Current medicinal chemistry最新文献

{"title":"Pioneering of New Generation Therapies for Oral Cancer Involves the Integration of Small Molecules, Nanotechnology, and Artificial Intelligence - A Review.","authors":"Ayşe Hale Alkan, Fatma Zeynep Bozkurt, Dilara Nur Şengün, Kaan Orhan, Pelin Mutlu, Demet Cansaran-Duman","doi":"10.2174/0109298673430314251208225457","DOIUrl":"https://doi.org/10.2174/0109298673430314251208225457","url":null,"abstract":"<p><p>Oral cancer remains a significant global health challenge, characterized by high morbidity, poor survival rates, and a tendency for late-stage diagnosis. Although conventional treatment modalities-namely surgery, radiotherapy, and chemotherapy- are partially effective, they are frequently accompanied by substantial functional and aesthetic morbidity, therapeutic resistance, and limited long-term efficacy. In light of these limitations, a paradigm shift is underway in the therapeutic landscape of oral squamous cell carcinoma (OSCC). This shift is driven by three converging innovations: small molecule inhibitors, nanotechnology-based targeted drug delivery systems, and artificial intelligence (AI)-enabled diagnostic and prognostic tools. This review provides a comprehensive synthesis of recent preclinical and clinical advancements in these areas, emphasizing their underlying mechanisms, therapeutic benefits, and potential for synergy. Small molecule therapies modulate oncogenic signaling cascades in a pathway-specific manner, while nanocarrier platforms deliver cytotoxic and immunomodulatory agents precisely and locally, thereby reducing systemic toxicity. Concurrently, AI-driven models are transforming early detection, risk stratification, and outcome prediction by leveraging high-throughput omics data and imaging analytics. Together, these transformative technologies represent a significant advancement in precision oncology and underscore the importance of translating laboratory innovations into clinical applications. This review critically evaluates these emerging strategies, highlighting the potential of an interdisciplinary approach to redefine therapeutic standards and overcome long-standing clinical challenges in oral cancer management.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147467158","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":"Antibacterial Depsipeptides: One Common Feature, Diversity of Structures and Mechanisms of Action.","authors":"Elena B Guglya, Aleksandr S Shcheglov, Ilia V Yampolsky","doi":"10.2174/0109298673428505251208173220","DOIUrl":"https://doi.org/10.2174/0109298673428505251208173220","url":null,"abstract":"<p><p>The emergence and spread of drug-resistant pathogens have made the development of new antibiotics a global priority. Innovative agents with new mechanisms of action and/or membership in new drug classes are urgently needed. Antimicrobial peptides have been widely studied and show promise as therapeutics. Depsipeptides are a large group of peptides in which one or more amide bonds are replaced by ester bonds. They are nonribosomal peptides that typically contain up to 20 amino acids, often arranged in cyclic scaffolds with diverse side chains, and they display varied biological activities. Many depsipeptide antibiotics have now been identified, and this class merits focused attention. This review surveys roughly two dozen compounds with pronounced antibacterial properties that have been discovered or actively investigated in recent years. These include daptomycin, a clinically important systemic antibiotic; teixobactin, a candidate in clinical development; acyldepsipeptides, which are preclinical leads; and several recent hits with drug-development potential, such as clovibactin, lysocin E, ecumicin, and empedopeptin. We also discuss ramoplanin, which underwent clinical evaluation but is no longer considered a leading candidate, and the enniatins, once used clinically but now recognized as mycotoxins. The review focuses primarily on mechanisms of action and summarizes each compound to the extent these mechanisms have been characterized.