Toxics最新文献

{"title":"Oxidative Stress, DNA Damage, DNA Repair Inhibition, and Apoptosis Induced by Lead and Cadmium Combined Exposure in TK6 Cells.","authors":"Xin Liu, Zhiyuan Han, Kuibin Han, Yuhan Pang, Xiaoyue Zhao, Yuting Wang, Xiaoyan Wu, Tuanwei Wang","doi":"10.3390/toxics14040341","DOIUrl":"https://doi.org/10.3390/toxics14040341","url":null,"abstract":"<p><p>Lead (Pb) and cadmium (Cd) are common environmental pollutants. Our previous population study revealed a significant positive association between Pb and Cd exposure and the micronuclei frequency among lead smelting workers. However, the underlying mechanisms remain unclear. In this study, human lymphoblastoid TK6 cells were used to investigate the genotoxicity and its mechanisms induced by individual or combined exposure to Pb and Cd. Our results showed that Pb and Cd exposure, alone or in combination, triggered oxidative stress, as evidenced by reduced antioxidant enzyme activity (GSH, SOD and CAT) and increased content of ROS and GSSG. Both metals induced pronounced DNA damage, as shown by elevated Tail DNA% in the Comet assay and γ-H2AX fluorescence intensity. Furthermore, Pb and/or Cd exposure caused inhibition of the DNA repair proteins, including BRCA1, CtIP, RAD52, and XRCC2, indicating impaired DNA repair capacity; and upregulated Bax expression and the Bax/Bcl-2 ratio and Caspase-3 with downregulation of Bcl-2. Notably, Pb and Cd co-exposure produced an antagonistic effect, modulating oxidative stress indicators, cell-cycle arrest, DNA damage markers, DNA repair and apoptosis-related proteins. These findings demonstrate that Pb and Cd induce oxidative stress, DNA damage, inhibition of DNA repair, and apoptosis in TK6 cells. Our study provides new insights into the mechanisms of heavy metal combined exposure-induced genotoxicity and identifies potential molecular targets for intervention.</p>","PeriodicalId":23195,"journal":{"name":"Toxics","volume":"14 4","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13120129/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147782030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing the Interactive Effects of Graphene Oxide and Marine Heatwave Stressors on Estuarine Bivalves.","authors":"Valéria Giménez, Beatriz Neves, Etelvina Figueira, Paula Marques, Adília Pires","doi":"10.3390/toxics14040339","DOIUrl":"https://doi.org/10.3390/toxics14040339","url":null,"abstract":"<p><p>Coastal ecosystems are increasingly threatened by climate change, especially the rising frequency of marine heatwaves (MHWs), which often co-occur with emerging nanomaterials such as graphene oxide (GO), whose ecological risks are still being evaluated. While the effects of GO have been studied in isolation, little is known about its interaction with thermal stress events. This research studied the combined effects of temperature (18 °C and 23 °C, simulating control and MHW conditions) and GO nanosheets exposure (0.01 mg/L) on two key estuarine bivalves: the clam <i>Scrobicularia plana</i> and the mussel <i>Mytilus galloprovincialis</i>. After 7 days of exposure (duration of many MHWs), energy metabolism, antioxidant defenses, oxidative damage, and neurotransmission were assessed. The results revealed that clams exhibited lower ETS and SOD activity when exposed to MHWs and lower SOD and AChE activities at MHW + GO, compared to the control treatment. Mussels relied primarily on SOD activity across treatments but showed increased susceptibility to GO nanosheets, with higher LPO levels and a significant reduction in AChE activity when exposed to GO at both temperatures. Overall, our findings suggest that <i>S. plana</i> shows a stronger response to the environmental alterations tested than <i>M. galloprovincialis</i>. Combined exposure to GO + MHW triggers species-specific biochemical responses in estuarine bivalves, highlighting how physiological traits shape the assessment of ecological risks posed by nanomaterial pollution under climate change.