Current opinion in toxicology最新文献

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Adverse outcome pathway networks as the basis for the development of new approach methodologies: Liver toxicity as a case study 将不良后果路径网络作为开发新方法的基础:以肝脏毒性为例
IF 4.6
Current opinion in toxicology Pub Date : 2024-09-29 DOI: 10.1016/j.cotox.2024.100504
Mathieu Vinken
{"title":"Adverse outcome pathway networks as the basis for the development of new approach methodologies: Liver toxicity as a case study","authors":"Mathieu Vinken","doi":"10.1016/j.cotox.2024.100504","DOIUrl":"10.1016/j.cotox.2024.100504","url":null,"abstract":"<div><div>The fields of toxicology and risk assessment are witnessing a paradigm shift moving away from animal testing towards the use of nonanimal and human-based new approach methodologies (NAMs). NAMs are fed by mechanistic information captured in adverse outcome pathway (AOP) networks, which are being developed and optimized at high pace. The present paper demonstrates this (r)evolution for the case of liver toxicity induced by pharmaceutical drugs. NAMs, <em>in casu</em> designed to predict hepatotoxicity, are composed of an <em>in vitro</em> system linked with a suite of assays mechanistically anchored in relevant AOP networks. These NAMs allow tiered testing at the transcriptional, translational and functionality level at high predictive capacity. Although promising, however, several challenges in NAM development still need to be tackled and are discussed in this paper.</div></div>","PeriodicalId":93968,"journal":{"name":"Current opinion in toxicology","volume":"40 ","pages":"Article 100504"},"PeriodicalIF":4.6,"publicationDate":"2024-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142445122","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
New approach methodologies (NAMs) in drug safety assessment: A vision of the future 药物安全性评估中的新方法(NAMs):未来展望
IF 4.6
Current opinion in toxicology Pub Date : 2024-09-04 DOI: 10.1016/j.cotox.2024.100502
Ruth A. Roberts
{"title":"New approach methodologies (NAMs) in drug safety assessment: A vision of the future","authors":"Ruth A. Roberts","doi":"10.1016/j.cotox.2024.100502","DOIUrl":"10.1016/j.cotox.2024.100502","url":null,"abstract":"<div><div>Much progress has been made in reducing and refining animal use in toxicology testing, but progress in the use of new approach methodologies (NAMs) to replace animals is disappointing. There are many highly sophisticated NAMs available, but societal, regulatory and political barriers to their implementation remain. Change requires vision, starting with imagining a future where we are successful. Specifically, this would comprise the registration of safe and effective medicines without animal tests. How do we achieve this vision? Thinking differently, in silico methods could be used to provide a detailed assessment of target- and modality-related toxicological risks, coupled with modelling of exposure. In vitro NAMs such as microphysiological systems, microelectrode array and ion channel panels could then be employed to address hypothetical risks. Finally, the safety of first time in human trials could be assessed and assured using circulating nanobots that measure conventional clinical pathology parameters alongside new biomarkers such as circulating tissue DNA. This may seem the stuff of fantasy, but imagination is key to shaping a better future and all change starts with a vision, however far-fetched it may seem today.</div></div>","PeriodicalId":93968,"journal":{"name":"Current opinion in toxicology","volume":"40 ","pages":"Article 100502"},"PeriodicalIF":4.6,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142314942","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
Editorial: Transforming toxicology one cell at a time: A special issue on the application of scRNA-seq to the study of environmental response 社论:一次改变一个细胞的毒理学:关于应用 scRNA-seq 研究环境反应的特刊
IF 4.6
Current opinion in toxicology Pub Date : 2024-09-02 DOI: 10.1016/j.cotox.2024.100503
Patrick Allard, Justin A. Colacino, Kristine L. Willett
{"title":"Editorial: Transforming toxicology one cell at a time: A special issue on the application of scRNA-seq to the study of environmental response","authors":"Patrick Allard,&nbsp;Justin A. Colacino,&nbsp;Kristine L. Willett","doi":"10.1016/j.cotox.2024.100503","DOIUrl":"10.1016/j.cotox.2024.100503","url":null,"abstract":"","PeriodicalId":93968,"journal":{"name":"Current opinion in toxicology","volume":"40 ","pages":"Article 100503"},"PeriodicalIF":4.6,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142271004","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
