炎症性肠病(IBD)是一种以反复腹痛、腹泻、血便和体重降低为主要表现的慢性特发性性疾病,主要分为溃疡性结肠炎与克罗恩病两种类型。近年来,IBD的患病率随着城市化和工业化进展迅速升高,给中国和全球的公共健康带来沉重的负担。随着人类基因组技术的发展,越来越多的证据表明,遗传学因素在IBD发病过程中起着不可或缺的作用。在亚欧人群中,通过大规模全基因组关联研究现已明确了320个IBD易感基因位点。IBD易感基因在影响机体的细胞代谢、免疫功能调节、肠道上皮屏障和微生物清除等多个方面发挥着重要作用。本文就IBD相关易感基因及其多态性的研究进展进行综述,从基因层面揭示IBD发病的分子机制,并对探索IBD因人而异的个性化治疗方案提供帮助。
Inflammatory bowel disease(IBD)is a chronic idiopathic disease characterized by recurrent abdominal pain,diarrhea,bloody stools,and weight loss.Ulcerative colitis and Crohn’s disease represent the two main types of IBD.In recent years,the prevalence of IBD has increased rapidly with the advancement of industrialization,imposing a heavy burden on public health in China and globally.Currently,with the development of genomics,a growing body of evidence suggests that genetic factors play an indispensable role in the pathogenesis of IBD.In the Eurasian population,320 IBD susceptibility gene loci have been identified through large-scale genome-wide association studies.IBD susceptibility genes play a crucial role in various aspects affecting cellular metabolism,immune function regulation,intestinal epithelial barrier,and microbial clearance.This article reviews the susceptibility genes and their polymorphisms associated with IBD,revealing the molecule mechanisms of IBD from gene perspectives and contributing to the development of personalized treatment strategies tailored to individual IBD patients.
结直肠癌(CRC)是全球第三大最常见的癌症,也是癌症相关死亡的第二大常见原因。结直肠癌肝转移(CRLM)是导致CRC患者死亡的主要原因,根治性肝切除术是目前有望治愈CRLM的唯一途径,但大部分患者不能进行根治性肝切除术。通过早期发现并进行针对性干预,能够改善患者的治疗效果及预后。文章通过综述CRLM的发病机制、诊疗现状及最新纳米诊疗方法,为深入探索高效诊疗方法提供思路。
Colorectal cancer(CRC)is the third most common cancer and the second most common cause of cancer-related death worldwide.Colorectal cancer liver metastases(CRLM)are the leading cause of death in patients with CRC.Radical hepatectomy is the only way to cure CRLM so far,while most patients cannot undergo radical hepatectomy.CRLM treatment efficacy and prognosis can be improved by early diagnosis and specialized intervention.This paper reviews the pathogenesis,diagnosis,and treatment status of CRLM and the latest nano-diagnosis and treatment methods so as to provide ideas for in-depth exploration of efficient diagnosis and treatment methods.
目的 采用网络药理学方法与分子对接技术分析白头翁汤治疗细菌性痢疾(BD)的潜在活性成分与作用机制。方法 借助中药系统药理学数据库与分析平台(TCMSP)及PubChem数据库检索筛选白头翁汤方的化学成分和作用靶点,通过Uniprot数据库校正基因名,同时通过比较毒物基因组学数据库(CTD)、药物靶标数据库(TTD)、GeneCards数据库和药物和药物靶标数据库(DRUGBANK)获得BD相关疾病靶点。经在线绘图平台微生信分析“活性成分-疾病”交集靶点,使用Cyoscape 3.7.2软件构建可视化的中药-活性成分-靶点网络、蛋白质互作网络,筛选潜在的关键活性成分与核心靶点;通过Metascape数据库对进行靶点的基因本体(GO)功能分析和京都百科全书基因和基因组通路数据库(KEGG)通路富集分析,同时使用Cyoscape 3.7.2软件构建基因-通路网络,筛选潜在的通路及其作用机制。同时采用分子对接技术对白头翁汤中关键活性成分和BD核心靶点进行分析。结果 白头翁汤共筛选出266个潜在活性成分,其中,槲皮素、β-谷甾醇、异鼠李素、异延胡索单酚碱、小檗红碱、豆甾醇等66个关键活性成分可通过肿瘤坏死因子(TNF)、白细胞介素-6(IL-6)、前列腺素内过氧化物合酶2(PTGS2)、丝氨酸/苏氨酸蛋白激酶1(AKT1)、血管内皮生长因子A(VEGFA)、V-rel网状内皮细胞病毒癌基因同源物A(RELA)、半胱氨酸天冬氨酸蛋白酶3(CASP3)、白细胞介素-8(CXCL8)、白细胞介素-1B(IL-1B)、丝裂原活化蛋白激酶1(MAPK1)、白细胞介素-10(IL-10)等33个潜在交集靶点作用于BD。GO基因功能分析共得到生物过程(BP)条目20个、细胞组成(CC)条目6个、分子功能(MF)条目9个(P<0.01),主要涉及外部凋亡过程、细胞迁移正向调控、细胞因子受体结合、蛋白同源二聚活性、TNF受体超家族结合等生物进程。KEGG通路富集分析确定13条信号通路(P<0.01),主要涉及癌症信号通路、白细胞介素-17(IL-17)信号通路等关键通路。分子对接结果显示槲皮素、β-谷甾醇、异鼠李素、异延胡索单酚碱等核心活性成分与TNF、IL-6、PTGS2核心靶点具有良好的结合效应(结合能<-5 kJ/mol)。结论 白头翁汤主要通过槲皮素、β-谷甾醇等潜在的多种活性成分作用于TNF、IL-6、IL-1B、PTGS2、AKT1、VEGFA等潜在的关键靶点调控IL-17等信号通路,从而发挥治疗细菌性痢疾的作用,符合中药复方多成分、多靶标、多途径起效的显著特征。
