Current medicinal chemistry最新文献

{"title":"A Combined Network Toxicology and Docking Study to Identify Putative Molecular Targets Linking Styrene Exposure to Atherosclerosis.","authors":"Shuai Yan, Geng Shen, Yu-Qing Huang, Guo-Dong He","doi":"10.2174/0109298673522628261007063935","DOIUrl":"https://doi.org/10.2174/0109298673522628261007063935","url":null,"abstract":"<p><strong>Background: </strong>Styrene is a ubiquitous volatile organic compound linked to hematologic and vascular alterations; however, the molecular mechanisms connecting exposure to atherosclerosis remain poorly characterized.</p><p><strong>Methods: </strong>We integrated peripheral blood mononuclear cell transcriptomic profiles (GSE23746) with toxicogenomic data from the Comparative Toxicogenomics Database, applying support vector machine recursive feature elimination and least absolute shrinkage and selection operator machine learning algorithms to identify core targets at the styrene-atherosclerosis intersection. Immune infiltration was assessed using CIBERSORT and single-sample gene set enrichment analysis, and molecular docking evaluated binding potential.</p><p><strong>Results: </strong>Four model genes-CCND3, CCR1, MYC, and MYD88-were identified and constituted a diagnostic signature with high accuracy (area under the curve > 0.9). These genes were enriched in IL-17 and NF-κB inflammatory pathways and correlated with distinct immune cell alterations, particularly neutrophils and T cell subsets. Molecular docking predicted direct, moderate-affinity binding of styrene to CCND3 (Vina score = -6.4 kcal/mol), involving multiple contacts within the cyclin domain.</p><p><strong>Discussion: </strong>The convergence of transcriptomic screening and molecular docking identifies CCND3 as a putative target for styrene-protein interaction and suggests a mechanistic hypothesis linking styrene to atherosclerosis via inflammatory and immune dysregulation. The computational framework provides a basis for future experimental validation.</p><p><strong>Conclusion: </strong>This computational framework generates the hypothesis that styrene may contribute to atherosclerosis through coordinated perturbations of immune signaling and cell cycle regulation, with CCND3 representing a candidate molecular target for future experimental validation in styrene-exposed populations.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179925","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 Cuproptosis-Related Genes and Immunological Roles in Steroid-Induced Osteonecrosis of the Femoral Head.","authors":"Jinyuan Zeng, Juncheng Li, Ruan Chen, Xinyu Fang, Wenming Zhang","doi":"10.2174/0109298673490905261006061550","DOIUrl":"https://doi.org/10.2174/0109298673490905261006061550","url":null,"abstract":"<p><strong>Objective: </strong>Steroid-induced Osteonecrosis of the Femoral Head (SONFH) is a disabling disorder arising from chronic glucocorticoid exposure. Cuproptosis, a copper- dependent form of cell death, has been implicated in various diseases, but its role in SONFH remains unclear. This study aimed to characterize cuproptosis-related molecular subtypes and develop a predictive model for SONFH.</p><p><strong>Methods: </strong>Using the GSE123568 cohort (30 SONFH cases, 10 controls), we analyzed Differentially Expressed Cuproptosis-related Genes (DE-CRGs) and immune infiltration via CIBERSORT. Unsupervised clustering and Weighted Gene Coexpression Network Analysis (WGCNA) identified molecular subtypes and module genes. Three machine learning models (Random Forest (RF), Generalized Linear Models (GLMs), Support Vector Machines (SVMs)) were compared; the RF model was validated using a nomogram, calibration, decision curve analysis, and the GSE74089 cohort. Target genes were confirmed by immunohistochemistry on clinical femoral head tissue.</p><p><strong>Results: </strong>NLRP3, NFE2L2, and PDHB were differentially expressed in SONFH and confirmed by immunohistochemistry. Two molecular clusters with distinct immune infiltration profiles were identified. The RF model performed best (AUC = 0.889), and five predictive genes-KCNE3, SOD1, ACAP1, ALDH2, and ITGAL-were selected. The nomogram demonstrated high predictive accuracy in external validation.