Current medicinal chemistry最新文献

{"title":"Ginsenosides in Ovarian Cancer Therapy: Mechanistic Insights with an Emphasis on microRNA Regulation and Translational Prospects.","authors":"Sobhan Jalali, Mohammadreza Besharatloo, Mojtaba Zehtabi, Dorrin Alipour Amini, Amir Hossein Barjasteh, Mohammad Hossein Pourhanifeh","doi":"10.2174/0109298673451112260813064135","DOIUrl":"https://doi.org/10.2174/0109298673451112260813064135","url":null,"abstract":"<p><p>Ovarian cancer remains one of the most lethal gynecological malignancies due to late diagnosis, high recurrence rates, and resistance to conventional therapies. Emerging evidence underscores the therapeutic potential of natural compounds, among which ginsenosides, the principal bioactive components of ginseng, exhibit remarkable anticancer properties. This review summarizes current insights into the anti-ovarian cancer activities of ginsenosides, with particular focus on their regulatory effects on non-- coding RNAs, especially microRNAs. Ginsenosides modulate diverse molecular pathways, including apoptosis induction, autophagy regulation, epithelial-to-mesenchymal transition suppression, angiogenesis inhibition, and epigenetic reprogramming. Increasing evidence demonstrates that ginsenosides exert tumor-suppressive effects by restoring tumor-suppressor microRNAs and repressing oncogenic ones, thereby interfering with cancer stem cell maintenance, metabolic reprogramming, and metastatic progression. Furthermore, ginsenosides enhance the efficacy of chemotherapeutic agents such as paclitaxel and cisplatin while reducing associated toxicity. Despite promising preclinical findings, clinical translation remains limited due to challenges in bioavailability and pharmacokinetics. Collectively, ginsenosides represent a promising class of phytochemicals for ovarian cancer treatment, particularly through microRNA-centered mechanisms, warranting further investigation into optimized formulations, nanodelivery systems, and well-designed clinical trials.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148905353","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":"KLK6 is Associated with a Neutrophil-Dominant Immunosuppressive Microenvironment and Epigenetic Deregulation in Lung Adenocarcinoma.","authors":"Ling-Jie Chen, Wen-Bo Zhou, Jiong Wang, Qing-Kui Guo","doi":"10.2174/0109298673476481260730114934","DOIUrl":"https://doi.org/10.2174/0109298673476481260730114934","url":null,"abstract":"<p><strong>Introduction: </strong>Lung adenocarcinoma (LUAD) is the most prevalent histological subtype of lung cancer and is associated with poor survival despite advances in targeted therapies. Kallikrein-related peptidase 6 (KLK6) has been implicated in several malignancies, but its expression pattern, clinical relevance, and biological function in LUAD remain incompletely characterized. This study aimed to evaluate KLK6 expression and its associations with prognosis, epigenetic regulation, immune infiltration, and migratory phenotypes in LUAD.</p><p><strong>Methods: </strong>RNA-seq expression and clinical data were obtained from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Gene Expression Omnibus (GEO) databases. KLK6 expression was analyzed in relation to clinicopathological parameters, survival outcomes, promoter methylation status (via UALCAN), and tumor-infiltrating immune cell abundance (via TIMER2.0). In vitro, KLK6 was knocked down using shRNA in A549 and H1299 LUAD cell lines. Cell migration was assessed by transwell assays, and the expression of Epithelial-Mesenchymal Transition (EMT)- and Wnt signaling-related markers was examined by qRT-PCR and Western blotting.</p><p><strong>Results: </strong>KLK6 expression was significantly upregulated in LUAD tissues compared with normal lung tissues. High KLK6 expression was associated with poorer overall survival (HR = 1.52, P = 0.009) and disease-specific survival (HR = 1.55, P = 0.03). ROC analysis showed that KLK6 discriminated stage I LUAD from normal tissues with an AUC of 0.73. Promoter hypomethylation was observed in LUAD tumors and correlated with increased KLK6 expression. Immune infiltration analysis revealed that KLK6-high tumors exhibited reduced B-cell infiltration and increased neutrophil infiltration. Functional experiments demonstrated that KLK6 knockdown significantly suppressed cell migration, accompanied by increased E-cadherin and decreased N-cadherin, Vimentin, Wnt5a, and β-catenin expression.