Toxicology Research最新文献

{"title":"Zearalenone induces GnRH neurons activation related to central precocious puberty by triggering MKRN3 auto-ubiquitination and down-regulation.","authors":"Yan Sun","doi":"10.1093/toxres/tfaf106","DOIUrl":"10.1093/toxres/tfaf106","url":null,"abstract":"<p><p>Central precocious puberty (CPP) refers to gonadotropin-dependent sexual precocity that results from the early activation of the hypothalamic-pituitary-gonadal (HPG) axis. Zearalenone (ZEA), a non-steroidal mycotoxin, is one of the important triggering factors for the development of CPP; however, its regulatory mechanism remains unclear. In this study, the correlation between urinary zearalenone (ZEA) levels and the blood expression of MKRN3 (makorin RING-finger protein-3) in patients with central precocious puberty (CPP) was investigated. Subsequently, the regulatory mechanism of ZEA on MKRN3, as well as its association with gonadotropin-releasing hormone (GnRH) production, cell proliferation, and the expression and localization of the G protein-coupled estrogen receptor (GPER) were explored in the hypothalamic cell line GT1-7. Analysis of clinical samples revealed that urinary ZEA levels were negatively correlated with blood MKRN3 expression in CPP patients. The in vitro experiments revealed that ZEA treatment up-regulated cell proliferation as well as the expressions of GnRH and GPER and re-location of GPER in GT1-7 cells by triggering MKRN3 auto-ubiquitination and down-regulation. However, such effects were attenuated by GPER overexpression. In conclusion, this study reveals a novel mechanism by which ZEA influences CPP using clinical samples and an in vitro model. The findings suggest that MKRN3 may serve as a potential therapeutic target and a diagnostic biomarker for CPP.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 4","pages":"tfaf106"},"PeriodicalIF":2.1,"publicationDate":"2025-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12296353/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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 an epitope-based vaccine from <i>mycoplasma genitalium</i> adhesion protein: addressing antibiotic resistance through immune-informatics.","authors":"Hafiz Muhammad Rehman, Muhammad Bilal, Muhammad Shoaib, Tahir Latif, Rabbani Syed, Fahid Khalid, Muhammad Naveed Khan, Saira Asif Khan, Nadeem Ahmed, Saad Tahir, Hamid Bashir","doi":"10.1093/toxres/tfaf102","DOIUrl":"10.1093/toxres/tfaf102","url":null,"abstract":"<p><p><i>Mycoplasma genitalium</i> is increasingly recognized for its role in severe health conditions, including sexually transmitted infections, ovarian and prostate cancer. The adhesion protein plays a crucial role in the pathogen's ability to attach to and invade host cells, making it a key target for vaccine development. The need to develop a vaccine against <i>M. genitalium</i> stems from its rising antibiotic resistance, limited treatments and effectiveness. This study focuses on the design and computational evaluation of adhesion protein-based epitope vaccine. Through an immunoinformatic approach, multiple novel cytotoxic T lymphocyte (CTL), helper T lymphocyte (HTL), and linear B-cell epitopes were identified from the adhesion protein, demonstrating strong antigenic, non-allergenic, and immunogenic properties. The vaccine construct's 3D structure was validated using Ramachandran plot analysis, ProSA, and ERRAT servers, confirming its stability and suitability. Molecular docking studies revealed a high binding affinity of the vaccine with the TLR-2 receptor, further supported by 100 ns molecular dynamics (MD) simulations that confirmed the structural stability and robust interaction of the vaccine with immune receptors. In silico immune simulations using the C-ImmSim server demonstrated the vaccine's potential to elicit strong humoral and cell-mediated immune responses. Codon optimization for expression in <i>E. coli</i> using the pET-29a(+) vector predicted efficient production of the vaccine. The comprehensive computational analysis, underscores the potential of this epitope-based vaccine as a promising candidate against <i>M. genitalium</i> infections. However, the study emphasizes the necessity of in vitro and in vivo experiments to validate the vaccine's efficacy and safety before advancing to clinical trials.