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基于转录组测序和网络药理学探究青蒿琥酯干预U87和U251脑胶质瘤细胞的药效差异机制
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作者 李涛 毛霞 +5 位作者 张彦琼 林娜 sato takashi MIZUNO Koji OKUYAMA Katsuki 黄丰 《药学学报》 CAS CSCD 北大核心 2023年第6期1475-1483,共9页
青蒿琥酯具有干预脑胶质瘤的潜能,但其药理作用机制尚不明确。本研究首先基于U87和U251两种人源脑胶质瘤细胞,探究青蒿琥酯对细胞活性、增殖和凋亡的影响,发现青蒿琥酯对U87细胞活性和增殖能力的抑制作用强于对U251细胞;Hoechst和TUNEL... 青蒿琥酯具有干预脑胶质瘤的潜能,但其药理作用机制尚不明确。本研究首先基于U87和U251两种人源脑胶质瘤细胞,探究青蒿琥酯对细胞活性、增殖和凋亡的影响,发现青蒿琥酯对U87细胞活性和增殖能力的抑制作用强于对U251细胞;Hoechst和TUNEL细胞凋亡染色实验也发现,青蒿琥酯可以显著促进U87细胞的凋亡(P <0.05),而仅大剂量的青蒿琥酯可促进U251细胞的凋亡(P <0.01)。接着,利用青蒿琥酯处理前后的U87和U251细胞裂解液,通过转录组测序检测和差异数据分析,分别获得青蒿琥酯敏感性和非敏感性细胞株的差异基因集以及青蒿琥酯效应相关基因集,旨在挖掘青蒿琥酯对两类细胞敏感性不一的分子机制。通过构建上述各对比组差异基因互作网络和计算网络拓扑特征值,筛选药效相关的关键网络靶标;生物功能富集分析结果表明,上述关键网络靶标显著富集于多条与脑胶质瘤病理环节相关的信号通路,其中,与细胞凋亡相关的转录激活因子4 (ATF4)-DNA损伤诱导转录因子3 (DDIT3)-聚腺苷二磷酸核糖聚合酶1 (PARP1)信号轴的富集显著性最高。分子对接结果也表明,青蒿琥酯与ATF4和DDIT3均具有较好的结合能力。本研究初步揭示了青蒿琥酯干预U87脑胶质瘤细胞的潜能与其抑制肿瘤细胞内异常活化的ATF4-DDIT3-PARP1信号轴,进而诱导细胞凋亡有关;同时也表明了PARP1可能是U251细胞对青蒿琥酯产生耐药的重要靶标。相关结果为青蒿琥酯治疗脑胶质瘤,以及解决脑胶质瘤治疗药物耐药的现状提供了新的实验依据。 展开更多
关键词 青蒿琥酯 脑胶质瘤 转录组测序 网络药理学 药理机制
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Action Mechanisms of Complementary and Alternative Medicine Therapies for Rheumatoid Arthritis 被引量:1
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作者 Imada Keisuke 边宝林 +2 位作者 李向东 sato takashi Ito Akira 《Chinese Journal of Integrative Medicine》 SCIE CAS 2011年第10期723-730,共8页
Rheumatoid arthritis (RA) is characterized as a chronic inflammatory disease in joints and concomitant destruction of cartilage and bone. Cartilage extracellular matrix components, such as type Ⅱ collagen and aggre... Rheumatoid arthritis (RA) is characterized as a chronic inflammatory disease in joints and concomitant destruction of cartilage and bone. Cartilage extracellular matrix components, such as type Ⅱ collagen and aggrecan are enzymatically degraded by matrix metalloproteinases (MMPs) and aggrecanases in RA. Currently, treatments targeting cytokines, including anti-tumor necrosis factor (TNF) α antibodies, soluble TNF receptor, anti-interleukin (IL)-6 receptor antibody, and IL-1 receptor antagonist, are widely used for treating RA in addition to anti- inflammatory agents and disease-modifying antirheumatic drugs (DMARDs), such as methotrexate, but these treatments have some problems, especially in terms of cost and the increased susceptibility of patients to infection in addition to the existence of Iow-responders to these treatments. Therefore, therapeutics that can be safely used for an extended period of time would be preferable. Complementary and alternativemedicines including traditional Chinese medicines (TCM) have been used for the arthritic diseases through the ages. Recently, there are many reports concerning the anti-arthritic action mechanisms of TCM-based herbal formulas and crude herbal extracts or isolated ingredients. These natural herbal medicines are thought to moderately improve RA, but they exert various actions for the treatment of RA. In this review, the current status of the mechanism exploration of natural compounds and TCM-based herbal formulas are summarized, focusing on the protection of cartilage destruction in arthritic diseases including RA and osteoarthritis. 展开更多
关键词 rheumatoid arthritis extracellular matrix AGGRECANASE matrix metalloproteinase complementary and alternative medicine
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