs Using Imaging Mass Spectrometry
Int. J. Mol. Sci. 2014, 15(7), 11234-11244; doi:10.3390/ijms150711234
Received: 20 March 2014 / Revised: 2 June 2014 / Accepted: 9 June 2014 / Published: 25 June 2014
PDF Full-text (1626 KB) | HTML Full-text | XML Full-text
Abstract
Recently, combined therapy using chemotherapy and photodynamic therapy (PDT) has been proposed as a means of improving treatment outcomes. In order to evaluate the efficacy of combined therapy, it is necessary to determine the distribution of the anticancer drug and the photosensitizer. We
[...] Read more.
Recently, combined therapy using chemotherapy and photodynamic therapy (PDT) has been proposed as a means of improving treatment outcomes. In order to evaluate the efficacy of combined therapy, it is necessary to determine the distribution of the anticancer drug and the photosensitizer. We investigated the use of imaging mass spectrometry (IMS) to simultaneously observe the distributions of an anticancer drug and photosensitizer administered to cancer cells. In particular, we sought to increase the sensitivity of detection of the anticancer drug docetaxel and the photosensitizer protoporphyrin IX (PpIX) by optimizing the ionization-assisting reagents. When we used a matrix consisting of equal weights of a zeolite (NaY5.6) and a conventional organic matrix (6-aza-2-thiothymine) in matrix-assisted laser desorption/ionization, the signal intensity of the sodium-adducted ion of docetaxel (administered at 100 μM) increased about 13-fold. Moreover, we detected docetaxel with the zeolite matrix using the droplet method, and detected PpIX by fluorescence and IMS with α-cyano-4-hydroxycinnamic acid (CHCA) using the spray method. Full article
(This article belongs to the Special Issue Mass Spectrometry Application in Biology) Print Edition available
Open AccessArticle Elucidating Polypharmacological Mechanisms of Polyphenols by Gene Module Profile Analysis
Int. J. Mol. Sci. 2014, 15(7), 11245-11254; doi:10.3390/ijms150711245
Received: 13 May 2014 / Revised: 4 June 2014 / Accepted: 17 June 2014 / Published: 25 June 2014
Cited by 4 | PDF Full-text (239 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Due to the diverse medicinal effects, polyphenols are among the most intensively studied natural products. However, it is a great challenge to elucidate the polypharmacological mechanisms of polyphenols. To address this challenge, we establish a method for identifying multiple targets of chemical agents
[...] Read more.
Due to the diverse medicinal effects, polyphenols are among the most intensively studied natural products. However, it is a great challenge to elucidate the polypharmacological mechanisms of polyphenols. To address this challenge, we establish a method for identifying multiple targets of chemical agents through analyzing the module profiles of gene expression upon chemical treatments. By using FABIA algorithm, we have performed a biclustering analysis of gene expression profiles derived from Connectivity Map (cMap), and clustered the profiles into 49 gene modules. This allowed us to define a 49 dimensional binary vector to characterize the gene module profiles, by which we can compare the expression profiles for each pair of chemical agents with Tanimoto coefficient. For the agent pairs with similar gene expression profiles, we can predict the target of one agent from the other. Drug target enrichment analysis indicated that this method is efficient to predict the multiple targets of chemical agents. By using this method, we identify 148 targets for 20 polyphenols derived from cMap. A large part of the targets are validated by experimental observations. The results show that the medicinal effects of polyphenols are far beyond their well-known antioxidant activities. This method is also applicable to dissect the polypharmacology of other natural products. Full article
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Open AccessArticle A Novel Human TGF-β1 Fusion Protein in Combination with rhBMP-2 Increases Chondro-Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells
Int. J. Mol. Sci. 2014, 15(7), 11255-11274; doi:10.3390/ijms150711255
Received: 1 May 2014 / Revised: 3 June 2014 / Accepted: 10 June 2014 / Published: 25 June 2014
Cited by 5 | PDF Full-text (2379 KB) | HTML Full-text | XML Full-text
Abstract
Transforming growth factor-beta (TGF-β) is involved in processes related to the differentiation and maturation of osteoprogenitor cells into osteoblasts. Rat bone marrow (BM) cells were cultured in a collagen-gel containing 0.5% fetal bovine serum (FBS) for 10 days in the presence of rhTGF
[...] Read more.
Transforming growth factor-beta (TGF-β) is involved in processes related to the differentiation and maturation of osteoprogenitor cells into osteoblasts. Rat bone marrow (BM) cells were cultured in a collagen-gel containing 0.5% fetal bovine serum (FBS) for 10 days in the presence of rhTGF (recombinant human TGF)-β1-F2, a fusion protein engineered to include a high-affinity collagen-binding decapeptide derived from von Willebrand factor. Subsequently, cells were moderately expanded in medium with 10% FBS for 4 days and treated with a short pulse of rhBMP (recombinant human bone morphogenetic protein)-2 for 4 h. During the last 2 days, dexamethasone and β-glycerophosphate were added to potentiate osteoinduction. Concomitant with an up-regulation of cell proliferation, DNA synthesis levels were determined. Polymerase chain reaction was performed to reveal the possible stemness of these cells. Osteogenic differentiation was evaluated in terms of alkaline phosphatase activity and mineralized matrix formation as well as by mRNA expression of osteogenic marker genes. Moreover, cells were placed inside diffusion chambers and implanted subcutaneously into the backs of adult rats for 4 weeks. Histological study provided evidence of cartilage and bone-like tissue formation. This experimental procedure is capable of selecting cell populations from BM that, in the presence of rhTGF-β1-F2 and rhBMP-2, achieve skeletogenic potential in vitro and in vivo. Full article
(This article belongs to the Special Issue The Chondrocyte Phenotype in Cartilage Biology)
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Open AccessArticle Human Mesenchymal Stem Cells Modulate Inflammatory Cytokines after Spinal Cord Injury in Rat
Int. J. Mol. Sci. 2014, 15(7), 11275-11293; doi:10.3390/ijms150711275
Received: 15 May 2014 / Revised: 11 June 2014 / Accepted: 16 June 2014 / Published: 25 June 2014
Cited by 18 | PDF Full-text (1780 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Transplantation of mesenchymal stem cells (MSC) improves functional recovery in experimental models of spinal cord injury (SCI); however, the mechanisms underlying this effect are not completely understood. We investigated the effect of intrathecal implantation of human MSC on functional recovery, astrogliosis and levels
[...] Read more.
Transplantation of mesenchymal stem cells (MSC) improves functional recovery in experimental models of spinal cord injury (SCI); however, the mechanisms underlying this effect are not completely understood. We investigated the effect of intrathecal implantation of human MSC on functional recovery, astrogliosis and levels of inflammatory cytokines in rats using balloon-induced spinal cord compression lesions. Transplanted cells did not survive at the lesion site of the spinal cord; however, functional recovery was enhanced in the MSC-treated group as was confirmed by the Basso, Beattie, and Bresnahan (BBB) and the flat beam test. Morphometric analysis showed a significantly higher amount of remaining white matter in the cranial part of the lesioned spinal cords. Immunohistochemical analysis of the lesions indicated the rearrangement of the glial scar in MSC-treated animals. Real-time PCR analysis revealed an increased expression of Irf5, Mrc1, Fgf2, Gap43 and Gfap. Transplantation of MSCs into a lesioned spinal cord reduced TNFα, IL-4, IL-1β, IL-2, IL-6 and IL-12 and increased the levels of MIP-1α and RANTES when compared to saline-treated controls. Intrathecal implantation of MSCs reduces the inflammatory reaction and apoptosis, improves functional recovery and modulates glial scar formation after SCI, regardless of cell survival. Therefore, repeated applications may prolong the beneficial effects induced by MSC application. Full article
(This article belongs to the Special Issue Neurological Injuries’ Monitoring, Tracking and Treatment)
Open AccessArticle Impact of Serum Chemerin Levels on Liver Functional Reserves and Platelet Counts in Patients with Hepatocellular Carcinoma
Int. J. Mol. Sci. 2014, 15(7), 11294-11306; doi:10.3390/ijms150711294
Received: 28 February 2014 / Revised: 12 June 2014 / Accepted: 16 June 2014 / Published: 25 June 2014
Cited by 1 | PDF Full-text (771 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Obesity-related metabolic abnormalities, including adipokine imbalance and chronic inflammation, are involved in liver carcinogenesis. Chemerin, a novel adipokine, plays a critical role in adipogenesis, energy metabolism, and inflammation. We evaluated the impact of serum chemerin levels on liver functional reserves in hepatocellular carcinoma
[...] Read more.
Obesity-related metabolic abnormalities, including adipokine imbalance and chronic inflammation, are involved in liver carcinogenesis. Chemerin, a novel adipokine, plays a critical role in adipogenesis, energy metabolism, and inflammation. We evaluated the impact of serum chemerin levels on liver functional reserves in hepatocellular carcinoma (HCC) patients and on the recurrence and prognosis of HCC. This study included 44 patients with any stage of HCC who underwent curative treatment at Gifu Municipal Hospital (Gifu, Japan) between 2006 and 2007. Recurrence-free survival and overall survival were estimated using the Kaplan-Meier method. Serum albumin levels (Pearson’s correlation coefficient; r = 0.3110, p = 0.0399), platelet counts (r = 0.4159, p = 0.0050), and prothrombin times (r = 0.3775, p = 0.0115) were significantly correlated with serum chemerin levels in patients with HCC, and they were inversely correlated with Child-Pugh scores (r = −0.3732, p = 0.0126), serum alanine aminotransferase levels (r = −0.3864, p = 0.0105), and total bilirubin levels (r = −0.4023, p = 0.0068). Among these variables, a multiple comparison test identified that platelet counts and total bilirubin levels were associated with serum chemerin levels (p < 0.0083). No significant correlation was found between serum chemerin levels and recurrence-free survival (p = 0.3691) or overall survival (p = 0.7916). In HCC patients, serum chemerin concentrations were correlated with liver functional reserves and platelet counts, but not with recurrence or prognosis. Full article
(This article belongs to the collection Molecular Mechanisms of Human Liver Diseases)
Open AccessArticle Genetic Diversity and Population Structure of the Critically Endangered Yangtze Finless Porpoise (Neophocaena asiaeorientalis asiaeorientalis) as Revealed by Mitochondrial and Microsatellite DNA
Int. J. Mol. Sci. 2014, 15(7), 11307-11323; doi:10.3390/ijms150711307
Received: 27 January 2014 / Revised: 8 May 2014 / Accepted: 9 May 2014 / Published: 25 June 2014
Cited by 2 | PDF Full-text (980 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Ecological surveys have indicated that the population of the critically endangered Yangtze finless porpoise (YFP, Neophocaena asiaeorientalis asiaeorientalis) is becoming increasingly small and fragmented, and will be at high risk of extinction in the near future. Genetic conservation of this population will
[...] Read more.
Ecological surveys have indicated that the population of the critically endangered Yangtze finless porpoise (YFP, Neophocaena asiaeorientalis asiaeorientalis) is becoming increasingly small and fragmented, and will be at high risk of extinction in the near future. Genetic conservation of this population will be an important component of the long-term conservation effort. We used a 597 base pair mitochondrial DNA (mtDNA) control region and 11 microsatellite loci to analyze the genetic diversity and population structure of the YFP. The analysis of both mtDNA and microsatellite loci suggested that the genetic diversity of the YFP will possibly decrease in the future if the population keeps declining at a rapid rate, even though these two types of markers revealed different levels of genetic diversity. In addition, mtDNA revealed strong genetic differentiation between one local population, Xingchang–Shishou (XCSS), and the other five downstream local populations; furthermore, microsatellite DNA unveiled fine but significant genetic differentiation between three of the local populations (not only XCSS but also Poyang Lake (PY) and Tongling (TL)) and the other local populations. With an increasing number of distribution gaps appearing in the Yangtze main steam, the genetic differentiation of local populations will likely intensify in the future. The YFP is becoming a genetically fragmented population. Therefore, we recommend attention should be paid to the genetic conservation of the YFP. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Rapid Carbonation for Calcite from a Solid-Liquid-Gas System with an Imidazolium-Based Ionic Liquid
Int. J. Mol. Sci. 2014, 15(7), 11350-11363; doi:10.3390/ijms150711350
Received: 8 May 2014 / Revised: 4 June 2014 / Accepted: 10 June 2014 / Published: 25 June 2014
Cited by 4 | PDF Full-text (6946 KB) | HTML Full-text | XML Full-text
Abstract
Aqueous carbonation of Ca(OH)2 is a complex process that produces calcite with scalenohedral calcite phases and characterized by inadequate carbonate species for effective carbonation due to the poor dissolution of CO2 in water. Consequently, we report a solid-liquid-gas carbonation system with
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Aqueous carbonation of Ca(OH)2 is a complex process that produces calcite with scalenohedral calcite phases and characterized by inadequate carbonate species for effective carbonation due to the poor dissolution of CO2 in water. Consequently, we report a solid-liquid-gas carbonation system with an ionic liquid (IL), 1-butyl-3-methylimidazolium bromide, in view of enhancing the reaction of CO2 with Ca(OH)2. The use of the IL increased the solubility of CO2 in the aqueous environment and enhanced the transport of the reactive species (Ca2+ and CO32−) and products. The presence of the IL also avoided the formation of the CaCO3 protective and passivation layer and ensured high carbonation yields, as well as the production of stoichiometric rhombohedral calcite phases in a short time. Full article
(This article belongs to the Special Issue Ionic Liquids 2014 & Selected Papers from ILMAT 2013)
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Open AccessArticle DNA Sequencing Diagnosis of Off-Season Spirochetemia with Low Bacterial Density in Borrelia burgdorferi and Borrelia miyamotoi Infections
Int. J. Mol. Sci. 2014, 15(7), 11364-11386; doi:10.3390/ijms150711364
Received: 12 May 2014 / Revised: 17 June 2014 / Accepted: 19 June 2014 / Published: 25 June 2014
PDF Full-text (4698 KB) | HTML Full-text | XML Full-text
Abstract
A highly conserved 357-bp segment of the 16S ribosomal RNA gene (16S rDNA) of Borrelia burgdorferi sensu lato and the correspondent 358-bp segment of the Borrelia miyamotoi gene were amplified by a single pair of nested polymerase chain reaction (PCR) primers for detection,
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A highly conserved 357-bp segment of the 16S ribosomal RNA gene (16S rDNA) of Borrelia burgdorferi sensu lato and the correspondent 358-bp segment of the Borrelia miyamotoi gene were amplified by a single pair of nested polymerase chain reaction (PCR) primers for detection, and the amplicons were used as the templates for direct Sanger DNA sequencing. Reliable molecular diagnosis of these borreliae was confirmed by sequence alignment analysis of the hypervariable regions of the PCR amplicon, using the Basic Local Alignment Search Tool (BLAST) provided by the GenBank. This methodology can detect and confirm B. burgdorferi and B. miyamotoi in blood samples of patients with off-season spirochetemia of low bacterial density. We found four B. miyamotoi infections among 14 patients with spirochetemia, including one patient co-infected by both B. miyamotoi and B. burgdorferi in a winter month when human exposure to tick bites is very limited in the Northeast of the U.S.A. We conclude that sensitive and reliable tests for these two Borrelia species should be implemented in the microbiology laboratory of hospitals located in the disease-endemic areas, for timely diagnosis and appropriate treatment of the patients at an early stage of the infection to prevent potential tissue damages. Full article
(This article belongs to the Section Molecular Diagnostics)
Open AccessArticle Insights on Antioxidant Assays for Biological Samples Based on the Reduction of Copper Complexes—The Importance of Analytical Conditions
Int. J. Mol. Sci. 2014, 15(7), 11387-11402; doi:10.3390/ijms150711387
Received: 23 May 2014 / Revised: 16 June 2014 / Accepted: 17 June 2014 / Published: 25 June 2014
Cited by 6 | PDF Full-text (616 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Total antioxidant capacity assays are recognized as instrumental to establish antioxidant status of biological samples, however the varying experimental conditions result in conclusions that may not be transposable to other settings. After selection of the complexing agent, reagent addition order, buffer type and
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Total antioxidant capacity assays are recognized as instrumental to establish antioxidant status of biological samples, however the varying experimental conditions result in conclusions that may not be transposable to other settings. After selection of the complexing agent, reagent addition order, buffer type and concentration, copper reducing assays were adapted to a high-throughput scheme and validated using model biological antioxidant compounds of ascorbic acid, Trolox (a soluble analogue of vitamin E), uric acid and glutathione. A critical comparison was made based on real samples including NIST-909c human serum certified sample, and five study samples. The validated method provided linear range up to 100 µM Trolox, (limit of detection 2.3 µM; limit of quantification 7.7 µM) with recovery results above 85% and precision <5%. The validated developed method with an increased sensitivity is a sound choice for assessment of TAC in serum samples. Full article
(This article belongs to the Section Molecular Diagnostics)
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Open AccessArticle Genetic Variants of APOC3 Promoter and HLA-B Genes in an HIV Infected Cohort in Northern South Africa: A Pilot Study
Int. J. Mol. Sci. 2014, 15(7), 11403-11415; doi:10.3390/ijms150711403
Received: 28 December 2013 / Revised: 17 March 2014 / Accepted: 11 April 2014 / Published: 26 June 2014
Cited by 4 | PDF Full-text (867 KB) | HTML Full-text | XML Full-text
Abstract
Metabolic disorders and hypersensitivities affect tolerability and impact adherence to highly active antiretroviral therapy (HAART). The aim of this study was to determine the prevalence of C-482T/T-455C variants in the Apolipoprotein C3 (APOC3) promoter gene and Human leukocyte antigen (HLA)-B*57:01, known to impact
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Metabolic disorders and hypersensitivities affect tolerability and impact adherence to highly active antiretroviral therapy (HAART). The aim of this study was to determine the prevalence of C-482T/T-455C variants in the Apolipoprotein C3 (APOC3) promoter gene and Human leukocyte antigen (HLA)-B*57:01, known to impact lipid metabolic disorders and hypersensitivity respectively; and to correlate genotypes with gender, CD4+ cell count and viral load in an HIV infected cohort in northern South Africa. Frequencies of C-482 and T-455 polymorphisms in APOC3 were determined by restriction fragment length polymorphism analysis. Allele determination for HLA-B was performed with Assign SBT software in an HLA library. Analysis of APOC3 C-482 site revealed a prevalence of 196/199 (98.5%) for CC, 1/199 (0.5%) for CT and 2/199 (1.0%) for TT genotype (p = 0.000 with 1° of freedom; χ2 = 126.551). For the T-455 site, prevalences were: 69/199 (35%) for TT and 130/199 (65%) for the CC genotype (p = 0.000 with 1° of freedom; χ2 = 199). There was no association between gender and the presence of −482 (p = 1; χ2 = 0.00001) or −455 genotypes (p = 0.1628; χ2 = 1.9842). There was no significant difference in the increase in CD4+ cell count irrespective of genotypes. Significant increases in CD4+ cell count were observed in males and females considering the −455C genotype, but not in males for the −455T genotype. Viral load decreases were significant with the −455C and −482C genotypes irrespective of gender. HLA-B*57:01 was not identified in the study cohort. The apparently high prevalence of APOC3 T-455CC genotype needs confirmation with a larger samples size and triglyceride measurements to support screening of patients to pre-empt HAART associated lipid disorders. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle The Dipeptidyl Peptidase-4 Inhibitor Sitagliptin Protects against Dyslipidemia-Related Kidney Injury in Apolipoprotein E Knockout Mice
Int. J. Mol. Sci. 2014, 15(7), 11416-11434; doi:10.3390/ijms150711416
Received: 1 April 2014 / Revised: 16 June 2014 / Accepted: 20 June 2014 / Published: 26 June 2014
Cited by 6 | PDF Full-text (5563 KB) | HTML Full-text | XML Full-text
Abstract
The goal of this study was to investigate the possible protective effects of sitagliptin against dyslipidemia-related kidney injury in apolipoprotein E knockout (apoE−/−) mice. Eight-week-old male apoE−/− mice were randomized to receive either a high fat diet (HFD, apoE−/−
[...] Read more.
The goal of this study was to investigate the possible protective effects of sitagliptin against dyslipidemia-related kidney injury in apolipoprotein E knockout (apoE−/−) mice. Eight-week-old male apoE−/− mice were randomized to receive either a high fat diet (HFD, apoE−/− group) or HFD mixed with sitagliptin (sita + apoE−/− group) for 16 weeks. A control group of age- and gender-matched C57BL/6J mice were fed a HFD. The apoE−/− group exhibited increases in body weight and serum lipid levels in addition to high-density lipoprotein, and increases in 24-h urinary 8-hydroxy-2-deoxyguanosine and albuminuria excretion. Decreased insulin sensitivity was also observed in the apoE−/− group. These mice additionally contained enlargements of the glomerular mesangial matrix area, lipid deposition area, and renal interstitium collagen area. The apoE−/− group also demonstrated down-regulation of phosphorylated AMP-activated protein kinase (AMPK), increases in renal mRNA expression of transforming growth factor-beta 1 (TGF-β1) and fibronectin (FN), and increased protein expression of Akt, TGF-β1, FN and p38/ERK mitogen-activated protein kinase (MAPK). Sitagliptin treatment successfully ameliorated all the deleterious effects of dyslipidemia tested. To our knowledge, this is the first time that sitagliptin has been shown to reverse the renal dysfunction and structural damage induced by dyslipidemia in apoE−/− mice. Our results suggest that the renoprotective mechanism of sitagliptin may be due to a reduction in Akt levels, a restoration of AMPK activity, and inhibition of TGF-β1, FN, and p38/ERK MAPK signaling pathways. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
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Open AccessArticle Structural Characterization and Antioxidant Activities of Polysaccharides Extracted from the Pulp of Elaeagnus angustifolia L.
Int. J. Mol. Sci. 2014, 15(7), 11446-11455; doi:10.3390/ijms150711446
Received: 2 April 2014 / Revised: 12 May 2014 / Accepted: 28 May 2014 / Published: 26 June 2014
Cited by 8 | PDF Full-text (1113 KB) | HTML Full-text | XML Full-text
Abstract
In this study, two polysaccharides (Elaeagnus angustifolia L. polysaccharide-1 (PEA-1) and PEA-2) were prepared from Elaeagnus angustifolia L. Then, the preliminary structure and antioxidant activities of all the samples were investigated. The results showed that the average molecular weights for PEA-1 and
[...] Read more.
In this study, two polysaccharides (Elaeagnus angustifolia L. polysaccharide-1 (PEA-1) and PEA-2) were prepared from Elaeagnus angustifolia L. Then, the preliminary structure and antioxidant activities of all the samples were investigated. The results showed that the average molecular weights for PEA-1 and PEA-2 were 9113 and 5020 Da, respectively. And, PEA-1 was mainly composed of rhamnose, xylose, mannose, glucose, and galactose, respectively. The components of PEA-2 were rhamnose, mannose, glucose, and galactose, respectively. Moreover, the Antioxidant assays demonstrated that PEA-1 possessed of strong free radicals scavenging activity and hydroxyl radicals scavenging activities, suggesting that PEA-1 could potentially be used as natural antioxidant. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
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Open AccessArticle The Influence of MgH2 on the Assessment of Electrochemical Data to Predict the Degradation Rate of Mg and Mg Alloys
Int. J. Mol. Sci. 2014, 15(7), 11456-11472; doi:10.3390/ijms150711456
Received: 9 April 2014 / Revised: 13 June 2014 / Accepted: 20 June 2014 / Published: 26 June 2014
Cited by 1 | PDF Full-text (1859 KB) | HTML Full-text | XML Full-text
Abstract
Mg and Mg alloys are becoming more and more of interest for several applications. In the case of biomaterial applications, a special interest exists due to the fact that a predictable degradation should be given. Various investigations were made to characterize and predict
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Mg and Mg alloys are becoming more and more of interest for several applications. In the case of biomaterial applications, a special interest exists due to the fact that a predictable degradation should be given. Various investigations were made to characterize and predict the corrosion behavior in vitro and in vivo. Mostly, the simple oxidation of Mg to Mg2+ ions connected with adequate hydrogen development is assumed, and the negative difference effect (NDE) is attributed to various mechanisms and electrochemical results. The aim of this paper is to compare the different views on the corrosion pathway of Mg or Mg alloys and to present a neglected pathway based on thermodynamic data as a guideline for possible reactions combined with experimental observations of a delay of visible hydrogen evolution during cyclic voltammetry. Various reaction pathways are considered and discussed to explain these results, like the stability of the Mg+ intermediate state, the stability of MgH2 and the role of hydrogen overpotential. Finally, the impact of MgH2 formation is shown as an appropriate base for the prediction of the degradation behavior and calculation of the corrosion rate of Mg and Mg alloys. Full article
(This article belongs to the Special Issue Biodegradable Magnesium Alloys and Implants)
Open AccessArticle Biochemical Alterations during the Obese-Aging Process in Female and Male Monosodium Glutamate (MSG)-Treated Mice
Int. J. Mol. Sci. 2014, 15(7), 11473-11494; doi:10.3390/ijms150711473
Received: 24 April 2014 / Revised: 11 June 2014 / Accepted: 12 June 2014 / Published: 27 June 2014
Cited by 4 | PDF Full-text (1438 KB) | HTML Full-text | XML Full-text
Abstract
Obesity, from children to the elderly, has increased in the world at an alarming rate over the past three decades, implying long-term detrimental consequences for individual’s health. Obesity and aging are known to be risk factors for metabolic disorder development, insulin resistance and
[...] Read more.
