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放线菌中与抗生素合成相关TetR家族转录因子的研究进展
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作者 倪静姝 汪焰胜 +1 位作者 吴杭 张部昌 《微生物学通报》 CAS CSCD 北大核心 2019年第2期407-414,共8页
放线菌是天然抗生素的重要来源,放线菌中存在着种类繁多的转录因子,精细控制着作为次级代谢产物的抗生素生物合成。作为原核生物单组分信号传递系统中的一个重要家族,TetR家族转录调控因子(TetR family transcriptional regulators,TFRs... 放线菌是天然抗生素的重要来源,放线菌中存在着种类繁多的转录因子,精细控制着作为次级代谢产物的抗生素生物合成。作为原核生物单组分信号传递系统中的一个重要家族,TetR家族转录调控因子(TetR family transcriptional regulators,TFRs)广泛参与调控抗生素生物合成、药物外排、初级代谢等多种生理过程。本文综述了近几年放线菌TFRs的研究进展,并结合本实验室的研究工作,从TFRs作用靶基因的角度着重阐述了放线菌TFRs参与几种重要抗生素生物合成的分子调控机制,概述其应答的配体,并总结与展望了放线菌TFRs在抗生素产量提高、沉默基因簇激活、调控元件设计与开发等方面的应用进展。 展开更多
关键词 TetR家族调控因子 放线菌 抗生素 靶基因 配体
Conserving plants within and beyond protected areas-still problematic and future uncertain
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作者 Vernon H. Heywood 《植物多样性:英文版》 CAS CSCD 2019年第2期36-49,共14页
Against a background of continuing loss of biodiversity, it is argued that for the successful conservation of threatened plant species we need to ensure the more effective integration of the various conservation actio... Against a background of continuing loss of biodiversity, it is argued that for the successful conservation of threatened plant species we need to ensure the more effective integration of the various conservation actions employed, clarify the wording of the CBD targets and provide clearer operational guidance as to how they are to be implemented and their implementation monitored. The role and effectiveness of protected areas in conserving biodiversity and in particular plant species in situ are discussed as are rece nt proposals for a massive in crease of their exte nt. The need for much greater effort and investment in the conservation or protection of threatened species outside protected areas where most plant diversity occurs is highlighted. The difficulties involved in implementing effective in situ conservation of plant diversity both at an area- and species/population-based level are discussed. The widespread neglect of species recovery for plants is noted and the desirability of making a clearer distinction between species recovery and reintroduction is emphasized. Key messages from a global overview of species recovery are outlined and recommendations made, including the desirability of each country preparing a national species recovery strategy. The projected impacts of global change on protected areas and on species conservation and recovery, and ways of addressing them are discussed. 展开更多
关键词 Plant CONSERVATION CBD TARGETS Protected areas Species recovery CONSERVATION approaches
基于网络药理学的补肾益心片治疗高血压分子机制研究 预览
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作者 刘云娣 高佳珠 +4 位作者 杨智华 麦喆钘 孙治中 李俊哲 温俊茂 《中国中医药信息杂志》 CAS CSCD 2019年第8期104-109,共6页
目的采用网络药理学方法分析补肾益心片治疗高血压的作用机制,为其临床与应用提供参考。方法检索中药系统药理学数据库分析平台(TCMSP)获取补肾益心片活性成分,运用DRAR-CPI服务器、GeneCards和OMIM等数据库筛选活性成分治疗高血压的作... 目的采用网络药理学方法分析补肾益心片治疗高血压的作用机制,为其临床与应用提供参考。方法检索中药系统药理学数据库分析平台(TCMSP)获取补肾益心片活性成分,运用DRAR-CPI服务器、GeneCards和OMIM等数据库筛选活性成分治疗高血压的作用靶点。采用Cytoscape3.6.0软件构建补肾益心片活性成分-高血压靶点网络。结合String数据库和Cytoscape的NetworkAnalyzer分析蛋白相互作用关系。采用Systems Dock Web Site进行活性成分与靶点分子对接。并进行GO分析、KEGG通路富集分析。结果筛选出补肾益心片活性成分30个,作用于62个靶点,主要通过调节肾素-血管紧张素系统、Toll样受体信号通路、PI3K-AKT信号通路和Jak-STAT信号通路等发挥治疗高血压的作用。结论本研究初步揭示了补肾益心片治疗高血压的多成分、多靶点作用机制,可为后续研究提供参考。 展开更多