Practical lessons of the 3Rs: Learning from the past and looking toward the future 3Rs 的实践经验:总结过去,展望未来
IF 4.6
Current opinion in toxicology Pub Date : 2024-08-16 DOI: 10.1016/j.cotox.2024.100499
Alan M. Hoberman , Barbara L.F. Kaplan
{"title":"Practical lessons of the 3Rs: Learning from the past and looking toward the future","authors":"Alan M. Hoberman ,&nbsp;Barbara L.F. Kaplan","doi":"10.1016/j.cotox.2024.100499","DOIUrl":"10.1016/j.cotox.2024.100499","url":null,"abstract":"<div><p>Replacement, reduction, and refinement, known as the 3Rs, is a well-known and broadly applied concept in biomedical science. Since its formal introduction in 1959, application of the 3Rs have refined approaches to reduce or eliminate distress, reduced overall use through repeated measures approaches and use of appropriate numbers of animals, or have replaced animals altogether. However, adoption of the 3Rs is not always easy, due in part to initial lack of awareness of the importance of animal well-being to the outcome of scientific investigation, a lack of understanding of use of results from <em>in vivo</em> model verses <em>in vitro</em> models, lack of effective communication about model benefits, or other technical issues with the development or use of an assay. In understanding the history of the 3Rs, we can learn from or avoid previous challenges as we look to the future of the application of the 3Rs. For instance, there is little doubt that awareness and use of the 3Rs influenced the concept of new approach methods (NAMs), a term describing assays that include traditional <em>in vitro</em> cultures, microphysiological systems, and <em>in silico</em> approaches, and is certainly part of the 3Rs future and the ultimate replacement of an animal-based assay.</p></div>","PeriodicalId":93968,"journal":{"name":"Current opinion in toxicology","volume":"40 ","pages":"Article 100499"},"PeriodicalIF":4.6,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142162046","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
Advances in genomic toxicology: In vitro developmental toxicity test based on signal network disruption dynamics 基因组毒理学的进展:基于信号网络中断动力学的体外发育毒性测试
IF 4.6
Current opinion in toxicology Pub Date : 2024-07-14 DOI: 10.1016/j.cotox.2024.100489
Yusuke Okubo , Yoko Hirabayashi , Junji Fukuda
{"title":"Advances in genomic toxicology: In vitro developmental toxicity test based on signal network disruption dynamics","authors":"Yusuke Okubo ,&nbsp;Yoko Hirabayashi ,&nbsp;Junji Fukuda","doi":"10.1016/j.cotox.2024.100489","DOIUrl":"10.1016/j.cotox.2024.100489","url":null,"abstract":"<div><p>Developmental toxicity outcomes in humans and animals often exhibit variability; hence, the demand for predictive non-animal alternatives, particularly human cell-based models, are increasing. Despite advancements in genomic toxicology, which have facilitated the identification of toxicity mechanisms and potential biomarkers, existing transcriptome analysis-based methods have yet to yield highly predictive <em>in vitro</em> developmental toxicity assays. One possible reason is that assays at a single time point could not capture the entire dynamic signal network during developmental processes. This article addresses the challenges in comprehensive gene expression analysis and introduces novel <em>in vitro</em> developmental toxicity assays focused on the time-dependent dynamics of signaling pathway responses crucial to human development.</p></div>","PeriodicalId":93968,"journal":{"name":"Current opinion in toxicology","volume":"39 ","pages":"Article 100489"},"PeriodicalIF":4.6,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2468202024000317/pdfft?md5=24008ba91be5c75a73de9c26ba156ac6&pid=1-s2.0-S2468202024000317-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141705549","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
NAMs: Beta testing needed NAM:需要测试版
IF 4.6
Current opinion in toxicology Pub Date : 2024-07-14 DOI: 10.1016/j.cotox.2024.100490
Denise Bloch, Philip Marx-Stoelting, Tewes Tralau
