Current medicinal chemistry最新文献

{"title":"Eco-Friendly Zinc Oxide Nanoparticles from <i>Trachystemon orientalis</i> L.: Examination of Their Antibacterial, Anti-Alzheimer, and Antidiabetic Potentials.","authors":"Nilay Akkuş Taş, Recep Taş, Hasan Ufuk Celebioglu, Parham Taslimi, Savaş Kaya, Avni Berisha","doi":"10.2174/0109298673493377260828095834","DOIUrl":"https://doi.org/10.2174/0109298673493377260828095834","url":null,"abstract":"<p><strong>Introduction: </strong>This study aimed to biogenically synthesize and characterize Zinc Oxide Nanoparticles (ZnONPs) using the <i>Trachystemon orientalis</i> L. plant extract. It also aimed to evaluate the antibacterial potential and metabolic enzyme-inhibitory activities of these green-synthesized nanoparticles for medical and industrial applications.</p><p><strong>Methods: </strong>Nanoparticles were synthesized using a green chemistry approach, where the plant extract acted as a reducing agent for zinc ions. The structural and morphological properties of ZnONPs were analyzed using X-ray Diffraction (XRD), Fourier-transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), and Energy-dispersive X-ray Spectroscopy (EDX). Antibacterial efficacy was evaluated by determining the Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) against <i>Staphylococcus aureus</i> and <i>Escherichia coli</i>. Additionally, the inhibitory effects on α-glycosidase, Acetylcholinesterase (AChE), and Butyrylcholinesterase (BChE) enzymes were investigated to determine the inhibition constant (K_i) values. All experiments were conducted in triplicate, and the results are expressed as mean ± standard deviation.</p><p><strong>Results: </strong>XRD analysis confirmed the crystalline metallic structure of ZnONPs, SEM imaging revealed a predominantly rod-shaped morphology, and EDX analysis verified that the elemental composition was predominantly zinc, consistent with ZnO nanoparticle formation. FTIR spectra confirmed the successful capping of the nanoparticles by plant-derived bioactive compounds. Antibacterial assays showed significant activity, with MIC values of 125 μg/mL for S. aureus and 250 μg/mL for E. coli. Enzyme inhibition studies yielded potent results, with Ki values of 47.10 ± 3.72 μM for α-glycosidase, 3.55 ± 0.43 μM for BChE, and 15.47 ± 1.24 μM for AChE, all of which outperformed standard inhibitors such as tacrine and acarbose.</p><p><strong>Discussion: </strong>The results demonstrate that the biogenic synthesis of ZnONPs using T. orientalis is an effective and eco-friendly method for producing nanoparticles with high biological activity. The superior enzyme inhibition and antibacterial performance compared to conventional standards suggest that these nanoparticles possess unique surface properties owing to the plant-derived organic shell, enhancing their interaction with biological targets.</p><p><strong>Conclusion: </strong>This study successfully synthesized rod-shaped zinc oxide nanoparticles with significant antimicrobial and enzyme-inhibitory properties. These findings highlight the potential of biogenically synthesized ZnONPs as multifunctional agents in the development of new therapeutic strategies for managing bacterial infections and metabolic disorders.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149012068","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":"Glutamine Metabolism-associated Molecular Heterogeneity and Prognosis in Pancreatic Adenocarcinoma.","authors":"Wenyu Li, Min Luo, Xuehong Wang, Yuqian Zhou","doi":"10.2174/0109298673488452260827110054","DOIUrl":"https://doi.org/10.2174/0109298673488452260827110054","url":null,"abstract":"<p><strong>Background: </strong>Pancreatic Adenocarcinoma (PAAD) is characterized by pronounced molecular heterogeneity and profound metabolic reprogramming. Glutamine metabolism plays a critical role in sustaining tumor growth and shaping the tumor microenvironment; however, its contribution to molecular heterogeneity, immune characteristics, and clinical outcomes in PAAD remains incompletely understood.</p><p><strong>Methods: </strong>We conducted an integrative transcriptomic analysis utilizing transcriptomic and clinical data from TCGA, GTEx, and an independent GEO cohort to focus on genes involved in glutamine metabolism. Unsupervised consensus clustering was performed to define molecular subtypes associated with glutamine metabolism. Differential expression analysis, pathway enrichment analysis, and established transcriptome-based methods were applied to characterize subtype-specific biological features. Using LASSO-- Cox regression, a prognostic risk model was created and validated in internal and external cohorts. Multilevel biological validation was further conducted using immunohistochemistry data, pancreatic cancer cell line profiles, and single-cell RNA sequencing resources.