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 4","pages":"tfaf102"},"PeriodicalIF":2.1,"publicationDate":"2025-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12296348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hormetic association between sodium nitrate and liver enzymes: a study in female and male rats.","authors":"Ramin Zeinodini, Sajad Jeddi, Khosrow Kashfi, Asghar Ghasemi","doi":"10.1093/toxres/tfaf104","DOIUrl":"10.1093/toxres/tfaf104","url":null,"abstract":"<p><p>This study aims to evaluate the long-term dose-dependent effects of sodium nitrate on serum ALT, AST, and ALP in healthy female and male rats. A total of 120 rats (60 females and 60 males) were divided into 6 subgroups (n = 10). In each sex, a control group received regular tap water, while five treatment groups received sodium nitrate in tap water (50, 100, 150, 250, and 500 mg/L). Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and nitric oxide (NO) metabolites (NOx) were measured at baseline (month 0) and after 6 mo. Hormetic zones for sodium nitrate in female rats were 10-230 mg/L for ALT, 20-180 mg/L for AST, and 8-270 mg/L for ALP. In males, the zones were 5-190 mg/L for ALT, 7-180 mg/L for AST, and 7-265 mg/L for ALP. Serum NOx levels were negatively correlated with ALT (r = -0.498) and AST (r = -0.320) at moderate doses (100-150 mg/dL) but positively correlated with ALT (r = 0.500) and AST (r = 0.300) at higher doses (250-500 mg/dL (all P < 0.05). Sodium nitrate exhibited a J-shaped dose-response relationship with liver function tests (LFTs) in both female and male rats. Protective effects were observed at moderate doses (100 mg/L for ALT and AST; 150 mg/L for ALP), while low doses (<10 mg/L) were ineffective, and high doses (>200 mg/L for ALT/AST; >250 mg/L for ALP) were toxic. These findings highlight the dual potential of sodium nitrate as both beneficial and harmful, depending on the dosage in healthy state.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 4","pages":"tfaf104"},"PeriodicalIF":2.1,"publicationDate":"2025-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12296356/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulating intracellular calcium dynamics with alkaloids: A novel strategy against oxidative neurodegeneration.","authors":"Serap Niğdelioğlu Dolanbay","doi":"10.1093/toxres/tfaf100","DOIUrl":"10.1093/toxres/tfaf100","url":null,"abstract":"<p><p>Calcium homeostasis plays a pivotal role in neuronal function, and its dysregulation is closely associated with oxidative stress-induced neurotoxicity. This study investigated the protective effects of a methanol alkaloid extract (MAE), rich in allocryptopine, tetrahydropalmatine, and tetrahydroberberine N-oxide, on H₂O₂-induced calcium dysregulation in fPC12 cells. Flow cytometry analysis revealed that MAE pretreatment significantly attenuated intracellular Ca²⁺ accumulation caused by oxidative stress. In line with this, MAE markedly downregulated the mRNA and protein expression levels of CACNA1C (Cav1.2 subunit) and CACNA1D (Cav1.3 subunit), two L-type voltage-gated calcium channels responsible for calcium influx. Furthermore, MAE suppressed the expression of key calcium regulatory proteins, including CALM1, CaMK2A, PMCA (ATP2B1), SERCA (ATP2A1), RyR1, and IP3R (ITPR1), as confirmed by ELISA and Western Blot analysis. Protein-protein interaction (PPI) network analysis demonstrated a highly interconnected and functionally enriched network among these targets, indicating coordinated regulation of calcium signaling pathways. Molecular docking studies supported these findings by showing strong binding affinities of MAE's isoquinoline alkaloids, particularly tetrahydropalmatine, to SERCA (ATP2A1) and IP3R (ITPR1). These interactions suggest a direct modulatory effect on calcium-handling proteins. Overall, this study provides experimental and <i>in silico</i> evidence that MAE exerts multifaceted neuroprotective effects by restoring calcium homeostasis and modulating oxidative stress responses, highlighting its therapeutic potential in calcium-related neurodegenerative conditions.