Obesity, from children to the elderly, has increased in the world at an alarming rate over the past three decades, implying long-term detrimental consequences for individual’s health. Obesity and aging are known to be risk factors for metabolic disorder development, insulin resistance and inflammation, but their relationship is not fully understood. Prevention and appropriate therapies for metabolic disorders and physical disabilities in older adults have become a major public health challenge. Hence, the aim of this study was to evaluate inflammation markers, biochemical parameters and glucose homeostasis during the obese-aging process, to understand the relationship between obesity and health span during the lifetime. In order to do this, the monosodium glutamate (MSG) obesity mice model was used, and data were evaluated at 4, 8, 12, 16 and 20 months in both female and male mice. Our results showed that obesity was a major factor contributing to premature alterations in MSG-treated mice metabolism; however, at older ages, obesity effects were attenuated and MSG-mice became more similar to normal mice. At a younger age (four months old), the Lee index, triglycerides, total cholesterol, TNF-α and transaminases levels increased; while adiponectin decreased and glucose tolerance and insulin sensitivity levels were remarkably altered. However, from 16 months old-on, the Lee index and TNF-α levels diminished significantly, while adiponectin increased, and glucose and insulin homeostasis was recovered. In summary, MSG-treated obese mice showed metabolic changes and differential susceptibility by gender throughout life and during the aging process. Understanding metabolic differences between genders during the lifespan will allow the discovery of specific preventive treatment strategies for chronic diseases and functional decline. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Exposure to AT1 Receptor Autoantibodies during Pregnancy Increases Susceptibility of the Maternal Heart to Postpartum Ischemia-Reperfusion Injury in Rats
Int. J. Mol. Sci. 2014, 15(7), 11495-11509; doi:10.3390/ijms150711495
Received: 10 March 2014 / Revised: 4 June 2014 / Accepted: 10 June 2014 / Published: 27 June 2014
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Abstract
Epidemiological studies have demonstrated that women with a history of preeclampsia have a two-fold increased risk of developing cardiovascular diseases in later life. It is not known whether or not this risk is associated with angiotensin II receptor type 1 autoantibody (AT1-AA), an
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Epidemiological studies have demonstrated that women with a history of preeclampsia have a two-fold increased risk of developing cardiovascular diseases in later life. It is not known whether or not this risk is associated with angiotensin II receptor type 1 autoantibody (AT1-AA), an agonist acting via activation of AT1 receptor (AT1R), which is believed to be involved in the pathogenesis of preeclampsia. The objective of the present study was to confirm the hypothesis that AT1-AA exposure during pregnancy may change the maternal cardiac structure and increase the susceptibility of the postpartum heart to ischemia/reperfusion injury (IRI). In the present study, we first established a preeclampsia rat model by intravenous injection of AT1-AA extracted from the plasma of rats immunized with AT1R, observed the susceptibility of the postpartum maternal heart to IRI at 16 weeks postpartum using the Langendorff preparation, and examined the cardiac structure using light and transmission electron microscopy. The modeled animals presented with symptoms very similar to the clinical symptoms of human preeclampsia during pregnancy, including hypertension and proteinuria. The left ventricular weight (LVW) and left ventricular mass index (LVMI) in AT1-AA treatment group were significantly increased as compared with those of the control group (p < 0.01), although there was no significant difference in final weight between the two groups. AT1-AA acting on AT1R not only induced myocardial cell hypertrophy, mitochondrial swelling, cristae disorganization and collagen accumulation in the interstitium but affected the left ventricular (LV) function and delayed recovery from IRI. In contrast, co-treatment with AT1-AA + losartan completely blocked AT1-AA-induced changes in cardiac structure and function. These data indicate that the presence of AT1-AA during pregnancy was strongly associated with the markers of LV geometry changes and remodeling, and increased the cardiac susceptibility to IRI in later life of postpartum maternal rats. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Chrysin, Apigenin and Acacetin Inhibit Tumor Necrosis Factor-Related Apoptosis—Inducing Ligand Receptor-1 (TRAIL-R1) on Activated RAW264.7 Macrophages
Int. J. Mol. Sci. 2014, 15(7), 11510-11522; doi:10.3390/ijms150711510
Received: 14 April 2014 / Revised: 15 May 2014 / Accepted: 10 June 2014 / Published: 27 June 2014
Cited by 6 | PDF Full-text (1343 KB) | HTML Full-text | XML Full-text
Abstract
Expression level of Tumor Necrosis Factor—related apoptosis—inducing ligand (TRAIL) receptors is one of the most important factors of TRAIL-mediated apoptosis in cancer cells. We here report for the first time data concerning TRAIL-R1 and TRAIL-R2 receptor expression on RAW264.7 macrophages. Three substances belonging
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Expression level of Tumor Necrosis Factor—related apoptosis—inducing ligand (TRAIL) receptors is one of the most important factors of TRAIL-mediated apoptosis in cancer cells. We here report for the first time data concerning TRAIL-R1 and TRAIL-R2 receptor expression on RAW264.7 macrophages. Three substances belonging to flavones: chrysin, apigenin and acacetin which differ from their substituents at the 4' position in the phenyl ring were used in assays because of the variety of biological activities (e.g., anticancer activity) of the polyphenol compounds. The expression of TRAIL-R1 and TRAIL-R2 death receptors on non-stimulated and LPS (lipopolysaccharide)-stimulated macrophages was determined using flow cytometry. We demonstrate that RAW264.7 macrophages exhibit TRAIL-R1 surface expression and that the tested compounds: chrysin, apigenin and acacetin can inhibit TRAIL-R1 death receptor expression level on macrophages. Full article
(This article belongs to the Special Issue Bioactive Phenolics and Polyphenols)
Open AccessArticle Phosphorylation Stoichiometries of Human Eukaryotic Initiation Factors
Int. J. Mol. Sci. 2014, 15(7), 11523-11538; doi:10.3390/ijms150711523
Received: 20 March 2014 / Revised: 11 April 2014 / Accepted: 29 April 2014 / Published: 27 June 2014
Cited by 4 | PDF Full-text (821 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Eukaryotic translation initiation factors are the principal molecular effectors regulating the process converting nucleic acid to functional protein. Commonly referred to as eIFs (eukaryotic initiation factors), this suite of proteins is comprised of at least 25 individual subunits that function in a coordinated,
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Eukaryotic translation initiation factors are the principal molecular effectors regulating the process converting nucleic acid to functional protein. Commonly referred to as eIFs (eukaryotic initiation factors), this suite of proteins is comprised of at least 25 individual subunits that function in a coordinated, regulated, manner during mRNA translation. Multiple facets of eIF regulation have yet to be elucidated; however, many of the necessary protein factors are phosphorylated. Herein, we have isolated, identified and quantified phosphosites from eIF2, eIF3, and eIF4G generated from log phase grown HeLa cell lysates. Our investigation is the first study to globally quantify eIF phosphosites and illustrates differences in abundance of phosphorylation between the residues of each factor. Thus, identification of those phosphosites that exhibit either high or low levels of phosphorylation under log phase growing conditions may aid researchers to concentrate their investigative efforts to specific phosphosites that potentially harbor important regulatory mechanisms germane to mRNA translation. Full article
(This article belongs to the Special Issue Mass Spectrometry Application in Biology) Print Edition available
Open AccessArticle Up-Regulated FASN Expression Promotes Transcoelomic Metastasis of Ovarian Cancer Cell through Epithelial-Mesenchymal Transition
Int. J. Mol. Sci. 2014, 15(7), 11539-11554; doi:10.3390/ijms150711539
Received: 30 April 2014 / Revised: 17 June 2014 / Accepted: 20 June 2014 / Published: 27 June 2014
Cited by 8 | PDF Full-text (1937 KB) | HTML Full-text | XML Full-text
Abstract
Fatty acid synthase (FASN), responsible for the de novo synthesis of fatty acids, has been shown to act as an oncogene in various human cancers. However, the mechanisms by which FASN favors the progression of ovarian carcinoma remain unknown. In this study, we
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Fatty acid synthase (FASN), responsible for the de novo synthesis of fatty acids, has been shown to act as an oncogene in various human cancers. However, the mechanisms by which FASN favors the progression of ovarian carcinoma remain unknown. In this study, we evaluated FASN expression in ovarian cancer and investigated how FASN regulates the aggressiveness of ovarian cancer cells. Our results show that increased FASN is associated with the peritoneal metastasis of ovarian cancers. Over-expression of FASN results in a significant increase of tumor burden in peritoneal dissemination, accompanied by augment in cellular colony formation and metastatic ability. Correspondingly, FASN knockdown using RNA interference in ovarian cancer cells inhibits the migration in vitro and experimental peritoneal dissemination in vivo. Mechanistic studies reveal that FASN promotes Epithelial-mesenchymal Transition (EMT) via a transcriptional regulation of E-cadherin and N-cadherin, which is also confirmed by luciferase promoter activity analysis. Taken together, our work demonstrates that FASN promotes the peritoneal dissemination of ovarian cancer cells, at least in part through the induction of EMT. These findings suggest that FASN plays a critical role in the peritoneal metastasis of ovarian cancer. Targeting de novo lipogenesis may have a therapeutic potential for advanced ovarian cancer. Full article
(This article belongs to the Special Issue Advances in Molecular Oncology 2014)
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Open AccessArticle Critical Role for the Protons in FRTL-5 Thyroid Cells: Nuclear Sphingomyelinase Induced-Damage
Int. J. Mol. Sci. 2014, 15(7), 11555-11565; doi:10.3390/ijms150711555
Received: 7 May 2014 / Revised: 20 June 2014 / Accepted: 24 June 2014 / Published: 27 June 2014
Cited by 1 | PDF Full-text (1085 KB) | HTML Full-text | XML Full-text
Abstract
Proliferating thyroid cells are more sensitive to UV-C radiations than quiescent cells. The effect is mediated by nuclear phosphatidylcholine and sphingomyelin metabolism. It was demonstrated that proton beams arrest cell growth and stimulate apoptosis but until now there have been no indications in
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Proliferating thyroid cells are more sensitive to UV-C radiations than quiescent cells. The effect is mediated by nuclear phosphatidylcholine and sphingomyelin metabolism. It was demonstrated that proton beams arrest cell growth and stimulate apoptosis but until now there have been no indications in the literature about their possible mechanism of action. Here we studied the effect of protons on FRTL-5 cells in culture. We showed that proton beams stimulate slightly nuclear neutral sphingomyelinase activity and inhibit nuclear sphingomyelin-synthase activity in quiescent cells whereas stimulate strongly nuclear neutral sphingomyelinase activity and do not change nuclear sphingomyelin-synthase activity in proliferating cells. The study of neutral sphingomyelinase/sphingomyelin-synthase ratio, a marker of functional state of the cells, indicated that proton beams induce FRTL-5 cells in a proapoptotic state if the cells are quiescent and in an initial apoptotic state if the cells are proliferating. The changes of cell life are accompanied by a decrease of nuclear sphingomyelin and increase of bax protein. Full article
(This article belongs to the collection Radiation Toxicity in Cells)
Open AccessArticle Two Diterpenoids and a Cyclopenta[c]pyridine Derivative from Roots of Salvia digitaloids
Int. J. Mol. Sci. 2014, 15(7), 11566-11577; doi:10.3390/ijms150711566
Received: 2 April 2014 / Revised: 28 May 2014 / Accepted: 29 May 2014 / Published: 27 June 2014
Cited by 3 | PDF Full-text (305 KB) | HTML Full-text | XML Full-text
Abstract
Two new glucosides, salviadigitoside A (1) and salviatalin A-19-O-β-glucoside (2), belonging to the salviatalin type diterpenoids, and a new cyclopenta[c]pyridine, salviadiginine A (3), were isolated from the roots of Salvia digitaloids. Structures
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Two new glucosides, salviadigitoside A (1) and salviatalin A-19-O-β-glucoside (2), belonging to the salviatalin type diterpenoids, and a new cyclopenta[c]pyridine, salviadiginine A (3), were isolated from the roots of Salvia digitaloids. Structures of these compounds were determined on the basis of spectroscopic analysis. In addition, compounds 13 were evaluated for their anti-inflammatory activity, but the results showed a weak anti-inflammatory activity. Full article
(This article belongs to the Section Green Chemistry)
Open AccessArticle Conservation Genetics of an Endangered Lady’s Slipper Orchid: Cypripedium japonicum in China
Int. J. Mol. Sci. 2014, 15(7), 11578-11596; doi:10.3390/ijms150711578
Received: 22 April 2014 / Revised: 30 May 2014 / Accepted: 10 June 2014 / Published: 30 June 2014
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Abstract
Knowledge about the population genetic variation of the endangered orchid, Cypripedium japonicum, is conducive to the development of conservation strategies. Here, we examined the levels and partitioning of inter-simple sequence repeat (ISSR) diversity (109 loci) in five populations of this orchid to
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Knowledge about the population genetic variation of the endangered orchid, Cypripedium japonicum, is conducive to the development of conservation strategies. Here, we examined the levels and partitioning of inter-simple sequence repeat (ISSR) diversity (109 loci) in five populations of this orchid to gain insight into its genetic variation and population structure in Eastern and Central China. It harbored considerably lower levels of genetic diversity both at the population (percentage of polymorphic loci (PPL) = 11.19%, Nei’s gene diversity (H) = 0.0416 and Shannon’s information index (I) = 0.0613) and species level (PPL = 38.53%, H = 0.1273 and I = 0.1928) and a significantly higher degree of differentiation among populations (the proportion of the total variance among populations (Φpt) = 0.698) than those typical of ISSR-based studies in other orchid species. Furthermore, the Nei’s genetic distances between populations were independent of the corresponding geographical distances. Two main clusters are shown in an arithmetic average (UPGMA) dendrogram, which is in agreement with the results of principal coordinate analysis (PCoA) analysis and the STRUCTURE program. In addition, individuals within a population were more similar to each other than to those in other populations. Based on the genetic data and our field survey, the development of conservation management for this threatened orchid should include habitat protection, artificial gene flow and ex situ measures. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Characterization of the Zebrafish Homolog of Zipper Interacting Protein Kinase
Int. J. Mol. Sci. 2014, 15(7), 11597-11613; doi:10.3390/ijms150711597
Received: 20 May 2014 / Revised: 12 June 2014 / Accepted: 23 June 2014 / Published: 30 June 2014
PDF Full-text (11322 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Zipper-interacting protein kinase (ZIPK) is a conserved vertebrate-specific regulator of actomyosin contractility in smooth muscle and non-muscle cells. Murine ZIPK has undergone an unusual divergence in sequence and regulation compared to other ZIPK orthologs. In humans, subcellular localization is controlled by phosphorylation of
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Zipper-interacting protein kinase (ZIPK) is a conserved vertebrate-specific regulator of actomyosin contractility in smooth muscle and non-muscle cells. Murine ZIPK has undergone an unusual divergence in sequence and regulation compared to other ZIPK orthologs. In humans, subcellular localization is controlled by phosphorylation of threonines 299 and 300. In contrast, ZIPK subcellular localization in mouse and rat is controlled by interaction with PAR-4. We carried out a comparative biochemical characterization of the regulation of the zebrafish ortholog of ZIPK. Like the human orthologs zebrafish ZIPK undergoes nucleocytoplasmic-shuttling and is abundant in the cytoplasm, unlike the primarily nuclear rat ZIPK. Rat ZIPK, but not human or zebrafish ZIPK, interacts with zebrafish PAR-4. Mutation of the conserved residues required for activation of the mammalian orthologs abrogated activity of the zebrafish ZIPK. In contrast to the human ortholog, mutation of threonine 299 and 300 in the zebrafish ZIPK has no effect on the activity or subcellular localization. Thus, we found that zebrafish ZIPK functions in a manner most similar to the human ZIPK and quite distinct from murine orthologs, yet the regulation of subcellular localization is not conserved. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Mitochondrial Control Region Variability in Mytilus galloprovincialis Populations from the Central-Eastern Mediterranean Sea
Int. J. Mol. Sci. 2014, 15(7), 11614-11625; doi:10.3390/ijms150711614
Received: 15 May 2014 / Revised: 17 June 2014 / Accepted: 23 June 2014 / Published: 30 June 2014
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Abstract
The variable domain 1 (VD1) domain of the control region and a small segment of the rrnaL gene of the F mtDNA type were sequenced and analyzed in 174 specimens of Mytilus galloprovincialis. Samples were collected from eight locations in four Central-Eastern
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The variable domain 1 (VD1) domain of the control region and a small segment of the rrnaL gene of the F mtDNA type were sequenced and analyzed in 174 specimens of Mytilus galloprovincialis. Samples were collected from eight locations in four Central-Eastern (CE) Mediterranean countries (Italy, Croatia, Greece and Turkey). A new primer, specific for the F mtDNA type, was designed for the sequencing procedure. In total 40 different haplotypes were recorded, 24 of which were unique. Aside from the two populations situated in Thermaikos gulf (Northern Aegean, Greece), relatively high levels of haplotype and nucleotide diversity were estimated for both Central and Eastern Mediterranean populations. Eight out of the 40 haplotypes were shared by at least three populations while two of them were found in all populations. ΦST and cluster analysis revealed lack of structuring among CE Mediterranean populations with the exception of those located at the Sea of Marmara and Croatian coast which were highly differentiated. Apart from the species’ inherit dispersal ability, anthropogenic activities, such as the repeated translocations of mussel spat, seem to have played an important role in shaping the current genetic population structure of CE M. galloprovincialis mussels. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessCommunication Immunomodulating Activity of Aronia melanocarpa Polyphenols
Int. J. Mol. Sci. 2014, 15(7), 11626-11636; doi:10.3390/ijms150711626
Received: 19 May 2014 / Revised: 18 June 2014 / Accepted: 20 June 2014 / Published: 30 June 2014
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Abstract
The immunomodulating effects of isolated proanthocyanidin-rich fractions, procyanidins C1, B5 and B2 and anthocyanins of Aronia melanocarpa were investigated. In this work, the complement-modulating activities, the inhibitory activities on nitric oxide (NO) production in LPS-induced RAW 264.7 macrophages and effects on cell viability
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The immunomodulating effects of isolated proanthocyanidin-rich fractions, procyanidins C1, B5 and B2 and anthocyanins of Aronia melanocarpa were investigated. In this work, the complement-modulating activities, the inhibitory activities on nitric oxide (NO) production in LPS-induced RAW 264.7 macrophages and effects on cell viability of these polyphenols were studied. Several of the proanthocyanidin-rich fractions, the procyanidins C1, B5 and B2 and the cyanidin aglycone possessed strong complement-fixing activities. Cyanidin 3-glucoside possessed stronger activity than the other anthocyanins. Procyanidins C1, B5 and B2 and proanthocyanidin-rich fractions having an average degree of polymerization (PD) of 7 and 34 showed inhibitory activities on NO production in LPS-stimulated RAW 264.7 mouse macrophages. All, except for the fraction containing proanthocyanidins with PD 34, showed inhibitory effects without affecting cell viability. This study suggests that polyphenolic compounds of A. melanocarpa may have beneficial effects as immunomodulators and anti-inflammatory agents. Full article
(This article belongs to the Special Issue Bioactive Phenolics and Polyphenols)
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Open AccessArticle Supraspliceosomes at Defined Functional States Portray the Pre-Assembled Nature of the Pre-mRNA Processing Machine in the Cell Nucleus
Int. J. Mol. Sci. 2014, 15(7), 11637-11664; doi:10.3390/ijms150711637
Received: 10 April 2014 / Revised: 5 June 2014 / Accepted: 18 June 2014 / Published: 30 June 2014
Cited by 4 | PDF Full-text (2835 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
When isolated from mammalian cell nuclei, all nuclear pre-mRNAs are packaged in multi-subunit large ribonucleoprotein complexes—supraspliceosomes—composed of four native spliceosomes interconnected by the pre-mRNA. Supraspliceosomes contain all five spliceosomal U snRNPs, together with other splicing factors, and are functional in splicing. Supraspliceosomes studied
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When isolated from mammalian cell nuclei, all nuclear pre-mRNAs are packaged in multi-subunit large ribonucleoprotein complexes—supraspliceosomes—composed of four native spliceosomes interconnected by the pre-mRNA. Supraspliceosomes contain all five spliceosomal U snRNPs, together with other splicing factors, and are functional in splicing. Supraspliceosomes studied thus far represent the steady-state population of nuclear pre-mRNAs that were isolated at different stages of the splicing reaction. To analyze specific splicing complexes, here, we affinity purified Pseudomonas aeruginosa phage 7 (PP7)-tagged splicing complexes assembled in vivo on Adenovirus Major Late (AdML) transcripts at specific functional stages, and characterized them using molecular techniques including mass spectrometry. First, we show that these affinity purified splicing complexes assembled on PP7-tagged AdML mRNA or on PP7-tagged AdML pre-mRNA are assembled in supraspliceosomes. Second, similar to the general population of supraspliceosomes, these defined supraspliceosomes populations are assembled with all five U snRNPs at all splicing stages. This study shows that dynamic changes in base-pairing interactions of U snRNA:U snRNA and U snRNA:pre-mRNA that occur in vivo during the splicing reaction do not require changes in U snRNP composition of the supraspliceosome. Furthermore, there is no need to reassemble a native spliceosome for the splicing of each intron, and rearrangements of the interactions will suffice. Full article
(This article belongs to the Special Issue Pre-mRNA Splicing)
Open AccessArticle Protein Tyrosine Kinase 7 (PTK7) as a Predictor of Lymph Node Metastases and a Novel Prognostic Biomarker in Patients with Prostate Cancer
Int. J. Mol. Sci. 2014, 15(7), 11665-11677; doi:10.3390/ijms150711665
Received: 27 April 2014 / Revised: 28 May 2014 / Accepted: 12 June 2014 / Published: 1 July 2014
Cited by 8 | PDF Full-text (1041 KB) | HTML Full-text | XML Full-text
Abstract
Protein tyrosine kinase 7 (PTK7) has been studied in various tumors, but its role in prostate cancer remains unknown. This study is aimed to investigate the prognostic and predictive significance of PTK7 in patients with prostate cancer. PTK7 expression was evaluated by real-time
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Protein tyrosine kinase 7 (PTK7) has been studied in various tumors, but its role in prostate cancer remains unknown. This study is aimed to investigate the prognostic and predictive significance of PTK7 in patients with prostate cancer. PTK7 expression was evaluated by real-time reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis in 20 pairs of benign prostatic hyperplasia specimens and prostate cancer specimens. Then, we examined the immunohistochemical expression of PTK7 in 180 prostate cancer specimens and evaluated its clinical significances. Elevated PTK7 expression was significantly associated with lymph node metastases, seminal vesicle invasion, prostate cancer stage, the higher preoperative prostate-specific antigen, the higher Gleason score, angiolymphatic invasion, and biochemical recurrence. The results revealed that the overexpression of PTK7 in prostate cancer was an independent prognostic factor for poor overall survival and biochemical recurrence-free survival. The present data provide evidence that PTK7 predicts lymph node metastasis and poor overall survival and biochemical recurrence-free survival, highlighting its potential function as a therapeutic target for prostate cancer. Full article
(This article belongs to the Special Issue Molecular Research in Urology 2014)
Open AccessArticle The Involvement of miR-23a/APAF1 Regulation Axis in Colorectal Cancer
Int. J. Mol. Sci. 2014, 15(7), 11713-11729; doi:10.3390/ijms150711713
Received: 13 May 2014 / Revised: 2 June 2014 / Accepted: 4 June 2014 / Published: 2 July 2014
Cited by 6 | PDF Full-text (940 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Recent advances in microRNAome have made microRNAs (miRNAs) a compelling novel class of biomarker in cancer biology. In the present study, the role of miR-23a in the carcinogenesis of colorectal cancer (CRC) was investigated. Cell viability, apoptosis, and caspase 3/7 activation analyses were
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Recent advances in microRNAome have made microRNAs (miRNAs) a compelling novel class of biomarker in cancer biology. In the present study, the role of miR-23a in the carcinogenesis of colorectal cancer (CRC) was investigated. Cell viability, apoptosis, and caspase 3/7 activation analyses were conducted to determine the potentiality of apoptosis resistance function of miR-23a in CRC. Luciferase assay was performed to verify a putative target site of miR-23a in the 3'-UTR of apoptosis protease activating factor 1 (APAF1) mRNA. The expression levels of miR-23a and APAF1 in CRC cell lines (SW480 and SW620) and clinical samples were assessed using reverse transcription-quantitative real-time PCR (RT-qPCR) and Western blot. We found that the inhibition of miR-23a in SW480 and SW620 cell lines resulted in significant reduction of cell viability and promotion of cell apoptosis. Moreover, miR-23a up-regulation was coupled with APAF1 down-regulation in CRC tissue samples. Taken together, miR-23a was identified to regulate apoptosis in CRC. Our study highlights the potential application of miR-23a/APAF1 regulation axis in miRNA-based therapy and prognostication. Full article
(This article belongs to the Special Issue Regulation by non-coding RNAs 2013)
Open AccessArticle Biodegradable and Multifunctional Polymer Micro-Tubes for Targeting Photothermal Therapy
Int. J. Mol. Sci. 2014, 15(7), 11730-11741; doi:10.3390/ijms150711730
Received: 2 May 2014 / Revised: 30 May 2014 / Accepted: 24 June 2014 / Published: 2 July 2014
Cited by 1 | PDF Full-text (1567 KB) | HTML Full-text | XML Full-text
Abstract
We describe an innovative form of polymer micro-tubes with diverse functions including biodegradation, magnetic manipulation, and photothermal effect that employs and activates photothermal therapy to target cancer cells. The micro-tube comprised soybean protein isolate, poly-l-glutamic acid, magnetite nanoparticles, plus gold nanoparticles. Through electrostatic
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We describe an innovative form of polymer micro-tubes with diverse functions including biodegradation, magnetic manipulation, and photothermal effect that employs and activates photothermal therapy to target cancer cells. The micro-tube comprised soybean protein isolate, poly-l-glutamic acid, magnetite nanoparticles, plus gold nanoparticles. Through electrostatic force, these components, with opposite charges, formed pairs of layers in the pores of the template, various bilayers of soybean protein isolate and poly-l-glutamic acid served as the biodegradable building wall to each micro-tube. The layers of magnetite nanoparticle functionalized micro-tubes enabled the micro-tube manipulate to target the cancer cells by using an external magnetic field. The photo-thermal effect of the layer of gold nanoparticles on the outer surface of the micro-tubes, when under irradiation and when brought about by the near infrared radiation, elevated each sample’s temperature. In addition, and when under the exposure of the near infrared radiation, the elevated temperature of the suspension of the micro-tubes, likewise with a concentration of 0.2 mg/mL, and similarly with a power of 2 W and as well maintained for 10 min, elevated the temperature of the suspension beyond 42 °C. Such temperatures induced apoptosis of target cancer cells through the effect of photothermal therapy. The findings assert that structured micro-tubes have a promising application as a photothermal agent. From this assertion, the implications are that this multifunctional agent will significantly improve the methodology for cancer diagnosis and therapy. Full article
(This article belongs to the Section Material Sciences and Nanotechnology)
Open AccessArticle Effects of Silica and Titanium Oxide Particles on a Human Neural Stem Cell Line: Morphology, Mitochondrial Activity, and Gene Expression of Differentiation Markers
Int. J. Mol. Sci. 2014, 15(7), 11742-11759; doi:10.3390/ijms150711742
Received: 13 March 2014 / Revised: 25 May 2014 / Accepted: 16 June 2014 / Published: 2 July 2014
Cited by 6 | PDF Full-text (2136 KB) | HTML Full-text | XML Full-text
Abstract
Several in vivo studies suggest that nanoparticles (smaller than 100 nm) have the ability to reach the brain tissue. Moreover, some nanoparticles can penetrate into the brains of murine fetuses through the placenta by intravenous administration to pregnant mice. However, it is not
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Several in vivo studies suggest that nanoparticles (smaller than 100 nm) have the ability to reach the brain tissue. Moreover, some nanoparticles can penetrate into the brains of murine fetuses through the placenta by intravenous administration to pregnant mice. However, it is not clear whether the penetrated nanoparticles affect neurogenesis or brain function. To evaluate its effects on neural stem cells, we assayed a human neural stem cell (hNSCs) line exposed in vitro to three types of silica particles (30 nm, 70 nm, and <44 µm) and two types of titanium oxide particles (80 nm and < 44 µm). Our results show that hNSCs aggregated and exhibited abnormal morphology when exposed to the particles at concentrations = 0.1 mg/mL for 7 days. Moreover, all the particles affected the gene expression of Nestin (stem cell marker) and neurofilament heavy polypeptide (NF-H, neuron marker) at 0.1 mg/mL. In contrast, only 30-nm silica particles at 1.0 mg/mL significantly reduced mitochondrial activity. Notably, 30-nm silica particles exhibited acute membrane permeability at concentrations =62.5 µg/mL in 24 h. Although these concentrations are higher than the expected concentrations of nanoparticles in the brain from in vivo experiments in a short period, these thresholds may indicate the potential toxicity of accumulated particles for long-term usage or continuous exposure. Full article
(This article belongs to the Special Issue Bioactive Nanoparticles 2014)
Open AccessArticle Paeonol Suppresses Chondrosarcoma Metastasis through Up-Regulation of miR-141 by Modulating PKCδ and c-Src Signaling Pathway
Int. J. Mol. Sci. 2014, 15(7), 11760-11772; doi:10.3390/ijms150711760
Received: 16 April 2014 / Revised: 10 June 2014 / Accepted: 13 June 2014 / Published: 2 July 2014
Cited by 7 | PDF Full-text (1384 KB) | HTML Full-text | XML Full-text
Abstract
Chondrosarcoma, a primary malignant bone cancer, has potential for local invasion and distant metastasis, especially to the lungs. Patients diagnosed with it show poor prognosis. Paeonol (2'-hydroxy-4'-methoxyacetophenone), the main active compound of traditional Chinese remedy Paeonia lactiflora Pallas, exhibits anti-inflammatory and anti-tumor activity;
