Transcriptome-wide association study reveals two genes that influence mismatch negativity

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白头翁汤对炎症性肠病中促炎细胞因子表达的影响

目的：探讨白头翁汤治疗炎症性肠病的分子机制。方法：40只Wistar雄性大鼠随机分为5组（n=8）：正常对照组、模型组、模型＋阳性药物对照组（美沙拉嗪）、模型＋白头翁中、高剂量治疗组。阳性对照组、中药治疗组分别灌胃给药。疗程结束后取大鼠结肠组织提取RNA,利用realtimePCR的方法检测白介素-1β（IL-1β）、白介素-6（IL-6）YL肿瘤坏死因子-α（TNF-α）在各组中的表达变化。结果：相对于模型组,阳性药物及白头翁汤治疗组尤其是高剂量组可有效抑制IL-1β、IL-6及TNF-α的表达。结论：白头翁汤可通过抑制促炎因子的表达从而发挥了在炎症性肠病中的治疗作用。     

炎症性肠病与艰难梭菌感染相关性研究的文献计量学和可视化分析

【背景】近年来,炎症性肠病患者中艰难梭菌（Clostridium difficile）感染率逐年上升,受到国内外学者广泛关注。我国在该领域的研究起步较晚,但患者数量众多,学习国际上对于炎症性肠病合并艰难梭菌感染的研究,对推动我国在该领域的深入发展具有重要意义。【目的】通过文献计量和可视化分析帮助研究者把握炎症性肠病与艰难梭菌感染相关性研究中的研究主题、方向、热点与前沿。【方法】同时检索Web of Science （WOS）中Science Citation Index Expanded （SCI-E）和CNKI中收录的关于炎症性肠病和艰难梭菌的相关文献,应用CiteSpace 6.2.2r软件进行国家/地区、机构、作者、关键词共现及被引文献、期刊共被引分析,同时进行可视化分析。【结果】经过数据检索和查重,最终可供分析的文献为WOS数据库1 030篇、CNKI数据库80篇。全球范围内,发文最多的国家是美国,主要研究机构有Harvard University、University of California System和Mayo Clinic等,高产作者有Khanna S、Shen B和Ananthakrishnan AN等,高频关键词包括Inflammatory bowel disease、Ulcerative colitis、Clostridium difficile、Clostridium difficile infection和Crohn’s disease等,聚类方向有#0 Diarrhea、#1 Ulcerative colitis、#2 Probiotics、#3 Pouchitis、#4 Gut microbiota、#5 Fecal microbiota transplantation、#6 Depression、#7 Entamoeba histolytica、#8 Pseudomembranous colitis、#9 Clostridium difficile和#10 Clindamycin。国内主要研究机构有南方医科大学和河北医科大学,高产作者有王浦、王斯淇等,高频关键词包括粪菌移植、艰难梭菌、肠道菌群、危险因素和克罗恩病等,聚类方向有#0艰难梭菌、#1益生菌、#2危险因素、#3腹泻和#4粪菌移植。【结论】利用CiteSpace软件对炎症性肠病和艰难梭菌感染相关性研究进行计量及可视化分析可知,该方向仍得到全球各医疗机构及研究者的关注,腹泻及粪菌移植这两个关键词分别代表了WOS数据库和CNKI数据库关于炎症性肠病合并艰难梭菌感染研究的热点。     

炎症性肠病生物检测器的构建与调试

利用工程改造过的肠道微生物进行无创、便宜便捷的肠道炎症检测、治疗可有效应用于医药行业。肠道炎症通常伴随着肠道中硫代硫酸盐和连四硫酸盐的增加,双组分系统ThsSR和TtrSR是两套分别检测这两种小分子的生物感受器系统。采用荧光蛋白作为指示剂需要复杂的测试仪器,不适用于家用检测环境,而肉眼可见的色素蛋白和有色小分子作为指示剂将可能扩大ThsSR和TtrSR的应用前景。两套系统分别被转入大肠杆菌EscherichiacoliTop10和益生菌E. coli Nissle 1917中,sfGFP信号表达效果证明了这两套系统可用。考虑实际应用,sfGFP被一系列色素蛋白和显色小分子替换,在E. coli Top10中,一系列色素蛋白和紫色杆菌素前体protoviolaceinic acid的显色效果明显,表明了该系统具有用于实际肠道炎症检测的可行性。结果表明,改进后的ThsSR和TtrSR系统能够针对不同浓度的肠道炎症标记物作出相应程度的反应,具备用于家庭环境人体肠道炎症检测的潜力。     

Immune chromatin reader SP140 regulates microbiota and risk for inflammatory bowel disease

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Therapeutic effects of lentinan on inflammatory bowel disease and colitis‐associated cancer

In this study, we investigated the therapeutic potential of lentinan in mouse models of inflammatory bowel disease (IBD) and colitis‐associated cancer (CAC). Lentinan decreased the disease activity index and macroscopic and microscopic colon tissue damage in dextran sulphate sodium (DSS)‐induced or TNBS‐induced models of colitis. High‐dose lentinan was more effective than salicylazosulfapyridine in the mouse models of colitis. Lentinan decreased the number of tumours, inflammatory cell infiltration, atypical hyperplasia and nuclear atypia in azoxymethane/DSS‐induced CAC model. It also decreased the expression of pro‐inflammatory cytokines, such as IL‐13 and CD30L, in IBD and CAC model mice possibly by inhibiting Toll‐like receptor 4 (TLR4)/NF‐κB signalling and the expression of colon cancer markers, such as carcinoembryonic antigen, cytokeratin 8, CK18 and p53, in CAC model mice. In addition, lentinan restored the intestinal bacterial microbiotal community structure in IBD model mice. Thus, it shows therapeutic potential in IBD and CAC model mice possibly by inhibiting TLR4/NF‐κB signalling‐mediated inflammatory responses and disruption of the intestinal microbiotal structure.     

