Current medicinal chemistry最新文献

{"title":"Exploring the Role of tRNA-Derived Fragments in Pterygium: Molecular Insights into tsRNA-Mediated Fibroblast Regulation and Disease Progression.","authors":"Qiaodan Yang, Xinyu Tang, Ruiying Zhang, Yulian Dou, Ming Yan, Fang Zheng","doi":"10.2174/0109298673361701250321082610","DOIUrl":"https://doi.org/10.2174/0109298673361701250321082610","url":null,"abstract":"<p><strong>Background: </strong>Pterygium is a common ocular surface disorder characterized by fibrovascular overgrowth, with recurrence remaining a major clinical challenge. While non-coding RNAs have been implicated in pterygium pathogenesis, the role of tRNA- derived small RNAs (tsRNAs) remains unexplored.</p><p><strong>Methods: </strong>We performed small RNA sequencing on pterygium and adjacent normal conjunctiva tissues to profile tsRNA expression. Differentially expressed tsRNAs were validated using qRT-PCR, and their biological functions were investigated via cell proliferation and wound healing assays in human pterygium fibroblasts (HPF). Potential target genes and enriched pathways were analyzed using bioinformatics approaches, including KEGG and GO enrichment analysis.</p><p><strong>Results: </strong>We identified significantly dysregulated tsRNAs in pterygium, with tRF- 1_30-His- GTG-1, tRF-1_31-Val-CAC-2, tRF-1_31-Gly-GCC-1, and tRF-1_30-Gly- CCC-1-M4 exhibiting notable upregulation. Functional assays demonstrated that tRF- 1_30-His- GTG-1 promotes fibroblast proliferation and migration, while the other three tsRNAs enhance fibroblast migration. Pathway enrichment analysis revealed their involvement in cellular proliferation, extracellular matrix remodeling, and angiogenesis.</p><p><strong>Conclusion: </strong>This study provides the first evidence of tsRNA involvement in pterygium pathogenesis, highlighting their potential as biomarkers and therapeutic targets. Future studies should focus on deciphering their precise regulatory mechanisms and developing RNA-based therapeutic strategies to mitigate disease progression.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526779","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 Putative GyrB Inhibitors against Mycobacterium tuberculosis: A Combined Virtual Screening and Experimental Study.","authors":"Likun Zhao, Xiaofei Qiu, Hongfu Li, Zixin Liu, Zhenzhen Du, Jianhong Xie, Henry H Y Tong, Mingxing Huang, Xiaojun Yao, Qianqian Zhang, Huanxiang Liu","doi":"10.2174/0109298673374736250527040516","DOIUrl":"https://doi.org/10.2174/0109298673374736250527040516","url":null,"abstract":"<p><strong>Introduction: </strong>With the rapid emergence of drug-resistant strains of tuberculosis, resistance to current first-line and second-line anti-tuberculosis drugs is becoming increasingly prevalent. Consequently, the discovery of new lead compounds is essential to address this challenge. GyrB has emerged as a promising target for tuberculosis treatment due to its pivotal role in DNA replication and topology regulation in Mycobacterium tuberculosis.</p><p><strong>Methods: </strong>In this study, a multi-conformational virtual screening approach, complemented by antibacterial activity assays, was utilized to identify novel GyrB inhibitors from the ChemDiv database.</p><p><strong>Results: </strong>Among the 27 compounds purchased, 10 exhibited significant inhibitory effects against the H37Rv strain, with 8 featuring novel core scaffolds. Notably, three compounds (V027-7669, V017-8710, and 5132-0213) demonstrated a minimum inhibitory concentration (MIC) of 8 μg/mL. Compounds V027-7669 and V017-8710, in particular, showed antibacterial activity against a multidrug-resistant tuberculosis strain, with MIC values of 32 μg/mL and 16 μg/mL, respectively. Molecular dynamics simulations revealed that both V027-7669 and V017-8710 bind stably to GyrB, which are primarily driven by nonpolar interactions. Furthermore, both of them occupy a novel sub-pocket formed by residues Val99, Gly106, Val123, Gly124, and Val125, where they establish hydrogen bonds with Val125.</p><p><strong>Conclusion: </strong>Our study underscores the effectiveness of a multi-conformational virtual screening strategy in identifying novel GyrB inhibitors and suggests V027-7669 and V017-8710 as promising lead compounds for the development of treatments against multidrug- resistant tuberculosis.