Current Research in Toxicology最新文献_第3页

Indoor airborne carcinogen synergy in children: systematic interdisciplinary approach to PM2.5-nicotine driven lung tumorigenesis and targeted intervention 儿童室内空气致癌物协同作用：pm2.5 -尼古丁驱动的肺肿瘤发生和靶向干预的系统跨学科方法

IF 2.9

Current Research in Toxicology Pub Date : 2025-01-01 DOI: 10.1016/j.crtox.2025.100255

Boyu Pan , Xiwen Feng , Fujian Jiang , Rui Li , Han Zhu , Kunpeng Wang

{"title":"Indoor airborne carcinogen synergy in children: systematic interdisciplinary approach to PM2.5-nicotine driven lung tumorigenesis and targeted intervention","authors":"Boyu Pan , Xiwen Feng , Fujian Jiang , Rui Li , Han Zhu , Kunpeng Wang","doi":"10.1016/j.crtox.2025.100255","DOIUrl":"10.1016/j.crtox.2025.100255","url":null,"abstract":"<div><div>The indoor air environment has become an essential environmental factor affecting children’s health and safety, among which nicotine and PM2.5, two common combined factors, have become pathogenic factors in indoor area that induce lung cancer in children. In order to reveal the specific mechanism of that, we developed the model of Systematic Environmental Information Medicine Engineering (SEIME), which combines environmental engineering, bioinformatics, and computational biology multidisciplinary approaches. We initially developed a comprehensive computational fluid dynamics (CFD) model, which was subsequently integrated with data from the GEO database, TCGA database, single-cell online databases, and molecular docking analyses to enhance our research framework. CFD results revealed that indoor concentrations of PM2.5 and nicotine were significantly higher than the recommended values of 15 µg/m<sup>3</sup> and 1 µg/m<sup>3</sup> in the WHO Global Air Quality Guidelines. Meanwhile, bioinformatics results indicated that MAPK and PI3K-Akt were important signaling pathways for inducing non-small cell lung cancer (NSCLC) in children. In addition, GADD45A and NPAS2, as key targets affecting children’s NSCLC, were identified. Subsequently, drug repositioning and molecular docking assays were conducted, and more importantly, related small molecule targeted drugs were screened. Therefore, this study has set up a new interdisciplinary analysis model-SEIME, using environmental information medicine engineering to solve environmental disease models under the influence of multiple factors, and providing theoretical basis for molecular target screening and disease treatment.</div></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"9 ","pages":"Article 100255"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145018600","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}

引用次数: 0

Differential effect of targeting cisplatin-induced nitrative stress using MnTBAP in auditory and cancer cells 利用mnttap靶向顺铂诱导的听觉细胞和癌细胞的硝化应激的差异效应

IF 2.9

Current Research in Toxicology Pub Date : 2025-01-01 DOI: 10.1016/j.crtox.2025.100241

Shomaila Mehmood, Pankaj Bhatia, Nicole Doyon-Reale, Samson Jamesdaniel

{"title":"Differential effect of targeting cisplatin-induced nitrative stress using MnTBAP in auditory and cancer cells","authors":"Shomaila Mehmood, Pankaj Bhatia, Nicole Doyon-Reale, Samson Jamesdaniel","doi":"10.1016/j.crtox.2025.100241","DOIUrl":"10.1016/j.crtox.2025.100241","url":null,"abstract":"<div><div>Ototoxicity is a major dose-limiting side effect of cisplatin, a highly effective anti-cancer drug used to treat many solid tumors. Oxidative stress plays a central role in mediating cisplatin-induced ototoxicity. However, broad-spectrum antioxidants that prevent ototoxicity compromise the anti-cancer activity of cisplatin. Therefore, there is a need to identify novel interventional targets/compounds for otoprotection. Recent reports indicated that cisplatin-induced nitration of cochlear proteins is a critical factor in causing ototoxicity, and inhibition of cochlear nitrative stress mitigated cisplatin-induced ototoxicity. The use of peroxynitrite decomposition catalysts that selectively target nitrative stress appears to be an attractive strategy for mitigating the ototoxic effects of cisplatin because they do not scavenge free radicals. We hypothesized that cotreatment with selective inhibitors of nitrative stress prevents cisplatin-induced ototoxicity without compromising the anti-cancer effects. Here, we test this hypothesis by investigating the effect of MnTBAP cotreatment on cell viability, nitrative stress, DNA damage, and cell migration in cisplatin-treated organ of Corti as well as cancer cells. Our results indicate that cisplatin treatment decreases cell viability in both auditory and cancer cells, while cotreatment with MnTBAP mitigates cisplatin-induced cytotoxicity in the auditory cells but not in the cancer cells. Collectively, the findings of this study suggest that selective targeting of cisplatin-induced nitrative stress is a promising strategy for mitigating the ototoxic effects of cisplatin because it does not compromise the anti-cancer effects.</div></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"8 ","pages":"Article 100241"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144106152","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}

