International Journal of Immunopathology and Pharmacology最新文献

{"title":"Impact of hepatitis C virus on oral health: Clinical lesions, immunopathology, and dental management: A narrative review.","authors":"Mario Alberto Alarcón-Sánchez, Valeria Henao-Díaz, Lilibeth-Stephania Escoto-Vasquez, Melissa Martínez-Nieto, Gustavo Eder González-Alvarez, Armen A Muradyan, Artak Heboyan, Sarah Monserrat Lomelí-Martínez","doi":"10.1177/03946320261419189","DOIUrl":"10.1177/03946320261419189","url":null,"abstract":"<p><p>Hepatitis C virus (HCV) infection is a major global public health problem. Although it has traditionally been linked to liver damage, several studies have demonstrated its extrahepatic impact, specifically in the oral cavity. Oral manifestations can be considered early signs of infection or contribute to clinical progression. This narrative review aims to describe the oral alterations associated with HCV, integrating the pathophysiological mechanisms and clinical implications for dental management. The most prevalent manifestations include periodontal disease, oral lichen planus, Sjögren's syndrome-like sialadenitis, and squamous cell carcinoma of the oral cavity. Recent findings suggest that HCV triggers dysbiosis of the oral microbiome, promotes exacerbated immune responses with overproduction of pro-inflammatory cytokines, and disrupts the homeostatic environment, thereby promoting the progression of inflammatory and neoplastic diseases. In addition, viral RNA has been identified in saliva and gingival crevicular fluid, which could be considered a non-parenteral route of transmission, particularly important in dental interventions. In parallel, direct-acting antiviral therapy, in addition to achieving virus elimination, could also partially correct immunological and microbial disruptions in the cavity, with favorable clinical responses. Understanding these oral alterations can guide dentists in early detection and improve systemic outcomes.</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"40 ","pages":"3946320261419189"},"PeriodicalIF":2.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12901906/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146167601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Silencing RPL9 promotes malignant proliferation in breast cancer cells.","authors":"Tong Zhu, Junze Dai, Wenxin Li, Huiyu Zhang, Yuxuan Song, Dingye Zhang, Ruibin Liu, Xin Wang, Zhaohu Shi, Hailin Tang, Xudong Zhu, Yefu Liu","doi":"10.1177/03946320261422055","DOIUrl":"10.1177/03946320261422055","url":null,"abstract":"<p><strong>Objective: </strong>To identify key RNA-binding proteins (RBPs) associated with breast cancer (BRCA) prognosis and to construct an RBP-based prognostic scoring model and clinical nomogram. Additionally, to explore the functional role of RPL9 in BRCA cell proliferation and apoptosis.</p><p><strong>Introduction: </strong>Breast cancer is a molecularly heterogeneous malignancy in which posttranscriptional dysregulation contributes significantly to tumor progression. RNAbinding proteins regulate multiple steps of RNA metabolism and have emerged as promising prognostic biomarkers and therapeutic targets in BRCA.</p><p><strong>Methods: </strong>RNA-sequencing data and clinical information of BRCA patients were obtained from TCGA. Differential expressions, Cox, and LASSO regression analyses were performed to identify prognosis-related RBPs and establish a risk scoring model. A clinical nomogram integrating the model with clinicopathological features was generated. Tumor mutational burden (TMB), tumor immune microenvironment (TIME), and immune checkpoint expression were analyzed between risk groups. Functional assays, including CCK-8 proliferation and flow cytometry-based apoptosis analyses, were conducted in BRCA cell lines to determine the role of RPL9.</p><p><strong>Results: </strong>Nine prognosis-related RBPs were identified and used to construct the RBPbased prognostic scoring model, which effectively predicted 3-, 5-, and 9-year survival outcomes. The model remained robust in an external validation cohort. A clinical nomogram based on the model showed strong predictive performance. High-risk patients displayed higher TMB, lower immune scores, reduced CD8⁺ T-cell infiltration, and decreased immune checkpoint expression. RPL9 was markedly downregulated in BRCA tissues and cells, and RPL9 overexpression inhibited cell proliferation and significantly increased apoptosis, supporting its tumor-suppressive role.