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51.
Jaykant Vora Shivani Patel Sonam Sinha Sonal Sharma Anshu Srivastava Mahesh Chhabria 《Journal of biomolecular structure & dynamics》2019,37(12):3150-3161
The transmission of mosquito-borne Chikungunya virus (CHIKV) has large epidemics worldwide. Till date, there are neither anti-viral drugs nor vaccines available for the treatment of Chikungunya. Accumulated evidences suggest that some natural compounds i.e., Epigallocatechin gallate, Harringtonine, Apigenin, Chrysin, Silybin, etc. have the capability to inhibit CHIKV replication in vitro. Natural compounds are known to possess less or no side effects. Therefore, natural compound in its purified or crude extracts form could be the preeminent and safe mode of therapies for Chikungunya. Wet lab screening and identification of natural compounds against Chikungunya targets is a time consuming and expensive exercise. In the present study, we used in silico techniques like receptor-ligand docking, Molecular dynamic (MD), Three Dimensional Quantitative Structure Activity Relation (3D-QSAR) and ADME properties to screen out potential compounds. Aim of the study is to identify potential lead/s from natural sources using in silico techniques that can be developed as a drug like molecule against Chikungunya infection and replication. Three softwares were used for molecular docking studies. Potential ligands selected by docking studies were subsequently subjected 3D-QSAR studies to predict biological activity. Based on docking scores and pIC50 value, potential anti-Chikungunya compounds were identified. Best docked receptor-ligands were also subjected to MD for more accurate estimation. Lipinski’s rule and ADME studies of the identified compounds were also studied to assess their drug likeness properties. Results of in silico findings, led to identification of few best fit compounds of natural origin against targets of Chikungunya virus which may lead to discovery of new drugs for Chikungunya.
Communicated by Ramaswamy H. Sarma 相似文献
52.
Norimah AK H. C. Koo Hamid Jan JM Mohd Nasir MT S. Y. Tan Mahendran Appukutty Nurliyana AR Frank Thielecke Sinead Hopkins M. K. Ong C. Ning E. S. Tee 《PloS one》2015,10(10)
Background
Diets rich in whole grain are associated with several health benefits. Little is known however, about whole grain consumption patterns in Malaysia. The aim of this study was to assess whole grain intakes and dietary source in Malaysian children and adolescents.Methods
This analysis is from the MyBreakfast study, a national cross sectional study investigating eating habits among primary and secondary school children throughout Malaysia, conducted in 2013. Children (n = 5,165) and adolescents (n = 2,947) who completed two days of dietary assessment using a food record or recall respectively were included. The whole grain content of foods was estimated mainly through the use of quantitative ingredient declarations on food labels. All wholegrain foods were considered irrespective of the amount of whole grain they contained.Results
Overall, only 25% of children and 19% of adolescents were wholegrain consumers. Mean daily intakes in the total sample were 2.3g/d (SD 5.8g/d) in children and 1.7g/d (SD 4.7g/d) in adolescents and in the consumer’s only sample, mean intakes reached 9.1g/d (SD 8.6) and 9.2g/d (SD 7.1g/d) respectively. Wheat was the main grain source of whole grain while ready to eat breakfast cereals and hot cereals were the main food contributors. Less than 3% of the children and adolescents reached the US quantitative whole grain recommendation of 48g/day.Conclusion
Whole grain is consumed by only a minority of Malaysian children and adolescents and even among consumers, intakes are well below recommendations. Efforts are needed to firstly understand the barriers to whole grain consumption among Malaysian children in order to design effective health promotion initiatives to promote an increase in whole grain consumption. 相似文献53.