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505070","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 Ubiquitination-Related Gene Prognostic Signature and the Oncogenic Role of RNF149 in Nasopharyngeal Carcinoma: scRNAseq-Based Bioinformatics and Experimental Validation.","authors":"Haiyan Deng, Juan Zhang, Shuaijun Chen, Tingfeng Liang, Xueyong Hu, Jing Li, Yong He, Feng Yu, Chaosheng Yu","doi":"10.2174/0109298673378818250610053439","DOIUrl":"https://doi.org/10.2174/0109298673378818250610053439","url":null,"abstract":"<p><strong>Introduction: </strong>Nasopharyngeal carcinoma (NPC) is an aggressive malignancy with a poor prognosis. Ubiquitination is a complex post translational modification involved in cancer progression. However, ubiquitination related genes (URGs) in immunotherapy of NPC remains largely unexplored.</p><p><strong>Methods: </strong>Differentially expressed URGs were screened based on the single-cell RNA sequencing (scRNA-seq) dataset and a risk model of NPC was constructed and evaluated for prognostic significance. The oncogenic role of RNF149 in NPC was investigated through in vitro and in vivo experiments, including tumor cells, NPC-like organoids, and tumor-bearing mice.</p><p><strong>Results: </strong>scRNA-seq data showed that URGs scores were higher in cancer cells than in normal epithelial cells. We identified 216 differentially expressed URGs between cancer and normal epithelial cells, but only 33 differentially expressed URGs associated with prognosis. Based on 33 URGs, TCGA-HNSC samples were classified into two distinct subtypes with significant differences in the tumor immune microenvironment, immunotherapy effect, and survival-prognostic genes. Using LASSO algorithm, 13 URGs were selected to construct a risk model, which demonstrated high predictive performance. The expression profiles of these 13 URGs were analyzed in TCGA-HNSC tumor and adjacent non-cancerous samples, and six URGs (BSPRY, OTUB1, PJA1, RNF149, RNF181, USP10) exhibited consistent expression trends. Moreover, quantitative real-- time PCR revealed that RNF149 was up-regulated expression in NPC cell compared to the NP69 cells. RNF149 knockdown significantly impeded the proliferative, migratory, and invasive capabilities and exaggerated apoptosis of NPC cells. RNF149 knockdown cells exhibited a reduced capacity to form NPC organoids in a 3D culture system. shRNA- RNF149 diminished subcutaneous tumorigenic capacity of HK-1 cells compared to the control group.</p><p><strong>Discussion: </strong>The URGs-based prognostic risk model offers a robust tool for predicting immunotherapy efficacy in NPC and RNF9 promotes NPC progression.</p><p><strong>Conclusion: </strong>A URGs-related prognostic risk model capable of predicting clinical outcomes in NPC patients and RNF9 promotes NPC progression. Our findings are expected to provide new strategies to improve outcomes for NPC patients.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505069","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":"Thirty Years of Structural Studies on Cyclin-Dependent Kinases: Implications for Drug Discovery.","authors":"Marco Tutone, Walter Filgueira de Azevedo","doi":"10.2174/0109298673420332250618094707","DOIUrl":"https://doi.org/10.2174/0109298673420332250618094707","url":null,"abstract":"","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505075","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":"Quinoline Heterocyclic Clubbed Hydrazone Derivatives as Potential Inhibitors of Mutant S. aureus DNA Gyrase A; An In-silico Drug Discovery Approach -Molecular Docking/MD Simulation, DFT Analysis and ADMET Predictions.","authors":"Sangeeta Verma, Sukhbir Lal, Rakesh Narang, Somdutt Mujwar, Tanuj Hooda","doi":"10.2174/0109298673370267250607160438","DOIUrl":"https://doi.org/10.2174/0109298673370267250607160438","url":null,"abstract":"<p><strong>Background: </strong>Staphylococcus aureus infections have become a significant public health issue due to increasing the resistance against known antibiotics, especially by Methicillin-Resistant Staphylococcus aureus (MRSA). Fluoroquinolones are broad- -spectrum class of antibiotics mostly utilized in treating various bacterial infections and those caused by S. aureus. Reported data indicated that mutations of Ser84 to Leu, Ser85 to Pro and Glu88 to Lys in DNA gyrase A enzyme are the major cause of fluoroquinolone resistance against S. aureus. Therefore, the development of a novel targeted molecule with potential activity against mutant S. aureus is essential. The antibacterial activity of quinoline-clubbed hydrazone derivatives against S. aureus is noteworthy. However, the mechanism of action of quinoline hydrazone derivatives has not been reported by inhibiting these common mutations of DNA gyrase A.