Inflammation-mediated carcinogenesis develops in the context of chronic inflammation and is a significant cause of cancer within the digestive system.In the chronic inflammation microenvironment,the metabolic activity...Inflammation-mediated carcinogenesis develops in the context of chronic inflammation and is a significant cause of cancer within the digestive system.In the chronic inflammation microenvironment,the metabolic activity of tissue cells undergoes extensive changes,which interfere with the normal function of immune cells.Dysregulation of cell metabolism and immune function has been identified as a key factor contributing to inflammation-mediated carcinogenesis within the major digestive organs,such as the stomach,liver,and colorectum.This metabolic-immune imbalance also corresponds to traditional Chinese medicine(TCM)theories of“yin-yang disharmony”and“disharmony between Ying-nutrients and Wei-defense.”The metabolic-immune imbalance has also been regarded as the key factor supporting“treatment of different diseases with the same method”,in which the same approach is adopted in the treatment of different conditions.In the TCM treatment process,it is necessary to first identify TCM patterns and then apply the corresponding TCM to correct the dysregulated metabolic and immune function,thereby blocking the progression from inflammation to malignancy.Our study findings deepen the TCM understanding of metabolic-immune dysregulation and the relationship between metabolic-immune dysregulation,pattern identification,and treatment method.They also provide new insights for the treatment of inflammation-mediated carcinogenesis in major digestive organs and help us further explore the scientific connotation of the TCM strategy of“treating different diseases with the same method”.展开更多
Kidney disease in patients with liver disease is serious and increases mortality.Up to 50%of patients hospitalized experience an episode of acute kidney injury.In general,men with liver disease are thought to be at in...Kidney disease in patients with liver disease is serious and increases mortality.Up to 50%of patients hospitalized experience an episode of acute kidney injury.In general,men with liver disease are thought to be at increased risk of kidney disease.However,this association should be considered with caution because most studies use creatinine-based inclusion criteria,which is negatively biased against women.In this review,we synthesize data on sex differences in kidney disease in patients with chronic liver disease in the clinical setting and discuss potential physiologic underpinnings.展开更多
目的:基于网络药理学探讨二仙汤“异病同治”乳腺增生和围绝经期综合征的作用机制。方法:通过中药系统药理学数据库与分析平台(traditional Chinese medicine systems pharmacology database and analysis platform,TCMSP)筛选二仙汤中...目的:基于网络药理学探讨二仙汤“异病同治”乳腺增生和围绝经期综合征的作用机制。方法:通过中药系统药理学数据库与分析平台(traditional Chinese medicine systems pharmacology database and analysis platform,TCMSP)筛选二仙汤中6味中药的活性成分并预测其潜在靶点;通过人类基因数据库(the human gene database,GeneCards)及在线人类孟德尔遗传数据库(online mendelian inheritance in man,OMIM)平台检索乳腺增生和围绝经期综合征的疾病靶点,借助Venn在线工具构建药物与两种疾病的交集靶点。运用Cytoscape 3.7.2软件构建“药物-成分-靶点-疾病”网络;利用STRING数据库构建PPI网络,按Dgree值大于等于平均值进一步筛选核心靶点;采用DAVID数据库进行基因本体论(gene ontology,GO)富集分析,同时实现京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)通路富集分析。结果 :根据口服生物利用度(oral bioavailability,OB)≥30%和药物类药性(druglikeness,DL)≥0.18筛选得到二仙汤有效活性成分104个,预测潜在作用靶点147个;通过筛选得到乳腺增生靶点4153个,围绝经期综合征靶点155个,药物与疾病的交集靶点29个,其中IL-6、VEGFA、TNF、TP53、ESR1、CAT、IL-1β等可能是二仙汤治疗乳腺增生和围绝经期综合征的关键靶点。活性成分及靶点主要参与DNA模板转录正调控、基因表达的正调控、胞外间隙、胞外区、类固醇结合、酶结合等;靶基因主要富集在TNF、NOD样体、HIF-1、癌症、PI3K-Akt等信号通路。结论:二仙汤可能通过调控PI3K-Akt、HIF-1等信号通路达到防治乳腺增生和围绝经期综合征的目的。展开更多
