Toxicology Mechanisms and Methods最新文献

{"title":"Choriocapillaris and blood flow alterations in smokers naïve to heated tobacco products: a cross-sectional study.","authors":"Marcella Nebbioso, Francesca Calzolaio, Valentina Castellani, Magda Gharbiya, Simona Bartimoccia, Giuseppe Biondi-Zoccai, Giacomo Frati, Giovanni Enrico Casciaro, Roberto Carnevale, Lorenzo Loffredo, Mattia D'Andrea, Annarita Vestri, Alessandro Avitabile, Vincenza Maria Elena Bonfiglio","doi":"10.1080/15376516.2026.2678476","DOIUrl":"10.1080/15376516.2026.2678476","url":null,"abstract":"<p><strong>Purpose: </strong>Heated tobacco products (HTPs) are devices that heat tobacco to high temperatures, rather than combusting it to generate smoke. The potential impact of HTPs on the body is not yet fully understood, as they are relatively recent products. The aim of this multidisciplinary study was to evaluate potential associations between the use of HTPs and both general and system-specific vital parameters in the enrolled subjects in order to determine whether these devices may be harmful and capable of inducing clinical, biochemical, or functional alterations compared to nonsmokers (non-SMs).</p><p><strong>Materials and methods: </strong>In this pilot study, the population consisted of 18 exclusive HTP users and 10 non-SMs. Spirometry was performed to assess respiratory function and blood sampling was used to evaluate the presence of oxidative stress (OS) biomarkers. Hemostatic variations and platelet aggregation were assessed using the total thrombus formation analysis system (T-TAS). Finally, ophthalmological examinations and optical coherence tomography angiography (OCTA) were performed to analyze the structural characteristics and chorioretinal vascular flow parameters.</p><p><strong>Results: </strong>Hemorheological parameters revealed accelerated thrombus formation and prolonged thrombus stability on T-TAS, along with increased nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2), or NADPH oxidase 2, levels. OCTA also revealed a statistically significant reduction in choriocapillaris flow (Ch-Flow) in HTP users.</p><p><strong>Conclusions: </strong>Alterations in primary hemostasis, OS, and chorioretinal microvascular perfusion highlight the need for further research in a larger cohort with higher mean age and longer cumulative exposure to HTPs to confirm these preliminary findings.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1364-1378"},"PeriodicalIF":2.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148017466","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":"Combined treatment of zingerone and nilotinib induces cytotoxicity and reverses nilotinib resistance in chronic myeloid leukemia cells via inhibition of the PI3K signaling.","authors":"Chong Chen, Fang Wang, Suludefu","doi":"10.1080/15376516.2026.2691543","DOIUrl":"10.1080/15376516.2026.2691543","url":null,"abstract":"<p><strong>Introduction: </strong>Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of chronic myeloid leukemia (CML); however, TKI resistance remains a persistent challenge. This study investigates the effects of zingerone on CML cell growth and nilotinib resistance.</p><p><strong>Methods: </strong>K562 and LAMA84 cells were treated with zingerone (5-100 μM) or nilotinib (1-50 nM), and cytotoxicity was assessed using cell counting Kit-8 assay. Nilotinib-resistant cells (K562R, LAMA84R) were generated through gradual exposure to increasing nilotinib concentrations (1-10 nM) over six months. Subsequently, cells were treated with 10 μM zingerone and/or 5 nM nilotinib. Cell survival and apoptosis were measured by Trypan blue staining and flow cytometry. Protein levels of Bcr-Abl, apoptotic markers and PI3K pathway components were analyzed by Western blotting.</p><p><strong>Results: </strong>Zingerone, nilotinib and their combination reduced parental CML cell survival and increased apoptosis. Resistant cells showed no significant response to nilotinib alone, confirming acquired resistance. However, the addition of zingerone markedly reduced survival and increased apoptosis in these resistant cells. The combination of zingerone and nilotinib increased levels of cleaved PARP, cleaved caspase-3, -9 and -8, while decreasing Bcl-2. Zingerone alone or in combination with nilotinib also reduced phosphorylation of PI3K, AKT and mTOR in resistant cells.</p><p><strong>Conclusion: </strong>Zingerone enhances the inhibitory effects of nilotinib on CML cell survival and overcomes nilotinib resistance by suppressing the PI3K pathway.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1444-1455"},"PeriodicalIF":2.