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147467091","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":"Biomarker-Based Analysis of the Association Between Obstructive Sleep Apnea Syndrome and Oxidative Stress: A Univariable, Bidirectional, and Multivariable Mendelian Randomization Study.","authors":"Yuyin Liu, Suru Liu, Jianhong Deng, Wen Li, Dan Chen, Li Zhou, Li Tian","doi":"10.2174/0109298673424572251205201414","DOIUrl":"https://doi.org/10.2174/0109298673424572251205201414","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to investigate the potential genetic association between obstructive sleep apnea syndrome (OSAS) and oxidative stress (OS) using multi- -dimensional Mendelian randomization (MR) analysis.</p><p><strong>Methods: </strong>We conducted bidirectional univariable MR analyses using FinnGen-derived OSAS genetic data and summary statistics for 16 oxidative stress biomarker indicators (OSBIs) from IEU OpenGWAS and GWAS Catalog, employing five methods with sensitivity analyses to evaluate robustness and heterogeneity. Multivariable MR (MVMR) was further applied to adjust for confounders and estimate the direct effect of OSAS on OSBIs.</p><p><strong>Results: </strong>OSAS might be a risk factor for elevated lactate (OR = 1.06, 95% CI = 1.02-1.11, p < 0.01). MVMR supported an independent causal effect (OR = 1.16, 95% CI = 1.02-1.32, p = 0.03), although significant heterogeneity suggests interpretation requires caution. Reverse MR suggested that decreased superoxide dismutase (OR = 0.96, 95% CI = 0.93-0.98, p < 0.01) and matrix metalloproteinase-9 (OR = 0.98, 95% CI = 0.96-0.99, p < 0.01) were associated with OSAS. Furthermore, MVMR suggested a potential effect of OSAS on elevated vitamin E levels (OR = 1.15, 95% CI = 1.01-1.32, p = 0.04).</p><p><strong>Discussion: </strong>Our study provides genetic evidence for a bidirectional causal relationship between OSAS and OSBIs. Potential mechanisms may include hypoxia-disordered glucose metabolism and a compensatory upregulation of the antioxidant system. Future research should utilize larger, multi-ethnic samples and incorporate a broader range of OSBIs to systematically delineate these relationships.</p><p><strong>Conclusion: </strong>OS is both a driver and a pathological consequence of OSAS.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147467148","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":"Research Prospects for the Mitochondria in Glaucoma: A Bibliometric Analysis.","authors":"Lu Liang, Mei-Juan Wang, Zhao-Yang Liu, Shu-Chao Wang","doi":"10.2174/0109298673417791251204121930","DOIUrl":"https://doi.org/10.2174/0109298673417791251204121930","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Growing evidence implicates mitochondrial dysfunction as a pivotal contributor to glaucoma pathogenesis through oxidative stress, autophagy, and apoptotic pathways. However, systematic analyses of research collaboration patterns, key themes, and emerging trends in this field remain limited.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We retrieved relevant publications from the Web of Science (WOS) database (1999-2024) for bibliometric analysis. Visualization was generated using VOSviewer and CiteSpace, with complementary analysis in Charticulator and Excel. Journal impact factors from WOS were used to assess publication influence.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;This study analyzed 397 publications and found a fluctuating annual increase in both publications and citations in this research area. The United States emerged as the most productive nation in terms of publication volume. Investigative Ophthalmology & Visual Science was identified as the predominant journal in this field. Among individual researchers, Dr. Kim Keun Young was distinguished as a leading contributor. The most frequently occurring terms were: glaucoma, mitochondria, Oxidative Stress (OS), apoptosis, and Ischemia-Reperfusion Injury (IRI). Notably, the mitochondrial inhibitors were identified as promising therapeutic candidates for ophthalmic disorders. Our findings demonstrated the therapeutic potential of mitochondria through metabolic modulation and neuroprotective mechanisms, while identifying oxidative stress, autophagy dysregulation, and apoptotic pathways as critical pathological mediators. The analysis offered valuable insights for developing mitochondria-targeted therapies.