关键词 补肾益心片 高血压 网络药理学 靶点 通路
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左金丸活性成分-靶点-多维作用机制 预览
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作者 李跃文 刘志强 +2 位作者 易增兴 秦后响 王博龙 《中成药》 CAS CSCD 北大核心 2019年第5期1022-1031,共10页
目的分析左金丸活性成分-靶点-多维作用机制。方法通过中药系统药理学分析平台(TCMSP)数据库获取左金丸活性成分及对应靶点,TTD数据库预测分析左金丸潜在治疗疾病,Cytoscape软件分别构建活性成分-靶点、靶点-疾病网络,STRING平台构建靶... 目的分析左金丸活性成分-靶点-多维作用机制。方法通过中药系统药理学分析平台(TCMSP)数据库获取左金丸活性成分及对应靶点,TTD数据库预测分析左金丸潜在治疗疾病,Cytoscape软件分别构建活性成分-靶点、靶点-疾病网络,STRING平台构建靶蛋白互作网络,BINGO和MCODE插件对靶基因进行GO生物过程富集和聚类分析,生物学信息注释数据库(DAVID)对靶点进行KEGG信号通路分析。结果左金丸中13种活性成分作用于49个潜在靶点,涉及炎症反应调节、突触传递、细胞分化、凋亡等19个生物子簇;KEGG富集得到消化液分泌、癌症、内分泌、神经递质、炎症、信号转导、心血管7大类22条信号通路,在消化、神经、心血管系统疾病以及炎症、癌症等方面具有治疗价值。结论本研究揭示了左金丸活性成分、靶点、多维作用机制,可为其临床治疗价值拓展提供新的线索。 展开更多
关键词 左金丸 活性成分 靶点 多维作用机制 网络药理学
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Tsc1/Tsc2 complex: A molecular target of capsaicin for protection against testicular torsion induced injury in rats
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作者 Nasim Javdan Seyed Abdulmajid Ayatollahi +5 位作者 Muhammad Iqbal Choudhary Safaa Al-Hasani Farzad Kobarfard Kobra Mokhtarian Majid Khoshmirsafa Athar Ata 《中草药:英文版》 CAS 2019年第2期216-221,共6页
Objective: The detailed knowledge about protective effects of capsaicin(cap) and involved mechanisms against testicular torsion(TT) is still not available completely.Methods: Male Wistar rats were assigned into four m... Objective: The detailed knowledge about protective effects of capsaicin(cap) and involved mechanisms against testicular torsion(TT) is still not available completely.Methods: Male Wistar rats were assigned into four major cohorts:(i) sham,(ii) TT,(iii) three subgroups subjected to TT and different doses of cap(100, 500, and 1000 μg/mL), and(iv) three subgroups of healthy animals subjected to various concentrations of cap. The animals were decapitated at 24 h after reperfusion, and the evaluation of protein expression was performed by Western blotting assay. At 72 h after reperfusion, apoptotic cell death and tissue injury were evaluated by TUNEL nuclear and H&E staining,respectively.Results: The results showed that cap administration following TT significantly increased the expression of tuberous sclerosis proteins 1 and 2(Tsc1/Tsc2) in a dose-dependent manner(P < 0.05). Cap decreased cell apoptosis at highest dose. Likewise, cap contributed to the preservation of tubular morphology and decreased tissue injury at the highest tested concentration(1000 μg/m L).Conclusion: Collectively, our findings demonstrate the validity of cap as a therapeutic agent against TT through targeting Tsc1/Tsc2 in a dose-dependent manner. 展开更多
关键词 CAPSAICIN cell SURVIVAL molecular TARGETS TESTICULAR TORSION Tsc1/Tsc2 COMPLEX
基于网络药理学的黄芪和三七主要有效成分配伍抗缺血性脑损伤作用机制研究 预览
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作者 唐标 唐文静 邓常清 《中国中医药信息杂志》 CAS CSCD 2019年第7期109-113,共5页