</p><p><strong>Results: </strong>Two reproducible glutamine metabolism-associated molecular subtypes were identified, exhibiting distinct survival outcomes and immune landscapes. The metabolically aggressive subtype was associated with increased immune evasion potential and enrichment of pathways related to cell cycle progression, hypoxia, and metabolic dysregulation. An eight-gene prognostic signature demonstrated stable predictive performance across cohorts and remained independently associated with overall survival. Protein-level expression and single-cell analyses further supported the biological relevance of key prognostic genes.</p><p><strong>Discussion: </strong>These findings suggest that glutamine metabolism-associated heterogeneity may contribute to immune modulation and clinical divergence in PAAD. The integration of metabolic stratification with immune landscape characterization provides a biologically coherent framework for understanding tumor progression and therapeutic resistance.</p><p><strong>Conclusion: </strong>This study establishes a glutamine metabolism-centered integrative framework that links molecular heterogeneity with immune modulation and clinical outcomes in PAAD. The identified biomarkers and stratification strategy provide biologically interpretable insights and may facilitate metabolic-based risk stratification and personalized therapeutic decision-making in pancreatic adenocarcinoma.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148966956","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":"Ergothioneine Alleviated the Apoptosis of HK Cells by Regulating Ferroptosis.","authors":"Fei Yan, Hui Sun, Jian Wang, Junzheng Yang, Qian He, Li Yu","doi":"10.2174/0109298673482107260902063150","DOIUrl":"https://doi.org/10.2174/0109298673482107260902063150","url":null,"abstract":"<p><strong>Introduction/objective: </strong>Ergothioneine (EGT) is a naturally occurring antioxidant with protective effects on various human cell types. The impact of this substance on HK-2 cells, a human renal proximal tubular epithelial cell line, and the associated molecular mechanisms remain incompletely elucidated.</p><p><strong>Methods: </strong>The present study aims to elucidate the effects of EGT on apoptosis induced by RAS-selective Lethal Molecule 3 (RSL3) and Erastin in HK-2 cells, as well as the potential mechanisms involved. The renal cortical proximal tubular epithelial HK-2 cells were cultured and exposed to RSL3 and Erastin, with or without EGT treatment. Cell viability and apoptosis were assessed using the Cell Counting Kit-8 (CCK-8) assay, while the detection of ferrous ion content and mitochondrial membrane potential changes was accomplished through the utilisation of flow cytometry and the JC-1 staining method, respectively. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, proteomic analysis, and western blotting were employed to explore the molecular pathways involved.</p><p><strong>Results: </strong>The data demonstrated that RSL3 and Erastin exhibited a substantial inhibitory effect on HK-2 cell proliferation, concomitant with the accumulation of intracellular ferrous ions and a shift in mitochondrial membrane potential. The EGT treatment effectively mitigated RSL3- and Erastin-induced apoptosis in HK-2 cells. GO and KEGG enrichment analysis demonstrated that EGT suppressed pathways and functions associated with oxidative stress during ferroptosis. Proteomics analysis further demonstrated that EGT modulated various biological processes, molecular functions, and cellular components in HK-2 cells. The protective mechanism of EGT against RSL3- and Erastin-induced HK-2 cells was potentially mediated through regulation of ferroptosis. The results of the western blot analysis demonstrated that EGT modulated the expression levels of Glutathione Peroxidase 4 (GPX4) and Solute Carrier Family 7 member 11 (SLC7A11) in HK-2 cells.</p><p><strong>Conclusion: </strong>These data demonstrated that EGT exerts an alleviating effect on the apoptosis of HK-2 cells induced by RSL3 and Erastin by modulating ferroptosis. These findings suggest that EGT has the potential to serve as a therapeutic candidate for the treatment of kidney diseases in the future.