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Discussion: &lt;/strong&gt;This comprehensive bibliometric analysis reveals a steady growth in research focusing on mitochondrial dysfunction in glaucoma, with the United States leading in scholarly output. The identified trends underscore a critical shift: emerging cellular and molecular insights are actively guiding the development of targeted and personalized therapeutic strategies for glaucoma. We acknowledge that our study has limitations inherent to bibliometric methodology. The literature search was restricted to articles and reviews within the Web of Science Core Collection. However, the exclusion of other major databases and clinical publication types may create a bias, overrepresenting basic research and underrepresenting clinical findings. Additionally, variations in the analytical algorithms of tools such as VOSviewer and CiteSpace may influence the resultant data patterns. Despite these limitations, the study offers a systematic mapping of the research landscape and provides a clear guide for future research directions in this field.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;This study provided a comprehensive analysis of scientific advancements in this field, highlighting the pivotal role of mitochondrial dysfunction in glaucoma pathogenesis and proposing strategic","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147467114","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":"Plasma Proteins Mediate the Causal Effect of Diet on the Development of Osteoporosis: A Mendelian Randomization Study.","authors":"Wenkang Luan, Shujun Fan, Chuan Li","doi":"10.2174/0109298673389377251128092427","DOIUrl":"https://doi.org/10.2174/0109298673389377251128092427","url":null,"abstract":"<p><strong>Introduction: </strong>The causal relationship between dietary intake, plasma proteins, and osteoporosis (OP) remains uncertain. We investigated whether 38 dietary factors and 2,940 plasma proteins have a causal effect on OP using Mendelian randomization (MR).</p><p><strong>Methods: </strong>Single-nucleotide polymorphisms (SNPs) robustly associated with 38 dietary factors and 2,940 plasma proteins were used as instrumental variables (IVs). We performed four MR approaches, including inverse variance weighted (IVW), weighted mode, MR-Egger, and weighted median. Multivariate MR analysis and mediation effect estimation were employed to evaluate potential mediating effects.</p><p><strong>Results: </strong>Higher consumption of ground coffee and instant coffee was statistically associated with increased OP prevalence, whereas greater water intake showed a protective trend. Among plasma proteins, 152 demonstrated significant associations with OP, with 26 linked to ground coffee consumption, 23 to instant coffee, and 5 to water intake. Notably, RAB GTPase-activating protein 1-like (RABGAP1L) appeared to mediate the association between ground coffee consumption and OP.</p><p><strong>Discussion: </strong>MR analysis indicated that ground coffee and instant coffee intake are risk factors, while water consumption is a protective factor for OP, and suggested a potential mediating role of RABGAP1L in ground coffee-induced OP. These findings should be interpreted as potential mechanistic insights rather than definitive causal proof.</p><p><strong>Conclusion: </strong>The observed associations between coffee consumption and OP likely involve complex biological pathways, and the protective effect of water intake warrants further investigation in longitudinal studies.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147467142","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":"Discovery of New Hydrazonothiazolines as Bovine and Human Carbonic Anhydrase-II Inhibitors: In-vitro, Kinetics, Selectivity and Molecular Dynamics Exploration.","authors":"Sobia Ahsan Halim, Majid Khan, Muhammad Tariq Shehzad, Fazal Mabood, Suraj N Mali, Srutee Rout, Afnan Jan, Abdullatif Bin Muhsinah, Zahid Shafiq, Hamdy Kashtoh, Ajmal Khan, Ahmed Al-Harrasi","doi":"10.2174/0109298673344914250522110445","DOIUrl":"https://doi.org/10.2174/0109298673344914250522110445","url":null,"abstract":"<p><strong>Introduction: </strong>Carbonic Anhydrase II (CA-II) is crucial for several physiopathological processes, including bone calcification, osteoporosis, tumorigenicity, and epilepsy, among others. Usually, the intraocular pressure observed in glaucoma exacerbates the condition, and CA-II inhibitors have the potential to be used for the reduction of this pressure.