Current medicinal chemistry最新文献

{"title":"Toxic Mechanisms Underlying Prostate Cancer Induction by Water Pollutants: Based on Network Toxicology, Molecular Docking, and Molecular Dynamics Simulations.","authors":"Tao Zheng, Xiao Lin, Chuandong Song, Bin Yang","doi":"10.2174/0109298673447968260721033454","DOIUrl":"https://doi.org/10.2174/0109298673447968260721033454","url":null,"abstract":"<p><strong>Introduction: </strong>Addressing water pollutants remains a key priority in contemporary environmental governance, as waterborne pollutants pose significant risks to human health. We focus on four major classes of environmentally persistent water pollutants, namely volatile organic compounds (VOCs), polycyclic aromatic hydrocarbons (PAHs), organochlorine pesticides (OCPs), and polybrominated diphenyl ethers (PBDEs), due to their widespread occurrence and potential carcinogenicity. Integrating network toxicology, molecular docking, and molecular dynamics simulations, this study elucidates the molecular mechanisms by which these pollutants may contribute to prostate carcinogenesis.</p><p><strong>Methods: </strong>We initially employed ProTox-3.0 and ADMETLAB 3.0 to predict the toxicity of the selected water pollutants. Potential targets for compounds representing four major classes of water pollutants were retrieved from the ChEMBL and SwissTargetPrediction databases. Disease genes related to prostate cancer were collected from the GeneCards, OMIM, and TTD databases. Utilizing the STRING database and Cytoscape software, a molecular regulatory network of toxicological targets and a protein-protein interaction (PPI) network associated with water pollutant-induced prostate cancer were constructed. Then, core genes were screened. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed, followed by molecular docking. Finally, molecular dynamics (MD) simulations were conducted based on the molecular docking results.</p><p><strong>Results: </strong>Enrichment analysis revealed that multiple pathways associated with water pollutant exposure were significantly enriched among prostate cancer-related genes, indicating a potential link between pollutant carcinogenicity and prostate carcinogenesis. Molecular docking results indicated that 80 % of the 75 tested protein-ligand complexes exhibited binding energies lower than -5.0 kcal/mol. MD simulation results demonstrated that all four selected protein-ligand complexes maintained remarkable structural stability throughout the simulation trajectory.</p><p><strong>Discussion: </strong>The integration of network toxicology, molecular docking, and MD simulations in this study provides a systematic framework for deciphering the molecular toxicological mechanisms by which water pollutants contribute to the development of prostate cancer. By integrating target information from multiple authoritative databases, we identified five core targets (TP53, EGFR, MYC, STAT3, and TNF) that play pivotal roles in mediating the carcinogenic effects of water pollutants. These targets offer key molecular anchors for understanding the pathogenic link between water pollution and prostate cancer. GO and KEGG enrichment analyses further elucidated the critical biological processes and signaling pathways involved (including the hypoxic response and the PI3K-Akt sig","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phytochemical-Chemotherapeutic Interactions in Gastrointestinal Cancers: Synergistic Mechanisms, Pharmacokinetic Barriers, and Translational Challenges.","authors":"Mojtaba Tarin, Mahsa Akbari Oryani, Mahsa Attarian, Hossein Javid, Ali Mehri, Mehdi Karimi-Shahri","doi":"10.2174/0109298673452684260721061102","DOIUrl":"https://doi.org/10.2174/0109298673452684260721061102","url":null,"abstract":"<p><p>Phytochemicals have garnered substantial interest as potential adjuncts to standard chemotherapy, particularly in gastrointestinal (GI) cancers, owing to their ability to modulate cancer-associated signaling pathways and potentially improve chemosensitivity. In this review, we critically examine preclinical findings alongside early-phase clinical data addressing phyto-chemotherapeutic interactions, with emphasis on widely investigated agents such as curcumin, epigallocatechin gallate (EGCG), resveratrol, quercetin, berberine, thymoquinone, and triptolide. We review the proposed mechanisms in support of synergy, including modulation of apoptosis, oxidative stress responses, cell-cycle progression, and survival signaling pathways, while also addressing major translational obstacles that continue to limit clinical success. Major translational barriers include poor oral bioavailability, rapid