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专家述评

造血干细胞治疗多囊肾的机制及治疗前景

Mechanisms and therapeutic prospects of hematopoietic stem cells in polycystic kidney disease

:545-553
 
       常染色体显性多囊肾病(ADPKD)是导致遗传性肾衰竭的主要病因之一,目前仍缺乏有效的手段来逆转其疾病进展。干细胞疗法因其在组织修复和免疫调节方面的潜力,成为研究的热点领域。本研究系统阐述了造血干细胞(HSCs)通过旁分泌作用、代谢重塑及免疫调控干预ADPKD病理进程的机制,并总结了其在急性肾损伤和慢性肾病中的临床转化证据。此外,文章比较分析了间充质干细胞(MSCs)和诱导多能干细胞(iPSCs)在ADPKD治疗中的独特优势与面临的挑战,为多模态干细胞疗法的开发提供理论支持。
    Autosomal dominant polycystic kidney disease(ADPKD)stands as a leading cause of inherited renal failure,with current therapeutic strategies lacking effective means to reverse disease progression.Stem cell therapy,owing to its potential in tissue repair and immunomodulation,has emerged as a focal point of research.This review systematically elucidates the mechanisms by which hematopoietic stem cells(HSCs)intervene in ADPKD pathology through paracrine effects,metabolic reprogramming,and immune regulation.Furthermore,it summarizes clinical translational evidence of HSCs in both acute kidney injury and chronic kidney disease.This article also comparatively analyzes the unique advantages and challenges of mesenchymal stem cells(MSCs)and induced pluripotent stem cells(iPSCs)in the context of ADPKD treatment,thereby providing theoretical support for the development of multimodal stem cell therapies.

专家述评

细胞外囊泡来源异质性在乳腺癌转移中的机制及临床转化潜力

Research progress on heterogeneity of extracellular vesicle origins,metastatic mechanisms and clinical translational potential in breast cancer

:798-810
 
       乳腺癌(BC)发病率持续上升,已成为严重威胁公共健康的重大挑战,转移仍是导致患者死亡的主要原因。目前,切除肿瘤并辅以放化疗后仍有较大几率发生转移。此外,早期转移隐匿性强,干预措施不完善及耐药发生迅速均是预后不良的重要因素。细胞外囊泡(EVs)是由细胞释放的、具有膜结构的纳米级颗粒,是细胞间通讯的重要介质。EVs通过转运膜性组分、胞质蛋白及核酸等,调控乳腺癌的发生、进展及转移定植,其来源异质性决定了其在乳腺癌转移中发挥独特作用。本文重点总结了不同来源EVs作为液体活检标志物在转移预警中的价值,以及靶向EVs分泌或阻断其通讯网络在克服免疫治疗耐药中的潜在临床应用,以期为临床医生提供有价值的诊疗参考。
     The incidence of breast cancer(BC) continues to rise and has become a major public health challenge.Metastasis remains the principal cause of BC-related mortality.Currently,there remains a high probability of metastasis even after surgical tumor resection followed by radiotherapy and chemotherapy.The insidious nature of early metastasis,inadequate intervention strategies,and rapid development of drug resistance are all critical factors contributing to poor prognosis.Extracellular vesicles(EVs) are membrane-enclosed,nanoscale particles released by cells.As mediators of intercellular communication,EVs transfer membrane components,cytosolic proteins,and nucleic acids to recipient cells,thereby modulating BC initiation,progression,and metastatic dissemination.The heterogeneity of EV origins determines their distinct roles in breast cancer metastasis.This review focuses on summarizing the value of EVs from different sources as liquid biopsy biomarkers for metastasis warning,as well as their potential clinical applications in targeting EV secretion or blocking their communication networks to overcome immunotherapy resistance,aiming to provide valuable diagnostic and therapeutic references for clinicians.

专题:体重管理

葛根芩连汤治疗代谢性疾病的分子机制研究进展

Molecular mechanisms of Gegen Qinlian decoction in metabolic diseases

:688-693
 
       葛根芩连汤作为一种传统中药复方,在治疗代谢性疾病方面展现出显著的疗效。随着中草药现代研究方法的进步,逐渐揭示了葛根芩连汤在代谢性疾病中的治疗作用及其分子机制,包括葛根素、黄芩苷、小檗碱等活性成分的抗炎作用。然而,中草药研究领域的新理论和新机制被不断发现,如影响肠道菌群、产生植物外囊泡、中药汤剂成分自组装等,使得对葛根芩连汤作用机制的理解亟待更新。本文旨在综述葛根芩连汤在代谢性疾病中的作用及机制,并结合最新的研究成果,重点分析其在肠道菌群、植物外囊泡和中药自组装领域的相关发现,探讨其潜在的治疗靶点和未来研究方向,为临床应用和基础研究提供指导。
      Gegen Qinlian decoction(GQD),as a traditional Chinese herbal formula,has demonstrated significant efficacy in treating metabolic diseases.With advancements in modern research methodologies for Chinese herbal medicine,the therapeutic effects and molecular mechanisms of GQD in metabolic diseases have been progressively uncovered,including the anti-inflammatory properties of its active components such as puerarin,baicalin,and berberine.However,emerging theories and mechanisms in the field of herbal research,such as modulation of gut microbiota,production of plant-derived extracellular vesicles,and self-assembly of components in herbal decoctions,continuously refine our understanding,highlighting the need to update insights into GQD’s mechanisms of action.This review aims to summarize the roles and mechanisms of GQD in metabolic diseases,integrating the latest research progress with a focus on findings related to gut microbiota,plant-derived extracellular vesicles,and self-assembly phenomena.It further seeks to explore potential therapeutic targets and future research directions,thereby providing guidance for clinical applications and fundamental studies.