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148966930","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":"Dexamethasone Sustained-Release Implant Enhances Early Visual Recovery Following Minimally Invasive Vitrectomy for Idiopathic Epiretinal Membrane: A Retrospective Cohort Study.","authors":"Jing Yuan, Biyue Tu, Zhen Zhao, Yanxia Tong, Xiaojie Ou","doi":"10.2174/0109298673474636260830071623","DOIUrl":"https://doi.org/10.2174/0109298673474636260830071623","url":null,"abstract":"<p><strong>Introduction/objective: </strong>Idiopathic epiretinal membrane (iERM) is a common cause of visual distortion and central acuity loss, driven by fibrocellular traction on the macula. Although vitrectomy with membrane peeling effectively releases mechanical traction, surgical trauma disrupts the inner blood-retinal barrier, leading to postoperative inflammation and delayed early recovery. This retrospective cohort study evaluated whether adjunctive use of an intravitreal dexamethasone sustained-release (DEX-SR) implant during 23-gauge minimally invasive vitrectomy enhances early anatomical and functional recovery in stage 4 iERM.</p><p><strong>Methods: </strong>Medical records of 100 patients (100 eyes) undergoing surgery between 2022 and 2024 were reviewed. The Study Group (n=50) received an intraoperative DEX-SR implant (Ozurdex® 0.7 mg), while the Control Group (n=50) underwent surgery alone. Best-corrected visual acuity (BCVA, logMAR), central macular thickness (CMT), ectopic inner foveal layer (EIFL) thickness, and OCT angiography parameters (deep capillary plexus vessel density (DCP VD) and foveal avascular zone (FAZ) area) were compared preoperatively and at 2 weeks, 1, 3, and 6 months postoperatively. Effect sizes (partial η2) and 95% confidence intervals were calculated.</p><p><strong>Results: </strong>The DEX-SR group showed significantly greater BCVA improvement from 2 weeks onward (1-month: 0.41±0.09 vs. 0.52±0.16, adjusted p < 0.001, partial η2 = 0.32) and faster CMT reduction (1-month: 331.97±39.29 vs. 377.47±78.84 μm, adjusted p < 0.001, partial η2 = 0.28). EIFL thickness decreased more rapidly in the study group (2- weeks: 161.54±30.10 vs. 181.23±21.82 μm, adjusted p = 0.015, partial η2 = 0.19). DCP VD recovered to preoperative levels by 6 months in the study group (51.78±1.86% vs. baseline 48.51±3.02%, adjusted p = 0.087) but remained lower in controls (46.93±3.34%, adjusted p = 0.041). FAZ area was more stable in the DEX-SR group (0.30±0.03 vs. 0.26±0.04 mm2, adjusted p = 0.001). Transient IOP elevation occurred but was manageable.</p><p><strong>Discussion: </strong>The DEX-SR implant accelerated early anatomical restoration and visual gain, likely through sustained suppression of postoperative inflammation and blood-retinal barrier stabilization. However, the retrospective, non-randomized design and lack of propensity score adjustment limit causal inference. Findings should be considered hypothesis- generating.</p><p><strong>Conclusion: </strong>Intraoperative DEX-SR implantation was associated with accelerated early anatomical and functional recovery in this retrospective cohort, with a tolerable safety profile. Prospective randomized trials are needed to confirm these preliminary findings.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148966974","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":"Current Advances and Future Perspectives of Small Molecule Targeted Therapy in Cancer Treatment.","authors":"Renhao Xue","doi":"10.2174/0109298673542601260903113443","DOIUrl":"https://doi.org/10.2174/0109298673542601260903113443","url":null,"abstract":"","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148966927","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":"Aromatic Sulfonamides Emerge as a Promising Frontier in Advanced Cancer Therapy.","authors":"Faiz Ullah, Sami Ullah, Muhammad Mustaqeem, Muhammad Fayyaz Ur Rehman, Sania Nazir, Esra Küpeli Akkol, Muhammad Junaid Tariq, Muhammad Ibrar Khan, Zeliha Selamoglu, Eduardo Sobarzo-Sánchez","doi":"10.2174/0109298673477523260828075423","DOIUrl":"https://doi.org/10.2174/0109298673477523260828075423","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction/objective: &lt;/strong&gt;Current cancer chemotherapy is limited by severe adverse effects, poor