International Journal of Toxicology最新文献_第2页

DEHP and Its Metabolite MEHP Alter the Insr and Glut4 Gene Expression by Blunting the Interaction of Transcription Factors in L6 Myotubes. DEHP及其代谢产物MEHP通过减弱L6肌管中转录因子的相互作用来改变Insr和Glut4基因的表达。

IF 1.2 4区医学

International Journal of Toxicology Pub Date : 2025-03-01 Epub Date: 2024-12-10 DOI: 10.1177/10915818241305090

Mangala Priya Viswanathan, Vigneswari Mullainadhan, Balasubramanian Karundevi

{"title":"DEHP and Its Metabolite MEHP Alter the Insr and Glut4 Gene Expression by Blunting the Interaction of Transcription Factors in L6 Myotubes.","authors":"Mangala Priya Viswanathan, Vigneswari Mullainadhan, Balasubramanian Karundevi","doi":"10.1177/10915818241305090","DOIUrl":"10.1177/10915818241305090","url":null,"abstract":"Endocrine-disrupting chemicals (EDCs) play an important role in the incidence of type-2 diabetes. Di-2-ethyl hexyl Phthalate (DEHP) is one of the endocrine-disrupting chemicals used as a plasticizer to impart flexibility and softness to plastic-containing materials. Mono-2-ethylhexyl Phthalate (MEHP), a DEHP's primary metabolite, is preferentially absorbed once metabolized. A previous study from our laboratory showed that DEHP and MEHP altered the key proteins such as insulin receptor (INSR) and glucose transporter-4 (GLUT4) in L6 myotubes. In a sequel to the previous study, the present study hypothesized that DEHP and its metabolite MEHP may alter the Insr and Glut4 gene expression in L6 myotubes. Therefore, to find out the molecular mechanism behind the decreased INSR and GLUT4 protein levels in the previous study, the direct effect of DEHP and its metabolite MEHP in regulating Insr and Glut4 gene transcription in L6 myotubes was studied. The L6 myotubes were exposed to 50 and 100 μM DEHP and MEHP for 24 h, followed by insulin stimulation for 20 min. We observed decreased Insr and Glut4 mRNA levels in DEHP and MEHP-treated groups. Western blot data showed decreased protein levels of MEF2A and MyoD in treated groups. ChIP assay detected a decreased association of MEF2A and MyoD to the Glut4 gene promoter and HMGA1 to the Insr gene promoter. The study revealed that DEHP and MEHP diminished the Insr and Glut4 gene expression through weakened interaction of their transcription factors on the respective promoter.","PeriodicalId":14432,"journal":{"name":"International Journal of Toxicology","volume":" ","pages":"170-180"},"PeriodicalIF":1.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142800583","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}

引用次数: 0

Identifying and Understanding Seizure Liability in Drug Development. 识别和理解药物开发中的扣押责任。

IF 1.2 4区医学

International Journal of Toxicology Pub Date : 2025-03-01 Epub Date: 2025-01-06 DOI: 10.1177/10915818241307851

Katie Sokolowski, Laura Erwin, Judy Liu, Simon Authier, Owen McMaster, Brandon Pressly, Brad Bolon, Marcus S Delatte

{"title":"Identifying and Understanding Seizure Liability in Drug Development.","authors":"Katie Sokolowski, Laura Erwin, Judy Liu, Simon Authier, Owen McMaster, Brandon Pressly, Brad Bolon, Marcus S Delatte","doi":"10.1177/10915818241307851","DOIUrl":"https://doi.org/10.1177/10915818241307851","url":null,"abstract":"Seizures are complex electrophysiological disturbances affecting one or more populations of brain neurons. Seizures following test article (TA) exposure pose significant challenges in drug development. This paper considers the diverse neurological manifestations, mechanisms, and functional and structural assessments needed to investigate TA-related seizure liabilities, with a particular focus on nonclinical species. Accurate discrimination of seizures from convulsions (irregular involuntary body and/or limb movements) and the nuanced presentation of different seizure types (partial vs. general) and phases (prodromal, ictal, and postictal) are essential for discerning their clinical implications. In nonclinical safety testing, the most direct evaluation method to confirm existence of seizures is electroencephalography (EEG) while clinical endpoints (e.g., functional observational batteries [FOB], comprehensive neurological examinations) and neuropathological findings (e.g., neuronal necrosis in tissue sections, raised biomarker levels in cerebrospinal fluid or serum) can indicate a seizure liability and provide additional guidance to identify the origin, frequency, and severity of seizures needed to align nonclinical effects with clinical relevance. In general, the regulatory perspective is that seizures identified in nonclinical species as well as potential risk management strategies (e.g., safety margin considerations, dosing paradigms, and clinical monitoring) translate effectively for purposes of clinical risk assessment.","PeriodicalId":14432,"journal":{"name":"International Journal of Toxicology","volume":"44 2","pages":"99-124"},"PeriodicalIF":1.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143982891","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}