metabolic degradation, uncertain dose-response relationships, interindividual pharmacogenomic variability, and medicinal chemistry concerns such as PAINS-related behavior and target promiscuity. Particular attention is given to the discrepancy between robust in vitro findings and the often modest or inconsistent outcomes reported in clinical settings to avoid overstating therapeutic efficacy. Available clinical data remains heterogeneous and largely derived from small-scale or regional studies, underscoring the need for rigorously designed clinical trials using standardized formulations with pharmacokinetic profiling and strict safety assessment. This review highlights mechanistic insights together with pharmacokinetic and drug-likeness considerations in order to clarify why many phytochemicals demonstrating promising preclinical activity ultimately fail to progress into approved anticancer therapies.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Integrated Multi-Omics and Causal Inference Study Identifies a DNA Repair-Related Prognostic Biomarker in Gastric Cancer.","authors":"Jianhua Yang, Zheng Qiu, Wenchao Song, Xing Liu, Jinghui Wang, Yinfeng Yang","doi":"10.2174/0109298673490992260707001109","DOIUrl":"https://doi.org/10.2174/0109298673490992260707001109","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to identify biologically relevant genes associated with DNA repair pathways in gastric cancer (GC) by integrating multi-omics analyses with causal inference approaches.</p><p><strong>Methods: </strong>Public GC datasets were integrated to identify consensus differentially expressed genes (DEGs). Candidate genes were screened using WGCNA and intersected with DEGs. Key genes were selected via the machine learning algorithm Lasso+plsRglm and validated by the Area Under the Receiver Operating Characteristic Curve (AUC) analysis. The Protein-Protein Interaction (PPI) network determines the hub genes associated with GC. Single-cell RNA sequencing characterized the cell-type-specific gene expression. Kaplan-Meier analysis assessed the prognostic relevance. Immune infiltration was evaluated using CIBERSORT and ESTIMATE algorithms. Mendelian Randomization (MR) examined causal relationships among BRCA1, NADPH, and GC risk. Experimental validation was performed using qRT-PCR and Western blot in GC cell lines and clinical samples.</p><p><strong>Results: </strong>Five hub genes, i.e., BRCA1, CCNA2, CHEK1, KIF14, and KIF15, predominantly enriched in mesenchymal stem cells and fibroblasts, were identified. BRCA1 was consistently overexpressed in GC and associated with improved survival and enhanced antitumor immune activity. MR analysis suggested indirect associations between BRCA1, NAD(P)H metabolism, and GC risk, without a direct causal effect. Experimental results confirmed significant overexpression of BRCA1 at both mRNA and protein levels in GC.</p><p><strong>Discussion: </strong>These findings suggest that BRCA1 is not an independent prognostic factor but reflects broader tumor biological processes, particularly DNA repair and redox regulation. Its upregulation likely represents a compensatory response to genomic instability. The identified BRCA1-NAD(P)H axis highlights a potential mechanistic link between DNA repair and metabolic regulation, underscoring its relevance in tumor progression and therapeutic targeting.</p><p><strong>Conclusion: </strong>This study reveals a regulatory link between DNA repair, redox metabolism and GC progression, positioning BRCA1 as a key component of tumor biology and a potential target for precision oncology strategies.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148705847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Green Synthesis of PVA-Stabilized Gold Nanoparticles from Aloe vera: Physicochemical Characterization and Biocompatibility Under Mild UV Exposure.","authors":"Yandi Syukri, Hannie Fitriani, Fia Nur Halimah, Bambang Hernawan Nugroho, Sista Werdyani, Muhammad Taher, Ganjar Fadillah","doi":"10.2174/0109298673458372260721064432","DOIUrl":"https://doi.org/10.2174/0109298673458372260721064432","url":null,"abstract":"<p><strong>Background: </strong>Aloe vera is widely used for dermatological applications due to its bioactive phenolic compounds, including aloin, aloesin, aloe-emodin, and tannins. Gold nanoparticles (AuNPs) have pharmacological properties such as antioxidant and antibacterial activities and may enhance skin elasticity.</p><p><strong>Objective: </strong>This study developed polyvinyl alcohol (PVA) stabilized gold nanoparticles from Aloe vera extract and evaluated their physicochemical properties, preliminary stability, and in vitro biocompatibility under mild UV exposure.