Toxicology Mechanisms and Methods最新文献

{"title":"Correction.","authors":"","doi":"10.1080/15376516.2026.2735512","DOIUrl":"https://doi.org/10.1080/15376516.2026.2735512","url":null,"abstract":"","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1"},"PeriodicalIF":2.7,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149012768","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":"Statement of Retraction: Long non-coding RNA maternally expressed 3 (MEG3) regulates isoflurane-induced cognitive dysfunction by targeting miR-7-5p.","authors":"","doi":"10.1080/15376516.2026.2732286","DOIUrl":"https://doi.org/10.1080/15376516.2026.2732286","url":null,"abstract":"","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1"},"PeriodicalIF":2.7,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148983558","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":"A dose-unit-aware predictive toxicology framework for literature-derived <i>in vitro</i> carbon nanotube cytotoxicity.","authors":"Deniz Özkan Vardar, Necati Vardar","doi":"10.1080/15376516.2026.2725744","DOIUrl":"10.1080/15376516.2026.2725744","url":null,"abstract":"<p><p>Carbon nanotubes (CNTs) are increasingly used as engineered nanomaterials, but their <i>in vitro</i> cytotoxicity remains difficult to synthesize because reported viability outcomes vary across dose metrics, exposure durations, CNT types, functionalization states, cell models, and assay systems. This study developed an exploratory, literature-derived, dose-unit-aware predictive toxicology framework for binary classification of CNT-induced cytotoxicity using standardized cell viability data. Experimental-condition-level records were extracted from eligible <i>in vitro</i> CNT studies and harmonized according to dose, dose unit, exposure duration, CNT type, functionalization, cell line, assay type, and viability outcome. Cytotoxicity was defined as cell viability below 70%. A primary-core dataset, including 146 µg/mL records from 11 articles, was used for nominal concentration-based modeling, whereas a secondary unit-aware dataset, including 212 records from 13 articles, incorporated both µg/mL and µg/cm² observations while retaining dose-unit identity as an explicit predictor. Logistic Regression and Random Forest classifiers were trained using log-transformed dose-related variables and experimental-context predictors. Performance was assessed using stratified cross-validation, article-grouped cross-validation, leave-one-article-out validation, and leave-one-family-out validation with fold-level variability considered to reflect uncertainty and to mitigate overoptimistic estimates arising from within-study similarity. Random Forest showed higher point estimates under conventional stratified validation, whereas Logistic Regression provided comparatively stable discrimination under stricter grouped-validation settings. Ablation-based stress testing identified high-dose nontoxic A549/MTT observations as a major source of false-positive toxicity predictions, particularly for Random Forest. A dose × dose-unit interaction sensitivity analysis did not consistently improve grouped or leave-one-out validation; therefore, the additive unit-aware model was retained as the primary unit-aware analysis. The unit-aware analysis demonstrated that surface-dose records can be incorporated without assuming equivalence between nominal mass concentration and surface-area-normalized exposure. The framework provides a transparent strategy for curating, validating, stress-testing, and cautiously modeling heterogeneous literature-derived CNT viability data in nanosafety research.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-19"},"PeriodicalIF":2.7,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148832413","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":"Alternative tobacco and nicotine products during anticancer therapy: a systematic review of mechanistic toxicology evidence, treatment-resistance signals, and potential hazards.","authors":"Paulina Natalia Kopa-Stojak, Rafał Pawliczak","doi":"10.1080/15376516.2026.2726966","DOIUrl":"https://doi.org/10.1080/15376516.2026.2726966","url":null,"abstract":"<p><p>The aim of this review is to determine the effect of alternative tobacco/nicotine products on response to chemotherapy, including mechanistic toxicology evidence, treatment-resistance signals and potential hazard. The literature was searched in PubMed, Embase and Web of Science databases in June 2026. Currently, there has been no epidemiological study investigating effects of alternative products on chemotherapy response. There are some evidence that snus using increases risk of cancer-related death and reduces survival rate. However, for e-cigarettes the weight of such evidence is lower. Furthermore, there is one <i>in vitro</i> study, which found that cisplatin resistance can be associated with EC-induced changes in expression of drug influx/efflux transporters. However, multi-center