</p><p><strong>Methods: </strong>In this concern, some quinoline hydrazone derivatives as antibacterial agents reported by several research groups have been further studied as mutated S. aureus DNA gyrase A (Pdb id: 8bp2) inhibitors using in-silico techniques viz., molecular docking, MD simulation, DFT analysis, and ADMET predictions.</p><p><strong>Results: </strong>Among the studied compounds, 48 and 49 were found to be the most active and showed the highest docking score (-9.29 kcalmol-1 and -8.47 kcalmol-1, respectively) by interaction with mutant (Leu84 and Pro85) of S. aureus DNA gyrase A. Further, MD simulation results indicated that both compounds exhibited good stability with the targeted macromolecule under dynamic conditions. The most active compound 49 (ʌE = 0.159 eV) attributed to its lower HOMO-LUMO gap, which was an indicator of a potential inhibitor of fluoroquinolone- resistant S. aureus DNA gyrase A enzyme. ADMET prediction study emphasized that both compounds showed a significant safety profile.</p><p><strong>Conclusion: </strong>The future perspective emphasized that compounds 48 and 49 could be developed as novel inhibitors against fluoroquinolone-resistant DNA gyrase A enzyme on the completion of drug discovery approaches.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505073","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":"Identify Key Genes and Construct the lncRNA-miRNA-mRNA Regulatory Networks Associated with Glioblastoma by Bioinformatics Analysis.","authors":"Dong Xingli, Ilgiz Gareev, Sergey Roumiantsev, Ozal Beylerli, Valentin Pavlov, Shiguang Zhao, Jianing Wu","doi":"10.2174/0109298673372488250530173615","DOIUrl":"https://doi.org/10.2174/0109298673372488250530173615","url":null,"abstract":"<p><strong>Introduction: </strong>Glioblastoma is the most common and aggressive brain tumor, with low survival rates and high recurrence rates. Therefore, it is crucial to understand the precise molecular mechanisms involved in the oncogenesis of glioblastoma.</p><p><strong>Material and methods: </strong>To investigate the regulatory mechanisms of long non-coding RNA (lncRNA)-microRNA (miRNA)-messenger RNA (miRNA) network related to glioblastoma, in the present study, a comprehensive analysis of the genomic landscape between glioblastoma and normal brain tissues from the Gene Expression Omnibus (GEO) dataset was first conducted to identify differentially expressed genes (DEGs) in glioblastoma. Following a series of analyses, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, protein-protein interaction (PPI), and key model analyses. In addition, we used the L1000CDS2 database bioinformatic tool to identify candidates for therapy based on glioblastoma specific genetic profile.</p><p><strong>Results: </strong>In our results, 100 key genes, 50 upregulated and 50 downregulated, were ultimately identified. The results of KEGG pathway enrichment gene analysis showed that the five regulatory pathways. Furthermore, 3 small molecule signatures (trichostatin A, TG-101348, and vorinostat) were recommended as the top-ranked candidate therapeutic agents. Nevertheless, the constructed miRNA-mRNA network revealed a convergence on 40 miRNAs. We found that dysregulation of lncRNAs such as KCNQ1OT1 and RP11-13N13.5 could sequester several miRNAs such as hsa-miR-27a-3p, hsamiR- 27b-3p, hsa-miR-106a-5p, etc., and promote the development and progression of glioblastoma.</p><p><strong>Conclusions: </strong>Our study identified key genes and related lncRNA-miRNA-mRNA network that contribute to the oncogenesis of glioblastoma.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505072","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 Role of DPF1 in Hepatocellular Carcinoma: Implications for Prognosis and Therapy.","authors":"Fan Yang, Yinyi Li, Dan Chen, Xiuju Wang, Mei Sun, Dongbing Li, Niansong Qian","doi":"10.2174/0109298673363347250529114300","DOIUrl":"https://doi.org/10.2174/0109298673363347250529114300","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) is a life-threatening cancer with rising incidence and mortality rates. Identifying new prognostic biomarkers is crucial for improving HCC management.</p><p><strong>Objectives: </strong>This study investigates the role of Double PHD Fingers 1 (DPF1) in hepatocellular carcinoma (HCC), exploring its potential as a prognostic indicator and therapeutic target.