学术前沿

纤毛发育中基因的转录调控机制综述

A review on the transcriptional regulatory mechanisms of ciliary development

:270-276
 
       纤毛是细胞表面的重要细胞器,广泛参与细胞运动、感知外界信号和维持器官功能等生理过程。纤毛的形成,即纤毛发生(ciliogenesis)是一个高度复杂且受精密调控的过程,涉及大量与纤毛结构和功能相关基因的表达与调控。近年来,随着基因组学和发育生物学的发展,越来越多的研究揭示了多种关键转录因子在纤毛发生中的调控作用,包括RFX家族、FOXJ1、MCIDAS、GEMC1、MYB、E2F等。这些转录因子共同构成了一个多层次、多通路交织的调控网络,调控纤毛组装、基体复制、纤毛定位和功能维持等多个方面。本文系统综述了纤毛相关基因转录调控的研究进展,特别是关键转录因子的功能、相互作用及其在纤毛病中的作用,为深入理解纤毛的发育机制和疾病治疗提供参考。
       Cilia are crucial cell-surface organelles involved in cell movement,signal sensing,and organ function maintenance.Their formation,or ciliogenesis,is a complex and  precisely controlled  process that  requires the expression and regulation of numerous cilia-related genes.Recent advances in genomics and developmental biology have uncovered the  regulatory roles of key transcription factors like the RFX family,FOXJ1,MCIDAS,GEMC1,MYB,and E2F in ciliogenesis.These factors form a multi-level,interconnected regulatory network that oversees cilium assembly,basal body replication,ciliary positioning,and function preservation.This review systematically examines current research on transcriptional regulation of ciliary genes,with a focus on the roles,interactions,and contributions of these key transcription factors to ciliopathies,offering insights into ciliary development and disease treatment.
论著

二氢丹参酮I在胃癌AGS细胞中作用机制的生物信息学分析

Bioinformatics analysis of potential mechanisms of dihydrotanshinone I in AGS cell in gastric cancer

:85-93
 
目的 利用GEPIA数据库,包括TCGA数据库和GTEX数据库,探讨二氢丹参酮I通过氧化应激治疗胃癌的潜在靶点。方法 在数据库中检索二氢丹参酮I在胃癌中潜在靶点的文献,利用GEPIA数据库工具分析二氢丹参酮I在胃癌中的潜在作用机制,分析潜在靶基因与表达关键抗氧化应激蛋白基因的相关性;二氢丹参酮I对胃癌潜在靶基因表达水平的分析;二氢丹参酮I对胃癌潜在靶基因的预后分析。结果 二氢丹参酮I对潜在靶基因的主要靶向基因(蛋白)为缺氧诱导因子-1(hif-1)和瓜氨酸组蛋白h3(cith3),其基因分别为HIF1 A和NOS2;GEPIA数据库显示HIF1 A与CAT(P=e-04,r=0.18)、GPX1(P=0.033,r=0.11)或NFE2L2呈正相关。(P=0,r=0.41),而NOS2与SOD1仅呈正相关(P=0.21,r=0.18),与其它三个基因均无相关性;HIF1 A和NOS2在胃癌组织中的表达水平高于正常胃旁组织;HIF1 A的高表达降低了胃癌患者的总生存率。结论 二氢丹参酮I可通过活性氧介导的氧化应激诱导AGS细胞凋亡,抑制HIF1 A和NOS2的表达,从而抑制AGS细胞的抗氧化应激,提高胃癌患者的总生存率。
Objective In this study, GEPIA database, including TCGA database and GTEx database, were used to explore the potential targets of dihydrotanshinone I on gastric cancer through oxidative stress. Methods Literatures on potential targets of dihydrotanshinone I in gastric cancer were searched in the database;GEPIA database tool was used to analyze the potential mechanism of dihydrotanshinone I on gastric cancer;taking analysis of the correlation between potential target genes and genes expressing key antioxidant stress proteins;We had analysis of expression level of dihydrotanshinone I on potential target genes in gastric cancer patients;and prognostic analysis of dihydrotanshinone I on potential target genes in gastric cancer patients. Results The main targeting genes(proteins) of dihydrotanshinone I on potential target genes were hypoxia inducible factor-1(hif-1) and citrulline histone H3(CITH3), whose genes were HIF1 A and NOS2, respectively;GEPIA database showed that there was a positive correlation between HIF1 A and CAT(P=2e-04, R=0.18), GPX1(P=0.033, R=0.11), or NFE2L2(P=0, R=0.41), while NOS2 only had a positive correlation with SOD1(P=0.21, R=0.18), and no correlation with other three genes. The expression levels of HIF1 A and NOS2 in gastric cancer tissues were higher than those in normal adjacent gastric tissues. The overall survival rate of patients with gastric cancer decreased with the high expression of HIF1 A. Conclusion Dihydrotanshinone I may induce apoptosis of AGS cells through reactive oxygen species mediated oxidative stress, and inhibit the expression of HIF1 A and NOS2, thus inhibit their antioxidative stress, which may improve the overall survival rate of gastric cancer patients.
论著