</p><p><strong>Methods: </strong>Moreover, to search for novel CA-II inhibitors with high potency, a series of hydrazonothiazoline derivatives (5a-q) were synthesized. The inhibitory potency of our synthesized compounds was investigated for human and bovine CA-II through in-vitro and computational methods. The in vitro screening revealed that 5a-5f, 5g, 5h, and 5l have significant inhibitory action for bCA-II (IC50 = 13.1 μM to 44.6 μM), whereas 5a, 5d, 5f, 5h, and 5l exhibited excellent inhibition of hCA-II (IC50 = 7.0 μM to 33.1 μM). Therefore, binding pattern of those active hits was elucidated by in silico docking, which reflects that the thiazole group of ligands is responsible for binding of compounds with the target proteins and consequent functional inhibition of the enzyme. Moreover, the type of inhibition of active hits (5a and 5h for hCA-II and bCA-II, respectively) was explored by kinetics experiment in which both 5a (for hCA-II, Ki = 5.25±0.004 μM) and 5h (for bCA-II, Ki = 5.5±0.001 μM) competitively inhibited CA-II.</p><p><strong>Results: </strong>The molecular dynamics simulation, MMPBSA analysis, revealed that 5a has better stability in 1BN1 than 5h in 1V9E.</p><p><strong>Conclusion: </strong>Those identified inhibitors could serve as a skeleton to design more potent CA-II inhibitors in the future.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147467179","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":"The Efficacy of Palbociclib-Conjugated ZnO-Ordered Mesoporous Carbon Nanohybrid against MCF-7 Breast Cancer Cell Line.","authors":"Fatemeh Zahra Fallah Lajimi, Bahare Sabeti, Fereshteh Chekin, Bahman Rahimi Esboei","doi":"10.2174/0109298673403024251129174213","DOIUrl":"https://doi.org/10.2174/0109298673403024251129174213","url":null,"abstract":"<p><strong>Introduction: </strong>Breast cancer is the most common cancer in females. The inhibitors of cyclin-dependent kinase 4/6 (CDK 4/6) have revolutionized the treatment of breast cancer. Palbociclib (Pal) is a highly potent CDK 4/6 inhibitor. The side effects and poor absorption of Pal may influence efficiency. This prompted us to conjugate Pal drug into the nanomaterial based on ZnO-ordered mesoporous carbon (ZnO-OMC) as a nanocarrier in drug delivery and investigate the anticancer activity of the Pal-conjugated ZnO-OMC (Pal@ZnO-OMC) on breast cancer cells (MCF-7).</p><p><strong>Methods: </strong>The ZnO-OMC composite was synthesized by the green method using Callicarpa plant extract, and Pal anticancer drug was loaded on the mentioned composite at different pHs, times, and ratios of drug to composite. The loading of Pal on ZnO-OMC composite was investigated by FE-SEM, UV-Vis, Raman, and FT-IR spectroscopy methods. The controlled Pal release from Pal@ZnO-OMC hybrid was investigated at different pH values and times. Moreover, the cytotoxicity of Pal@ZnO-OMC was evaluated on MCF-7 cells by MTT assay.</p><p><strong>Results: </strong>The results showed that ZnO-OMC is a highly efficient carrier with high loading of Pal, 82.5% at pH 7.0 for 3 h. The prepared Pal@ZnO-OMC exhibited favorable physico-chemical characteristics such as the controlled and targeted release pattern (15.2% of Pal is released at pH 7.4 for 10 h, while 58.1% of Pal is released at pH 4.0) and efficient cytotoxicity (cell viability of 50.4% and 38.8% at 24 and 48 h, respectively). Free Pal was significantly less efficient (with half-maximal inhibitory concentration (IC50) of 151.9 μg/mL for 48 h) than Pal@ZnO-OMC (with IC50 of 2.6 μg/mL for 48 h).</p><p><strong>Discussion: </strong>The synergistic effects of Pal@ZnO-OMC nanoformulation due to the presence of ZnO in hybrid seemed to improve antiproliferation efficacies against MCF-7 cells compared with the free Pal.</p><p><strong>Conclusion: </strong>All findings demonstrated that the designed Pal@ZnO-OMC hybrid can be a potent nanoformulation for the treatment of MCF-7 breast cancer.