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国家自然科学基金(31100701)

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用于药物研发的细胞色素P450酶3A4体外肝细胞模型的研究进展被引量:1
2013年
药物研发中生理性功能的体外细胞模型是非常重要的。细胞色素P450酶3A4(CYP3A4)是最重要的临床药物代谢酶之一,其作用底物谱广泛。相应地由这些底物作用于CYP3A4酶而产生的酶活性被抑制或诱导,直观表现为复杂化的药物代谢相互作用。因此,CYP3A4体外细胞模型在药物研发过程中具有重要应用价值。目前常用CYP3A4表达的一些体外模型,相比体内有不同程度的差距。这些差距有望通过加深机制了解、基因工程学技术以及体外微环境模拟功能单元构建组织工程技术的进步,而逐步得以缩减或消除。如何构建接近生理性表达的体外CYP3A4细胞模型是本研究领域一直探索的热点。本文就目前已知的CYP3A4生理功能特征、表达调控机制以及基于已知相关机制研究进行体外细胞模型构建的细胞种类、构建策略和方式进行综述。
饶小惠陈锋潘明新汪艳
关键词:细胞色素P450CYP3A4肝细胞体外
Current Strategies for Quantitating Fibrosis in Liver Biopsy被引量:12
2015年
Objective:The present mini-review updated the progress in methodologies based on using liver biopsy.Data Sources:Articles for study of liver fibrosis,liver biopsy or fibrosis assessment published on high impact peer review journals from 1980 to 2014.Study Selection:Key articles were selected mainly according to their levels of relevance to this topic and citations.Results:With the recently mounting progress in chronic liver disease therapeutics,comes by a pressing need for precise,accurate,and dynamic assessment of hepatic fibrosis and cirrhosis in individual patients.Histopathological information is recognized as the most valuable data for fibrosis assessment.Conventional histology categorical systems describe the changes of fibrosis patterns in liver tissue; but the simplified ordinal digits assigned by these systems cannot reflect the fibrosis dynamics with sufficient precision and reproducibility.Morphometric assessment by computer assist digital image analysis,such as collagen proportionate area (CPA),detects change of fibrosis amount in tissue section in a continuous variable,and has shown its independent diagnostic value for assessment of advanced or late-stage of fibrosis.Due to its evident sensitivity to sampling variances,morphometric measurement is feasible to be taken as a reliable statistical parameter for the study of a large cohort.Combining state-of-art imaging technology and fundamental principle in Tissue Engineering,structure-based quantitation was recently initiated with a novel proof-of-concept tool,qFibrosis.qFibrosis showed not only the superior performance to CPA in accurately and reproducibly differentiating adjacent stages of fibrosis,but also the possibility for facilitating analysis of fibrotic regression and cirrhosis sub-staging.Conclusions:With input from multidisciplinary innovation,liver biopsy assessment as a new "gold standard" is anticipated to substantially support the accelerated progress of Hepatology medicine.
Yan WangJin-Lin Hou
关键词:CIRRHOSIS
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