Fernando M Botelho Jake K Nikota Carla MT Bauer Mathieu C Morissette Yoichiro Iwakura Roland Kolbeck Donna Finch Alison A Humbles Martin R St?mpfli 《Respiratory research》2012,13(1):81
Background
Evidence suggests that dendritic cells accumulate in the lungs of COPD patients and correlate with disease severity. We investigated the importance of IL-1R1 and its ligands IL-1α and β to dendritic cell accumulation and maturation in response to cigarette smoke exposure.Methods
Mice were exposed to cigarette smoke using a whole body smoke exposure system. IL-1R1-, TLR4-, and IL-1α-deficient mice, as well as anti-IL-1α and anti-IL-1β blocking antibodies were used to study the importance of IL-1R1 and TLR4 to dendritic cell accumulation and activation.Results
Acute and chronic cigarette smoke exposure led to increased frequency of lung dendritic cells. Accumulation and activation of dendritic cells was IL-1R1/IL-1α dependent, but TLR4- and IL-1β-independent. Corroborating the cellular data, expression of CCL20, a potent dendritic cells chemoattractant, was IL-1R1/IL-1α-dependent. Studies using IL-1R1 bone marrow-chimeric mice revealed the importance of IL-1R1 signaling on lung structural cells for CCL20 expression. Consistent with the importance of dendritic cells in T cell activation, we observed decreased CD4+ and CD8+ T cell activation in cigarette smoke-exposed IL-1R1-deficient mice.Conclusion
Our findings convey the importance of IL-1R1/IL-1α to the recruitment and activation of dendritic cells in response to cigarette smoke exposure. 相似文献54.
55.
The influence of several metabolic inhibitors and pharmacologic agents on macrophage deformation (induced by fluid shear stress) was examined in relationship to changes in ATP content and phagocytosis of latex beads. Two relatively specific inhibitors of glycolysis (iodoacetate [IA], and sodium fluoride [NaF]) and a sulfhydryl-binding agent (N-ethylmaleimide [NEM] markedly inhibited phagocytosis and reduced cell deformability. A microtubule-disrupting agent (vinblastine) and a highly specific inhibitor of glycolysis (2-deoxyglucose) markedly inhibited phagocytosis without influencing cell deformability. An organomercurial sulfhydryl binding agent p-chloromercuribenzene (PCMBS) and a microfilament-disrupting agent (cytochalasin B) inhibited phagocytosis and increased cell deformability. The effects of these agents on phagocytosis and cell deformability bore no consistent relationship to alterations in cellular content of ATP. The observation that 2-deoxyglucose, the most specific inhibitor of glycolysis examined, reduced ATP content to levels far lower (15 percent of control values) than those achieved by any other agent examined and inhibited phagocytosis without altering cell deformability, suggests that alterations in cell deformability induced by NaF, IA, NEM, PCMBS, and cytochalasin B are not due to inhibition of glycolysis per se, but instead result from direct or indirect effects of these agents on cell constituents, possibly contractile proteins, which are determinants of cell deformability. The finding that cytochalasin B, NEM, PCMBS, and IA interfere with phagocytosis and alter cell deformability, together with evidence that these agents interact with isolated actin and myosin, suggests that contractile proteins are important both in phagocytosis and as determinants of cell deformability. The observation that vinblastine, colchicines, and heavy water (D(2)O) did not alter cell deformability, even though vinblastine caused formation of intracellular crystals of microtubular protein, indicates that microtubules are not major determinants of cell deformability. The observations that beads adhered normally to surfaces of cytochalasin B- and of PCMBS-treated cells and that shear-stress induced deformation was increased whereas phagocytosis was markedly inhibited, suggest that deformation of cells around beads associated with ingestion depends on some form of cellular (contractile?) activity, whereas deformation of cells by fluid shear stress is a passive phenomenon. 相似文献
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57.