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Chondrosarcoma, a primary malignant bone cancer, has potential for local invasion and distant metastasis, especially to the lungs. Patients diagnosed with it show poor prognosis. Paeonol (2'-hydroxy-4'-methoxyacetophenone), the main active compound of traditional Chinese remedy Paeonia lactiflora Pallas, exhibits anti-inflammatory and anti-tumor activity; whether paeonol regulates metastatic chondrosarcoma is largely unknown. Here, we find paeonol do not increase apoptosis. By contrast, at non-cytotoxic concentrations, paeonol suppresses migration and invasion of chondrosarcoma cells. We also demonstrate paeonol enhancing miR-141 expression and miR-141 inhibitor reversing paeonol-inhibited cell motility; paeonol also reduces protein kinase C (PKC)d and c-Src kinase activity. Since paeonol inhibits migration and invasion of human chondrosarcoma via up-regulation of miR-141 via PKCd and c-Src pathways, it thus might be a novel anti-metastasis agent for treatment of metastatic chondrosarcoma. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle TupA: A Tungstate Binding Protein in the Periplasm of Desulfovibrio alaskensis G20
Int. J. Mol. Sci. 2014, 15(7), 11783-11798; doi:10.3390/ijms150711783
Received: 31 March 2014 / Revised: 29 May 2014 / Accepted: 29 May 2014 / Published: 2 July 2014
PDF Full-text (597 KB) | HTML Full-text | XML Full-text
Abstract
The TupABC system is involved in the cellular uptake of tungsten and belongs to the ABC (ATP binding cassette)-type transporter systems. The TupA component is a periplasmic protein that binds tungstate anions, which are then transported through the membrane by the TupB component
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The TupABC system is involved in the cellular uptake of tungsten and belongs to the ABC (ATP binding cassette)-type transporter systems. The TupA component is a periplasmic protein that binds tungstate anions, which are then transported through the membrane by the TupB component using ATP hydrolysis as the energy source (the reaction catalyzed by the ModC component). We report the heterologous expression, purification, determination of affinity binding constants and crystallization of the Desulfovibrio alaskensis G20 TupA. The tupA gene (locus tag Dde_0234) was cloned in the pET46 Enterokinase/Ligation-Independent Cloning (LIC) expression vector, and the construct was used to transform BL21 (DE3) cells. TupA expression and purification were optimized to a final yield of 10 mg of soluble pure protein per liter of culture medium. Native polyacrylamide gel electrophoresis was carried out showing that TupA binds both tungstate and molybdate ions and has no significant interaction with sulfate, phosphate or perchlorate. Quantitative analysis of metal binding by isothermal titration calorimetry was in agreement with these results, but in addition, shows that TupA has higher affinity to tungstate than molybdate. The protein crystallizes in the presence of 30% (w/v) polyethylene glycol 3350 using the hanging-drop vapor diffusion method. The crystals diffract X-rays beyond 1.4 Å resolution and belong to the P21 space group, with cell parameters a = 52.25 Å, b = 42.50 Å, c = 54.71 Å, β = 95.43°. A molecular replacement solution was found, and the structure is currently under refinement. Full article
(This article belongs to the collection Proteins and Protein-Ligand Interactions)
Open AccessArticle Base Flip in DNA Studied by Molecular Dynamics Simulationsof Differently-Oxidized Forms of Methyl-Cytosine
Int. J. Mol. Sci. 2014, 15(7), 11799-11816; doi:10.3390/ijms150711799
Received: 30 May 2014 / Revised: 23 June 2014 / Accepted: 25 June 2014 / Published: 3 July 2014
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Abstract
Distortions in the DNA sequence, such as damage or mispairs, are specifically recognized and processed by DNA repair enzymes. Many repair proteins and, in particular, glycosylases flip the target base out of the DNA helix into the enzyme’s active site. Our molecular dynamics
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Distortions in the DNA sequence, such as damage or mispairs, are specifically recognized and processed by DNA repair enzymes. Many repair proteins and, in particular, glycosylases flip the target base out of the DNA helix into the enzyme’s active site. Our molecular dynamics simulations of DNA with intact and damaged (oxidized) methyl-cytosine show that the probability of being flipped is similar for damaged and intact methyl-cytosine. However, the accessibility of the different 5-methyl groups allows direct discrimination of the oxidized forms. Hydrogen-bonded patterns that vary between methyl-cytosine forms carrying a carbonyl oxygen atom are likely to be detected by the repair enzymes and may thus help target site recognition. Full article
(This article belongs to the Special Issue Identification and Roles of the Structure of DNA)
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Open AccessArticle Inhibition of TRPM7 Channels Reduces Degranulation and Release of Cytokines in Rat Bone Marrow-Derived Mast Cells
Int. J. Mol. Sci. 2014, 15(7), 11817-11831; doi:10.3390/ijms150711817
Received: 18 May 2014 / Revised: 9 June 2014 / Accepted: 19 June 2014 / Published: 3 July 2014
Cited by 4 | PDF Full-text (2491 KB) | HTML Full-text | XML Full-text
Abstract
Background: mast cells play an important role in airway inflammation in asthma. The transient receptor potential melastatin-like 7 (TRPM7) channel is expressed in primary human lung mast cells and plays a critical role for cell survival. This study aimed to investigate the role
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Background: mast cells play an important role in airway inflammation in asthma. The transient receptor potential melastatin-like 7 (TRPM7) channel is expressed in primary human lung mast cells and plays a critical role for cell survival. This study aimed to investigate the role of TRPM7 on degranulation and release of cytokines in rat bone marrow-derived mast cells (BMMCs). Methods: the expression levels of TRPM7 were observed by immunocytochemistry and RT-PCR between normal and asthmatic rat BMMCs. TRPM7-specific shRNA and 2-aminoethoxydiphenyl borate (2-APB) and specific shTRPM7 were used to inhibit the function of TRPM7. Degranulation levels were analyzed by beta-hexosaminidase assay. Histamine, TNF-α, IL-6 and IL-13 levels were measured by ELISA. Results: the expression of TRPM7 was significantly higher in asthmatic rat BMMCs than in the normal control group. After application of 2-APB and down-regulation of TRPM7, the beta-hexosaminidase activity and secretion of histamine, IL-6, IL-13 and TNF-α were significantly decreased in the asthmatic group compared to the control group. Conclusion: this study indicates that TRPM7 channels may be involved in the process of degranulation and release of cytokines in rat bone marrow-derived mast cells. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Quantitative Trait Loci Mapping for Bacterial Blight Resistance in Rice Using Bulked Segregant Analysis
Int. J. Mol. Sci. 2014, 15(7), 11847-11861; doi:10.3390/ijms150711847
Received: 15 May 2014 / Revised: 24 June 2014 / Accepted: 24 June 2014 / Published: 3 July 2014
Cited by 4 | PDF Full-text (1396 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Oryza meyeriana is highly resistant to rice bacterial blight (BB) and this resistance trait has been transferred to cultivated rice (O. sativa) using asymmetric somatic hybridization. However, no resistance genes have yet been cloned. In the present study, a progeny of
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Oryza meyeriana is highly resistant to rice bacterial blight (BB) and this resistance trait has been transferred to cultivated rice (O. sativa) using asymmetric somatic hybridization. However, no resistance genes have yet been cloned. In the present study, a progeny of the somatic hybridization with high BB resistance was crossed with a rice cultivar with high BB susceptibility to develop an F2 population. Using bulked segregant analysis (BSA), 17 polymorphic markers that were linked to rice BB resistance were obtained through scanning a total of 186 simple sequence repeats (SSR) and sequence-tagged site (STS) markers, evenly distributed on 12 chromosomes. A genetic linkage map was then constructed based on the 17 linkage markers and the F2 segregating population, which was followed by mapping for quantitative trait loci (QTLs) for BB resistance. Three QTLs were identified on chromosomes 1, 3 and 5, respectively, and the alleles of the resistant parent at any of the QTLs increased BB resistance. All of the three QTLs had a strong effect on resistance, explaining about 21.5%, 12.3% and 39.2% of the resistance variance, respectively. These QTLs were different from the loci of the BB resistance genes that have been identified in previous studies. The QTLs mapped in this work will facilitate the isolation of novel BB resistance genes and their utilization in rice resistance breeding. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
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Open AccessArticle Proanthocyanidin Accumulation and Biosynthesis Are Modulated by the Irrigation Regime in Tempranillo Seeds
Int. J. Mol. Sci. 2014, 15(7), 11862-11877; doi:10.3390/ijms150711862
Received: 6 May 2014 / Revised: 3 June 2014 / Accepted: 16 June 2014 / Published: 4 July 2014
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Abstract
The main effects of three different irrigation regimes, i.e., sustained deficit irrigation (SDI), regulated deficit irrigation (RDI) and non-irrigated (NI), on seed traits namely proanthocyanidins (PAs) were evaluated in the wine grape cultivar Aragonez (syn. Tempranillo) grown in Alentejo (Portugal) over two
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The main effects of three different irrigation regimes, i.e., sustained deficit irrigation (SDI), regulated deficit irrigation (RDI) and non-irrigated (NI), on seed traits namely proanthocyanidins (PAs) were evaluated in the wine grape cultivar Aragonez (syn. Tempranillo) grown in Alentejo (Portugal) over two growing seasons. Results showed that while the number of seeds per berry was not affected by water availability, seed fresh weight differed among treatments, the NI treatment exhibiting the lowest values. The biosynthetic pathway of flavanols appeared to be modified by the irrigation treatment, and several genes responsible for PA synthesis were up-regulated in the most stressed seeds (RDI and NI). However, this effect had no impact on PA content, suggesting the influence of other factors such as oxidation and/or degradation of PAs at late stages of maturation in grape seeds. The seeds’ non-enzymatic antioxidant capacities (oxygen radical absorbance capacity (ORAC) and hydroxyl radical adverting capacity (HORAC)) were modulated by water deficit and correlated well with PA content. The impact of irrigation strategy on PA biosynthesis, content, and anti-radical activity during seed ripening is discussed in the context of increasing interest in the role of PAs in the color and taste of wine, and the potential health benefits relating to their antioxidant capacity. Full article
(This article belongs to the Special Issue Bioactive Phenolics and Polyphenols)
Open AccessArticle Overcoming Hypoxic-Resistance of Tumor Cells to TRAIL-Induced Apoptosis through Melatonin
Int. J. Mol. Sci. 2014, 15(7), 11941-11956; doi:10.3390/ijms150711941
Received: 7 May 2014 / Revised: 13 June 2014 / Accepted: 18 June 2014 / Published: 4 July 2014
Cited by 5 | PDF Full-text (1637 KB) | HTML Full-text | XML Full-text
Abstract
A solid tumor is often exposed to hypoxic or anoxic conditions; thus, tumor cell responses to hypoxia are important for tumor progression as well as tumor therapy. Our previous studies indicated that tumor cells are resistant to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced
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A solid tumor is often exposed to hypoxic or anoxic conditions; thus, tumor cell responses to hypoxia are important for tumor progression as well as tumor therapy. Our previous studies indicated that tumor cells are resistant to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced cell apoptosis under hypoxic conditions. Melatonin inhibits cell proliferation in many cancer types and induces apoptosis in some particular cancer types. Here, we examined the effects of melatonin on hypoxic resistant cells against TRAIL-induced apoptosis and the possible mechanisms of melatonin in the hypoxic response. Melatonin treatment increased TRAIL-induced A549 cell death under hypoxic conditions, although hypoxia inhibited TRAIL-mediated cell apoptosis. In a mechanistic study, hypoxia inducible factor-1α and prolyl-hydroxylase 2 proteins, which increase following exposure to hypoxia, were dose-dependently down-regulated by melatonin treatment. Melatonin also blocked the hypoxic responses that reduced pro-apoptotic proteins and increased anti-apoptotic proteins including Bcl-2 and Bcl-xL. Furthermore, melatonin treatment reduced TRAIL resistance by regulating the mitochondrial transmembrane potential and Bax translocation. Our results first demonstrated that melatonin treatment induces apoptosis in TRAIL-resistant hypoxic tumor cells by diminishing the anti-apoptotic signals mediated by hypoxia and also suggest that melatonin could be a tumor therapeutic tool by combining with other apoptotic ligands including TRAIL, particularly in solid tumor cells exposed to hypoxia. Full article
(This article belongs to the Special Issue Advances in the Research of Melatonin 2014)
Open AccessArticle Catalpol Ameliorates Sodium Taurocholate-Induced Acute Pancreatitis in Rats via Inhibiting Activation of Nuclear Factor Kappa B
Int. J. Mol. Sci. 2014, 15(7), 11957-11972; doi:10.3390/ijms150711957
Received: 11 May 2014 / Revised: 3 June 2014 / Accepted: 20 June 2014 / Published: 4 July 2014
Cited by 20 | PDF Full-text (3543 KB) | HTML Full-text | XML Full-text
Abstract
Catalpol, an iridoid glucoside extracted from the traditional Chinese herbal medicine, Rehmannia glutinosa, is reported to exert neuroprotective, anti-inflammatory, anti-tumor and anti-apoptotic effects. The main aim of the present study was to investigate whether catalpol ameliorates experimental acute pancreatitis (AP) induced by
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Catalpol, an iridoid glucoside extracted from the traditional Chinese herbal medicine, Rehmannia glutinosa, is reported to exert neuroprotective, anti-inflammatory, anti-tumor and anti-apoptotic effects. The main aim of the present study was to investigate whether catalpol ameliorates experimental acute pancreatitis (AP) induced by sodium taurocholate (STC). AP was induced in rats via retrograde injection of 4% STC (0.1 mL/100 g) into the biliopancreatic duct. Rats were pre-treated with saline or catalpol (50 mg/kg) 2 h before STC injection. At 12, 24 and 48 h after injection, the severity of AP was evaluated using biochemical and morphological analyses. Pretreatment with catalpol led to a significant reduction in serum amylase and lipase activities, pancreatic histological damage, myeloperoxidase (MPO) activity, interleukin (IL)-1β, IL-6 and TNF-α levels, and activation of nuclear factor kappa B (NF-κB). Moreover, administration of catalpol increased the viability of pancreatic acinar cells and inhibited NF-κB expression in vitro. Our results collectively support the potential of catalpol as a highly effective therapeutic agent for treatment of AP. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
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Open AccessArticle miR-143 Inhibits NSCLC Cell Growth and Metastasis by Targeting Limk1
Int. J. Mol. Sci. 2014, 15(7), 11973-11983; doi:10.3390/ijms150711973
Received: 7 May 2014 / Revised: 9 June 2014 / Accepted: 16 June 2014 / Published: 7 July 2014
Cited by 16 | PDF Full-text (740 KB) | HTML Full-text | XML Full-text
Abstract
MicroRNAs (miRNAs) have essential roles in carcinogenesis and tumor progression. Here, we investigated the roles and mechanisms of miR-143 in non-small cell lung cancer (NSCLC). miR-143 was significantly decreased in NSCLC tissues and cell lines. Overexpression of miR-143 suppressed NSCLC cell proliferation, induced
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MicroRNAs (miRNAs) have essential roles in carcinogenesis and tumor progression. Here, we investigated the roles and mechanisms of miR-143 in non-small cell lung cancer (NSCLC). miR-143 was significantly decreased in NSCLC tissues and cell lines. Overexpression of miR-143 suppressed NSCLC cell proliferation, induced apoptosis, and inhibited migration and invasion in vitro. Integrated analysis identified LIM domain kinase 1 (Limk1) as a direct and functional target of miR-143. Overexpression of Limk1 attenuated the tumor suppressive effects of miR-143 in NSCLC cells. Moreover, miR-143 was inversely correlated with Limk1 expression in NSCLC tissues. Together, our results highlight the significance of miR-143 and Limk1 in the development and progression of NSCLC. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessCommunication Association of TNFRSF10D DNA-Methylation with the Survival of Melanoma Patients
Int. J. Mol. Sci. 2014, 15(7), 11984-11995; doi:10.3390/ijms150711984
Received: 1 May 2014 / Revised: 30 June 2014 / Accepted: 1 July 2014 / Published: 7 July 2014
Cited by 2 | PDF Full-text (737 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In this retrospective pilot study, the DNA-methylation status of genes that have been demonstrated to be involved in melanoma carcinogenesis was analyzed in order to identify novel biomarkers for the risk assessment of melanoma patients. We analyzed DNA extracted from punch-biopsies from 68
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In this retrospective pilot study, the DNA-methylation status of genes that have been demonstrated to be involved in melanoma carcinogenesis was analyzed in order to identify novel biomarkers for the risk assessment of melanoma patients. We analyzed DNA extracted from punch-biopsies from 68 formalin-fixed paraffin-embedded (FFPE) melanoma specimens. Using MethyLight PCR, we examined 20 genes in specimens from a training set comprising 36 melanoma patients. Selected candidate genes were validated in a test set using FFPE tissue samples from 32 melanoma patients. First, we identified the TNFRSF10D DNA-methylation status (TNFRSF10D methylated vs. unmethylated) as a prognostic marker for overall (p = 0.001) and for relapse-free survival (p = 0.008) in the training set. This finding was confirmed in the independent test set (n = 32; overall survival p = 0.041; relapse-free survival p = 0.012). In a multivariate Cox-regression analysis including all patients, the TNFRSF10D DNA-methylation status remained as the most significant prognostic parameter for overall and relapse-free survival (relative-risk (RR) of death, 4.6 (95% CI: 2.0–11.0; p < 0.001), RR of relapse, 7.2 (95% CI: 2.8–18.3; p < 0.001)). In this study, we demonstrate that TNFRSF10D DNA-methylation analysis of a small tissue-punch from archival FFPE melanoma tissue is a promising approach to provide prognostic information in patients with melanoma. Full article
(This article belongs to the Section Molecular Diagnostics)
Open AccessArticle Polymorphisms of Leptin-b Gene Associated with Growth Traits in Orange-Spotted Grouper (Epinephelus coioides)
Int. J. Mol. Sci. 2014, 15(7), 11996-12006; doi:10.3390/ijms150711996
Received: 25 April 2014 / Revised: 26 May 2014 / Accepted: 6 June 2014 / Published: 7 July 2014
Cited by 5 | PDF Full-text (983 KB) | HTML Full-text | XML Full-text
Abstract
In mammals, leptin has been demonstrated to perform important roles in many physiological activities and to influence development, growth, metabolism and reproduction. However, in fish, its function is still unclear. Duplicate leptin genes, leptin-a and leptin-b, have been identified in the orange-spotted grouper.
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In mammals, leptin has been demonstrated to perform important roles in many physiological activities and to influence development, growth, metabolism and reproduction. However, in fish, its function is still unclear. Duplicate leptin genes, leptin-a and leptin-b, have been identified in the orange-spotted grouper. In the present study, the polymorphisms in the leptin-b gene of the orange-spotted grouper were detected, and the relation between these polymorphisms and 12 growth traits were analyzed. Six polymorphisms (including 3 single nucleotide polymorphisms (c.14G>A, c.93A>G, c.149G>A) in exon 1, 2 SNPs (c.181A>G, c.193G>A) in intron 1, and 1 SNP (c.360C>T) in exon 2) were identified and genotyped from 200 different individuals. The results revealed that the SNP c.149G>A was significantly associated with growth traits, that the heterozygous mutation genotype GA having negative effects on growth traits. However, the other five SNPs (c.14G>A, c.93A>G, c.181A>G, c.193G>A, c.360C>T) did not show significant associations with all the growth traits. Compared with our findings in leptin-a gene, the results suggested that the leptin-a hormone has more important physiological effects in fish bodies than the leptin-b type. Moreover, leptin genes were supposed to be one class of major candidate genes of regulating growth traits in the orange-spotted grouper. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Radiosensitization of Human Leukemic HL-60 Cells by ATR Kinase Inhibitor (VE-821): Phosphoproteomic Analysis
Int. J. Mol. Sci. 2014, 15(7), 12007-12026; doi:10.3390/ijms150712007
Received: 28 March 2014 / Revised: 18 April 2014 / Accepted: 28 April 2014 / Published: 7 July 2014
Cited by 5 | PDF Full-text (1173 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
DNA damaging agents such as ionizing radiation or chemotherapy are frequently used in oncology. DNA damage response (DDR)—triggered by radiation-induced double strand breaks—is orchestrated mainly by three Phosphatidylinositol 3-kinase-related kinases (PIKKs): Ataxia teleangiectasia mutated (ATM), DNA-dependent protein kinase (DNA-PK) and ATM and Rad3-related
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DNA damaging agents such as ionizing radiation or chemotherapy are frequently used in oncology. DNA damage response (DDR)—triggered by radiation-induced double strand breaks—is orchestrated mainly by three Phosphatidylinositol 3-kinase-related kinases (PIKKs): Ataxia teleangiectasia mutated (ATM), DNA-dependent protein kinase (DNA-PK) and ATM and Rad3-related kinase (ATR). Their activation promotes cell-cycle arrest and facilitates DNA damage repair, resulting in radioresistance. Recently developed specific ATR inhibitor, VE-821 (3-amino-6-(4-(methylsulfonyl)phenyl)-N-phenylpyrazine-2-carboxamide), has been reported to have a significant radio- and chemo-sensitizing effect delimited to cancer cells (largely p53-deficient) without affecting normal cells. In this study, we employed SILAC-based quantitative phosphoproteomics to describe the mechanism of the radiosensitizing effect of VE-821 in human promyelocytic leukemic cells HL-60 (p53-negative). Hydrophilic interaction liquid chromatography (HILIC)-prefractionation with TiO2-enrichment and nano-liquid chromatography—tandem mass spectrometry (LC-MS/MS) analysis revealed 9834 phosphorylation sites. Proteins with differentially up-/down-regulated phosphorylation were mostly localized in the nucleus and were involved in cellular processes such as DDR, all phases of the cell cycle, and cell division. Moreover, sequence motif analysis revealed significant changes in the activities of kinases involved in these processes. Taken together, our data indicates that ATR kinase has multiple roles in response to DNA damage throughout the cell cycle and that its inhibitor VE-821 is a potent radiosensitizing agent for p53-negative HL-60 cells. Full article
(This article belongs to the Special Issue Mass Spectrometry Application in Biology) Print Edition available
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Open AccessArticle Value of Micro-CT for Monitoring Spinal Microvascular Changes after Chronic Spinal Cord Compression
Int. J. Mol. Sci. 2014, 15(7), 12061-12073; doi:10.3390/ijms150712061
Received: 31 March 2014 / Revised: 23 June 2014 / Accepted: 25 June 2014 / Published: 7 July 2014
Cited by 2 | PDF Full-text (1630 KB) | HTML Full-text | XML Full-text
Abstract
Neurological degeneration can occur after compression of the spinal cord. It is widely accepted that spinal cord compression leads to ischemic lesions and ultimately neurological dysfunction due to a narrowed spinal canal. Therefore, an in-depth understanding of the pathogenesis of spinal cord compression
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Neurological degeneration can occur after compression of the spinal cord. It is widely accepted that spinal cord compression leads to ischemic lesions and ultimately neurological dysfunction due to a narrowed spinal canal. Therefore, an in-depth understanding of the pathogenesis of spinal cord compression injury is required to help develop effective clinical interventions. In the present study, we propose a new method of quantitative 3D micro-CT to observe microvascular events in a chronic spinal cord compression rat model. A total of 36 rats were divided into two groups: sham control group (n = 12) and compressive spinal cord injury group (n = 24). Rats were scarified at four weeks after surgery. In each group, CD34 micro-vessel immunohistochemical staining was performed in half of the animals, while micro-CT scanning was performed in the other half. Microvessel density (MVD) was measured after immunohistochemical staining, while the vascular index (VI) was measured in 3D micro-CT. In comparison with sham control, abnormal somatosensory evoked potentials (SEP) can be seen in all 24 cases of the compression group, and VI shows the amount of microvessels reduced consistently and significantly (p < 0.01). A significant correlation is also found between MVD and VI (r = 0.95, p < 0.01). These data suggest that quantitative 3D micro-CT is a sensitive and promising tool for investigating microvascular changes during chronic compressive spinal cord injury. Full article
(This article belongs to the Special Issue Neurological Injuries’ Monitoring, Tracking and Treatment)
Open AccessArticle Morphology and Quantitative Monitoring of Gene Expression Patterns during Floral Induction and Early Flower Development in Dendrocalamus latiflorus
Int. J. Mol. Sci. 2014, 15(7), 12074-12093; doi:10.3390/ijms150712074
Received: 26 March 2014 / Revised: 4 June 2014 / Accepted: 16 June 2014 / Published: 7 July 2014
PDF Full-text (2805 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The mechanism of floral transition in bamboo remains unclear. Dendrocalamus latiflorus (Bambusease, Bambusoideae, Poaceae) is an economically and ecologically important clumping bamboo in tropical and subtropical areas. We evaluated morphological characteristics and gene expression profiling to study floral induction and early flower
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The mechanism of floral transition in bamboo remains unclear. Dendrocalamus latiflorus (Bambusease, Bambusoideae, Poaceae) is an economically and ecologically important clumping bamboo in tropical and subtropical areas. We evaluated morphological characteristics and gene expression profiling to study floral induction and early flower development in D. latiflorus. The detailed morphological studies on vegetative buds and floral organography were completed using paraffin sectioning and scanning electron microscopy. The 3 mm floral buds commence the development of stamen primordia and pistil primordium. Furthermore, homologs of floral transition-related genes, including AP1, TFL1, RFL, PpMADS1, PpMADS2, SPL9, FT, ID1, FCA, and EMF2, were detected and quantified by reverse transcriptase PCR and real-time PCR in vegetative and floral buds, respectively. Distinct expression profiles of ten putative floral initiation homologues that corresponded to the developmental stages defined by bud length were obtained and genes were characterized. Six of the genes (including DlTFL1, DlRFL, DlMADS2, DlID1, DlFCA, DlEMF2) showed statistically significant changes in expression during floral transition. DlAP1 demonstrated a sustained downward trend and could serve as a good molecular marker during floral transition in D. latiflorus. The combined analysis provided key candidate markers to track the transition from the vegetative to reproductive phase. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Melatonin Promotes Superovulation in Sika Deer (Cervus nippon)
Int. J. Mol. Sci. 2014, 15(7), 12107-12118; doi:10.3390/ijms150712107
Received: 21 May 2014 / Revised: 19 June 2014 / Accepted: 30 June 2014 / Published: 8 July 2014
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Abstract
In this study, the effects of melatonin (MT) on superovulation and reproductive hormones (melatonin, follicle-stimulating hormone (FSH), luteinizing hormone (LH) and PRL) were investigated in female sika deer. Different doses (40 or 80 mg/animal) of melatonin were subcutaneously implanted into deer before the
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In this study, the effects of melatonin (MT) on superovulation and reproductive hormones (melatonin, follicle-stimulating hormone (FSH), luteinizing hormone (LH) and PRL) were investigated in female sika deer. Different doses (40 or 80 mg/animal) of melatonin were subcutaneously implanted into deer before the breeding season. Exogenous melatonin administration significantly elevated the serum FSH levels at the time of insemination compared with levels in control animals. During superovulation, the serum LH levels in donor sika deer reached their highest values (7.1 ± 2.04 ng/mL) at the point of insemination, compared with the baseline levels (4.98 ± 0.07 ng/mL) in control animals. This high level of LH was sustained until the day of embryo recovery. In contrast, the serum levels of PRL in the 80 mg of melatonin-treated group were significantly lower than those of control deer. The average number of corpora lutea in melatonin-treated deer was significantly higher than that of the control (p < 0.05). The average number of embryos in the deer treated with 40 mg of melatonin was higher than that of the control; however, this increase did not reach significant difference (p > 0.05), which may be related to the relatively small sample size. In addition, embryonic development in melatonin-treated groups was delayed. Full article
(This article belongs to the Special Issue Advances in the Research of Melatonin 2014)
Open AccessArticle Cordycepin Inhibits Lipopolysaccharide (LPS)-Induced Tumor Necrosis Factor (TNF)-α Production via Activating AMP-Activated Protein Kinase (AMPK) Signaling
Int. J. Mol. Sci. 2014, 15(7), 12119-12134; doi:10.3390/ijms150712119
Received: 19 April 2014 / Revised: 6 June 2014 / Accepted: 18 June 2014 / Published: 8 July 2014
Cited by 8 | PDF Full-text (1602 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Tumor necrosis factor (TNF)-α is elevated during the acute phase of Kawasaki disease (KD), which damages vascular endothelial cells to cause systemic vasculitis. In the current study, we investigated the potential role of cordycepin on TNFα expression in both lipopolysaccharide (LPS)-stimulated macrophages and
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Tumor necrosis factor (TNF)-α is elevated during the acute phase of Kawasaki disease (KD), which damages vascular endothelial cells to cause systemic vasculitis. In the current study, we investigated the potential role of cordycepin on TNFα expression in both lipopolysaccharide (LPS)-stimulated macrophages and ex vivo cultured peripheral blood mononuclear cells (PBMCs) of KD patients. We found that cordycepin significantly suppressed LPS-induced TNFα expression and production in mouse macrophages (RAW 264.7 cells and bone marrow-derived macrophages (BMDMs)). Meanwhile, cordycepin alleviated TNFα production in KD patients’ PBMCs. PBMCs from healthy controls had a much lower level of basal TNF-α content than that of KD patients. LPS-induced TNF-α production in healthy controls’ PBMCs was also inhibited by cordycepin. For the mechanism study, we discovered that cordycepin activated AMP-activated protein kinase (AMPK) signaling in both KD patients’ PBMCs and LPS-stimulated macrophages, which mediated cordycepin-induced inhibition against TNFα production. AMPK inhibition by its inhibitor (compound C) or by siRNA depletion alleviated cordycepin’s effect on TNFα production. Further, we found that cordycepin inhibited reactive oxygen species (ROS) production and nuclear factor kappa B (NF-κB) activation in LPS-stimulate RAW 264.7 cells or healthy controls’ PBMCs. PBMCs of KD patients showed higher basal level of ROS and NF-κB activation, which was also inhibited by cordycepin co-treatment. In conclusion, our data showed that cordycepin inhibited TNFα production, which was associated with AMPK activation as well as ROS and NF-κB inhibition. The results of this study should have significant translational relevance in managing this devastating disease. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Antinociceptive Effect of Intrathecal Microencapsulated Human Pheochromocytoma Cell in a Rat Model of Bone Cancer Pain
Int. J. Mol. Sci. 2014, 15(7), 12135-12148; doi:10.3390/ijms150712135
Received: 19 May 2014 / Revised: 10 June 2014 / Accepted: 18 June 2014 / Published: 8 July 2014
Cited by 3 | PDF Full-text (1771 KB) | HTML Full-text | XML Full-text
Abstract
Human pheochromocytoma cells, which are demonstrated to contain and release met-enkephalin and norepinephrine, may be a promising resource for cell therapy in cancer-induced intractable pain. Intrathecal injection of alginate-poly (l) lysine-alginate (APA) microencapsulated human pheochromocytoma cells leads to antinociceptive effect in a rat
[...] Read more.
