Current medicinal chemistry最新文献

{"title":"Inflammatory Biomarkers in Hypertension.","authors":"Panagiotis Tsioufis, Panagiotis Theofilis, Kyriakos Dimitriadis, Panayotis K Vlachakis, Panayotis Iliakis, Dimitrios Tsiachris, Konstantinos Tsioufis, Dimitris Tousoulis","doi":"10.2174/0109298673348789250604113545","DOIUrl":"https://doi.org/10.2174/0109298673348789250604113545","url":null,"abstract":"<p><p>Hypertension remains a leading modifiable risk factor for cardiovascular diseases, yet its underlying mechanisms are not fully understood. Emerging evidence suggests that inflammation plays a central role in the pathogenesis and progression of hypertension. This review explores the association between inflammatory biomarkers, such as C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α), and hypertension. These biomarkers are not only indicators of inflammation but also active participants in the processes that elevate blood pressure, including endothelial dysfunction, oxidative stress, and immune system activation. Cytokines play a pivotal role in vascular remodeling and renal dysfunction, underscoring the inflammatory underpinnings of hypertension. Additionally, novel composite biomarkers like the monocyte-to-high-density lipoprotein ratio (MHR), systemic inflammation response index (SIRI), and systemic immune-inflammation index (SII) have been identified as valuable tools for assessing the inflammatory state in hypertensive patients. While renal denervation has emerged as a promising treatment for resistant hypertension, its impact on inflammatory biomarkers remains inconclusive, highlighting the need for further research.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648732","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 Cuproptosis-related Genes in Acute Myeloid Leukemia Through WGCNA, Single-cell Sequencing and Experiments.","authors":"Leping Liu, Haixia Zhang, Phoebe Abonyo Ouru, Pan Chen, Minghua Yang","doi":"10.2174/0109298673363210250618120652","DOIUrl":"https://doi.org/10.2174/0109298673363210250618120652","url":null,"abstract":"<p><strong>Background: </strong>Cuproptosis, a newly discovered form of programmed cell death, has potential implications for tumorigenesis and cancer progression. This study investigates the role of cuproptosis in Acute Myeloid Leukemia (AML) and identifies associated biomarkers using bulk and single-cell RNA sequencing. Despite recent advances, the mechanisms of cuproptosis in AML remain unclear, and its relationship with immune cell infiltration could reveal novel therapeutic targets.</p><p><strong>Methods: </strong>RNA-seq data from 151 AML patients and 70 healthy controls were obtained from TCGA and GTEx databases, and single-cell RNA-seq data from 10 AML patients (GEO) were used for validation. Differential expression of Cuproptosis-Related Genes (CRGs) was analyzed via RCircos and correlation analysis. Immune cell infiltration was assessed using CIBERSORT and ssGSEA. WGCNA identified key genes for AML and cuproptosis subtypes, which were validated with single-cell data. Intercellular communication was analyzed through ligand-receptor interactions. RNA interference experiments validated TLR4 and NCF2, with gene expression measured through RT-qPCR. Apoptosis and CCK-8 assays assessed cell viability.</p><p><strong>Results: </strong>We identified 18 CRGs with differential expression between AML subtypes linked to immune cell infiltration. Subtype analysis classified AML patients into C1 and C2 subgroups enriched in biosynthesis and metabolism pathways. WGCNA identified 2701 genes associated with AML and 92 with cuproptosis, leading to 15 intersecting genes. RETN was highlighted as key in intercellular communication. Experimental validation showed that elesclomol-induced cell death in THP-1 cells is reversible by TTM. Knockout of TLR4 and NCF2 promoted cuproptosis.</p><p><strong>Conclusion: </strong>These findings offer new insights into the role of cuproptosis in AML, highlighting novel biomarkers, such as TLR4 and NCF2, which may provide promising targets for the development of future therapeutic strategies in AML treatment.