</p>","PeriodicalId":23195,"journal":{"name":"Toxics","volume":"14 4","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13120203/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147781973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Per- and Polyfluoroalkyl Substances and Endometriosis: A Systematic Review and Meta-Analysis.","authors":"Sarah Pilling, Kerry Mitchell, Prakash V A K Ramdass","doi":"10.3390/toxics14040337","DOIUrl":"https://doi.org/10.3390/toxics14040337","url":null,"abstract":"<p><p>Per- and polyfluoroalkyl substances (PFASs) are persistent endocrine-disrupting chemicals implicated in reproductive dysfunction. Epidemiologic evidence examining their association with endometriosis remains inconsistent. Thus, we conducted a PRISMA-compliant systematic review and meta-analysis using PubMed, Embase, EBSCO Host, and Google Scholar databases. RStudio software was used for all analyses. Random-effects or fixed-effects model was applied to estimate pooled odds ratios (ORs) and standardized mean difference (SMD) in PFAS levels between endometriosis patients and controls. Heterogeneity was assessed using I² statistics. Publication bias was evaluated using funnel plots, and Egger's and Begg's tests. Twelve studies met the inclusion criteria for the systematic review and eleven were included in the quantitative synthesis. Overall, PFSAs (OR: 1.50; 95% CI: 1.12-2.00) and PFCAs (OR: 1.46; 95% CI: 1.12-1.90) were significantly associated with increased odds of endometriosis, particularly PFOS and PFOA. However, analyses of pooled SMD did not demonstrate consistent concentration differences between endometriosis cases and controls. Heterogeneity was moderate to high for most compounds. Funnel plot symmetry and Egger's and Begg's tests suggest no publication bias. Exposure to PFASs, particularly PFOS and PFOA, may be associated with increased odds of endometriosis. Further prospective studies incorporating mixture modeling and emerging PFASs are warranted.</p>","PeriodicalId":23195,"journal":{"name":"Toxics","volume":"14 4","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13120307/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147782109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"QSAR Models for Repeated Dose Toxicity in Rats Using the CORAL Software.","authors":"Alla P Toropova, Andrey A Toropov, Nadia Iovine, Gianluca Selvestrel, Alessandra Roncaglioni, Emilio Benfenati","doi":"10.3390/toxics14040338","DOIUrl":"https://doi.org/10.3390/toxics14040338","url":null,"abstract":"<p><p>The evaluation of the safety of chemical substances requires the identification of a safe dose, which has no adverse effects on humans. This is obtained through animal studies, with exposure prolonged for months. Repeated-dose toxicity is a term in toxicology and pharmacology referring to the highest tested dose of a substance, so-called No Observed Adverse Effect Level (NOAEL). Experimental data on NOAEL taken from the literature and the OpenFoodTox database (total <i>n</i> = 848). To speed up the processing of the enormous number of substances we are exposed to, in silico models are an attractive solution. Monte Carlo technique, incorporating the Las Vegas algorithm, was applied to develop models for repeated-dose toxicity in rats. Optimal descriptors were calculated using correlation weights for attributes of the Simplified Molecular Input Line Entry System (SMILES). Computational experiments were conducted 5 times, with splits obtained using the Las Vegas algorithm. Good predictive potential was observed for these models, with an average determination coefficient on the validation set of 0.77 ± 0.04.</p>","PeriodicalId":23195,"journal":{"name":"Toxics","volume":"14 4","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13120275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147782091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Removal Performance and Mechanistic Insights into As(V) Transport in Natural Manganese Minerals.","authors":"Zhicheng Zhao, Huimei Shan, Song Wei, Zheying Li, Qingsheng Li","doi":"10.3390/toxics14040340","DOIUrl":"https://doi.org/10.3390/toxics14040340","url":null,"abstract":"<p><p>Arsenic contamination in polymetallic mining areas is closely linked to surrounding iron-rich manganese minerals. However, conclusive evidence remains limited regarding the retention and migration process of As(V) in naturally manganese-rich manganese ores (especially those with different manganese/iron mass ratios) under dynamic flow conditions. This study investigated As(V) adsorption and transport by four natural manganese minerals (FM1-FM4) through batch/column experiments, characterization, and numerical modeling. Their Mn/Fe mass ratios were 22.7 for FM1, 4.2 for FM2, 3.7 for FM3, and 16.4 for FM4. Batch experiments showed that As(V) adsorption on FM1-FM3 was better described by the Freundlich model, indicating heterogeneous adsorption behavior. Under the tested experimental conditions, the apparent Langmuir <i>q</i>_m values of these minerals decreased from 0.066 to 0.015 mmol·g^-1 with decreasing Mn/Fe ratio. However, As(V) adsorption on FM4, which had the lowest Mn and Fe contents, followed the Langmuir model (<i>q</i>_m = 0.012 mmol·g^-1), suggesting monolayer adsorption. Column