The Experts below are selected from a list of 285 Experts worldwide ranked by ideXlab platform
Kenneth M.y. Leung - One of the best experts on this subject based on the ideXlab platform.
-
Thermal extremes can intensify Chemical Toxicity to freshwater organisms and hence exacerbate their impact to the biological community
Chemosphere, 2019Co-Authors: Zhen Wang, Gilbert C. S. Lui, G. Allen Burton, Kenneth M.y. LeungAbstract:Temperature in freshwater ecosystems fluctuates daily, seasonally and yearly. Climate change further induces temperature variations. In this study, we hypothesise that water temperatures, in particular thermal extremes, can significantly influence Chemical Toxicity to ectothermic organisms. Although temperature-dependent Chemical Toxicity (TDCT) is a classic research area in ecotoxicology, a unified model for predicting TDCT for freshwater species is yet to be developed. This study aimed to address this challenging issue through a meta-analysis by comparing acute Toxicity endpoints (i.e. median lethal or effective concentration data; LC50 or EC50) of 13 Chemicals for various freshwater species generated from different temperatures. Our results suggest that in most cases, freshwater species exhibit the highest tolerance towards Chemicals at their physical optimal temperature (Topt), and Chemical Toxicity exacerbates when temperature is higher or lower than Topt (i.e. inverted V-shaped model between temperature and LC50 or EC50). Such observations are further supported by temperature-dependent hazardous concentration 10% (HC10) values derived from species sensitivity distributions constructed using Toxicity data generated at different temperatures. A unified mathematical model was also developed to describe the inverted V-shape relationship between temperature and HC10 derivations. Overall, considering the natural variations of freshwater temperatures, the inverted V-shaped TDCT model can be readily applied to derive water quality guidelines and assess ecological risks of Chemical contaminants.
-
Can we predict temperature-dependent Chemical Toxicity to marine organisms and set appropriate water quality guidelines for protecting marine ecosystems under different thermal scenarios?
Marine Pollution Bulletin, 2014Co-Authors: Guang-jie Zhou, Zhen Wang, Edward Tak Chuen Lau, Kenneth M.y. LeungAbstract:Temperature changes due to climate change and seasonal fluctuation can have profound implications on Chemical Toxicity to marine organisms. Through a comprehensive meta-analysis by comparing median lethal or effect concentration data of six Chemicals for various saltwater species obtained at different temperatures, we reveal that the Chemical Toxicity generally follows two different models: (1) it increases with increasing temperature and (2) it is the lowest at an optimal temperature and increases with increasing or decreasing temperature from the optimal temperature. Such observations are further supported by temperature-dependent hazardous concentration 10% (HC10) values derived from species sensitivity distributions which are constructed using the acute Toxicity data generated at different temperatures. Considering these two models and natural variations of seawater temperature, we can scientifically assess whether applying an assessment factor (e.g. 10) to modify water quality guidelines of the Chemicals can adequately protect marine ecosystems in tropics, subtropics and temperate regions, respectively.
Daojing Wang - One of the best experts on this subject based on the ideXlab platform.
-
Omics-Based Platform for Studying Chemical Toxicity Using Stem Cells
Journal of proteome research, 2017Co-Authors: Yan Han, Jinghua Zhao, Ruili Huang, Menghang Xia, Daojing WangAbstract:The new strategy for Chemical Toxicity testing and modeling is to use in vitro human cell-based assays in conjunction with quantitative high-throughput screening (qHTS) technology, to identify molecular mechanisms and predict in vivo responses. Stem cells are more physiologically relevant than immortalized cell lines because of their unique proliferation and differentiation potentials. We established a robust two stem cells-two lineages assay system, encompassing human mesenchymal stem cells (hMSCs) along osteogenesis and human induced pluripotent stem cells (hiPSCs) along hepatogenesis. We performed qHTS phenotypic screening of LOPAC1280 and identified 38 preliminary hits for hMSCs. This was followed by validation of a selected number of hits and determination of their IC50 values and mechanistic studies of idarubicin and cantharidin treatments using proteomics and bioinformatics. In general, hiPSCs were more sensitive than hMSCs to Chemicals, and differentiated progenies were less sensitive than their p...
