Current Research in Toxicology最新文献

{"title":"CC16 alleviates PM2.5-induced airway inflammation in asthmatic mice by targeting the E-cadherin-mediated ferroptosis regulatory axis","authors":"Aili Wang,&nbsp;Shuo Yang,&nbsp;Fang Xu,&nbsp;Jianling Liu,&nbsp;Jinle Lin,&nbsp;Jian Wu","doi":"10.1016/j.crtox.2026.100310","DOIUrl":"10.1016/j.crtox.2026.100310","url":null,"abstract":"<div><div>Airway epithelial ferroptosis is critically involved in PM2.5-driven asthmatic airway damage, and our previous studies have demonstrated the protective role of club cell protein 16 (CC16) against fine particulate matter (PM2.5)-induced airway inflammation by inhibiting airway epithelial ferroptosis using C57BL/6 J mouse and TC-1 cell model. Nevertheless, it remains unclarified whether CC16 exerts its anti-ferroptotic effects through interacting with E-cadherin, which represents a core research gap absent in our previous studies. Herein, we established PM2.5-intervened asthmatic mice and TC-1 cell models to explore the undiscovered molecular mechanism. Quantitative proteomics combined with bioinformatics screening identified E-cadherin as a pivotal downstream target of CC16. PM2.5 exposure markedly inhibited E-cadherin expression and aggravated epithelial ferroptosis, while CC16 intervention efficiently restored E-cadherin levels, elevated NRF2/GPX4/SLC7A11 expression, suppressed ACSL4, and reduced lipid peroxidation. This study first verified the direct binding interaction between CC16 and E-cadherin via molecular docking, Co-IP and pull-down assays. Furthermore, CDH1 knockdown completely abolished CC16-mediated inhibition of ferroptosis and epithelial injury. Collectively, this work establishes a novel CC16/E-cadherin/ferroptosis signaling axis, demonstrating that E-cadherin is an indispensable mediator for CC16 to relieve PM2.5-triggered airway damage. These findings substantially complement and advance the mechanistic system of CC16-related airway protection, providing novel targets for environmental asthma therapy.</div></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"11 ","pages":"Article 100310"},"PeriodicalIF":4.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13320470/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148367506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exposure to PFOS and PFOA through drinking water is associated with greater cigarette smoke-induced COPD-like lung injury and enhanced NF-κB-related inflammatory signaling in mice","authors":"Manyi Pan,&nbsp;Yuxin Zou,&nbsp;Yuqing Lv,&nbsp;Hongbin Wang,&nbsp;Chengcheng Hou,&nbsp;Haiyang Zhang,&nbsp;Tianyu Zhou,&nbsp;Lifeng Yan,&nbsp;Weining Xiong,&nbsp;Xiahui Ge,&nbsp;Hui Yin,&nbsp;Huaqi Guo","doi":"10.1016/j.crtox.2026.100319","DOIUrl":"10.1016/j.crtox.2026.100319","url":null,"abstract":"<div><div>Chronic obstructive pulmonary disease (COPD) is a major global health burden, and environmental pollutants may modify its progression. Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) are persistent <em>per</em>- and polyfluoroalkyl substances with known immunotoxic and proinflammatory effects, but their contribution to smoke-related lung injury remains unclear. Here, we investigated whether chronic PFOS or PFOA exposure was associated with greater cigarette smoke (CS)-induced COPD-like lung injury. Mice were exposed to CS for 3 months with concurrent PFOS or PFOA exposure in drinking water at the same nominal concentration (2 mg/L). Lung function, histopathology, transcriptomic profiling, and supportive <em>in vitro</em> assays in RAW264.7 cells were performed. Compared with CS alone, PFOS or PFOA co-exposure with CS was associated with greater pulmonary impairment, including greater alveolar destruction, enhanced airway inflammation, and more pronounced impairment of pulmonary function, as reflected by a lower forced expiratory volume in one second to forced vital capacity ratio (FEV₁/FVC). Transcriptomic and <em>in vitro</em> analyses were consistent with enhanced nuclear factor-κB (NF-κB)-related inflammatory signaling. These findings support a potential role for drinking-water PFAS exposure as a modifier of smoke-induced pulmonary injury.</div></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"11 ","pages":"Article 100319"},"PeriodicalIF":4.