Objective To analyze the potential active ingredients and mechanism of Baitouweng Decoction in the treatment of bacillary dysentery(BD)by means of network pharmacology and molecular docking technology.Methods With the help of the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(Traditional Chinese Medicine Systems Pharmacology Database,TCMSP)and PubChem database to search and screen the chemical composition and target of Baitouweng Decoction,the gene name was corrected through the Uniprot database,and the CTD database,TTD database,GeneCards database and DRUGBANK database obtain BD-related disease targets.The intersection target was obtained through the online drawing platform,and Cytoscape 3.7.2 was used to construct a network of Pulsatilla active ingredient-component disease intersection target.The protein-protein interaction analysis of the intersection target was performed through the String database,and the Cytoscape 3.7.2 software was used for visualization.The Metascape database platform performed GO function analysis and KEGG pathway enrichment analysis on the target to predict its mechanism of action.The key active ingredient compounds in Baitouweng Decoction were molecularly docked with the core protein in the intersection target.Results A total of 266 potential active ingredients in Baitouweng Decoction were screened,of which 66 key active ingredients such as quercetin,β-sitosterol,isorhamnetin,Isocorypalmine,berberine,stigmasterol,etc.It acts on BD through 33 potential intersection targets such as TNF,IL-6,PTGS2,AKT1,VEGFA,RELA,CASP3,CXCL8,IL-1B,MAPK1,IL-10.GO gene function analysis yielded a total of 20 biological process(BP)entries,6 cell composition(CC)entries,and 9 molecular function(MF)entries(P<0.01),which mainly involve external apoptosis process and positive regulation of cell migration,Cytokine receptor binding,protein homodimerization activity,tumor necrosis factor receptor superfamily binding and other biological processes.KEGG pathway enrichment analysis identified 13 signal pathways(P<0.01),mainly related to key pathways such as cancer signal pathway and IL-17 signal pathway.The results of molecular docking showed that the core active ingredients such as quercetin,β-sitosterol,isorhamnetin,Isocorypalmine and TNF,IL-6,PTGS2 core targets have good binding effects(binding energy <-5 KJ /mol).Conclusions Baitouweng Decoction modulated signaling pathways involving IL-17 through its active constituents like quercetin and β-sitosterol,targeting key molecules such as TNF,IL-6,IL-1β,PTGS2,AKT1,and VEGFA,reflecting the multi-target therapeutic approach of traditional Chinese medicine.
近几十年来,全球近视患病率不断上升,已成为全世界主要的公共卫生问题之一。众多研究表明户外活动能有效控制近视的发生和发展。本文综述了户外活动对近视防控作用的研究进展及其作用机制,以期为近视防控提供新的思路。
In recent decades, the prevalence of myopia has been increasing globally, becoming one of the major public health issues worldwide. Numerous studies indicate that outdoor activities can effectively control the onset and progression of myopia. This article reviews the research progress on prevention and control effect and mechanism of outdoor activities on myopia, hoping to provide new insights for myopia prevention and control.