</p><p><strong>Methods: </strong>Gold nanoparticles were biosynthesized by reacting Aloe vera extract with 1 mM chloroauric acid (HAuCl4) in the presence of PVA. The formulations were characterized by UV-Vis spectroscopy, particle size and polydispersity index (PDI), TEM, SEM-EDS, and FTIR. The optimized formulation was further evaluated in a preliminary accelerated stability study and tested for cytotoxicity in B16F10 melanoma cells using the MTT assay under mild UVA and UVB exposure.</p><p><strong>Results: </strong>Formula 4 was selected as the optimized formulation after preliminary screening, showing stable dispersion without visible aggregation, a particle size of 101.40 ± 1.51 nm, and a PDI of 0.24 ± 0.06. After optimization, this formulation was subjected to accelerated stability testing, with Day-1 particle size and PDI values of 107.00 ± 1.11 nm and 0.25 ± 0.04, respectively. During accelerated storage, the particle size remained within the nanoscale range. Cytotoxicity testing showed that NGA was non-cytotoxic toward B16F10 melanoma cells, with an IC50 value of 2873.20 μg/mL. Under the mild UVA and UVB conditions used in this study, treated cells also maintained high viability.</p><p><strong>Conclusion: </strong>PVA-stabilized gold nanoparticles synthesized from Aloe vera showed favorable physicochemical properties, preliminary storage stability, and low in vitro cytotoxicity. Under the mild UV exposure conditions applied in this study, NGA remained biocompatible; however, the present findings do not yet establish a definitive photoprotective effect. Further studies using stronger irradiation settings and appropriate positive controls are required.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148705857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Construction and Validation of an Early Diagnosis Model for Atherosclerosis Based on Lactate Metabolism-related Genes.","authors":"Xiaoying Wang, Xiumin Hou, Hang Yu, Shaoshen Wang, Xinxin Yang","doi":"10.2174/0109298673437096260529220743","DOIUrl":"https://doi.org/10.2174/0109298673437096260529220743","url":null,"abstract":"<p><strong>Introduction/objective: </strong>Atherosclerosis (AS), a chronic inflammatory disease characterized by arterial plaque formation, remains a leading global cause of cardiovascular mortality; however, the molecular pathways that contribute to AS, particularly the role of lactate metabolism-related genes (LMRGs), remain poorly understood. This study aims to identify novel biomarkers and diagnostic models for early AS diagnosis by examining LMRGs.</p><p><strong>Methods: </strong>The AS datasets GSE100927, GSE40231, and GSE28829 were acquired from the Gene Expression Omnibus (GEO) database. Using bioinformatics approaches, including differential gene expression, functional enrichment, gene set enrichment analysis, random forest algorithm, Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis, and immune infiltration profiling, we analyzed integrated AS datasets, developed a diagnostic model using key LMRGs, and validated this model through quantitative polymerase chain reaction (qPCR) using clinical AS samples.</p><p><strong>Results: </strong>We identified 15 differentially expressed LMRGs (LMRDEGs) and developed a LASSO regression model with five genes predictive of AS. The diagnostic model achieved high accuracy (area under the curve (AUC) > 0.9). Functional enrichment indicated that LMRDEGs play roles in lactate metabolism, small molecule catabolism, and pathways such as HIF-1 signaling and glycolysis/gluconeogenesis. Immune-cell infiltration analysis further indicated notable immune-cell variations across risk categories, with activated B cells, CD4+ T cells, and natural killer T cells exhibiting strong positive correlations. Clinical validation via qPCR confirmed significant expression differences for two genes (DISC1 and PIK3C2A), achieving AUCs of 0.730 and 0.758 and supporting the model's clinical relevance.</p><p><strong>Discussion: </strong>This study demonstrates that LMRGs are critically involved in the pathogenesis of AS, providing a novel molecular framework for early diagnosis and mechanistic insight. Functional analyses underscore the role of lactate-driven metabolic reprogramming in linking immune inflammation to plaque instability. Furthermore, immune infiltration analysis indicates that LMRGs may regulate immune cell recruitment, further supporting the \"metabolism-inflammation\" cycle concept in AS. Clinical validation confirms the differential expression and diagnostic value of DISC1 and PIK3C2A, reinforcing their relevance in human AS pathology.