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148273109","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":"Comprehensive assessment of hyperoside: cytotoxic, anti-cancer, genoprotective, radical scavenging and computational toxicity properties through <i>in vitro</i> and <i>in silico</i> approaches.","authors":"Aysen Yagmur Burgazli, Ece Avuloglu Yilmaz, Sevcan Mamur, Fatma Okus, Busenaz Tuncay, Deniz Yuzbasioglu, Fatma Unal","doi":"10.1080/15376516.2026.2691542","DOIUrl":"10.1080/15376516.2026.2691542","url":null,"abstract":"<p><p>Hyperoside (HYP), a plant-derived flavonoid, was evaluated for its cytotoxic, anti-cancer, genotoxic, antigenotoxic, and antioxidant properties, and potential mechanisms of action using an integrated <i>in vitro</i> and <i>in silico</i> approach. Cytotoxicity and anti-cancer activities were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in CCD18-Co healthy colon epithelial and DLD-1 colon cancer cells. At the same time, genotoxicity and antigenotoxicity potentials were examined in human lymphocytes using COMET assay. Antioxidant activity was determined by 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay, and molecular docking was performed with key regulatory proteins (p53, ATM, 7O7B, and Keap1), and <i>in silico</i> toxicity profiling was conducted using the Percepta platform. HYP selectively reduced the viability of colon cancer cells (43.43%-70.24%) without inducing cytotoxicity in healthy colon epithelial cells (cell viability percentage ranging from 82.25% to 111.88%) after 24 and 48 h of exposure. HYP did not significantly increase DNA damage at 7.81-62.5 μg/mL; however, it exhibited antigenotoxic effects at all concentrations, significantly reducing H₂O₂-induced DNA damage. HYP also showed significant antioxidant activity, with DPPH inhibition ranging from 53.09% to 78.64%. Docking analyses revealed strong binding affinities for ATM and Keap1, supporting its potential role in modulating oxidative stress and DNA damage response pathways. Percepta-based toxicity profiling predicted low to moderate acute systemic toxicity, limited oral bioavailability, and no major cardiotoxic or CYP-mediated safety liabilities; notably, predicted mutagenicity alerts were not corroborated by <i>in vitro</i> DNA damage assessments. Overall, these findings suggest that HYP exhibits selective anticancer and antigenotoxic properties, potentially mediated by its antioxidant activity.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1424-1443"},"PeriodicalIF":2.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148273165","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":"Combined effects and potential mechanisms of volatile organic compounds on childhood asthma in the US population: an integrated epidemiological and computational toxicology study.","authors":"Beizhang Liang, Meizhu Cao, Huiyuan Tan, Zhiwen Liu, Xiaoting Liu","doi":"10.1080/15376516.2026.2675338","DOIUrl":"10.1080/15376516.2026.2675338","url":null,"abstract":"<p><strong>Background: </strong>Childhood asthma is a major public health concern, with its incidence continuing to rise in many industrialized countries. While genetic factors contribute to asthma development, environmental exposures, particularly volatile organic compounds (VOCs), have been increasingly recognized as key risk factors. This study investigates the association between blood VOC levels and childhood asthma risk in the U.S. adolescent population using a combination of epidemiological and computational modeling approaches.</p><p><strong>Methods: </strong>NHANES 2013-2016 data were analyzed to investigate associations between blood VOC levels and childhood asthma. Weighted Quantile Sum (WQS) regression was applied to assess VOC mixture effects, and weighted logistic regression models were used to evaluate individual VOC associations. Potential targets related to 1,4-Dichlorobenzene and childhood asthma were collected from ChEMBL, TargetNet, GeneCards, OMIM, and TTD. Overlapping targets were used to construct a protein-protein interaction (PPI) network <i>via</i> STRING, followed by GO and KEGG enrichment analyses using DAVID. Molecular docking and tissue-expression plausibility assessment of core targets were performed using AutoDock Vina 1.1.2, GEPIA, and the Human Protein Atlas (HPA).</p><p><strong>Results: </strong>The WQS regression model showed a significant positive association between the VOC mixture and childhood asthma, with 1,4-dichlorobenzene receiving the largest weight in the mixture. In single-pollutant models, 1,4-dichlorobenzene and o-xylene showed positive associations with childhood asthma after adjustment, although these findings should be interpreted cautiously. Integrative target-based analyses highlighted EGFR, PIK3CA, PIK3CD, SRC, and AKT1 as candidate genes potentially relevant to the observed association, and enrichment analyses suggested involvement of pathways such as MAPK, TNF, and PI3K-Akt signaling.