</p><p><strong>Conclusion: </strong>We identified and constructed a 9-RBP based scoring model and a clinical prognostic nomogram for accurately predicting the survival probability and assessing the tumor microenvironment of patients with BRCA. Moreover, our findings firstly demonstrated that RPL9 downregulation correlated with poor clinical outcomes and functionally drives tumor cell proliferation, establishing it as a potential therapeutic target and prognostic biomarker for BRCA.</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"40 ","pages":"3946320261422055"},"PeriodicalIF":2.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13018688/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147515778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glycolysis and neutrophil extracellular traps in atherosclerosis: Mechanisms, association, and therapeutic strategies.","authors":"Lingling Li, Xiaonan Zhang, Zongliang Yu, Xiaoya Li, Changxin Sun, Lanqing Hu, Kaidong Zhou, Xinyi Liu, Yongfang Yuan, Min Wu, Longtao Liu","doi":"10.1177/03946320261450099","DOIUrl":"10.1177/03946320261450099","url":null,"abstract":"<p><p>Atherosclerosis (AS) is a chronic inflammatory disorder of the medium and large arteries, characterized by lipid accumulation within the arterial wall and a sustained inflammatory milieu, and it remains a leading cause of cardiovascular morbidity and mortality worldwide. Glycolysis and neutrophil extracellular traps (NETs) are both involved in the initiation and progression of AS in part through effects on endothelial function, platelet activation, lipid metabolism, and the inflammatory microenvironment. This article reviews the roles of NETs and glycolysis in AS, elucidates the mechanisms underlying NETosis, and discusses the association between glycolysis and NETosis. Finally, the article discusses the potential value of glycolytic inhibitors in the treatment of AS, with the aim of providing new perspectives for the diagnosis and treatment of AS and related cardiovascular diseases.</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"40 ","pages":"3946320261450099"},"PeriodicalIF":2.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13219874/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148036706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nasopharyngeal mass containing B-cell small lymphocytic lymphoma in a human immunodeficiency virus-positive patient: A case report and review of the literature.","authors":"Milica Labus, Aleksandar Perić, Merida Mehmedović, Jelena Sotirović, Stevan Matić, Milena Jović, Biserka Vukomanović Đurđević","doi":"10.1177/03946320261435768","DOIUrl":"10.1177/03946320261435768","url":null,"abstract":"<p><p>The spectrum of pathological conditions affecting the nasopharynx includes infections, congenital anomalies, and tumoral lesions, particularly angiofibroma, nasopharyngeal carcinoma, and lymphoma. Hypertrophy of adenoid tissue is a frequent phenomenon in children, but it is less common in the adult population. With this case report, we wanted to point out the importance of rhinological and otological manifestations of adenoid hypertrophy in adult patients. A 48-year-old man presented with impaired hearing in both ears, difficulty breathing through the nose, impaired sense of smell, hyponasal speech, and occasional scanty bleeding from the right side of the nose. After taking detailed data, the diagnostics included a classic ENT examination, endoscopy of the nasal cavity and nasopharynx, audiological diagnostics, allergy tests, computerized tomography of the paranasal sinuses and the skull base, and serological analysis for viruses and protozoa. A soft tissue lesion that filled the entire nasopharynx was surgically removed, and the pathohistological analysis indicated B-cell small lymphocytic lymphoma (SLL) with polyclonal plasma cell differentiation. Serological analyses showed that it was a human immunodeficiency virus (HIV)-positive patient, who also had a high blood titer of IgG to the Epstein-Barr virus. The patient was admitted to another institution for oncology treatment under the supervision of an infectious disease specialist. Although rare, malignant transformation of nasopharyngeal lymphoid tissue is possible. B-cell SLL with polyclonal plasma cell differentiation represents a minority of malignancies originating from the nasopharynx, and there are limited data regarding epidemiologic and treatment outcomes. Early recognition and thorough evaluation are essential to distinguish benign enlargement from more serious conditions.