</p><p><strong>Discussion: </strong>These findings suggest that KLK6 overexpression in LUAD is driven in part by promoter hypomethylation and is closely linked to a neutrophil-dominant immunosuppressive microenvironment. Furthermore, KLK6 appears to promote LUAD cell migration through EMT- and Wnt-related signaling pathways. Collectively, these multi-layered data position KLK6 as a potential driver of aggressive tumor behavior and a candidate biomarker for risk stratification.</p><p><strong>Conclusion: </strong>KLK6 is aberrantly overexpressed in LUAD and is associated with poor prognosis and enhanced migratory capacity. It may serve as a promising prognostic biomarker and a potential therapeutic target for LUAD.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148905373","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":"Scutellaria Barbata Flavonoids Mitigate Alzheimer's Disease-related Aβ25-35 Toxicity in N2a Cells through CREB Phosphorylation.","authors":"Xiaomin Yu, Yan Yi, Xinyang Liu, Chunying Zhao, Caixia Li, Yazhen Shang, Ke He, Yujian Zhai","doi":"10.2174/0109298673438931260822121059","DOIUrl":"https://doi.org/10.2174/0109298673438931260822121059","url":null,"abstract":"<p><strong>Background: </strong>Mouse neuroblastoma cells (N2a) are spontaneously derived from mice and possess the characteristics of neural stem cells. The proliferation, differentiation, and protrusion growth of N2a cells in vitro are consistent with those in vivo. Flavonoids isolated from the aerial parts of Scutellaria barbata (SBFs) can improve learning and memory deficits and protect against neuronal injury in many in vivo AD-- like models. N2a cells exposed to Aβ25-35 for Alzheimer's disease-related toxicity were subsequently used to observe the ameliorative effects of SBFs, and the effective mechanism through which SBFs promote the phosphorylation of CREB was further studied by using BI-D1870, an indirect inhibitor, and Rolipram, an activator of CREB phosphorylation.</p><p><strong>Methods: </strong>Immunofluorescence (IF) was used to detect the protein expression of the neuron-specific proteins NeuN, NeuroD1, and DCX. N2a cells were exposed to 100 μM Aβ25-35 and treated with SBFs at doses of 17.5, 35 and 75 mg·L-1 or 363 μM Rolipram. Cell morphology was observed under an inverted microscope, the cell survival rate was detected by the Cell Counting Kit-8 (CCK-8) method, and the release of lactate dehydrogenase (LDH) into the cell culture medium was determined by the pyruvate reduction method. The mRNA expression levels of ERK, RSK, CREB, and EGR-1 in cells were detected by real-time quantitative polymerase chain reaction (qPCR). IF and/or western blotting (WB) were used to measure the protein expression levels of BDNF, NGF, TrkB, Ras, ERK/p-ERK, Rsk/p90RSK, CREB/p-CREB-Ser133, and EGR-1 in N2a cells.</p><p><strong>Results: </strong>NeuN, NeuroD1, and DCX expression in N2a cells was positive, as indicated by green fluorescence. Both Aβ25-35 and BI-D1870 resulted in abnormal morphological changes in N2a cells, reduced the cell survival rate (P<0.01), increased the release of LDH (P<0.01) into the culture medium, and decreased the mRNA expression levels of ERK, RSK, and CREB and the protein expression levels of p-ERK, TrkB, p90RSK, pCreb-SER133, BDNF, NGF and EGR-1 (P<0.01) in cells. However, SBFs, to varying degrees, reversed the aforementioned abnormal changes in N2a cells caused by Aβ25-35 or BI-D1870, and the effects of SBFs were consistent with those of Rolipram.</p><p><strong>Conclusion: </strong>SBFs protected against N2a cell damage induced by toxic Aβ25-35, and the effective mechanism by which SBFs promote the phosphorylation of CREB at the Ser133 site was confirmed through the application of the indirect CREB phosphorylation inhibitor BI-D1870 and the activator Rolipram. These findings suggest that SBFs may be helpful in the treatment of AD by intervening in CREB phosphorylation.