Human pheochromocytoma cells, which are demonstrated to contain and release met-enkephalin and norepinephrine, may be a promising resource for cell therapy in cancer-induced intractable pain. Intrathecal injection of alginate-poly (l) lysine-alginate (APA) microencapsulated human pheochromocytoma cells leads to antinociceptive effect in a rat model of bone cancer pain, and this effect was blocked by opioid antagonist naloxone and alpha 2-adrenergic antagonist rauwolscine. Neurochemical changes of cerebrospinal fluid are in accordance with the analgesic responses. Taken together, these data support that human pheochromocytoma cell implant-induced antinociception was mediated by met-enkephalin and norepinephrine secreted from the cell implants and acting at spinal receptors. Spinal implantation of microencapsulated human pheochromocytoma cells may provide an alternative approach for the therapy of chronic intractable pain. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
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Open AccessArticle Nrf2-Mediated HO-1 Induction Coupled with the ERK Signaling Pathway Contributes to Indirect Antioxidant Capacity of Caffeic Acid Phenethyl Ester in HepG2 Cells
Int. J. Mol. Sci. 2014, 15(7), 12149-12165; doi:10.3390/ijms150712149
Received: 26 May 2014 / Revised: 17 June 2014 / Accepted: 25 June 2014 / Published: 9 July 2014
Cited by 19 | PDF Full-text (773 KB) | HTML Full-text | XML Full-text
Abstract
The objective of this study is to investigate the contributing effect of the nuclear transcription factor-erythroid 2-related factor 2 (Nrf2)-mediated signaling pathway on the indirect antioxidant capacity of caffeic acid phenethyl ester (CAPE) against oxidative stress in HepG2 cells. The result of an
[...] Read more.
The objective of this study is to investigate the contributing effect of the nuclear transcription factor-erythroid 2-related factor 2 (Nrf2)-mediated signaling pathway on the indirect antioxidant capacity of caffeic acid phenethyl ester (CAPE) against oxidative stress in HepG2 cells. The result of an antioxidant response element (ARE)-luciferase assay showed that CAPE stimulated ARE promoter activity resulting in increased transcriptional and translational activities of heme oxygenase-1 (HO-1). In addition, CAPE treatment enhanced Nrf2 accumulation in the nucleus and the post-translational phosphorylation level of extracellular signal-regulated kinase (ERK) among several protein kinases tested. Treatment with ERK inhibitor U126 completely suppressed CAPE-induced ERK phosphorylation and HO-1 expression, but it only partly inhibited CAPE-induced Nrf2 accumulation and ARE promoter. Using the 2',7'-dichlorofluorescein-diacetate (DCFH-DA) method, the cellular antioxidant capacity of CAPE against 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH)- or H2O2-induced oxidative stress also was shown to be partially suppressed by the ERK inhibitor. From the overall results it is proposed that the indirect antioxidant activity of CAPE against oxidative stress in HepG2 cells is partially attributed to induction of HO-1, which is regulated by Kelch-like erythroid-cell-derived protein with CNC homology (ECH)-associated protein 1 (Keap1)-independent Nrf2 activation relying on post-translational phosphorylation of ERK. Full article
(This article belongs to the Special Issue Bioactive Phenolics and Polyphenols)
Open AccessArticle First Isolation of New Canine Parvovirus 2a from Tibetan Mastiff and Global Analysis of the Full-Length VP2 Gene of Canine Parvoviruses 2 in China
Int. J. Mol. Sci. 2014, 15(7), 12166-12187; doi:10.3390/ijms150712166
Received: 21 May 2014 / Revised: 20 June 2014 / Accepted: 25 June 2014 / Published: 9 July 2014
Cited by 3 | PDF Full-text (18739 KB) | HTML Full-text | XML Full-text
Abstract
Canine parvovirus 2 (CPV-2) was first identified in 1978, and is responsible for classic parvoviral enteritis. Despite the widespread vaccination of domestic carnivores, CPVs have remained important pathogens of domestic and wild carnivores. In this study, we isolated CPV-2 from Tibetan mastiffs and
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Canine parvovirus 2 (CPV-2) was first identified in 1978, and is responsible for classic parvoviral enteritis. Despite the widespread vaccination of domestic carnivores, CPVs have remained important pathogens of domestic and wild carnivores. In this study, we isolated CPV-2 from Tibetan mastiffs and performed a global analysis of the complete VP2 gene sequences of CPV-2 strains in China. Six isolates were typed as new CPV-2a, according to key amino acid positions. On a phylogenetic tree, these six sequences formed a distinct clade. Five isolates occurred on the same branch as KF785794 from China and GQ379049 from Thailand; CPV-LS-ZA1 formed a separate subgroup with FJ435347 from China. One hundred ninety-eight sequences from various parts of China and the six sequences isolated here formed seven distinct clusters, indicating the high diversity of CPVs in China. Of 204 VP2 sequences, 183 (91.04%) encoded the mutation Ser297Ala, regardless of the antigenic type, implying that most Chinese CPV-2 strains contain the VP2 mutation Ser297Ala. However, the biological significance of this change from prototype CPV-2a/2b to new CPV-2a/2b types remains unclear. This study is the first to isolate new CPV-2a from the Tibetan mastiff. Our data show that new CPV-2a/2b variants are now circulating in China. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessCommunication Novel Inhibitory Effect of N-(2-Hydroxycyclohexyl)valiolamine on Melanin Production in a Human Skin Model
Int. J. Mol. Sci. 2014, 15(7), 12188-12195; doi:10.3390/ijms150712188
Received: 30 April 2014 / Revised: 24 June 2014 / Accepted: 26 June 2014 / Published: 9 July 2014
Cited by 2 | PDF Full-text (1378 KB) | HTML Full-text | XML Full-text
Abstract
Hyper-pigmentation causes skin darkness and medical disorders, such as post-inflammatory melanoderma and melasma. Therefore, the development of anti-melanogenic agents is important for treating these conditions and for cosmetic production. In our previous paper, we demonstrated that the anti-diabetic drug voglibose, a valiolamine derivative,
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Hyper-pigmentation causes skin darkness and medical disorders, such as post-inflammatory melanoderma and melasma. Therefore, the development of anti-melanogenic agents is important for treating these conditions and for cosmetic production. In our previous paper, we demonstrated that the anti-diabetic drug voglibose, a valiolamine derivative, is a potent anti-melanogenic agent. In addition, we proposed an alternative screening strategy to identify valiolamine derivatives with high skin permeability that act as anti-melanogenic agents when applied topically. In this study, we synthesized several valiolamine derivatives with enhanced lipophilicity and examined their inhibitory effects in a human skin model. N-(2-hydroxycyclohexyl)valiolamine (HV) possesses a stronger inhibitory effect on melanin production than voglibose in a human skin model, suggesting that HV is a more potent anti-melanogenic agent for the skin. Full article
Open AccessArticle Development of an Intergeneric Conjugal Transfer System for Xinaomycins-Producing Streptomyces noursei Xinao-4
Int. J. Mol. Sci. 2014, 15(7), 12217-12230; doi:10.3390/ijms150712217
Received: 13 February 2014 / Revised: 21 March 2014 / Accepted: 24 March 2014 / Published: 9 July 2014
Cited by 2 | PDF Full-text (810 KB) | HTML Full-text | XML Full-text
Abstract
To introduce DNA into Streptomyces noursei xinao-4, which produces xinaomycins, we explored an intergeneric conjugal transfer system. High efficiency of conjugation (8 × 10−3 exconjugants per recipient) was obtained when spores of S. noursei xinao-4 were heat-shocked at 50 °C for 10
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To introduce DNA into Streptomyces noursei xinao-4, which produces xinaomycins, we explored an intergeneric conjugal transfer system. High efficiency of conjugation (8 × 10−3 exconjugants per recipient) was obtained when spores of S. noursei xinao-4 were heat-shocked at 50 °C for 10 min, mixed with Escherichia coli ET12567 (pUZ8002/pSET152) in the ratio of 1:100, plated on 2CMY medium containing 40 mmol/L MgCl2, and incubated at 30 °C for 22 h. With this protocol, the plasmids pKC1139 and pSET152 were successfully transferred from E. coli ET12567 (pUZ8002) with different frequencies. Among all parameters, the ratio of donor to recipient cell number had the strongest effect on the transformation efficiency. In order to validate the above intergeneric conjugal transfer system, a glycosyltransferase gene was cloned and efficiently knocked out in S. noursei xinao-4 using pSG5-based plasmid pKC1139. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Alternating Current Electrophoretic Deposition of Antibacterial Bioactive Glass-Chitosan Composite Coatings
Int. J. Mol. Sci. 2014, 15(7), 12231-12242; doi:10.3390/ijms150712231
Received: 5 May 2014 / Revised: 10 June 2014 / Accepted: 16 June 2014 / Published: 9 July 2014
Cited by 10 | PDF Full-text (3939 KB) | HTML Full-text | XML Full-text
Abstract
Alternating current (AC) electrophoretic deposition (EPD) was used to produce multifunctional composite coatings combining bioactive glass (BG) particles and chitosan. BG particles of two different sizes were used, i.e., 2 μm and 20–80 nm in average diameter. The parameter optimization and characterization
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Alternating current (AC) electrophoretic deposition (EPD) was used to produce multifunctional composite coatings combining bioactive glass (BG) particles and chitosan. BG particles of two different sizes were used, i.e., 2 μm and 20–80 nm in average diameter. The parameter optimization and characterization of the coatings was conducted by visual inspection and by adhesion strength tests. The optimized coatings were investigated in terms of their hydroxyapatite (HA) forming ability in simulated body fluid (SBF) for up to 21 days. Fourier transform infrared (FTIR) spectroscopy results showed the successful HA formation on the coatings after 21 days. The first investigations were conducted on planar stainless steel sheets. In addition, scaffolds made from a TiAl4V6 alloy were considered to show the feasibility of coating of three dimensional structures by EPD. Because both BG and chitosan are antibacterial materials, the antibacterial properties of the as-produced coatings were investigated using E. coli bacteria cells. It was shown that the BG particle size has a strong influence on the antibacterial properties of the coatings. Full article
(This article belongs to the Special Issue Biologic Coatings for Orthopaedic Implant)
Open AccessArticle Use of Propolis in the Sanitization of Lettuce
Int. J. Mol. Sci. 2014, 15(7), 12243-12257; doi:10.3390/ijms150712243
Received: 17 May 2014 / Revised: 28 June 2014 / Accepted: 1 July 2014 / Published: 9 July 2014
Cited by 4 | PDF Full-text (704 KB) | HTML Full-text | XML Full-text
Abstract
The present study aimed to determine the effectiveness of propolis in reducing the microbial load in ready-to-eat (RTE) and fresh whole head (FWH) lettuces (Lactuca sativa L.) type Batavia. Two sanitizing solutions were employed: sodium hypochlorite (SH) and propolis (PS), during 15
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The present study aimed to determine the effectiveness of propolis in reducing the microbial load in ready-to-eat (RTE) and fresh whole head (FWH) lettuces (Lactuca sativa L.) type Batavia. Two sanitizing solutions were employed: sodium hypochlorite (SH) and propolis (PS), during 15 and 30 min. Tap water (TW) was used as a control. Regarding the mean reduction on aerobic mesophiles, psychrotrophic and fecal coliforms, the SH and PS treatments showed the same pattern of variation. In all cases, PS was slightly more effective in the microbiological reduction in comparison with commercial SH. Reductions between two and three log cycles were obtained with PS on aerobic mesophiles and psychrotrophic counts. The information obtained in the present study can be used to evaluate the potential use of propolis as product for sanitizing other vegetables and for developing other food preservation technologies, with impact on human health. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Association of STAT3 Common Variations with Obesity and Hypertriglyceridemia: Protective and Contributive Effects
Int. J. Mol. Sci. 2014, 15(7), 12258-12269; doi:10.3390/ijms150712258
Received: 8 May 2014 / Revised: 9 June 2014 / Accepted: 19 June 2014 / Published: 10 July 2014
Cited by 1 | PDF Full-text (678 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Signal transducer and activator of transcription 3 (STAT3) plays an important role in energy metabolism. Here we explore whether STAT3 common variations influence risks of obesity and other metabolic disorders in a Chinese Han population. Two tagging single nucleotide polymorphisms (tagSNPs), rs1053005 and
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Signal transducer and activator of transcription 3 (STAT3) plays an important role in energy metabolism. Here we explore whether STAT3 common variations influence risks of obesity and other metabolic disorders in a Chinese Han population. Two tagging single nucleotide polymorphisms (tagSNPs), rs1053005 and rs957970, were used to capture the common variations of STAT3. Relationships between genotypes and obesity, body mass index, plasma triglyceride and other metabolic diseases related parameters were analyzed for association study in 1742 subjects. Generalized linear model and logistic regression model were used for quantitative data analysis and case-control study, respectively. rs1053005 was significantly associated with body mass index and waist circumference (p = 0.013 and p = 0.02, respectively). rs957970 was significantly associated with plasma level of triglyceride (p = 0.007). GG genotype at rs1053005 had lower risks of both general obesity and central obesity (OR = 0.40, p = 0.034; OR = 0.42, p = 0.007, respectively) compared with AA genotype. CT genotype at rs957970 had a higher risk of hypertriglyceridemia (OR = 1.43, p = 0.015) compared with TT genotype. Neither of the two SNPs was associated with othermetabolic diseases related parameters. Our observations indicated that common variations of STAT3 could significantly affect the risk of obesity and hypertriglyceridemia in Chinese Han population. Full article
(This article belongs to the collection Human Single Nucleotide Polymorphisms and Disease Diagnostics)
Open AccessArticle Chrysin Suppressed Inflammatory Responses and the Inducible Nitric Oxide Synthase Pathway after Spinal Cord Injury in Rats
Int. J. Mol. Sci. 2014, 15(7), 12270-12279; doi:10.3390/ijms150712270
Received: 28 April 2014 / Revised: 29 May 2014 / Accepted: 3 June 2014 / Published: 10 July 2014
Cited by 9 | PDF Full-text (975 KB) | HTML Full-text | XML Full-text
Abstract
Chrysin (CH), a natural plant flavonoid, has shown a variety of beneficial effects. Our present study was conducted to evaluate the therapeutic potential of CH three days after spinal cord injury (SCI) in rats and to probe the underlying neuroprotective mechanisms. SCI was
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Chrysin (CH), a natural plant flavonoid, has shown a variety of beneficial effects. Our present study was conducted to evaluate the therapeutic potential of CH three days after spinal cord injury (SCI) in rats and to probe the underlying neuroprotective mechanisms. SCI was induced using the modified weight-drop method in Wistar rats. Then, they were treated with saline or CH by doses of 30 and 100 mg/kg for 26 days. Neuronal function was assessed with the Basso Beattle Bresnahan locomotor rating scale (BBB). The water content of spinal cord was determined after traumatic SCI. The NF-κB p65 unit, TNF-α, IL-1β and IL-6 in serums, as well as the apoptotic marker, caspase-3, of spinal cord tissues were measured using commercial kits. The protein level and activity of inducible nitric oxide synthase (iNOS) were detected by western blot and a commercial kit, respectively. NO (nitric oxide) production was evaluated by the determination of nitrite concentration. The rats with SCI showed marked reductions in BBB scores, coupled with increases in the water content of spinal cord, the NF-κB p65 unit, TNF-α, IL-1β, IL-6, iNOS, NO production and caspase-3. However, a CH supplement dramatically promoted the recovery of neuronal function and suppressed the inflammatory factors, as well as the iNOS pathway in rats with SCI. Our findings disclose that CH improved neural function after SCI in rats, which might be linked with suppressing inflammation and the iNOS pathway. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Association between STAT4 Gene Polymorphisms and Autoimmune Thyroid Diseases in a Chinese Population
Int. J. Mol. Sci. 2014, 15(7), 12280-12293; doi:10.3390/ijms150712280
Received: 14 May 2014 / Revised: 29 May 2014 / Accepted: 26 June 2014 / Published: 11 July 2014
Cited by 5 | PDF Full-text (163 KB) | HTML Full-text | XML Full-text
Abstract
The STAT4 gene encodes a transcriptional factor that transmits signals induced by several key cytokines which play important roles in the development of autoimmune diseases. The aim of this study was to explore the association of STAT4 polymorphism with Graves’ disease (GD) and
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The STAT4 gene encodes a transcriptional factor that transmits signals induced by several key cytokines which play important roles in the development of autoimmune diseases. The aim of this study was to explore the association of STAT4 polymorphism with Graves’ disease (GD) and Hashimoto’s thyroiditis (HT). A total of 1048 autoimmune thyroid diseases (AITDs) patients (693 with GD and 355 with HT) and 909 age- and gender-matched controls were examined. STAT4 polymorphisms (rs7574865/rs10181656/ rs7572482) were genotyped by multiplex polymerase chain reaction (PCR) and ligase detection reaction (LDR). The results indicated that the frequencies of rs7574865 genotypes in patients with GD differed significantly from the controls (p = 0.028), the T allele frequency of GD patients was also significantly higher than the controls (p = 0.020). The genotypes of rs10181656 differed significantly in GD patients from controls (p = 0.012); G allele frequencies were significantly higher in AITD patients than the controls (p = 0.014 and 0.031, respectively). The frequencies of haplotype GC with GD and HT patients were significantly lower than their controls (p = 0.015 and 0.030, respectively). In contrast, the frequencies of haplotype TG with GD and HT patients were significantly higher than their controls (p = 0.016 and 0.048, respectively). These findings strongly suggest that STAT4 rs7574865/rs10181656 polymorphisms increase the risk of AITD in a Chinese population. Full article
(This article belongs to the Section Molecular Diagnostics)
Open AccessArticle Exploring Neighborhoods in the Metagenome Universe
Int. J. Mol. Sci. 2014, 15(7), 12364-12378; doi:10.3390/ijms150712364
Received: 31 March 2014 / Revised: 23 June 2014 / Accepted: 25 June 2014 / Published: 14 July 2014
PDF Full-text (1211 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The variety of metagenomes in current databases provides a rapidly growing source of information for comparative studies. However, the quantity and quality of supplementary metadata is still lagging behind. It is therefore important to be able to identify related metagenomes by means of
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The variety of metagenomes in current databases provides a rapidly growing source of information for comparative studies. However, the quantity and quality of supplementary metadata is still lagging behind. It is therefore important to be able to identify related metagenomes by means of the available sequence data alone. We have studied efficient sequence-based methods for large-scale identification of similar metagenomes within a database retrieval context. In a broad comparison of different profiling methods we found that vector-based distance measures are well-suitable for the detection of metagenomic neighbors. Our evaluation on more than 1700 publicly available metagenomes indicates that for a query metagenome from a particular habitat on average nine out of ten nearest neighbors represent the same habitat category independent of the utilized profiling method or distance measure. While for well-defined labels a neighborhood accuracy of 100% can be achieved, in general the neighbor detection is severely affected by a natural overlap of manually annotated categories. In addition, we present results of a novel visualization method that is able to reflect the similarity of metagenomes in a 2D scatter plot. The visualization method shows a similarly high accuracy in the reduced space as compared with the high-dimensional profile space. Our study suggests that for inspection of metagenome neighborhoods the profiling methods and distance measures can be chosen to provide a convenient interpretation of results in terms of the underlying features. Furthermore, supplementary metadata of metagenome samples in the future needs to comply with readily available ontologies for fine-grained and standardized annotation. To make profile-based k-nearest-neighbor search and the 2D-visualization of the metagenome universe available to the research community, we included the proposed methods in our CoMet-Universe server for comparative metagenome analysis. Full article
(This article belongs to the Special Issue Metagenomics: a Powerful Lens Viewing the Microbial World)
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Open AccessArticle Subchronic Toxicity of Copper Oxide Nanoparticles and Its Attenuation with the Help of a Combination of Bioprotectors
Int. J. Mol. Sci. 2014, 15(7), 12379-12406; doi:10.3390/ijms150712379
Received: 7 May 2014 / Revised: 12 June 2014 / Accepted: 19 June 2014 / Published: 14 July 2014
Cited by 8 | PDF Full-text (1955 KB) | HTML Full-text | XML Full-text
Abstract
In the copper metallurgy workplace air is polluted with condensation aerosols, which a significant fraction of is presented by copper oxide particles <100 nm. In the scientific literature, there is a lack of their in vivo toxicity characterization and virtually no attempts of
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In the copper metallurgy workplace air is polluted with condensation aerosols, which a significant fraction of is presented by copper oxide particles <100 nm. In the scientific literature, there is a lack of their in vivo toxicity characterization and virtually no attempts of enhancing organism’s resistance to their impact. A stable suspension of copper oxide particles with mean (±SD) diameter 20 ± 10 nm was prepared by laser ablation of pure copper in water. It was being injected intraperitoneally to rats at a dose of 10 mg/kg (0.5 mg per mL of deionized water) three times a week up to 19 injections. In parallel, another group of rats was so injected with the same suspension against the background of oral administration of a “bio-protective complex” (BPC) comprising pectin, a multivitamin-multimineral preparation, some amino acids and fish oil rich in ω-3 PUFA. After the termination of injections, many functional and biochemical indices for the organism’s status, as well as pathological changes of liver, spleen, kidneys, and brain microscopic structure were evaluated for signs of toxicity. In the same organs we have measured accumulation of copper while their cells were used for performing the Random Amplification of Polymorphic DNA (RAPD) test for DNA fragmentation. The same features were assessed in control rats infected intraperitoneally with water with or without administration of the BPC. The copper oxide nanoparticles proved adversely bio-active in all respects considered in this study, their active in vivo solubilization in biological fluids playing presumably an important role in both toxicokinetics and toxicodynamics. The BPC proposed and tested by us attenuated systemic and target organs toxicity, as well as genotoxicity of this substance. Judging by experimental data obtained in this investigation, occupational exposures to nano-scale copper oxide particles can present a significant health risk while the further search for its management with the help of innocuous bioprotectors seems to be justified. Full article
(This article belongs to the Special Issue Bioactive Nanoparticles 2014)
Open AccessArticle Joint Identification of Genetic Variants for Physical Activity in Korean Population
Int. J. Mol. Sci. 2014, 15(7), 12407-12421; doi:10.3390/ijms150712407
Received: 23 April 2014 / Accepted: 11 June 2014 / Published: 14 July 2014
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Abstract
There has been limited research on genome-wide association with physical activity (PA). This study ascertained genetic associations between PA and 344,893 single nucleotide polymorphism (SNP) markers in 8842 Korean samples. PA data were obtained from a validated questionnaire that included information on PA
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There has been limited research on genome-wide association with physical activity (PA). This study ascertained genetic associations between PA and 344,893 single nucleotide polymorphism (SNP) markers in 8842 Korean samples. PA data were obtained from a validated questionnaire that included information on PA intensity and duration. Metabolic equivalent of tasks were calculated to estimate the total daily PA level for each individual. In addition to single- and multiple-SNP association tests, a pathway enrichment analysis was performed to identify the biological significance of SNP markers. Although no significant SNP was found at genome-wide significance level via single-SNP association tests, 59 genetic variants mapped to 76 genes were identified via a multiple SNP approach using a bootstrap selection stability measure. Pathway analysis for these 59 variants showed that maturity onset diabetes of the young (MODY) was enriched. Joint identification of SNPs could enable the identification of multiple SNPs with good predictive power for PA and a pathway enriched for PA. Full article
(This article belongs to the collection Human Single Nucleotide Polymorphisms and Disease Diagnostics)
Open AccessArticle DADS Suppresses Human Esophageal Xenograft Tumors through RAF/MEK/ERK and Mitochondria-Dependent Pathways
Int. J. Mol. Sci. 2014, 15(7), 12422-12441; doi:10.3390/ijms150712422
Received: 5 May 2014 / Revised: 22 June 2014 / Accepted: 7 July 2014 / Published: 14 July 2014
Cited by 9 | PDF Full-text (3145 KB) | HTML Full-text | XML Full-text
Abstract
Diallyl disulfide (DADS) is a natural organosulfur compound isolated from garlic. DADS has various biological properties, including anticancer, antiangiogenic, and antioxidant effects. However, the anticancer mechanisms of DADS in human esophageal carcinoma have not been elucidated, especially in vivo. In this study,
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Diallyl disulfide (DADS) is a natural organosulfur compound isolated from garlic. DADS has various biological properties, including anticancer, antiangiogenic, and antioxidant effects. However, the anticancer mechanisms of DADS in human esophageal carcinoma have not been elucidated, especially in vivo. In this study, MTT assay showed that DADS significantly reduced cell viability in human esophageal carcinoma ECA109 cells, but was relatively less toxic in normal liver cells. The pro–apoptotic effect of DADS on ECA109 cells was detected by Annexin V-FITC/propidium iodide (PI) staining. Flow cytometry analysis showed that DADS promoted apoptosis in a dose-dependent manner and the apoptosis rate could be decreased by caspase-3 inhibitor Ac-DEVD-CHO. Xenograft study in nude mice showed that DADS treatment inhibited the growth of ECA109 tumor in both 20 and 40 mg/kg DADS groups without obvious side effects. DADS inhibited ECA109 tumor proliferation by down-regulating proliferation cell nuclear antigen (PCNA). DADS induced apoptosis by activating a mitochondria-dependent pathway with the executor of caspase-3, increasing p53 level and Bax/Bcl-2 ratio, and downregulating the RAF/MEK/ERK pathway in ECA109 xenograft tumosr. Based on studies in cell culture and animal models, the findings here indicate that DADS is an effective and safe anti-cancer agent for esophageal carcinoma. Full article