experiments demonstrated rapid As(V) retention for all minerals. In the time domain, increasing the flow rate from 0.5 to 2.0 mL·min^-1 generally advanced breakthrough and shortened the desorption tail, although the breakthrough behavior expressed in pore-volume coordinates was not strictly monotonic for all minerals. The Two-Site Kinetic Attachment Model (TSKAM) successfully simulated these dynamics (R² > 0.90, RMSE < 0.05), revealing adsorption controlled by fast and slow kinetic sites, with slow-site contributions diminishing at higher flow rates. Characterization results indicated that adsorbed arsenic on FM1 remained mainly as As(V) and was immobilized primarily through surface complexation involving surface hydroxyl and Fe/Mn-O groups. XRD and SEM-EDS suggested the participation of Fe/Mn-bearing phases, while XPS on FM1 showed pronounced changes in Mn surface species during adsorption. Therefore, As(V) removal by these natural manganese minerals is a coupled physicochemical process influenced by both mineral properties, including Mn/Fe ratio, specific surface area, pore structure, pH_PZC, and Mn surface-state changes, and hydrodynamic conditions in the polymetallic mining areas.</p>","PeriodicalId":23195,"journal":{"name":"Toxics","volume":"14 4","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13120385/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147782097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association Between Exposure to Air Pollutant Mixture and Risk of Inflammatory Bowel Disease: Modifying Effects of Healthy Lifestyle and Residential Greenspace.","authors":"Runze Bai, Xiaochi Zhang, Guoao Li, Yiyi Wang, Hujia Zhang, Baopeng Liu, Xiuli Zuo, Jie Yan, Qi Zhao","doi":"10.3390/toxics14040333","DOIUrl":"https://doi.org/10.3390/toxics14040333","url":null,"abstract":"<p><p><b>Background:</b> Although air pollution is increasingly considered an environmental hazard for inflammatory bowel disease (IBD), existing evidence predominantly relies on single-pollutant models that fail to capture mixed exposures, with modifying effects of individual lifestyle and residential environments remaining largely unexplored. <b>Methods:</b> We conducted a prospective cohort study using UK Biobank data, including 323,608 participants followed for incident IBD. Annual mean concentrations of five air pollutants [nitrogen dioxide (NO₂), nitrogen oxides (NO_x), and PM with aerodynamic diameters of ≤2.5, 2.5-10, and ≤10 μm (PM_2.5, PM_2.5-10, PM₁₀)] and greenspace percentage within 300 m and 1000 m buffers were assigned to each participant's residential address. A healthy lifestyle score was defined by five factors: smoking status, alcohol consumption, physical activity, sleep patterns, and dietary quality. Cox proportional hazards models with quantile g-computation (QGC) were employed to examine associations between single- and mixed-air-pollutant exposures and IBD risk. Stratified analyses were performed by healthy lifestyle, lifestyle score, and greenspace percentage. <b>Results:</b> During the follow-up period, 1649 and 805 participants developed ulcerative colitis (UC) and Crohn's disease (CD), respectively. Single-pollutant models suggested that exposures to most air pollutants were substantially associated with increased risk of IBD, and the association strengths were more pronounced for UC than for CD. QGC analyses indicated that the hazard ratios (<i>HR</i>) of IBD risk were 1.068 (95%<i>CI</i>: 1.018-1.121) for each one-quantile increase in the air pollutant mixture, with NO₂ weighted as the largest contributor. High physical activity was significantly linked to an attenuated UC-pollutant mixture association. <b>Conclusions:</b> This study found that exposure to an air pollutant mixture was associated with increased risk of IBD, especially for UC, with NO₂ contributing the largest effect size. The certain attenuated air pollution effects of healthy lifestyles and residential greenspaces underscore the need for integrated public health strategies with environmental management.