</p><p><strong>Conclusion: </strong>This study highlights potential diagnostic biomarkers for early-stage AS. The results also imply that lactate metabolism-related pathways are intertwined with inflammatory and immune responses, offering new insights into AS mechanisms.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148705875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Osteoblast-Derived HIF-1α Drives Compartment-Specific H-Type Angiogenesis in Knee Osteoarthritis via VEGFA Signaling.","authors":"Bo Chen, Jibing Wang, Xing Jin, Zhaoxiang Meng, Mohamad Ikhwan Bin Jamaludin","doi":"10.2174/0109298673501087260720094335","DOIUrl":"https://doi.org/10.2174/0109298673501087260720094335","url":null,"abstract":"<p><strong>Introduction: </strong>Pathological H-type angiogenesis in medial subchondral bone plays a critical role in Knee Osteoarthritis (KOA); however, the cellular crosstalk remains unclear. We investigated whether osteoblast-derived hypoxia-inducible factor-1 alpha (HIF-1α) drives medial vascular remodeling via vascular Endothelial Growth Factor A (VEGFA) paracrine signaling to Endothelial Cells (ECs).</p><p><strong>Methods: </strong>The bulk and single-cell RNA sequencing (scRNA-seq) data for KOA and control samples were collected from the Gene Expression Omnibus (GEO) databases. Differential expression analysis was performed using the limma R package. scRNA-seq analysis was performed using the Seurat package, HIF-1α activity was scored by AUCell, and cell-cell communication was inferred using CellChat. An osteoblast-EC Transwell co-culture system was established to explore the role of osteoblast-derived HIF-1α in regulating endothelial function under inflammatory conditions. After HIF-1α knockdown in osteoblasts, we performed quantitative Polymerase Chain Reaction (qPCR) and Western blotting, and assessed tube formation ability.</p><p><strong>Results: </strong>Integrated bulk RNA-seq analysis revealed significant upregulation of HIF-1α signaling and Extracellular Matrix (ECM)-related pathways in medial subchondral bone of KOA patients. scRNA-seq analysis further revealed distinct osteoblast and endothelial cell populations in the medial compartment, with AUCell scoring confirming higher HIF-1α pathway activity in medial osteoblasts. CellChat analysis computationally inferred VEGF-mediated macrophage-EC communication, including VEGFA-VEGFR2 and VEGFB-VEGFR1 interactions. In functional validation, HIF-1α knockdown in osteoblasts reduced VEGFA expression, attenuated the levels of H-type vessel markers CD31 and EMCN in ECs, and impaired capillary tube formation.</p><p><strong>Discussion: </strong>This study revealed a compartment-specific HIF-1α signaling that drove KOA pathological angiogenesis in medial subchondral bone via an osteoblast-endothelial feed-forward axis, providing a targeted therapeutic strategy.</p><p><strong>Conclusion: </strong>The findings suggest that osteoblast-derived HIF-1α drives compartment-specific H-type angiogenesis in KOA via VEGFA-dependent endothelial activation, highlighting the osteoblast-endothelial axis as a therapeutic target.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148705223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Potential Therapeutic Targets and Drugs for Depression: A Genome-Wide Druggable Mendelian Randomization and Molecular Docking Study.","authors":"Zehua Luo, Jiaqian Ma, Fan Wu, Tingting Li, Changlan Gao, Mei Sun, Qian Du, Songqing Liu, Wenjun Li","doi":"10.2174/0109298673458126260715114327","DOIUrl":"https://doi.org/10.2174/0109298673458126260715114327","url":null,"abstract":"<p><strong>Introduction: </strong>Depression is a common and complex mental health condition. It is shaped by many genetic, environmental, and social factors that influence when it starts and how it progresses. The main biological changes behind depression are still not well understood. Current treatments help some patients, but many only experience partial or unstable benefits. There is a clear need for treatments that are both more effective and more precise for depression. In this study, up-to-date genetic and pharmacogenomic data were used to identify genes targeted by drugs and potential therapy targets for depression. Information from several independent resources was brought together, and these datasets were combined in a stepwise way. With this strategy, the aim was to provide a practical starting point for the development of more targeted antidepressant therapies.