</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"40 ","pages":"3946320261435768"},"PeriodicalIF":2.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13009950/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147505285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Agmatine suppresses the imidazoline I₂ receptor/ribosomal S6 kinase 2/NF-κB signaling pathway regulating alveolar macrophage polarization and ameliorating sepsis-associated acute lung injury.","authors":"Linguo Bai, Kun Yu, Qiuyu Dai, Jie Zheng, Kangjie Qin, Junjie Li, Feiyan Li, Song Qin, Hong Mei, Xinxin Liu, Tao Chen, Liting Cheng","doi":"10.1177/03946320261425360","DOIUrl":"10.1177/03946320261425360","url":null,"abstract":"<p><p>Acute respiratory distress syndrome (ARDS) is an acute diffuse inflammatory lung injury characterized by damage to alveolar epithelial cells and pulmonary capillary endothelial cells. Compared with ARDS caused by other causes, the subtypes of ARDS caused by sepsis are more serious and lead to poor prognosis and higher mortality. Agmatine (AGM) is a biological metabolite of L-arginine decarboxylation, proven to ameliorate sepsis-induced acute lung injury (SALI), but the mechanism remains unclear. Therefore, this study aims to explore the role of AGM in SALI, clarify the relationship between the I₂R/RSK2/NF-κB signaling pathway regulated by AGM and macrophage polarization, and provide a theoretical basis for the clinical treatment of SALI. Cellular and animal models of lung injury in sepsis were established with lipopolysaccharide (LPS). We conducted a series of experiments to examine the oxygenation index (OI), wet/dry ratio (W/D) of the lung, pathological changes, levels of inflammation, Apoptosis and related protein expression in different groups of mice. Finally, we found that AGM can ameliorate sepsis-induced acute lung injury by suppressing the I₂R/RSK2/NF-κB signaling pathway and modulating polarization of alveolar macrophage.</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"40 ","pages":"3946320261425360"},"PeriodicalIF":2.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12929822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147272483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated transcriptomic and immunogenomic analysis unravels the immunological functions and prognostic landscape of WD repeat domain 76.","authors":"Yifan Wang, Rong Zhou, Shenglong Guo, Shaoting Nan, Yanlong Duan, Lei Cao, Xiujuan Huang, Hailong Yan","doi":"10.1177/03946320261486727","DOIUrl":"10.1177/03946320261486727","url":null,"abstract":"<p><p>BackgroundWD Repeat Domain 76 (WDR76) plays a potential role in cellular regulation; however, its comprehensive landscape across human malignancies and its specific biological function in hepatocellular carcinoma (HCC) remain largely unexplored.MethodsWe conducted a systematic pan-cancer analysis utilizing multi-omics data from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Cancer Cell Line Encyclopedia (CCLE) atabases to evaluate WDR76 expression, subcellular localization, and its correlation with clinicopathologic features, genomic instability, and immune infiltration. Diagnostic and prognostic values were assessed via Receiver operating characteristic (ROC) and Kaplan-Meier analyses. Furthermore, the functional role of WDR76 in HCC was validated <i>in vitro</i> using Hep-3B and Huh7 cell lines through siRNA-mediated knockdown, followed by CCK-8, wound-healing, and transwell assays.ResultsWDR76 was significantly upregulated in the majority of tumor types, including LIHC, LUAD, and COAD, while exhibiting nuclear localization. Elevated WDR76 expression correlated with advanced tumor staging, metastasis, and poor clinical outcomes across multiple cohorts, particularly in ACC, KIRP, and LIHC. ROC analysis highlighted its exceptional diagnostic precision in cancers such as GBM and LIHC. Immunologically, WDR76 expression was intricately linked to immune cell infiltration, immune checkpoint markers, and genomic instability parameters, suggesting a role in shaping the tumor microenvironment. Drug sensitivity profiling revealed that high WDR76 levels correlate with resistance to specific chemotherapeutic agents. Experimentally, silencing WDR76 in HCC cells significantly suppressed cell proliferation, migration, and invasion capabilities.ConclusionOur study establishes WDR76 as a robust pan-cancer prognostic biomarker and a potential immunotherapeutic target. Specifically, we provide experimental evidence that WDR76 functions as an oncogenic driver in liver cancer, promoting malignant phenotypes and offering a novel avenue for targeted therapeutic intervention.