-
Omics-Based Platform for Studying Chemical Toxicity Using Stem Cells
2017Co-Authors: Yan Han, Jinghua Zhao, Ruili Huang, Menghang Xia, Daojing WangAbstract:The new strategy for Chemical Toxicity testing and modeling is to use in vitro human cell-based assays in conjunction with quantitative high-throughput screening (qHTS) technology, to identify molecular mechanisms and predict in vivo responses. Stem cells are more physiologically relevant than immortalized cell lines because of their unique proliferation and differentiation potentials. We established a robust two stem cells-two lineages assay system, encompassing human mesenchymal stem cells (hMSCs) along osteogenesis and human induced pluripotent stem cells (hiPSCs) along hepatogenesis. We performed qHTS phenotypic screening of LOPAC1280 and identified 38 preliminary hits for hMSCs. This was followed by validation of a selected number of hits and determination of their IC50 values and mechanistic studies of idarubicin and cantharidin treatments using proteomics and bioinformatics. In general, hiPSCs were more sensitive than hMSCs to Chemicals, and differentiated progenies were less sensitive than their progenitors. We showed that Chemical Toxicity depends on both stem cell types and their differentiation stages. Proteomics identified and quantified over 3000 proteins for both stem cells. Bioinformatics identified apoptosis and G2/M as the top pathways conferring idarubicin Toxicity. Our Omics-based assays of stem cells provide mechanistic insights into Chemical Toxicity and may help prioritize Chemicals for in-depth toxicological evaluations
Wataru Fujibuchi - One of the best experts on this subject based on the ideXlab platform.
-
Stem Cell-Based Methods to Predict Developmental Chemical Toxicity.
Methods in molecular biology (Clifton N.J.), 2018Co-Authors: Hiroki Takahashi, Xian-yang Qin, Hideko Sone, Wataru FujibuchiAbstract:Human pluripotent stem cells such as embryonic stem (ES) and induced pluripotent stem (iPS) cells, combined with sophisticated bioinformatics methods, are powerful tools to predict developmental Chemical Toxicity. Because cell differentiation is not necessary, these cells can facilitate cost-effective assays, thus providing a practical system for the Toxicity assessment of various types of Chemicals. Here we describe how to apply machine learning techniques to different types of data, such as qRT-PCRs, gene networks, and molecular descriptors, for toxic Chemicals, as well as how to integrate these data to predict Toxicity categories. Interestingly, our results using 20 Chemical data for neurotoxins (NTs), genotoxic carcinogens (GCs), and nongenotoxic carcinogens (NGCs) demonstrated that the highest and most robust prediction performance was obtained by using gene networks as the input. We also observed that qRT-PCR and molecular descriptors tend to contribute to specific Toxicity categories.
-
High-performance gene expression module analysis tool and its application to Chemical Toxicity data.
Methods in molecular biology (Clifton N.J.), 2009Co-Authors: Wataru Fujibuchi, Hyeryung Kim, Yoshifumi Okada, Takeaki Taniguchi, Hideko SoneAbstract:Gene clustering is one of the main themes of data mining approaches in bioinformatics. Although it has the power to analyze gene function, interpretation of the results becomes increasingly difficult when the number of experiments (samples) exceeds hundreds or more. A new type of clustering called "biclustering," where genes and experiments are coclustered in a large-scale of gene expression data, has been extensively studied in the last decade. We have developed "SAMURAI," an original program that detects all the biclusters or "gene modules" whose genes have similar expression patterns to query profile using the ultrafast data mining algorithm called Linear-time Closed itemset Miner (LCM). Using Chemical Toxicity dataset from J&J rat liver experiments, we compiled an exhaustive dictionary of gene modules by searching datasets of gene modules with each Chemical exposure experiment as query. Through the module analysis, we found that our program can detect up/down-regulated gene sets that significantly represent particular GO functions or KEGG pathways, thereby unraveling reactions and mechanisms common to different toxicoChemical treatments of hepatocytes.
Yan Han - One of the best experts on this subject based on the ideXlab platform.
-
Omics-Based Platform for Studying Chemical Toxicity Using Stem Cells
Journal of proteome research, 2017Co-Authors: Yan Han, Jinghua Zhao, Ruili Huang, Menghang Xia, Daojing WangAbstract:The new strategy for Chemical Toxicity testing and modeling is to use in vitro human cell-based assays in conjunction with quantitative high-throughput screening (qHTS) technology, to identify molecular mechanisms and predict in vivo responses. Stem cells are more physiologically relevant than immortalized cell lines because of their unique proliferation and differentiation potentials. We established a robust two stem cells-two lineages assay system, encompassing human mesenchymal stem cells (hMSCs) along osteogenesis and human induced pluripotent stem cells (hiPSCs) along hepatogenesis. We performed qHTS phenotypic screening of LOPAC1280 and identified 38 preliminary hits for hMSCs. This was followed by validation of a selected number of hits and determination of their IC50 values and mechanistic studies of idarubicin and cantharidin treatments using proteomics and bioinformatics. In general, hiPSCs were more sensitive than hMSCs to Chemicals, and differentiated progenies were less sensitive than their p...