引用次数: 0

Metabolomic profiling reveals systemic metabolic disruptions induced by combined exposure to particulate matter and ozone 代谢组学分析揭示了由颗粒物和臭氧联合暴露引起的全身代谢紊乱

IF 2.9

Current Research in Toxicology Pub Date : 2025-01-01 DOI: 10.1016/j.crtox.2025.100216

Yue Ge , Maliha S. Nash , Aimen K. Farraj

{"title":"Metabolomic profiling reveals systemic metabolic disruptions induced by combined exposure to particulate matter and ozone","authors":"Yue Ge , Maliha S. Nash , Aimen K. Farraj","doi":"10.1016/j.crtox.2025.100216","DOIUrl":"10.1016/j.crtox.2025.100216","url":null,"abstract":"<div><div>Air pollution exposure, especially particulate matter (PM) and ozone (O<sub>3</sub>), poses significant health risks, but the systemic metabolic consequences of combined exposures to PM and O<sub>3</sub>, remain poorly understood. This study investigated systemic metabolic changes in male spontaneously hypertensive (SH) rats following inhalation exposure to concentrated ambient particles (CAPs) (PM2.5, 150 μg/m<sup>3</sup>), ozone (O<sub>3</sub>) (0.2 ppm), and their combination. Rats were exposed for 4 h, and serum samples were collected 1-hour post-exposure. Using targeted metabolomics, we identified significant alterations in metabolites involved in lipid metabolism (phosphatidylcholines), energy metabolism (acylcarnitine C3), and oxidative stress (glutamine). Notably, the combination exposure induced distinct metabolic changes, including increased acylcarnitine C3 levels, suggesting heightened mitochondrial dysfunction. Principal component analysis revealed overlapping profiles between CAPs and controls, indicating a subtler impact of CAPs compared to ozone or combined exposure. These systemic metabolic alterations are aligned with our previously published proteomics findings in cardiac tissues from the same rats, which showed elevated inflammatory markers (e.g., IL-6, TNF-α) and mitochondrial dysfunction. In conclusion, this study provides new insights into the systemic metabolic effects of air pollutant exposure, identifies novel metabolic targets of pollutant-induced toxicity, highlights the complex interactions resulting from combined exposure to multiple pollutants, and underscores the importance of assessing the combined effects of multiple pollutants in air pollution risk assessments.</div></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"8 ","pages":"Article 100216"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143161099","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}

引用次数: 0

Exacerbation of polyethylene microplastics in animal models of DSS-induced colitis through damage to intestinal epithelial cell conjunctions 聚乙烯微塑料通过损伤肠上皮细胞连接加重dss诱导的结肠炎动物模型

IF 2.9

Current Research in Toxicology Pub Date : 2025-01-01 DOI: 10.1016/j.crtox.2025.100217

Minkyoung Sung , Yeon-Ji Lee , Soo-Eun Sung , Kyung-Ku Kang , Jae Woo Park , Yujeong Lee , Dongmin Kim , Sunjong Lee , Joo-Hee Choi , Sijoon Lee