</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"40 ","pages":"3946320261486727"},"PeriodicalIF":2.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13542525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148888918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of RNase P ribozyme-based therapy against oral herpesvirus infections by HSV-1 and KSHV.","authors":"Thomas Sorrell, Fenyong Liu","doi":"10.1177/03946320261451393","DOIUrl":"10.1177/03946320261451393","url":null,"abstract":"<p><p>Infections with human herpesviruses are known to be associated with oral lesions and other oral complications. For example, herpes simplex virus 1 (HSV-1) is the causative agent for cold sores. Kaposi's sarcoma-associated herpesvirus (KSHV) causes oral Kaposi's sarcoma (KS) and other oral complications among immunocompromised patients, such as HIV-positive individuals. Novel antiviral strategies are needed to effectively treat oral infections caused by HSV-1 and KSHV, given the limitations of current FDA-approved anti-HSV-1 and anti-KSHV therapies. Nucleic acid-based gene-interfering molecules, such as antisense oligonucleotides, ribozymes, and small interfering RNA (siRNA), are promising gene-targeting agents for therapeutic applications. Ribozymes derived from the catalytic RNA subunit of RNase P in <i>Escherichia coli</i> represent a novel class of RNA-based gene targeting molecules for degrading target mRNAs and modulating gene expression. Methods have been developed to engineer RNase P ribozymes that more effectively suppress gene expression. In this review, we summarize the recent advances in using RNase P ribozymes to block the expression of HSV-1 and KSHV genes and inhibit the infection of HSV-1 and KSHV. Moreover, we discuss the potential of engineered RNase P ribozymes as therapeutics to treat infections and associated diseases caused by HSV-1 and KSHV in the oral cavity.</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"40 ","pages":"3946320261451393"},"PeriodicalIF":2.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13198646/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148007071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Liposomal nanotherapeutics for cancer treatment: Targeted delivery and immunotherapy.","authors":"Mahin Zubair Butt, Zahra Tariq, Maryam Imran, Ahood A Al-Eidan, Shahzadi Mahjabeen, Seerat Fatima, Ghayyas Ud Din, Sumaira Anjum, Elham Abdullatif M Sharif, Wisam Nabeel Ibrahim","doi":"10.1177/03946320261438337","DOIUrl":"10.1177/03946320261438337","url":null,"abstract":"<p><p>Cancer has become a major global health crisis and the second leading cause of death worldwide. With over 270 different types, it is estimated to claim 13 million lives by 2030. The complex pathophysiology of cancer, with its diverse genetic, epigenetic, and biochemical pathways, complicates the diagnostic criteria. Therapeutic approaches such as surgical interventions, radiotherapy, chemotherapy, and immunotherapy have been developed. However, the treatment is still challenging due to higher costs, toxicity, off-target effects, and comorbid conditions. Over the decades, liposomes, based on their particle size, surface charge, lipid composition, and lamellarity, have been explored for different therapeutic modalities for other cancers. They offer unique advantages, including improved drug efficacy, controlled site-specific release, enhanced cellular uptake, reduced systemic toxicity, and greater capacity to overcome tumor-induced resistance mechanisms. Researchers have explored liposomal treatment modalities for breast, lung, adenocarcinoma, ovarian, liver, fibrosarcoma, glioblastoma, and brain cancers. The tumor targeting drugs, for example, doxorubicin and paclitaxel, are delivered at the tumor microenvironment (TME) by passive and active transport, utilizing both the enhanced permeability and resistance (EPR) effect and cellular targets, for example, receptors, proteins, and organelles, in response to physical stimuli, for example, temperature, pH, fluid pressure, and nutrient and metabolic regulation. However, liposomes also face several limitations, including endosomal entrapment, heterogeneous targeting, suboptimal uptake by antigen-presenting cells (APCs), and storage instability. This review focuses on the advancements in liposomal nanocarriers for targeted cancer therapy. It emphasizes the evolution of their formulations to overcome potential limitations, making them highly tumor-specific and effective.