</p><p><strong>Discussion: </strong>These findings reveal the potential role of cuproptosis-related genes in SONFH pathogenesis and immune regulation, providing biomarkers for molecular subtyping and risk prediction.</p><p><strong>Conclusion: </strong>NLRP3, NFE2L2, and PDHB are key modulators of SONFH pathogenesis, and the 5-gene RF-based nomogram offers a novel, effective diagnostic approach for clinical application.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179998","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":"Genetic Evidence for the Associations of Alcohol Intake Frequency and Dietary Salt Intake with Non-Alcoholic Fatty Liver Disease Risk and Hepatic Steatosis: A Mendelian Randomization Study.","authors":"Yongxin Ma, Jiawei Wang, Zhenyao Tan, Xin Ma, Bendong Chen, Yang Bu","doi":"10.2174/0109298673487454260921063434","DOIUrl":"https://doi.org/10.2174/0109298673487454260921063434","url":null,"abstract":"<p><strong>Objective: </strong>Non-Alcoholic Fatty Liver Disease (NAFLD) poses a significant global health burden, yet causal relationships with modifiable dietary factors remain incompletely defined. This Mendelian Randomization (MR) study evaluated the causal associations between dietary exposures and NAFLD risk, as well as related hepatic traits.</p><p><strong>Methods: </strong>We performed univariable, Bayesian Weighted MR (BWMR), and Multivariable MR (MVMR) analyses using genetic variants as instrumental variables. Data from 335,394 to 462,630 European-ancestry individuals (IEU OpenGWAS) were analyzed for 20 dietary exposures. Outcomes included NAFLD diagnosis, liver volume, liver fat content, and percent liver fat. Primary analysis used Inverse-Variance Weighted (IVW) regression, supplemented by sensitivity analyses (MR-Egger, MR-PRESSO) to assess pleiotropy and heterogeneity.</p><p><strong>Results: </strong>Genetically predicted higher alcohol intake frequency (OR = 1.348, 95% CI = 1.110-1.638, P = 0.003) and salt added to food (OR = 1.544, 95% CI = 1.160-2.054, P = 0.003) significantly increased NAFLD risk in IVW analysis. These findings were robust in BWMR and MVMR analyses adjusting for potential confounders. Cheese (OR = 0.718) and dried fruit intake (OR = 0.406) showed protective associations. Alcohol frequency positively correlated with liver volume (β = 0.152, P = 0.002), while added salt was associated with increased liver volume (β = 0.244, P = 0.002) and liver fat content (β = 0.196, P = 0.038). Sensitivity analyses revealed no significant horizontal pleiotropy (MR-Egger intercept P > 0.05) or heterogeneity affecting primary results.</p><p><strong>Discussion: </strong>We identified alcohol intake frequency and dietary salt as genetically determined risk factors for NAFLD through MR analysis, while suggesting potential protective associations of cheese and dried fruit intake. By integrating BWMR and MVMR approaches with hepatic steatosis indices, we further revealed positive correlations between these exposures and liver volume/fat content, providing evidence-based dietary insights for NAFLD prevention.</p><p><strong>Conclusion: </strong>This MR study provides genetic evidence supporting potential causal associations of alcohol consumption frequency and dietary salt intake with NAFLD risk. It further associates these exposures with adverse changes in liver morphology and fat content. These findings highlight the importance of moderating the frequency of alcohol intake and salt consumption in NAFLD prevention strategies.