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吴茱萸肝毒性机制的阐明——基于QSAR毒性预测和代谢组学研究
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作者 杨春启 赖成材 +11 位作者 茹毅 沈宝英 吴香军 崔佳露 李方杨 张程 师卓 钱庆元 肖成荣 王宇光 张伯礼 高月 《Acupuncture and Herbal Medicine》 2024年第2期257-270,I0013,I0014,共16页
[目的]吴茱萸是临床上治疗胃肠道疾病的中药,已被广泛应用。然而,吴茱萸在《中国药典》及本草著作中被认为是一种“小毒”的中药。本研究采用毒性预测与体内外研究相结合的方法,鉴定吴茱萸的毒性成分和毒性靶器官,并从代谢角度探讨其毒... [目的]吴茱萸是临床上治疗胃肠道疾病的中药,已被广泛应用。然而,吴茱萸在《中国药典》及本草著作中被认为是一种“小毒”的中药。本研究采用毒性预测与体内外研究相结合的方法,鉴定吴茱萸的毒性成分和毒性靶器官,并从代谢角度探讨其毒性机制。[方法]通过体外和体内研究,对吴茱萸的毒性靶器官进行鉴定。通过生物碱富集和分离进行体外毒性筛选。基于定量构效关系(QSAR)构建,通过吸收、分布、代谢、排泄和毒性预测因子(ADMET Prodictor)预测化合物的潜在毒性。此外,研究整合了服用潜在毒性成分后的血清代谢组学分析,以阐明潜在毒性物质对小鼠代谢的影响。[结果]比较不同提取方法及炮制前后对小鼠的急性毒性,吴茱萸醇提物毒性最高,吴茱萸毒性的靶器官为肝脏。吴茱萸醇提物的生物碱组分具有较强的细胞毒性。ADMET Predictor对吴茱萸的潜在毒性进行了计算和预测,认为生物碱是导致吴茱萸毒性的主要原因。而吴茱萸碱在体外显著减少细胞数量,提高线粒体膜电位。吴茱萸碱给药后,小鼠血清代谢组学对不同的代谢产物进行了显著鉴定,其中胆汁酸代谢和类固醇激素生物合成是肝毒性的关键途径。[结论]通过比较不同提取方法在加工前后的急性毒性,阐明吴茱萸炮制品临床应用的科学意义。将基于QSAR的毒性预测与体内外毒性筛选相结合,可以鉴定吴茱萸的潜在毒性靶器官和毒性成分。通过代谢组学研究,初步揭示吴茱萸的肝毒性可能与胆汁酸代谢和类固醇激素生物合成有关。本研究为阐明吴茱萸的作用机理、评价其安全性和质量奠定了基础。 展开更多
关键词 ADMET Prodictor 吴茱萸 吴茱萸碱 肝毒性 LD50 代谢组学
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A novel pseudo-random coupled LP spatiotemporal chaos and its application in image encryption 被引量:4
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作者 Xingyuan Wang Yu Wang +2 位作者 Siwei Wang Yingqian Zhang xiangjun wu 《Chinese Physics B》 SCIE EI CAS CSCD 2018年第11期419-429,共11页
In this paper, first, we investigate a novel one-dimensional logistic-PWLCM(LP) modulation map which is derived from the logistic and PWLCM maps. Second, we propose a novel PCLML spatiotemporal chaos in pseudo-rando... In this paper, first, we investigate a novel one-dimensional logistic-PWLCM(LP) modulation map which is derived from the logistic and PWLCM maps. Second, we propose a novel PCLML spatiotemporal chaos in pseudo-random coupling method that can accelerate the system behavior of the fully spatial chaos. Here, because the better chaotic properties include a wide range of parameter settings and better ergodicity than a logistic map, the LP is used in PCLML as f(x). The Kolmogorov–Sinai entropy density and universality and the bifurcation diagram are employed to investigate the chaotic behaviors of the proposed PCLML model. Finally, we apply the LP and PCLML chaotic systems to image encryption to improve the effectiveness and security of the encryption scheme. By combining self-generating matrix model M and dynamic substitution box(S-Box) methods, we design a new image encryption algorithm. Numerical simulations and security analysis have been carried out to demonstrate that the proposed algorithm has a high security level and can efficiently encrypt several different kinds of images into random-like images. 展开更多
关键词 logistic-PWLCM map PCLML spatiotemporal chaos matrix model M dynamic S-Box image encryption
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Profiling the responsiveness of focal adhesions of human cardiomyocytes to extracellular dynamic nano-topography 被引量:1
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作者 Huaiyu Shi xiangjun wu +7 位作者 Shiyang Sun Chenyan Wang Zacharias Vangelatos Ariel Ash-Shakoor Costas P.Grigoropoulos Patrick T.Mather James H.Henderson Zhen Ma 《Bioactive Materials》 SCIE 2022年第4期367-377,共11页
Focal adhesion complexes function as the mediators of cell-extracellular matrix interactions to sense and transmit the extracellular signals.Previous studies have demonstrated that cardiomyocyte focal adhesions can be... Focal adhesion complexes function as the mediators of cell-extracellular matrix interactions to sense and transmit the extracellular signals.Previous studies have demonstrated that cardiomyocyte focal adhesions can be modulated by surface topographic features.However,the response of focal adhesions to dynamic surface topographic changes remains underexplored.To study this dynamic responsiveness of focal adhesions,we utilized a shape memory polymer-based substrate that can produce a flat-to-wrinkle surface transition triggered by an increase of temperature.Using this dynamic culture system,we analyzed three proteins(paxillin,vinculin and zyxin)from different layers of the focal adhesion complex in response to dynamic extracellular topographic change.Hence,we quantified the dynamic profile of cardiomyocyte focal adhesion in a time-dependent manner,which provides new understanding of dynamic cardiac mechanobiology. 展开更多
关键词 Stimuli-responsive biomaterials Shape memory polymer Focal adhesion Costamere Dynamic mechanobiology Human induced pluripotent stem cells
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