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目的 运用网络药理学方法及分子对接技术探讨黄芪干预腹膜纤维化的可能机制。方法 利用中药系统药理学数据库及分析平台(TCMSP)检索黄芪的主要化学成分及靶点,并补充文献报道相关药理作用的成分作为潜在活性成分。以"peritoneal fibrosis"为关键词分别在OMIM、Genecards获取目前已知的与腹膜纤维化相关的疾病靶点,后取两者的交集靶点;对交集基因通过STRING数据库与Cytoscape 3.7.2软件构建"药物-成分-靶点-疾病"网络及蛋白互作(PPI)网络并筛选核心网络。基于R软件使用Bioconductor生物信息软件对核心靶点进行GO及KEGG富集分析,最终采用AutoDock软件将主要有效成分与核心靶点进行分子对接,得出其结合能力。结果 筛选出20个黄芪活性成分及文献报道有相关药理作用4个, 457药物作用靶点,与674个腹膜纤维化病靶点取交集,得到86个共同靶点。GO功能富集分析提示黄芪拮抗腹膜纤维化主要参与了蛋白激酶B信号转导的调节、细胞对化学的应激反应、炎症反应的调节等通路; KEGG通路富集分析主要涉及调控肿瘤、磷脂酰肌醇-3-羟激酶-蛋白激酶B(PI3K-Akt)、晚期糖基化终末产物/晚期糖基化终末产物受体(AGE-RAGE)、人类巨细胞病毒感染、HIF-1信号通路等;分子对接结果显示关键靶点与活性成分具有较好的结合能力。结论 黄芪治疗腹膜纤维化的分子机制,可能与抑制炎症及氧化应激反应、调节多种信号通路等相关。 相似文献
3.
Weina Cheng Yazhi Wang Jingxian Liu Xiaofei Li Ming Yu Cancan Duan Liu Liu Jianyong Zhang 《Journal of applied toxicology : JAT》2022,42(6):970-980
Cantharidin (CTD) is an effective antitumor agent. However, it exhibits significant hepatotoxicity, the mechanism of which remains unclear. In this study, biochemical and histopathological analyses complemented with ultra-high-performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS)-based targeted metabolomic analysis of bile acids (BAs) were employed to investigate CTD-induced hepatotoxicity in rats. Sixteen male and female Sprague–Dawley rats were randomly divided into two groups: control and CTD (1.0 mg/kg) groups. Serum and liver samples were collected after 28 days of intervention. Biochemical, histopathological, and BA metabolomic analyses were performed for all samples. Further, the key biomarkers of CTD-induced hepatotoxicity were identified via multivariate and metabolic pathway analyses. In addition, metabolite–gene–enzyme network and Kyoto Encyclopedia of Genes and Genomes pathway analyses were used to identify the signaling pathways related to CTD-induced hepatotoxicity. The results revealed significantly increased levels of biochemical indices (alanine aminotransferase, aspartate aminotransferase, and total bile acid). Histopathological analysis revealed that the hepatocytes were damaged. Further, 20 endogenous BAs were quantitated via UHPLC-MS/MS, and multivariate and metabolic pathway analyses of BAs revealed that hyocholic acid, cholic acid, and chenodeoxycholic acid were the key biomarkers of CTD-induced hepatotoxicity. Meanwhile, primary and secondary BA biosynthesis and taurine and hypotaurine metabolism were found to be associated with the mechanism by which CTD induced hepatotoxicity in rats. This study provides useful insights for research on the mechanism of CTD-induced hepatotoxicity. 相似文献
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《Drug discovery today》2022,27(10):103321
Pain is a constant in our lives. The efficacy of drug therapy administered by the parenteral route is often limited either by the physicochemical characteristics of the drug itself or its adsorption–distribution–metabolism–excretion (ADME) mechanisms. One promising alternative is the design of innovative drug delivery systems that can improve the pharmacokinetics |(PK) and/or reduce the toxicity of traditionally used drugs. In this review, we discuss several products that have been approved by the main regulatory agencies (i.e., nano- and microsystems, implants, and oil-based solutions), highlighting the newest technologies that govern both locally and systemically the delivery of drugs. Finally, we also discuss the risk assessment of the scale-up process required, given the impact that this approach could have on drug manufacturing.Teaser: The management of pain by way of the parenteral route can be improved using complex drug delivery systems (e.g., micro- and nanosystems) which require high-level assessment and shorten the regulatory pathway. 相似文献
6.
社会力量具备相应的经济基础和技术条件,对于公立互联网医院体系建设具有积极的促进作用。但是实践中仍然存在商业模式不完善、监管制度不健全等问题。基于经济学契约理论要义,提出在坚持激励与约束机制并举、平衡公私益关系的前提下,通过完善医保政策、构建互联网医疗服务价格分类管理机制来促进社会力量向医疗服务公益性目标回归,并通过构建完善的监督体制来约束部分社会力量的盲目逐利性行为。 相似文献
7.
