Identifying changed protein-protein interactions in biological processes by gene coexpression analysis

The interaction strength between 2 proteins is not constant but variable under different conditions. For a given biological process, identification of protein-protein interactions (PPIs) undergoing dynamic change in interaction strength is highly valuable but never achieved before. In this work, we presented a computational approach to identify changed PPIs (cPPIs) on a global scale by analyzing the coexpression level of genes encoding the interacting protein pairs. This approach stemmed from the biological...     

藏药翁布提取物对SD大鼠FCA诱导性关节炎的试验研究

目的：研究单味藏药翁布（Myricaria germanica（L.）Desv.）对SD大鼠佐剂性关节炎（AA）的作用.方法：以SD大鼠为实验动物,采用Freund’s佐剂作为致炎因子,复制急性关节炎症并伴随继发性风湿性关节模型,用不同提取物灌胃24d,测定体重、关节炎指数、足趾肿胀度.结果：藏药翁布各提取物显著抑制SD大鼠关节炎指数、足趾肿胀度.结论：藏药翁布提取物对Freund’s佐剂诱导性关节炎有显著的抗炎作用.     

桂枝芍药知母汤加减治疗类风湿性关节炎60例

目的 :探讨桂枝芍药知母汤加减治疗类风湿关节炎的临床效果。方法 :运用桂枝芍药知母汤加减辨证分型治疗类风湿性关节炎患者60例 ,并进行临床观察和疗效分析。结果 :服药1疗程显效48例 ,好转9例 ,无效3例。结论 :类风湿关节炎为虚实寒热夹杂之证 ,解决好清热与温阳的矛盾 ,治疗上以通为要 ,则能达到理想的治疗效果     

The association between the CASP5 rs7939842 polymorphism and the risk of rheumatoid arthritis in Chinese Han individuals

BackgroundThe association between inflammatory cysteinyl aspartate protease-5 (CASP5) and the susceptibility to rheumatoid arthritis (RA) remains unclear. This study examined whether the CASP5 rs7939842 polymorphism affects RA risk in Chinese Han individuals.MethodsThis study recruited 805 RA patients and 1095 healthy controls to investigate the association between the CASP5 rs7939842 polymorphism and RA risk. Genotype was examined using the 48-Plex SNPscan? Kit. Plasma CASP5 levels were determined using enzyme-linked immunosorbent assays, and CASP5 gene expression was detected by quantitative polymerase chain reaction in 40 RA patients and 40 healthy controls.ResultThe CASP5 rs7939842 polymorphism G allele is a putative risk factor for RA. After stratified analyses, this polymorphism increased the risk of RA among CRP-, ACPA-, RF-, and ESR-positive individuals, as well as individuals with DAS28 ≥ 3.20 and functional class III + IV. Furthermore, the plasma CASP5 levels and CASP5 mRNA expression were higher in RA patients than in healthy controls.ConclusionThe CASP5 rs7939842 polymorphism appears to be associated with an elevated risk of RA in Chinese Han individuals. Blood CASP5 protein and mRNA levels were significantly higher in RA patients than in healthy controls.     

五味甘露药浴散加减方对佐剂型关节炎大鼠血清RF和滑膜组织JNK1的影响

观察五味甘露药浴散加减方对佐剂型关节炎大鼠的疗效及对大鼠血清RF和踝关节滑膜组织JNK1的的影响.采用弗氏完全佐剂关节炎(Adjuvant Arthritis Rats,AA)大鼠模型,用大鼠致炎侧足跖肿胀率评价五味甘露药浴散加减方对AA大鼠的治疗效果,ELISA法测定血清中RF的水平,免疫组化法测定踝关节滑膜组织蛋白激酶JNK1的表达.实验结果表明,与模型组比较,给药四周,五味甘露药浴散加减方高剂量能有效减少致炎侧足跖肿胀率(P0.05);给药两周和四周,五味甘露药浴散加减方高剂量能明显降低血清中RF的水平(P0.05).五味甘露药浴散加减方各剂量均能显著降低踝关节滑膜组织JNK1的表达(P0.05或P0.01).五味甘露药浴散加减方能有效的减小佐剂性关节炎大鼠致炎侧足跖肿胀率,其作用机制可能与其降低血清中RF的水平和滑膜组织JNK1的表达有关.     

自拟方“通痹祛风汤”对大鼠急性痛风性关节炎抗炎作用研究

目的:观察"通痹祛风汤"对急性痛风性关节炎模型大鼠不同时相的影响,探讨其治疗急性痛风性关节炎的作用机制.方法:注射尿酸钠建立大鼠痛风性关节炎模型,大鼠灌胃给药,观察对大鼠关节肿胀率及关节滑膜囊表达IL-1 mRNA和TNF-mRNA(RT-PCR)的影响.结果:"通痹祛风汤"可有效抑制大鼠踝关节肿胀程度;关节滑膜囊TNF-mRNA和IL-1 mRNAr的表达明显减低.结论:"通痹祛风汤"可抑制痛风性关节炎TNF-和IL-1的产生而发挥抗炎作用,明显减轻关节的病理性损伤,有效抑制关节炎的临床进程.     