Open AccessArticle Induction of Apurinic Endonuclease 1 Overexpression by Endoplasmic Reticulum Stress in Hepatoma Cells
Int. J. Mol. Sci. 2014, 15(7), 12442-12457; doi:10.3390/ijms150712442
Received: 7 April 2014 / Revised: 19 June 2014 / Accepted: 20 June 2014 / Published: 14 July 2014
PDF Full-text (2827 KB) | HTML Full-text | XML Full-text
Abstract
Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide with poor prognosis due to resistance to conventional chemotherapy and limited efficacy of radiotherapy. Previous studies have noted the induction of endoplasmic reticulum stress or apurinic endonuclease 1 (APE1) expression in many
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Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide with poor prognosis due to resistance to conventional chemotherapy and limited efficacy of radiotherapy. Previous studies have noted the induction of endoplasmic reticulum stress or apurinic endonuclease 1 (APE1) expression in many tumors. Therefore, the aim of this study was to investigate the relationship between endoplasmic reticulum (ER stress) and APE1 in hepatocellular carcinoma. Here we investigate the expression of APE1 during ER stress in HepG2 and Huh-7 cell lines. Tunicamycin or brefeldin A, two ER stress inducers, increased APE1 and GRP78, an ER stress marker, expression in HepG2 and Huh-7 cells. Induction of APE1 expression was observed through transcription level in response to ER stress. APE1 nuclear localization during ER stress was determined using immunofluorescence assays in HepG2 cells. Furthermore, expression of Hepatitis B virus pre-S2∆ large mutant surface protein (pre-S2∆), an ER stress-induced protein, also increased GRP78 and APE1 expression in the normal hepatocyte NeHepLxHT cell line. Similarly, tumor samples showed higher expression of APE1 in ER stress-correlated liver cancer tissue in vivo. Our results demonstrate that ER stress and HBV pre-S2∆ increased APE1 expression, which may play an important role in resistance to chemotherapeutic agents or tumor development. Therefore, these data provide an important chemotherapeutic strategy in ER stress and HBV pre-S2∆-associated tumors. Full article
(This article belongs to the collection Molecular Mechanisms of Human Liver Diseases)
Open AccessArticle Copy Number Analysis of 24 Oncogenes: MDM4 Identified as a Putative Marker for Low Recurrence Risk in Non Muscle Invasive Bladder Cancer
Int. J. Mol. Sci. 2014, 15(7), 12458-12468; doi:10.3390/ijms150712458
Received: 25 March 2014 / Revised: 26 June 2014 / Accepted: 4 July 2014 / Published: 14 July 2014
PDF Full-text (745 KB) | HTML Full-text | XML Full-text
Abstract
Patients with non-muscle invasive bladder cancer (NMIBC) generally have a high risk of relapsing locally after primary tumor resection. The search for new predictive markers of local recurrence thus represents an important goal for the management of this disease. We studied the copy
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Patients with non-muscle invasive bladder cancer (NMIBC) generally have a high risk of relapsing locally after primary tumor resection. The search for new predictive markers of local recurrence thus represents an important goal for the management of this disease. We studied the copy number variations (CNVs) of 24 oncogenes (MDM4, MYCN, ALK, PDGFRA, KIT, KDR, DHFR, EGFR, MET, SMO, FGFR1, MYC, ABL1, RET, CCND1, CCND2, CDK4, MDM2, AURKB, ERBB2, TOP2A, AURKA, AR and BRAF) using multiplex ligation probe amplification technique to verify their role as predictive markers of recurrence. Formalin-fixed paraffin-embedded tissue samples from 43 patients who underwent transurethral resection of the bladder (TURB) were used; 23 patients had relapsed and 20 were disease-free after 5 years. Amplification frequencies were analyzed for all genes and MDM4 was the only gene that showed significantly higher amplification in non recurrent patients than in recurrent ones (0.65 vs. 0.3; Fisher’s test p = 0.023). Recurrence-free survival analysis confirmed the predictive role of MDM4 (log-rank test p = 0.041). Our preliminary results indicate a putative role for the MDM4 gene in predicting local recurrence of bladder cancer. Confirmation of this hypothesis is needed in a larger cohort of NMIBC patients. Full article
(This article belongs to the Special Issue Molecular Research in Urology 2014)
Open AccessArticle Ficus carica Polysaccharides Promote the Maturation and Function of Dendritic Cells
Int. J. Mol. Sci. 2014, 15(7), 12469-12479; doi:10.3390/ijms150712469
Received: 18 December 2013 / Revised: 25 February 2014 / Accepted: 20 March 2014 / Published: 14 July 2014
Cited by 7 | PDF Full-text (1366 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Various polysaccharides purified from plants are considered to be biological response modifiers and have been shown to enhance immune responses. Ficus carica L. is a Chinese traditional plant and has been widely used in Asian countries for its anti-tumor properties. Ficus carica polysaccharides
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Various polysaccharides purified from plants are considered to be biological response modifiers and have been shown to enhance immune responses. Ficus carica L. is a Chinese traditional plant and has been widely used in Asian countries for its anti-tumor properties. Ficus carica polysaccharides (FCPS), one of the most essential and effective components in Ficus carica L., have been considered to be a beneficial immunomodulator and may be used in immunotherapy. However, the immunologic mechanism of FCPS is still unclear. Dectin-1 is a non-toll-like pattern recognition receptor, predominately expressed on dendritic cells (DCs). Activation of DCs through dectin-1 signaling can lead to the maturation of DC, thus inducing both innate and adaptive immune responses against tumor development and microbial infection. In our study, we found that FCPS could effectively stimulate DCs, partially through the dectin-1/Syk pathway, and promote their maturation, as shown by the up-regulation of CD40, CD80, CD86, and major histocompatibility complex II (MHCII). FCPS also enhanced the production of cytokines by DCs, including IL-12, IFN-γ, IL-6, and IL-23. Moreover, FCPS-treated DCs showed an enhanced capability to stimulate T cells and promote T cell proliferation. Altogether, these results demonstrate that FCPS are able to activate and maturate DCs, thereby up-regulating the immunostimulatory capacity of DCs, which leads to enhanced T cell responses. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Cloning and Expression Characteristics of the Pig Stra8 Gene
Int. J. Mol. Sci. 2014, 15(7), 12480-12494; doi:10.3390/ijms150712480
Received: 19 May 2014 / Revised: 16 June 2014 / Accepted: 16 June 2014 / Published: 15 July 2014
Cited by 3 | PDF Full-text (1807 KB) | HTML Full-text | XML Full-text
Abstract
Stra8 (Stimulated by Retinoic Acid 8) is considered a meiotic gatekeeper gene. Using reverse transcriptase PCR and rapid amplification of cDNA ends (RACE), the complete sequence of the pig Stra8 gene was cloned. Bioinformatics analyses of this sequence were performed. Using semi-quantitative methods,
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Stra8 (Stimulated by Retinoic Acid 8) is considered a meiotic gatekeeper gene. Using reverse transcriptase PCR and rapid amplification of cDNA ends (RACE), the complete sequence of the pig Stra8 gene was cloned. Bioinformatics analyses of this sequence were performed. Using semi-quantitative methods, the expression characteristics of Stra8 in Testis, cauda epididymis, body epididymis, caput epididymis, seminal vesicles, prostate gland, Cowper’s gland, heart, liver, spleen, lung, kidney, stomach, hypothalamus, pituitary gland, cerebrum, cerebellum, and hippocampus of adult Meishan boar and sow tissues were examined. The expression pattern in the testis of 2-, 30-, 60-, 90-, and 150-day old Meishan boars were analyzed using real-time PCR. We constructed a eukaryotic expression vector for the Stra8 gene and used it to transfect NIH-3T3 cells and third generation pig spermatogonial stem cells (SSCs) cultured in vitro. Testes weight and sperm count in the cauda epididymis were evaluated at various time points. The results showed that the length of the pig Stra8 gene cDNA was 1444 bp encoding 366 amino acids with one typical helix-loop-helix (HLH) domain. It is testes-specific expression. Expression was first detected in boar testis starting at day 2, and its expression significantly (p < 0.05) increased with age and body weight. When NIH-3T3 cells and pig SSCs were transfected with the eukaryotic expression vector EGFP (enhanced green fluorescent protein)-N1-pStra8, it was expressed in the cytoplasm of NIH-3T3 cells. However, in SSCs, Stra8 was expressed predominantly in cytoplasm and few in nucleus. Our data suggest that perhaps Stra8 acts as a transcription factor to initiate meiosis in young boar. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Stromal Cell-Derived Factor 1 Gene Polymorphism Is Associated with Susceptibility to Adverse Long-Term Allograft Outcomes in Non-Diabetic Kidney Transplant Recipients
Int. J. Mol. Sci. 2014, 15(7), 12495-12506; doi:10.3390/ijms150712495
Received: 8 May 2014 / Revised: 30 June 2014 / Accepted: 1 July 2014 / Published: 15 July 2014
Cited by 1 | PDF Full-text (1035 KB) | HTML Full-text | XML Full-text
Abstract
Although the genetic polymorphism of Stromal Cell-Derived Factor 1 (SDF-1) is associated with higher mortality of liver allograft recipients, the role of SDF-1 in the modulation of renal allograft outcomes is unclear. Between March 2000 and January 2008, we recruited 252 non-diabetic renal
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Although the genetic polymorphism of Stromal Cell-Derived Factor 1 (SDF-1) is associated with higher mortality of liver allograft recipients, the role of SDF-1 in the modulation of renal allograft outcomes is unclear. Between March 2000 and January 2008, we recruited 252 non-diabetic renal transplant recipients (RTRs). Baseline characteristics and blood chemistry were recorded. Genomic DNA extraction with polymerase chain reaction-restriction fragment length polymorphism was utilized to analyze the genetic polymorphisms of SDF-1 (rs1801157). The influence of SDF-1 on an adverse renal allograft outcome, defined as either a doubling of serum creatinine, graft failure, or patient death was evaluated. Sixteen patients with the SDF-1 AA/AG genotype and nine with the SDF-1 GG genotype reached an adverse outcome. According to Kaplan-Meier analysis, patients carrying the SDF-1 AA/AG genotype or A allele showed a significantly higher risk of reaching an adverse outcome than those carrying the SDF-1 GG genotype or G allele (p = 0.041; p = 0.0051, respectively; log rank test). Stepwise multivariate Cox proportional regression analysis revealed that patients carrying the SDF-1 AA/AG genotype and A allele had a 2.742-fold (95% CI. 1.106–6.799, p = 0.03) and 2.306-fold (95% CI. 1.254–4.24, p = 0.008) risk of experiencing an adverse outcome. The SDF-1 AA/AG genotype and A allele have a detrimental impact on the long-term outcome of RTRs. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Baicalin Ameliorates H2O2 Induced Cytotoxicity in HK-2 Cells through the Inhibition of ER Stress and the Activation of Nrf2 Signaling
Int. J. Mol. Sci. 2014, 15(7), 12507-12522; doi:10.3390/ijms150712507
Received: 16 April 2014 / Revised: 20 June 2014 / Accepted: 24 June 2014 / Published: 15 July 2014
Cited by 14 | PDF Full-text (1382 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Renal ischemia-reperfusion injury plays a key role in renal transplantation and greatly affects the outcome of allograft. Our previous study proved that Baicalin, a flavonoid glycoside isolated from Scutellaria baicalensis, protects kidney from ischemia-reperfusion injury. This study aimed to study the underlying
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Renal ischemia-reperfusion injury plays a key role in renal transplantation and greatly affects the outcome of allograft. Our previous study proved that Baicalin, a flavonoid glycoside isolated from Scutellaria baicalensis, protects kidney from ischemia-reperfusion injury. This study aimed to study the underlying mechanism in vitro. Human renal proximal tubular epithelial cell line HK-2 cells were stimulated by H2O2 with and without Baicalin pretreatment. The cell viability, apoptosis and oxidative stress level were measured. The expression of endoplasmic reticulum (ER) stress hallmarks, such as binding immunoglobulin protein (BiP) and C/EBP homologous protein (CHOP), were analyzed by western blot and real-time PCR. NF-E2-related factor 2 (Nrf2) expression was also measured. In the H2O2 group, cell viability decreased and cell apoptosis increased. Reactive Oxygen Species (ROS) and Glutathione/Oxidized Glutathione (GSH/GSSG) analysis revealed increased oxidative stress. ER stress and Nrf2 signaling also increased. Baicalin pretreatment ameliorated H2O2-induced cytotoxicity, reduced oxidative stress and ER stress and further activated the anti-oxidative Nrf2 signaling pathway. The inducer of ER stress and the inhibitor of Nrf2 abrogated the protective effects, while the inhibitor of ER stress and the inducer of Nrf2 did not improve the outcome. This study revealed that Baicalin pretreatment serves a protective role against H2O2-induced cytotoxicity in HK-2 cells, where the inhibition of ER stress and the activation of downstream Nrf2 signaling are involved. Full article
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Open AccessArticle The Critical Role of Membrane Cholesterol in Salmonella-Induced Autophagy in Intestinal Epithelial Cells
Int. J. Mol. Sci. 2014, 15(7), 12558-12572; doi:10.3390/ijms150712558
Received: 8 May 2014 / Revised: 6 June 2014 / Accepted: 27 June 2014 / Published: 15 July 2014
Cited by 4 | PDF Full-text (749 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
It was previously observed that plasma membrane cholesterol plays a critical role in the Salmonella-induced phosphatidylinositol 3-kinase-dependent (PI3K)-dependent anti-inflammatory response in intestinal epithelial cells (IECs). The PI3K/Akt pathway is associated with autophagy which has emerged as a critical mechanism of host defense
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It was previously observed that plasma membrane cholesterol plays a critical role in the Salmonella-induced phosphatidylinositol 3-kinase-dependent (PI3K)-dependent anti-inflammatory response in intestinal epithelial cells (IECs). The PI3K/Akt pathway is associated with autophagy which has emerged as a critical mechanism of host defense against several intracellular bacterial pathogens. Plasma membrane contributes directly to the formation of early Atg16L1-positive autophagosome precursors. Therefore, this study aimed to investigate the role of plasma membrane cholesterol on the Salmonella-induced autophagy in IECs. By using methyl-beta-cyclodextrin (MBCD), it was demonstrated that disruption of membrane cholesterol by MBCD enhanced NOD2 and Atg16L1 proteins expression in membrane, and autophagic LC3II proteins expression and LC3 punctae in Salmonella-infected Caco-2 cells, which was counteracted by Atg16L1 siRNA. Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) siRNA enhanced the Salmonella-induced activation of Akt in Caco-2 cells. However, inhibitors of Akt or extracellular signal-regulated kinases (ERK) had no significant effect on Salmonella-induced autophagy Beclin 1 or LC3 proteins expression. In conclusion, our study suggests that cholesterol accumulation in the plasma membrane at the entry site of Salmonella results in the formation of Salmonella-containing vacuole (SCV) and decreased autophagy. Our results offer mechanistic insights on the critical role of membrane cholesterol in the pathogenesis of Salmonella infection in intestinal epithelial cells and the therapeutic potential of its antagonists. Full article
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Open AccessArticle Proteomic Analyses Reveal that Sky1 Modulates Apoptosis and Mitophagy in Saccharomyces cerevisiae Cells Exposed to Cisplatin
Int. J. Mol. Sci. 2014, 15(7), 12573-12590; doi:10.3390/ijms150712573
Received: 11 April 2014 / Revised: 2 July 2014 / Accepted: 2 July 2014 / Published: 15 July 2014
Cited by 1 | PDF Full-text (1972 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Sky1 is the only member of the SR (Serine–Arginine) protein kinase family in Saccharomyces cerevisiae. When yeast cells are treated with the anti-cancer drug cisplatin, Sky1 kinase activity is necessary to produce the cytotoxic effect. In this study, proteome changes in response to
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Sky1 is the only member of the SR (Serine–Arginine) protein kinase family in Saccharomyces cerevisiae. When yeast cells are treated with the anti-cancer drug cisplatin, Sky1 kinase activity is necessary to produce the cytotoxic effect. In this study, proteome changes in response to this drug and/or SKY1 deletion have been evaluated in order to understand the role of Sky1 in the response of yeast cells to cisplatin. Results reveal differential expression of proteins previously related to the oxidative stress response, DNA damage, apoptosis and mitophagy. With these precedents, the role of Sky1 in apoptosis, necrosis and mitophagy has been evaluated by flow-cytometry, fluorescence microscopy, biosensors and fluorescence techniques. After cisplatin treatment, an apoptotic-like process diminishes in the ∆sky1 strain in comparison to the wild-type. The treatment does not affect mitophagy in the wild-type strain, while an increase is observed in the ∆sky1 strain. The increased resistance to cisplatin observed in the ∆sky1 strain may be attributable to a decrease of apoptosis and an increase of mitophagy. Full article
(This article belongs to the collection Advances in Proteomic Research)
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Open AccessArticle A Disease Marker for Aspirin-Induced Chronic Urticaria
Int. J. Mol. Sci. 2014, 15(7), 12591-12603; doi:10.3390/ijms150712591
Received: 20 April 2014 / Revised: 21 May 2014 / Accepted: 21 June 2014 / Published: 15 July 2014
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Abstract
There are currently no diagnostic methods in vitro for aspirin-induced chronic urticaria (AICU) except for the provocation test in vivo. To identify disease markers for AICU, we investigated the single nucleotide polymorphism (SNP) of the promoter loci of high-affinity IgE receptor (
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There are currently no diagnostic methods in vitro for aspirin-induced chronic urticaria (AICU) except for the provocation test in vivo. To identify disease markers for AICU, we investigated the single nucleotide polymorphism (SNP) of the promoter loci of high-affinity IgE receptor (FcεRIα) and CD203c expression level in Chinese patients with AICU. We studied two genotypic and allelic frequencies of rs2427827 (–344C/T) and rs2251746 (–66T/C) gene polymorphisms of FcεRIα in 20 patients with AICU, 52 subjects with airway hypersensitivity without aspirin intolerance, and 50 controls in a Chinese population. The results showed that the frequencies of two SNPs (–344C>T, –66C>T) were similar to the normal controls. The allele frequency of –344CC was significantly higher in the patients with AICU compared to those with airway sensitivity (p = 0.019). We also studied both histamine release and CD203c expression on KU812 cells to assess aspirin-induced basophil activation. We found that the activity of basophil activation of AICU was significantly higher in the patients with AICU compared to those with airway hypersensitivity without aspirin intolerance. The mean fluorescence intensity of the CD203c expression were 122.5 ± 5.2 vs. 103.3 ± 3.3 respectively, (p < 0.05), and the percentages of histamine release were 31.3% ± 7.4% vs. −24.0% ± 17.5%, (p < 0.05) respectively. Although the mean fluorescence intensity of CD203c expression and the percentage of histamine release were significantly up-regulated by aspirin, they were not affected by anti-IgE antibodies. These results suggest that a single SNP of FcεRIα (–344C>T) is less likely to develop AICU and the basophil activation activity in the sera by measuring CD203c expression can be applicable to confirm the diagnosis of AICU. Full article
(This article belongs to the collection Human Single Nucleotide Polymorphisms and Disease Diagnostics)
Open AccessArticle Diurnal Profiles of Melatonin Synthesis-Related Indoles, Catecholamines and Their Metabolites in the Duck Pineal Organ
Int. J. Mol. Sci. 2014, 15(7), 12604-12630; doi:10.3390/ijms150712604
Received: 5 June 2014 / Revised: 1 July 2014 / Accepted: 3 July 2014 / Published: 16 July 2014
Cited by 3 | PDF Full-text (2687 KB) | HTML Full-text | XML Full-text
Abstract
This study characterizes the diurnal profiles of ten melatonin synthesis-related indoles, the quantitative relations between these compounds, and daily variations in the contents of catecholamines and their metabolites in the domestic duck pineal organ. Fourteen-week-old birds, which were reared under a 12L:12D cycle,
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This study characterizes the diurnal profiles of ten melatonin synthesis-related indoles, the quantitative relations between these compounds, and daily variations in the contents of catecholamines and their metabolites in the domestic duck pineal organ. Fourteen-week-old birds, which were reared under a 12L:12D cycle, were killed at two-hour intervals. The indole contents were measured using HPLC with fluorescence detection, whereas the levels of catecholamines and their metabolites were measured using HPLC with electrochemical detection. All indole contents, except for tryptophan, showed significant diurnal variations. The 5-hydroxytryptophan level was approximately two-fold higher during the scotophase than during the photophase. The serotonin content increased during the first half of the photophase, remained elevated for approximately 10 h and then rapidly decreased in the middle of the scotophase. N-acetylserotonin showed the most prominent changes, with a more than 15-fold increase at night. The melatonin cycle demonstrated only an approximately 5-fold difference between the peak and nadir. The 5-methoxytryptamine content was markedly elevated during the scotophase. The 5-hydroxyindole acetic acid, 5-hydroxytryptophol, 5-methoxyindole acetic acid and 5-methoxytryptophol profiles were analogous to the serotonin rhythm. The norepinephrine and dopamine contents showed no significant changes. The DOPA, DOPAC and homovanillic acid levels were higher during the scotophase than during the photophase. Vanillylmandelic acid showed the opposite rhythm, with an elevated level during the daytime. Full article
(This article belongs to the Special Issue Advances in the Research of Melatonin 2014)
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Open AccessArticle Association between Toll-Like Receptor 4 Expression and Neural Stem Cell Proliferation in the Hippocampus Following Traumatic Brain Injury in Mice
Int. J. Mol. Sci. 2014, 15(7), 12651-12664; doi:10.3390/ijms150712651
Received: 30 April 2014 / Revised: 3 July 2014 / Accepted: 4 July 2014 / Published: 17 July 2014
Cited by 5 | PDF Full-text (3141 KB) | HTML Full-text | XML Full-text
Abstract
Whether or how neural stem cells (NSCs) respond to toll-like receptor 4 (TLR4) in an inflammatory environment caused by traumatic brain injury (TBI) has not been understood. In the present study, association between TLR4 expression and NSCs proliferation in the hippocampus was investigated
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Whether or how neural stem cells (NSCs) respond to toll-like receptor 4 (TLR4) in an inflammatory environment caused by traumatic brain injury (TBI) has not been understood. In the present study, association between TLR4 expression and NSCs proliferation in the hippocampus was investigated in a mouse model of TBI using controlled cortical impact (CCI). Hippocampal proliferating cells were labeled with the thymidine analog 5-bromo-2-deoxyuridine (BrdU). In order to identify NSCs, the proliferating cells were further co-labeled with BrdU/sex determination region of Y chromosome related high mobility group box gene 2 (SOX2). Morphological observation on the expression of BrdU, SOX2, and TLR4 in the hippocampus was performed by inmmunofluorescence (IF). Relative quantification of TLR4 expression at the protein and mRNA level was performed using Western blotting and real-time polymerase chain reaction (PCR). It was observed that BrdU+/SOX2+cells accounted for 95.80% ± 7.91% among BrdU+ cells; several BrdU+ cells and SOX2+ cells in the hippocampus were also TLR4-positive post injury, and that BrdU+ cell numbers, together with TLR4 expression at either protein or mRNA level, increased significantly in TBI mice over 1, 3, 7, 14, and 21 days survivals and changed in a similar temporal pattern with a peak at 3 day post-injury. These results indicate that hippocampal proliferating cells (suggestive of NSCs) expressed TLR4, and that there was a potential association between increased expression of TLR4 and the proliferation of NSCs post TBI. It is concluded that hippocampal TLR4 may play a potential role in endogenous neurogenesis after TBI. Full article
(This article belongs to the Special Issue Neurological Injuries’ Monitoring, Tracking and Treatment)
Open AccessArticle Transforming Growth Factor-β1 (TGF-β1) Induces Mouse Precartilaginous Stem Cell Proliferation through TGF-β Receptor II (TGFRII)-Akt-β-Catenin Signaling
Int. J. Mol. Sci. 2014, 15(7), 12665-12676; doi:10.3390/ijms150712665
Received: 24 May 2014 / Revised: 24 June 2014 / Accepted: 26 June 2014 / Published: 17 July 2014
Cited by 4 | PDF Full-text (1220 KB) | HTML Full-text | XML Full-text
Abstract
Precartilaginous stem cells (PSCs) could self-renew or differentiate into chondrocytes to promote bone growth. In the current study, we aim to understand the role of transforming growth factor-β1 (TGF-β1) in precartilaginous stem cell (PSC) proliferation, and to study the underlying mechanisms. We successfully
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Precartilaginous stem cells (PSCs) could self-renew or differentiate into chondrocytes to promote bone growth. In the current study, we aim to understand the role of transforming growth factor-β1 (TGF-β1) in precartilaginous stem cell (PSC) proliferation, and to study the underlying mechanisms. We successfully purified and primary-cultured PSCs from the neonate mice’ perichondrial mesenchyme, and their phenotype was confirmed by the PSC marker fibroblast growth factor receptor-3 (FGFR-3) overexpression. We found that TGF-β1 induced Akt-glycogen synthase kinase-3β (GSK3β) phosphorylation and β-catenin nuclear translocation in the mouse PSCs, which was almost blocked by TGF-β receptor-II (TGFRII) shRNA knockdown. Further, perifosine and MK-2206, two Akt-specific inhibitors, suppressed TGF-β1-induced GSK3β phosphorylation and β-catenin nuclear translocation. Akt inhibitors, as well as β-catenin shRNA knockdown largely inhibited TGF-β1-stimulated cyclin D1/c-myc gene transcription and mouse PSC proliferation. Based on these results, we suggest that TGF-β1 induces Akt activation to promote β-catenin nuclear accumulation, which then regulates cyclin D1/c-myc gene transcription to eventually promote mouse PSC proliferation. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Novel and Functional DNA Sequence Variants within the GATA6 Gene Promoter in Ventricular Septal Defects
Int. J. Mol. Sci. 2014, 15(7), 12677-12687; doi:10.3390/ijms150712677
Received: 29 April 2014 / Revised: 16 June 2014 / Accepted: 8 July 2014 / Published: 17 July 2014
Cited by 2 | PDF Full-text (1068 KB) | HTML Full-text | XML Full-text
Abstract
Congenital heart disease (CHD) is the most common birth defect in humans. Genetic causes and underlying molecular mechanisms for isolated CHD remain largely unknown. Studies have demonstrated that GATA transcription factor 6 (GATA6) plays an essential role in the heart development.