selectivity toward malignant cells, and the emergence of multidrug resistance, highlighting the need for novel therapeutic strategies with enhanced potency and safety. Sulfonyl-containing compounds and sulfonamide derivatives have attracted sustained attention as anticancer scaffolds because of their structural diversity, favorable physicochemical properties, and broad pharmacological profiles. This review critically examines how structural variation within aromatic sulfonamides controls target engagement, anticancer activity, and translational potential. Rather than cataloguing individual derivatives, it integrates cross-family structure-activity relationships with mechanistic evidence involving carbonic anhydrases, tubulin dynamics, survival signaling, apoptosis, and tumorassociated metabolic adaptation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Recent experimental and preclinical studies were reviewed, with special emphasis on sulfonyl and sulfonamide derivatives as multifunctional pharmacophores and their emerging role in cancer therapy, supported by extensive chemical and pharmacological evidence. Emphasis was placed on heterocyclic sulfonyl compounds and macrocyclic hybrid systems.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Several sulfonamide derivatives have demonstrated potent antiproliferative activity against a broad range of human cancer cell lines, including MCF-7 and MIA PaCa-2, by interacting with multiple targets and disrupting pathways involved in tumor growth and survival. Calixarenesulfonyl hybrids demonstrate selective and potent cytotoxicity against several cancer cell lines, including breast and pancreatic cancer models. These compounds inhibit tubulin dynamics, reduce the proliferation of multiple human cancer cell lines, induce apoptosis, and modulate molecular targets associated with the phosphoinositide 3-kinase/protein kinase B signaling pathway. The clinical success of sulfonamide-containing agents further validates this pharmacophore in oncology.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Discussion: &lt;/strong&gt;The available evidence indicates that structural optimization of aromatic sulfonamides can improve antiproliferative activity and target selectivity, although cellular potency alone is insufficient to establish therapeutic relevance. Direct target validation, mechanistic characterization, tumor selectivity, and pharmacokinetic assessment remain necessary to distinguish pharmacologically relevant activity from non-specific cytotoxicity.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Aromatic sulfonamides constitute a chemically adaptable platform from which compounds acting on carbonic anhydrases, tubulin, survival signaling, and apoptosis-related processes have been developed. The available evidence supports their continued investigation in anticancer drug discovery; however, multi-target activity should be considered advantageous only when target engagement, t","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148944417","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 TIPARP, BCL6 and PLIN2 as Potential Ferroptosisrelated Biomarkers for Osteoarthritis.","authors":"Hanyu Wang, Zhikang Chen, Shikai Chen, Honglin Pi, Qianqian Liang, Li Wang","doi":"10.2174/0109298673492605260827055611","DOIUrl":"https://doi.org/10.2174/0109298673492605260827055611","url":null,"abstract":"<p><strong>Introduction: </strong>Studies have shown that ferroptosis may be related to the occurrence of OA. This study aimed to identify Ferroptosis-related Genes (FRGs) in OA synovium and the Infrapatellar Fat Pad (IPFP) and to analyze the potential molecular mechanisms.</p><p><strong>Methods: </strong>The single-cell RNA sequencing (scRNA-seq) and gene expression microarray datasets used in this study were downloaded from public databases and systematically preprocessed for subsequent analytical procedures. The gene expression microarray dataset originated from human synovial samples, and scRNA-seq data were obtained from the IPFP and synovial tissues. Thereafter, the machine learning algorithms were applied to determine key FRGs. Thereafter, immune infiltration analysis and molecular docking were performed to reveal the molecular mechanism of the key FRGs in OA.