以琼脂凝胶固定热聚IgG制备类风湿关节炎免疫吸附剂的研究

以环氧氯丙烷对琼脂凝胶珠进行活化反应后键联热聚ＩｇＧ,制成一种新型类风湿关节炎免疫吸附剂。确定了最佳制备条件,使凝胶上环氧基的含量达１１０μｍｏｌ／ｇ,对热苯ＩｇＧ的固定量达６ｍｇ／ｇ。在体外条件下吸附剂对三种类风湿因子ＩｇＭＲＦ,ＩｇＧＲＦ及ＩｇＡＲＦ的吸附量分别达３４００,２２５０和２４００ＩＵ／ｇ,具有良好的应用前景。     

Functional Analysis of Autoantibody Signatures in Rheumatoid Arthritis

For the identification of antigenic protein biomarkers for rheumatoid arthritis (RA), we conducted IgG profiling on high density protein microarrays. Plasma IgG of 96 human samples (healthy controls, osteoarthritis, seropositive and seronegative RA, n = 24 each) and time-series plasma of a pristane-induced arthritis (PIA) rat model (n = 24 total) were probed on AIT’s 16k protein microarray. To investigate the analogy of underlying disease pathways, differential reactivity analysis was conducted. A total of n = 602 differentially reactive antigens (DIRAGs) at a significance cutoff of p < 0.05 were identified between seropositive and seronegative RA for the human samples. Correlation with the clinical disease activity index revealed an inverse correlation of antibodies against self-proteins found in pathways relevant for antigen presentation and immune regulation. The PIA model showed n = 1291 significant DIRAGs within acute disease. Significant DIRAGs for (I) seropositive, (II) seronegative and (III) PIA were subjected to the Reactome pathway browser which also revealed pathways relevant for antigen presentation and immune regulation; of these, seven overlapping pathways had high significance. We therefore conclude that the PIA model reflects the biological similarities of the disease pathogenesis. Our data show that protein array analysis can elucidate biological differences and pathways relevant in disease as well be a useful additional layer of omics information.     

Gene Interaction Network Analysis Reveals IFI44L as a Drug Target in Rheumatoid Arthritis and Periodontitis

Simple SummaryIn spite of substantial investigation, the biological link between periodontitis and rheumatoid arthritis remains unexplained. This study intended to correlate periodontitis and rheumatoid arthritis gene expression patterns to find shared targets for both the disease. We identified the differentially expressed genes (DEGs) in periodontitis and rheumatoid arthritis. The network was built by integrating DEGs and ranking the genes using GeneMANIA. FINDSITEcomb2.0 was used to find a possible inhibitor for the top-ranked gene. Further, the binding effectiveness and protein-ligand complex stability were then determined by molecular docking and molecular dynamics. The network analysis showed IFI44L as a highly ranking gene implicated in most immunological pathways. A virtual screening of 6507 compounds revealed vemurafenib as the best candidate for the IFI44L target. Molecular docking and molecular dynamics modelling revealed the stability of the IFI44L-vemurafenib complex, which suggest IFI44L is potential target and vemurafenib could be the better candidate to treat both diseases.AbstractObjective: Despite extensive research on periodontitis and rheumatoid arthritis, the underlying molecular connectivity between these condition remains largely unknown. This research aimed to integrate periodontitis and rheumatoid arthritis gene expression profiles to identify interconnecting genes and focus to develop a common lead molecule against these inflammatory conditions. Materials and Methods: Differentially expressed genes (DEGs) of periodontitis and rheumatoid arthritis were identified from the datasets retrieved from the Gene Expression Omnibus database. The network was constructed by merging DEGs, and the interconnecting genes were identified and ranked using GeneMANIA. For the selected top ranked gene, the potential inhibitor was searched using FINDSITE^comb2.0. Subsequently, the molecular docking and molecular dynamics were performed to determine the binding efficiency and protein-ligand complex stability, respectively. Results: From the network analysis, IFN-induced protein 44-like (IFI44L) was identified as a top ranked gene involved in most of the immunological pathway. With further virtual screening of 6507 molecules, vemurafenib was identified to be the best fit against the IFI44L target. The binding energy and stability of IFI44L with vemurafenib were investigated using molecular docking and molecular dynamics simulation. Docking results show binding energy of −7.7 Kcal/mol, and the simulation results show stability till 100 ns. Conclusions: The identified IFI44L may represent a common drug target for periodontitis and rheumatoid arthritis. Vemurafenib could be a potent anti-inflammatory drug for both diseases.     

类风湿关节炎活动期患者血清血小板活化因子含量测定及临床意义

目的探讨血小板活化因子(PAF)在类风湿关节炎(RA)活动期中的水平变化及临床意义。方法采用酶联免疫吸附方法检测43例活动期RA患者血清PAF含量,并与30例健康人血清PAF含量进行比较。结果RA活动期组血清PAF含量(116.02±20.15)明显高于健康对照组(44.27±18.98),差异具有非常显著性意义(t=15.325 6,P<0.001)。结论活动期RA患者血清PAF水平明显升高,可作为反映RA患者风湿活动的评估指标之一。