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147467154","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":"A Lactylation-based Gene Signature in Lung Adenocarcinoma Provides a Novel Perspective to Predict the Prognosis and Therapeutic Response.","authors":"Ming Zhao, Ben Li, Honghai Li, Haoning Nan, Yafei Sun, Yanbin Pei, Xuguang Zhang, Nan Geng","doi":"10.2174/0109298673433855251202003730","DOIUrl":"https://doi.org/10.2174/0109298673433855251202003730","url":null,"abstract":"<p><strong>Introduction: </strong>Lactylation, a novel post-translational modification in tumor cells, is studied here to explore its relevant gene signature in lung adenocarcinoma (LUAD).</p><p><strong>Materials and methods: </strong>Transcriptome data of LUAD from The Cancer Genome Atlas (TCGA) were retrieved from UCSC Xena, while the gene expression dataset GSE31210 was acquired from the Gene Expression Omnibus (GEO) database. Lactation-related genes (LRGs) were identified based on previous literature. Lactation levels were quantified using single-sample gene set enrichment analysis (ssGSEA). After screening LRGs associated with prognosis, the ConsensusClusterPlus package was employed for clustering. Subsequently, a RiskScore model was constructed through univariate Cox and LASSO analyses. The prognostic relevance and robustness of the RiskScore were evaluated, and the association of the RiskScore with both immunotherapy response and the tumor microenvironment (TME) was determined.</p><p><strong>Results: </strong>An overall high lactylation score was noticed in the LUAD sample, which could be assigned into 2 molecular subtypes (C1 and C2). Meanwhile, 83 LRGs were preliminarily explored to have prognostic relevance, of which 5 genes (CDKN3, FSCN1, PKP2, FAM83A, and ABCC2) were further revealed as the hub genes for the RiskScore model. Such RiskScore, independent of other clinicopathological features, displayed a satisfying efficacy in predicting the prognosis and the response to immunotherapy. Additionally, the formulated RiskScore, including the expression level of each gene, displayed a varied correlation with the predicted drug candidates.</p><p><strong>Discussion: </strong>From the lactylation perspective, this study reveals LUAD's molecular heterogeneity, proposes and externally validates a 5-gene RiskScore model. The model independently predicts prognosis, correlates with immunotherapeutic response and drug sensitivity, and points to potential links among lactate metabolism, key signaling pathways, and clinical outcomes.</p><p><strong>Conclusion: </strong>5 prognosis-relevant LRGs could provide a novel perspective for the individualized therapeutic regimens for LUAD.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147467116","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":"A Multimodal Diagnostic Model for Hepatocellular Carcinoma Integrating Biomarkers Related to Programmed Cell Death and Radiomics Features.","authors":"Lixing Lei, Nian Liu, Lingling Tang, Qianqian Liu, Ke Pan, Xiaohua Huang","doi":"10.2174/0109298673425647251129163133","DOIUrl":"https://doi.org/10.2174/0109298673425647251129163133","url":null,"abstract":"<p><strong>Introduction: </strong>Hepatocellular carcinoma (HCC) is characterized by its insidious onset and rapid progression. Investigating diagnostic and therapeutic strategies targeting programmed cell death (PCD) represents a promising research direction.</p><p><strong>Methods: </strong>PCD pathway activation in HCC was assessed via single-sample GSEA (ss- GSEA). Differentially expressed genes (DEGs) were screened by WGCNA, FindMarkers, and the limma package from bulk and single-cell data. Intersecting DEGs were refined by LASSO regression in the glmnet package, and diagnostic performance was validated using ROC analysis. Functional enrichment analysis was conducted with the clusterProfiler package, and drug prediction was performed with Enrichr package. Py- MOL, AutoDockTools, and AutoDock Vina software were employed to perform molecular docking simulations. A radiomics-driven LASSO model was applied to construct a diagnostic nomogram.