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648731","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":"Targeted Protein Degradation in Lung Cancer: The Emerging Role of PROTAC Technology and E3 Ligases.","authors":"Md Sadique Hussain, M Arockia Babu, Muhammad Afzal, R Roopashree, Madan Lal, A Rekha, Brian G Oliver, Ronan MacLoughlin, Amlan Chakraborty, Kamal Dua, Haider Ali, Moyad Shahwan, Gaurav Gupta","doi":"10.2174/0109298673382742250619055201","DOIUrl":"https://doi.org/10.2174/0109298673382742250619055201","url":null,"abstract":"<p><p>Lung cancer remains one of the most prevalent and lethal malignancies, with poor drug response and high mortality rates. Proteolysis-targeting chimeras (PROTACs) are emerging as a novel therapeutic strategy, leveraging E3 ligases to degrade oncogenic proteins selectively via the ubiquitin-proteasome pathway. These degraders offer higher selectivity and bioavailability compared to traditional inhibitors. This review explores how PROTACs eliminate oncogenic proteins in lung cancer and examines the role of E3 ligases in this process. Commonly utilized ligases include Cereblon (CRBN) and Von Hippel-Lindau (VHL), while newer ones, such as MDM2 and Kelch-like ECH-associated protein 1 (KEAP1), are being investigated for therapeutic potential. We discuss key factors in PROTAC design, including ligand selection, linker optimization, and pharmacokinetic properties, which influence tumor specificity and efficacy while minimizing off- target effects. Additionally, we highlight targetable oncogenic drivers in lung cancer, such as KRAS, EGFR, and ALK fusion proteins, and evaluate preclinical and clinical studies that demonstrate PROTACs' potential for overcoming drug resistance. The challenges associated with clinical translation, tumor microenvironment interactions, and E3 ligase selection are also discussed. Finally, we present future perspectives, including expanding the range of E3 ligases, developing multitargeting strategies, and integrating next-generation molecular glue degraders. By offering a comparative analysis of E3 ligase- specific PROTACs, this review underscores the potential of PROTAC technology to advance precision oncology in lung cancer.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating Microarray Analysis, Machine Learning, and Molecular Docking to Explore the Mechanism of Doxorubicin-induced Cardiotoxicity.","authors":"Yidong Zhu, Jun He, Rong Wei","doi":"10.2174/0109298673401752250709101602","DOIUrl":"https://doi.org/10.2174/0109298673401752250709101602","url":null,"abstract":"<p><strong>Introduction: </strong>Doxorubicin (DOX) is a chemotherapeutic agent widely used for the treatment of various cancers; however, its clinical use is limited by its cardiotoxicity. However, the underlying molecular mechanisms remain poorly understood, hindering the development of effective preventive and treatment strategies. This study aimed to identify core target genes and explore the mechanisms involved in DOX-induced cardiotoxicity by integrating microarray analysis, machine learning, and molecular docking.</p><p><strong>Materials and methods: </strong>Differential expression analysis was performed using microarray data from DOX-induced cardiotoxic samples and healthy controls. Multiple machine learning algorithms were applied to identify core target genes. The predictive performance of these genes was evaluated using receiver operating characteristic (ROC) curves. Molecular docking was conducted to evaluate the binding affinity of DOX to the target genes. Functional analysis was performed to investigate potential toxic mechanisms.</p><p><strong>Results: </strong>In total, 276 differentially expressed genes were identified in DOX-induced cardiotoxicity samples and controls. The support vector machine algorithm demonstrated the best performance, leading to the identification of five core target genes: RAP1A, CTLA4, OR2M1P, TRIM53, and LOC149837. The ROC curves confirmed the strong predictive power of these genes, with area under the curve values greater than 0.85. Molecular docking showed stable binding between DOX and the target genes. Functional analysis suggested that the Rap1 signaling pathway and immune system regulation may be involved in DOX-induced cardiotoxicity.</p><p><strong>Discussion: </strong>Traditional toxicological studies often rely on limited experimental approaches that do not fully capture the complexity of disease mechanisms. The integration of microarray analysis, machine learning, and molecular docking in this study offers a comprehensive framework for investigating the toxicological pathways of DOXinduced cardiotoxicity, thereby providing insights into therapeutic development and safety regulations.