目的采用网络药理学方法探讨黄芪和三七主要有效成分配伍抗缺血性脑损伤作用机制,为成分筛选提供参考。方法文献检索结合前期研究确定黄芪和三七抗缺血性脑损伤主要有效成分,通过DRAR-CPI数据库预测有效成分作用靶点,多数据库联合检索... 目的采用网络药理学方法探讨黄芪和三七主要有效成分配伍抗缺血性脑损伤作用机制,为成分筛选提供参考。方法文献检索结合前期研究确定黄芪和三七抗缺血性脑损伤主要有效成分,通过DRAR-CPI数据库预测有效成分作用靶点,多数据库联合检索脑缺血相关疾病靶点。采用Cytoscape3.2.1软件构建有效成分-靶点网络、作用靶点蛋白相互作用(PPI)网络及疾病靶点PPI网络,交叉融合并筛选核心靶点。利用DAVID数据库对核心靶点进行生物过程和信号通路富集分析。结果筛选出的194个核心靶点主要关联脑缺血凋亡、自噬、神经营养因子的保护作用、血管新生及炎症反应等多个过程。此外,靶点参与了脑缺血中PI3K-Akt信号通路、MAPK信号通路、神经营养因子信号通路、血管新生途径及多种炎症反应途径。结论上述生物过程和通路介导了黄芪和三七主要有效成分抗缺血性脑损伤的潜在机制,可为成分筛选提供参考。 展开更多
关键词 黄芪 三七 脑缺血 网络药理学 靶点 信号通路
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白芷治疗痤疮的网络药理学作用机制
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作者 陈湘君 刘靖 《广州中医药大学学报》 CAS 2019年第10期1624-1631,共8页
【目的】基于网络药理学探究中药白芷治疗痤疮的可能作用机制。【方法】通过中药系统药理学数据库与分析平台(TCMSP)及文献检索获取白芷的活性成分。采用反向分子对接服务器(DRAR-CPI)获取白芷作用靶标,并利用GeneCards和在线人类孟德... 【目的】基于网络药理学探究中药白芷治疗痤疮的可能作用机制。【方法】通过中药系统药理学数据库与分析平台(TCMSP)及文献检索获取白芷的活性成分。采用反向分子对接服务器(DRAR-CPI)获取白芷作用靶标,并利用GeneCards和在线人类孟德尔遗传(OMIM)数据库筛选白芷活性成分治疗痤疮的潜在靶标。结合String数据库和Cytoscape的Network Analyzer工具,得出潜在靶标蛋白的相互作用关系。通过Systems Dock Web Site将靶标蛋白分别与白芷的活性成分进行分子对接。利用DAVID数据库,对潜在靶标基因进行基因本体论(GO)分类富集分析与京都基因和基因组百科全书(KEGG)通路富集分析。【结果】从白芷中筛选出活性成分20个,作用于55个靶标,主要通过调控磷脂酰肌醇-3-激酶(PI3K)/丝苏氨酸蛋白激酶Akt、核因子kappa B(NF-κB)、丝裂原活化蛋白激酶(MAPK)、成纤维细胞生长因子受体2(FGFR2)等信号通路来发挥治疗痤疮的作用。【结论】应用网络药理学的方法初步预测出白芷治疗痤疮的可能活性成分和信号通路。 展开更多
关键词 白芷 痤疮 网络药理学 靶标 信号通路
基于分子对接技术探讨残黄片退黄作用机制 被引量:1
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作者 吉日木巴图 范娜 +3 位作者 王蕊 牛莹 王啸洋 韩晋 《中国实验方剂学杂志》 CAS CSCD 北大核心 2019年第10期154-161,共8页
目的:通过分子对接技术研究残黄片治疗黄疸的作用机制。方法:在中药系统药理学分析平台(TCMSP)中筛选残黄片的化学成分,从比较毒理基因组数据库(CTD)和Drug Bank数据库中搜集黄疸治疗相关靶点,利用Discovery Studio2016软件Lib Dock模... 目的:通过分子对接技术研究残黄片治疗黄疸的作用机制。方法:在中药系统药理学分析平台(TCMSP)中筛选残黄片的化学成分,从比较毒理基因组数据库(CTD)和Drug Bank数据库中搜集黄疸治疗相关靶点,利用Discovery Studio2016软件Lib Dock模块进行分子对接,分析成分和靶点的相互作用和网络特征。结果:分子对接发现残黄片37个成分与锁定的孕烷受体,雄烷受体,法尼醇X受体,环氧合酶-2,单胺氧化酶A,诱导型一氧化氮合酶等14个靶点作用较强,可通过调节胆红素代谢、调控胆汁酸合成与转运、抑制免疫与炎症反应、影响肝脏胶原形成等多个途径发挥治疗黄疸作用。成分-靶点作用网络分析发现,残黄片中穆坪马兜铃酰胺,氢化小檗碱,槲皮素,去甲氧基姜黄素,黄柏酮,姜黄素,黄麻甲苷,小檗浸碱,桤木酮,柚皮素共10个成分作用于7个以上靶点,可能为其退黄主要活性成分。结论:通过分子对接揭示了残黄片可能的退黄活性成分和作用机制,有助于后续质控标准的提升和退黄机制的研究。 展开更多
关键词 残黄片 黄疸 胆汁淤积 分子对接 成分 靶点 网络药理学
基于网络药理学的小青龙汤治疗支气管哮喘作用机制分析 被引量:1
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作者 范荣荣 罗子清 +1 位作者 唐丽娟 张忠德 《中药新药与临床药理》 CAS CSCD 北大核心 2019年第1期52-59,共8页
目的基于网络药理学方法探讨小青龙汤治疗支气管哮喘的作用机制。方法基于中药系统药理学技术平台(TCMSP)获取小青龙汤化学成分及其对应靶点,通过OMIM、Drugbank、Disgenet数据库获取哮喘相关靶点,将药物靶点与疾病靶点映射得到小青龙... 目的基于网络药理学方法探讨小青龙汤治疗支气管哮喘的作用机制。方法基于中药系统药理学技术平台(TCMSP)获取小青龙汤化学成分及其对应靶点,通过OMIM、Drugbank、Disgenet数据库获取哮喘相关靶点,将药物靶点与疾病靶点映射得到小青龙汤作用于哮喘的预测靶点。利用Cytoscape软件构建化合物-靶点网络及蛋白与蛋白相互作用网络,利用DAVID数据库分析预测靶点的基因百科全书(KEGG)信号通路。结果预测结果表明,小青龙汤作用于哮喘的有效成分有96个,靶点47个,关键有效成分包括槲皮素、山奈酚、麻黄碱等,关键靶点包括血管内皮生长因子A、肿瘤坏死因子、过氧化氢酶等。通路富集分析得到CGMP-PKG信号通路、NF-κB信号通路、TNF信号通路等7条信号通路。结论小青龙汤主要通过减轻气道炎症反应、抑制气道重塑和平滑肌收缩等发挥治疗哮喘的作用。 展开更多
关键词 小青龙汤 支气管哮喘 网络药理学 靶点 作用机制
Placental Origins of Preeclampsia:Potential Therapeutic Targets 预览
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作者 Jian-li WU Jing JIA +7 位作者 Meng-zhou HE Yu ZENG Jing-yi ZHANG Er-jiao SHI Shao-yang LAI Xuan ZHOU Lali Mwamaka Sharifu Ling FENG 《当代医学科学(英文)》 SCIE CAS 2019年第2期190-195,共6页