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149050723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Zearalenone exposure may increase the risk of non-alcoholic fatty liver disease by activating CYP1B1-SCD1","authors":"Haonan Ruan ,&nbsp;Jing Zhang ,&nbsp;Yunyun Wang ,&nbsp;Dan Zhang ,&nbsp;Jiaoyang Luo ,&nbsp;Meihua Yang","doi":"10.1016/j.crtox.2025.100277","DOIUrl":"10.1016/j.crtox.2025.100277","url":null,"abstract":"<div><div>Zearalenone (ZEN) is an oestrogen-like mycotoxin that widely contaminates food and feed worldwide. Current research suggests that ZEN causes liver injury by disrupting hepatic lipid metabolism. Furthermore, prolonged disturbances in hepatic lipid metabolism are believed to play a role in the progression of non-alcoholic fatty liver disease (NAFLD). However, the exact association between ZEN exposure and the development of NAFLD is unclear. In this study, we established a rat model of ZEN-induced hepatic lipid accumulation (2.5, 5, 10 mg/kg/d b.w.,14 d, i.g.) to investigate the key targets of ZEN-induced hepatic lipid accumulation and to explore the potential link between ZEN exposure and NAFLD. Histological staining of rat liver showed that ZEN caused significant pathological changes and lipid accumulation; biochemical analysis showed that ZEN significantly and dose-dependently increased serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and disrupted the serum lipid profile in rats; proteomic analysis showed that ZEN significantly altered protein expression levels in rat liver, especially SOAT1, SOAT2, CYP1B1 and SCD1 (p &lt; 0.05). Through bioinformatics analyses, we combined ZEN exposure with a database of NAFLD clinical samples to reveal that ZEN exposure may increase the risk of NAFLD through activation of the CYP1B1-SCD1 pathway, and further animal experiments confirmed this. This study identifies the key target of ZEN-induced lipid accumulation and provides a basis for further research on the intrinsic link between ZEN exposure and NAFLD.</div></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"10 ","pages":"Article 100277"},"PeriodicalIF":2.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145788188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ca2+-independent cytotoxicity of menthol in the A549 lung cancer cell line","authors":"Kenji Takahashi,&nbsp;Toshio Ohta","doi":"10.1016/j.crtox.2025.100271","DOIUrl":"10.1016/j.crtox.2025.100271","url":null,"abstract":"<div><div>Menthol evokes cooling sensations by activating the transient receptor potential melastatin 8 (TRPM8) channel, resulting in relaxing, anti-inflammatory, and analgesic effects when administered through inhalation and topical application. Although the toxicity of menthol is relatively low, the mechanism underlying menthol-induced cytotoxic effects remains unclear. Thus, this study aimed to investigate the cytotoxic effects of menthol in the A549 lung cancer cell line. Menthol induced increases in intracellular Ca²⁺ concentrations ([Ca²⁺]_i) in distinct modes depending on its concentration. A relatively low concentration (0.3 mM) of menthol activated transient receptor potential ankyrin 1 (TRPA1) despite the expression of TRPM8 in A549 cells. A higher concentration (3 mM) of menthol nonspecifically induced Ca²⁺ release from intracellular stores. Menthol inhibited Ca²⁺-ATPase in the organelle membrane. At 3 mM, menthol elicited necrotic cell death accompanied by morphological changes within 60 min. This cytotoxicity was not prevented by HC-030031 (a TRPA1 blocker) or BAPTA-AM (an intracellular Ca²⁺ chelator). Furthermore, the analysis of the cytotoxicity of monoterpene analogs of menthol revealed structure-related activity in menthol-induced cytotoxicity. These findings indicate that menthol-induced cytotoxic effects are concentration-dependent and may provide valuable insights into novel therapeutic strategies for lung cancer.</div></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"10 ","pages":"Article 100271"},"PeriodicalIF":2.