IL‐35 recombinant protein reverses inflammatory bowel disease and psoriasis through regulation of inflammatory cytokines and immune cells

Interleukin‐35 (IL‐35), a member of the IL‐12 family, functions as a new anti‐inflammatory factor involved in arthritis, psoriasis, inflammatory bowel disease (IBD) and other immune diseases. Although IL‐35 can significantly prevent the development of inflammation in many diseases, there have been no early studies accounting for the role of IL‐35 recombinant protein in IBD and psoriasis. In this study, we assessed the therapeutic potential of IL‐35 recombinant protein in three well‐known mouse models: the dextransulfate sodium (DSS)‐induced colitis mouse model, the keratin14 (K14)‐vascular endothelial growth factor A (VEGF‐A)‐transgenic (Tg) psoriasis mouse model and the imiquimod (IMQ)‐induced psoriasis mouse model. Our results indicated that IL‐35 recombinant protein can slow down the pathologic process in DSS‐induced acute colitis mouse model by decreasing the infiltrations of macrophages, CD4⁺T and CD8⁺T cells and by promoting the infiltration of Treg cells. Further analysis demonstrated that IL‐35 recombinant protein may regulate inflammation through promoting the secretion of IL‐10 and inhibiting the expression of pro‐inflammatory cytokines such as IL‐6, TNF‐α and IL‐17 in acute colitis model. In addition, lower dose of IL‐35 recombinant protein could achieve long‐term treatment effects as TNF‐α monoclonal antibody did in the psoriasis mouse. In summary, the remarkable therapeutic effects of IL‐35 recombinant protein in acute colitis and psoriasis mouse models indicated that IL‐35 recombinant protein had a variety of anti‐inflammatory effects and was expected to become an effective candidate drug for the treatment of inflammatory diseases.     

Pathway analysis for genome-wide genetic variation data: Analytic principles,latest developments,and new opportunities

Pathway analysis, also known as gene-set enrichment analysis, is a multilocus analytic strategy that integrates a priori, biological knowledge into the statistical analysis of high-throughput genetics data. Originally developed for the studies of gene expression data, it has become a powerful analytic procedure for indepth mining of genome-wide genetic variation data. Astonishing discoveries were made in the past years,uncovering genes and biological mechanisms underlying common and complex disorders. However, as massive amounts of diverse functional genomics data accrue, there is a pressing need for newer generations of pathway analysis methods that can utilize multiple layers of high-throughput genomics data. In this review, we provide an intellectual foundation of this powerful analytic strategy, as well as an update of the state-of-the-art in recent method developments. The goal of this review is threefold:(1) introduce the motivation and basic steps of pathway analysis for genome-wide genetic variation data;(2) review the merits and the shortcomings of classic and newly emerging integrative pathway analysis tools; and(3)discuss remaining challenges and future directions for further method developments.     

Gene set analysis of genome-wide association studies: methodological issues and perspectives

Recent studies have demonstrated that gene set analysis, which tests disease association with genetic variants in a group of functionally related genes, is a promising approach for analyzing and interpreting genome-wide association studies (GWAS) data. These approaches aim to increase power by combining association signals from multiple genes in the same gene set. In addition, gene set analysis can also shed more light on the biological processes underlying complex diseases. However, current approaches for gene set analysis are still in an early stage of development in that analysis results are often prone to sources of bias, including gene set size and gene length, linkage disequilibrium patterns and the presence of overlapping genes. In this paper, we provide an in-depth review of the gene set analysis procedures, along with parameter choices and the particular methodology challenges at each stage. In addition to providing a survey of recently developed tools, we also classify the analysis methods into larger categories and discuss their strengths and limitations. In the last section, we outline several important areas for improving the analytical strategies in gene set analysis.     

An analysis of genetic factors related to risk of inflammatory bowel disease and colon cancer

Background and aimsPatients with inflammatory bowel disease (IBD) have a higher risk of developing colorectal cancer than the general population. Genome-wide association studies have identified and replicated several loci associated with risk of IBD; however, it is currently unknown whether these loci are also associated with colon cancer risk.MethodsWe selected 15 validated SNPs associated with risk of either Crohn's disease, ulcerative colitis, or both in previous GWAS and tested whether these loci were also associated with colon cancer risk in a two-stage study design.ResultsWe found that rs744166 in STAT3 was associated with colon cancer risk in two studies; however, the direction of the observation was reversed in TP53 mutant tumors possibly due to a nullification of the effect by mutant p53. The SNP, which lies within intron 1 of the STAT3 gene, was associated with lower expression of STAT3 mRNA in TP53 wild-type, but not mutant, tumors.ConclusionsThese data suggest that the STAT3 locus is associated with both IBD and cancer. Further understanding the function of this variant in relation to TP53 could possibly explain the role of this gene in autoimmunity and cancer. Furthermore, an analysis of this locus, specifically in a population with IBD, could help to resolve the relationship between this SNP and cancer.