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Congenital heart disease (CHD) is the most common birth defect in humans. Genetic causes and underlying molecular mechanisms for isolated CHD remain largely unknown. Studies have demonstrated that GATA transcription factor 6 (GATA6) plays an essential role in the heart development. Mutations in GATA6 gene have been associated with diverse types of CHD. As GATA6 functions in a dosage-dependent manner, we speculated that changed GATA6 levels, resulting from DNA sequence variants (DSVs) within the gene regulatory regions, may mediate the CHD development. In the present study, GATA6 gene promoter was genetically and functionally analyzed in large groups of patients with ventricular septal defect (VSD) (n = 359) and ethnic-matched healthy controls (n = 365). In total, 11 DSVs, including four SNPs, were identified in VSD patients and controls. Two novel and heterozygous DSVs, g.22169190A>T and g.22169311C>G, were identified in two VSD patients, but in none of controls. In cultured cardiomyocytes, the activities of the GATA6 gene promoter were significantly reduced by the DSVs g.22169190A>T and g.22169311C>G. Therefore, our findings suggested that the DSVs within the GATA6 gene promoter identified in VSD patients may change GATA6 levels, contributing to the VSD development as a risk factor. Full article
(This article belongs to the collection Human Single Nucleotide Polymorphisms and Disease Diagnostics)
Open AccessArticle Role of EZH2 Polymorphisms in Esophageal Squamous Cell Carcinoma Risk in Han Chinese Population
Int. J. Mol. Sci. 2014, 15(7), 12688-12697; doi:10.3390/ijms150712688
Received: 28 May 2014 / Revised: 5 July 2014 / Accepted: 8 July 2014 / Published: 17 July 2014
Cited by 2 | PDF Full-text (727 KB) | HTML Full-text | XML Full-text
Abstract
Gene single nucleotide polymorphisms play a critical role in the development of esophageal squamous cell carcinoma (ESCC). The aim of this study is to investigate the associations between EZH2 gene polymorphisms and ESCC risk. We undertook a case-control study to analyze three EZH2
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Gene single nucleotide polymorphisms play a critical role in the development of esophageal squamous cell carcinoma (ESCC). The aim of this study is to investigate the associations between EZH2 gene polymorphisms and ESCC risk. We undertook a case-control study to analyze three EZH2 polymorphisms (148505302C > T, 2110 + 6A > C and 626 − 394T > C) in an Han Chinese population, by extraction of genomic DNA from the peripheral blood of 476 patients with ESCC and 492 control participants, and performed EZH2 genotyping using DNA sequencing. The obtained results indicated that overall, no statistically significant association was observed in 148505302C > T and 2110 + 6A > C. However, 626 − 394T > C genotype was at increased risk of ESCCs (p = 0.006; odds ratio (OR) = 1.131, CI 95%: 1.034–1.236). Moreover, 626 − 394C/C genotype ESCCs were more significantly common in patients with tumor size of >5 cm than T allele ESCC and in cases of poor differentiation and lower advanced pathological stage. In conclusion, polymorphism in 626 − 394T > C was observed to be associated with susceptibility of ESCC. Nevertheless, further investigation with a larger sample size is needed to support our results. Full article
(This article belongs to the collection Human Single Nucleotide Polymorphisms and Disease Diagnostics)
Open AccessArticle Carnosic Acid Inhibits the Epithelial-Mesenchymal Transition in B16F10 Melanoma Cells: A Possible Mechanism for the Inhibition of Cell Migration
Int. J. Mol. Sci. 2014, 15(7), 12698-12713; doi:10.3390/ijms150712698
Received: 16 June 2014 / Revised: 12 July 2014 / Accepted: 14 July 2014 / Published: 17 July 2014
Cited by 5 | PDF Full-text (490 KB) | HTML Full-text | XML Full-text
Abstract
Carnosic acid is a natural benzenediol abietane diterpene found in rosemary and exhibits anti-inflammatory, antioxidant, and anti-carcinogenic activities. In this study, we evaluated the effects of carnosic acid on the metastatic characteristics of B16F10 melanoma cells. When B16F10 cells were cultured in an
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Carnosic acid is a natural benzenediol abietane diterpene found in rosemary and exhibits anti-inflammatory, antioxidant, and anti-carcinogenic activities. In this study, we evaluated the effects of carnosic acid on the metastatic characteristics of B16F10 melanoma cells. When B16F10 cells were cultured in an in vitro Transwell system, carnosic acid inhibited cell migration in a dose-dependent manner. Carnosic acid suppressed the adhesion of B16F10 cells, as well as the secretion of matrix metalloproteinase (MMP)-9, tissue inhibitor of metalloproteinase (TIMP)-1, urokinase plasminogen activator (uPA), and vascular cell adhesion molecule (VCAM)-1. Interestingly, secretion of TIMP-2 increased significantly in B16F10 cells treated with 10 μmol/L carnosic acid. Additionally, carnosic acid suppressed the mesenchymal markers snail, slug, vimentin, and N-cadherin and induced epithelial marker E-cadherin. Furthermore, carnosic acid suppressed phosphorylation of Src, FAK, and AKT. These results indicate that inhibition of the epithelial-mesenchymal transition may be important for the carnosic acid-induced inhibition of B16F10 cell migration. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Study on the Characteristics of Gas Molecular Mean Free Pathin Nanopores by Molecular Dynamics Simulations
Int. J. Mol. Sci. 2014, 15(7), 12714-12730; doi:10.3390/ijms150712714
Received: 12 May 2014 / Revised: 2 July 2014 / Accepted: 7 July 2014 / Published: 18 July 2014
Cited by 5 | PDF Full-text (2709 KB) | HTML Full-text | XML Full-text
Abstract
This paper presents studies on the characteristics of gas molecular mean freepath in nanopores by molecular dynamics simulation. Our study results indicate that themean free path of all molecules in nanopores depend on both the radius of the nanoporeand the gas-solid interaction strength.
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This paper presents studies on the characteristics of gas molecular mean freepath in nanopores by molecular dynamics simulation. Our study results indicate that themean free path of all molecules in nanopores depend on both the radius of the nanoporeand the gas-solid interaction strength. Besides mean free path of all molecules in thenanopore, this paper highlights the gas molecular mean free path at different positions ofthe nanopore and the anisotropy of the gas molecular mean free path at nanopores. Themolecular mean free path varies with the molecule’s distance from the center of thenanopore. The least value of the mean free path occurs at the wall surface of the nanopore.The present paper found that the gas molecular mean free path is anisotropic when gas isconfined in nanopores. The radial gas molecular mean free path is much smaller than themean free path including all molecular collisions occuring in three directions. Our studyresults also indicate that when gas is confined in nanopores the gas molecule number densitydoes not affect the gas molecular mean free path in the same way as it does for the gas inunbounded space. These study results may bring new insights into understanding the gasflow’s characteristic at nanoscale. Full article
(This article belongs to the Section Physical Chemistry, Theoretical and Computational Chemistry)
Open AccessArticle A Novel Feature Extraction Scheme with Ensemble Coding for Protein–Protein Interaction Prediction
Int. J. Mol. Sci. 2014, 15(7), 12731-12749; doi:10.3390/ijms150712731
Received: 7 May 2014 / Revised: 23 June 2014 / Accepted: 14 July 2014 / Published: 18 July 2014
Cited by 3 | PDF Full-text (1796 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Protein–protein interactions (PPIs) play key roles in most cellular processes, such as cell metabolism, immune response, endocrine function, DNA replication, and transcription regulation. PPI prediction is one of the most challenging problems in functional genomics. Although PPI data have been increasing because of
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Protein–protein interactions (PPIs) play key roles in most cellular processes, such as cell metabolism, immune response, endocrine function, DNA replication, and transcription regulation. PPI prediction is one of the most challenging problems in functional genomics. Although PPI data have been increasing because of the development of high-throughput technologies and computational methods, many problems are still far from being solved. In this study, a novel predictor was designed by using the Random Forest (RF) algorithm with the ensemble coding (EC) method. To reduce computational time, a feature selection method (DX) was adopted to rank the features and search the optimal feature combination. The DXEC method integrates many features and physicochemical/biochemical properties to predict PPIs. On the Gold Yeast dataset, the DXEC method achieves 67.2% overall precision, 80.74% recall, and 70.67% accuracy. On the Silver Yeast dataset, the DXEC method achieves 76.93% precision, 77.98% recall, and 77.27% accuracy. On the human dataset, the prediction accuracy reaches 80% for the DXEC-RF method. We extended the experiment to a bigger and more realistic dataset that maintains 50% recall on the Yeast All dataset and 80% recall on the Human All dataset. These results show that the DXEC method is suitable for performing PPI prediction. The prediction service of the DXEC-RF classifier is available at http://ailab.ahu.edu.cn:8087/ DXECPPI/index.jsp. Full article
(This article belongs to the collection Proteins and Protein-Ligand Interactions)
Open AccessArticle S-(−)-10,11-Dihydroxyfarnesoic Acid Methyl Ester Inhibits Melanin Synthesis in Murine Melanocyte Cells
Int. J. Mol. Sci. 2014, 15(7), 12750-12763; doi:10.3390/ijms150712750
Received: 31 March 2014 / Revised: 1 July 2014 / Accepted: 8 July 2014 / Published: 18 July 2014
Cited by 3 | PDF Full-text (5097 KB) | HTML Full-text | XML Full-text
Abstract
The development of antimelanogenic agents is important for the prevention of serious aesthetic problems such as melasmas, freckles, age spots, and chloasmas. In the course of screening for melanin synthesis inhibitors, we found that the culture broth from an insect morphopathogenic fungus, Beauveria
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The development of antimelanogenic agents is important for the prevention of serious aesthetic problems such as melasmas, freckles, age spots, and chloasmas. In the course of screening for melanin synthesis inhibitors, we found that the culture broth from an insect morphopathogenic fungus, Beauveria bassiana CS1029, exhibits potent antimelanogenic activity. We isolated and purified an active metabolite and identified it as S-(−)-10,11-dihydroxyfarnesoic acid methyl ester (dhFAME), an insect juvenile hormone. To address whether dhFAME inhibits melanin synthesis, we first measured the size of the melanin biosynthesis inhibition zone caused by dhFAME. dhFAME also showed inhibitory activity against mushroom tyrosinase in Melan-a cells. Intracellular, dose-dependent tyrosinase inhibition activity was also confirmed by zymography. In addition, we showed that dhFAME strongly inhibits melanin synthesis in Melan-a cells. Furthermore, we compared levels of TYR, TRP-1, TRP-2, MITF, and MC1R mRNA expression by reverse-transcription polymerase chain reaction and showed that treatment of Melan-a cells with 35 μM dhFAME led to an 11-fold decrease in TYR expression, a 6-fold decrease in TRP-2 expression, and a 5-fold decrease in MITF expression. Together, these results indicate that dhFAME is a potent inhibitor of melanin synthesis that can potentially be used for cosmetic biomaterial(s). Full article
Open AccessArticle Clinical Significance of POU5F1P1 rs10505477 Polymorphism in Chinese Gastric Cancer Patients Receving Cisplatin-Based Chemotherapy after Surgical Resection
Int. J. Mol. Sci. 2014, 15(7), 12764-12777; doi:10.3390/ijms150712764
Received: 26 April 2014 / Revised: 30 June 2014 / Accepted: 9 July 2014 / Published: 18 July 2014
Cited by 6 | PDF Full-text (731 KB) | HTML Full-text | XML Full-text
Abstract
This study aimed to investigate the association between POU class5 homeobox 1 pseudogene 1 gene (POU5F1P1) rs10505477 polymorphism and the prognosis of Chinese gastric cancer patients, who received cisplatin-based chemotherapy after surgical resection. POU5F1P1 rs10505477 was genotyped using the SNaPshot method
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This study aimed to investigate the association between POU class5 homeobox 1 pseudogene 1 gene (POU5F1P1) rs10505477 polymorphism and the prognosis of Chinese gastric cancer patients, who received cisplatin-based chemotherapy after surgical resection. POU5F1P1 rs10505477 was genotyped using the SNaPshot method in 944 gastric cancer patients who received gastrectomy. The association of rs10505477 G > A polymorphism with the progression and prognosis in gastric cancer patients was statistically analyzed using the SPSS version 18.0 for Windows. The results reveal that rs10505477 polymorphism has a negatively effect on the overall survival of gastric cancer patients in cisplatin-based chemotherapy subgroup (HR = 1.764, 95% CI = 1.069–2.911, p = 0.023). Our preliminary study indicates for the first time that POU5F1P1 rs10505477 is correlated with survival of gastric cancer patients who receving cisplatin-based chemotherapy after gastrectomy. Further studies are warranted to investigate the mechanism and to verify our results in different populations. Full article
Open AccessArticle Cordycepin Down-Regulates Multiple Drug Resistant (MDR)/HIF-1α through Regulating AMPK/mTORC1 Signaling in GBC-SD Gallbladder Cancer Cells
Int. J. Mol. Sci. 2014, 15(7), 12778-12790; doi:10.3390/ijms150712778
Received: 20 May 2014 / Revised: 13 June 2014 / Accepted: 4 July 2014 / Published: 18 July 2014
Cited by 9 | PDF Full-text (1405 KB) | HTML Full-text | XML Full-text
Abstract
Gallbladder cancer is the most common malignancy of the bile duct, with low 5-year survival rate and poor prognosis. Novel effective treatments are urgently needed for the therapy of this disease. Here, we showed that cordycepin, the bioactive compound in genus Cordyceps, induced
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Gallbladder cancer is the most common malignancy of the bile duct, with low 5-year survival rate and poor prognosis. Novel effective treatments are urgently needed for the therapy of this disease. Here, we showed that cordycepin, the bioactive compound in genus Cordyceps, induced growth inhibition and apoptosis in cultured gallbladder cancer cells (Mz-ChA-1, QBC939 and GBC-SD lines). We found that cordycepin inhibited mTOR complex 1 (mTORC1) activation and down-regulated multiple drug resistant (MDR)/hypoxia-inducible factor 1α (HIF-1α) expression through activating of AMP-activated protein kinase (AMPK) signaling in gallbladder cancer GBC-SD cells. Contrarily, AMPKα1-shRNA depletion dramatically inhibited cordycepin-induced molecular changes as well as GBC-SD cell apoptosis. Further, our results showed that co-treatment with a low concentration cordycepin could remarkably enhance the chemosensitivity of GBC-SD cells to gemcitabine and 5-fluorouracil (5-FU), and the mechanism may be attributed to AMPK activation and MDR degradation. In summary, cordycepin induces growth inhibition and apoptosis in gallbladder cancer cells via activating AMPK signaling. Cordycepin could be a promising new drug or chemo-adjuvant for gallbladder cancer. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Antibacterial Effect of Dental Adhesive Containing Dimethylaminododecyl Methacrylate on the Development of Streptococcus mutans Biofilm
Int. J. Mol. Sci. 2014, 15(7), 12791-12806; doi:10.3390/ijms150712791
Received: 9 June 2014 / Revised: 27 June 2014 / Accepted: 2 July 2014 / Published: 18 July 2014
Cited by 8 | PDF Full-text (1084 KB) | HTML Full-text | XML Full-text
Abstract
Antibacterial bonding agents and composites containing dimethylaminododecyl methacrylate (DMADDM) have been recently developed. The objectives of this study were to investigate the antibacterial effect of novel adhesives containing different mass fractions of DMADDM on Streptococcus mutans (S. mutans) biofilm at different
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Antibacterial bonding agents and composites containing dimethylaminododecyl methacrylate (DMADDM) have been recently developed. The objectives of this study were to investigate the antibacterial effect of novel adhesives containing different mass fractions of DMADDM on Streptococcus mutans (S. mutans) biofilm at different developmental stages. Different mass fractions of DMADDM were incorporated into adhesives and S. mutans biofilm at different developmetal stages were analyzed by MTT assays, lactic acid measurement, confocal laser scanning microscopy and scanning electron microscopy observations. Exopolysaccharides (EPS) staining was used to analyze the inhibitory effect of DMADDM on the biofilm extracellular matrix. Dentin microtensile strengths were also measured. Cured adhesives containing DMADDM could greatly reduce metabolic activity and lactic acid production during the development of S. mutans biofilms (p < 0.05). In earlier stages of biofilm development, there were no significant differences of inhibitory effects between the 2.5% DMADDM and 5% DMADDM group. However, after 72 h, the anti-biofilm effects of adhesives containing 5% DMADDM were significantly stronger than any other group. Incorporation of DMADDM into adhesive did not adversely affect dentin bond strength. In conclusion, adhesives containing DMADDM inhibited the growth, lactic acid production and EPS metabolism of S. mutans biofilm at different stages, with no adverse effect on its dentin adhesive bond strength. The bonding agents have the potential to control dental biofilms and combat tooth decay, and DMADDM is promising for use in a wide range of dental adhesive systems and restoratives. Full article
(This article belongs to the Special Issue Antimicrobial Polymers)
Open AccessArticle Coexpression and Secretion of Endoglucanase and Phytase Genes in Lactobacillus reuteri
Int. J. Mol. Sci. 2014, 15(7), 12842-12860; doi:10.3390/ijms150712842
Received: 24 March 2014 / Revised: 19 May 2014 / Accepted: 1 July 2014 / Published: 21 July 2014
Cited by 7 | PDF Full-text (1533 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A multifunctional transgenic Lactobacillus with probiotic characteristics and an ability to degrade β-glucan and phytic acid (phytate) was engineered to improve nutrient utilization, increase production performance and decrease digestive diseases in broiler chickens. The Bacillus subtilis WL001 endoglucanase gene (celW) and
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A multifunctional transgenic Lactobacillus with probiotic characteristics and an ability to degrade β-glucan and phytic acid (phytate) was engineered to improve nutrient utilization, increase production performance and decrease digestive diseases in broiler chickens. The Bacillus subtilis WL001 endoglucanase gene (celW) and Aspergillus fumigatus WL002 phytase gene (phyW) mature peptide (phyWM) were cloned into an expression vector with the lactate dehydrogenase promoter of Lactobacillus casei and the secretion signal peptide of the Lactococcus lactis usp45 gene. This construct was then transformed into Lactobacillus reuteri XC1 that had been isolated from the gastrointestinal tract of broilers. Heterologous enzyme production and feed effectiveness of this genetically modified L. reuteri strain were investigated and evaluated. Sodium dodecyl sulfate polyacrylamide gel electrophoresis analysis showed that the molecular mass of phyWM and celW was approximately 48.2 and 55 kDa, respectively, consistent with their predicted molecular weights. Endoglucanase and phytase activities in the extracellular fraction of the transformed L. reuteri culture were 0.68 and 0.42 U/mL, respectively. Transformed L. reuteri improved the feed conversion ratio of broilers from 21 to 42 days of age and over the whole feeding period. However, there was no effect on body weight gain and feed intake of chicks. Transformed L. reuteri supplementation improved levels of ash, calcium and phosphorus in tibiae at day 21 and of phosphorus at day 42. In addition, populations of Escherichia coli, Veillonella spp. and Bacteroides vulgatus were decreased, while populations of Bifidobacterium genus and Lactobacillus spp. were increased in the cecum at day 21. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle 4-Hydroxyphenylacetic Acid Attenuated Inflammation and Edema via Suppressing HIF-1α in Seawater Aspiration-Induced Lung Injury in Rats
Int. J. Mol. Sci. 2014, 15(7), 12861-12884; doi:10.3390/ijms150712861
Received: 6 April 2014 / Revised: 24 June 2014 / Accepted: 2 July 2014 / Published: 21 July 2014
Cited by 9 | PDF Full-text (2613 KB) | HTML Full-text | XML Full-text
Abstract
4-Hydroxyphenylacetic acid (4-HPA) is an active component of Chinese herb Aster tataricus which had been widely used in China for the treatment of pulmonary diseases. The aim of this study is to investigate the effect of 4-HPA on seawater aspiration-induced lung injury. Pulmonary
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4-Hydroxyphenylacetic acid (4-HPA) is an active component of Chinese herb Aster tataricus which had been widely used in China for the treatment of pulmonary diseases. The aim of this study is to investigate the effect of 4-HPA on seawater aspiration-induced lung injury. Pulmonary inflammation and edema were assessed by enzyme-linked immunosorbent assay (ELISA), bronchoalveolar lavage fluid (BALF) white cell count, Evans blue dye analysis, wet to dry weight ratios, and histology study. Hypoxia-inducible factor-1α (HIF-1α) siRNA and permeability assay were used to study the effect of 4-HPA on the production of inflammatory cytokines and monolayer permeability in vitro. The results showed that 4-HPA reduced seawater instillation-induced mortality in rats. In lung tissues, 4-HPA attenuated hypoxia, inflammation, vascular leak, and edema, and decreased HIF-1α protein level. In primary rat alveolar epithelial cells (AEC), 4-HPA decreased hypertonicity- and hypoxia-induced HIF-1α protein levels through inhibiting the activations of protein translational regulators and via promoting HIF-1α protein degradation. In addition, 4-HPA lowered inflammatory cytokines levels through suppressing hypertonicity- and hypoxia-induced HIF-1α in NR8383 macrophages. Moreover, 4-HPA decreased monolayer permeability through suppressing hypertonicity and hypoxia-induced HIF-1α, which was mediated by inhibiting vascular endothelial growth factor (VEGF) in rat lung microvascular endothelial cell line (RLMVEC). In conclusion, 4-HPA attenuated inflammation and edema through suppressing hypertonic and hypoxic induction of HIF-1α in seawater aspiration-induced lung injury in rats. Full article
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Open AccessArticle Effects of β2-Adrenergic Receptor Gene Polymorphisms on Ritodrine Therapy in Pregnant Women with Preterm Labor: Prospective Follow-Up Study
Int. J. Mol. Sci. 2014, 15(7), 12885-12894; doi:10.3390/ijms150712885
Received: 27 May 2014 / Revised: 25 June 2014 / Accepted: 11 July 2014 / Published: 21 July 2014
Cited by 1 | PDF Full-text (705 KB) | HTML Full-text | XML Full-text
Abstract
This study aimed to evaluate the effects of β2-adrenergic receptor (ADRB2) gene polymorphisms on ritodrine therapy outcomes in patients with preterm labor. Genotyping analysis of ADRB2 gene (rs1042713, rs1042714, rs1042717, rs1042718, and rs1042719) was performed on 137 patients with preterm
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This study aimed to evaluate the effects of β2-adrenergic receptor (ADRB2) gene polymorphisms on ritodrine therapy outcomes in patients with preterm labor. Genotyping analysis of ADRB2 gene (rs1042713, rs1042714, rs1042717, rs1042718, and rs1042719) was performed on 137 patients with preterm labor. Survival analysis was conducted for the effects of SNPs on the median time to delivery as a primary outcome. The median time to delivery in the study patients was 349.3 h. Gestational age at admission and modified Bishop scores revealed significant effects on time to delivery (p < 0.001). Among studied SNPs, rs1042717 and rs1042718 showed linkage disequilibrium in this population, and their effects on time to delivery were marginally significant (p < 0.1). Patients with variant-homozygotes in the rs1042713 showed considerably shortened time to delivery compared to wild-allele carriers. The rs1042719 polymorphism significantly affected time to delivery in both univariate and multivariate analysis; the GC and CC carriers showed 64% decrease in time to delivery compared to the wild-type homozygote carriers. Based on the results, it was concluded that the gene polymorphisms of ADRB2 could affect ritodrine therapy in patients with preterm labor. However, given the single-center and the relatively small sample size, our hypothesis requires further independent validation using multi-center and large sample size. Full article
(This article belongs to the collection Human Single Nucleotide Polymorphisms and Disease Diagnostics)
Open AccessArticle Rapid Adsorption of Heavy Metals by Fe3O4/Talc Nanocomposite and Optimization Study Using Response Surface Methodology
Int. J. Mol. Sci. 2014, 15(7), 12913-12927; doi:10.3390/ijms150712913
Received: 31 May 2014 / Revised: 23 June 2014 / Accepted: 1 July 2014 / Published: 21 July 2014
Cited by 12 | PDF Full-text (1391 KB) | HTML Full-text | XML Full-text
Abstract
Fe3O4/talc nanocomposite was used for removal of Cu(II), Ni(II), and Pb(II) ions from aqueous solutions. Experiments were designed by response surface methodology (RSM) and a quadratic model was used to predict the variables. The adsorption parameters such as adsorbent
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Fe3O4/talc nanocomposite was used for removal of Cu(II), Ni(II), and Pb(II) ions from aqueous solutions. Experiments were designed by response surface methodology (RSM) and a quadratic model was used to predict the variables. The adsorption parameters such as adsorbent dosage, removal time, and initial ion concentration were used as the independent variables and their effects on heavy metal ion removal were investigated. Analysis of variance was incorporated to judge the adequacy of the models. Optimal conditions with initial heavy metal ion concentration of 100, 92 and 270 mg/L, 120 s of removal time and 0.12 g of adsorbent amount resulted in 72.15%, 50.23%, and 91.35% removal efficiency for Cu(II), Ni(II), and Pb(II), respectively. The predictions of the model were in good agreement with experimental results and the Fe3O4/talc nanocomposite was successfully used to remove heavy metals from aqueous solutions. Full article
(This article belongs to the Section Material Sciences and Nanotechnology)
Open AccessArticle WNT16B from Ovarian Fibroblasts Induces Differentiation of Regulatory T Cells through β-Catenin Signal in Dendritic Cells
Int. J. Mol. Sci. 2014, 15(7), 12928-12939; doi:10.3390/ijms150712928
Received: 16 May 2014 / Revised: 4 July 2014 / Accepted: 14 July 2014 / Published: 21 July 2014
Cited by 5 | PDF Full-text (1485 KB) | HTML Full-text | XML Full-text
Abstract
Treatment for cancer can induce a series of secreted factors into the tumor microenvironment, which can affect cancer progression. Wingless-type MMTV (mouse mammary tumor virus) integration site 16B (WNT16B) is a new member of the WNT family and has been reported to play
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Treatment for cancer can induce a series of secreted factors into the tumor microenvironment, which can affect cancer progression. Wingless-type MMTV (mouse mammary tumor virus) integration site 16B (WNT16B) is a new member of the WNT family and has been reported to play growth-related roles in previous studies. In this study, we found WNT16B could be expressed and secreted into the microenvironment by human ovarian fibroblasts after DNA damage-associated treatment, including chemotherapy drugs and radiation. We also demonstrated that fibroblast-derived WNT16B could result in accumulation of β-catenin in dendritic cells and secretion of interleukin-10 (IL-10) and transforming growth factor beta (TGF-β), which contributed to the differentiation of regulatory T cells in a co-culture environment. These results shed light on the roles of WNT16B in immune regulation, especially in regard to cancer treatment. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Identifying the Subfamilies of Voltage-Gated Potassium Channels Using Feature Selection Technique