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145735324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Scoparone induces mitophagy and apoptosis via ROS accumulation in pancreatic cancer cells","authors":"Ningna Weng ,&nbsp;Luping Lin ,&nbsp;Tong Lin ,&nbsp;Jinlu Liu ,&nbsp;Kai Zhu ,&nbsp;Sha Huang","doi":"10.1016/j.crtox.2026.100281","DOIUrl":"10.1016/j.crtox.2026.100281","url":null,"abstract":"<div><div>Pancreatic cancer (PC) is one of the deadliest malignancies worldwide. In the present study, we demonstrated that a traditional Chinese medicine extract monomer, scoparone (Scop), significantly inhibited the growth of PC cells both <em>in vitro</em> and <em>in vivo</em>. Further studies revealed that Scop could induce PINK1/Parkin-mediated mitophagy and apoptosis in PC cells; thus, inhibition of mitophagy could alleviate the anti-PC effect and apoptosis of Scop. Mechanistically, Scop exerts its anti-PC effects via the Akt/mTOR pathway. In addition, Scop increases the level of cellular reactive oxygen species (ROS) in PC cells, which may be a key factor, as the ROS inhibitor N-acetylcysteine significantly reversed the effects of mitophagy and apoptosis in PC cells. Our findings highlight Scop shows potential as a therapeutic lead candidate, offering novel insights into the antitumor potential of traditional Chinese medicine. This study elucidates the critical role of Scop in regulating mitophagy and apoptosis in PC cells, providing a foundation for future therapeutic development.</div></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"10 ","pages":"Article 100281"},"PeriodicalIF":2.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146022357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polylactic acid microplastics as metabolic disruptors: Linking gut dysbiosis to systemic toxicity by disrupting microbiota-host co-metabolism","authors":"Yumiao Li ,&nbsp;Ziyi Zhou ,&nbsp;Hui Xu ,&nbsp;Ruilin Qi ,&nbsp;Jing Xu ,&nbsp;Qihao Hu ,&nbsp;Zhi Tang","doi":"10.1016/j.crtox.2026.100298","DOIUrl":"10.1016/j.crtox.2026.100298","url":null,"abstract":"<div><div>The increasing application of polylactic acid (PLA) in consumer products leads to the widespread environmental distribution of its micro- and nano-plastics (PLA-MNPs). These particles pose potential health risks following environmental exposure, yet the mechanisms underlying their systemic toxicity remain inadequately defined. This review synthesizes current evidence demonstrating that PLA-MNPs accumulate in the intestine, compromising the gut barrier and inducing dysbiosis of the gut microbiota. We also explore the hypothetical role of disrupted gut microbiota-host co-metabolism — particularly involving aromatic amino acid pathways such as tryptophan metabolism — as a potential mechanism linking PLA-MNPs exposure to intestinal inflammation and injury, while acknowledging the current lack of direct experimental evidence for PLA-MNPs-specific effects on these pathways. By integrating literature on the gut-liver axis, we further elucidate how intestinal injury propagates to systemic metabolic disturbances. This overview aims to provide a structured synthesis of existing findings, identify key knowledge gaps, and suggest targeted approaches for future mechanistic and exposure-informed risk assessment of PLA-MNPs.</div></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"10 ","pages":"Article 100298"},"PeriodicalIF":2.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147850084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating the potential carcinogenic hazard of diisononyl phthalate in humans via systematic integration of human, animal cancer studies, and mechanistic data","authors":"Isabel A. Lea ,&nbsp;Amanda N. Buerger ,&nbsp;Melissa J. Vincent ,&nbsp;Brianna N. Rivera ,&nbsp;Neepa Y. Choksi ,&nbsp;Heather Schaefer ,&nbsp;Janice Britt ,&nbsp;Seneca Fitch ,&nbsp;Laurie Haws ,&nbsp;Susan J. Borghoff","doi":"10.1016/j.crtox.2026.100295","DOIUrl":"10.1016/j.crtox.2026.100295","url":null,"abstract":"<div><div>Diisononyl phthalate (DINP) is a high molecular weight phthalate used in commercial products and polyvinyl chloride production. Herein, a systematic evaluation of DINP evidence streams (i.e., human cancer, animal cancer, and mechanistic data) was carried out to inform carcinogenic hazard in humans. Relevant data from peer-reviewed literature and publicly available laboratory reports were extracted and critically appraised. Mechanistic data were organized according to the Key Characteristics of Carcinogens (KCCs) and integrated into key events in rodent cancer modes of action (MoAs). Evidence from epidemiological studies is limited, but does not indicate an association between DINP exposure and