</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"40 ","pages":"3946320261438337"},"PeriodicalIF":2.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13111859/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147786145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction: Gut Microbiota and the Immune System: An Intimate Partnership in Health and Disease.","authors":"","doi":"10.1177/03946320261432321","DOIUrl":"10.1177/03946320261432321","url":null,"abstract":"","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"40 ","pages":"3946320261432321"},"PeriodicalIF":2.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13051171/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147595576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mendelian randomization implicates circulating plasma proteins in gout risk and identifies candidate therapeutic targets.","authors":"Han Zhang, Zixian Dang, Pixue Yu, GuanHong Chen, Yingze Zhang, Tianrui Wang, Tengbo Yu, Yongtao Zhang, Zhen Shang","doi":"10.1177/03946320261428859","DOIUrl":"10.1177/03946320261428859","url":null,"abstract":"<p><strong>Objective: </strong>To explore whether circulating plasma proteins have potential causal effects on gout risk by integrating genome-wide association study (GWAS) data with protein quantitative trait loci (pQTL) information, aiming to identify candidate proteins and pathways for therapeutic targeting.</p><p><strong>Introduction: </strong>Despite advances in gout pathophysiology, personalized therapies and validated drug targets remain limited. We conducted an exploratory Mendelian randomization (MR) analysis to assess whether circulating plasma proteins show evidence consistent with potential causal effects on gout risk, integrating GWAS with pQTL data to prioritize proteins and pathways for follow-up.</p><p><strong>Methods: </strong>We applied an integrated genetics framework combining proteome-wide MR, reverse MR, Bayesian colocalization, and sensitivity analyses. Plasma pQTL datasets were obtained from Zheng et al. and deCODE Genetics; gout GWAS were from UK Biobank and the FinnGen R12 study. Primary inference used inverse-variance weighting (IVW) with MR-Egger and complementary sensitivity tests. Colocalization used Bayesian methods; reverse MR evaluated potential reverse causation. Where available, findings were checked in external datasets. Analyses followed STROBE-MR guidance and were implemented in R with standard MR/colocalization packages.</p><p><strong>Results: </strong>Five circulating proteins (FN1, PLAU, CPQ, SPOCK2, and FAM213A) met the predefined discovery threshold. Reverse Mendelian randomization provided no evidence supporting reverse causality from gout to protein levels, while Steiger directionality tests supported the protein-to-gout causal orientation. Bayesian colocalization indicated moderate to strong evidence of shared genetic signals for PLAU, FAM213A, and FN1, whereas the evidence for CPQ and SPOCK2 was comparatively weak. In the independent replication analysis, genetically predicted higher levels of PLAU and CPQ were directionally associated with an increased risk of gout, while higher FN1 levels showed a consistent protective association. Nevertheless, effect estimates and precision varied across datasets, and the overall findings should be interpreted as exploratory rather than confirmatory.</p><p><strong>Conclusion: </strong>This exploratory, assumption-dependent MR work nominates five circulating proteins as hypothesis-generating candidates for gout risk and potential therapeutic targeting. Given method assumptions and cross-dataset heterogeneity, functional validation and independent replication are required to clarify mechanisms, confirm targetability, and assess translational relevance.</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"40 ","pages":"3946320261428859"},"PeriodicalIF":2.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13031745/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147515679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}