Toxicology Mechanisms and Methods最新文献

{"title":"CircRNA-mediated ceRNA network: micron-sized quartz silica particles induce apoptosis in primary human airway epithelial cells.","authors":"Jiazi Ma, Bing Han, Yong Yang, Yu Zhang, Mao Cao, Wenyue Cao, Wei Zhang, Mengjie Cheng, Guanqun Cui, Zhongjun Du, Shangya Chen","doi":"10.1080/15376516.2025.2539335","DOIUrl":"https://doi.org/10.1080/15376516.2025.2539335","url":null,"abstract":"<p><p>This paper studies the toxic effect of micron-sized quartz silica particles on primary human airway epithelial cells (AECs) and the molecular mechanism of its induction of apoptosis. Studies have found that micron-sized quartz silica particles cause AECs damage by activating cell apoptosis. By constructing a competitive endogenous RNA (ceRNA) network, it was identified that three circRNAs (hsa_circ_0052203, hsa_circ_0022429, hsa_circ_0052264) and four key miRNAs (hsa-miR-4646-5p, hsa-miR-150-3p, hsa-miR-6798-3p, hsa-miR-6756-5p) play key roles in regulating apoptosis. In addition, seven mRNAs (LMNB1, TP53AIP1, CASP10, BCL2, LMNB2, CFLAR and ITPR1) were significantly associated with the apoptosis. Functional enrichment analysis indicated that these genes were involved in biological processes such as nuclear lysis, hypoxia response and DNA damage. This study has for the first time revealed the role of the ceRNA network in the apoptosis of AECs induced by micron-sized quartz silica particles, providing new molecular targets and therapeutic ideas for the early pathogenesis of silicosis.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-18"},"PeriodicalIF":2.7,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144856429","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":"Cilostazol Ameliorates Cisplatin-induced Nephrotoxicity via Modulation of PI3K/AKT/mTOR Signaling Pathway and Autophagy in Rats.","authors":"Salma A El-Marasy, Nesma M E Abo El-Nasr, Dina E ElMosbah, Marawan Elbaset","doi":"10.1080/15376516.2025.2545577","DOIUrl":"https://doi.org/10.1080/15376516.2025.2545577","url":null,"abstract":"<p><p>This study aimed to evaluate the nephroprotective effect of Cilostazol on Cisplatin-induced nephrotoxicity. Female Wistar albino rats were divided into four groups: normal, Cis (8 mg/kg), and two Cilostazol treatment groups (30 and 60 mg/kg) with cisplatin. Cisplatin application significantly deteriorated renal function- manifested by increased serum creatinine (261%) and BUN (134%)-and enhanced oxidative stress-characterized by increased MDA (234%) and decreased GSH (64%). Cisplatin also affected autophagy markers, which included a 62% decrease in P62 and a doubling of LC3II. The PI3K/AKT/mTOR signaling pathway was significantly downregulated with reductions in PI3K (72%), mTOR (73%), and p-AKT/AKT ratio. NF-κB p65 was also increased by 1.5-fold. Moreover, an observed pronounced increase in the expression of TNF-α, caspase-3, and beclin-1 of the cisplatin-intoxicated rats. At the same time, Cilostazol (30 or 60 mg/kg) significantly reversed these changes, with a dose-dependent nephroprotective effect. At a higher dose (60 mg/kg), most parameters were comparable to the normal group, demonstrating superiority over the 30 mg/kg dose. These findings underpin that cilostazol modulates oxidative stress, inflammation, and autophagy pathways mainly via the PI3K/AKT/mTOR signaling axis to exert its renoprotective effect. Thus, cilostazol provides a promising potential in preventing cisplatin-induced nephrotoxicity. This outcome paves the way for the possible co-administration of cilostazol in the clinical realm to spare the deleterious effects of cisplatin.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-15"},"PeriodicalIF":2.7,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144837739","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":"Elucidating the impact of PFAS exposure on diabetes through integrated network toxicology.","authors":"Danyan Chen","doi":"10.1080/15376516.2025.2544030","DOIUrl":"https://doi.org/10.1080/15376516.2025.2544030","url":null,"abstract":"<p><p>Per- and polyfluoroalkyl substances (PFAS) are environmental pollutants linked to various health concerns, including metabolic disorders like diabetes. This study investigates the molecular mechanisms by which PFAS exposure influences diabetes through network toxicology and functional genomics approaches. We utilized the GSE25724 diabetes-related dataset to identify differentially expressed genes (DEGs) associated with PFAS exposure using the Comparative Toxicogenomics Database (CTD). Our methodologies included enrichment analyses, single-sample Gene Set Enrichment Analysis (ssGSEA), Protein-Protein Interaction (PPI) network construction, immune cell infiltration analysis, molecular docking, and validation experiments on HepG2 cells. Our analysis identified 34 DEGs