</p>","PeriodicalId":23195,"journal":{"name":"Toxics","volume":"14 4","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13119546/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147782022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Per- and Polyfluoroalkyl Substances in Fish: Global Occurrence, Bioaccumulation, Analytical Approaches, and Human Exposure Risks-A Review.","authors":"Ines Varga, Nina Bilandžić, Jelena Kaurinović, Andrea Gross Bošković, Tomislav Klapec","doi":"10.3390/toxics14040336","DOIUrl":"https://doi.org/10.3390/toxics14040336","url":null,"abstract":"<p><p>Per- and polyfluoroalkyl substances (PFAS) are highly stable and persistent environmental contaminants. Their exceptional chemical stability prevents natural breakdown, leading to global distribution and bioaccumulation in aquatic organisms. Long-chain PFAS, such as perfluorooctane sulfonic acid (PFOS), tend to accumulate in the liver, kidneys, and muscle tissues, whereas short-chain PFAS remain largely dissolved in water and show lower accumulation. Freshwater fish generally contain higher PFAS levels than marine fish, with concentrations varying according to species, habitat, trophic level, contamination site, and other factors. Human exposure primarily occurs through the consumption of contaminated fish and seafood, as well as through drinking water, inhalation, and skin contact. Such exposure is associated with immunosuppression, high cholesterol, hormonal disruption, cancer, and other health risks. Regulatory limits exist for four PFAS compounds, while many others, including emerging compounds, remain unregulated. This review synthesizes the current knowledge on the global distribution of PFAS across various fish species, analytical approaches including sample preparation (e.g., SPE, QuEChERS) and instrumental techniques (e.g., LC-MS/MS, HRMS), human dietary exposure, and the related health risks. By integrating environmental distribution, bioaccumulation, analytical challenges, and health issues, this review provides an up-to-date perspective on PFAS in fish and emphasizes the need for ongoing monitoring and stricter regulatory frameworks to ensure food safety and protect both human health and ecosystems.</p>","PeriodicalId":23195,"journal":{"name":"Toxics","volume":"14 4","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13120487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147782138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Explainable Deep Learning for Research on the Synergistic Mechanisms of Multiple Pollutants: A Critical Review.","authors":"Chang Liu, Anfei He, Jie Gu, Mulan Ji, Jie Hu, Shufeng Qiao, Fenghe Wang, Jing Hua, Jian Wang","doi":"10.3390/toxics14040335","DOIUrl":"https://doi.org/10.3390/toxics14040335","url":null,"abstract":"<p><p>The synergistic control of multiple pollutants is critically challenged by complex nonlinear interactions, strong spatiotemporal heterogeneity, and the difficulty of tracing causal drivers. Deep learning offers high predictive power but suffers from the \"black-box\" problem, limiting its acceptance in environmental decision-making. Explainable Deep Learning (XDL) integrates physical mechanisms with interpretable algorithms, achieving both prediction accuracy and explanatory transparency. This review systematically evaluates the effectiveness and limitations of XDL in analyzing multi-pollutant interactions, with a comparative focus on atmospheric and aquatic environments. Key techniques, including SHAP, attention mechanisms, and physics-informed neural networks, are examined for their roles in synergistic monitoring, source apportionment, and regulatory optimization. The main findings reveal that: (1) XDL, particularly the \"tree model + SHAP\" paradigm, has become a dominant tool for quantifying driving factors, yet most attributions remain correlational rather than causal; (2) physics-informed fusion (soft vs. hard constraints) improves physical consistency but faces unresolved conflicts between data and physical laws, with current models lacking a conflict detection mechanism; (3) cross-media comparison shows a unified technical logic of \"physical mechanism guidance + post hoc feature attribution\", but atmospheric applications lead in embedding advection-diffusion constraints, while aquatic research excels in spatial topology modeling via graph neural networks; (4) critical bottlenecks include the lack of causal inference, uncertainty-unaware interpretations, and data scarcity. Future directions demand a shift from correlation-only to causal-aware attribution, from blind fusion to conflict-detecting systems, and from no evaluation standards to domain-specific validation benchmarks. XDL is poised to transform multi-pollutant governance from experience-driven to intelligence-driven approaches, provided that verifiable interpretability and physical consistency become core design principles.