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149164123","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":"Finding Novel Inhibitors of FMS-like Tyrosine Kinase 3 from Selected FDA-approved Anticancer Drugs: Insights from Molecular Docking, MD Simulations, and ADMET Profiling.","authors":"Mohammed H Al Mughram, Leye Jonathan Babatola, Md Nazim Uddin, Adeniyi A Adebayo, Rasheedat Anike Akeeb, Mahmud Lawal, Haruna Isiyaku Umar, Mohammed Dauelbait, Ridwan Opeyemi Bello, Yousef A Bin Jardan, Ahmad Mohammad Salamatullah","doi":"10.2174/0109298673467036260907115659","DOIUrl":"https://doi.org/10.2174/0109298673467036260907115659","url":null,"abstract":"<p><strong>Background: </strong>Wild-type FLT3 (WT-FLT3) has emerged as a relevant molecular target in Acute Myeloid Leukemia (AML), with increasing evidence implicating its role in leukemic proliferation and resistance, even in the absence of FLT3 mutations. Although gilteritinib is an approved FLT3 inhibitor, its efficacy in WT-FLT3 AML remains limited, underscoring the need for alternative strategies.</p><p><strong>Method: </strong>We filtered 1,737 FDA-approved anticancer agents from the Selleckchem database using computational techniques to identify possible WT-FLT3 inhibitors. A total of 118 druglike compounds were docked against the WT-FLT3 binding site as determined by gilteritinib using AutoDock Vina; ADMET screening and MD simulations of 150 ns were executed on hit compounds using the ADMETSar server and GROMACS software, respectively.</p><p><strong>Results: </strong>In the end, 56 compounds with binding energies between -8.0 and -10.3 kcal/- mol were obtained, while the control, gilteritinib, returned -6.4 kcal/mol. Among this subset, Amlexanox (-9.5), sanguinarine (-10.3), crizotinib (-9.7), (S)-crizotinib (-9.7), and rutaecarpine (-10.0) showed high predicted affinity. Predictions from ADMET and 150 ns MD simulations indicated that amlexanox had stable, specific interactions with the WT-FLT3 active site, superior ADMET, and a concentrated free-energy basin with increased conformational stability. In contrast, sanguinarine and others raised significant toxicity risks.</p><p><strong>Conclusion: </strong>These results suggest amlexanox is a potential new repurposing agent as a WT-FLT3 inhibitor in AML. This potential outcome needs urgent experimental confirmation through in vitro and in vivo models.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149164424","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":"Role of Serum Metabolites in Mediating the Effect of Circulating Inflammatory Proteins on NK/T Cell Lymphoma.","authors":"Dian Lou, Chen Zhang, Li Liu, Zhuojun Shi, Zhuo Wan, Weiwei Qin","doi":"10.2174/0109298673456330260925101143","DOIUrl":"https://doi.org/10.2174/0109298673456330260925101143","url":null,"abstract":"<p><strong>Introduction: </strong>NK/T Cell Lymphomas (NKTCL) are highly aggressive types of Non-Hodgkin's Lymphoma (NHL) that have a predilection for Asian and South American populations. Identifying new drug targets or prognostic markers is essential for developing future strategies for NKTCL treatment.</p><p><strong>Methods: </strong>This study employed a two-step and bidirectional Mendelian Randomization (MR) study with an Inverse Variance Weighted (IVW) approach to investigate the potential association of Circulating Inflammatory Proteins (CIPs) with NKTCL and the mediation effect of serum metabolites in the relationship between CIPs and NKTCL. Data on 91 CIPs from a proteomic study of 14,824 individuals conducted with the Olink Target platform were collected. Genetic information for NKTCL was obtained from the finngen_ R10_CD2_TNK_LYMPHOMA, including 363 cases and 324,650 controls. Data for 1,091 plasma metabolites and 309 metabolite ratios (Ebi-a- GCST90199621 to Ebia- GCST90201020) were derived from the GWAS Catalog.</p><p><strong>Results: </strong>MR analyses identified 4 plasma proteins significantly associated with NKTCL. Increased levels of TGF-α and TNFRSF9 were associated with increased NKTCL risk, with Odds Ratios (OR) of 1.6388 (95% CI 1.0158-2.6440) and 1.6863 (95% CI 1.1757-2.4187), respectively. Conversely, LIF-R (OR 0.6265, 95% CI 0.4427-0.8866) and SULT1A1 (OR 0.5425, 95% CI 0.3758-0.7833) exhibited protective effects. Notably, none of these proteins showed evidence of reverse causality. Furthermore, the mediation MR suggested that the effect of TNFRSF9 on NKTCL (total effect IVW: OR = 1.6863, 95% CI 1.1757-2.4187, P = 0.010) was partially mediated by Isobutyrylcarnitine (C4) levels (0.739, 95% CI 0.609-0.895, P = 0.002), accounting for 5.77% of the total effect.