replication study failed to validate such findings, concluded that e-cigarette aerosols do not significantly increase cisplatin resistance in head and neck squamous cell carcinoma cell lines. Finally, there is some evidence that alternative products affects cancer cells proliferation, growth, epithelial-to-mesenchymal transition, oxidative stress, which may influence survival and metastasis of cancer cells. Due to limited evidence, we are unable to clearly determine effects of using alternative tobacco/nicotine products on patients' response to chemotherapy, cancer progression, metastasis and risk of cancer-related death. The evidence supports cautious interpretation of findings and highlights the need for standardized, reproducible methods and further <i>in vivo</i> preclinical and clinical data before drawing conclusions about the use of alternative products during chemotherapy. Therefore, well-designed prospective cohort studies, real-world evidence studies and cancer patient registries are critical to fully understand potential risks associated with their use during anticancer therapy.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-23"},"PeriodicalIF":2.7,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148963698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling the neurodevelopmental toxicity of PFOA and PFOS: evidence from integration of <i>in silico</i> and <i>in vitro</i> study.","authors":"Lili Xin, Rui Guo, Jiawei Sun, Yue Su, Jiahang Cai, Wanzhen Li, Zhongxiao Wan, Jianshu Wang","doi":"10.1080/15376516.2026.2723920","DOIUrl":"10.1080/15376516.2026.2723920","url":null,"abstract":"<p><p>Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) are well-known neurodevelopmental toxicants, but the potential molecular mechanism needs to be further clarified. This study aimed to investigate the underlying mechanism of PFOA and PFOS-induced neurodevelopmental toxicity by integrating network toxicology, transcriptomic data from autism spectrum disorder patients and <i>in vitro</i> study. Network toxicology identified 42 core targets that enriched in a total of 105 significant GO entries and 142 KEGG pathways. With the disease-context comparison from the transcriptomic, 10 hub targets and 22 common KEGG pathways were identified. Cellular senescence-associated responses including cellular senescence and cell cycle were proposed as one of the potential mechanisms underlying PFOA and PFOS co-exposure-induced neurodevelopmental toxicity. Molecular docking analysis showed that PFOA and PFOS elicits potential binding capacities with hub targets, with TP53 and MAPK 13 exhibiting lower binding energies with both PFASs, further predicting the potential role of these targets in PFASs-induced neurodevelopmental toxicity. After PFOA and PFOS co-treatment, reduced cell viability, a senescence-like phenotype characterized by cell cycle arrest and increased positive senescence β-galactosidase, upregulation of senescence-associated biomarkers including TP53, p53, p21 and IL-6 as well as the significant up-regulation of <i>MAPK1</i>, <i>MAPK3</i>, <i>MAPK13</i> and <i>MAPK14</i> genes were observed in human neuroblastoma SH-SY5Y cells. Thereafter, these findings suggested the multi-target and multi-pathway characteristic of PFOA and PFOS co-exposure-induced neurodevelopmental toxicity with cellular senescence-associated responses as one of the potential molecular mechanisms.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-15"},"PeriodicalIF":2.7,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148809077","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":"Protective effect of dapagliflozin on hepatic encephalopathy induced by thioacetamide in rats: involvement of ERK, JNK, and Nrf2/HO-1 pathways.","authors":"Hadir Farouk, Salma A El-Marasy, Marwa S Khattab, Yasmin M Abd El-Aziz, Rasha E Mostafa","doi":"10.1080/15376516.2026.2725745","DOIUrl":"10.1080/15376516.2026.2725745","url":null,"abstract":"<p><p>Hepatic encephalopathy (HE) is a neuropsychiatric disorder associated with oxidative stress, neuroinflammation, and hyperammonemia secondary to hepatic dysfunction. This study aimed to investigate dapagliflozin's effects (DAPA) against HE induced by thioacetamide (TAA) in rats and to elucidate the roles of the extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and nuclear factor erythroid 2-related factor 2/Heme oxygenase-1 (Nrf2/HO-1) signaling pathways. HE was induced by injection of TAA (200 mg/kg) intraperitoneally 2 times every other day. Two groups were pretreated with DAPA at 5 and 10 mg/kg for 15 days; on the 13th day, rats were given TAA (200 mg/kg, i.p.) twice, 2 days apart. Behavioral assessments, including object recognition and rotarod tests, were conducted, and serum and tissue samples were collected for biochemical and molecular analyses. DAPA pretreatment ameliorated TAA effects, improved recognition memory, enhanced muscular tone and motor coordination. DAPA also reduced ALT (alanine