{"title":"NAMs: Beta testing needed","authors":"Denise Bloch,&nbsp;Philip Marx-Stoelting,&nbsp;Tewes Tralau","doi":"10.1016/j.cotox.2024.100490","DOIUrl":"10.1016/j.cotox.2024.100490","url":null,"abstract":"<div><p>A variety of new approach methodologies (NAMs) have already been developed for acute systemic and short-term toxicity, including <em>in vitro</em>, <em>in silico</em>, and omics methods. To advance their regulatory implementation, we suggest that beta testing of these methods in regulatory settings is urgently needed. There are several limitations to the use of NAMs for acute systemic and short-term toxicity, such as the lack of definitions for applicability domains, skewed reference data for validation, and the absence of representation of kinetic processes and multi-organ complexity. These limitations may lead to risks associated with the ordinary regulatory implementation, such as the application of methods to substances outside of their intended applicability domain or reduced predictivity due to a lack of mechanistic information or consideration of kinetics. We argue that this could be avoided by beta testing. Further benefits of beta testing would be the filling of <em>in vivo</em> data gaps and potentially improved validation with regard to human relevance of methods. In order to enhance the improvement, familiarisation, and acceptance of NAMs in the near future, it is essential for such concept of beta testing to rely on feedback loops between method testers and developers.</p></div>","PeriodicalId":93968,"journal":{"name":"Current opinion in toxicology","volume":"39 ","pages":"Article 100490"},"PeriodicalIF":4.6,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2468202024000329/pdfft?md5=43c34608e921555b7f5665fb5635a6ef&pid=1-s2.0-S2468202024000329-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141691074","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
Application of single cell methods in immunometabolism and immunotoxicology 单细胞方法在免疫代谢和免疫毒理学中的应用
IF 4.6
Current opinion in toxicology Pub Date : 2024-06-22 DOI: 10.1016/j.cotox.2024.100488
Peer W.F. Karmaus
{"title":"Application of single cell methods in immunometabolism and immunotoxicology","authors":"Peer W.F. Karmaus","doi":"10.1016/j.cotox.2024.100488","DOIUrl":"https://doi.org/10.1016/j.cotox.2024.100488","url":null,"abstract":"<div><p>Recent developments of novel single-cell analysis techniques have rapidly advanced the fields of immunotoxicology and immunometabolism. Single-cell analyses enable the characterization of immune cells, unraveling heterogeneity, and population dynamics in response to cellular perturbations, including toxicant insults and changes in cellular metabolism. This review provides an overview of current technologies and recent discoveries, illustrating an emerging role of single-cell analyses in the field of immunotoxicology and immunometabolism. Various single-cell techniques, including flow cytometry, mass cytometry, multiplexed imaging, and sequencing, together with their applications to studying immunotoxicology and immunometabolism are discussed. This review emphasizes the potential for single-cell analyses to revolutionize our understanding of immune cell heterogeneity, uncover novel cellular therapeutic targets, and pave the way for novel mechanistic insights.</p></div>","PeriodicalId":93968,"journal":{"name":"Current opinion in toxicology","volume":"39 ","pages":"Article 100488"},"PeriodicalIF":4.6,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141596855","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
Single cell multiomics systems biology for molecular toxicity 针对分子毒性的单细胞多组学系统生物学
IF 4.6
Current opinion in toxicology Pub Date : 2024-05-23 DOI: 10.1016/j.cotox.2024.100477
Graciel Diamante , Sung Min Ha , Darren Wijaya , Xia Yang
{"title":"Single cell multiomics systems biology for molecular toxicity","authors":"Graciel Diamante ,&nbsp;Sung Min Ha ,&nbsp;Darren Wijaya ,&nbsp;Xia Yang","doi":"10.1016/j.cotox.2024.100477","DOIUrl":"10.1016/j.cotox.2024.100477","url":null,"abstract":"<div><p>Exposure to environmental chemicals has been associated with increased risks for various diseases, but our understanding of their molecular targets and how they drive disease progression remains limited. Environmental toxicants can trigger a multitude of effects on the epigenome, transcriptome, proteome, and other molecular entities in individual cells and tissues. The recent advances in high throughput single cell multiomics technologies are enabling a deeper understanding of these complex molecular alterations and interactions underlying exposure mode of action at a single cell resolution. Accompanying the increased capacity to generate single cell multiomics data is the rapid advancement in computational tools for data analysis of individual omics layers, multimodal data integration and molecular network modeling. Recent applications of single cell omics technologies and analytical methods have enabled the elucidation of cell type specific genes and pathways affected by various environmental exposures. Further adoption of advanced single cell multiomics methodologies in the molecular toxicology field promises a more comprehensive understanding of the regulatory networks within and between cell types underlying the perturbations in physiological systems and disease risks posed by environmental toxicants.