引用次数: 0

Exploring the Biological Effects of Polystyrene Nanoplastics on Spermatogenesis: Insights From Transcriptomic Analysis in Mouse Spermatocytes. 探索聚苯乙烯纳米塑料对精子发生的生物学效应：来自小鼠精母细胞转录组学分析的见解。

IF 1.2 4区医学

International Journal of Toxicology Pub Date : 2025-03-01 Epub Date: 2024-12-08 DOI: 10.1177/10915818241305086

Ying Jiang, Kexuan He, Qianyi Shen, Can Yang, Xin Huang, Junjie Fan, Miaomiao Du, Jianrong Wu, Huajuan Ruan, Jun Yang, Yeting Hong

{"title":"Exploring the Biological Effects of Polystyrene Nanoplastics on Spermatogenesis: Insights From Transcriptomic Analysis in Mouse Spermatocytes.","authors":"Ying Jiang, Kexuan He, Qianyi Shen, Can Yang, Xin Huang, Junjie Fan, Miaomiao Du, Jianrong Wu, Huajuan Ruan, Jun Yang, Yeting Hong","doi":"10.1177/10915818241305086","DOIUrl":"10.1177/10915818241305086","url":null,"abstract":"The presence of polystyrene plastics in the human testis has raised concerns, yet their biological activity remains poorly characterized. This study aimed to investigate the biological effects and potential regulatory genes of polystyrene nanoplastics on spermatocyte line, GC-2spd(ts). After a 24-h exposure to polystyrene nanoplastics, the results indicated cell membrane disruption, impairment of mitochondrial membrane potential, increased levels of reactive oxygen species (ROS), and induced DNA damage. Furthermore, a comprehensive transcriptomic analysis was conducted, revealing differential gene expression patterns in GC-2spd(ts) cells in response to polystyrene nanoplastics. A total of 134 differentially expressed genes (DEGs) were identified, with 48 genes upregulated and 86 genes downregulated. The Gene Ontology analysis highlighted the involvement of these genes in various spermatogenesis-related biological processes, including acrosome reaction, sperm mitochondrial organization, sperm annulus, and outer acrosomal membrane. Subsequently, the quantification of gene expression through qRT-PCR identified five key genes (NSUN7, SEPTIN4, TRIM36, EQTN, and SYT8) screened from the DEGs. In conclusion, this study provides valuable insights into the biological effects of polystyrene nanoplastics on mouse spermatocytes using comprehensive transcriptomic analysis, contributing to the establishment of a foundation for future investigations into these relevant pathways.","PeriodicalId":14432,"journal":{"name":"International Journal of Toxicology","volume":" ","pages":"141-152"},"PeriodicalIF":1.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794422","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}

引用次数: 0

I Wish I Had Known That! Impactful Guidance and Perspectives for a Fulfilling Career in Toxicology. 我要是知道就好了！毒理学职业生涯的有效指导和前景。

IF 1.2 4区医学

International Journal of Toxicology Pub Date : 2025-02-14 DOI: 10.1177/10915818251319250

Jessica C Graham, Joel Bercu, Marie C Fortin, Andy Kiorpes, Sunjay Sethi, Robert Roy

{"title":"I Wish I Had Known That! Impactful Guidance and Perspectives for a Fulfilling Career in Toxicology.","authors":"Jessica C Graham, Joel Bercu, Marie C Fortin, Andy Kiorpes, Sunjay Sethi, Robert Roy","doi":"10.1177/10915818251319250","DOIUrl":"https://doi.org/10.1177/10915818251319250","url":null,"abstract":"Have you ever reflected on your career or other experiences and thought, if I knew 10 or 20 years ago, what I know now, it would have enabled me to do this or that better-or I would have had a different attitude or perhaps even taken a different path? This article presents the proceedings from the symposium entitled \"I Wish I Had Known That! Impactful Guidance and Perspectives for a Fulfilling Career in Toxicology\" held at the 2023 annual meeting of the American College of Toxicology. In this session, toxicology professionals reflected on the highlights of their careers, the most impactful advice/mentoring they received or wish they had received, and the characteristics that have been key components of their success. This session consisted of didactic talks from a diverse panel representing various career stages and backgrounds, followed by a panel discussion and the opportunity for the audience to ask questions. Using a structured approach, speakers actively engaged the audience, providing insights gained through their professional journeys. This article offers experiential-based insights to help guide individuals in achieving successful and fulfilling careers in toxicology, considering both professional aspirations and the integration of personal values with life goals.","PeriodicalId":14432,"journal":{"name":"International Journal of Toxicology","volume":" ","pages":"10915818251319250"},"PeriodicalIF":1.2,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143416776","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}

引用次数: 0

Mutagenesis and Carcinogenesis Risk Evaluation for AAV and Lentiviral Gene Therapies. AAV和慢病毒基因治疗的突变和致癌风险评估。

IF 1.2 4区医学

International Journal of Toxicology Pub Date : 2025-02-11 DOI: 10.1177/10915818251318248