[目的]运用网络药理学与分子对接技术探究桂枝茯苓丸“异病同治”治疗缺血性卒中、蛛网膜下腔出血、轻度认知障碍、失眠障碍、癫痫以及血管性头痛的作用机制。[方法]通过中药系统药理学数据库与分析平台(Traditional Chinese Medicine S...[目的]运用网络药理学与分子对接技术探究桂枝茯苓丸“异病同治”治疗缺血性卒中、蛛网膜下腔出血、轻度认知障碍、失眠障碍、癫痫以及血管性头痛的作用机制。[方法]通过中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)、Swiss Target Prediction数据库以及PubChem平台预测桂枝茯苓丸组方药物的核心活性成分及对应靶点;检索DrugBank、疾病基因网络(Disease Gene Network,DisGeNET)、基因组注释数据平台(Genome Annotation Database Platform,GeneCards)及在线人类孟德尔遗传(Online Mendelian Inheritance in Man,OMIM)数据库获取疾病相关靶点,得到药物-疾病交集靶点;采用Cytoscape 3.9.1软件构建“药物-疾病-成分-靶点”网络和蛋白互作(protein-protein interaction,PPI)网络图,通过Metascape数据库对交集靶点进行核心靶点的基因本体(gene ontology,GO)功能和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路富集分析。利用AutoDock Vina软件对核心成分和关键靶点进行分子对接验证。[结果]筛选去重后共获取桂枝茯苓丸核心活性成分155个,相关靶点672个,脑病靶点196个,药物-疾病交集靶点78个,其中桂枝茯苓丸“异病同治”脑病的5个核心活性成分为丹皮酚、槲皮素、芍药苷、肉桂醛、苦杏仁苷,PPI筛选得到5个关键靶点分别为白细胞介素-6(interleukin-6,IL6)、肿瘤坏死因子(tumor necrosis factor,TNF)、胰岛素(insulin,INS)、RAC-α丝氨酸/苏氨酸蛋白激酶(RAC-alpha serine/threonine-protein kinase,AKT1)、白细胞介素-1β(interleukin-1β,IL1B),KEGG富集分析显示主要通路分别为脂质与动脉粥样硬化、流体剪切力与动脉粥样硬化、癌症中的通路、糖尿病并发症中的高级糖基化终末产物-受体(advanced glycation end products-receptor of advanced glycation end products,AGEs-RAGE)信号通路、阿尔茨海默病、神经退行性变-多发性疾病中的通路。分子对接结果显示核心活性成分和关键靶点之间结合活性较好。[结论]本研究阐述了桂枝茯苓丸“异病同治”脑病多成分、多靶点、多通路的可能机制,为进一步了解桂枝茯苓丸的作用机制,探索新的临床应用和实验探究提供了一定的理论依据和参考。展开更多
基金supported by National Natural Science Foundation of China(92059102 and 81630080)the National Key Research and Development Plan of China(2018YFC1704106).
文摘Inflammation-mediated carcinogenesis develops in the context of chronic inflammation and is a significant cause of cancer within the digestive system.In the chronic inflammation microenvironment,the metabolic activity of tissue cells undergoes extensive changes,which interfere with the normal function of immune cells.Dysregulation of cell metabolism and immune function has been identified as a key factor contributing to inflammation-mediated carcinogenesis within the major digestive organs,such as the stomach,liver,and colorectum.This metabolic-immune imbalance also corresponds to traditional Chinese medicine(TCM)theories of“yin-yang disharmony”and“disharmony between Ying-nutrients and Wei-defense.”The metabolic-immune imbalance has also been regarded as the key factor supporting“treatment of different diseases with the same method”,in which the same approach is adopted in the treatment of different conditions.In the TCM treatment process,it is necessary to first identify TCM patterns and then apply the corresponding TCM to correct the dysregulated metabolic and immune function,thereby blocking the progression from inflammation to malignancy.Our study findings deepen the TCM understanding of metabolic-immune dysregulation and the relationship between metabolic-immune dysregulation,pattern identification,and treatment method.They also provide new insights for the treatment of inflammation-mediated carcinogenesis in major digestive organs and help us further explore the scientific connotation of the TCM strategy of“treating different diseases with the same method”.
文摘Kidney disease in patients with liver disease is serious and increases mortality.Up to 50%of patients hospitalized experience an episode of acute kidney injury.In general,men with liver disease are thought to be at increased risk of kidney disease.However,this association should be considered with caution because most studies use creatinine-based inclusion criteria,which is negatively biased against women.In this review,we synthesize data on sex differences in kidney disease in patients with chronic liver disease in the clinical setting and discuss potential physiologic underpinnings.