{"title":"Exacerbation of polyethylene microplastics in animal models of DSS-induced colitis through damage to intestinal epithelial cell conjunctions","authors":"Minkyoung Sung , Yeon-Ji Lee , Soo-Eun Sung , Kyung-Ku Kang , Jae Woo Park , Yujeong Lee , Dongmin Kim , Sunjong Lee , Joo-Hee Choi , Sijoon Lee","doi":"10.1016/j.crtox.2025.100217","DOIUrl":"10.1016/j.crtox.2025.100217","url":null,"abstract":"<div><div>Microplastics are pollutants that occur in various environments and habitats. Inflammatory bowel disease (IBD) is a chronic inflammatory disease accompanied with diarrhea, and the number of patients has increased worldwide. In this study, manufactured fragmented polyethylene-microplastics in the size range of 10–30 ㎛, were oxidized by exposure to ultraviolet light, and then administered to a dextran sodium sulfate-induced colitis mouse model to observe the effects of polyethylene-microplastics on IBD. In the microplastics-treated groups, an increase in disease activity index score, histopathological score, and a decrease in the areas of goblet cells were observed. In addition, the tight junction proteins, ZO-1 and Occludin, were significantly decreased, whereas MPO was significantly increased. Interestingly, E-cadherin, which is an adheren junction, was also decreased, presumably because of the physical effects of microplastics. The results suggest that polyethylene-microplastics worsen IBD and microplastics can affect not only tight junctions, but also adheren junctions.</div></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"8 ","pages":"Article 100217"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143161100","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}

引用次数: 0

New approach methodologies to assess wanted and unwanted drugs-induced immunostimulation 评估想要和不想要的药物诱导免疫刺激的新方法方法

IF 2.9

Current Research in Toxicology Pub Date : 2025-01-01 DOI: 10.1016/j.crtox.2025.100222

Valeria Bettinsoli , Gloria Melzi , Irene Marchese , Sofia Pantaleoni , Francesca Carlotta Passoni , Emanuela Corsini

引用次数: 0

Genotoxicity testing of the anthraquinone dye Alizarin Red S 蒽醌染料茜素红S的遗传毒性试验。

IF 2.9

Current Research in Toxicology Pub Date : 2025-01-01 DOI: 10.1016/j.crtox.2024.100208

Benedikt Bauer, Helena Rossi, Henning Hintzsche

引用次数: 0

The role of the gut microbiota and the nicotinate/nicotinamide pathway in rotenone-induced neurotoxicity 肠道菌群和烟酸/烟酰胺途径在鱼藤酮诱导的神经毒性中的作用。

IF 2.9

Current Research in Toxicology Pub Date : 2025-01-01 DOI: 10.1016/j.crtox.2024.100212

Yan Sai, Wei Ge, Li Zhong, Qifu Zhang, Jingsong Xiao, Yaohui Shan, Wenqi Ye, Haoyin Liu, Shulin Liu, Feng Ye, Xiaogang Wang, He Tang, Yuanpeng Zhao, Guorong Dan

{"title":"The role of the gut microbiota and the nicotinate/nicotinamide pathway in rotenone-induced neurotoxicity","authors":"Yan Sai, Wei Ge, Li Zhong, Qifu Zhang, Jingsong Xiao, Yaohui Shan, Wenqi Ye, Haoyin Liu, Shulin Liu, Feng Ye, Xiaogang Wang, He Tang, Yuanpeng Zhao, Guorong Dan","doi":"10.1016/j.crtox.2024.100212","DOIUrl":"10.1016/j.crtox.2024.100212","url":null,"abstract":"<div><div>Rotenone is a natural compound from plants. It is widely used in pesticides because of highly toxic to insects and fish. However, lots of research has reported that rotenone has neurotoxic effects in humans. It is confirmed there is a correlation between rotenone exposure and Parkinson’s disease (PD). Therefore, the role of gut microbiota and related metabolic pathways was investigated in rotenone-induced neurotoxicity. The results showed that the abundance of gut microbiota changed significantly. The differential metabolites were enriched in the nicotinate and nicotinamide metabolism pathways, which had the greatest impact on the entire metabolic system. The contents of acetic acid and butyric acid in intestinal tissues decreased significantly. Additionally, Interleukin-6 (IL-6), Tumor necrosis factor alpha (TNF-α) and vasoactive intestinal peptide (VIP) were significantly up-regulated, while gastrin (GAS) and Ghrelin were significantly down-regulated. Expression of intestinal tight junction protein was significantly reduced. Moreover, nicotinamide adenine dinucleotide (NAD<sup>+</sup>), a the product of the nicotinate/nicotinamide pathways, decreased significantly. And the expression levels of nicotinamide phosphoribosyl transferase (NAMPT) and Solute Carrier Family 25 Member 51 (SLC25A51) also reduced significantly. Therefore, gut microbiota was influenced obviously in rats exposed to rotenone, leading to a decrease of acetic acid and butyric acid contents, which might in turn affect the change of intestinal barrier permeability and induce inflammatory reactions. Meanwhile, the nicotinate/nicotinamide metabolic pathways might play an important role in rats exposed to rotenone.</div></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"8 ","pages":"Article 100212"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11743872/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001650","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}