</p><p><strong>Methods: </strong>Cross-tissue expression quantitative trait loci (eQTL) were first used to analyze data, and these data were combined with Genome-Wide Association Study (GWAS) summary statistics for depression. Then Mendelian Randomization (MR) was applied to identify candidate druggable genes. Colocalization analyses were also performed to check whether the eQTL and depression signals were likely to share the same causal variants. To further assess biological and therapeutic relevance, Phenome-Wide Association Studies (PheWAS), functional enrichment analyses, computational drug prediction, molecular docking, and molecular dynamics simulations were carried out.</p><p><strong>Results: </strong>Using Mendelian randomization, 34 blood-derived genes and 25 brain-derived genes were identified that showed evidence of association with depression. Colocalization further supported causal roles for 23 blood-and 14 brain-derived genes, with SNRK, MANF, and P4HTM showing significant signals in both tissues. Enrichment analyses implicated immune-related pathways. Docking and dynamics confirmed stable binding between key targets and compounds such as quercetagetin and myricetin.</p><p><strong>Discussion: </strong>In this study, 34 potential druggable targets for depression were found, with SNRK, MANF, and P4HTM showing consistent importance across tissues. In addition, quercetagetin and myricetin emerged as promising candidates for depression therapy.</p><p><strong>Conclusion: </strong>These findings provide new therapeutic candidates and help establish a mechanistic framework for the development of targeted antidepressants.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148705792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating Network Pharmacology, Bioinformatics, Transcriptome Sequencing, And Experiments To Explore Mechanisms of Danggui Shaoyao San Against Breast Cancer.","authors":"Jing Wang, Li Zhang, Ying Yu, Yuting Lei, Jingliang Wei, Haixiong Lin, Lifang Li","doi":"10.2174/0109298673476479260630105807","DOIUrl":"https://doi.org/10.2174/0109298673476479260630105807","url":null,"abstract":"<p><strong>Introduction/objective: </strong>Breast cancer is one of the most common malignant tumors in women worldwide, and Danggui Shaoyao San (DGSY San) is commonly used in the clinical treatment of breast cancer.</p><p><strong>Methods: </strong>This study integrates UHPLC-QE-MS/MS, network pharmacology, transcriptomics, and in vitro experiments to explore the mechanism of DGSY San's anti-breast cancer effects.</p><p><strong>Results: </strong>Mass spectrometry identified 70 active ingredients. Network analysis predicted that it regulates apoptosis and proliferation through the MAPK pathway. in vitro experiments showed that DGSY San inhibited the proliferation, migration, and invasion of MCF-7 cells in a concentration-dependent manner and induced G2-phase arrest and apoptosis. Transcriptome sequencing and comprehensive analyses of network pharmacology and clinical databases simultaneously confirmed enrichment of the MAPK pathway. Western blot confirmed that it downregulated p-p38 and p-ERK phosphorylation and promoted the expression of apoptosis-related proteins.</p><p><strong>Discussion: </strong>The results indicate that DGSY San inhibits breast cancer proliferation and induces apoptosis through the MAPK pathway.</p><p><strong>Conclusion: </strong>This study developed a multidimensional, integrated analysis model of \"components-transcriptome-clinical data\" to systematically elucidate the mechanisms underlying TCM prescriptions.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148705845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Construction and Validation of a Ubiquitination-Related Gene Signature Based on WGCNA and Single-cell RNA Sequencing in Bladder Cancer.","authors":"Zhibiao Li, Ting Yan, Chuxian Hu, Zechao Lu, Jiahao Zhang, Xiujun Wu, Yushu Chen, Zhicheng Tang, Hanxiong Zheng, Zhaohui He, Fucai Tang","doi":"10.2174/0109298673470246260702000813","DOIUrl":"https://doi.org/10.2174/0109298673470246260702000813","url":null,"abstract":"<p><strong>Background: </strong>The potential pathogenesis and reliable biomarkers of Bladder cancer (BC) remain to be explored. Ubiquitination plays a crucial role in BC progression, warranting the necessity to develop prognostic gene signatures.</p><p><strong>Methods: </strong>By integrating weighted gene co-expression network analysis (WGCNA) and single-cell RNA sequencing (scRNA-seq), we identified the genes related to the single-- cell ubiquitination activity. A prognostic gene signature was established using univariate Cox analysis, LASSO analysis, and multivariate Cox analysis. BC patients were stratified into high-risk and low-risk groups according to the median risk score. The nomogram was constructed and validated. Potential biological processes of common ubiquitination-related genes anisk groups were explored. The immune infiltration, immunotherapy response, and drug sensitivity were evaluated.