Preeclampsia(PE)remains a leading cause of maternal and perinatal morbidity and mortality in obstetrics worldwide.No effective treatments to reduce its incidence and severity in clinical practice are currently availab... Preeclampsia(PE)remains a leading cause of maternal and perinatal morbidity and mortality in obstetrics worldwide.No effective treatments to reduce its incidence and severity in clinical practice are currently available.A variety of hypotheses have been generated aiming to explain the origins of PE,notably being the genetic predispositions and placental dysfunction.As regard to placental dysfunction,much progress has been made in basic research and several potential therapeutic targets have been identified.This review will discuss in detail the potential therapeutic targets in PE models including uteroplacental blood flow,oxidative stress,vasoactive factors and inflammation/immune response,and introduce the evolving technologies for placental research nowadays. 展开更多
关键词 PREECLAMPSIA PLACENTAL DYSFUNCTION THERAPEUTIC TARGETS
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基于生物信息技术的薏苡附子散网络药理学研究
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作者 王博龙 《中药新药与临床药理》 CAS CSCD 北大核心 2019年第5期564-570,共7页
目的利用生物信息技术研究薏苡附子散网络药理学机制。方法依托BATMAN-TCM数据库对薏苡附子散进行成分筛选和靶点预测,利用STRING平台构建靶蛋白相互作用网络,利用BiNG0和MCODE插件对靶基因进行GO生物过程富集和聚类模块分析,通过DAVID... 目的利用生物信息技术研究薏苡附子散网络药理学机制。方法依托BATMAN-TCM数据库对薏苡附子散进行成分筛选和靶点预测,利用STRING平台构建靶蛋白相互作用网络,利用BiNG0和MCODE插件对靶基因进行GO生物过程富集和聚类模块分析,通过DAVID服务器对薏苡附子散潜在靶基因进行KEGG信号通路富集。结果薏苡附子散中去甲乌药碱、薏苡素、苯甲酰乌头原碱、薏苡酯等14个活性成分,作用于5-羟色胺受体、多巴胺受体、M2胆碱受体、前列腺素受体E2、肾上腺素受体等66个靶点,涉及cAMP信号转导、钙离子调节、神经调节、细胞周期、细胞凋亡等多种生物过程,参与神经调节、内分泌调节、信号转导、糖类代谢、精神疾病、炎症及其他7大类19条信号通路。结论薏苡附子散不仅具有治疗胸痹急痛、强心、中枢止痛的作用,还可能具有抗癌、抗炎、抗抑郁及调节血糖等作用。 展开更多
关键词 网络药理学 薏苡附子散 靶点 通路 蛋白互作
The function and potential drug targets of tumour-associated Tregs for cancer immunotherapy
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作者 Shanshan Yan Yaguang Zhang Bing Sun 《中国科学:生命科学英文版》 SCIE CAS CSCD 2019年第2期179-186,共8页
Regulatory T cells(Tregs) play an important role in maintaining self-tolerance and immune homeostasis, but they also play a negative role in evoking effective antitumour immune responses. There is ample evidence indic... Regulatory T cells(Tregs) play an important role in maintaining self-tolerance and immune homeostasis, but they also play a negative role in evoking effective antitumour immune responses. There is ample evidence indicating that the depletion of Tregs or the inhibition of Treg function will enhance antitumour effects. However, it is unclear which surface molecules of Tregs are suitable targets for tumour immunotherapy with minimal toxic side effects, which is a central theme in the field of Treg-targeted immunotherapy. In this review, we focus on the regulatory mechanisms of Tregs, including intrinsic and extrinsic factors within the tumour microenvironment, and we address potential drug targets on Tregs for immunotherapy. 展开更多
关键词 tumour-associated TREGS regulation TARGETS IMMUNOTHERAPY
脂肪肉瘤潜在作用靶点的研究进展 预览
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作者 邢志超(综述) 麦威(审校) 《实用肿瘤学杂志》 CAS 2019年第1期82-86,共5页
