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1.
目的:通过生物信息学技术比较哮喘患者与健康人的基因芯片数据,初步鉴定与哮喘相关的基因以及治疗哮喘的潜在药物。方法:从基因表达数据库下载GSE74986基因芯片,使用GEO2R分析得出差异表达基因,采用Morpheus制作差异表达基因的热图;通过DAVID 6.8对差异表达基因进行基因本体及京都基因与基因组百科全书分析,使用String 10.5构建蛋白质-蛋白质相互作用网络,筛选核心基因。进一步使用Cytoscape 3.6.1的插件MCODE对差异表达基因进行模块分析。通过医学本体信息检索平台筛选治疗哮喘的小分子药物。结果:筛选出510个差异表达基因,包括29个上调基因和481个下调基因。差异表达基因生物过程与通路主要富集在染色质沉默、核糖核酸聚合酶Ⅱ启动子的转录调节、蛋白质转运、信使核糖核酸加工、核糖核酸剪接以及泛素介导的蛋白水解、内质网中的蛋白质加工、核糖核酸转运、髓样分化因子依赖性Toll样受体信号通路、血小板激活、核苷酸结合寡聚化结构域样受体信号通路等。共得出9个核心基因,包括T-复合蛋白1θ亚基(CCT8),T复合物蛋白1α亚单位(TCP1),26S蛋白酶调节亚单位S10B(PSMC6),热休克蛋白90α(HSP90A) A1,细胞周期蛋白C(CCNC),HSP90AB1,26S蛋白酶体非ATP酶调节亚基6(PSMD6),泛素特异性蛋白酶14(USP14),真核细胞翻译起始因子4E(EIF4E)。得出2个重要模块,模块里的基因主要涉及剪接体和泛素介导的蛋白水解、蛋白修饰以及核糖核酸修饰等生物过程。治疗哮喘的潜在小分子药物有茴香霉素和金雀异黄素等。结论:差异表达基因和核心基因促进了对哮喘发病分子机制的理解,为哮喘的诊治提供了潜在的基因靶标与治疗药物。  相似文献   
2.
Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) is the fourth commonest female malignancy worldwide. CESC progresses in immune-microenvironment mainly composed of infiltrating immune and stromal cells. Here, we performed an integrated analysis incorporating the expression profiles from the Cancer Genome Atlas (TCGA) database and scores of immune and stromal cells calculated by Estimation of Stromal and Immune cells in Malignant Tumours using Expression data (ESTIMATE) algorithm. A two-gene signature (CD1C and CD6 genes) was established to predict the prognosis of CESC. Based on this signature, patients were divided into the high- and low-risk groups, and this signature showed good prognostic performance according to the results of Kaplan-Meier analysis and receiver operating characteristic (ROC) analysis in train set and two validation sets. A nomogram was built for evaluating the clinical applicability of this signature. In addition, based on Tumor Immune Estimation Resource (TIMER) database, 2 hub genes showed negative correlations with tumor purity and positive correlations with infiltrating levels of immune filtrating cells. What’s more, we propose new treatment strategies for the two prognostic subtypes. Low- risk patients were found presenting with a higher level of immune checkpoint molecules and showing higher immunogenicity in immunophenoscore (IPS) analysis, which indicated a better response for immunotherapy. Meanwhile, estimated by Genomics of Drug Sensitivity in Cancer (GDSC) database, the high-risk patients showed sensitive responses to five chemotherapy drugs. Finally, 10 candidate small-molecule drugs for CESC were defined. In summary, the CD1C-CD6 signature can accurately predict the prognosis of CESC.  相似文献   
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4.
ObjectivesSjögren's syndrome (SS) is a chronic autoimmune disease characterized by inflammatory lesions in the salivary and lacrimal glands, which are caused by distinct lymphocytic infiltrates. Female non-obese diabetic (NOD) mice spontaneously develop inflammatory lesions of the salivary glands with SS-like pathological features. Previous studies have shown that MyD88, a crucial adaptor protein that activates innate immune signaling, affects lymphocytic infiltration, but its detailed role remains unclear. In this study, we investigated the role of MyD88 through gene expression profiling in the early phase of pathogenesis in the salivary glands of female NOD mice.MethodsSubmandibular glands collected from 10-week-old female wild-type and Myd88-deficient NOD mice were used for RNA preparation, followed by microarray analysis. The microarray dataset was analyzed to identify Myd88-dependent differentially expressed genes (DEGs). Data generated were used for GO enrichment, KEGG pathway, STRING database, and INTERFEROME database analyses.ResultsMyd88 deficiency was found to affect 230 DEGs, including SS-associated genes, such as Cxcl9 and Bpifa2. Most of the DEGs were identified as being involved in immunological processes. KEGG pathway analysis indicated that the DEGs were putatively involved in autoimmune diseases, such as systemic lupus erythematosus and rheumatoid arthritis. Furthermore, the DEGs included 149 interferon (IFN)-regulated genes.ConclusionsMyD88 is involved in the expression of specific genes associated with IFN-associated immunopathological processes in the salivary glands of NOD mice. Our findings are important for understanding the role of MyD88-dependent innate immune signaling in SS manifestation.  相似文献   
5.