</p><p><strong>Conclusion: </strong>By combining microarray analysis, machine learning, and molecular docking, we identified five key target genes associated with DOX-induced cardiotoxicity. Functional analysis further suggested the involvement of the Rap1 signaling pathway and immune system regulation in DOX-induced cardiotoxicity. These findings offer insights into the molecular mechanisms underlying DOX-induced cardiotoxicity and have implications for the development of protective strategies and therapeutic interventions.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648733","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":"Characterization of Tumor Microenvironment and Prognosis of Regulatory T cells-Related Subtypes.","authors":"Xinwei Li, Meiyun Nie, Keke Yang, Xiaodong Qi, Xiong Wan, Ling Yang","doi":"10.2174/0109298673375015250513094405","DOIUrl":"https://doi.org/10.2174/0109298673375015250513094405","url":null,"abstract":"<p><p><p>Introduction: Regulatory T cells (Tregs) play an important role in the tumor microenvironment (TME). Currently, there have been no studies of Treg-related genes (TRGs) in lung adenocarcinoma (LUAD). </p><p> Methods: We integrated the Cancer Genome Atlas (TCGA) dataset with the Gene Expression Omnibus (GEO) dataset and divided the TCGA-GEO dataset patient samples into different cohorts by unsupervised clustering analysis based on the expression of TRGs in LUAD. By analyzing the TME characteristics of different cohorts, we assessed immune cell infiltration and function. In addition, we constructed Cox risk proportional regression models based on TRGs to predict patient prognosis.</p><p> Results: The results of unsupervised cluster analysis classified the TCGA-GEO dataset as \"immune desert\", \"immune evasion\" and \"immune inflammation\". Moreover, there was a significant survival differential among the three cohorts (p-value < 0.05). Based on the expression of 61 TRGs in LUAD, we screened TFRC, CTLA4, IL1R2, NPTN NPTN and METTL7A to construct a Cox risk proportional regression model to divide the TCGA-GEO dataset into a training cohort and a test cohort. Survival was significantly worse in the high-risk group than in the low-risk group in both the training and test cohorts (p-value < 0.05). Finally, the nomogram scoring system constructed by integrating the model risk scores with clinical parameters can well predict the 1, 3 and 5 year survival of patients.</p><p> Conclusion: In conclusion, based on our analysis of the TRGs of LUAD patients, we can classify the patient TME into different immune statuses, which provides insights into adopting appropriate treatment regimens for different patients.</p>.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144625564","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":"Designing of Peptide Vaccine by Investigating Monkeypox Virus Membrane Glycoprotein: An Integrated In Silico and Immunoinformatics Approach.","authors":"Saurav Kumar Mishra, Prerna Priya, Abdul Basit, Nikita Krishna, Shopnil Akash, Turki M Dawoud, Mohammed Bourhia, John J Georrge","doi":"10.2174/0109298673374742250327041841","DOIUrl":"https://doi.org/10.2174/0109298673374742250327041841","url":null,"abstract":"<p><strong>Background: </strong>In 2022, the World Health Organisation (WHO) announced new cases of the developing Monkeypox Virus (MPXV), a zoonotic orthopoxvirus viral infection that mimics smallpox signs. Despite the ongoing infection, no proper medication is available to completely overcome this infection.</p><p><strong>Aim: </strong>The study aims to construct a multi-epitope vaccine targeting Monkeypox Virus (MPXV) membrane glycoprotein to provoke robust immune responses.</p><p><strong>Objective: </strong>To construct a potential immuno-dominant epitope vaccine to combat MPXV.</p><p><strong>Methods: </strong>The target sequence, sourced from the UAE-to-India travel case, was analyzed to identify potential B-cell and T-cell epitopes (MHC-I and MHC-II). Immunodominant epitopes were selected and fused with β-defensin-I and PADRE to increase immunogenicity. The vaccine was modeled, docked with TLR3, and subjected to a 500 ns molecular dynamics simulation for stability analysis. Immune responses and bacterial expression were also evaluated.