</p><p><strong>Methods: </strong>We analyzed DPF1 expression in 374 hepatocellular carcinoma (HCC) tissues and 50 normal tissues from the TCGA-HCC database, as well as in 240 HCC tissues and 202 normal tissues from the ICGC-HCC repository. We examined the correlation between DPF1 expression and clinical parameters, immune cell infiltration, drug response profiles, cancer stem cell (CSC) characteristics, and its diagnostic/prognostic potential using various bioinformatics tools and statistical analyses. Validation was performed using the ICGC and HPA databases, and qRT-PCR was used to confirm DPF1 expression in HCC cell lines.</p><p><strong>Results: </strong>DPF1 exhibited abnormal expression in HCC and several other malignancies. Elevated DPF1 levels were significantly associated with higher Alpha-fetoprotein (AFP) levels (p = 0.043) and poorer clinical outcomes, including diminished overall survival (OS) (p = 0.002), progression-free survival (PFS) (p = 0.018), and disease-specific survival (DSS) (p = 0.001). DPF1 expression was also linked to immune cell infiltration, immune checkpoint gene expression, drug sensitivity, and CSC characteristics. Notably, DPF1 was significantly overexpressed in HCC tissues and cell lines at both transcriptional and translational levels.</p><p><strong>Conclusion: </strong>Our study reveals that DPF1 is a novel prognostic biomarker in HCC, with potential implications for immunotherapy and drug resistance. Elevated DPF1 expression is associated with adverse clinical outcomes and may serve as a target for future therapeutic interventions in HCC.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505071","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 Progress of Wound Dressing Based on Sodium Alginate Composite Hydrogel.","authors":"Fengchao Zhou, Shibin Deng, Guorong Lin, Jiandong Shen, Dianping Tang","doi":"10.2174/0109298673362140250530094233","DOIUrl":"https://doi.org/10.2174/0109298673362140250530094233","url":null,"abstract":"<p><p>Hydrogel wound dressing has significant advantages in wound treatment. It can shorten the time of wound healing, control the process of wound healing, and effectively promote the healing of damaged tissues in a hydrated environment. Sodium alginate (SA) is a commonly used hydrogel wound dressing material, which can quickly form a three-dimensional network structure hydrogel in a relatively mild environment, but the mechanical properties and stability of a single SA hydrogel are poor. The composite hydrogel prepared by mixing SA with other substances can not only exert the performance of a single substance but also improve the mechanical properties, stability and adsorption of the hydrogel and has a wider application prospect in the field of sustained release control of bioactive substances. Natural polymers have been widely used in the preparation of hemostatic and wound healing materials due to their excellent biocompatibility, degradability, viscoelasticity and easy processing. This paper introduces the research progress of composite hydrogels prepared by SA and natural polymers in mechanical properties, antibacterial, anti-inflammatory, tissue repair and sustained release control of bioactive substances, and provides a theoretical basis for the application of SAbased composite hydrogels in wound dressings.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505074","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":"Paneth Cells: Recent Updates on Elucidating Therapeutic Implications in Gastroenterological Disease Management.","authors":"Maria V Sankova, Vladimir N Nikolenko, Anastasia A Bolotskaia, Marine V Oganesyan, Negoriya A Rizaeva, Aleksey V Sankov, Tatyana S Zharikova, André Pontes-Silva, Narasimha Murthy Beeraka, Hemanth Vikram P R, Padmanabha Reddy Y, Dilip Kumar Reddy Kandula, B M Gurupadayya, Yury O Zharikov","doi":"10.2174/0109298673357073250526104619","DOIUrl":"10.2174/0109298673357073250526104619","url":null,"abstract":"<p><strong>Background: </strong>The human intestine is continuously exposed to a variety of aggressive agents, including food antigens, xenobiotics, numerous pathogenic microorganisms, metabolic products, and toxins. Consequently, it has developed a specialized system for protection against these adverse factors.</p><p><strong>Objective: </strong>This study aims to investigate the biochemical compounds synthesized by Paneth cells and their mechanisms of action to develop new therapeutic approaches for gastroenterological diseases.