</p></div>","PeriodicalId":93968,"journal":{"name":"Current opinion in toxicology","volume":"39 ","pages":"Article 100477"},"PeriodicalIF":4.6,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2468202024000196/pdfft?md5=0b57f1b89e2ea33581a8cfdd65aac38f&pid=1-s2.0-S2468202024000196-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141131202","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
Network medicine and artificial intelligence in cancer precision therapy: Path to prevent drug-induced toxic side effect 网络医学和人工智能在癌症精准治疗中的应用:预防药物毒副作用的途径
IF 4.6
Current opinion in toxicology Pub Date : 2024-04-18 DOI: 10.1016/j.cotox.2024.100476
Asim Bikas Das
{"title":"Network medicine and artificial intelligence in cancer precision therapy: Path to prevent drug-induced toxic side effect","authors":"Asim Bikas Das","doi":"10.1016/j.cotox.2024.100476","DOIUrl":"10.1016/j.cotox.2024.100476","url":null,"abstract":"<div><p>The discovery of cancer-specific therapeutics and determining their sensitivity is a critical step in preventing drug-induced toxicity. Drug sensitivity varies among cancer patients due to intra-tumor heterogeneity. It demands rational drug design, target identification, and novel treatment modalities. This review discusses the use of network medicine in targeted therapy and AI-based drug response prediction for personalized cancer therapy. The network medicine is successfully implemented to integrate multiple omics data to identify the disease modules in cancer. The cancer-specific disease modules are utilized for drug screening and targeted therapy. Additionally, the model developed using AI, and genomic data shows superior performance and also reveals relationships between the genomic variability of cancer and their response to drugs. There is significant promise for network medicine and AI to handle large-scale omics data, leading to the identification of a novel cancer-specific treatment strategy and improved patient care.</p></div>","PeriodicalId":93968,"journal":{"name":"Current opinion in toxicology","volume":"38 ","pages":"Article 100476"},"PeriodicalIF":4.6,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140769633","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
Unique challenges and best practices for single cell transcriptomic analysis in toxicology 毒理学中单细胞转录组分析的独特挑战和最佳实践
IF 4.6
Current opinion in toxicology Pub Date : 2024-03-29 DOI: 10.1016/j.cotox.2024.100475
David Filipovic , Omar Kana , Daniel Marri , Sudin Bhattacharya
{"title":"Unique challenges and best practices for single cell transcriptomic analysis in toxicology","authors":"David Filipovic ,&nbsp;Omar Kana ,&nbsp;Daniel Marri ,&nbsp;Sudin Bhattacharya","doi":"10.1016/j.cotox.2024.100475","DOIUrl":"10.1016/j.cotox.2024.100475","url":null,"abstract":"<div><p>The application and analysis of single-cell transcriptomics in toxicology presents unique challenges. These include identifying cell sub-populations sensitive to perturbation; interpreting dynamic shifts in cell type proportions in response to chemical exposures; and performing differential expression analysis in dose–response studies spanning multiple treatment conditions. This review examines these challenges while presenting best practices for critical single cell analysis tasks. This covers areas such as cell type identification; analysis of differential cell type abundance; differential gene expression; and cellular trajectories. Towards enhancing the use of single-cell transcriptomics in toxicology, this review aims to address key challenges in this field and offer practical analytical solutions. Overall, applying appropriate bioinformatic techniques to single-cell transcriptomic data can yield valuable insights into cellular responses to toxic exposures.</p></div>","PeriodicalId":93968,"journal":{"name":"Current opinion in toxicology","volume":"38 ","pages":"Article 100475"},"PeriodicalIF":4.6,"publicationDate":"2024-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140405743","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
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