脂肪肉瘤(Liposarcoma,LPS)是软组织肉瘤(Soft-tissue sarcoma,STS)中最常见的一种。目前的治疗方法仍然以手术完整切除为主,放、化疗作为辅助治疗手段,但远处转移、不可切除性脂肪肉瘤主要治疗方法疗效有限,未获得广泛认可。随着LPS分... 脂肪肉瘤(Liposarcoma,LPS)是软组织肉瘤(Soft-tissue sarcoma,STS)中最常见的一种。目前的治疗方法仍然以手术完整切除为主,放、化疗作为辅助治疗手段,但远处转移、不可切除性脂肪肉瘤主要治疗方法疗效有限,未获得广泛认可。随着LPS分子靶向治疗的广泛深入研究,该方面的研究成果显著。新出现的LPS作用靶点包括受体类如酪氨酸激酶受体AXL、成纤维生长因子受体(Fibroblast growth factor receptor,FGFR)、胰岛素样生长因子1受体(Insulin-like growth factor-1 receptor,IGF-1R)、核输出受体XPO1(Exportin-1)、蛋白/酶类如热休克蛋白90(Heat shock protein 90,Hsp90)、双特异性酪氨酸(Y)磷酸化调节激酶1B(Dual-specificity tyrosine(Y)phosphorylation-regulated kinase1B,DYRK1B),信号通路类如SRC/FAK/RHO/ROCK等,它们的抑制在临床前研究中都展现出了良好的抗LPS前景,现将该方面的研究进展情况综述如下。 展开更多
关键词 脂肪肉瘤 作用靶点 治疗
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基于网络药理学六君子汤治疗胃癌的物质基础与作用机制研究
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作者 余平 郑建红 楼婷婷 《中国现代应用药学》 CAS CSCD 北大核心 2019年第12期1508-1515,共8页
目的探讨六君子汤治疗胃癌的药效物质基础与潜在的作用机制。方法依托TCMSP 和TCM-MESH 数据库平台对六君子汤中的活性成分进行检索和筛选;利用SwissTargetPrediction,TTD,CTD,GeneCards 等数据库对六君子汤活性成分以及胃癌相关靶点进... 目的探讨六君子汤治疗胃癌的药效物质基础与潜在的作用机制。方法依托TCMSP 和TCM-MESH 数据库平台对六君子汤中的活性成分进行检索和筛选;利用SwissTargetPrediction,TTD,CTD,GeneCards 等数据库对六君子汤活性成分以及胃癌相关靶点进行预测和筛选,进而构建活性成分-靶点网络图。对得到的靶点通过STRING 进行蛋白互作(protein-protein interaction,PPI)网络构建并筛选核心靶点,进而通过ONCOMINE 数据库分析核心靶点在胃癌中的表达。利用DAVID 在线数据库对靶点进行基因本体论(gene ontology,GO)和KEGG 通路富集分析以探讨靶点的生物学意义。对于得到的活性成分,作用于胃癌的靶点以及所富集的通路,构建六君子汤成分-靶点-通路网络图。结果从六君子汤中筛选得到21 个活性有效成分和43 个作用于胃癌的相关靶点。靶点的PPI 网络分析得到6 个核心靶点,在ONCOMINE 数据库的胃癌样本和正常样本中均存在显著的表达差异。对靶点的GO 和KEGG 通路富集分析结果显示这些靶点富集在生物过程的条目有74 个,细胞组分的有9 个,分子功能的有15 个,而富集的KEGG 通路有78 条,涉及肿瘤、信号通路、病毒致癌、凋亡、癌症中的蛋白多糖等多种与胃癌密切相关的通路。六君子汤成分-靶点-通路网络图揭示了六君子汤中的药效物质和作用靶点,以及靶点与疾病通路之间的互作关系。结论本研究初步明确了六君子汤通过多成分-多靶点-多通路治疗胃癌的作用机制,为深入研究六君子汤的药效物质基础和作用机制奠定基础。 展开更多
关键词 六君子汤 胃癌 活性成分 靶点 通路
杜仲治疗骨质疏松的网络药理学作用机制探讨
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作者 董航 严娇 +4 位作者 谢铱子 纪树亮 孙伟鹏 孙治中 李宗瑶 《广州中医药大学学报》 CAS 2019年第9期1413-1420,共8页
【目的】利用网络药理学的方法探讨杜仲治疗骨质疏松(OP)的可能作用机制。【方法】通过中药系统药理学数据库与分析平台(TCMSP)、文献检索获取杜仲的活性成分,利用反向分子对接服务器(DRAR-CPI)、GeneCards和在线人类孟德尔遗传(OMIM)... 【目的】利用网络药理学的方法探讨杜仲治疗骨质疏松(OP)的可能作用机制。【方法】通过中药系统药理学数据库与分析平台(TCMSP)、文献检索获取杜仲的活性成分,利用反向分子对接服务器(DRAR-CPI)、GeneCards和在线人类孟德尔遗传(OMIM)数据库筛选杜仲的活性成分治疗骨质疏松的潜在作用靶点。应用Cytoscape软件构建杜仲的活性成分—作用靶点网络。应用String数据库和Cytoscape软件获得蛋白质相互作用网络。采用Systems Dock Web Site网络服务器与杜仲的活性成分进行分子对接。利用DAVID数据库对杜仲的作用靶点进行基因本体论(GO)分类富集分析和京都基因和基因组百科全书(KEGG)通路富集分析。【结果】从杜仲中筛选出活性成分12个,作用靶标35个。杜仲治疗骨质疏松主要涉及磷脂酰肌醇-3-激酶(PI3K)/丝苏氨酸蛋白激酶Akt、血管内皮生长因子(VEGF)、腺苷酸活化蛋白激酶(AMPK)、Notch、核因子kappaB(NF-κB)、叉头框蛋白(FoxO)、人嗜T淋巴细胞病毒I型(HTLV-I)等信号通路。【结论】杜仲可能通过PTH、BGP、PPAR、ALP、RUNX2等靶标达到治疗骨质疏松的目的,其治疗骨质疏松的过程可能涉及PI3K-Akt、VEGF、AMPK、Notch等信号通路。 展开更多
关键词 杜仲 骨质疏松 网络药理学 靶标 信号通路
A clue to potential therapeutic targets: application of integrative medicine and bioinformatics 预览
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作者 Shi-Lin Xia Han Liu +1 位作者 Shinobu Mizushima Akio Mizushima 《药物联合治疗》 2019年第3期165-172,共8页
More and more evidence show that the targets of traditional Chinese medicine are a resource pool that contributes to the modern medicine. A key aspect of medicine research is to address the issue how to look for a clu... More and more evidence show that the targets of traditional Chinese medicine are a resource pool that contributes to the modern medicine. A key aspect of medicine research is to address the issue how to look for a clue of potential therapeutic molecular targets by interdisciplinary approaches. With the development of high throughput technology, a considerable amount of data has been emerging. The application of these big data is not so efficient as the generation of them. This paper attempts to show that interdisciplinary analysis contributes to the discovery of targets at the initial stage of drug research, indicating that it is necessary to explore the drug research and development with interdisciplinary approaches between integrative medicine and bioinformatics. 展开更多