</p><p><strong>Results: </strong>The hub genes in the green module were enriched in pathways associated with immune cells and cytokines/chemokines. Machine learning identified three key FRGs, including TCDD-inducible Poly (ADP-ribose) Polymerase (TIPARP), BCL6 Transcription Repressor (BCL6), and Perilipin 2 (PLIN2). All three genes showed lower expression in OA cases and were negatively correlated with immune infiltration. Further single- cell analyses revealed their expression in monocytes/macrophages and smooth muscle cells. Molecular docking revealed a stable binding between Vorinostat and BCL6.</p><p><strong>Discussion: </strong>This study identified TIPARP, BCL6, and PLIN2 as key FRGs in OA using WGCNA and machine learning algorithms. These genes were correlated with immune infiltration. Specifically, BCL6 stably bound to vorinostat, showing the potential to serve as a target for OA treatment. This study relies on bioinformatics analysis of public data and lacks experimental validation, with conclusions needing confirmation via functional assays and larger, well-annotated clinical cohorts.</p><p><strong>Conclusion: </strong>In conclusion, our study identified TIPARP, BCL6, and PLIN2 as potential key FRGs in OA, providing novel insights for understanding the pathogenesis of OA.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148966938","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 Causal Plasma Proteins and Immune Mediators for Lung Cancer in Never-Smokers: A Large-Scale Integrative Analysis Combining Mendelian Randomization, Colocalization, and Mediation.","authors":"Jian-Cong Wu, Qi Zhang, Yan-Ming Lin, Xiao-Rao Chen, Xiao-Bi Huang, Hai-Yin Ye, Jie Li, Zhi-Xiong Yang, Qi-Biao Wu, Wen-Mei Su","doi":"10.2174/0109298673488490260824103946","DOIUrl":"https://doi.org/10.2174/0109298673488490260824103946","url":null,"abstract":"<p><strong>Objective: </strong>As global smoking rates decline, Lung Cancer in Never-Smokers (LCINS) has emerged as a distinct and increasingly important clinical entity. However, its underlying pathogenesis remains poorly understood, highlighting the need to identify circulating molecular determinants and candidate biomarkers.</p><p><strong>Methods: </strong>Genetic instruments for plasma proteins were obtained from pQTL datasets (Fenland study and UK Biobank Pharma Proteomics Project), while summary statistics for LCINS were sourced from TRICL-ILCCO. Two-sample Mendelian Randomization (MR) was performed using inverse-variance weighting as the primary approach, complemented by sensitivity analyses for heterogeneity (Cochran's Q), horizontal pleiotropy (MR-Egger intercept), and outlier detection (MR-PRESSO). Tissue-level validation was conducted using CPTAC proteomic data. Further analyses, including Bayesian colocalization, Protein-Protein Interaction (PPI) network construction, Gene Ontology (GO) enrichment, and mediation analysis, were applied to investigate shared genetic architecture, functional pathways, and immune-mediated mechanisms.</p><p><strong>Results: </strong>Among 543 cis-acting plasma proteins evaluated in the discovery phase, 35 exhibited evidence of association with LCINS risk, including 15 positively and 20 inversely associated proteins. After False Discovery Rate (FDR) correction, only genetically proxied plasma RARRES1 remained statistically significant (OR = 1.17, adjusted P = 2.72 × 10-5), and this finding was replicated in an independent cohort. Bayesian colocalization supported a shared causal variant (PPH4 = 0.83). Functional enrichment analyses implicated RARRES1-related networks in immune regulation and extracellular processes. Two-step MR mediation analysis nominated CD16-CD56 intensity on NKT cells as a potential immune-mediated pathway, accounting for an estimated 11.8% of the genetic effect.</p><p><strong>Discussion: </strong>This study prioritizes genetically proxied plasma RARRES1 as a candidate protein associated with LCINS risk and highlights CD16-CD56 intensity on NKT cells as a potential immune-related mechanism. These findings provide biologically plausible evidence supporting a role for RARRES1 in LCINS pathogenesis and its potential utility in biomarker development.</p><p><strong>Conclusion: </strong>Genetically proxied plasma RARRES1 is associated with increased LCINS risk and may contribute to disease susceptibility through immune-related alterations involving NKT-cell phenotypes. RARRES1 represents a promising candidate for future mechanistic studies and blood-based diagnostic biomarker development in LCINS.