aminotransferase), AST (aspartate aminotransferase), and ammonia serum levels. Additionally, it restored antioxidant balance, decreased malonaldehyde (MDA) and increased reduced glutathione (GSH). Moreover, it reduced tissue inflammation and inhibited apoptosis; where tumor necrosis factor-alpha (TNF-α) and caspase-3 expression were suppressed. DAPA was associated with increased Nrf2/HO-1 pathway-related protein expression while decreasing pERK/total ERK and pJNK/total JNK ratios, along with nuclear factor kappa-light-chain-enhancer of activated B cells, p65 subunit (NF-κB-p65) protein expression. Histopathologically, DAPA improved hepatic and brain architecture. Collectively, DAPA exhibits hepatoprotective and neuroprotective effects against TAA-induced HE accompanied by modulation in oxidative-, inflammatory-, and apoptotic-related protein expression, highlighting its therapeutic potential in hepatic encephalopathy.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-19"},"PeriodicalIF":2.7,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148832367","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":"Molecular insights and translational potential of ferulic acid in radiation protection.","authors":"Tamizh Selvan Gnanasekaran","doi":"10.1080/15376516.2026.2726973","DOIUrl":"https://doi.org/10.1080/15376516.2026.2726973","url":null,"abstract":"<p><p>Ferulic acid, a common dietary phenolic abundant in plant cell walls, has been identified as a potential drug candidate with radiation-protective effects in experimental models. This review summarizes new developments regarding the molecular mechanisms, experimental models and translational potential of ferulic acid-induced radioprotection. Mechanistically, ferulic acid attenuates ionizing radiation-induced damage by scavenging free radicals, inhibiting lipid peroxidation, maintaining mitochondrial fitness, modulating inflammation signaling pathways and upregulating endogenous antioxidant systems partially through nuclear translocation of the Nrf2 pathway. Preclinical studies across <i>in vitro</i> (human and animal cell lines), <i>ex vivo</i> (human blood chromosomal aberration, micronucleus, and γ-H2AX assays), and <i>in vivo</i> rodent models consistently show that ferulic acid reduces DNA damage and chromosomal alterations, supports cell survival pathways, and, in some conditions, enhances DNA repair, translating into improved tissue histology, hematopoietic recovery, and post-irradiation survival. Despite promising efficacy signals, there are still issues with pharmacokinetics, optimal dosing schedules, long-term safety/adverse events, and bioavailability in humans. This review discusses the priority directions for translation: (1) systematic pharmacokinetic and toxicology profiling, (2) discovery of ferulic acid derivatives and delivery systems (e.g. nanoparticles, prodrugs) that facilitate tissue targeting, and (3) rigorous clinical trials in prophylactic and post-exposure settings, with combination strategies involving established radioprotectors. Bridging preclinical mechanistic insights with rigorous clinical evaluation could position ferulic acid as a safe, low-cost, and widely accessible radioprotective adjunct suitable for both medical and occupational applications.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-19"},"PeriodicalIF":2.7,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148892244","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":"Acute oral toxicity evaluation of microencapsulated semi-purified fibrinolytic proteases using a modified OECD 423-aligned design for biotechnological applications.","authors":"Ragil Saptaningtyas, Sri Rejeki, Ana Hidayati Mukaromah, Amin Samiasih, Nanik Rahmani, Maya Dian Rakhmawatie, Stalis Norma Ethica","doi":"10.1080/15376516.2026.2666608","DOIUrl":"10.1080/15376516.2026.2666608","url":null,"abstract":"<p><p>The present study evaluated the acute oral toxicity profile of microencapsulated semi-purified fibrinolytic proteases derived from <i>Bacillus tequilensis</i> HSFI-5 (Indonesian Patent Application No. S00202313485) using a modified OECD Guideline 423-aligned fixed-dose parallel design. BALB/c mice (<i>n</i> = 50; equal sex distribution) received single oral doses of 50, 300, 2000, or 5000 mg/kg body weight and were monitored for 14 days for clinical signs, body weight progression, hematological indices, clinical biochemistry parameters, organ weights, and gross pathological changes. No mortality or treatment-related clinical abnormalities were observed at any dose level. Body weight gain remained progressive and comparable to controls. Hematological and biochemical parameters showed no consistent dose-dependent deviations indicative of systemic inflammatory, metabolic, hepatic, or renal dysfunction. Absolute and relative organ weights, including liver and kidneys, remained within physiological ranges, and necropsy revealed no macroscopic lesions. Based on OECD decision criteria, the median lethal dose (LD₅₀) was estimated to exceed 5000 mg/kg body weight, indicating that the formulation is not classified for acute oral toxicity under the Globally Harmonized System. Collectively, these findings indicate no evidence of acute treatment-related toxicological effects under the conditions of this study. Interpretation is limited to single-dose exposure and should be confirmed by further investigations incorporating detailed histopathological and extended toxicity assessments.