cancer, with three studies reporting no association with breast cancer, and one reporting an imprecise increase in prostate cancer risk. Four chronic bioassays demonstrated DINP causes cancer in rodents, with increases in liver tumors in mice and rats, kidney tumors in male F344 rats, and mononuclear cell leukemia (MNCL) in F344 rats. Mechanistic data strongly support that DINP is non-genotoxic (KCC2), and that in rodents DINP induces oxidative stress (KCC5) and alters cell proliferation (KCC10). Multiple evidence stream integration and interpretation support that DINP elicits rodent-specific liver tumors through the peroxisome proliferator-activated receptor alpha, a MoA widely considered to lack human relevance. Likewise, the weak kidney tumor response in male rats was attributed to α2u-globulin nephropathy, a male rat-specific response. MNCL, a common lesion in aging F344 rats, was not considered relevant for predicting human cancer. Together, these data indicate that DINP is unlikely to pose a carcinogenic hazard to humans.</div></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"10 ","pages":"Article 100295"},"PeriodicalIF":2.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147797264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A mechanistic evaluation of the metabolism disrupting potential of methyl tert-butyl ether","authors":"A.N. Buerger ,&nbsp;M.J. Vincent ,&nbsp;S. Fitch ,&nbsp;B. Rivera ,&nbsp;N. Engel ,&nbsp;J. Zhang ,&nbsp;E.K. Rushton ,&nbsp;S.J. Borghoff","doi":"10.1016/j.crtox.2026.100290","DOIUrl":"10.1016/j.crtox.2026.100290","url":null,"abstract":"<div><div>European authoritative and regulatory assessments of endocrine disruption increasingly incorporate evaluation of metabolism disrupting potential, yet there are no regulatory- or authority-validated models or guidance to identify metabolism disrupting agents (MDAs), which are agents that increase the risk of developing metabolic disorders. Methyl <em>tert</em>-butyl ether (MTBE), a volatile organic compound utilized as a fuel additive in many countries, was recently concluded to be a suspected endocrine disruptor based on its potential to elicit insulin resistance in rodents via an endocrine mode of action (MOA) in a Regulatory Management Option Analysis (RMOA). Therefore, a thorough mechanistic assessment was conducted to evaluate the metabolism disrupting potential of MTBE. This novel approach included review of any mechanistic data including study/endpoint relevance and study reliability. Reliable data were mapped to the twelve key characteristics (KCs) of MDAs for critical evaluation of the strength of the evidence for activity within each KC. Next, the mechanistic data were contextualized and integrated within an MOA framework. No reliable epidemiological studies of MTBE were identified. Across eight KCs, largely inconsistent activity was identified in reliable <em>in vivo</em> and <em>in vitro</em> studies related to lipid, insulin, and glucose processes. MOA analysis further demonstrated inconsistent (endocrine) activity related to metabolism disruption and a lack of biologically plausible links between MTBE and metabolism disruption. Based on the current evidence identified, MTBE does not consistently perturb insulin signaling or lipid metabolism via proposed MOAs for metabolic disorders. Overall, MTBE fails to show consistent activity and adverse effects related to metabolic disruption.</div></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"10 ","pages":"Article 100290"},"PeriodicalIF":2.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147739753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss of KLF15 expression characterizes proximal tubule injury in cisplatin-induced acute kidney injury: A multi-omics study","authors":"Lei Chen ,&nbsp;Shiying Xie ,&nbsp;Heqing Yang ,&nbsp;Xiangshen Liu ,&nbsp;Shunliang Yang ,&nbsp;Dong Wang","doi":"10.1016/j.crtox.2026.100300","DOIUrl":"10.1016/j.crtox.2026.100300","url":null,"abstract":"<div><div>Nephrotoxicity is a common side effect of cisplatin (CSP), a widely-used anti-tumor chemotherapy drug. Acute kidney injury (AKI) induced by it is characterized by inflammation, apoptosis, and metabolic reprogramming in proximal tubule (PT) cells. However, the key pathways and upstream transcriptional regulators orchestrating these pathological