Int. J. Mol. Sci. 2014, 15(7), 12940-12951; doi:10.3390/ijms150712940
Received: 10 June 2014 / Revised: 13 July 2014 / Accepted: 14 July 2014 / Published: 22 July 2014
Cited by 12 | PDF Full-text (957 KB) | HTML Full-text | XML Full-text
Abstract
Voltage-gated K+ channel (VKC) plays important roles in biology procession, especially in nervous system. Different subfamilies of VKCs have different biological functions. Thus, knowing VKCs’ subfamilies has become a meaningful job because it can guide the direction for the disease diagnosis and
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Voltage-gated K+ channel (VKC) plays important roles in biology procession, especially in nervous system. Different subfamilies of VKCs have different biological functions. Thus, knowing VKCs’ subfamilies has become a meaningful job because it can guide the direction for the disease diagnosis and drug design. However, the traditional wet-experimental methods were costly and time-consuming. It is highly desirable to develop an effective and powerful computational tool for identifying different subfamilies of VKCs. In this study, a predictor, called iVKC-OTC, has been developed by incorporating the optimized tripeptide composition (OTC) generated by feature selection technique into the general form of pseudo-amino acid composition to identify six subfamilies of VKCs. One of the remarkable advantages of introducing the optimized tripeptide composition is being able to avoid the notorious dimension disaster or over fitting problems in statistical predictions. It was observed on a benchmark dataset, by using a jackknife test, that the overall accuracy achieved by iVKC-OTC reaches to 96.77% in identifying the six subfamilies of VKCs, indicating that the new predictor is promising or at least may become a complementary tool to the existing methods in this area. It has not escaped our notice that the optimized tripeptide composition can also be used to investigate other protein classification problems. Full article
(This article belongs to the collection Advances in Proteomic Research)
Open AccessArticle Molecular Method for Sex Identification of Half-Smooth Tongue Sole (Cynoglossus semilaevis) Using a Novel Sex-Linked Microsatellite Marker
Int. J. Mol. Sci. 2014, 15(7), 12952-12958; doi:10.3390/ijms150712952
Received: 23 January 2014 / Revised: 28 March 2014 / Accepted: 23 April 2014 / Published: 22 July 2014
Cited by 1 | PDF Full-text (1331 KB) | HTML Full-text | XML Full-text
Abstract
Half-smooth tongue sole (Cynoglossus semilaevis) is one of the most important flatfish species for aquaculture in China. To produce a monosex population, we attempted to develop a marker-assisted sex control technique in this sexually size dimorphic fish. In this study, we
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Half-smooth tongue sole (Cynoglossus semilaevis) is one of the most important flatfish species for aquaculture in China. To produce a monosex population, we attempted to develop a marker-assisted sex control technique in this sexually size dimorphic fish. In this study, we identified a co-dominant sex-linked marker (i.e., CyseSLM) by screening genomic microsatellites and further developed a novel molecular method for sex identification in the tongue sole. CyseSLM has a sequence similarity of 73%–75% with stickleback, medaka, Fugu and Tetraodon. At this locus, two alleles (i.e., A244 and A234) were amplified from 119 tongue sole individuals with primer pairs CyseSLM-F1 and CyseSLM-R. Allele A244 was present in all individuals, while allele A234 (female-associated allele, FAA) was mostly present in females with exceptions in four male individuals. Compared with the sequence of A244, A234 has a 10-bp deletion and 28 SNPs. A specific primer (CyseSLM-F2) was then designed based on the A234 sequence, which amplified a 204 bp fragment in all females and four males with primer CyseSLM-R. A time-efficient multiplex PCR program was developed using primers CyseSLM-F2, CyseSLM-R and the newly designed primer CyseSLM-F3. The multiplex PCR products with co-dominant pattern could be detected by agarose gel electrophoresis, which accurately identified the genetic sex of the tongue sole. Therefore, we have developed a rapid and reliable method for sex identification in tongue sole with a newly identified sex-linked microsatellite marker. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Astragalus membranaceus Inhibits Peritoneal Fibrosis via Monocyte Chemoattractant Protein (MCP)-1 and the Transforming Growth Factor-β1 (TGF-β1) Pathway in Rats Submitted to Peritoneal Dialysis
Int. J. Mol. Sci. 2014, 15(7), 12959-12971; doi:10.3390/ijms150712959
Received: 16 June 2014 / Revised: 1 July 2014 / Accepted: 4 July 2014 / Published: 22 July 2014
Cited by 7 | PDF Full-text (5244 KB) | HTML Full-text | XML Full-text
Abstract
Inflammation and transforming growth factor-β1 (TGF-β1) contribute to the development of peritoneal fibrosis (PF), which is associated with peritoneal dialysis (PD). Astragalus membranaceus (Astragalus) has anti-inflammatory and anti-fibrotic effects in many diseases. The goal of this study was to determine the
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Inflammation and transforming growth factor-β1 (TGF-β1) contribute to the development of peritoneal fibrosis (PF), which is associated with peritoneal dialysis (PD). Astragalus membranaceus (Astragalus) has anti-inflammatory and anti-fibrotic effects in many diseases. The goal of this study was to determine the anti-fibrotic effects of Astragalus on the PF response to PD. A rat model of PD was induced using standard PD fluid, and PF was verified by HE and Masson’s staining, as well as through the expression of fibroblast surface protein (FSP) and collagen III. The expression levels of monocyte chemoattractant protein (MCP)-1, F4/80 (macrophage/monocyte marker in rat), TGF-β1 and the downstream proteins phospho-SMAD 2/3 in dialyzed peritoneal tissue treated with or without Astragalus was evaluated using immunohistochemistry analysis. Overall correlations between MCP-1 and TGF-β1 staining were analyzed using both the Spearman and Pearson methods. The results showed that Astragalus could inhibit the recruitment and activation of monocytes/macrophages, thereby reducing the production of TGF-β1 in the dialyzed peritoneal membrane. PF was also significantly decreased following treatment with Astragalus. MCP-1 expression had a strong positive correlation with TGF-β1 sensitivity, suggesting that the anti-fibrotic function of Astragalus was mediated by MCP-1 and the TGF-β1 pathway. Our results indicate that Astragalus could be a useful agent against PD-induced PF. Full article
Open AccessArticle Improved Fibroblast Functionalities by Microporous Pattern Fabricated by Microelectromechanical Systems
Int. J. Mol. Sci. 2014, 15(7), 12998-13009; doi:10.3390/ijms150712998
Received: 4 May 2014 / Revised: 31 May 2014 / Accepted: 9 July 2014 / Published: 22 July 2014
Cited by 1 | PDF Full-text (2197 KB) | HTML Full-text | XML Full-text
Abstract
Fibroblasts, which play an important role in biological seal formation and maintenance, determine the long-term success of percutaneous implants. In this study, well-defined microporous structures with micropore diameters of 10–60 µm were fabricated by microelectromechanical systems and their influence on the fibroblast functionalities
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Fibroblasts, which play an important role in biological seal formation and maintenance, determine the long-term success of percutaneous implants. In this study, well-defined microporous structures with micropore diameters of 10–60 µm were fabricated by microelectromechanical systems and their influence on the fibroblast functionalities was observed. The results show that the microporous structures with micropore diameters of 10–60 µm did not influence the initial adherent fibroblast number; however, those with diameters of 40 and 50 µm improved the spread, actin stress fiber organization, proliferation and fibronectin secretion of the fibroblasts. The microporous structures with micropore diameters of 40–50 µm may be promising for application in the percutaneous part of an implant. Full article
(This article belongs to the Special Issue Biologic Coatings for Orthopaedic Implant)
Open AccessArticle Arginine Enhances Osteoblastogenesis and Inhibits Adipogenesis through the Regulation of Wnt and NFATc Signaling in Human Mesenchymal Stem Cells
Int. J. Mol. Sci. 2014, 15(7), 13010-13029; doi:10.3390/ijms150713010
Received: 16 June 2014 / Revised: 2 July 2014 / Accepted: 10 July 2014 / Published: 22 July 2014
Cited by 5 | PDF Full-text (2422 KB) | HTML Full-text | XML Full-text
Abstract
Arginine, an α-amino acid, has been reported to exert beneficial effects that ameliorate health problems and prevent excessive fat deposition. In this study, we investigated whether the activation of cell signaling by arginine can induce osteogenic differentiation and modulate excessive adipogenic differentiation in
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Arginine, an α-amino acid, has been reported to exert beneficial effects that ameliorate health problems and prevent excessive fat deposition. In this study, we investigated whether the activation of cell signaling by arginine can induce osteogenic differentiation and modulate excessive adipogenic differentiation in human mesenchymal stem cells (MSCs). Arginine potently induced the expression of type Iα1 collagen, osteocalcin, and ALP in a dose-dependent manner without causing cytotoxicity. Arginine significantly increased the mRNA expression of the osteogenic transcription factors runt-related transcription factor 2 (Runx2), DIx5, and osterix. Furthermore, arginine demonstrated its antiadipogenicity by decreasing adipocyte formation and triglyceride (TG) content in MSCs and inhibiting the mRNA expression of the adipogenic transcription factors peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding protein α (C/EBPα), and fatty acid binding protein 4 (Fabp4). This effect was associated with increased expression of Wnt5a, and nuclear factor of activated T-cells (NFATc), and was abrogated by antagonists of Wnt and NFATc, which indicated a role of Wnt and NFATc signaling in the switch from adipogenesis to osteoblastogenesis induced by arginine. In conclusion, this is the first report of the dual action of arginine in promoting osteogenesis and inhibiting adipocyte formation through involving Wnt5a and NFATc signaling pathway. Full article
(This article belongs to the Special Issue Bioactive Proteins and Peptides Derived from Food)
Open AccessArticle Calcium and Zinc Containing Bactericidal Glass Coatings for Biomedical Metallic Substrates
Int. J. Mol. Sci. 2014, 15(7), 13030-13044; doi:10.3390/ijms150713030
Received: 25 April 2014 / Revised: 30 June 2014 / Accepted: 1 July 2014 / Published: 23 July 2014
Cited by 8 | PDF Full-text (2367 KB) | HTML Full-text | XML Full-text
Abstract
The present work presents new bactericidal coatings, based on two families of non-toxic, antimicrobial glasses belonging to B2O3–SiO2–Na2O–ZnO and SiO2–Na2O–Al2O3–CaO–B2O3 systems.Free of cracking,
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The present work presents new bactericidal coatings, based on two families of non-toxic, antimicrobial glasses belonging to B2O3–SiO2–Na2O–ZnO and SiO2–Na2O–Al2O3–CaO–B2O3 systems. Free of cracking, single layer direct coatings on different biomedical metallic substrates (titanium alloy, Nb, Ta, and stainless steel) have been developed. Thermal expansion mismatch was adjusted by changing glass composition of the glass type, as well as the firing atmosphere (air or Ar) according to the biomedical metallic substrates. Formation of bubbles in some of the glassy coatings has been rationalized considering the reactions that take place at the different metal/coating interfaces. All the obtained coatings were proven to be strongly antibacterial versus Escherichia coli (>4 log). Full article
(This article belongs to the Special Issue Biologic Coatings for Orthopaedic Implant)
Open AccessArticle BRCA1 Exon 11, a CERES (Composite Regulatory Element of Splicing) Element Involved in Splice Regulation
Int. J. Mol. Sci. 2014, 15(7), 13045-13059; doi:10.3390/ijms150713045
Received: 13 April 2014 / Revised: 17 June 2014 / Accepted: 4 July 2014 / Published: 23 July 2014
PDF Full-text (1325 KB) | HTML Full-text | XML Full-text
Abstract
Unclassified variants (UV) of BRCA1 can affect normal pre-mRNA splicing. Here, we investigate the UV c.693G>A, a “silent” change in BRCA1 exon 11, which we have found induces aberrant splicing in patient carriers and in vitro. Using a minigene assay, we show
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Unclassified variants (UV) of BRCA1 can affect normal pre-mRNA splicing. Here, we investigate the UV c.693G>A, a “silent” change in BRCA1 exon 11, which we have found induces aberrant splicing in patient carriers and in vitro. Using a minigene assay, we show that the UV c.693G>A has a strong effect on the splicing isoform ratio of BRCA1. Systematic site-directed mutagenesis of the area surrounding the nucleotide position c.693G>A induced variable changes in the level of exon 11 inclusion/exclusion in the mRNA, pointing to the presence of a complex regulatory element with overlapping enhancer and silencer functions. Accordingly, protein binding analysis in the region detected several splicing regulatory factors involved, including SRSF1, SRSF6 and SRSF9, suggesting that this sequence represents a composite regulatory element of splicing (CERES). Full article
(This article belongs to the Special Issue Pre-mRNA Splicing)
Open AccessArticle Antioxidant Capacities and Total Phenolic Contents Enhancement with Acute Gamma Irradiation in Curcuma alismatifolia (Zingiberaceae) Leaves
Int. J. Mol. Sci. 2014, 15(7), 13077-13090; doi:10.3390/ijms150713077
Received: 28 May 2014 / Revised: 24 June 2014 / Accepted: 7 July 2014 / Published: 23 July 2014
Cited by 3 | PDF Full-text (909 KB) | HTML Full-text | XML Full-text
Abstract
The present study was conducted in order to assess the effect of various doses of acute gamma irradiation (0, 10, 15, and 20 Gy) on the improvement of bioactive compounds and their antioxidant properties of Curcuma alismatifolia var. Sweet pink. The high
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The present study was conducted in order to assess the effect of various doses of acute gamma irradiation (0, 10, 15, and 20 Gy) on the improvement of bioactive compounds and their antioxidant properties of Curcuma alismatifolia var. Sweet pink. The high performance liquid chromatography (HPLC) and gas chromatography (GC) analysis uncovered that various types of phenolic, flavonoid compounds, and fatty acids gradually altered in response to radiation doses. On the other hand, antioxidant activities determined by 1,1-Diphenyl-2-picryl-hydrazyl (DPPH), ferric reduction, antioxidant power (FRAP), and 2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical scavenging assay showed a higher irradiation level significantly increased the antioxidant properties. This study revealed an efficient effect of varying levels of gamma radiation, based on the pharmaceutical demand to enhance the accumulation and distribution of bioactive compounds such as phenolic and flavonoid compounds, fatty acids, as well as their antioxidant activities in the leaves of C. alismatifolia var. Sweet pink. Full article
(This article belongs to the Special Issue Bioactive Phenolics and Polyphenols)
Open AccessArticle Effects of the Novel Compound DK223 ([1E,2E-1,2-Bis(6-methoxy-2H-chromen-3-yl)methylene]hydrazine) on Migration and Proliferation of Human Keratinocytes and Primary Dermal Fibroblasts
Int. J. Mol. Sci. 2014, 15(7), 13091-13110; doi:10.3390/ijms150713091
Received: 19 May 2014 / Revised: 26 June 2014 / Accepted: 14 July 2014 / Published: 23 July 2014
Cited by 2 | PDF Full-text (2637 KB) | HTML Full-text | XML Full-text
Abstract
Wound healing plays an important role in protecting the human body from external infection. Cell migration and proliferation of keratinocytes and dermal fibroblasts are essential for proper wound healing. Recently, several studies have demonstrated that secondary compounds produced in plants could affect skin
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Wound healing plays an important role in protecting the human body from external infection. Cell migration and proliferation of keratinocytes and dermal fibroblasts are essential for proper wound healing. Recently, several studies have demonstrated that secondary compounds produced in plants could affect skin cells migration and proliferation. In this study, we identified a novel compound DK223 ([1E,2E-1,2-bis(6-methoxy-2H-chromen-3-yl)methylene]hydrazine) that concomitantly induced human keratinocyte migration and dermal fibroblast proliferation. We evaluated the regulation of epithelial and mesenchymal protein markers, such as E-cadherin and Vimentin, in human keratinocytes, as well as extracellular matrix (ECM) secretion and metalloproteinase families in dermal fibroblasts. DK223 upregulated keratinocyte migration and significantly increased the epithelial marker E-cadherin in a time-dependent manner. We also found that reactive oxygen species (ROS) increased significantly in keratinocytes after 2 h of DK223 exposure, returning to normal levels after 24 h, which indicated that DK223 had an early shock effect on ROS production. DK223 also stimulated fibroblast proliferation, and induced significant secretion of ECM proteins, such as collagen I, III, and fibronectin. In dermal fibroblasts, DK223 treatment induced TGF-β1, which is involved in a signaling pathway that mediates proliferation. In conclusion, DK223 simultaneously induced both keratinocyte migration via ROS production and fibroblast proliferation via TGF-β1 induction. Full article
Open AccessCommunication DNA Break Mapping Reveals Topoisomerase II Activity Genome-Wide
Int. J. Mol. Sci. 2014, 15(7), 13111-13122; doi:10.3390/ijms150713111
Received: 31 May 2014 / Revised: 9 July 2014 / Accepted: 14 July 2014 / Published: 23 July 2014
Cited by 7 | PDF Full-text (1234 KB) | HTML Full-text | XML Full-text
Abstract
Genomic DNA is under constant assault by endogenous and exogenous DNA damaging agents. DNA breakage can represent a major threat to genome integrity but can also be necessary for genome function. Here we present approaches to map DNA double-strand breaks (DSBs) and single-strand
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Genomic DNA is under constant assault by endogenous and exogenous DNA damaging agents. DNA breakage can represent a major threat to genome integrity but can also be necessary for genome function. Here we present approaches to map DNA double-strand breaks (DSBs) and single-strand breaks (SSBs) at the genome-wide scale by two methods called DSB- and SSB-Seq, respectively. We tested these methods in human colon cancer cells and validated the results using the Topoisomerase II (Top2)-poisoning agent etoposide (ETO). Our results show that the combination of ETO treatment with break-mapping techniques is a powerful method to elaborate the pattern of Top2 enzymatic activity across the genome. Full article
(This article belongs to the Special Issue Identification and Roles of the Structure of DNA)
Open AccessArticle Crosslinking Liposomes/Cells Using Cholesteryl Group-Modified Tilapia Gelatin
Int. J. Mol. Sci. 2014, 15(7), 13123-13134; doi:10.3390/ijms150713123
Received: 1 May 2014 / Revised: 14 July 2014 / Accepted: 15 July 2014 / Published: 23 July 2014
Cited by 4 | PDF Full-text (1315 KB) | HTML Full-text | XML Full-text
Abstract
Cholesteryl group-modified tilapia gelatins (Chol-T-Gltns) with various Chol contents from 3 to 69 mol % per amino group of Gltn were prepared for the assembly of liposomes and cells. Liposomes were physically crosslinked by anchoring Chol groups of Chol-T-Gltns into lipid membranes. The
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Cholesteryl group-modified tilapia gelatins (Chol-T-Gltns) with various Chol contents from 3 to 69 mol % per amino group of Gltn were prepared for the assembly of liposomes and cells. Liposomes were physically crosslinked by anchoring Chol groups of Chol-T-Gltns into lipid membranes. The resulting liposome gels were enzymatically degraded by addition of collagenase. Liposome gels prepared using Chol-T-Gltn with high Chol content (69Chol-T-Gltn) showed slower enzymatic degradation when compared with gels prepared using Chol-T-Gltn with low Chol content (3Chol-T-Gltn). The hepatocyte cell line HepG2 showed good assembly properties and no cytotoxic effects after addition of 69Chol-T-Gltns. In addition, the number of HepG2 cells increased with concentration of 69Chol-T-Gltns. Therefore, Chol-T-Gltn, particularly, 69Chol-T-Gltn, can be used as an assembling material for liposomes and various cell types. The resulting organization can be applied to various biomedical fields, such as drug delivery systems, tissue engineering and regenerative medicine. Full article
(This article belongs to the Special Issue Biodegradable Materials)

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Open AccessReview Endothelial Dysfunction in Chronic Inflammatory Diseases
Int. J. Mol. Sci. 2014, 15(7), 11324-11349; doi:10.3390/ijms150711324
Received: 9 May 2014 / Revised: 23 May 2014 / Accepted: 6 June 2014 / Published: 25 June 2014
Cited by 57 | PDF Full-text (1016 KB) | HTML Full-text | XML Full-text
Abstract
Chronic inflammatory diseases are associated with accelerated atherosclerosis and increased risk of cardiovascular diseases (CVD). As the pathogenesis of atherosclerosis is increasingly recognized as an inflammatory process, similarities between atherosclerosis and systemic inflammatory diseases such as rheumatoid arthritis, inflammatory bowel diseases, lupus, psoriasis,
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Chronic inflammatory diseases are associated with accelerated atherosclerosis and increased risk of cardiovascular diseases (CVD). As the pathogenesis of atherosclerosis is increasingly recognized as an inflammatory process, similarities between atherosclerosis and systemic inflammatory diseases such as rheumatoid arthritis, inflammatory bowel diseases, lupus, psoriasis, spondyloarthritis and others have become a topic of interest. Endothelial dysfunction represents a key step in the initiation and maintenance of atherosclerosis and may serve as a marker for future risk of cardiovascular events. Patients with chronic inflammatory diseases manifest endothelial dysfunction, often early in the course of the disease. Therefore, mechanisms linking systemic inflammatory diseases and atherosclerosis may be best understood at the level of the endothelium. Multiple factors, including circulating inflammatory cytokines, TNF-α (tumor necrosis factor-α), reactive oxygen species, oxidized LDL (low density lipoprotein), autoantibodies and traditional risk factors directly and indirectly activate endothelial cells, leading to impaired vascular relaxation, increased leukocyte adhesion, increased endothelial permeability and generation of a pro-thrombotic state. Pharmacologic agents directed against TNF-α-mediated inflammation may decrease the risk of endothelial dysfunction and cardiovascular disease in these patients. Understanding the precise mechanisms driving endothelial dysfunction in patients with systemic inflammatory diseases may help elucidate the pathogenesis of atherosclerosis in the general population. Full article
(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease 2015)
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Open AccessReview PKM2: The Thread Linking Energy Metabolism Reprogramming with Epigenetics in Cancer
Int. J. Mol. Sci. 2014, 15(7), 11435-11445; doi:10.3390/ijms150711435
Received: 23 April 2014 / Revised: 20 May 2014 / Accepted: 10 June 2014 / Published: 26 June 2014
Cited by 12 | PDF Full-text (729 KB) | HTML Full-text | XML Full-text
Abstract
Cancer metabolism reprogramming or alterations in epigenetics are linked to an incidence of cancer. It is apparent that epigenetic changes have been found in tumors, therefore, the complete epigenome and entire pathways relevant to cell metabolism are subject to epigenetic dysregulation. Here, we
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Cancer metabolism reprogramming or alterations in epigenetics are linked to an incidence of cancer. It is apparent that epigenetic changes have been found in tumors, therefore, the complete epigenome and entire pathways relevant to cell metabolism are subject to epigenetic dysregulation. Here, we review the pyruvate kinase M2 (PKM2) isoform, a glycolytic enzyme involved in ATP generation and pyruvate production, which plays an essential role in tumor metabolism and growth, and also functions as a protein kinase that phosphorylates histones during genes transcription and chromatin remodeling. We also discuss the potential role of PKM2 in the dynamic integration between metabolic reprogramming and alterations in epigenetics during carcinogenesis and cancer progression. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessReview Mediterranean Diet and Health: Food Effects on Gut Microbiota and Disease Control
Int. J. Mol. Sci. 2014, 15(7), 11678-11699; doi:10.3390/ijms150711678
Received: 28 April 2014 / Revised: 4 June 2014 / Accepted: 11 June 2014 / Published: 1 July 2014
Cited by 14 | PDF Full-text (4841 KB) | HTML Full-text | XML Full-text
Abstract
The Mediterranean diet (MD) is considered one of the healthiest dietary models. Many of the characteristic components of the MD have functional features with positive effects on health and wellness. The MD adherence, calculated through various computational scores, can lead to a reduction
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The Mediterranean diet (MD) is considered one of the healthiest dietary models. Many of the characteristic components of the MD have functional features with positive effects on health and wellness. The MD adherence, calculated through various computational scores, can lead to a reduction of the incidence of major diseases (e.g., cancers, metabolic and cardiovascular syndromes, neurodegenerative diseases, type 2 diabetes and allergy). Furthermore, eating habits are the main significant determinants of the microbial multiplicity of the gut, and dietary components influence both microbial populations and their metabolic activities from the early stages of life. For this purpose, we present a study proposal relying on the generation of individual gut microbiota maps from MD-aware children/adolescents. The maps, based on meta-omics approaches, may be considered as new tools, acting as a systems biology-based proof of evidence to evaluate MD effects on gut microbiota homeostasis. Data integration of food metabotypes and gut microbiota “enterotypes” may allow one to interpret MD adherence and its effects on health in a new way, employable for the design of targeted diets and nutraceutical interventions in childcare and clinical management of food-related diseases, whose onset has been significantly shifted early in life. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
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Open AccessReview Interplay between Dioxin-Mediated Signaling and Circadian Clock: A Possible Determinant in Metabolic Homeostasis
Int. J. Mol. Sci. 2014, 15(7), 11700-11712; doi:10.3390/ijms150711700
Received: 22 April 2014 / Revised: 13 June 2014 / Accepted: 17 June 2014 / Published: 1 July 2014
Cited by 5 | PDF Full-text (970 KB) | HTML Full-text | XML Full-text
Abstract
The rotation of the earth on its axis creates the environment of a 24 h solar day, which organisms on earth have used to their evolutionary advantage by integrating this timing information into their genetic make-up in the form of a circadian clock.