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148905348","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":"New Frontiers in Cancer Treatment.","authors":"Rafael Coveñas","doi":"10.2174/0109298673542331260821045101","DOIUrl":"https://doi.org/10.2174/0109298673542331260821045101","url":null,"abstract":"","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891200","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":"Olfactory Receptor Dysfunction Induced by Fenton and Fenton-Like Reactions: Linking Molecular Damage to Behavior.","authors":"Khatuna Dondoladze","doi":"10.2174/0109298673485458260810061255","DOIUrl":"https://doi.org/10.2174/0109298673485458260810061255","url":null,"abstract":"<p><p>When inhaled, environmental toxins enter not only the respiratory system but also the olfactory system. Metallic compounds in the environment form various free radicals through Fenton reactions and Fenton-like reactions. These free radicals damage the olfactory system in various ways. Reactive oxygen species generated during Fenton and Fenton-like reactions damage olfactory G protein-coupled receptors, disrupting the receptor's coupling to GOₗf and cAMP- and IP3/Ca2+-dependent signaling. The cascade of reactions involves ion channels, mitochondria, enzymes, lipids, proteins, DNA, and antioxidant defense mechanisms, including Nrf2-dependent transcriptional programs, glutathione, and others. Essentially, Fenton and Fenton-like reactions both generate free radicals; however, the reactive hydroxyl radical (•OH) generated in the classical Fenton reaction rapidly and locally damages neuronal cell and receptor structural molecules, whereas Fenton-like reactions, through surface-mediated, prolonged ROS production, cause progressive, chronic damage that differentially alters GPCR-GOₗf signaling and neuronal function; the study of these mechanisms is essential for assessing oxidative neurotoxicity of the olfactory system. This review discusses damage to olfactory receptor structures by radicals generated during Fenton and Fenton-like reactions, the characteristics of these chemical reactions, and the corresponding behavioral clinical changes.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891174","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":"Immunotherapy, Gene Therapy and Big Data Analysis in Burns, Trauma and Cosmetic Surgery.","authors":"Peng Wang, Zexin Zhang, Yingjun Su","doi":"10.2174/0109298673537793260819070550","DOIUrl":"https://doi.org/10.2174/0109298673537793260819070550","url":null,"abstract":"","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891161","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":"Recent Updates on the Neuroprotective Effects of Nobiletin in Neurological Disorders: From Molecular Targets to Clinical Prospects.","authors":"Leila Mohammadi, Tourandokht Baluchnejadmojarad, Mehrdad Roghani","doi":"10.2174/0109298673467257260821042739","DOIUrl":"https://doi.org/10.2174/0109298673467257260821042739","url":null,"abstract":"<p><strong>Background: </strong>Neurological disorders are a significant and increasing public health concern due to their multifactorial pathogenesis, progressive clinical course, and limited long-term effectiveness of current therapeutic strategies. Recent experimental and clinical studies have increasingly focused on bioactive natural compounds as potential modulators of neuroinflammation, oxidative stress and neuronal apoptosis - processes that play a central role in neurodegeneration. Of these, nobiletin (a polymethoxylated flavonoid found in citrus peels) has attracted particular attention thanks to its reported antioxidant, anti-inflammatory and neuroprotective properties in preclinical models.</p><p><strong>Objective: </strong>We discuss the potential therapeutic role of nobiletin in neurological diseases, examining the relevant molecular mechanisms, preclinical findings, and emerging clinical data.</p><p><strong>Methods: </strong>We searched the electronic databases PubMed, Scopus, and Embase to identify studies examining the therapeutic effects of nobiletin on neurological disorders published up to October 2025.</p><p><strong>Results: </strong>This review discusses the neuroprotective actions of nobiletin, with particular attention to its anti-inflammatory, anti-apoptotic, and antioxidant activities and their involvement in major intracellular signaling pathways. In addition, available preclinical findings and emerging clinical data are examined to assess the therapeutic relevance of nobiletin in experimental and clinical models of neurological disorders.