血必净注射液对SAP大鼠TLR4信号通路介导肠黏膜屏障功能障碍的影响

Mechanisms of Xuebijing injection in interventing intestinal mucosal barrier dysfunction in SAP rats

:1-5
 
目的 探讨血必净注射液对SAP大鼠TLR4信号通路介导肠黏膜屏障功能障碍的影响。方法 24只SD大鼠随机分成空白组(n=8)、对照组(n=8)和治疗组(n=8)。对照组和治疗组用4.5%牛磺胆酸钠溶液胆胰管逆行注射制备SAP模型,空白组采用等量生理盐水逆行注射。治疗组在造模3 h后经鼠尾静脉注射血必净注射液(3 mL/kg)。三组大鼠造模后观察24 h,然后处死取胰腺和小肠组织送病理检查,采用荧光RT-PCR技术检测TLR4和NF-κB表达水平,采用ELSIA法检测血清TNF-α、IL-6、淀粉酶(AMS)及二胺氧化酶(DAO)水平,比较三组大鼠各项指标。结果 对照组和治疗组小肠组织TLR4和NF-κB表达以及血清TNF-α、IL-6、AMS及DAO水平均高于空白组(P>0.05),治疗组小肠组织TLR4和NF-κB表达以及血清TNF-α、IL-6、AMS及DAO水平低于对照组(P<0.05)。结论 血必净注射液通过干预SAP大鼠TLR4信号通路,降低小肠组织TLR4和NF-κB的表达,减轻小肠组织的炎症反应,对肠黏膜屏障具有一定的保护作用。
Objective To investigate the effect on intestinal mucosal barrier dysfunction (IBF) of Xuebijing injection mediated by Toll-like receptor 4 (TLR4) signal pathway in rats of severe acute pancreatitis (SAP). Methods 24 Sprague Dawley (SD) rats were randomly divided into Sham group (n=8), control group (n=8) and treatment group (n=8). The SAP model was established by retrograde injection of 4.5% sodium taurocholate into the biliopancreatic duct in control group and treatment group, while control group was injected with the same amount of saline. In treatment group, Xuebijing injection (3 mL/kg) was injected via tail vein after 3h of modeling. All rats were monitored and sacrificed after 24 hours of modeling. Samples of pancreas and intestine were collected for pathologic determination. A fluorescent RT-PCR was used to determine the expression of TLR4 and NF-κB of small intestine. The serum levels of TNF-α, IL-6, amylase (AMS) and diamine oxidase (DAO) were measured by using ELISA. All parameters of three groups were compared. Results The expression of TLR4 and NF-κB of small intestine in control group and treatment group were higher than it in control group (P<0.05), as well as the serum levels of TNF-α, IL-6, AMS and DAO (P<0.05). The expression of TLR4 and NF-κB of small intestine in treatment group were lower than it in control group (P<0.05), as well as the serum levels of TNF-α, IL-6, AMS and DAO (P<0.05). Conclusion Xuebijing injection may not only reduce the expression of TLR4 and NF-κB of small intestine, but also alleviate the inflammation reaction of small intestine by interfering with TLR4 signal pathway, which may have a protective effect on intestinal mucosal barrier in SAP rats.
专家述评

炎症性肠病相关易感基因及其作用机制的研究进展

Research progress on susceptibility genes and their mechanisms in inflammatory bowel disease

:300-309
 
       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.
专家述评

结直肠癌肝转移的分子机制及临床治疗的研究进展

Advances in the emerging mechanisms and treatment progress on liver metastasis of colorectal cancer

:288-299
 
       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.
论著

基于网络药理学与分子对接技术研究白头翁汤治疗细菌性痢疾的潜在活性成分及作用机制

Research on potential active ingredients and mechanisms of Baitouweng Decoction in the treatment of bacterial dysentery through network pharmacology and molecular docking

:216-227
 
       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.
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