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 4","pages":"tfaf100"},"PeriodicalIF":2.1,"publicationDate":"2025-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12296383/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Zebrafish in the spotlight: expanding Frontiers in toxicology and drug discovery.","authors":"Sudharsan Parthasarathy, Shaza H Aly, Siva Vijayakumar Tharumasivam, Durairaj Siva, Gobalan Krishnasamy, Ashajyothi Chavaan, Mohamed El-Shazly","doi":"10.1093/toxres/tfaf095","DOIUrl":"10.1093/toxres/tfaf095","url":null,"abstract":"<p><p>Zebrafish (<i>Danio rerio</i>) has emerged as a valuable model organism in toxicology and drug discovery research. This article provides an overview of the significant contributions of zebrafish to advancing our understanding of toxicology and drug development. Zebrafish offers several advantages, including high fecundity, transparent embryos, and genetic tractability, making it an ideal system for studying drug toxicity and efficacy. The review article highlights key areas where zebrafish has made substantial contributions, such as assessing chemical toxicity, understanding drug metabolism and pharmacokinetics, and identifying novel therapeutic compounds. Furthermore, zebrafish-based assays and screening platforms have been developed to evaluate drug candidates and identify potential toxic effects and researchers have used zebrafish-based tests to study the therapeutic properties of natural compounds. The unique capabilities of zebrafish with its physiological and genetic similarities to humans, have propelled it to the forefront of toxicology and drug discovery, expanding the frontiers of research in these fields.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 4","pages":"tfaf095"},"PeriodicalIF":2.1,"publicationDate":"2025-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12296346/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of combined exposure to low levels of aerosolised nickel, copper and arsenic on myocardial injury in rats.","authors":"Xinyue Mu, Shuxia Yu, Yiwen Zhang, Junpu Yu, Tingting Gao, Xin Wang, Li Ma, Ye Ruan, Tian Tian, Rentong Chen","doi":"10.1093/toxres/tfaf101","DOIUrl":"10.1093/toxres/tfaf101","url":null,"abstract":"<p><p>Chronic low-level exposure to nickel (Ni), copper (Cu), and arsenic (As) may contribute to myocardial injury via oxidative stress. This study investigated the effects of these metals in male Sprague-Dawley rats exposed to aerosols of Ni (0.106 mg/m³), Cu (0.048 mg/m³), and As (0.025 mg/m³) at environmental and 10-fold concentrations for 3 mo. Blood metal levels were analyzed using inductively coupled plasma-mass spectrometry (ICP-MS), and oxidative stress and myocardial injury biomarkers were measured with enzyme-linked immunosorbent assay (ELISA). Blood As levels showed a dose-dependent increase in both exposure groups. Myocardial ultrastructural damage, including mitochondrial swelling, disorganized myofibrils, and increased autolysosomes, was observed. Biomarkers of oxidative stress, including catalase (CAT), superoxide dismutase (SOD), and glutathione (GSH), were significantly elevated in both exposure groups, while malondialdehyde (MDA) levels were notably higher in the 10-fold group. Myocardial injury markers (TNNI3, LDHA, and α-HBDH) were elevated in both exposure groups. Significant correlations were found between Cu and As levels and oxidative stress and myocardial injury biomarkers. These findings demonstrate that prolonged low-level exposure to Ni, Cu, and As induces oxidative stress and myocardial injury in rats. The results highlight the potential cardiovascular risks associated with environmental exposure to mixed heavy metals and emphasize the importance of stricter regulatory measures to limit such pollutants.