引用次数: 0

Hepatocytes derived from human induced pluripotent stem cells: Towards establishing an in vitro model for assessing population variability in hepatotoxicity testing 从人诱导多能干细胞衍生的肝细胞：建立肝毒性试验中评估群体变异的体外模型

IF 2.9

Current Research in Toxicology Pub Date : 2025-01-01 DOI: 10.1016/j.crtox.2025.100238

Xiugong Gao, Rong Li, Kayla Campasino, Miranda R. Yourick, Yang Zhao, Robert L. Sprando, Jeffrey J. Yourick

{"title":"Hepatocytes derived from human induced pluripotent stem cells: Towards establishing an in vitro model for assessing population variability in hepatotoxicity testing","authors":"Xiugong Gao, Rong Li, Kayla Campasino, Miranda R. Yourick, Yang Zhao, Robert L. Sprando, Jeffrey J. Yourick","doi":"10.1016/j.crtox.2025.100238","DOIUrl":"10.1016/j.crtox.2025.100238","url":null,"abstract":"<div><div>Interindividual differences in response to chemicals have been typically addressed through the use of a 10-fold default “uncertainty” factor. It was only recently that <em>in vitro</em> models emerged to quantitatively assess interindividual variability in the human population for specific chemicals. In the current study, we attempted to establish an <em>in vitro</em> model for assessing population variability in hepatotoxicity testing using a panel of hepatocytes derived from nine human induced pluripotent stem cell (iPSC) lines belonging to three different ethnic groups, Black or African American, Latino or Hispanic, and Non-Hispanic White. We demonstrated that the panel of iPSC-derived hepatocytes manifested diversity in hepatic function assays, in global and hepatic gene expressions, and in cytotoxic responses to four well know hepatotoxicants with distinct mechanisms of toxicity: acetaminophen, troglitazone, diglycolic acid, and usnic acid. However, due to the unavailability of model compounds with ethnicity specific toxicity as well as the small number of individuals in each ethnic group (<em>n</em> = 3), ethnic-specific effects were not observed using the model.</div></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"8 ","pages":"Article 100238"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144106153","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}

引用次数: 0

Prediction of the classification, labelling and packaging regulation H-statements with confidence using conformal prediction with N-grams and molecular fingerprints 利用n -图和分子指纹的保形预测对分类、标签和包装法规h -陈述进行预测

IF 2.9

Current Research in Toxicology Pub Date : 2025-01-01 DOI: 10.1016/j.crtox.2025.100242

Ulf Norinder , Ziye Zheng , Ian Cotgreave

{"title":"Prediction of the classification, labelling and packaging regulation H-statements with confidence using conformal prediction with N-grams and molecular fingerprints","authors":"Ulf Norinder , Ziye Zheng , Ian Cotgreave","doi":"10.1016/j.crtox.2025.100242","DOIUrl":"10.1016/j.crtox.2025.100242","url":null,"abstract":"<div><div>Effective chemical hazard labelling systems are essential for safeguarding human health and the environment as a result of widespread chemical use, and machine-learning models can be used to predict hazard labels efficiently and reduce the use of animal tests. This investigation shows the utility of N-grams and other fingerprint featurization procedures for predicting classification, labelling and packaging (CLP). Regulation H-statements, particularly in an ensemble (consensus) setting. Consensus modelling by class or Conformal Prediction median p-values seems to be particularly advantageous in order to obtain both high conformal prediction validity and efficiency as well as good balanced accuracy, sensitivity and specificity. Utilization of the N-grams allows handling of all symbols in SMILES strings including those related to metals and salts that may be important for the compounds to exhibit their experimental determined toxicities. The models developed in this study are efficient tools to access hazard classification H-statements of chemicals, which can be useful for chemical hazard assessment, read-across as well as risk management.</div></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"8 ","pages":"Article 100242"},"PeriodicalIF":2.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144184903","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}

引用次数: 0

Neural organoids as advanced tools for neurotoxicity modeling 神经类器官作为神经毒性建模的先进工具

IF 2.9

Current Research in Toxicology Pub Date : 2025-01-01 DOI: 10.1016/j.crtox.2025.100249

Joydeb Majumder , William L. Murphy

引用次数: 0