linked to both diabetes and PFAS exposure. Enrichment analysis indicated these genes' involvement in critical pathways such as adipocytokine signaling, insulin secretion, and glucose homeostasis. ssGSEA revealed that inflammation-related pathways were significantly upregulated, while metabolic and stress response pathways were downregulated in the T2DM group. The PPI network pinpointed ATP2A2, INS, and NFE2L2 as key hub genes, which were validated to be significantly downregulated under PFAS exposure in HepG2 cells. The diagnostic potential of these genes was strong, with AUC values over 0.88. Immune cell infiltration analysis showed significantly altered immune profiles in the T2DM group. Molecular docking demonstrated stable binding between PFAS compounds and key genes, providing insights into potential molecular interactions. Our findings suggest that PFAS exposure disrupts crucial gene functions and biological pathways associated with diabetes, highlighting the significant impact of environmental toxicants on metabolic health. This underlines the need for further research into PFAS's role in diabetes pathophysiology.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-13"},"PeriodicalIF":2.7,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144849149","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":"Antioxidant and anti-inflammatory role of polysaccharides from the red alga <i>Osmundea pinnatifida</i> in countering bromuconazole-induced toxicity.","authors":"Zakaria Boujhoud, Marwa Lakhrem, Amal Feki, Intissar Kammoun, Abdelmonim Zeroual, Ibtissam Youlyouz Marfak, Sanah Essayagh, Said Hilali, Yahya Koulali, Manel Mellouli, Abderraouf Hilali, Jean Marc Pujo, Hatem Kallel, Ibtissem Ben Amara","doi":"10.1080/15376516.2025.2544906","DOIUrl":"https://doi.org/10.1080/15376516.2025.2544906","url":null,"abstract":"<p><p>Polysaccharides derived from marine algae are natural polymers with antioxidant, anti-inflammatory, and cytoprotectiveproperties, which make them promising for therapeutic use. In contrast, bromuconazole, a common triazole fungicide used in agriculture, has been associated with adverse effects such as oxidative stress, inflammation, and disruptions in cellular death pathways, raising safety concerns. This study investigates the potential of polysaccharides extracted from the red alga <i>Osmundea pinnatifida</i> (PSOP) to mitigate bromuconazole-induced toxicity. Through a subchronic 30-day exposure, 24 Wistar rats (6 per group) were divided into four groups: a control group, a bromuconazolegroup (32.8 mg/kg/day), a PSOP-only group (200 mg/kg/day), and a co-treatment group receiving both compounds. Bromuconazole exposure led to increased oxidative stress markers such as malondialdehyde (MDA), lipid hydroperoxides (LOOH), and advanced oxidation protein products (AOPP), along with decreased antioxidant defenses including glutathione peroxidase (GPx), reduced glutathione (GSH), non-protein thiols (NP-SH), and superoxide dismutase (SOD) in both liver and kidney tissues. These changes were accompanied by altered plasma biochemical parameters, indicating systemic toxicity. PSOP co-treatment alleviated oxidative stress by normalizing oxidation markers and enhancing antioxidant enzyme activities and non-enzymatic antioxidant defenses. Histopathological analyses confirmed PSOP's role in reducing tissue damage in the liver and kidneys. The HET-CAM assay also demonstrated PSOP's anti-irritant properties and ability to protect the vascular membrane during bromuconazole exposure. These results identify PSOP as an affordable, antioxidant-rich agent with significant biomedical potential,capable of protecting against oxidative damage induced by bromoconazole or xenobiotic.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-21"},"PeriodicalIF":2.7,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144837738","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":"Predicting the mechanisms and targets of PFOA nephrotoxicity via network toxicology, Mendelian randomization, molecular docking and molecular dynamics simulation.","authors":"Hang Zheng, Maohong Wang, Guoqing Wu, Fusheng Li, Weinong Wen, Xianfu Xu, Chengsheng Liu, Zhenzhen Zhang","doi":"10.1080/15376516.2025.2537893","DOIUrl":"10.1080/15376516.2025.2537893","url":null,"abstract":"<p><strong>Objectives: </strong>Perfluorooctanoic acid (PFOA), widely used in food-contact materials, industrial coatings, and other applications, enters the food chain <i>via</i> air, soil, and water, posing a potential public health risk.</p><p><strong>Methods: </strong>This study employs network toxicology, Mendelian randomization, molecular docking and molecular dynamics simulation to preliminarily elucidate the mechanisms by which PFOA's toxic targets contribute to renal impairment. Through integrated analysis of multi-database bioinformatics, we identified 85 cross-targets associated with PFOA-induced renal toxicity. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed significant enrichment of these targets in pathways related to ribosomes, lysosomes, complement and coagulation cascades, steroid hormone metabolism, immune-inflammatory diseases, and drug metabolism. STRING and Cytoscape tools identified five core targets (CYP3A4, CASP3, REN, PPARG, and IL-10). Mendelian randomization confirmed IL-10 as a central mediator of PFOA's nephrotoxicity. Molecular docking and molecular dynamics simulation demonstrated a high binding affinity between PFOA and IL-10.</p><p><strong>Results: </strong>Our findings suggest that PFOA likely exacerbates renal injury by suppressing IL-10 expression, thereby amplifying inflammatory responses, accelerating renal cell damage and fibrosis, and ultimately impairing kidney function.</p><p><strong>Conclusion: </strong>This study elucidates the molecular mechanisms underlying PFOA-induced nephrotoxicity, offering novel insights for environmental health research.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-13"},"PeriodicalIF":2.7,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144683150","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":"Bioinformatics analysis to identify endocrine-disrupting chemicals targeting key ESCC-related genes.","authors":"Yinnan Zhu, Weitao Shen, Mingyue Li","doi":"10.1080/15376516.2025.2543347","DOIUrl":"10.1080/15376516.2025.2543347","url":null,"abstract":"<p><p>Esophageal squamous cell carcinoma (ESCC), which has a high incidence and mortality rate in East Asia, arises from a complex interplay between genetic alterations and environmental exposures. Among environmental risk factors, endocrine-disrupting chemicals (EDCs) have attracted widespread attention, yet their impact on ESCC <i>via</i> gene interactions remains underexplored. This study integrated bioinformatics analysis to identify key genes and EDCs associated with ESCC pathogenesis. Chemical-gene interaction data were obtained from the Comparative Toxicogenomics Database(CTD), and differentially expressed genes(DEGs) were screened from the Gene Expression Omnibus (GEO) database. LASSO regression analysis prioritized five key genes (<i>BUB1B</i>, <i>TPM2</i>, <i>KRT17</i>, <i>ADH1B</i>, <i>SALL4</i>). Based on these genes, 25 EDCs potentially involved in ESCC were identified, of which 13 (such as benzo[a]pyrene) targeted at least three of the key genes. These findings suggested a novel EDC-gene-ESCC interaction network and provide insights into the environmental mechanisms underlying ESCC, offering potential targets for risk assessment and therapeutic intervention.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-12"},"PeriodicalIF":2.7,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144785394","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":"Zebrafish 24 hpf-embryos as a model organism for measuring oxygen consumption rate (OCR).","authors":"P V L Peixoto, C C da Silva, L C Pereira","doi":"10.1080/15376516.2025.2537894","DOIUrl":"10.1080/15376516.2025.2537894","url":null,"abstract":"<p><p>The alterations in mitochondrial function are involved in various pathological conditions and hence the evaluation of such damage is crucial to determine the mitotoxic potential of different chemicals. Due to their 71% genetic similarity to humans, the similar mitochondrial functions, and metabolic processes of zebrafish (<i>Danio rerio</i>) have been used in analyses for this purpose. The aim of this study was to establish a standardized technique to assess mitochondrial dysfunction by analyzing oxygen consumption rate (OCR) in zebrafish embryos 24 h post-fertilization using the OROBOROS O2k Oxygraph. The technique involved the use of mitochondrial modulators and the OROBOROS O2k Oxygraph to directly assess mitochondrial and electron transport chain complex activity during embryonic development. Embryos were treated with a respiratory medium supplemented with malate, succinate, and pyruvate, and with digitonin to permeabilize the chorion and membranes for mitochondrial analysis. OCR measurements were performed in the presence of specific mitochondrial modulators: oligomycin, FCCP, rotenone and antimycin A. Optimized evaluation was achieved using 20 embryos per assay. Therefore, through the development of a protocol for synchronization analysis of OCR in zebrafish embryos, several parameters related to the effectiveness of the oxidative phosphorylation process could be rapidly determined. Since zebrafish are particularly useful to study mitochondrial dysfunction in toxicants, this protocol describes the procedure to quantitate the effect of toxicants on mitochondrial activity which turns out to be valuable to understanding the mechanism of xenobiotic toxicity.