changes remain poorly understood. This study aimed to identify crucial transcription factors (TFs) involved in CSP-induced AKI and to explore potential therapeutic agents targeting them. An integrative multi-omics analysis of public bulk RNA-seq, proteomic, and single-cell RNA-seq datasets was performed to identify dysregulated pathways and key TFs. The expression of Krüppel-like factor 15 (KLF15), the lead candidate TF, was validated in a CSP-induced AKI mouse model (20 mg/kg intraperitoneal injection for 72 h) using RT-qPCR and Western blot. Molecular docking utilizing AutodockVina was employed to virtually screen an FDA-approved drug library for potential compounds targeting KLF15.Transcriptomics and proteomics analyses consistently identified KLF15 as a top-ranked, downregulated TF in CSP induced AKI. Single-cell analysis revealed that PT cells were the most affected, and the loss of <em>Klf15</em> expression in these cells was strongly associated with a proinflammatory, pro-apoptotic state and suppressed metabolic pathways, including the TCA cycle and fatty acid oxidation. In a murine model of CSP-induced AKI, <em>Klf15</em> mRNA and KLF15 protein levels were markedly reduced. Furthermore, virtual screening identified 6 drugs, including Simeprevir, Lomitapide, and Avodart, as potential high-affinity compounds targeting human KLF15. In conclusion, our study indicates that the downregulation of KLF15 is a prominent molecular feature in CSP-induced AKI, associated with metabolic failure and injury in proximal tubules.</div></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"10 ","pages":"Article 100300"},"PeriodicalIF":2.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148155821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aromatic aldehydes formed during heating of cinnamon-flavored e-liquids drive pro-inflammatory responses in human aortic smooth muscle cells","authors":"Mariam Bitar ,&nbsp;Jérémie Pourchez ,&nbsp;Mohamad Sleiman ,&nbsp;Laurent Bertoletti ,&nbsp;Valérie Forest","doi":"10.1016/j.crtox.2026.100299","DOIUrl":"10.1016/j.crtox.2026.100299","url":null,"abstract":"<div><div>Flavor additives can contribute to the biological effects of electronic cigarette (e-cigarette) aerosols, yet the mechanisms underlying flavor-related vascular toxicity remain poorly understood. We previously showed that exposure of human aortic smooth muscle cells (AoSMCs) to cinnamon-flavored e-cigarette aerosol induced a marked pro-inflammatory response that was amplified by heating. The present study aimed to identify thermal degradation products derived from cinnamon flavoring that may contribute to this effect. Aerosol condensates were generated from cinnamon-flavored e-liquids under controlled vaping conditions, and a chemical screening approach was used to identify degradation products. Benzaldehyde and phenylacetaldehyde were detected as specific to the heated cinnamon condensate and were subsequently selected for targeted <em>in vitro</em> testing. AoSMCs were exposed to aerosols, unheated e-liquids, or e-liquids supplemented with aldehydes (alone or in combination), and cytotoxicity and pro-inflammatory responses were assessed. Exposure to cinnamon aerosol induced a significant increase in IL-8 release without detectable cytotoxicity. Supplementation of e-liquids with benzaldehyde reproduced much of the IL-8 response observed with the aerosol, whereas phenylacetaldehyde alone elicited only a limited effect. Co-exposure to both aldehydes did not further enhance IL-8 production beyond that induced by benzaldehyde alone, suggesting potential interaction effects among cinnamon-derived degradation products.</div><div>Taken together, these findings indicate that thermal processing of cinnamon-flavored e-liquids generates aromatic aldehydes that contribute to pro-inflammatory signaling in human vascular smooth muscle cells, with benzaldehyde emerging as a major contributor under the present experimental conditions. This study highlights the importance of considering flavor-derived degradation products when evaluating the vascular toxicity of e-cigarette emissions.</div></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"10 ","pages":"Article 100299"},"PeriodicalIF":2.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147951281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}