</p><p><strong>Results: </strong>A six-gene signature comprising CAPG, EMP3, GMFG, HLA-B, ID1, and TNFRSF12A stratified patients into high-risk and low-risk groups with significantly different overall survival. In the training group, the area under the curve was 0.695 at 1 year, 0.725 at 3 years, and 0.739 at 5 years. The high-risk group generally showed worse overall survival compared to the low-risk group. The nomogram model showed satisfactory predictive performance. Significant differences in immune cell proportions were observed in different risk groups. The low-risk group exhibited higher Immune scores and Stromal scores and showed better survival outcomes following PD-L1 immunotherapy. Doxorubicin, Gemcitabine, Methotrexate, and Vinblastine exhibited significantly lower IC50 values in the low-risk group.</p><p><strong>Conclusion: </strong>The six-gene ubiquitination-related signature may provide a valuable reference for potential therapeutic targets and prognosis of BC. However, prospective and experimental validation is still required.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148705826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Therapeutic Effects and Mechanisms of Core Component from Taraxacum on Alcoholic Liver Disease by Integrating UPLC-QE-MS, Network Pharmacology, and Animal Experiments.","authors":"Mingyu Liu, Changqing Qin, Chuanguo Liu, Wenshu Feng, Ting Gui, Xuefang Kou","doi":"10.2174/0109298673450704260317064501","DOIUrl":"https://doi.org/10.2174/0109298673450704260317064501","url":null,"abstract":"<p><strong>Introduction: </strong>The global prevalence of Alcoholic Liver Disease (ALD) is rising, presenting a significant public health challenge. Taraxacum, a medicinal-food homologous plant, demonstrates hepatoprotective properties, yet its mechanisms remain unclear. This study aimed to identify the core bioactive components of Taraxacum and validate their mechanisms and therapeutic efficacy in ALD mice.</p><p><strong>Methods: </strong>In this study, comprehensive compositional analysis of Taraxacum was performed utilizing ultra-performance liquid chromatography coupled with UPLC-QE-MS. Active components of Taraxacum and their associated targets relevant to ALD were identified through integration of public databases. Subsequently, a Protein-Protein Interaction (PPI) network and a \"Drug-components-targets\" network were constructed. Key targets and key bioactive components were screened from these networks. The core component was further determined via molecular docking simulations, and its therapeutic efficacy was evaluated in the ALD mouse model by examining pertinent biochemical markers and conducting histopathological examination.</p><p><strong>Results: </strong>50 chemical components were identified from Taraxacum using UPLC-QE-MS analysis, with organic acids and flavonoids predominating. Subsequent screening via network pharmacology yielded 10 key components and 9 key targets, predominantly associated with inflammatory pathways. GO and KEGG enrichment analyses indicated significant involvement of oxidative stress responses and the HIF-1 signaling pathway, among others. Molecular docking results suggested that isorhamnetin may represent the primary active constituent against ALD, exhibiting the strongest binding affinity with MAPK3. An experiment in mouse models of alcohol-induced liver injury demonstrated that isorhamnetin significantly reduced the activities of hepatic injury markers, attenuated histopathological damage and the release of pro-inflammatory cytokines, while concurrently inhibiting oxidative stress and protecting hepatocytes.</p><p><strong>Discussion: </strong>Taraxacum therapy for ALD has the advantage of multi-component, multi-- target, and multi-pathway synergistic regulation. Comprehensive analysis demonstrated that its core component, isorhamnetin, alleviates ALD through synergistic multi-pathway mechanisms involving metabolic regulation, antioxidant defense, and anti-inflammatory effects.</p><p><strong>Conclusion: </strong>This study systematically characterized the bioactive components of Taraxacum, elucidating the therapeutic efficacy of the core component, isorhamnetin, against ALD. These findings provide a scientific foundation for the development of plant- derived therapeutics targeting ALD.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148705818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}