</p><p><strong>Discussion: </strong>This MR study suggests that CIPs may be associated with NKTCL pathogenesis and proposes that metabolite-mediated pathways represent a potential novel mechanistic link. It provides preliminary evidence consistent with serum metabolites playing a role as mediators in this relationship. These findings highlight the therapeutic potential of targeting specific metabolic pathways in NKTCL.</p><p><strong>Conclusion: </strong>Our proteome-wide MR analysis suggests an association between CIPs and NKTCL, which may be mediated by serum metabolites.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149165704","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":"Integrative Bioinformatics Identifies TTN as a Potential Diagnostic Marker for Rheumatoid Arthritis.","authors":"Yide Fang, Peihong Li, Zhujing Zhu, Zuoyuan Cao, Huanru Qu, Wei Wu, Liuqing Jing, Hao Li, Jinhai Xu, Bing Shu, Wen Mo","doi":"10.2174/0109298673488193261005044554","DOIUrl":"https://doi.org/10.2174/0109298673488193261005044554","url":null,"abstract":"<p><strong>Background: </strong>Rheumatoid arthritis (RA) is a chronic autoimmune disease with heterogeneous clinical manifestations, and its molecular mechanisms remain incompletely understood.</p><p><strong>Objective: </strong>To identify core genes associated with RA and evaluate their diagnostic utility, with an emphasis on immune relevance and causality.</p><p><strong>Methods: </strong>Differential expression analysis and weighted gene coexpression network analysis were used to prioritize hub genes. Functional enrichment and protein-protein interaction analyses supported biological interpretation. A nomogram and receiver operating characteristic analysis were used to evaluate diagnostic performance, and immune cell infiltration was analyzed to identify immune-associated core genes. The causal effect of titin on the risk of RA was estimated using genome-wide association study data and two-sample Mendelian randomization. Validation was conducted in independent public transcriptomic datasets and single-cell RNA sequencing (scRNA-seq) of synovial tissue.</p><p><strong>Results: </strong>Titin (TTN) was prioritized as an RA-associated core gene and demonstrated favorable diagnostic performance. TTN expression was consistently higher in RA than in controls across validation datasets. Public external validation datasets supported increased TTN expression in RA, and scRNA-seq analysis suggested enrichment of TTN expression in synovial T cells. Mendelian randomization supported a causal association between genetically predicted TTN and RA risk.</p><p><strong>Discussion: </strong>Collectively, evidence from bulk transcriptomics, immune cell infiltration profiling, single-cell localization, external validation, and genetic inference supports TTN as a previously underexplored candidate RA-associated biomarker with potential immune relevance. These findings extend current RA biomarker discovery by linking diagnostic performance with immune context and genetic support. Further mechanistic studies are needed to clarify whether TTN is involved in RA immunopathology or reflects inflammation-related tissue remodeling.</p><p><strong>Conclusion: </strong>Integrative analyses identify TTN as a potential RA-associated diagnostic biomarker requiring further experimental and clinical validation. Further studies are needed to clarify its mechanistic role and clinical utility in RA.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149164765","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":"Drug Discovery from Natural Products: In-Silico, In-Vitro and In-Vivo Perspectives.","authors":"Syed Shams Ul Hassan","doi":"10.2174/0109298673549543260915070825","DOIUrl":"https://doi.org/10.2174/0109298673549543260915070825","url":null,"abstract":"","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149164101","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":"Long Non-coding RNA 01296 in Cancer: A Review of the Current Landscape and Future Directions.","authors":"Shidong Wang, Sifan Liu, Yushuang Xu, Yanfang Wang, Guohong Liu, Jun Li, Shen Su, Tao