BackgroundIn the field of transplantation, inducing immune tolerance in recipients is of great importance. Blocking co-stimulatory molecule using anti-CD28 antibody could induce tolerance in a rat kidney transplantation model. Myeloid-derived suppressor cells (MDSCs) reveals strong immune suppressive abilities in kidney transplantation. Here we analyzed key genes of MDSCs leading to transplant tolerance in this model.MethodsMicroarray data of rat gene expression profiles under accession number GSE28545 in the Gene Expression Omnibus (GEO) database were analyzed. Running the LIMMA package in R language, the differentially expressed genes (DEGs) were found. Enrichment analysis of the DEGs was conducted in the Database for Annotation, Visualization and Integrated Discovery (DAVID) database to explore gene ontology (GO) annotation and their Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Their protein-protein interactions (PPIs) were provided by STRING database and was visualized in Cytoscape. Hub genes were carried out by CytoHubba.ResultsThree hundred and thirty-eight DEGs were exported, including 27 upregulated and 311 downregulated genes. The functions and KEGG pathways of the DEGs were assessed and the PPI network was constructed based on the string interactions of the DEGs. The network was visualized in Cytoscape; the entire PPI network consisted of 192 nodes and 469 edges. Zap70, Cdc42, Stat1, Stat4, Ccl5 and Cxcr3 were among the hub genes.ConclusionsThese key genes, corresponding proteins and their functions may provide valuable background for both basic and clinical research and could be the direction of future studies in immune tolerance, especially those examining immunocyte-induced tolerance.  相似文献   
6.
从学术体系与历史发展的角度分析中医学与儒家的关系。基于儒家经典阐述的思想体系,从本体、变动、显效三个维度,深入分析了儒家"独立守中"思想本质,提出了儒家思想一元论的原则和方法,并从本体角度分析了儒家"独立守中"思想与中医学的同一性,进一步探讨了其在中医诊疗过程中不可或缺的指导意义。  相似文献   
7.
The use of cadmium sulphide quantum dots (CdS QDs) is increasing, particularly in the electronics industry. Their size (1–10?nm in diameter) is, however, such that they can be taken up by living cells. Here, a bakers’ yeast (Saccharomyces cerevisiae) deletion mutant collection has been exploited to provide a high-throughput means of revealing the genetic basis for tolerance/susceptibility to CdS QD exposure. The deletion of 112 genes, some associated with the abiotic stress response, some with various metabolic processes, some with mitochondrial organization, some with transport and some with DNA repair, reduced the level of tolerance to CdS QDs. A gene ontology analysis highlighted the role of oxidative stress in determining the cellular response. The transformation of sensitive mutants with centromeric plasmids harbouring DNA from a wild type strain restored the wild type growth phenotype when the complemented genes encoded either HSC82, DSK2 or ALD3. The use of these simple eukaryote knock-out mutants for functional toxicogenomic analysis will inform studies focusing on higher organisms.  相似文献   
8.
Objectives The verification of biomedical ontologies is an arduous process that typically involves peer review by subject-matter experts. This work evaluated the ability of crowdsourcing methods to detect errors in SNOMED CT (Systematized Nomenclature of Medicine Clinical Terms) and to address the challenges of scalable ontology verification.Methods We developed a methodology to crowdsource ontology verification that uses micro-tasking combined with a Bayesian classifier. We then conducted a prospective study in which both the crowd and domain experts verified a subset of SNOMED CT comprising 200 taxonomic relationships.Results The crowd identified errors as well as any single expert at about one-quarter of the cost. The inter-rater agreement (κ) between the crowd and the experts was 0.58; the inter-rater agreement between experts themselves was 0.59, suggesting that the crowd is nearly indistinguishable from any one expert. Furthermore, the crowd identified 39 previously undiscovered, critical errors in SNOMED CT (eg, ‘septic shock is a soft-tissue infection’).Discussion The results show that the crowd can indeed identify errors in SNOMED CT that experts also find, and the results suggest that our method will likely perform well on similar ontologies. The crowd may be particularly useful in situations where an expert is unavailable, budget is limited, or an ontology is too large for manual error checking. Finally, our results suggest that the online anonymous crowd could successfully complete other domain-specific tasks.Conclusions We have demonstrated that the crowd can address the challenges of scalable ontology verification, completing not only intuitive, common-sense tasks, but also expert-level, knowledge-intensive tasks.  相似文献   
9.
目的:应用系统生物学方法模拟分析丹红注射液中丹参与红花配伍的分子机制。方法:采用TCMGene DIT和Agilent literature search(ALS)结合搜索方式,挖掘丹参、红花各自作用的蛋白,在BIND,Bio GRID等数据库中查询蛋白间关联,分别构建丹参、红花及丹红注射液蛋白相互作用网络,应用Merge程序中的difference和intersection功能比较网络间异同。结果:采用intersection分析得丹参和红花共有的高连接区蛋白网络含934个蛋白,经cluster ONE方法提取出P0.05的高连接区蛋白子网络4个,Bi NGO插件的基因本位论聚类分析表明,其主要与RNA代谢,核因子kappa B(nuclear factor kappa B,NF-κB)级联反应,脂质代谢,Rho蛋白及小GTP酶调节4类生物学途径相关。将丹红注射液蛋白相互作用网络与丹参、红花共有高连接区蛋白网络进行difference分析,得由1 431个蛋白构成的差异网络,其主要影响细胞增殖、迁移和自噬等。结论:本研究采用系统生物学方法模拟丹参和红花的配伍机制,其可能主要在RNA代谢,NF-κB级联反应以及细胞增殖、迁移和自噬等生物学途径上协同发挥防治疾病的作用。  相似文献   
10.