</p>","PeriodicalId":23195,"journal":{"name":"Toxics","volume":"14 4","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13119790/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147781881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hidden Hazards: Assessment of Exposure Risks from 3-Monochloropropane-1,2-diol Ester (3-MCPDE) and Glycidyl Ester (GE) Consumption Among Malaysian Consumers.","authors":"Siti Hajar Muhamad Rosli, Nurul Izzah Ahmad, Nurul Hidayati Surawi, Rohana Ani, Nor Kamilah Mohamad Alwi, Ami Fazlin Syed Mohamed","doi":"10.3390/toxics14040331","DOIUrl":"https://doi.org/10.3390/toxics14040331","url":null,"abstract":"<p><p>3-Monochloropropanediol esters (3-MCPDEs) and glycidyl esters (GEs) are food processing contaminants that raise significant food safety concerns due to their established potential for carcinogenicity. This study aimed to determine the occurrence of 3-MCPDEs and GEs in common Malaysian food items and to evaluate the associated health risks through dietary exposure assessment. A total of 251 samples, consisting of retail products and cooked/prepared meals, were analysed using GC-MS. The food consumption data were obtained from published national food surveys. Risk was characterised using health-based guidance values (HBGVs) and margin of exposure (MOE), lifetime cancer risk (LCR), and disability-adjusted life year (DALY) estimates. 3-MCPDE was detected in 94.8% of samples (range: ND to 7.77 mg/kg), while GE was found in 83.3% of samples (range: ND to 9.41 mg/kg). The highest levels were consistently observed in refined vegetable fats and oil products, specifically shortening (3-MCPDE: 3.53 [IQR 2.76-5.16] mg/kg; GE: 4.78 [IQR 3.52-6.14] mg/kg) and margarine (3-MCPDE: 2.50 [IQR 1.11-3.59] mg/kg; GE: 3.60 [IQR 1.18-5.26] mg/kg). Exposure assessment identified fried rice as the largest contributor to total daily intake (3-MCPDE: 3.16 μg/kg BW/day; GE: 1.36 μg/kg BW/day). Total exposure to 3-MCPDE exceeded the provisional maximum tolerable daily intake (PMTDI) established by JECFA by 39.5%, indicating a potential health concern. Low MOE estimates (<10,000) for 3-MCPDE and GE were determined for several food categories, including snacks, kuih-muih, and fried cooked dishes. Chronic GE exposure was estimated to cause up to 6.9 (for mean consumers) and 24.9 (for high consumers) cancer cases per year, with total the DALYs quantified at 124.2 years lost per 100,000 of the population. These data represent a worst-case scenario; however, risks could be minimised through continued surveillance, mitigation strategies by relevant authorities regarding food processing, and informed dietary choices.</p>","PeriodicalId":23195,"journal":{"name":"Toxics","volume":"14 4","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13119714/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147782052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reprogramming of the m⁶A Epitranscriptome Drives Triptolide-Induced Reproductive Toxicity in HTR-8/SVneo Cells.","authors":"Xinru Liu, Yunli Wu, Jin Tian, Jiaxin Wen, Yuan Shi, Lili Wang, An Zhu, Zekai Wu","doi":"10.3390/toxics14040334","DOIUrl":"https://doi.org/10.3390/toxics14040334","url":null,"abstract":"<p><p>Triptolide (TPL), the core active component of the traditional Chinese medicinal herb <i>Tripterygium wilfordii</i> Hook F (TwHF), possesses a wide spectrum of pharmacological activities, including anti-inflammatory, neuroprotective, immunosuppressive, and anti-tumor activities. However, its clinical application is severely limited by significant reproductive toxicity, the mechanism of which remains poorly understood. Using an integrated analysis of MeRIP-seq and mRNA-seq data, coupled with experimental validation in HTR-8/SVneo cells, we systematically elucidated the molecular mechanism by which TPL induces trophoblast cell injury. Our findings revealed that TPL significantly altered intracellular N⁶-methyladenosine (m⁶A) modification and gene expression profiles, with 1774 genes displaying hypomethylation concurrent with mRNA upregulation. According to the functional enrichment analysis, these genes showed significant enrichment in several key pathways associated with reproduction, including autophagy, DNA damage response, mitochondrial outer membrane, and positive regulation of apoptotic process. Molecular docking further demonstrated direct and stable binding of TPL to key m⁶A regulators, leading to specific demethylation of targets including <i>E2F1</i> and <i>PPP1CC</i>. This study uncovers a novel post-transcriptional mechanism where TPL disrupts m⁶A modification, thereby perturbing essential trophoblast functions and driving reproductive toxicity.</p>","PeriodicalId":23195,"journal":{"name":"Toxics","volume":"14 4","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13119796/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147782107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}