Zeyu Li Erwei Hao Rui Cao Si Lin Linghui Zou Tianyan Huang Zhengcai Du Xiaotao Hou Jiagang Deng 《中草药(英文版)》2022,14(4):479-493
Zedoary tumeric (Curcumae Rhizoma, Ezhu in Chinese) has a long history of application and has great potential in the treatment of liver cancer. The anti liver cancer effect of zedoary tumeric depends on the combined action of multiple pharmacodynamic substances. In order to clarify the specific mechanism of zedoary tumeric against liver cancer, this paper first analyzes the mechanism of its single pharmacodynamic substance against liver cancer, and then verifies the joint anti liver cancer mechanism of its "pharmacodynamic group". By searching the research on the anti hepatoma effect of active components of zedoary tumeric in recent years, we found that pharmacodynamic substances, including curcumol, zedoarondiol, curcumenol, curzerenone, curdione, curcumin, germacrone, β-elemene, can act on multi-target and multi-channel to play an anti hepatoma role. For example, curcumin can regulate miR, GLO1, CD133, VEGF, YAP, LIN28B, GPR81, HCAR-1, P53 and PI3K/Akt/mTOR, HSP70/TLR4 and NF-κB. Wnt/TGF/EMT, Nrf2/Keap1, JAK/STAT and other pathways play an anti hepatoma role. Network pharmacological analysis showed that the core targets of the "pharmacodynamic group" for anti-life cancer are AKT1, EGFR, MAPK8, etc, and the core pathways are neuroactive live receiver interaction, nitrogen metabolism, HIF-1 signaling pathway, etc. At the same time, by comparing and analyzing the relationship between the specific mechanisms of pharmacodynamic substance and "pharmacodynamic group", it is found that they have great reference significance in target, pathway, biological function, determination of core pharmacodynamic components, formation of core target protein interaction, in-depth research of single pharmacodynamic substance, increasing curative effect and so on. By analyzing the internal mechanism of zedoary tumeric pharmacodynamic substance and "pharmacodynamic group" in the treatment of liver cancer, this paper intends to provide some ideas and references for the deeper pharmacological research of zedoary tumeric and the relationship between pharmacodynamic substance and "pharmacodynamic group". 相似文献
8.
顺铂(DDP)作为第一个被发现的金属抗癌药物,是目前最有潜力和应用最广泛的抗肿瘤药物。顺铂在宫颈癌的治疗中尤为重要,目前已被推荐为同步放化疗的首选药物。但随着广泛的使用,顺铂的耐药性逐渐显露出来,并成为限制临床疗效和部分患者肿瘤治疗进展的主要原因之一。顺铂的耐药机制复杂,发生环节较多,但具体耐药机制尚不明确,目前按照顺铂耐药发生的环节可分为:①顺铂在血液循环过程中产生耐药;②顺铂通过细胞膜的流入或流出产生耐药;③顺铂在胞质中产生耐药;④顺铂与DNA结合后产生耐药。本文综述了宫颈癌顺铂耐药可能发生的四个环节及克服耐药常用的手段,为提高顺铂对宫颈癌的疗效提供依据。 相似文献
9.
彭秋连 《中国继续医学教育》2021,(1)
目的观察目标教学在手术室护理带教中的应用效果。方法选取2018年9月—2019年6月期间,医院手术室的48名实习护士,随机分为对照组和试验组,每组各24例。对照组行传统护理带教方法,试验组行目标教学带教。对比带教后两组考核成绩及带教满意度。结果带教后,试验组职业防护意识、风险意识、无菌观念、常见小中手术配合熟练度、常见小中手术护理要点掌握、基本工作职责及流程掌握等评分与对照组差异具有统计学意义(P<0.05)。试验组专科操作、操作测评及理论测评成绩与对照组差异具有统计学意义(P<0.05)。结论于手术室护理带教中应用目标教学,具有理想效果,有助于提升考核成绩及专业技能。 相似文献
10.
葸峰 《中国继续医学教育》2021,(10):114-117
目的研究分析腹内疝患者采用多排螺旋CT进行诊断的临床价值。方法将本院接收的32例腹内疝患者作为此次研究之中的观察主体,均通过手术证实,临床资料完整,均进行多排螺旋CT检查,对其诊断结果进行分析,对比CT与手术证实的符合率。结果多排螺旋CT确诊率高达90.63%,与手术证实结果无差异(P> 0.05);同时,通过多排螺旋CT检查,可清晰的观察到腹内疝相关征象,与手术证实结果高度一致,无显著差异(P> 0.05)。结论多排螺旋CT诊断技术能够较好的诊断腹内疝,且CT征象清晰,为临床有效诊治腹内疝提供了可靠指导,值得在临床中普及。 相似文献