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1183-1198"},"PeriodicalIF":2.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147781980","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":"Targeting lipid-fibrotic signaling crosstalk for antifibrotic therapy.","authors":"Sandeepa K N, Shilpa S Shetty","doi":"10.1080/15376516.2026.2659870","DOIUrl":"10.1080/15376516.2026.2659870","url":null,"abstract":"<p><p>Fibrosis is essentially a compromised wound-healing process in which fibroblasts remain engaged for an extended period of time, resulting in an excessive accumulation of extracellular matrix and ultimately leading to organ failure. Although well-known drivers, including transforming growth factor-β, Wnt/β-catenin, nuclear factor kappa-B, and sphingosine-1-phosphate signaling, are well-established, studies reveal that lipid metabolism is crucial for regulating these pathways. Inflammation, oxidative stress, cell energy consumption, and the conversion of cells into scar-forming myofibroblasts are all influenced by lipids, which are no longer only inert building blocks or fuel. Changes in phospholipids, fatty acids, sphingolipids, and cholesterol are examples of dysregulated lipid synthesis, remodeling, and oxidation that produce a metabolic milieu that supports fibrotic signaling and accelerates the course of the disease. This review deciphers the bidirectional crosstalk between fibrotic signaling pathways and how lipids are involved in different fibrotic signaling pathways in different organ systems, enumerating how profibrotic transcriptional programs and metabolic reprogramming are combined by lipid-derived mediators to form feed-forward loops that sustain fibrosis. Unraveling the underpinnings in lipid-fibrosis axis provides testament of lipid signaling and involvement as viable pathways for precision medicine and antifibrotic intervention by revealing new biomarkers and therapeutic targets.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1029-1044"},"PeriodicalIF":2.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147781970","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":"Mouse precision-cut liver and kidney slices: an optimized <i>ex vivo</i> model for organotoxicity testing.","authors":"Christiane Spruck, Ghizlan Bousejra, Ahmed Erbay, Sonja Herbrich, Andreas Dimitriadis, Zoe Röntgen, Frauke Roolfs, Isaac Musong Mboni-Johnston, Gerhard Fritz, Seddik Hammad, Nicole Schupp","doi":"10.1080/15376516.2026.2670503","DOIUrl":"10.1080/15376516.2026.2670503","url":null,"abstract":"<p><p>As excretion organs, the kidneys and liver are exposed to high concentrations of potentially toxic substances. While animal models remain the gold standard for organ-specific toxicity testing, meaningful alternative <i>ex vivo</i> approaches are essential in order to align with the 3 R principles (refinement, reduction, replacement). Precision-cut tissue slices (PCTS) retain native tissue architecture, cellular heterogeneity, the interplay of different cell types, and metabolic capacity, offering a promising link between <i>in vitro</i> and <i>in vivo</i> models. Here, we aimed to establish an optimized protocol for preparation and cultivation of precision-cut kidney and liver slices (PCKS and PCLS) from mice for use in substance-oriented toxicity testing. Key parameters - including slice thickness, media composition and oxygenation, glucose levels, and incubation time - were refined to preserve tissue viability and metabolic function. Five known prototypical toxins - acetaminophen, cyclosporin A, cisplatin, arsenic trioxide, and aristolochic acid I - were tested. While PCKS showed comparable sensitivity to established kidney cell lines, PCLS achieved IC₅₀ values closely matching <i>in vivo</i> toxicity data. High reproducibility across different experimenters was achieved, highlighting the robustness of the model. In conclusion, the optimization of this <i>ex vivo</i> system makes this valuable, reproducible, and ethically approved platform for testing nephrotoxicity and hepatotoxicity accessible to more laboratories, for example for dose finding or compound prioritization, thereby supporting 3 R-conform preclinical drug screening as well as hazard identification and potentially reducing reliance on animal experiments.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1211-1225"},"PeriodicalIF":2.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147933862","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}