</p><p><strong>Methods: </strong>We conducted a systematic review, excluding a comprehensive meta-analysis, of the current scientific literature sourced from electronic libraries (CyberLeninka, e-Library.ru, and Cochrane Library), search engines (Google Scholar, Embase, and Global Health), and scientific databases (Elsevier, Medline, PubMed-NCBI, and Scopus). Following PRISMA guidelines, a total of 104 articles were initially selected based on defined inclusion and exclusion criteria. After careful evaluation, 63 articles were included in this study.</p><p><strong>Results: </strong>Our findings indicate that Paneth cells play a crucial role in regulating small intestine homeostasis by secreting numerous biologically active molecules. A key feature of these cells is their ability to recognize soluble microbial products via pattern recognition receptors and respond by releasing a variety of antimicrobial peptides and enzymes. These secretions contribute to the formation of a biochemical barrier that prevents pathogen adhesion and translocation. Paneth cells are integral to immunological protection, maintaining protective inflammatory responses under both normal and pathological conditions. Additionally, they regulate the division, growth, and differentiation of intestinal stem cells, ensuring proper enterocyte localization. Paneth cells also aid digestive processes through enzyme secretion and are the only epithelial cells capable of eliminating activated autoreactive lymphocytes and abnormal enterocytes.</p><p><strong>Conclusion: </strong>Paneth cells are unique epithelial cells that, through the synthesis of numerous biologically active molecules, control the timely regeneration of the intestinal epithelium, maintain a healthy microbiota, and prevent infectious, autoimmune, and cancerous diseases. Understanding their role in these processes is crucial for developing new therapies for gastroenterological diseases.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144332631","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":"Knockdown of TRIM65 Inhibits Neoangiogenesis in Proliferative Diabetic Retinopathy by Regulating miR29a-3p.","authors":"Xinxin Chen, Xiaolong Chen, Shuai Huang, Yang Xian, Ruining Han","doi":"10.2174/0109298673325802240813103408","DOIUrl":"10.2174/0109298673325802240813103408","url":null,"abstract":"<p><strong>Introduction: </strong>High glucose-induced angiogenesis is the main component in Proliferative Diabetic Retinopathy (PDR) development. In PDR, ischemia and hypoxia have been identified as key stimuli that promote pathological neoangiogenesis by increasing Vascular Endothelial Growth Factor A (VEGFA). Furthermore, it has been demonstrated that TRIM65 knockdown in tumor cells reduces VEGFA expression. Building on these findings, the present study aimed to study the role of TRIM protein members in proliferative diabetic retinopathy.</p><p><strong>Method: </strong>In comparison to the control group, TRIM65 expression was significantly increased in human retinal endothelial cells (HREC) after high glucose treatment. Moreover, FITC/PI staining, cell wound scratch assay, transwell assay, tube formation assay, and immunofluorescence staining of VEGFA and HIF-3α were carried out, which indicated that TRIM65 knockdown inhibited high glucose-induced HREC cell apoptosis and angiogenesis and decreased the expression of VEGFA and HIF-3α, both of which are potential targets of miR-29a-3p. MIR-29a-3p inhibitor significantly reduced the effects of TRIM65 knockdown on VEGFA and HIF-3α expression levels in cells. TRIM65 induced ubiquitination and degradation of TNRC6A, resulting in suppressed miR-29a-3p expression.</p><p><strong>Result: </strong>Furthermore, in vivo studies revealed that intravitreal injection of miR-29a-3p inhibited neoangiogenesis in mice with Oxygen-Induced Retinopathy (OIR). The retinal tissues of OIR mice showed higher TRIM65 mRNA expression and lower miR-29a-3p expression than those of control mice. Furthermore, the analysis showed a negative correlation between the expression of miR-29a-3p and TRIM65 in the retinal tissues of OIR mice.</p><p><strong>Conclusion: </strong>In conclusion, this study demonstrated that the knockdown of TRIM65 inhibits neoangiogenesis in proliferative diabetic retinopathy by regulating miR-29a-3p.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144332630","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}