</p><p><strong>Discussion: </strong>Experimental evidence suggests that nobiletin has neuroprotective properties that could reduce pathological processes associated with neurodegenerative disorders, such as Alzheimer's and Parkinson's diseases. However, further well-designed studies are needed to clarify its mechanisms of action and determine whether these effects are beneficial in clinical practice, either as a standalone therapy or in combination with existing treatments.</p><p><strong>Conclusion: </strong>Overall, the available evidence indicates that nobiletin may have beneficial effects on a wide range of neurological conditions, such as Parkinson's disease, Alzheimer's disease, stroke, epilepsy, depression, schizophrenia, multiple sclerosis, glioma, and sciatic nerve injury.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891168","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":"Circulating lncRNA Landscapes: Redefining Biomarker Discovery in Ovarian Cancer.","authors":"Lidia Lorenzo-Catoira, Ángel Vizoso-Vázquez, Aida Barreiro-Alonso, María Esperanza Cerdán, Esther Rodríguez Belmonte, Monica Lamas-Maceiras","doi":"10.2174/0109298673492387260806065240","DOIUrl":"https://doi.org/10.2174/0109298673492387260806065240","url":null,"abstract":"<p><p>Ovarian cancer (OC) is an aggressive disease with nonspecific clinical manifestations that is frequently diagnosed at advanced stages, drastically reducing the 5- year survival rate, due in part to the absence of specific biomarkers. Owing to its high sensitivity and reproducibility, low cost, and minimal invasiveness, liquid biopsy is a promising technique for OC. Although proteins, ctDNA, and miRNAs have been widely studied as biomarkers, lncRNAs are more advantageous due to their cell- and tissue-specific expression and high stability. Several lncRNAs with potential as liquid biomarkers in OC have been characterized, but none are currently used clinically. The study has analysed 662 lncRNAs deregulated in OC to determine their ability to be detected in biofluids. Twenty-three have been identified in blood samples, four in ascites, and twenty- seven in extracellular vesicles isolated from biofluids. Most of these lncRNAs have an oncogenic role and have been associated with poor prognosis, primarily overall survival. Regarding their diagnostic value, some have even been positively associated with FIGO stages, but only one, included in the panel RP5-837J1.2/miR-361-3p/PELI3, allows differentiation between patients in early stages and healthy women. Information on lncRNAs detected in biofluids related to cancer hallmarks has also been included to identify gaps in the field and to serve as a guide for future research.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891180","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":"Unveiling the Mechanisms of Panax Notoginseng in Accelerating Postoperative Recovery after Lung Surgery: A Comprehensive Study.","authors":"Zhe Chen, Chi Wang, Yixing Li, Yilong Zhao, Xiao Xiao, Heng Zhao, Bin He, Haotian Bai, Rui Zhao, Guangjian Zhang, Jinteng Feng","doi":"10.2174/0109298673467455260805093422","DOIUrl":"https://doi.org/10.2174/0109298673467455260805093422","url":null,"abstract":"<p><strong>Background: </strong>Enhanced recovery after lung surgery is important as it impacts patient outcomes. Among Traditional Chinese Medicine (TCM) herbs, Panax Notoginseng (PN) has been studied for its remarkable properties, making it a promising candidate for accelerating postoperative healing. However, the mechanisms of PN in enhancing recovery after lung surgery remain incompletely understood.</p><p><strong>Methods: </strong>First, animal experiments were conducted to validate the efficacy of PN in postoperative recovery following lung surgery. Then, herb-component-target network and Protein-Protein Interaction (PPI) network were constructed to identify the bioactive components of PN and key protein targets. Molecular docking was employed to validate the interactions between the active components and candidate recovery targets.</p><p><strong>Results: </strong>Animal experiments demonstrated that PN significantly improved postoperative recovery by enhancing collagen deposition and reducing pulmonary edema around the wound. Eight active components from PN and 251 targets associated with its therapeutic effects were revealed; 650 targets were linked to postoperative recovery after lung surgery. Key protein targets, including SRC, PIK3R1, and EGFR, were identified, with Quercetin, Liquiritigenin, and Mandenol emerging as the core active ingredients. Molecular docking demonstrated that the core components exhibited favorable binding energies with target proteins. KEGG and GO enrichment analyses highlighted the PI3KAKT signaling pathway and epithelial cell proliferation as critical pathways and biological processes underlying PN's efficacy.