-
Omics-Based Platform for Studying Chemical Toxicity Using Stem Cells
2017Co-Authors: Yan Han, Jinghua Zhao, Ruili Huang, Menghang Xia, Daojing WangAbstract:The new strategy for Chemical Toxicity testing and modeling is to use in vitro human cell-based assays in conjunction with quantitative high-throughput screening (qHTS) technology, to identify molecular mechanisms and predict in vivo responses. Stem cells are more physiologically relevant than immortalized cell lines because of their unique proliferation and differentiation potentials. We established a robust two stem cells-two lineages assay system, encompassing human mesenchymal stem cells (hMSCs) along osteogenesis and human induced pluripotent stem cells (hiPSCs) along hepatogenesis. We performed qHTS phenotypic screening of LOPAC1280 and identified 38 preliminary hits for hMSCs. This was followed by validation of a selected number of hits and determination of their IC50 values and mechanistic studies of idarubicin and cantharidin treatments using proteomics and bioinformatics. In general, hiPSCs were more sensitive than hMSCs to Chemicals, and differentiated progenies were less sensitive than their progenitors. We showed that Chemical Toxicity depends on both stem cell types and their differentiation stages. Proteomics identified and quantified over 3000 proteins for both stem cells. Bioinformatics identified apoptosis and G2/M as the top pathways conferring idarubicin Toxicity. Our Omics-based assays of stem cells provide mechanistic insights into Chemical Toxicity and may help prioritize Chemicals for in-depth toxicological evaluations
Zhen Wang - One of the best experts on this subject based on the ideXlab platform.
-
Thermal extremes can intensify Chemical Toxicity to freshwater organisms and hence exacerbate their impact to the biological community
Chemosphere, 2019Co-Authors: Zhen Wang, Gilbert C. S. Lui, G. Allen Burton, Kenneth M.y. LeungAbstract:Temperature in freshwater ecosystems fluctuates daily, seasonally and yearly. Climate change further induces temperature variations. In this study, we hypothesise that water temperatures, in particular thermal extremes, can significantly influence Chemical Toxicity to ectothermic organisms. Although temperature-dependent Chemical Toxicity (TDCT) is a classic research area in ecotoxicology, a unified model for predicting TDCT for freshwater species is yet to be developed. This study aimed to address this challenging issue through a meta-analysis by comparing acute Toxicity endpoints (i.e. median lethal or effective concentration data; LC50 or EC50) of 13 Chemicals for various freshwater species generated from different temperatures. Our results suggest that in most cases, freshwater species exhibit the highest tolerance towards Chemicals at their physical optimal temperature (Topt), and Chemical Toxicity exacerbates when temperature is higher or lower than Topt (i.e. inverted V-shaped model between temperature and LC50 or EC50). Such observations are further supported by temperature-dependent hazardous concentration 10% (HC10) values derived from species sensitivity distributions constructed using Toxicity data generated at different temperatures. A unified mathematical model was also developed to describe the inverted V-shape relationship between temperature and HC10 derivations. Overall, considering the natural variations of freshwater temperatures, the inverted V-shaped TDCT model can be readily applied to derive water quality guidelines and assess ecological risks of Chemical contaminants.
-
Can we predict temperature-dependent Chemical Toxicity to marine organisms and set appropriate water quality guidelines for protecting marine ecosystems under different thermal scenarios?
Marine Pollution Bulletin, 2014Co-Authors: Guang-jie Zhou, Zhen Wang, Edward Tak Chuen Lau, Kenneth M.y. LeungAbstract:Temperature changes due to climate change and seasonal fluctuation can have profound implications on Chemical Toxicity to marine organisms. Through a comprehensive meta-analysis by comparing median lethal or effect concentration data of six Chemicals for various saltwater species obtained at different temperatures, we reveal that the Chemical Toxicity generally follows two different models: (1) it increases with increasing temperature and (2) it is the lowest at an optimal temperature and increases with increasing or decreasing temperature from the optimal temperature. Such observations are further supported by temperature-dependent hazardous concentration 10% (HC10) values derived from species sensitivity distributions which are constructed using the acute Toxicity data generated at different temperatures. Considering these two models and natural variations of seawater temperature, we can scientifically assess whether applying an assessment factor (e.g. 10) to modify water quality guidelines of the Chemicals can adequately protect marine ecosystems in tropics, subtropics and temperate regions, respectively.