</p><p><strong>Conclusion: </strong>This study suggests that higher exposure to multiple VOCs, particularly 1,4-dichlorobenzene, is associated with childhood asthma in U.S. adolescents. Integrative bioinformatics and docking analyses indicate biologically plausible pathways that may underlie this association. These findings are hypothesis-generating, and prospective and experimental studies are needed to further clarify temporality and mechanism.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1325-1340"},"PeriodicalIF":2.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147975720","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":"Cereulide-mediated emetic (vomiting) toxicity of <i>Bacillus cereus</i> in infant formula: mitochondrial mechanisms, analytical methods, and risk assessment.","authors":"Ghassan Sonji, Nada Sonji, Afaf El Katerji","doi":"10.1080/15376516.2026.2677629","DOIUrl":"10.1080/15376516.2026.2677629","url":null,"abstract":"<p><p>Cereulide is a heat stable cyclic dodecadepsipeptide and potassium selective ionophore produced by <i>Bacillus cereus</i>, recognized as the causative agent of emetic food poisoning. Data indicate it exerts potent mitochondrial toxicity by collapsing membrane potential, uncoupling oxidative phosphorylation, depleting ATP, and triggering apoptosis at nanomolar concentrations. Its extreme lipophilicity (logPₒw ≈ 4) suggests partitioning into lipid rich ingredients including microbial oils used in powdered infant formula. <i>In vitro</i> studies demonstrate dose dependent suppression of oxygen consumption rate (EC₅₀ = 98-127 nM), indicating high bioenergetic toxicity. Neonates are considered uniquely vulnerable because immature renal clearance may prolong exposure, lipid rich matrices could increase absorption, and developing mitochondria may contribute to increased susceptibility. However, no cereulide-specific toxicokinetic or toxicodynamic data in this age group have been published. LC-MS/MS is the accepted reference method, but performance varies substantially, with elevated LOQs in lipid matrices likely due to ion suppression, and no matrix matched certified reference materials exist to support standardized measurement. Critical gaps include lack of neonatal models, developmental dose response data, and sufficient exposure data to calculate quantitative risk. Artificial intelligence shows only theoretical potential with no validated models available for risk assessment. Contamination has been linked to biofilms in oil processing environments, and heat stability means thermal treatments applied during manufacture are unlikely to reduce levels once formed. This review synthesizes available evidence, explicitly identifying uncertainties and data gaps as the main limitation to robust regulation, and defines five priorities to guide future research and safety standards.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1267-1287"},"PeriodicalIF":2.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148017442","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":"Could e-cigarette devices generate inhalable micro- and nanoplastics? Exposure plausibility and reproductive relevance.","authors":"Ardie Barry Sailis","doi":"10.1080/15376516.2026.2695155","DOIUrl":"10.1080/15376516.2026.2695155","url":null,"abstract":"<p><p>Electronic cigarettes are widely used by individuals in their reproductive years, yet polymer materials in pods, wicks, seals, and casings remain underexamined as possible contributors to inhaled particulate exposure. This narrative review evaluates whether e-cigarette device components could plausibly generate microplastics or nanoplastics during use and whether such particles, if present, could have reproductive relevance. Evidence from device-material studies, polymer degradation chemistry, aerosol physics, inhalation toxicology, and reproductive microplastic models was synthesized. Current devices place polycarbonate, polydimethylsiloxane, nylon, and other polymers near heating and aerosolization zones, where thermal cycling, solvent contact, and mechanical stress could theoretically promote oxidation, chain scission, embrittlement, or fragmentation. However, no study has chemically identified or quantified device-derived microplastics or nanoplastics in e-cigarette aerosols using polymer-resolving methods. Thus, links between e-cigarette use, inhaled polymer particles, and reproductive harm remain hypothetical. Evidence from non-e-cigarette models shows that micro- and nanoplastics can induce oxidative stress, inflammation, endocrine disruption, barrier interaction, and cellular injury, but these findings cannot be extrapolated without confirming particle formation, polymer identity, dose, and biodistribution. Future research should prioritize polymer-resolved aerosol testing under realistic puffing regimens, including unused and aged devices, e-liquids, condensates, and emitted aerosols. Key endpoints should include polymer identity, particles per puff, particles per mL of e-liquid consumed, particle size distribution, polymer mass, pulmonary deposition, systemic translocation, and reproductive or placental effects. Device-derived microplastics should be treated as a plausible particle-safety concern requiring direct experimental evaluation.