Mao, Xiaoyu Li","doi":"10.2174/0109298673490617260929044547","DOIUrl":"https://doi.org/10.2174/0109298673490617260929044547","url":null,"abstract":"<p><p>A growing number of studies have shown that long non-coding RNAs (lncRNAs) are essential for the occurrence and progression of a broad spectrum of human malignancies. Long intergenic non-coding RNA 01296 (LINC01296), also known as double homeobox A pseudogene 9 (DUXAP9) and Lymph Node Metastasis-Associated Transcript 1 (LNMAT1), is an emerging oncogenic lncRNA widely documented to drive pathological processes in diverse tumor entities. Its oncogenic functions span digestive, urogenital and respiratory malignancies, alongside head and neck carcinomas, neuroblastoma, melanoma and osteosarcoma. LINC01296 acts predominantly as an oncogenic driver that orchestrates a cascade of malignant cellular phenotypes: uncontrolled proliferation, inhibited apoptosis, aberrant cell-cycle progression, augmented migration and invasion, epithelial-mesenchymal transition, maintenance of cancer stem cell properties, tumor microenvironment remodeling and multidrug chemoresistance. Notably, elevated LINC01296 expression is closely correlated with adverse prognoses and aggressive clinicopathological characteristics across tumors. Herein, this review systematically consolidates recent research advances regarding LINC01296, including its tissue-specific expression profiles, multifaceted biological functions, clinical prognostic significance, intrinsic molecular characteristics and elaborate regulatory mechanisms in various cancer subtypes. Taken together, current preclinical and clinical findings indicate that LINC01296 could represent a tentative biomarker for cancer diagnosis and prognosis, and may serve as a plausible therapeutic target warranting further translational investigation.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149165395","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":"Brain-Derived Tau as a Predictor of Prognosis in Patients with Stroke: A Meta-Analysis of Cohort Studies.","authors":"Han Tang, Chang Liu, Xiaoqin Yang, Siyin Gong, Yanru Chen, Jinfang Li, Yuqing Zhang","doi":"10.2174/0109298673495949260917075928","DOIUrl":"https://doi.org/10.2174/0109298673495949260917075928","url":null,"abstract":"<p><strong>Introduction/objective: </strong>Stroke remains a leading cause of global mortality and disability. Plasma Brain-Derived tau (BD-tau) is a brain-specific biomarker of neuronal injury, but its prognostic value in ischemic stroke remains unclear. This meta-analysis investigated the association between elevated plasma BD-tau levels and unfavorable functional outcomes in Acute Ischemic Stroke (AIS) patients.</p><p><strong>Methods: </strong>PubMed, Embase, Web of Science, Cochrane Library, Clinicaltrials.gov, and WHO-ICTRP were searched up to October 2025 for studies investigating BD-tau and prognosis in adult stroke patients. Pooled adjusted Odds Ratios (ORs) were calculated using effect sizes from multivariable logistic regressions to assess the predictive value of BD-tau for unfavorable 3-month outcomes (mRS ≥3). The study protocol was prospectively registered in PROSPERO (reference number: CRD42025640707).</p><p><strong>Results: </strong>The analysis included four prospective cohorts comprising 1,398 patients. Higher plasma BD-tau levels were significantly associated with unfavorable 3-month functional outcomes (pooled OR, 1.55; 95% CI, 1.26-1.91). Subgroup analysis showed a stronger association when BD-tau was measured within 24 hours of symptom onset (OR, 2.25; 95% CI, 1.70-2.96; I2 = 0%). When measured later, the correlation was relatively weak (OR, 1.32; 95% CI, 1.11-1.58; I2 = 91%). Meta-regression found that age, sex, baseline NIHSS score, endovascular treatment, and study quality did not significantly explain the heterogeneity.</p><p><strong>Discussion: </strong>Elevated plasma BD-tau levels were consistently associated with unfavorable functional outcomes after ischemic stroke, particularly when measured within 24 hours of symptom onset. These findings support the potential utility of BD-tau as an early prognostic biomarker, although further validation in larger and more diverse populations is required.