文摘目的:基于网络药理学探讨二仙汤“异病同治”乳腺增生和围绝经期综合征的作用机制。方法:通过中药系统药理学数据库与分析平台(traditional Chinese medicine systems pharmacology database and analysis platform,TCMSP)筛选二仙汤中6味中药的活性成分并预测其潜在靶点;通过人类基因数据库(the human gene database,GeneCards)及在线人类孟德尔遗传数据库(online mendelian inheritance in man,OMIM)平台检索乳腺增生和围绝经期综合征的疾病靶点,借助Venn在线工具构建药物与两种疾病的交集靶点。运用Cytoscape 3.7.2软件构建“药物-成分-靶点-疾病”网络;利用STRING数据库构建PPI网络,按Dgree值大于等于平均值进一步筛选核心靶点;采用DAVID数据库进行基因本体论(gene ontology,GO)富集分析,同时实现京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)通路富集分析。结果 :根据口服生物利用度(oral bioavailability,OB)≥30%和药物类药性(druglikeness,DL)≥0.18筛选得到二仙汤有效活性成分104个,预测潜在作用靶点147个;通过筛选得到乳腺增生靶点4153个,围绝经期综合征靶点155个,药物与疾病的交集靶点29个,其中IL-6、VEGFA、TNF、TP53、ESR1、CAT、IL-1β等可能是二仙汤治疗乳腺增生和围绝经期综合征的关键靶点。活性成分及靶点主要参与DNA模板转录正调控、基因表达的正调控、胞外间隙、胞外区、类固醇结合、酶结合等;靶基因主要富集在TNF、NOD样体、HIF-1、癌症、PI3K-Akt等信号通路。结论:二仙汤可能通过调控PI3K-Akt、HIF-1等信号通路达到防治乳腺增生和围绝经期综合征的目的。
文摘[目的]运用网络药理学与分子对接技术探究桂枝茯苓丸“异病同治”治疗缺血性卒中、蛛网膜下腔出血、轻度认知障碍、失眠障碍、癫痫以及血管性头痛的作用机制。[方法]通过中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)、Swiss Target Prediction数据库以及PubChem平台预测桂枝茯苓丸组方药物的核心活性成分及对应靶点;检索DrugBank、疾病基因网络(Disease Gene Network,DisGeNET)、基因组注释数据平台(Genome Annotation Database Platform,GeneCards)及在线人类孟德尔遗传(Online Mendelian Inheritance in Man,OMIM)数据库获取疾病相关靶点,得到药物-疾病交集靶点;采用Cytoscape 3.9.1软件构建“药物-疾病-成分-靶点”网络和蛋白互作(protein-protein interaction,PPI)网络图,通过Metascape数据库对交集靶点进行核心靶点的基因本体(gene ontology,GO)功能和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路富集分析。利用AutoDock Vina软件对核心成分和关键靶点进行分子对接验证。[结果]筛选去重后共获取桂枝茯苓丸核心活性成分155个,相关靶点672个,脑病靶点196个,药物-疾病交集靶点78个,其中桂枝茯苓丸“异病同治”脑病的5个核心活性成分为丹皮酚、槲皮素、芍药苷、肉桂醛、苦杏仁苷,PPI筛选得到5个关键靶点分别为白细胞介素-6(interleukin-6,IL6)、肿瘤坏死因子(tumor necrosis factor,TNF)、胰岛素(insulin,INS)、RAC-α丝氨酸/苏氨酸蛋白激酶(RAC-alpha serine/threonine-protein kinase,AKT1)、白细胞介素-1β(interleukin-1β,IL1B),KEGG富集分析显示主要通路分别为脂质与动脉粥样硬化、流体剪切力与动脉粥样硬化、癌症中的通路、糖尿病并发症中的高级糖基化终末产物-受体(advanced glycation end products-receptor of advanced glycation end products,AGEs-RAGE)信号通路、阿尔茨海默病、神经退行性变-多发性疾病中的通路。分子对接结果显示核心活性成分和关键靶点之间结合活性较好。[结论]本研究阐述了桂枝茯苓丸“异病同治”脑病多成分、多靶点、多通路的可能机制,为进一步了解桂枝茯苓丸的作用机制,探索新的临床应用和实验探究提供了一定的理论依据和参考。