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 4","pages":"tfaf101"},"PeriodicalIF":2.1,"publicationDate":"2025-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12296345/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ameliorating and therapeutic impact of nano ferrite-chitosan-curcumin nanoparticles against nandrolone decanote induced renal toxicity, inflammation, and oxidative stress in male rats.","authors":"Ehab Tousson, Afaf El Atrash, Somia Zaki, Marwa Negm","doi":"10.1093/toxres/tfaf103","DOIUrl":"10.1093/toxres/tfaf103","url":null,"abstract":"<p><p>The term ``anabolic-androgenic steroids'' (AASs) refers to a class of artificial substances that resemble the natural testosterone. The most often misused androgen, nandrolone decanoate (ND), is regarded as a public health concern that needs immediate action to raise public awareness of toxicology results on AAS usage. This study designed to investigate the therapeutics effect of nano ferrite-chitosan-curcumin nanoparticles (NF-CH-CurNPs) against ND induced renal toxicity, proliferation, inflammation, and oxidative stress in male rats. A total of 48 adult male rats were assigned randomly to 6 groups [1^st group was control; 2^nd group was CurNPs where rats received CurNPs (50 mg/kg BW/2 day) for two wk; 3^rd group was NF-CH-CurNPs where rats received NF-CH-CurNPs (24 mg/Kg BW/2 day) for 2 wk.; 4^th group was ND where rats received ND (25 mg/Kg BW/wk) for four wk; 5th group was ND + CurNPs in which rats received ND for 4 wk then treated with CurNPs for another 2 wk; 6^th group was ND + NF-CH-CurNPs where rats received ND for 4 wk then treated with NF-CH-CurNPs for another 2 wk]. A significant elevation in serum Urea, creatinine, kidney damage, MDA, PCNA, TNFα and a significant depletion in sodium, potassium ions, catalase, SOD, GSH after ND administration as compared to control. On the contrary, treatment of ND with CurNPs or/and NF-CH-CurNPs induced significant enhancements of the studied parameters, kidney structure and functions, oxidative stress, PCNA and TNFα expressions with best results for the treatments with NF-CH-CurNPs that may possibly scavenge free radicals creating valuable effects in contrast to ND.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 4","pages":"tfaf103"},"PeriodicalIF":2.1,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12286917/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Manganese exposure: a study on apoptosis and Ferroptosis in mouse Leydig and Sertoli cells.","authors":"Jiaqi He, Tongci Li, Yue Su, Yan Liang, Ying Tian, Renlian Cai, Jidong Zhang, Xiang Lu, Jun Tan","doi":"10.1093/toxres/tfaf098","DOIUrl":"10.1093/toxres/tfaf098","url":null,"abstract":"<p><p>Manganese (Mn), a vital trace element for biological functions, has raised health concerns due to potential toxicity. Excessive Mn impairs male reproduction by reducing testosterone, inducing oxidative stress, and disrupting spermatogenesis. However, its mechanisms targeting Leydig and Sertoli cells remain unclear. This study investigates Mn's reproductive toxicity by utilizing Leydig cell line TM3 and Sertoli cell line TM4, MTT assays revealed median lethal concentrations of 230 μM (TM3) and 170 μM (TM4), with AO/EB/DAPI staining confirming condensed nuclei and enhanced fluorescence. Apoptosis inhibitor Z-VAD-FMK (20 μM) suppressed cell death in both cell lines, whereas ferroptosis inhibitor Ferrostatin-1 (10 μM) specifically attenuated TM4 cell death. Necrosis inhibitor Necrostatin-1 (10 μM) showed no protective effect. Mn triggered ROS elevation in TM4 cells, accompanied by upregulated <i>Caspase 3, Casp8ap2, GPX4, Gtf3c1, Mtfr1, HMOX1, and SLC7A2</i>, while downregulating <i>SLC7A15</i>. These findings reveal Mn activates apoptosis in TM3 cells and concurrent apoptosis/ferroptosis in TM4 cells through ROS-dependent dysregulation of apoptosis- and ferroptosis-related genes. These findings establish distinct toxic mechanisms in TM4 cells and highlight the <i>SLC7A15/HMOX1</i> axis as a therapeutic target to mitigate Mn-induced spermatogenic damage.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 4","pages":"tfaf098"},"PeriodicalIF":2.1,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12286918/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A comparison of different scores for mortality prediction of acutely poisoned patients: a systematic review and meta-analysis.","authors":"Meng Wei, Xiaopeng Tu, Huan Li, Qiang Liu, Yu Tian","doi":"10.1093/toxres/tfaf080","DOIUrl":"10.1093/toxres/tfaf080","url":null,"abstract":"<p><p>Acute poisoning typically accounts for 1%-3% of all emergency department (ED) visits, and comprise 4%-40% of admissions to intensive care units (ICU), with a mortality rate of 3%-6%. Accurate