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-13"},"PeriodicalIF":2.7,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144691648","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":"Impact of ethanol as a vehicle for water-insoluble pollutants in BEAS-2B cell toxicity assays.","authors":"Emma Ann Landskroner, Candace Su-Jung Tsai","doi":"10.1080/15376516.2025.2540457","DOIUrl":"10.1080/15376516.2025.2540457","url":null,"abstract":"<p><p><i>In vitro</i> human cell models are the gold standard for toxicological screening of environmental pollutants, allowing precise profiling of cellular responses. Pollutants with limited water solubility require carrier vehicles for uniform exposure. Ethanol, a commonly used vehicle, is typically maintained at 0.05-1.0% (v/v) to minimize toxicity. However, definitive no-observed-adverse-effect levels (NOAELs) or lowest-observed-adverse-effect levels (LOAELs) for ethanol in non-tumorigenic human bronchial epithelial (BEAS-2B) cells, prevalent in inhalation studies, have not been established. Researchers thus apply a range of ethanol concentrations derived from diverse cell lines, increasing the risk of vehicle interference. This study evaluated ethanol as a cosolvent vehicle for four emerging high-flashpoint hydrocarbon (HFHC) dry cleaning solvents in BEAS-2B cells. HFHC solvents were solubilized 1:1 in 100% ethanol, then diluted in bronchial epithelial cell growth basal medium to final concentrations of 0.05%, 0.25%, 0.5%, and 2.5% (v/v). Vehicle, positive, and negative controls isolated ethanol-specific cytotoxic effects. Cytotoxicity was assessed via cellular viability (MTS assay) at 24 and 48 h, and lactate dehydrogenase (LDH) and interleukin-8 (IL-8) release after 24 h. Ethanol drove viability loss at ≥0.5% (24 h) and ≥0.25% (48 h), induced inflammation at concentrations ≥0.05%, and minimally impacted membrane integrity. Most HFHC solvents showed minimal effects beyond ethanol alone, except one HFHC, Intense, causing significant membrane disruption and cytotoxicity even at low doses (0.05-0.25%). Practical ethanol noninterference thresholds recommended are ≤0.5% for 24-hour assays, ≤0.25% for 48-hour viability, and ≤0.05% for inflammatory endpoints, establishing critical guidelines for ethanol use in BEAS-2B assays.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-13"},"PeriodicalIF":2.7,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12410134/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144733437","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":"Application and prospect of organoids in tobacco product safety and risk evaluation.","authors":"Yi Liu, ChengHao Luo, Jing Zhang, Yuanjing Huang, JunPeng Yang, Long Huang","doi":"10.1080/15376516.2025.2537314","DOIUrl":"10.1080/15376516.2025.2537314","url":null,"abstract":"<p><p>In recent years, with the emergence of various types of tobacco products, the safety and risk assessment of tobacco product has become the focus of social attention. Organoids, as a new research model, can simulate the basic properties of tissues and perform normal biological functions <i>in vitro</i> experiments, with the advantages of low cost and high efficiency, it has been tentatively used in the safety evaluation of tobacco products. This review summarizes the concept and types of organoids and introduces the model structure and corresponding fundamentals of organoids in tobacco product safety and risk research. In addition, the effects of tobacco products on phenotypic changes of various organoids (such as lung, intestine, brain, maternal and fetal organoids) and the corresponding mechanisms (including oxidative stress, inflammatory response, etc.) were further summarized. At the same time, the advantages of applying organoids, the development trend and direction of organoids in evaluating tobacco product safety and risk in the future were also summarized. In summary, this review systematically describes the application and prospects of organoids in the safety and risk assessment of tobacco product, which helps researchers draw attention to the important role of organoids in safety and risk assessment of tobacco product, and provides some theoretical and literary foundations for improving people's quality of life.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-13"},"PeriodicalIF":2.7,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144675664","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":"Toxicological mechanisms: moving forward with artificial intelligence.","authors":"Luis G Valerio","doi":"10.1080/15376516.2025.2540458","DOIUrl":"10.1080/15376516.2025.2540458","url":null,"abstract":"","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-2"},"PeriodicalIF":2.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144733439","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}