临床药物治疗杂志最新文献

{"title":"Multi-omics mendelian randomization identifies ferroptosis-related genetic variants linked to NAFLD risk","authors":"Xiao Liu, Huadi Zhou, Chenhan Shou, Weifeng Wu, Yizhong Bao, Ying Yuan, Jianjun Zhang, Yue Zhang, Xiaohu Yang, Zhen Wang","doi":"10.1016/j.prmedi.2025.100063","DOIUrl":"https://doi.org/10.1016/j.prmedi.2025.100063","url":null,"abstract":"Ferroptosis, an iron-dependent cell death, contributes to non-alcoholic fatty liver disease (NAFLD), but causal genes remain unclear. This study identifies ferroptosis-related genes driving NAFLD to fill this gap. Summary data-based Mendelian Randomization (SMR) analyzed 564 ferroptosis-related genes for causal links to NAFLD by integrating mQTL/eQTL/pQTL data with GWAS, validated in FinnGen and the GWAS Catalog. To further substantiate our findings, expression of lead candidate genes was validated in independent human liver tissue datasets from the Gene Expression Omnibus (GEO). HepG2 cells were used to assess candidate gene expression, oxidative stress, and ferroptosis under free fatty acids (FFA) treatment. We evaluated cell viability, lipid ROS levels, gene expression, protein levels, and oxidative stress markers. SMR analysis revealed an association between SLC2A6 methylation/expression and NAFLD risk. Hypermethylation at cg02257517 was associated with increased NAFLD risk (OR=1.032, 95 % CI=1.013–1.051), while higher SLC2A6 expression correlated with lower risk (OR=0.919, 95 % CI=0.87–0.97). Multi-omics analysis confirmed an inverse relationship between SLC2A6 expression and cg02257517 methylation (OR=0.741, 95 % CI=0.66–0.832), suggesting hypermethylation downregulates SLC2A6 , increasing NAFLD susceptibility. Those results were further validated in HepG2 cells, where the candidate gene demonstrated a protective role against FFA-induced oxidative stress and ferroptosis. Overexpression of the gene significantly mitigated these pathological effects, supporting its potential as a therapeutic target. Multi-omics Mendelian randomization identified SLC2A6 hypermethylation as a causal NAFLD risk factor by suppressing its expression. Functional validation in disease-relevant models revealed SLC2A6-mediated protection against oxidative stress and ferroptosis, highlighting its potential as a therapeutic target for NAFLD through epigenetic or gene-based interventions.","PeriodicalId":67256,"journal":{"name":"临床药物治疗杂志","volume":"2 4","pages":"100063-100063"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147912235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative multi-omics approach for drug repositioning in Alzheimer's disease","authors":"Jinna Yang, Kaimin Guo, Xiaxia Ren, Xiaolian Zhang, Shuang Zhao, Jiansong Fang, Wei Yu, Pengcheng Yang, Wenjia Wang, Hui Wang, Yunhui Hu","doi":"10.1016/j.prmedi.2025.100050","DOIUrl":"https://doi.org/10.1016/j.prmedi.2025.100050","url":null,"abstract":"Alzheimer's disease (AD) is a progressive neurodegenerative disorder with an insidious onset, and effective therapeutic agents are urgently needed. This study employed a multi-omics integration strategy for drug repurposing against AD. Firstly, transcriptomic and proteomic data from AD patients were utilized to identify differentially expressed genes. Potential anti-AD small-molecule compounds were screened by integrating the Reverse Gene Expression Score (RGES) and Connectivity Map (C-Map) approaches with drug-perturbed gene expression profiles from the Library of Integrated Network-Based Cellular Signatures (LINCS), followed by blood-brain barrier (BBB) permeability prediction and structural similarity analysis. Secondly, a drug-disease network was constructed, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. The therapeutic potential of candidate drugs was further evaluated via network proximity analysis. Finally, in vitro validation was conducted using Okadaic acid (OA) induced SH-SY5Y and Lipopolysaccharide (LPS) induced BV2 cell models to assess cell viability and nitric oxide (NO) levels. This integrated approach provides a novel framework for identifying repurposed drugs with potential efficacy against AD. Following the collection of omics data, 227 overlapping candidate compounds were identified through two computational approaches. After BBB prediction screening, 104 drugs were selected for subsequent structural similarity analysis and literature/patent review, ultimately leading to the selection of TNP-470 and Terreic acid for validation. Network pharmacology analysis revealed that potential targets of TNP-470 for AD treatment were significantly enriched in neuroactive ligand-receptor interaction, TNF signaling, and AD-related pathways, while anti-AD targets of Terreic acid primarily involved calcium signaling, AD pathway, and cAMP signaling. Network proximity analysis demonstrated significant associations between both candidates and AD. In vitro assays demonstrated that TNP-470 significantly enhanced the viability of OA-induced SH-SY5Y cells at concentrations of 10 μM and 50 μM ( p < 0.01 and p < 0.05, respectively). Additionally, within the concentration range of 0.016–10 μM, TNP-470 markedly inhibited NO production in the LPS-induced BV2 microglial cell model. Terreic acid also promoted the survival of OA-treated SH-SY5Y cells at concentrations ranging from 2 to 50 μM, and significantly reduced nitric oxide (NO) levels at a concentration of 10 μM. This drug repositioning strategy based on multi-omics integration provides a novel approach for AD therapeutic development, with both TNP-470 and Terreic acid demonstrating anti-AD potential.","PeriodicalId":67256,"journal":{"name":"临床药物治疗杂志","volume":"1 1","pages":"100050-100050"},"PeriodicalIF":0.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147881230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Simultaneous determination of concentration of sulfamethoxazole and trimethoprim in human plasma by dual-quaternary HPLC and its clinical application","authors":"Li Nong, Yunxia Tang, Xiaoning Qin, Zhou Zhou, Zongqiang Lai, WenXing Wei, Wenwen Tan","doi":"10.1016/j.prmedi.2025.100017","DOIUrl":"https://doi.org/10.1016/j.prmedi.2025.100017","url":null,"abstract":"Sulfamethoxazole compound, a combination of sulfamethoxazole and trimethoprim, is commonly prescribed to organ transplant recipients for infections caused by Nocardia , Burkholderia cepacia , and Pneumocystis jirovecii . The intricate pharmacokinetics and pharmacodynamics of this compound pose challenges in achieving optimal therapeutic drug levels. Therefore, monitoring the plasma concentration of this compound drug is necessary. To address this need, we have developed a rapid and straightforward dual-quaternary two-dimensional high-performance liquid chromatography (2D-HPLC) method for the simultaneous quantification of sulfamethoxazole and trimethoprim. This technique involves a one-step protein precipitation procedure, with the initial stage utilizing a solid-phase extraction column followed by an analytical column for the subsequent stage. Detection is achieved using a dual-quaternary 2D-HPLC system. Calibration curves for both sulfamethoxazole and trimethoprim were constructed, and the method underwent thorough validation in accordance with the Chinese Pharmacopoeia (Ch.P) standards, demonstrating remarkable accuracy and precision. This technique has been effectively employed for routine therapeutic drug monitoring (TDM) in organ transplant patients and other individuals requiring medical intervention.","PeriodicalId":67256,"journal":{"name":"临床药物治疗杂志","volume":"1 2","pages":"100017-100017"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147878999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}