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148905387","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":"HAMP, G6PD, and CCL18 as Potential Molecular Markers to Guide Treatment Decisions in Anti-PD-1/PD-L1 Immunotherapy for Hepatocellular Carcinoma.","authors":"Yamei Huang, Huanjun Tong, Qi Xin, Yuanfei Shi","doi":"10.2174/0109298673488277260820072854","DOIUrl":"https://doi.org/10.2174/0109298673488277260820072854","url":null,"abstract":"<p><strong>Introduction: </strong>This study explored the role of programmed death receptor 1 (PD-1) and programmed death-ligand 1 (PD-L1) in hepatocellular carcinoma (HCC) and established a gene-based model for predicting response to PD-1/PD-L1 treatment.</p><p><strong>Materials and methods: </strong>The anti-PD-1/PD-L1 treatment data of HCC were derived from the GEO dataset. Differentially expressed genes (DEGs) were analyzed using the DESeq2 package. LASSO regression was performed using the glmnet package. Immune composition was confirmed using CIBERSORTx. The PyCaret package was employed to predict the therapeutic response to anti-PD-1/PD-L1 treatment.</p><p><strong>Results: </strong>The HAMP, G6PD, and CCL18 genes influenced HCC progression and response to anti-PD-1/PD-L1. A Support Vector Machine (SVM) model was developed using gene expression data from three genes to predict the response of HCC patients to anti- PD-1/PD-L1 therapy. The model performed well on validation datasets, effectively distinguishing responders from non-responders.</p><p><strong>Discussion: </strong>This study identified novel molecular markers and developed a predictive tool for predicting the efficacy of anti-PD-1/PD-L1 therapy in patients with HCC.</p><p><strong>Conclusion: </strong>A novel SVM model comprising three genes was developed for predicting the treatment response in HCC patients.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148905370","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":"Functionalization of Mesoporous Carbon by Bovine Serum Albumin for Application in an Electrochemically Controlled Delivery System of Imatinib Anticancer Drug.","authors":"Zahra Zangeneh, Bahare Sabeti, Fereshteh Chekin","doi":"10.2174/0109298673476176260824045519","DOIUrl":"https://doi.org/10.2174/0109298673476176260824045519","url":null,"abstract":"<p><strong>Background: </strong>Imatinib (IM) is a tyrosine kinase inhibitor that targets the growth factor receptors. IM has demonstrated remarkable clinical efficacy across multiple cancer types. IM abrogates the activity of the Bcr-Abl oncoprotein, leading to the inhibition of cell proliferation and induction of apoptosis. However, side effects may negatively affect its efficiency.</p><p><strong>Objective: </strong>This prompted us to incorporate IM into nanostructured Bovine Serum Albumin- Coated Mesoporous carbon carriers (BSA/CMK-3) and to evaluate the electrochemically controlled release of the IM@BSA/CMK-3 nanoformulation in an in vitro model.</p><p><strong>Methods: </strong>The physicochemical characteristics of the IM@BSA/CMK-3 nanocapsules were examined using Field-Emission Scanning Electron Microscopy (FE-SEM), Ultraviolet- Visible (UV-Vis), Fourier Transform Infrared (FT-IR), X-ray Diffraction (XRD), and cyclic voltammetry analyses.</p><p><strong>Results: </strong>It was found that BSA/CMK-3 is an efficient carrier with IM loading as much as 84.6% in 0.1 M phosphate-buffered solution (PBS, pH 7.0) for 3 hours. BSA/CMK-3, due to the presence of functional groups (amino and carboxyl) in BSA, forms strong hydrogen bonds with the IM drug. We demonstrated that BSA/CMK-3 is a sensitive and efficient platform, and that BSA increases the stability of the IM@BSA/CMK-3 interface-- modified Screen-Printed Carbon Electrode (SPCE) and controls the release of the IM drug from the IM@BSA/CMK-3 hybrid. Furthermore, 81.4% of IM could be released upon application of +0.9 V for 2 hours at the IM@BSA/CMK-3 interface into PBS (0.1 M, pH 4.0). Furthermore, kinetic models were evaluated, and it was found that the drug release was best fit to the Higuchi model.</p><p><strong>Discussion: </strong>The BSA/CMK-3 nanohybrid, due to the presence of functional groups-rich BSA, seemed to provide effective loading and controlled electrochemical release of the IM drug.</p><p><strong>Conclusion: </strong>The electrochemically released IM drug loaded onto BSA/CMK-3 offers substantial potential for drug delivery applications.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148905367","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}