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The rotation of the earth on its axis creates the environment of a 24 h solar day, which organisms on earth have used to their evolutionary advantage by integrating this timing information into their genetic make-up in the form of a circadian clock. This intrinsic molecular clock is pivotal for maintenance of synchronized homeostasis between the individual organism and the external environment to allow coordinated rhythmic physiological and behavioral function. Aryl hydrocarbon receptor (AhR) is a master regulator of dioxin-mediated toxic effects, and is, therefore, critical in maintaining adaptive responses through regulating the expression of phase I/II drug metabolism enzymes. AhR expression is robustly rhythmic, and physiological cross-talk between AhR signaling and circadian rhythms has been established. Increasing evidence raises a compelling argument that disruption of endogenous circadian rhythms contributes to the development of disease, including sleep disorders, metabolic disorders and cancers. Similarly, exposure to environmental pollutants through air, water and food, is increasingly cited as contributory to these same problems. Thus, a better understanding of interactions between AhR signaling and the circadian clock regulatory network can provide critical new insights into environmentally regulated disease processes. This review highlights recent advances in the understanding of the reciprocal interactions between dioxin-mediated AhR signaling and the circadian clock including how these pathways relate to health and disease, with emphasis on the control of metabolic function. Full article
(This article belongs to the Special Issue Mechanisms of Toxicity of Dioxins and Related Compounds)
Open AccessReview Restoration of Asymmetric Dimethylarginine–Nitric Oxide Balance to Prevent the Development of Hypertension
Int. J. Mol. Sci. 2014, 15(7), 11773-11782; doi:10.3390/ijms150711773
Received: 27 May 2014 / Revised: 24 June 2014 / Accepted: 27 June 2014 / Published: 2 July 2014
Cited by 11 | PDF Full-text (883 KB) | HTML Full-text | XML Full-text
Abstract
Despite the use of extensive antihypertensive therapy in patients with hypertension, little attention has been paid to early identification and intervention of individuals at risk for developing hypertension. The imbalance between nitric oxide (NO) and reactive oxygen species (ROS) resulting in oxidative stress
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Despite the use of extensive antihypertensive therapy in patients with hypertension, little attention has been paid to early identification and intervention of individuals at risk for developing hypertension. The imbalance between nitric oxide (NO) and reactive oxygen species (ROS) resulting in oxidative stress has been implicated in the pathophysiology of hypertension. NO deficiency can precede the development of hypertension. Asymmetric dimethylarginine (ADMA) can inhibit nitric oxide synthase (NOS) and regulate local NO/ROS balance. Emerging evidence supports the hypothesis that ADMA-induced NO–ROS imbalance is involved in the development and progression of hypertension. Thus, this review summarizes recent experimental approaches to restore ADMA–NO balance in order to prevent the development of hypertension. Since hypertension might originate in early life, we also discuss the putative role of the ADMA–NO pathway in programmed hypertension. Better understanding of manipulations of the ADMA–NO pathway prior to hypertension in favor of NO will pave the way for the development of more effective medicine for the treatment prehypertension and programmed hypertension. However, more studies are needed to confirm the clinical benefit of these interventions. Full article
(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease 2015)
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Open AccessReview The Diagnosis and Treatment of Pseudoprogression, Radiation Necrosis and Brain Tumor Recurrence
Int. J. Mol. Sci. 2014, 15(7), 11832-11846; doi:10.3390/ijms150711832
Received: 31 March 2014 / Revised: 5 June 2014 / Accepted: 25 June 2014 / Published: 3 July 2014
Cited by 12 | PDF Full-text (943 KB) | HTML Full-text | XML Full-text
Abstract
Radiation therapy is an important modality used in the treatment of patients with brain metastatic disease and malignant gliomas. Post-treatment surveillance often involves serial magnetic resonance imaging. A challenge faced by clinicians is in the diagnosis and management of a suspicious gadolinium-enhancing lesion
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Radiation therapy is an important modality used in the treatment of patients with brain metastatic disease and malignant gliomas. Post-treatment surveillance often involves serial magnetic resonance imaging. A challenge faced by clinicians is in the diagnosis and management of a suspicious gadolinium-enhancing lesion found on imaging. The suspicious lesion may represent post-treatment radiation effects (PTRE) such as pseudoprogression, radiation necrosis or tumor recurrence. Significant progress has been made in diagnostic imaging modalities to assist in differentiating these entities. Surgical and medical interventions have also been developed to treat PTRE. In this review, we discuss the pathophysiology, clinical presentation, diagnostic imaging modalities and provide an algorithm for the management of pseudoprogression, radiation necrosis and tumor recurrence. Full article
(This article belongs to the Special Issue Brain Metastasis 2014)
Open AccessReview Bioactive Coatings for Orthopaedic Implants—Recent Trends in Development of Implant Coatings
Int. J. Mol. Sci. 2014, 15(7), 11878-11921; doi:10.3390/ijms150711878
Received: 25 April 2014 / Revised: 11 June 2014 / Accepted: 16 June 2014 / Published: 4 July 2014
Cited by 38 | PDF Full-text (4778 KB) | HTML Full-text | XML Full-text
Abstract
Joint replacement is a major orthopaedic procedure used to treat joint osteoarthritis. Aseptic loosening and infection are the two most significant causes of prosthetic implant failure. The ideal implant should be able to promote osteointegration, deter bacterial adhesion and minimize prosthetic infection. Recent
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Joint replacement is a major orthopaedic procedure used to treat joint osteoarthritis. Aseptic loosening and infection are the two most significant causes of prosthetic implant failure. The ideal implant should be able to promote osteointegration, deter bacterial adhesion and minimize prosthetic infection. Recent developments in material science and cell biology have seen the development of new orthopaedic implant coatings to address these issues. Coatings consisting of bioceramics, extracellular matrix proteins, biological peptides or growth factors impart bioactivity and biocompatibility to the metallic surface of conventional orthopaedic prosthesis that promote bone ingrowth and differentiation of stem cells into osteoblasts leading to enhanced osteointegration of the implant. Furthermore, coatings such as silver, nitric oxide, antibiotics, antiseptics and antimicrobial peptides with anti-microbial properties have also been developed, which show promise in reducing bacterial adhesion and prosthetic infections. This review summarizes some of the recent developments in coatings for orthopaedic implants. Full article
(This article belongs to the Special Issue Biologic Coatings for Orthopaedic Implant)
Open AccessReview Ionic Liquids and Cellulose: Dissolution, Chemical Modification and Preparation of New Cellulosic Materials
Int. J. Mol. Sci. 2014, 15(7), 11922-11940; doi:10.3390/ijms150711922
Received: 5 May 2014 / Revised: 13 June 2014 / Accepted: 23 June 2014 / Published: 4 July 2014
Cited by 40 | PDF Full-text (644 KB) | HTML Full-text | XML Full-text
Abstract
Due to its abundance and a wide range of beneficial physical and chemical properties, cellulose has become very popular in order to produce materials for various applications. This review summarizes the recent advances in the development of new cellulose materials and technologies using
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Due to its abundance and a wide range of beneficial physical and chemical properties, cellulose has become very popular in order to produce materials for various applications. This review summarizes the recent advances in the development of new cellulose materials and technologies using ionic liquids. Dissolution of cellulose in ionic liquids has been used to develop new processing technologies, cellulose functionalization methods and new cellulose materials including blends, composites, fibers and ion gels. Full article
(This article belongs to the Special Issue Ionic Liquids 2014 & Selected Papers from ILMAT 2013)
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Open AccessReview Microbial-Catalyzed Biotransformation of Multifunctional Triterpenoids Derived from Phytonutrients
Int. J. Mol. Sci. 2014, 15(7), 12027-12060; doi:10.3390/ijms150712027
Received: 22 May 2014 / Revised: 12 June 2014 / Accepted: 26 June 2014 / Published: 7 July 2014
Cited by 5 | PDF Full-text (910 KB) | HTML Full-text | XML Full-text
Abstract
Microbial-catalyzed biotransformations have considerable potential for the generation of an enormous variety of structurally diversified organic compounds, especially natural products with complex structures like triterpenoids. They offer efficient and economical ways to produce semi-synthetic analogues and novel lead molecules. Microorganisms such as
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Microbial-catalyzed biotransformations have considerable potential for the generation of an enormous variety of structurally diversified organic compounds, especially natural products with complex structures like triterpenoids. They offer efficient and economical ways to produce semi-synthetic analogues and novel lead molecules. Microorganisms such as bacteria and fungi could catalyze chemo-, regio- and stereospecific hydroxylations of diverse triterpenoid substrates that are extremely difficult to produce by chemical routes. During recent years, considerable research has been performed on the microbial transformation of bioactive triterpenoids, in order to obtain biologically active molecules with diverse structures features. This article reviews the microbial modifications of tetranortriterpenoids, tetracyclic triterpenoids and pentacyclic triterpenoids. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
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Open AccessReview Flavonoids and Wnt/β-Catenin Signaling: Potential Role in Colorectal Cancer Therapies
Int. J. Mol. Sci. 2014, 15(7), 12094-12106; doi:10.3390/ijms150712094
Received: 30 May 2014 / Revised: 20 June 2014 / Accepted: 23 June 2014 / Published: 8 July 2014
Cited by 13 | PDF Full-text (1431 KB) | HTML Full-text | XML Full-text
Abstract
It is now well documented that natural products have played an important role in anticancer therapy. Many studies focus on the ability of these natural compounds to modulate tumor-related signaling pathways and the relationship of these properties to an anticancer effect. According to
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It is now well documented that natural products have played an important role in anticancer therapy. Many studies focus on the ability of these natural compounds to modulate tumor-related signaling pathways and the relationship of these properties to an anticancer effect. According to the World Health Organization (WHO), colorectal cancer (CRC) is the third most common cancer and the fourth leading cause of cancer death among men and women. Therefore, finding strategies to fight against CRC is an emergent health problem. CRC has a strong association with deregulation of Wnt/β-catenin signaling pathway. As some types of natural compounds are capable of modulating the Wnt/β-catenin signaling, one important question is whether they could counteract CRC. In this review, we discuss the role of flavonoids, a class of natural compounds, on Wnt/β-catenin regulation and its possible potential for therapeutic usage on colorectal cancer. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
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Open AccessReview Applications and Mechanisms of Ionic Liquids in Whole-Cell Biotransformation
Int. J. Mol. Sci. 2014, 15(7), 12196-12216; doi:10.3390/ijms150712196
Received: 20 May 2014 / Revised: 13 June 2014 / Accepted: 1 July 2014 / Published: 9 July 2014
Cited by 7 | PDF Full-text (645 KB) | HTML Full-text | XML Full-text
Abstract
Ionic liquids (ILs), entirely composed of cations and anions, are liquid solvents at room temperature. They are interesting due to their low vapor pressure, high polarity and thermostability, and also for the possibility to fine-tune their physicochemical properties through modification of the chemical
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Ionic liquids (ILs), entirely composed of cations and anions, are liquid solvents at room temperature. They are interesting due to their low vapor pressure, high polarity and thermostability, and also for the possibility to fine-tune their physicochemical properties through modification of the chemical structures of their cations or anions. In recent years, ILs have been widely used in biotechnological fields involving whole-cell biotransformations of biodiesel or biomass, and organic compound synthesis with cells. Research studies in these fields have increased from the past decades and compared to the typical solvents, ILs are the most promising alternative solvents for cell biotransformations. However, there are increasing limitations and new challenges in whole-cell biotransformations with ILs. There is little understanding of the mechanisms of ILs’ interactions with cells, and much remains to be clarified. Further investigations are required to overcome the drawbacks of their applications and to broaden their application spectrum. This work mainly reviews the applications of ILs in whole-cell biotransformations, and the possible mechanisms of ILs in microbial cell biotransformation are proposed and discussed. Full article
(This article belongs to the Special Issue Ionic Liquids 2014 & Selected Papers from ILMAT 2013)
Open AccessReview Novel Bioactive Antimicrobial Lignin Containing Coatings on Titanium Obtained by Electrophoretic Deposition
Int. J. Mol. Sci. 2014, 15(7), 12294-12322; doi:10.3390/ijms150712294
Received: 5 May 2014 / Revised: 31 May 2014 / Accepted: 1 July 2014 / Published: 11 July 2014
Cited by 9 | PDF Full-text (1647 KB) | HTML Full-text | XML Full-text
Abstract
Hydroxyapatite (HAP) is the most suitable biocompatible material for bone implant coatings; its brittleness, however, is a major obstacle, and the reason why research focuses on creating composites with biopolymers. Organosolv lignin (Lig) is used for the production of composite coatings, and these
[...] Read more.
Hydroxyapatite (HAP) is the most suitable biocompatible material for bone implant coatings; its brittleness, however, is a major obstacle, and the reason why research focuses on creating composites with biopolymers. Organosolv lignin (Lig) is used for the production of composite coatings, and these composites were examined in this study. Titanium substrate is a key biomedical material due to its well-known properties, but infections of the implantation site still impose a serious threat. One approach to prevent infection is to improve antimicrobial properties of the coating material. Silver doped hydroxyapatite (Ag/HAP) and HAP coatings on titanium were obtained by an electrophoretic deposition method in order to control deposited coating mass and morphology by varying applied voltage and deposition time. The effect of lignin on microstructure, morphology and thermal behavior of biocomposite coatings was investigated. The results showed that higher lignin concentrations protect the HAP lattice during sintering, improving coating stability. The corrosion stability was evaluated in simulated body fluid (SBF) at 37 °C. Newly formed plate-shaped carbonate-HAP was detected, indicating enhanced bioactive performance. The antimicrobial efficiency of Ag/HAP/Lig was confirmed by its higher reduction of bacteria Staphylococcus aureus TL (S. aureus TL) than of HAP/Lig coating. Cytotoxicity assay revealed that both coatings can be classified as non-toxic against healthy immunocompetent peripheral blood mononuclear cells (PBMC). Full article
(This article belongs to the Special Issue Biologic Coatings for Orthopaedic Implant)
Open AccessReview Oleocanthal, a Phenolic Derived from Virgin Olive Oil: A Review of the Beneficial Effects on Inflammatory Disease
Int. J. Mol. Sci. 2014, 15(7), 12323-12334; doi:10.3390/ijms150712323
Received: 27 May 2014 / Revised: 25 June 2014 / Accepted: 26 June 2014 / Published: 11 July 2014
Cited by 20 | PDF Full-text (741 KB) | HTML Full-text | XML Full-text
Abstract
Virgin olive oil (VOO) is credited as being one of many healthful components of the Mediterranean diet. Mediterranean populations experience reduced incidence of chronic inflammatory disease states and VOO is readily consumed as part of an everyday dietary pattern. A phenolic compound contained
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Virgin olive oil (VOO) is credited as being one of many healthful components of the Mediterranean diet. Mediterranean populations experience reduced incidence of chronic inflammatory disease states and VOO is readily consumed as part of an everyday dietary pattern. A phenolic compound contained in VOO, named oleocanthal, shares unique perceptual and anti-inflammatory characteristics with Ibuprofen. Over recent years oleocanthal has become a compound of interest in the search for naturally occurring compounds with pharmacological qualities. Subsequent to its discovery and identification, oleocanthal has been reported to exhibit various modes of action in reducing inflammatory related disease, including joint-degenerative disease, neuro-degenerative disease and specific cancers. Therefore, it is postulated that long term consumption of VOO containing oleocanthal may contribute to the health benefits associated with the Mediterranean dietary pattern. The following paper summarizes the current literature on oleocanthal, in terms of its sensory and pharmacological properties, and also discusses the beneficial, health promoting activities of oleocanthal, in the context of the molecular mechanisms within various models of disease. Full article
(This article belongs to the Special Issue Bioactive Phenolics and Polyphenols)
Open AccessReview Making the Bend: DNA Tertiary Structure and Protein-DNA Interactions
Int. J. Mol. Sci. 2014, 15(7), 12335-12363; doi:10.3390/ijms150712335
Received: 21 May 2014 / Revised: 1 July 2014 / Accepted: 1 July 2014 / Published: 14 July 2014
Cited by 8 | PDF Full-text (1215 KB) | HTML Full-text | XML Full-text
Abstract
DNA structure functions as an overlapping code to the DNA sequence. Rapid progress in understanding the role of DNA structure in gene regulation, DNA damage recognition and genome stability has been made. The three dimensional structure of both proteins and DNA plays a
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DNA structure functions as an overlapping code to the DNA sequence. Rapid progress in understanding the role of DNA structure in gene regulation, DNA damage recognition and genome stability has been made. The three dimensional structure of both proteins and DNA plays a crucial role for their specific interaction, and proteins can recognise the chemical signature of DNA sequence (“base readout”) as well as the intrinsic DNA structure (“shape recognition”). These recognition mechanisms do not exist in isolation but, depending on the individual interaction partners, are combined to various extents. Driving force for the interaction between protein and DNA remain the unique thermodynamics of each individual DNA-protein pair. In this review we focus on the structures and conformations adopted by DNA, both influenced by and influencing the specific interaction with the corresponding protein binding partner, as well as their underlying thermodynamics. Full article
(This article belongs to the Special Issue Identification and Roles of the Structure of DNA)
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Open AccessReview Applications of Biosurfactants in the Petroleum Industry and the Remediation of Oil Spills
Int. J. Mol. Sci. 2014, 15(7), 12523-12542; doi:10.3390/ijms150712523
Received: 16 May 2014 / Revised: 26 June 2014 / Accepted: 7 July 2014 / Published: 15 July 2014
Cited by 28 | PDF Full-text (719 KB) | HTML Full-text | XML Full-text
Abstract
Petroleum hydrocarbons are important energy resources. However, petroleum is also a major pollutant of the environment. Contamination by oil and oil products has caused serious harm, and increasing attention has been paid to the development and implementation of innovative technologies for the removal
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Petroleum hydrocarbons are important energy resources. However, petroleum is also a major pollutant of the environment. Contamination by oil and oil products has caused serious harm, and increasing attention has been paid to the development and implementation of innovative technologies for the removal of these contaminants. Biosurfactants have been extensively used in the remediation of water and soil, as well as in the main stages of the oil production chain, such as extraction, transportation, and storage. This diversity of applications is mainly due to advantages such as biodegradability, low toxicity and better functionality under extreme conditions in comparison to synthetic counterparts. Moreover, biosurfactants can be obtained with the use of agro-industrial waste as substrate, which helps reduce overall production costs. The present review describes the potential applications of biosurfactants in the oil industry and the remediation of environmental pollution caused by oil spills. Full article
(This article belongs to the Section Green Chemistry)
Open AccessReview Cellular Levels of 8-Oxoguanine in either DNA or the Nucleotide Pool Play Pivotal Roles in Carcinogenesis and Survival of Cancer Cells
Int. J. Mol. Sci. 2014, 15(7), 12543-12557; doi:10.3390/ijms150712543
Received: 13 May 2014 / Revised: 23 June 2014 / Accepted: 8 July 2014 / Published: 15 July 2014
Cited by 21 | PDF Full-text (1243 KB) | HTML Full-text | XML Full-text
Abstract
8-Oxoguanine, a major oxidized base lesion formed by reactive oxygen species, causes G to T transversion mutations or leads to cell death in mammals if it accumulates in DNA. 8-Oxoguanine can originate as 8-oxo-dGTP, formed in the nucleotide pool, or by direct oxidation
[...] Read more.
8-Oxoguanine, a major oxidized base lesion formed by reactive oxygen species, causes G to T transversion mutations or leads to cell death in mammals if it accumulates in DNA. 8-Oxoguanine can originate as 8-oxo-dGTP, formed in the nucleotide pool, or by direct oxidation of the DNA guanine base. MTH1, also known as NUDT1, with 8-oxo-dGTP hydrolyzing activity, 8-oxoguanine DNA glycosylase (OGG1) an 8-oxoG DNA glycosylase, and MutY homolog (MUTYH) with adenine DNA glycosylase activity, minimize the accumulation of 8-oxoG in DNA; deficiencies in these enzymes increase spontaneous and induced tumorigenesis susceptibility. However, different tissue types have different tumorigenesis susceptibilities. These can be reversed by combined deficiencies in the defense systems, because cell death induced by accumulation of 8-oxoG in DNA is dependent on MUTYH, which can be suppressed by MTH1 and OGG1. In cancer cells encountering high oxidative stress levels, a high level of 8-oxo-dGTP accumulates in the nucleotide pool, and cells therefore express increased levels of MTH1 in order to eliminate 8-oxo-dGTP. Suppression of MTH1 may be an efficient strategy for killing cancer cells; however, because MTH1 and OGG1 protect normal tissues from oxidative-stress-induced cell death, it is important that MTH1 inhibition does not increase the risk of healthy tissue degeneration. Full article
(This article belongs to the Special Issue Genetic Susceptibility to Carcinogen-Induced Cancer)
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Open AccessReview Alzheimer’s Disease—A Panorama Glimpse
Int. J. Mol. Sci. 2014, 15(7), 12631-12650; doi:10.3390/ijms150712631
Received: 21 May 2014 / Revised: 26 June 2014 / Accepted: 10 July 2014 / Published: 16 July 2014
Cited by 7 | PDF Full-text (198 KB) | HTML Full-text | XML Full-text
Abstract
The single-mutation of genes associated with Alzheimer’s disease (AD) increases the production of Aβ peptides. An elevated concentration of Aβ peptides is prone to aggregation into oligomers and further deposition as plaque. Aβ plaques and neurofibrillary tangles are two hallmarks of AD. In
[...] Read more.
The single-mutation of genes associated with Alzheimer’s disease (AD) increases the production of Aβ peptides. An elevated concentration of Aβ peptides is prone to aggregation into oligomers and further deposition as plaque. Aβ plaques and neurofibrillary tangles are two hallmarks of AD. In this review, we provide a broad overview of the diverses sources that could lead to AD, which include genetic origins, Aβ peptides and tau protein. We shall discuss on tau protein and tau accumulation, which result in neurofibrillary tangles. We detail the mechanisms of Aβ aggregation, fibril formation and its polymorphism. We then show the possible links between Aβ and tau pathology. Furthermore, we summarize the structural data of Aβ and its precursor protein obtained via Nuclear Magnetic Resonance (NMR) or X-ray crystallography. At the end, we go through the C-terminal and N-terminal truncated Aβ variants. We wish to draw reader’s attention to two predominant and toxic Aβ species, namely Aβ4-42 and pyroglutamate amyloid-beta peptides, which have been neglected for more than a decade and may be crucial in Aβ pathogenesis due to their dominant presence in the AD brain. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessReview Modified Low Density Lipoprotein and Lipoprotein-Containing Circulating Immune Complexes as Diagnostic and Prognostic Biomarkers of Atherosclerosis and Type 1 Diabetes Macrovascular Disease
Int. J. Mol. Sci. 2014, 15(7), 12807-12841; doi:10.3390/ijms150712807
Received: 11 May 2014 / Revised: 29 June 2014 / Accepted: 3 July 2014 / Published: 21 July 2014
Cited by 14 | PDF Full-text (1850 KB) | HTML Full-text | XML Full-text
Abstract
In atherosclerosis; blood low-density lipoproteins (LDL) are subjected to multiple enzymatic and non-enzymatic modifications that increase their atherogenicity and induce immunogenicity. Modified LDL are capable of inducing vascular inflammation through activation of innate immunity; thus, contributing to the progression of atherogenesis. The immunogenicity
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In atherosclerosis; blood low-density lipoproteins (LDL) are subjected to multiple enzymatic and non-enzymatic modifications that increase their atherogenicity and induce immunogenicity. Modified LDL are capable of inducing vascular inflammation through activation of innate immunity; thus, contributing to the progression of atherogenesis. The immunogenicity of modified LDL results in induction of self-antibodies specific to a certain type of modified LDL. The antibodies react with modified LDL forming circulating immune complexes. Circulating immune complexes exhibit prominent immunomodulatory properties that influence atherosclerotic inflammation. Compared to freely circulating modified LDL; modified LDL associated with the immune complexes have a more robust atherogenic and proinflammatory potential. Various lipid components of the immune complexes may serve not only as diagnostic but also as essential predictive markers of cardiovascular events in atherosclerosis. Accumulating evidence indicates that LDL-containing immune complexes can also serve as biomarker for macrovascular disease in type 1 diabetes. Full article
(This article belongs to the Special Issue Bioactive Lipids and Lipidomics)
Open AccessReview Iodine Excess as an Environmental Risk Factor for Autoimmune Thyroid Disease
Int. J. Mol. Sci. 2014, 15(7), 12895-12912; doi:10.3390/ijms150712895
Received: 19 June 2014 / Revised: 3 July 2014 / Accepted: 15 July 2014 / Published: 21 July 2014
Cited by 12 | PDF Full-text (695 KB) | HTML Full-text | XML Full-text
Abstract
The global effort to prevent iodine deficiency disorders through iodine supplementation, such as universal salt iodization, has achieved impressive progress during the last few decades. However, iodine excess, due to extensive environmental iodine exposure in addition to poor monitoring, is currently a more
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The global effort to prevent iodine deficiency disorders through iodine supplementation, such as universal salt iodization, has achieved impressive progress during the last few decades. However, iodine excess, due to extensive environmental iodine exposure in addition to poor monitoring, is currently a more frequent occurrence than iodine deficiency. Iodine excess is a precipitating environmental factor in the development of autoimmune thyroid disease. Excessive amounts of iodide have been linked to the development of autoimmune thyroiditis in humans and animals, while intrathyroidal depletion of iodine prevents disease in animal strains susceptible to severe thyroiditis. Although the mechanisms by which iodide induces thyroiditis are still unclear, several mechanisms have been proposed: (1) excess iodine induces the production of cytokines and chemokines that can recruit immunocompetent cells to the thyroid; (2) processing excess iodine in thyroid epithelial cells may result in elevated levels of oxidative stress, leading to harmful lipid oxidation and thyroid tissue injuries; and (3) iodine incorporation in the protein chain of thyroglobulin may augment the antigenicity of this molecule. This review will summarize the current knowledge regarding excess iodide as an environmental toxicant and relate it to the development of autoimmune thyroid disease. Full article
(This article belongs to the Special Issue Environmental Toxicants and Autoimmune Disease)
Open AccessReview Molecular and Cellular Mechanisms of Sperm-Oocyte Interactions Opinions Relative to in Vitro Fertilization (IVF)
Int. J. Mol. Sci. 2014, 15(7), 12972-12997; doi:10.3390/ijms150712972
Received: 5 May 2014 / Revised: 7 June 2014 / Accepted: 24 June 2014 / Published: 22 July 2014
Cited by 4 | PDF Full-text (1245 KB) | HTML Full-text | XML Full-text
Abstract
One of the biggest prerequisites for pregnancy is the fertilization step, where a human haploid spermatozoon interacts and penetrates one haploid oocyte in order to produce the diploid zygote. Although fertilization is defined by the presence of two pronuclei and the extraction of
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One of the biggest prerequisites for pregnancy is the fertilization step, where a human haploid spermatozoon interacts and penetrates one haploid oocyte in order to produce the diploid zygote. Although fertilization is defined by the presence of two pronuclei and the extraction of the second polar body the process itself requires preparation of both gametes for fertilization to take place at a specific time. These preparations include a number of consecutive biochemical and molecular events with the help of specific molecules and with the consequential interaction between the two gametes. These events take place at three different levels and in a precise order, where the moving spermatozoon penetrates (a) the outer vestments of the oocyte, known as the cumulus cell layer; (b) the zona pellucida (ZP); where exocytosis of the acrosome contents take place and (c) direct interaction of the spermatozoon with the plasma membrane of the oocyte, which involves a firm adhesion of the head of the spermatozoon with the oocyte plasma membrane that culminates with the fusion of both sperm and oocyte membranes (Part I). After the above interactions, a cascade of molecular signal transductions is initiated which results in oocyte activation. Soon after the entry of the first spermatozoon into the oocyte and oocyte activation, the oocyte’s coat (the ZP) and the oocyte’s plasma membrane seem to change quickly in order to initiate a fast block to a second spermatozoon (Part II). Sometimes, two spermatozoa fuse with one oocyte, an incidence of 1%–2%, resulting in polyploid fetuses that account for up to 10%–20% of spontaneously aborted human conceptuses. The present review aims to focus on the first part of the human sperm and oocyte interactions, emphasizing the latest molecular and cellular mechanisms controlling this process. Full article
(This article belongs to the Special Issue Cellular and Molecular Mechanisms of Sperm-Egg Interaction)
Open AccessReview Possible Prognostic and Therapeutic Significance of c-Kit Expression, Mast Cell Count and Microvessel Density in Renal Cell Carcinoma
Int. J. Mol. Sci. 2014, 15(7), 13060-13076; doi:10.3390/ijms150713060
Received: 28 May 2014 / Revised: 17 July 2014 / Accepted: 17 July 2014 / Published: 23 July 2014
Cited by 10 | PDF Full-text (897 KB) | HTML Full-text | XML Full-text
Abstract
Renal cell carcinoma (RCC) is the most frequent renal tumor and its incidence is increasing worldwide. Tumor angiogenesis is known to play a crucial role in the etiopathogenesis of RCC and over the last few years an even deeper knowledge of its contribution
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Renal cell carcinoma (RCC) is the most frequent renal tumor and its incidence is increasing worldwide. Tumor angiogenesis is known to play a crucial role in the etiopathogenesis of RCC and over the last few years an even deeper knowledge of its contribution in metastatic RCC development has led to the development of numerous molecular targeting agents (such as sunitinib, sorafenib, pazopanib, axitinib, tivozanib, and dovitinib). The above agents are principally directed against vascular endothelial growth factor receptor (VEGFR) members and also against c-Kit receptor (c-KitR). The role of c-kitR inhibition on clear cell RCC (ccRCC), the main RCC subtype, is less well established. Whether c-kitR activation through its ligand, stem cell factor (SCF) contributes significantly to the effects of tyrosine kinase inhibitors (TKIs) treatment remains to be established. It is important to underscore that the c-KitR is expressed on mast cells (MCs) and cancer cells. After an examination of the c-KitR/SCF pathway, we review here the principal studies that have evaluated c-Kit expression in RCC. Moreover, we summarize some investigations that have observed the distribution of MCs in primary renal cancer and in adjacent normal tissue with appropriate histological immunohistochemical techniques. We also focus on few studies that have evaluated the correlation between RCC proliferation, MC count and microvessel density (MVD), as hallmarks of tumor angiogenesis. Thus, the aim of this review of the literature is to clarify if c-KitR expression, MC count and MVD could have prognostic significance and the possible predictive therapeutic implications in RCC. Full article
(This article belongs to the Special Issue Molecular Research in Urology 2014)

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