The cytochrome P450 3A (CYP3A) gene family’s role in early progression of gastric cancer was comprehensively investigated. Its potential as a therapeutic target was evaluated. Upon literature review, aberrant expression of the CYP3A gene family has a strong correlation with gastric cancer onset, although the precise underlying mechanisms remain unclear. To assess its potential as a biomarker for early diagnosis and a therapeutic target, we have provided a comprehensive review of the regulatory mechanisms governing CYP3A gene family expression in gastric cancer, as well as its relation with early tumor progression and the tumor microenvironment. The CYP3A gene family is crucial in the proliferation, migration, and invasion of gastric cancer cells and promotes cancer progression by modulating inflammatory responses and oxidative stress within the tumor microenvironment. Furthermore, genetic polymorphisms in CYP3Aenzymes highlight its potential value in personalized medicine. Based on these findings, this paper explores the feasibility of developing inhibitors and activators targeting CYP3A enzymes and discusses potential applications in gene therapy. This research provides crucial theoretical support for the CYP3A gene family as an early diagnostic marker and therapeutic target for gastric cancer. In the future, multi-omics studies and large-scale clinical trials will be essential to advance clinical translation of these findings.

• Gastric cancer
• Cytochrome P450 3A
• Early diagnosis
• Therapeutic target
• Precision medicine

• Anti-Epileptic drugs
• Drug resistance
• Gut microbiome
• Gut–brain axis
• Ketogenic diet
• Neuronal excitability
• Refractory epilepsy
• Sleep

• epilepsy
• ethics
• low-middle-income-countries
• research
• sustainable collaborations

Thermodynamic investigations provide information about the solute-solvent interactions in the selection of the proper solvent for different fields of pharmaceutical sciences. Especially, the study of antiepileptic drugs in solutions (ethanol/co-solvent) has been a subject of interest owing to their effect in the systems using interaction with a number of important biological membranes. This work focuses on the measurement of density and speed of sound of the phenytoin (PTH) in ethanol/deep eutectic solvents (choline chloride:ethylene glycol, and choline chloride:glycerol) solutions as the innovative class of green solvents at temperature range (288.15 to 318.15) K. It was determined Hansen solubility parameters for assessment of PTH interactions in the solvent media. Some thermophysical parameters including apparent molar volumes Vϕ, apparent molar isobaric expansion \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$E_\varphi^0$$\end{document}Eφ0, and Hepler’s constant, apparent molar isentropic compressibility κ_φ were obtained and calculated using these data. To correlate  the Vϕ and κ_φ values, the Redlich-Meyer equation was used to calculate the number of quantities containing standard partial molar volume and partial molar isentropic compressibility. Finally, \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\Delta \delta$$\end{document}Δδ values showed a strong interaction between PTH and solvent (ethanol/DES (ChCl:EG)). The thermodynamic analysis of the studied system also plays a crucial role in the pharmaceutical industry.

• Antiepileptic drugs
• drug combinations
• epilepsy
• pharmacoresistance
• seizures

• Drug resistance
• Experimental models
• Hypotheses

• CYP2C19
• CYP2C9
• meta-analysis
• pharmacokinetic parameters
• phenytoin
• polymorphism

• ATP-binding cassette efflux transporters
• Epilepsy
• Meta-analysis
• Polymorphism

• dolutegravir
• drug interaction
• efavirenz
• implementation research

• evidence-based medicine
• neurology
• pharmacogenetics
• psychiatry
• systematic review

We aimed to systematically examine the effects of enzymatic activity of 38 human CYP2C9 alleles and 21 human CYP3A4 alleles, including wild-type CYP2C9.1 and CYP3A4.1, which contain the 24 CYP2C9 novel alleles (*36–*60) and 6 CYP3A4 novel alleles (*28–*34) newly found in the Chinese population, on sildenafil metabolism through in vitro experiment.

The recombinant cytochrome P450 alleles protein of CYP2C9 and CYP3A4 expressed in insect baculovirus expression system were reacted with 10–500 µM sildenafil for 30 minutes at 37°C, and the reaction was terminated by cooling to −80°C immediately. Next, we used ultra-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) detection system to detect sildenafil and its active metabolite N-desmethyl sildenafil.

The intrinsic clearance (Vmax/Km) values of most CYP2C9 variants were significantly altered when compared with the wild-type CYP2C9*1, with most of these variants exhibiting either reduced Vmax and/or increased Km values. Four alleles (CYP2C9*11, *14, *31, *49) exhibited no markedly decreased relative clearance (1-fold). The relative clearance of the remaining thirty-three variants exhibited decrease in different levels, ranging from 1.81% to 88.42%. For the CYP3A4 metabolic pathway, when compared with the wild-type CYP3A4*1, the relative clearance values of four variants (CYP3A4*3, *10, *14 and *I335T) showed significantly higher relative clearance (130.7–134.9%), while five variants (CYP3A4*2, *5, *24, *L22V and *F113I) exhibited sharply reduced relative clearance values (1.80–74.25%), and the remaining nine allelic variants showed no statistical difference. In addition, the kinetic parameters of two CYP3A4 variants (CYP3A4*17 and CYP3A4*30) could not be detected, due to the defect of the CYP3A4 gene.

These findings were the first evaluation of all these infrequent CYP2C9 and CYP3A4 alleles for sildenafil metabolism; when treating people who carry these CYP2C9 and CYP3A4 variants, there should be more focus on the relation of dose intensity, side effects and therapeutic efficacy when administering sildenafil. The study will provide fundamental data on effect of CYP2C9 and CYP3A4 allelic variation on sildenafil metabolism for further clinical research.

• CYP2C9 polymorphisms
• CYP3A4 polymorphisms
• allelic variants
• enzymatic activity
• individual treatment
• sildenafil

• CYP2
• Drug-resistant epilepsy
• gene
• polymorphism

• Arab
• Jewish
• human leukocyte antigens
• hypersensitivity reactions

• Alleles
• Arabs/genetics
• Drug Discovery
• Gene Frequency
• Genetic Variation
• HLA Antigens/genetics
• Haplotypes
• Humans
• Hypersensitivity, Delayed/genetics
• Jews/genetics

• CYP2C9
• adverse effects
• antiepileptics
• cytochrome P450
• epilepsy
• phenytoin
• polymorphisms