Taking the interaction between a DNA damage repair module, an ATM module, and a P53--MDM2 oscillation module into account, this paper presents a mathematical model of a P53 oscillation network triggered by a DNA damag...Taking the interaction between a DNA damage repair module, an ATM module, and a P53--MDM2 oscillation module into account, this paper presents a mathematical model of a P53 oscillation network triggered by a DNA damage signal in individual cells. The effects of the DNA damage signal and the delay time of P53-induced MDM2 expression on the behaviours of the P53 oscillation network are studied. In the oscillatory state of the P53--MDM2 oscillator, it is found that the pulse number of P53--P oscillation increases with the increase of the initial DNA damage signal, whereas the amplitude and the period of P53--P oscillation are fixed for different initial DNA damage signals, and the period numbers of P53--P oscillations decrease with the increase of time delay of MDM2 expression induced by P53. These theoretical predictions are consistent with previous experimental results. The combined negative feedback of P53--MDM2 with the time delay of P53-induced MDM2 expression causes oscillation behaviour in the P53 network.展开更多
[目的]运用网络药理学联合生物信息学方法,探究黄芪四君子汤治疗肝细胞癌(hepatocelluar carcinoma,HCC)的潜在作用机制。[方法]利用中药系统药理学数据库和分析平台(Traditional Chinese Medicine Systems Pharmacology Database and A...[目的]运用网络药理学联合生物信息学方法,探究黄芪四君子汤治疗肝细胞癌(hepatocelluar carcinoma,HCC)的潜在作用机制。[方法]利用中药系统药理学数据库和分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)数据库对中药的生物活性成分及其靶点进行鉴定。采用差异分析和加权基因共表达网络分析(weighted gene coexpression net work analysis,WGCNA)鉴定HCC的差异基因和模块基因,在此基础上构建中药成分-靶点网络。随后研究靶点的生物学功能,并构建蛋白互作(protein-protein interaction,PPI)网络,识别药物治疗HCC的关键靶点。最后通过分子对接探索化合物与靶点之间的相互作用。[结果]共鉴定出5种草药的156种化合物和227个靶点,癌症基因组图谱(The Cancer Genome Atlas,TCGA)和基因表达综合(Gene Expression Omnibus,GEO)数据库数据集中差异基因2477和685个,WGCNA关联模块基因2104和2165个。构建了包含4种草药、85种化合物和9个靶点的中药成分-靶点网络。生物功能分析表明,9个靶点主要与细胞周期、p53信号通路、细胞衰老相关,筛选出山柰酚、槲皮素2个药物主要成分和细胞周期蛋白A2(cyclin A2,CCNA2)、雌激素受体1(estrogen receptor alpha,ESR1)、细胞周期蛋白B1(cyclin B1,CCNB1)、细胞周期蛋白依赖性激酶1(cyclin-dependent kinase 1,CDK1)、拓扑异构酶Ⅱα(topoisomeraseⅡalpha,TOP2A)5个核心靶点。分子对接结果显示,山柰酚、槲皮素与对应的核心靶点具有稳定的结合能力。[结论]黄芪四君子汤可能通过调节细胞周期蛋白以及相关通路发挥对HCC的治疗作用,本研究为黄芪四君子汤治疗HCC提供了研究思路和理论支撑。展开更多
基金Project supported by the National Natural Science Foundation of China (Grant No. 10875049)the Key Project of Chinese Ministry of Education (Grant No. 108096)the Programme of Introducing Talents of Discipline to Universities (Grant No. B08033)
文摘Taking the interaction between a DNA damage repair module, an ATM module, and a P53--MDM2 oscillation module into account, this paper presents a mathematical model of a P53 oscillation network triggered by a DNA damage signal in individual cells. The effects of the DNA damage signal and the delay time of P53-induced MDM2 expression on the behaviours of the P53 oscillation network are studied. In the oscillatory state of the P53--MDM2 oscillator, it is found that the pulse number of P53--P oscillation increases with the increase of the initial DNA damage signal, whereas the amplitude and the period of P53--P oscillation are fixed for different initial DNA damage signals, and the period numbers of P53--P oscillations decrease with the increase of time delay of MDM2 expression induced by P53. These theoretical predictions are consistent with previous experimental results. The combined negative feedback of P53--MDM2 with the time delay of P53-induced MDM2 expression causes oscillation behaviour in the P53 network.
文摘[目的]运用网络药理学联合生物信息学方法,探究黄芪四君子汤治疗肝细胞癌(hepatocelluar carcinoma,HCC)的潜在作用机制。[方法]利用中药系统药理学数据库和分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)数据库对中药的生物活性成分及其靶点进行鉴定。采用差异分析和加权基因共表达网络分析(weighted gene coexpression net work analysis,WGCNA)鉴定HCC的差异基因和模块基因,在此基础上构建中药成分-靶点网络。随后研究靶点的生物学功能,并构建蛋白互作(protein-protein interaction,PPI)网络,识别药物治疗HCC的关键靶点。最后通过分子对接探索化合物与靶点之间的相互作用。[结果]共鉴定出5种草药的156种化合物和227个靶点,癌症基因组图谱(The Cancer Genome Atlas,TCGA)和基因表达综合(Gene Expression Omnibus,GEO)数据库数据集中差异基因2477和685个,WGCNA关联模块基因2104和2165个。构建了包含4种草药、85种化合物和9个靶点的中药成分-靶点网络。生物功能分析表明,9个靶点主要与细胞周期、p53信号通路、细胞衰老相关,筛选出山柰酚、槲皮素2个药物主要成分和细胞周期蛋白A2(cyclin A2,CCNA2)、雌激素受体1(estrogen receptor alpha,ESR1)、细胞周期蛋白B1(cyclin B1,CCNB1)、细胞周期蛋白依赖性激酶1(cyclin-dependent kinase 1,CDK1)、拓扑异构酶Ⅱα(topoisomeraseⅡalpha,TOP2A)5个核心靶点。分子对接结果显示,山柰酚、槲皮素与对应的核心靶点具有稳定的结合能力。[结论]黄芪四君子汤可能通过调节细胞周期蛋白以及相关通路发挥对HCC的治疗作用,本研究为黄芪四君子汤治疗HCC提供了研究思路和理论支撑。