</p><p><strong>Conclusion: </strong>BD-tau shows promising prognostic potential for predicting 3-month unfavorable functional outcomes after stroke, with the highest predictive value within the first 24 hours. Consequently, hyperacute BD-tau assessment emerges as a reliable instrument for early risk stratification and guided clinical intervention.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149164374","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 Key Genes and Construction of miRNA-mRNA Regulatory Networks Associated with Glioma Grade by Bioinformatics Analysis.","authors":"Huan Xiang, Hongli Zhang, Ozal Beylerli, Olga Gurina, Svetlana Shport, Elena Zharova, Vladimir Chekhonin, Ilgiz Gareev, Guang Yang","doi":"10.2174/0109298673468802260903111711","DOIUrl":"https://doi.org/10.2174/0109298673468802260903111711","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;The malignant transformation of Low-Grade Gliomas (LGGs) represents a critical clinical event, leading to intensified therapeutic regimens, higher morbidity, and premature death. This study aimed to identify Differentially Expressed Genes (DEGs) between LGGs and High-Grade Gliomas (HGGs) and to build a regulatory network involving microRNAs (miRNAs) and messenger RNAs (mRNAs) to explore the mechanisms driving the malignant progression of LGGs.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;In this bioinformatics study, we obtained two microarray datasets, GSE30472 and GSE45921, from the Gene Expression Omnibus (GEO) database, where 24 LGG samples and 53 HGG samples from the Cancer Genome Atlas (TCGA), the Chinese Glioma Genome Atlas (CGGA), and the Human Protein Atlas (HPA) were included for analysis. After combining the datasets and correcting for batch effects, DEGs were identified. Further analyses included Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, Protein-Protein Interaction (PPI) network construction, and key gene modeling for DEGs with specific biological phenotypes. Key genes were selected, and miRNA-mRNA regulatory networks were constructed using miRWalk 3.0, TargetScan, and miRDB. Univariate logistic regression was used to identify independent prognostic factors for cancer-specific survival, which were then used to construct the nomogram. The nomogram was validated by the concordance index (C-index), Receiver Operating Characteristic (ROC) curve, and calibration curves.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;A total of 16 mRNAs were found to be significantly differentially expressed (fold change &gt;1.0, p &lt; 0.05) between LGG and HGG samples. 16 hub genes, AADAT, ABLIM1, ACADSB, BABAM1, BCO2, BIRC5, C1QBP, CADM3, CALU, DAXX, DAZAP1, DBF4, DCTPP1, DEPDC1, AAK1, and C19orf47, were more prominently expressed in HGG than in LGG samples. Six regulatory pathways were identified, including hsa-let-7d-5p-CALU, hsa-let-7d-5p-AAK1, hsa-let-7e-5p-CALU, hsa-let-7e-5p-AAK1, hsamiR- 3666-DEPDC1, and hsa-miR-3666-AAK1, which are implicated in HGG pathogenesis. Finally, the dysregulated expression of the six regulatory miRNA-mRNA axes was validated by the data from the TCGA, CGGA, and HPA.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Discussion: &lt;/strong&gt;The identified 16 hub genes and associated miRNA-mRNA axes (specifically, let-7d/let-7e to CALU/AAK1 and miR-3666 to DEPDC1/AAK1) point to potential molecular mechanisms underlying the malignancy of LGG into HGG and identify promising biomarkers and therapeutic targets. These findings require further functional validation in vitro and in vivo, as well as confirmation in larger clinical cohorts, to assess their causal role and clinical applicability.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Our research identified crucial hub genes and miRNA-mRNA regulatory pathways associated with glioma oncogenesis, shedding light on the mechanisms of malignant transformation in LGGs. Furthermore, t","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149164731","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}