Impact of sex and pregnancy on hepatic CYP3A4 expression and activity in a humanized mouse model [0.03%]
性别和妊娠对人源化小鼠模型肝CYP3A4表达及活性的影响
Muluneh M Fashe,Taryn A Miner,Valeria Laboy Collazo et al.
Muluneh M Fashe et al.
Cytochrome P450 (CYP) 3A4 is an essential drug-metabolizing enzyme in humans, which shows substantial interindividual variation in response to various intrinsic and extrinsic factors such as sex and pregnancy. In humans, higher CYP3A4 metab...
Exploring cytochrome P450 under hypoxia: potential pharmacological significance in drug metabolism and protection against high-altitude diseases [0.03%]
缺氧条件下细胞色素P450的探究：在药物代谢和高原疾病保护中的潜在药理学意义
Qian Wang,Guiqin Liu,Yabin Duan et al.
Qian Wang et al.
High-altitude hypoxia affects the human respiratory, central nervous, cardiovascular, and endocrine systems. These outcomes affect the expression of cytochrome P450 (CYP), the most important family of metabolic enzymes in the body that is i...
Improvement in static and dynamic projections of drug-drug interactions caused by cytochrome P4503A time-dependent inhibitors through in vitro allosteric modulation by progesterone [0.03%]
通过孕激素的体外别构调节改善CYTOCHROME P4503A时间依赖性抑制剂引起的药物-药物静态和动态投影交互作用
Pooja Hegde,Brianna Rodriguez,Alec Bell et al.
Pooja Hegde et al.
Current drug discovery screens to assess the drug-drug interaction (DDI) risk caused by time-dependent inhibition (TDI) of cytochrome P450 (CYP) 3A4 are known to overpredict or produce false positives that do not translate in vivo. Recent w...
Organic cation transporters 2: Structure, regulation, functions, and clinical implications [0.03%]
有机阳离子转运体2：结构、调控、功能及临床意义
Anoud Ailabouni,Bhagwat Prasad
Anoud Ailabouni
The SLC22A2 gene encodes organic cation transporter 2 (OCT2), which is predominantly expressed in renal proximal tubule cells. OCT2 is critical for the active renal excretion of various cationic drugs and endogenous metabolites. OCT2 expres...
Application of small interfering RNA technology in cytochrome P450 gene modulation [0.03%]
小分子干扰RNA技术在细胞色素P450基因调节中的应用
Wenzhao Jiang,Ruoyao Sang,Cai Zhang et al.
Wenzhao Jiang et al.
Cytochrome P450 plays key roles in the biotransformation of endogenous and exogenous chemicals including drugs and environmental pollutants. The inhibition and downregulation of P450s can have therapeutic effects, and/or modulate drug metab...
Cannabidiol and Δ9-tetrahydrocannabinol induce drug-metabolizing enzymes, but not transporters, in human hepatocytes: Implications for predicting complex cannabinoid-drug interactions [0.03%]
大麻二酚和Δ9-四氢大麻醇在人肝细胞中诱导药物代谢酶，而不是转运蛋白：对预测复杂的大麻素-药物相互作用的影响
Ankit Balhara,Yik Pui Tsang,Jashvant D Unadkat
Ankit Balhara
Cannabidiol (CBD) or delta-9-tetrahydrocannabinol (THC) can inhibit multiple CYPs and UGTs in vivo and/or in vitro. CBD, but not THC, is also a time-dependent inhibitor of CYP3A, CYP1A2, and CYP2C19. We showed that a single 640 mg oral dose...
Physiologically based pharmacokinetic modeling of midostaurin and metabolites at steady-state to bridge drug interaction scenarios in lieu of clinical trials [0.03%]
基于生理的稳态菲达乌汀和代谢物药代动力学建模以在无法进行临床试验的情况下预测药物相互作用场景
Helen Gu,Romain Sechaud,Imad Hanna et al.
Helen Gu et al.
Midostaurin and its active metabolites are substrates, mixed inhibitors/inducers of cytochrome P450 (CYP)3A4. The main objective of this study was to develop/refine a physiologically based pharmacokinetic (PBPK) model that incorporated rece...
Identification and characterization of a novel ergothioneine conjugate of raloxifene [0.03%]
新型麦角硫宁Raloxifene结合物的鉴定与表征
Abhijith Rao,Sivaprasad Putluru,Prasanth Eapen et al.
Abhijith Rao et al.
Raloxifene (RX) in the presence of liver microsomes and glutathione (GSH) has shown oxidative bioactivation to reactive intermediates that are conjugated by GSH. L-Ergothioneine (ET) is a naturally occurring sulfhydryl amino acid, similar t...
Deciphering the cell type-specific and zonal distribution of drug-metabolizing enzymes, transporters, and transcription factors in livers of mice using single-cell transcriptomics [0.03%]
采用单细胞转录组学解码小鼠肝细胞类型特异性及区室分布的药物代谢酶、转运体和转录因子
Joe Jongpyo Lim,Curtis Dean Klaassen,Julia Yue Cui
Joe Jongpyo Lim
The liver contains multiple cell types, including resident cell types and immune cells. The liver is also categorized into 3 zones: periportal (zone 1), midzonal (zone 2), and centrilobular (zone 3). The goal of this study was to characteri...
Investigating the sexual dimorphism in isoproterenol-induced cardiac hypertrophy in Sprague Dawley rats [0.03%]
异丙肾上腺素诱导的大鼠心肌肥厚的性别差异研究
Sara A Helal,Samar H Gerges,Sareh Panahi et al.
Sara A Helal et al.
Distinct differences between sexes exist in various cardiovascular diseases. Moreover, there is a significant correlation between the pathogenesis of cardiac hypertrophy (CH) and the metabolites of arachidonic acid (AA) mediated by cytochro...