关键词 INTEGRATIVE MEDICINE BIOINFORMATIC analysis DRUG TARGETS
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Silencing Huwe1 reduces apoptosis of cortical neurons exposed to oxygen-glucose deprivation and reperfusion 预览
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作者 Guo-Qian He Wen-Ming Xu +3 位作者 Hui-Juan Liao Chuan Jiang Chang-Qing Li Wei Zhang 《中国神经再生研究:英文版》 SCIE CAS CSCD 2019年第11期1977-1985,共9页
HECT, UBA and WWE domain-containing 1(Huwe1), an E3 ubiquitin ligase involved in the ubiquitin-proteasome system, is widely expressed in brain tissue. Huwe1 is involved in the turnover of numerous substrates, includin... HECT, UBA and WWE domain-containing 1(Huwe1), an E3 ubiquitin ligase involved in the ubiquitin-proteasome system, is widely expressed in brain tissue. Huwe1 is involved in the turnover of numerous substrates, including p53, Mcl-1, Cdc6 and N-myc, thereby playing a critical role in apoptosis and neurogenesis. However, the role of Huwe1 in brain ischemia and reperfusion injury remains unclear. Therefore, in this study, we investigated the role of Huwe1 in an in vitro model of ischemia and reperfusion injury. At 3 days in vitro, primary cortical neurons were transduced with a control or shRNA-Huwe1 lentiviral vector to silence expression of Huwe1. At 7 days in vitro, the cells were exposed to oxygen-glucose deprivation for 3 hours and reperfusion for 24 hours. To examine the role of the c-Jun N-terminal kinase(JNK)/p38 pathway, cortical neurons were pretreated with a JNK inhibitor(SP600125) or a p38 MAPK inhibitor(SB203508) for 30 minutes at 7 days in vitro, followed by ischemia and reperfusion. Neuronal apoptosis was assessed by TUNEL assay. Protein expression levels of JNK and p38 MAPK and of apoptosis-related proteins(p53, Gadd45 a, cleaved caspase-3, Bax and Bcl-2) were measured by western blot assay. Immunofluorescence labeling for cleaved caspase-3 was performed. We observed a significant increase in neuronal apoptosis and Huwe1 expression after ischemia and reperfusion. Treatment with the shRNA-Huwe1 lentiviral vector markedly decreased Huwe1 levels, and significantly decreased the number of TUNEL-positive cells after ischemia and reperfusion. The silencing vector also downregulated the pro-apoptotic proteins Bax and cleaved caspase-3, and upregulated the anti-apoptotic proteins Gadd45 a and Bcl-2. Silencing Huwe1 also significantly reduced p-JNK levels and increased p-p38 levels. Our findings show that downregulating Huwe1 affects the JNK and p38 MAPK signaling pathways as well as the expression of apoptosis-related genes to provide neuroprotection during ischemia and reperfusion. All animal experiments and 展开更多