Background

Exosomes secreted by tumor cells contain specific antigens that may have immunotherapeutic purposes. The aim of this study was to characterize the proteomic content of lymphoma cell-derived exosomes (LCEXs).

Methods

In this study, exosomes derived from Raji cells (EXORaji) were purified and proteins of EXORaji were separated by one-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis. Protein bands were identified by mass spectrometry. The protein components of EXORaji were analyzed using shotgun technology, and the function proteins of EXORaji were defined and described using the Gene Ontology (GO) database and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis.

Results

A total of 197 proteins were identified in EXORaji; 139 proteins were also identified in Raji cells, showing an overlap of 70.56% of the total proteins in EXORaji. Interestingly, the remaining 58 proteins were unique to EXORaji. The GO database and KEGG were used to define and describe the function of proteins. The data showed that some important proteins involved in antigen procession and presentation as well as cell migration and adhesion were also identified in EXORaji, such as MHC-I and II, HSC70, HSP90, and ICMA-1.

Conclusions

LCEXs express a discrete set of proteins involved in antigen presentation and cell migration and adhesion, suggesting that LCEXs play an important role in the regulation of immunity and interaction between lymphoma cells and their microenvironment. LCEXs harbor most of the proteins of lymphoma cells and could be one of the sources of lymphoma-associated antigens for immunotherapeutic purposes.  相似文献   
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