assessment of patient prognosis enables the early implementation of appropriate interventions and the effective allocation of limited resources, thereby preventing adverse outcomes. However, it remains unclear which tool offers superior predictive accuracy for the prognosis of poisoned patients. In this article, we review existing assessment tools used to predict mortality risk in poisoned patients and compare their performance. We conducted comprehensive searches in PubMed, EMBASE, Ovid, Scopus, Cochrane Library, CNKI, Wanfang Data, and SinoMed databases from their inception up to January 2025. Studies were included if they reported the performance of at least one scoring systems for predicting mortality in patients with acute poisoning. The PRISMA guidelines were followed (PROSPERO registration: CRD42024579941). Data of 60,403 patients across 65 studies were eligible for inclusion. The risk assessment tools reported in more than three studies included APACHE II (47), SOFA (19), SAPS II (11), PSS (16), MEWS (8), REMS (5), new-PMS (5). Significant heterogeneity was observed in the pooled analysis. In this study, PSS exhibited moderate sensitivity and specificity in predicting mortality among patients with acute poisoning, while MEWS demonstrated the highest sensitivity, and new-PMS showed the strongest specificity. The highest AUC values were observed for MEWS and APACHE II. Based on these findings, MEWS and new-PMS may represent the optimal tools for predicting in-hospital/28-day/30-day mortality in poisoned patients.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 3","pages":"tfaf080"},"PeriodicalIF":2.2,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12205934/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Network toxicology and immune-metabolic dysregulation: linking per- and polyfluoroalkyl substances exposure to osteoarthritis pathogenesis.","authors":"Qian Zhang, Wenqi Zhang, Zhuchen Liu, Chunyu Luo, Ning Han, Weixin Cai, Jiaxing Liu","doi":"10.1093/toxres/tfaf077","DOIUrl":"10.1093/toxres/tfaf077","url":null,"abstract":"<p><p>Per- and polyfluoroalkyl substances (PFAS) are emerging environmental contaminants linked to various health conditions. However, the molecular mechanisms by which PFAS contribute to OA remain unclear. This study integrates network toxicology and bioinformatics to explore PFAS-related toxicity targets and their roles in OA pathogenesis. Transcriptomic data from the GSE48556 dataset were analyzed to identify differentially expressed genes (DEGs). PFAS-related genes (PSRGs) were retrieved from the CTD. Cross-analysis revealed overlapping genes, which were further evaluated via protein-protein interaction (PPI) networks, pathway enrichment, immune infiltration analysis, and nomogram construction. A total of 1,703 DEGs (910 upregulated, 793 downregulated) were identified in OA. Cross-analysis with 346 PSRGs yielded 26 overlapping genes, highlighting PFAS-OA molecular links. Enrichment analysis implicated IL-17 signaling, Th1/Th2 differentiation, and fatty acid metabolism as key pathways disrupted by PFAS. Immune-inflammatory pathways were robustly enriched, with CD3E, CARD11, and IFNG driving synovial inflammation. A nomogram incorporating five core targets (CARD11, IFNG, PAX8, PLD1, ZNF609) predicted OA risk and demonstrated clinical utility via decision curve analysis. Immune profiling revealed elevated infiltration of T cells, Th1 cells, and NK CD56dim cells in OA, alongside upregulated antigen presentation and TCR/BCR signaling. Core PFAS-related targets correlated significantly with immune dysregulation. PFAS exposure exacerbates OA by dysregulating immune-inflammatory axes and metabolic pathways, promoting synovitis and cartilage degradation. The identified genetic targets and nomogram provide mechanistic insights and translational tools for OA risk prediction in PFAS-exposed populations. This study establishes a systems-level framework linking PFAS toxicity to OA progression, offering actionable targets for therapeutic intervention.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 3","pages":"tfaf077"},"PeriodicalIF":2.2,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204612/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}