Ruoqi Peng Sriram Sridhar Gaurav Tyagi Jonathan E. Phillips Rosario Garrido Paul Harris Lisa Burns Lorena Renteria John Woods Leena Chen John Allard Palanikumar Ravindran Hans Bitter Zhenmin Liang Cory M. Hogaboam Chris Kitson David C. Budd Jay S. Fine Carla MT. Bauer Christopher S. Stevenson 《PloS one》2013,8(4)
The preclinical model of bleomycin-induced lung fibrosis, used to investigate mechanisms related to idiopathic pulmonary fibrosis (IPF), has incorrectly predicted efficacy for several candidate compounds suggesting that it may be of limited value. As an attempt to improve the predictive nature of this model, integrative bioinformatic approaches were used to compare molecular alterations in the lungs of bleomycin-treated mice and patients with IPF. Using gene set enrichment analysis we show for the first time that genes differentially expressed during the fibrotic phase of the single challenge bleomycin model were significantly enriched in the expression profiles of IPF patients. The genes that contributed most to the enrichment were largely involved in mitosis, growth factor, and matrix signaling. Interestingly, these same mitotic processes were increased in the expression profiles of fibroblasts isolated from rapidly progressing, but not slowly progressing, IPF patients relative to control subjects. The data also indicated that TGFβ was not the sole mediator responsible for the changes observed in this model since the ALK-5 inhibitor SB525334 effectively attenuated some but not all of the fibrosis associated with this model. Although some would suggest that repetitive bleomycin injuries may more effectively model IPF-like changes, our data do not support this conclusion. Together, these data highlight that a single bleomycin instillation effectively replicates several of the specific pathogenic molecular changes associated with IPF, and may be best used as a model for patients with active disease. 相似文献
58.
Functional normalization of 450k methylation array data improves replication in large cancer studies
Jean-Philippe Fortin Aurélie Labbe Mathieu Lemire Brent W Zanke Thomas J Hudson Elana J Fertig Celia MT Greenwood Kasper D Hansen 《Genome biology》2014,15(11)
We propose an extension to quantile normalization that removes unwanted technical variation using control probes. We adapt our algorithm, functional normalization, to the Illumina 450k methylation array and address the open problem of normalizing methylation data with global epigenetic changes, such as human cancers. Using data sets from The Cancer Genome Atlas and a large case–control study, we show that our algorithm outperforms all existing normalization methods with respect to replication of results between experiments, and yields robust results even in the presence of batch effects. Functional normalization can be applied to any microarray platform, provided suitable control probes are available.
Electronic supplementary material
The online version of this article (doi:10.1186/s13059-014-0503-2) contains supplementary material, which is available to authorized users. 相似文献59.
Celia MT Greenwood Shuying Sun Justin Veenstra Nancy Hamel Bethany Niell Stephen Gruber William D Foulkes 《BMC genetics》2010,11(1):39
Background
Several founder mutations leading to increased risk of cancer among Ashkenazi Jewish individuals have been identified, and some estimates of the age of the mutations have been published. A variety of different methods have been used previously to estimate the age of the mutations. Here three datasets containing genotype information near known founder mutations are reanalyzed in order to compare three approaches for estimating the age of a mutation. The methods are: (a) the single marker method used by Risch et al., (1995); (b) the intra-allelic coalescent model known as DMLE, and (c) the Goldgar method proposed in Neuhausen et al. (1996), and modified slightly by our group. The three mutations analyzed were MSH2*1906 G->C, APC*I1307K, and BRCA2*6174delT.Results
All methods depend on accurate estimates of inter-marker recombination rates. The modified Goldgar method allows for marker mutation as well as recombination, but requires prior estimates of the possible haplotypes carrying the mutation for each individual. It does not incorporate population growth rates. The DMLE method simultaneously estimates the haplotypes with the mutation age, and builds in the population growth rate. The single marker estimates, however, are more sensitive to the recombination rates and are unstable. Mutation age estimates based on DMLE are 16.8 generations for MSH2 (95% credible interval (13, 23)), 106 generations for I1037K (86-129), and 90 generations for 6174delT (71-114).Conclusions
For recent founder mutations where marker mutations are unlikely to have occurred, both DMLE and the Goldgar method can give good results. Caution is necessary for older mutations, especially if the effective population size may have remained small for a long period of time.60.
Vu Thuy Khanh LeTrilling Sofia Banchenko Darius Paydar Pia Madeleine Leipe Lukas Binting Simon Lauer Andrea Graziadei Robin Klingen Christine Gotthold Jrg Bürger Thilo Bracht Barbara Sitek Robert Jan Lebbink Anna Malyshkina Thorsten Mielke Juri Rappsilber Christian MT Spahn Sebastian Voigt Mirko Trilling David Schwefel 《The EMBO journal》2023,42(5)