</p><p><strong>Results: </strong>PCD plays a crucial part in the development of HCC. Three genes (CAPG, MS4A6A, and TREM2) were identified as the PCD-related diagnostic genes for HCC. The reliability of the three genes was confirmed by ROC analysis, with AUC values exceeding 0.7. Drug prediction screened 46 candidate compounds, from which Tamibarotene and Vorinostat were selected for molecular docking. Finally, a nomogram was established based on the radiomics features of the CAPG gene, reaching an AUC above 0.8.</p><p><strong>Discussion: </strong>Using interpretable machine learning to integrate transcriptomic, single-- cell, and radiomic data, we revealed systemic dysregulation of PCD-related pathways in HCC and validated the diagnostic value of CAPG, MS4A6A, and TREM2 across datasets. A CAPG-based radiomics nomogram showed favorable discrimination and calibration, suggesting translational potential.</p><p><strong>Conclusion: </strong>We developed a reusable multimodal diagnostic framework with candidate biomarkers and a radiomics tool to facilitate the early detection and risk stratification of HCC.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147467132","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":"Cyasterone Improves Mitochondrial Function and Protects against Knee Osteoarthritis by Activating PPARγ.","authors":"Dingtian Liang, Zhicheng Yao, Yage Zhang, Weiping Lin, Huanyu Li, Junlang Zhu, Litong Ren, Xianfeng Zeng, Liangliang Xu","doi":"10.2174/0109298673421097251126150249","DOIUrl":"https://doi.org/10.2174/0109298673421097251126150249","url":null,"abstract":"<p><strong>Introduction: </strong>Studies have demonstrated that mitochondrial dysfunction plays an important role in the development of knee osteoarthritis. Our previous study reported that cyasterone accelerates fracture healing by promoting the migration and osteogenesis of mesenchymal stem cells (MSCs). However, the effect of cyasterone on osteoarthritis (OA) has not been investigated. Therefore, this study aimed to investigate the effects of cyasterone on mitochondrial function in chondrocytes of mice and its potential therapeutic impact on knee osteoarthritis (OA) in mice.</p><p><strong>Methods: </strong>Primary chondrocytes were isolated from C57BL/6 mice, and the optimal cyasterone concentration was determined via CCK-8 assay. An osteoarthritis chondrocyte model was established using lipopolysaccharide (LPS) induction. Chondrocytes were assigned to control, LPS, and cyasterone treatment groups. ATP production, NAD+/NADH ratio, oxidative stress levels, and mitochondrial membrane potential were measured in each group. Adult C57BL/6 mice were allocated into three groups (n=8 per group): control, model, and cyasterone treatment. After 4 weeks of cyasterone intervention, histopathological changes in knee joints and expression of extracellular matrix-related proteins in cartilage tissue were assessed.</p><p><strong>Results: </strong>Compared to the LPS group, cyasterone treatment significantly increased ATP production, elevated the NAD+/NADH ratio, and reduced oxidative stress levels in LPS- induced chondrocytes. Mechanically, we found that the expression of Peroxisome proliferator- activated receptor γ (PPARγ) was significantly increased by cyasterone. In the OA group treated with cyasterone, the mice exhibited marked improvement in cartilage histopathological scores compared to the model group, with enhanced expression of aggrecan and PPARγ proteins and decreased expression levels of MMP13 and phosphorylated- p65.</p><p><strong>Discussion: </strong>Consistent with previous findings, our results showed that cyasterone significantly increased PPARγ expression in primary chondrocytes, thereby maintaining chondrocyte function and preventing the progression of OA.</p><p><strong>Conclusion: </strong>In summary, the results indicated that cyasterone could restore mitochondrial function in LPS-induced mouse chondrocytes by upregulating PPARγ expression. in vivo, cyasterone was found to reduce extracellular matrix degradation and inhibit the progression of osteoarthritis (OA). These findings suggest that cyasterone could be a potential natural compound for the effective treatment of OA.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147467087","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}