关键词 nerve REGENERATION ischemic stroke oxygen-glucose DEPRIVATION and REPERFUSION ischemia/reperfusion cortical neuron ubiquitin proteasome system Huwe1 APOPTOSIS therapeutic targets CELL culture CELL death neural REGENERATION
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Economic evaluation of the hepatitis C elimination strategy in Greece in the era of affordable direct-acting antivirals 预览
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作者 Ilias Gountas Vana Sypsa +4 位作者 George Papatheodoridis Kyriakos Souliotis Kostas Athanasakis Homie Razavi Angelos Hatzakis 《世界胃肠病学杂志:英文版》 SCIE CAS 2019年第11期1327-1340,共14页
BACKGROUND Hepatitis C virus(HCV) is a leading cause of worldwide liver-related morbidity and mortality. The World Health Organization released an integrated strategy targeting HCV-elimination by 2030. This study aims... BACKGROUND Hepatitis C virus(HCV) is a leading cause of worldwide liver-related morbidity and mortality. The World Health Organization released an integrated strategy targeting HCV-elimination by 2030. This study aims to estimate the required interventions to achieve elimination using updated information for direct-acting antiviral(DAA) treatment coverage, to compute the total costs(including indirect/societal costs) of the strategy and to identify whether the elimination strategy is cost-effective/cost-saving in Greece.AIM To estimate the required interventions and subsequent costs to achieve HCV elimination in Greece.METHODS A previously validated mathematical model was adapted to the Greek HCVinfected population to compare the outcomes of DAA treatment without the additional implementation of awareness or screening campaigns versus an HCV elimination strategy, which includes a sufficient number of treated patients. We estimated the total costs(direct and indirect costs), the disability-adjusted life years and the incremental cost-effectiveness ratio using two different price scenarios.RESULTS Without the implementation of awareness or screening campaigns,approximately 20000 patients would be diagnosed and treated with DAAs by2030. This strategy would result in a 19.6% increase in HCV-related mortality in2030 compared to 2015. To achieve the elimination goal, 90000 patients need to be treated by 2030. Under the elimination scenario, viremic cases would decrease by78.8% in 2030 compared to 2015. The cumulative direct costs to eliminate the disease would range from 2.1-2.3 billion euros(€) by 2030, while the indirect costs would be €1.1 billion. The total elimination cost in Greece would range from €3.2-3.4 billion by 2030. The cost per averted disability-adjusted life year is estimated between €10100 and €13380, indicating that the elimination strategy is very costeffective. Furthermore, HCV elimination strategy would save €560-895 million by2035.CONCLUSION Without large screening programs, eliminati 展开更多
关键词 Hepatitis C ELIMINATION COST effectiveness COST of ELIMINATION Indirect COSTS Projections Mathematical modelling AWARENESS and screening PROGRAMS World Health Organization TARGETS
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丹参饮治疗糖尿病心肌病的网络药理学研究
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作者 陈亚红 刘传鑫 +7 位作者 何涛 袁付丽 王文鑫 田悦 刘彦玲 张丛 李正坤 黄建梅 《中草药》 CAS CSCD 北大核心 2019年第5期1164-1174,共11页