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1305-1324"},"PeriodicalIF":2.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148333201","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":"Matrine enhances cisplatin sensitivity in oral squamous cell carcinoma through regulation of oxidative stress and apoptosis.","authors":"Yuqing Xu, Yanlan Yu, Zenan Xu, Hanzhe Liu, Xinzhu Lian, Danjun Chen","doi":"10.1080/15376516.2026.2691548","DOIUrl":"10.1080/15376516.2026.2691548","url":null,"abstract":"<p><p>Cisplatin resistance remains a major limitation in the treatment of oral squamous cell carcinoma (OSCC), often associated with altered oxidative stress. This study aimed to evaluate whether matrine can enhance cisplatin sensitivity in OSCC cells and explore its potential underlying mechanisms. Bioinformatics analysis and molecular docking were used to predict potential targets and pathways. <i>In vitro</i> experiments were conducted using CAL27 and cisplatin-resistant CAL27/DDP cells. Cell viability was assessed by CCK-8 assay, and drug interaction was evaluated using combination index (CI). Colony formation, reactive oxygen species (ROS), glutathione (GSH), apoptosis, and protein expression were analyzed.A total of 104 matrine-related targets and 21 overlapping genes were identified. Enrichment analysis suggested that oxidative stress-related pathways may be involved. Matrine alone showed limited cytotoxicity, while it significantly enhanced cisplatin sensitivity, reducing IC₅₀ from 8.340 μM to 2.703 μM (<i>p</i> < 0.01) with CI values <1. Combined treatment decreased GSH and increased ROS (<i>p</i> < 0.001), accompanied by increased apoptosis (<i>p</i> < 0.001). The expression of Nrf2-related antioxidant proteins was reduced, while apoptotic protein levels were increased. Matrine enhances cisplatin sensitivity in OSCC cells, which may be associated with the regulation of oxidative stress and apoptosis. These findings suggest that matrine may serve as a potential chemosensitizing agent.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1456-1467"},"PeriodicalIF":2.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148318644","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":"Quercetin attenuates vancomycin-induced acute hepatotoxicity in rats through modulation of Nrf2 and NF-κB related oxidative stress and inflammatory signaling pathways.","authors":"Gokhan Akcakavak, Ozhan Karatas, Filiz Kazak Akcakavak, Ademola C Famurewa, Eren Ceylan, Mehmet Tuzcu","doi":"10.1080/15376516.2026.2687793","DOIUrl":"10.1080/15376516.2026.2687793","url":null,"abstract":"<p><p>Vancomycin (VM) therapy is one of the cornerstone options in the treatment of resistant Gram-positive bacterial infections. However, its drawback is associated with the side effect hepatotoxicity during optimal high doses. It is unknown whether quercetin (Que), a natural bioactive flavonoid, could protect the liver against VM-induced hepatotoxicity. The study thus aimed to explore the potential protective effects of Que on VM-induced hepatotoxicity in male Wistar rats. Rats were randomized into groups and administered VM (200 mg/kg body weight, twice a day) and/or Que (100 mg/kg body weight) for 7 consecutive days. The VM injection induced liver dysfunction revealed <i>via</i> significantly elevated serum activities of ALT, AST, and GGT compared to the control group (<i>p</i> < 0.001). VM markedly decreased hepatic activities of SOD, CAT and GPx, while MDA level increased compared to the control group (<i>p</i> < 0.001). Additionally, VM increased TNF-α levels while decreasing IL-10 levels. There were considerable increases in the hepatic expression of caspase-3, NF-κB, Keap1, NOX4, 4-HNE and NLRP3, whereas the expression of HO1, Nrf2, PI3K, p-Akt decreased significantly as revealed by qRT-PCR and immunohistochemical analyses (<i>p</i> < 0.001). Interestingly, the Que administration attenuated the VM-induced alterations on the liver enzymes and antioxidant enzymes, including the MDA and 4-HNE. Que exerted prominent modulatory effects on the mechanistic proteins and mRNA expression in a manner comparable to the control. Overall, the present findings suggest that quercetin may mitigate vancomycin-induced hepatotoxicity in rats by modulating oxidative stress, inflammatory signaling, and apoptosis-related pathways.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1408-1423"},"PeriodicalIF":2.