</p><p><strong>Results: </strong>The vaccine, comprising 230 amino acids, demonstrated antigenicity (0.6620), non-allergenicity, and broad population coverage. Selected epitopes included 3 B-cells, 4 MHC-I, and 2 MHC-II, ensuring a potent immunodominant profile. Docking with TLR3 revealed a binding affinity of -17.2 kcal/mol, while simulations confirmed their stability. Cloning (pET28a (+)) and immune response analyses showed a strong immunogenic profile, including elevated IgG1, IgM, and antigen levels, supported by a Codon Adaptation Index (CAI) of 1.0.</p><p><strong>Conclusion: </strong>The proposed multi-epitope vaccine shows promise against MPXV. However, further in vivo and in vitro investigations are essential to confirm its immune efficacy.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607762","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":"Ozone-induced Neurotoxicity: Mechanistic Insights and Implications for Neurodegenerative Diseases.","authors":"Geir Bjørklund, Leonard Gurgas, Tony Hangan","doi":"10.2174/0109298673375058250624070823","DOIUrl":"https://doi.org/10.2174/0109298673375058250624070823","url":null,"abstract":"<p><p>Ozone (O3), a reactive gas produced by sunlight-driven reactions involving nitrogen oxides and volatile organic compounds, presents serious risks to both respiratory and brain health. While its harmful effects on the lungs are well established, there is increasing evidence connecting ozone exposure to cognitive decline and neurodegenerative conditions like Alzheimer's and Parkinson's diseases. Ozone induces oxidative stress and systemic inflammation, and activates microglia, with the potential to reach the brain directly through the olfactory pathway. These mechanisms play a role in key neurodegenerative processes, such as the buildup of amyloid-beta, abnormal tau phosphorylation, and mitochondrial dysfunction. Drawing from findings in both animal and human studies, this review highlights the critical need to reduce ozone exposure to safeguard brain health and alleviate the growing impact of neurological disorders.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607763","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":"Vitamin D and Diabetes: Exploring the Link, Prevention, and Management.","authors":"Geir Bjørklund, Monica Butnariu, Leonard Gurgas, Tony Hangan","doi":"10.2174/0109298673360987250621042131","DOIUrl":"https://doi.org/10.2174/0109298673360987250621042131","url":null,"abstract":"<p><p>Vitamin D is a crucial nutrient that plays a significant role in various aspects of health. This review explores the importance of vitamin D and its cofactors in preventing and managing diseases, mainly focusing on diabetes and its complications. The evidence reveals a strong link between low vitamin D levels and increased risks of type 2 diabetes (T2D), gestational diabetes, and type 1 diabetes. Vitamin D supplementation, which has shown promising results in reducing the incidence of these diseases and improving outcomes, offers hope in the fight against diabetes. Additionally, vitamin D deficiency has been linked to an increased risk of complications in diabetes, including depression, cancer, peripheral neuropathy, and diabetic foot ulcers. Adequate vitamin D levels have been shown to prevent and treat these complications, improving symptoms and overall outcomes. The review also highlights the global vitamin D deficiency pandemic. It explores strategies for optimizing vitamin D levels, including sun exposure, dietary sources, supplementation, and the role of cofactors such as magnesium and vitamin K2. It underscores the importance of raising awareness about the significance of vitamin D optimization and the need for everyone to play a role in implementing these strategies, as it can profoundly impact disease prevention and management.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607764","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":"Development and Validation of a Prognostic Signature Based on Transcription Factors Associated with Endoplasmic Reticulum Stress in Pancreatic Adenocarcinoma.","authors":"Shan Gao, Zhenchu Tang, Yuqian Zhou","doi":"10.2174/0109298673364512250611034932","DOIUrl":"https://doi.org/10.2174/0109298673364512250611034932","url":null,"abstract":"<p><strong>Background: </strong>Endoplasmic reticulum stress (ER stress) plays a crucial role in influencing the malignant behaviors of various tumors. Targeting the expression or degradation of transcription factors (TFs) offers a promising avenue for cancer treatment. However, a detailed understanding of how ER stress affects TF function and their interactions remains limited. This study aims to develop a prognostic model and identify TFs associated with ER stress in pancreatic ductal adenocarcinoma (PDAC).