目的 通过整合网络药理学和生物信息学方法,构建活性成分-作用靶点、蛋白-蛋白相互作用(PPI)、关键靶点相应的生物功能和通路网络,预测丹参饮治疗糖尿病心肌病的分子作用机制。方法 采用中药系统药理学数据库和分析平台(TCMSP)数据库筛... 目的 通过整合网络药理学和生物信息学方法,构建活性成分-作用靶点、蛋白-蛋白相互作用(PPI)、关键靶点相应的生物功能和通路网络,预测丹参饮治疗糖尿病心肌病的分子作用机制。方法 采用中药系统药理学数据库和分析平台(TCMSP)数据库筛选及预测丹参饮的生物活性成分及其潜在作用靶点,同时检索PharmGKB等4个数据库挖掘糖尿病心肌病的相关靶点,对2种靶点进行PPI网络构建,交互处理得到丹参饮治疗糖尿病心肌病的关键靶点,并利用SystemsDock WebSite对其进行分子对接验证;运用DAVID(Version 6.8)平台对关键靶点进行Pathway分析,结合Omicshare数据库筛选核心通路并利用Reactome数据库进行注释。结果 以口服生物利用度(OB)和类药性(DL)数值作为筛选标准,从丹参饮中共获得78个活性成分,涉及到506个丹参饮治疗糖尿病心肌病的可能靶点,这些靶点主要富集在磷脂酰肌醇3-激酶/蛋白激酶B(PI3K-Akt)、丝裂原活化蛋白激酶(MAPK)等多条信号通路上。结论 本研究揭示了丹参饮治疗糖尿病心肌病可能的作用机制,体现了中药复方多成分、多靶点、多途径治疗疾病的特点,为进一步深入研究其作用机制提供了新思路。 展开更多
关键词 网络药理学 丹参饮 糖尿病心肌病 分子对接 作用靶点
Methionine adenosyltransferases in liver cancer 预览
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作者 Ben Murray Lucia Barbier-Torres +2 位作者 Wei Fan JoséM Mato Shelly C Lu 《世界胃肠病学杂志:英文版》 SCIE CAS 2019年第31期4300-4319,共20页
Methionine adenosyltransferases(MATs)are essential enzymes for life as they produce S-adenosylmethionine(SAMe),the biological methyl donor required for a plethora of reactions within the cell.Mammalian systems express... Methionine adenosyltransferases(MATs)are essential enzymes for life as they produce S-adenosylmethionine(SAMe),the biological methyl donor required for a plethora of reactions within the cell.Mammalian systems express two genes,MAT1A and MAT2A,which encode for MATα1 and MATα2,the catalytic subunits of the MAT isoenzymes,respectively.A third gene MAT2B,encodes a regulatory subunit known as MATβwhich controls the activity of MATα2.MAT1A,which is mainly expressed in hepatocytes,maintains the differentiated state of these cells,whilst MAT2A and MAT2B are expressed in extrahepatic tissues as well as non-parenchymal cells of the liver(e.g.,hepatic stellate and Kupffer cells).The biosynthesis of SAMe is impaired in patients with chronic liver disease and liver cancer due to decreased expression and inactivation of MATα1.A switch from MAT1A to MAT2A/MAT2B occurs in multiple liver diseases and during liver growth and dedifferentiation,but this change in the expression pattern of MATs results in reduced hepatic SAMe level.Decades of study have utilized the Mat1a-knockout(KO)mouse that spontaneously develops non-alcoholic steatohepatitis(NASH)and hepatocellular carcinoma(HCC)to elucidate a variety of mechanisms by which MAT proteins dysregulation contributes to liver carcinogenesis.An increasing volume of work indicates that MATs have SAMe-independent functions,distinct interactomes and multiple subcellular localizations.Here we aim to provide an overview of MAT biology including genes,isoenzymes and their regulation to provide the context for understanding consequences of their dysregulation.We will highlight recent breakthroughs in the field and underscore the importance of MAT’s in liver tumorigenesis as well as their potential as targets for cancer therapy. 展开更多
关键词 METHIONINE adenosyltransferases S-ADENOSYLMETHIONINE Liver cancer Hepatocellular carcinoma CHOLANGIOCARCINOMA Biomarkers THERAPEUTIC TARGETS
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