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148340577","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":"Analysis of neonicotinoid pesticides and their metabolites by liquid chromatography-electrospray ionization-tandem mass spectrometry.","authors":"Andreas F Lehner, Julia Dickie, Justin Zyskowski, John Buchweitz","doi":"10.1080/15376516.2026.2736531","DOIUrl":"10.1080/15376516.2026.2736531","url":null,"abstract":"<p><p>Neonicotinoid insecticides were first introduced in the 1990s as an alternative to older, more toxic types such as organophosphates, carbamates, and chlorinated hydrocarbons and have since become the most widely used class of insecticides globally. However, their use comes at a significant cost due to high toxicity to pollinators such as bees, beneficial predatory insects, and even insectivorous birds. To further the study of neonicotinoid effects, we developed a method for the LC-ESI-MS/MS (liquid chromatography-electrospray ionization-tandem mass spectrometry) analysis of imidacloprid, clothianidin, and nitenpyram. Standards enabled optimization of tandem quadrupole (MS/MS) detection for specific multiple reaction monitoring (MRM) method fragmentations and separation was achieved by UPLC (ultra-high performance liquid chromatography). However, mammalian samples that tested positive for neonicotinoids on enzyme-linked immunosorbent assays (ELISAs) disclosed none of the parent compounds by the LC-ESI-MS/MS method. Upon researcher request, neonicotinoid metabolites 6-hydroxynicotinic acid; 2-chloro-1,3-thiazole-5-carboxylic acid; 2-imidazolidone; 6-chloronicotinic acid; imidacloprid urea; imidacloprid olefin; desnitro-imidacloprid; and 5-hydroxyimidacloprid were included. The method was validated for linear response, limits of detection/quantitation, retention time stability, instrumental carryover, intraday- and interday-precision, standard curve stability, accuracy, and specificity. Limits of quantitation were measured at 0.1 ppb for the majority of compounds, although desnitro-imidacloprid and 5-hydroxyimidacloprid ranged above 1 ppb. The method was applied to extracted produce samples as a pilot study to test the method's utility. Red grapes contained imidacloprid, while pickles contained imidacloprid and clothianidin. Of concern to researchers studying the collapse of honeybee colonies, two of four samples of honey contained the imidacloprid metabolite 6-hydroxynicotinic acid at levels above 5 ppb.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-17"},"PeriodicalIF":2.7,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149017408","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":"Puerarin attenuates binge ethanol-induced cortical neurotoxicity in association with AKT/mTOR signaling and autophagy-related responses.","authors":"Fu Liu, Shuying Huang, Hongwen Xiao, Yuhong Zhou, Long Lin, Zaiqiang Liu, Jumei Lan, Xiaohong Chen, Hua Tian","doi":"10.1080/15376516.2026.2733168","DOIUrl":"10.1080/15376516.2026.2733168","url":null,"abstract":"<p><p>Puerarin (Pue), a major isoflavone derived from <i>Pueraria lobata</i>, has demonstrated neuroprotective potential in multiple neurological disorders; however, its effects on ethanol (EtOH)-induced cortical injury and the associated molecular responses remain incompletely understood. In the present study, network pharmacology was combined with <i>in vivo</i> and <i>in vitro</i> experiments to investigate molecular responses associated with the effects of Pue on EtOH-induced neurotoxicity. Public databases were used to predict targets of Pue and alcohol-related brain injury, followed by protein-protein interaction analysis, Gene Ontology annotation, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment. A total of 101 overlapping targets were identified, among which TNF, AKT1, EGFR, TP53, and PPARG emerged as major hub targets, and PI3K-Akt signaling pathway was among the pathways that remained significantly enriched after FDR correction. In a 4-day binge EtOH rat model, Pue attenuated EtOH-associated increases in oxidative stress, neuronal degeneration, and apoptotic markers in cortical tissue. This was accompanied by attenuation of the EtOH-associated reductions in the p-AKT/AKT and p-mTOR/mTOR ratios, as well as an attenuation of EtOH-associated changes in LC3, ATG5, and Beclin-1 expression. In primary cortical neurons, Pue partially attenuated the EtOH-associated loss of neuronal viability and preserved neurite morphology. Bafilomycin A1 (BafA1)-based analysis of LC3-II and p62/SQSTM1 showed an overall BafA1-sensitive increase in LC3-II without a significant treatment-dependent difference in the BafA1 response. Collectively, these findings suggest that Pue attenuates binge EtOH-induced cortical neurotoxicity in association with changes in AKT/mTOR phosphorylation and autophagy-related responses.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-17"},"PeriodicalIF":2.7,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148963763","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}