</p><p><strong>Discussion: </strong>PN may offer a novel strategy to enhance postoperative lung repair, as it may activate the PI3K/AKT pathway, which links traditional Chinese medicine with postoperative recovery. In this work, PN contributes to ERAS protocols in thoracic surgery, bridging molecular insights with clinical outcomes.</p><p><strong>Conclusion: </strong>The active components of PN, including Quercetin, Liquiritigenin, and Mandenol, can accelerate postoperative recovery after lung surgery by potentially activating the PI3K-AKT pathway and promoting collagen deposition processes.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891183","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":"Single-Cell Sequencing Combined with Mendelian Randomization to Explore Potential Diagnostic Biomarkers and Therapeutic Targets for Rheumatoid Arthritis.","authors":"Shikai Chen, Hanyu Wang, Cheng Wang, Yubo Shao, Hao Xu, Jinman Chen, Qianqian Liang, Ning Li","doi":"10.2174/0109298673448346260805114910","DOIUrl":"https://doi.org/10.2174/0109298673448346260805114910","url":null,"abstract":"<p><strong>Background: </strong>Rheumatoid Arthritis (RA) is a common autoimmune disease with complex pathogenesis and high prevalence, severely affecting patients' quality of life. Multi-omics analysis has emerged as a powerful tool in RA research, providing insights into cell heterogeneity, genetic mechanisms, and immune microenvironment characteristics. This research looks into important genes linked to rheumatoid arthritis(RA) using single-cell data and Mendelian randomization analysis, while also uncovering the characteristics of the immune microenvironment and its mechanisms linking to these key genes.</p><p><strong>Methods: </strong>Gene expression, eQTL, and GWAS data were collected. Analyses included single-cell data processing (quality control, dimensionality reduction, clustering, cell annotation, and cell subset contribution assessment), subgroup non-negative matrix factorization, Mendelian randomization, co-localization analysis, immune infiltration analysis, and GSEA/GSVA.</p><p><strong>Results: </strong>This study analyzed 95,036 single-cell samples and found that alterations in B cells are closely associated with disease progression. Further analysis identified seven distinct B cell subpopulations, with immune responses and the tumor microenvironment exerting significant influence on their dynamics. Mendelian randomization analysis revealed key genes, CD83 and CRIP2, that are linked to the risk of RA. Subsequent investigation demonstrated strong associations between these genes and immune cell populations. GSEA and GSVA analyses showed that CD83 is involved in pathways related to allograft rejection and antigen processing, while CRIP2 is associated with interactions of extracellular matrix receptors and the IL-17 signaling pathway. Additionally, immunometabolism pathway analysis highlighted potential therapeutic targets and underlying mechanisms.</p><p><strong>Discussion: </strong>The findings suggest that B cells play a major role in the RA immune microenvironment and identify CD83 and CRIP2 as potential biomarkers and therapeutic targets. CD83 may contribute to RA through immune regulation, antigen presentation, and inflammatory signaling, whereas CRIP2 may be involved in metal ion homeostasis, cellular stress responses, and immune-related pathological processes. Immune infiltration analyses further indicate that these genes are closely associated with immune-cell activity in RA. Overall, the study provides new insight into RA pathogenesis and supports the potential clinical relevance of CD83 and CRIP2, although further experimental and clinical validation is required.</p><p><strong>Conclusion: </strong>This study offers valuable understanding about RA pathogenesis and identifies probable diagnostic biomarkers as well as therapeutic targets (CD83 and CRIP2), which could improve our awareness of the illness and help with formulating more successful care plans.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891147","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}