Toufan Parman, Daniella M Pizzurro, Jacquelynn Lucas, Zhechu Peng

{"title":"Mutagenesis and Carcinogenesis Risk Evaluation for AAV and Lentiviral Gene Therapies.","authors":"Toufan Parman, Daniella M Pizzurro, Jacquelynn Lucas, Zhechu Peng","doi":"10.1177/10915818251318248","DOIUrl":"https://doi.org/10.1177/10915818251318248","url":null,"abstract":"Fueled by the identification and invention of novel gene delivery vectors, gene therapy efforts now hold promise for treating a wide range of diseases and are seen as a crucial part of growth for the biopharmaceutical industry. Currently, recombinant adeno-associated virus vectors (rAAVs) and lentiviral vectors (LVs) are the main vectors used in gene therapies that are approved or tested in human clinical trials. Meanwhile, ongoing research continuously reveals unprecedented knowledge of viral vectors on the host genome, which may subsequently affect the mutagenic and carcinogenic potential of these therapies. This article summarizes the content and addresses the commentary from the scientific symposium entitled \"Mutagenesis and Carcinogenesis Risk Evaluation for AAV and Lentiviral Gene Therapies,\" conducted at the 43rd Annual Meeting of the American College of Toxicology, November 2022 in Denver, CO. The objective is to summarize the current understanding of rAAV and LV related mutagenicity/carcinogenicity risk, describe the methods and interpretation of results to guide risk assessments, as well as the current regulatory landscape on the carcinogenicity and mutagenicity assessment of rAAV and LV gene therapy products.","PeriodicalId":14432,"journal":{"name":"International Journal of Toxicology","volume":" ","pages":"10915818251318248"},"PeriodicalIF":1.2,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399131","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}

引用次数: 0

Isobutane, Isopentane, Butane, and Propane. 异丁烷、异戊烷、丁烷和丙烷。

IF 1.2 4区医学

International Journal of Toxicology Pub Date : 2025-02-01 Epub Date: 2024-06-14 DOI: 10.1177/10915818241260280

Regina Tucker, Wilma F Bergfeld, Donald V Belsito, David E Cohen, Curtis D Klaassen, Allan E Rettie, David Ross, Thomas J Slaga, Paul W Snyder, Susan Tilton, Monice Fiume, Bart Heldreth

引用次数: 0

Safety Assessment of Mannitol, Sorbitol, and Xylitol as Used in Cosmetics. 化妆品中使用的甘露醇、山梨醇和木糖醇的安全性评估。

IF 1.2 4区医学

International Journal of Toxicology Pub Date : 2025-02-01 Epub Date: 2024-11-18 DOI: 10.1177/10915818241297097

Priya Cherian, Wilma F Bergfeld, Donald V Belsito, Curtis D Klaassen, Daniel C Liebler, James G Marks, Lisa A Peterson, Ronald C Shank, Thomas J Slaga, Paul W Snyder, Monice Fiume, Bart Heldreth

引用次数: 0

Safety Assessment of Ascorbyl Glucoside and Sodium Ascorbyl Glucoside as Used in Cosmetics. 化妆品中使用的抗坏血酸葡萄糖苷和抗坏血酸葡萄糖苷钠的安全性评估。

IF 1.2 4区医学

International Journal of Toxicology Pub Date : 2025-02-01 Epub Date: 2024-11-08 DOI: 10.1177/10915818241297075

Wilbur Johnson, Wilma F Bergfeld, Donald V Belsito, Curtis D Klaassen, Daniel C Liebler, James G Marks, Lisa A Peterson, Ronald C Shank, Thomas J Slaga, Paul W Snyder, Monice Fiume, Bart Heldreth

引用次数: 0

Safety Assessment of Wheat-Derived Ingredients as Used in Cosmetics. 化妆品中使用的小麦提取成分的安全性评估。

IF 1.2 4区医学

International Journal of Toxicology Pub Date : 2025-02-01 Epub Date: 2024-11-08 DOI: 10.1177/10915818241294063

Christina L Burnett, Wilma F Bergfeld, Donald V Belsito, David E Cohen, Curtis D Klaassen, Daniel C Liebler, James G Marks, Lisa A Peterson, Ronald C Shank, Thomas J Slaga, Paul W Snyder, Monice Fiume, Bart Heldreth

引用次数: 0

Safety Assessment of Triphenyl Phosphate as Used in Cosmetics. 化妆品中使用的磷酸三苯酯的安全性评估。

IF 1.2 4区医学

International Journal of Toxicology Pub Date : 2025-02-01 Epub Date: 2024-06-14 DOI: 10.1177/10915818241259692

Christina L Burnett, Wilma F Bergfeld, Donald V Belsito, Ronald A Hill, Curtis D Klaassen, Daniel C Liebler, James G Marks, Ronald C Shank, Thomas J Slaga, Paul W Snyder, Monice Fiume, Bart Heldreth

引用次数: 0