</p><p><strong>Methods: </strong>We obtained gene expression profiles and corresponding clinical data from The Cancer Genome Atlas (TCGA). To develop a prognostic signature, we performed several analyses, including unsupervised clustering, enrichment analysis, immune infiltration assessment, as well as univariate, LASSO, and multivariate Cox regression analyses. Four transcription factors-STAT1, IRF6, NRF1, and RXRA-were incorporated into a risk model, which was subsequently validated using the GSE dataset. Additionally, we examined IRF6 through quantitative PCR, western blotting, flow cytometry, and immunohistochemistry in vitro using pancreatic cancer cell lines and a tissue microarray.</p><p><strong>Results: </strong>The high-risk group identified by the model exhibited significant associations with immune cell infiltration and poorer survival outcomes, though there was no significant correlation with tumor purity (p = 0.19). Furthermore, IRF6 downregulation in vitro was found to inhibit pancreatic cancer cell proliferation and promote apoptosis. IRF6 depletion also increased the expression of key molecules involved in ER stress at both the transcriptional and translational levels. Immunohistochemical analysis revealed marked differences in IRF6 expression between tumor and adjacent non-tumor tissues (59.29±29.88 vs. 95.22±40.80, p<0.001).</p><p><strong>Conclusion: </strong>This study provides evidence that the constructed risk model can effectively predict prognosis in PDAC patients. Transcription factors related to ER stress, such as IRF6, show promise as both prognostic biomarkers and potential therapeutic targets for PDAC.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599703","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 miRNA-mRNA Regulatory Networks Associated with Intracranial Aneurysm Progression by Integrative Bioinformatics Analysis.","authors":"Xi'ao Wang, Valentin Pavlov, Ilgiz Gareev, Shancai Xu","doi":"10.2174/0109298673356665250612135856","DOIUrl":"https://doi.org/10.2174/0109298673356665250612135856","url":null,"abstract":"<p><strong>Background: </strong>Intracranial aneurysms (IAs) are the leading cause of nontraumatic subarachnoid hemorrhage (SAH), accounting for up to 85% of all cases of intracranial hemorrhage. The aim of this study was to identify core genes and pathways revealing IAs progression.</p><p><strong>Materials and methods: </strong>We screened differentially expressed genes (DEGs) using mRNA expression profile data from Gene Expression Omnibus (GEO). Then functional and pathway enrichment analyses of DEGs were performed utilizing the database for annotation, visualization, and integrated discovery (DAVID) and the GEO Data Analysis Module within the ACBI Bioinformation tool. Target genes with differential expression of miRNAs were predicted using the miRWalk (Version 3.0) database, and the intersection between these predictions and DEGs was selected as differentially expressed miRNAtarget genes. In addition, a protein-protein interaction (PPI) network and an miRNAmRNA regulatory network were constructed. Finally, L1000CDS2 database analyses were performed to identify the potential therapeutic targets for IAs.</p><p><strong>Results: </strong>In total, 742 DEGs and 171 DEGs were identified from the GSE13353 and GSE15629 datasets, respectively. The PPI of DEGs consisted of 868 nodes and 618 edges, including 392 upregulated genes and 521 downregulated genes, respectively, while 10 hub genes were identified. Among the top 10 hub genes, justification of CXCR4, IL6, CCR5, CCL5, CXCR2, CXCL1, CCL2, CCL20, CD4, and CXCL10. These hub genes were primarily augmented in the atherosclerosis process, cytokine-cytokine receptor interaction and cell adhesion molecules pathways. Through the miRNAs-hub gene network construction, 7 miRNAs associated with the hub genes were identified. The results suggest that the sensitivity toward simvastatin, curcumin, parthenolide, celastrol, BMS-345541, etc., correlates with the expression of 10 hub genes.</p><p><strong>Conclusion: </strong>In summary, this study reveals some crucial genes and pathways potentially involved in the pathogenesis of IAs progression. These findings provide a new insight into the research and treatment of IAs.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599705","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}