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Toxicogenomics

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https://www.readbyqxmd.com/read/29453537/toxicogenomics-a-new-paradigm-for-nanotoxicity-evaluation
#1
Sourabh Dwivedi, Quaiser Saquib, Bilal Ahmad, Sabiha M Ansari, Ameer Azam, Javed Musarrat
The wider applications of nanoparticles (NPs) has evoked a world-wide concern due to their possible risk of toxicity in humans and other organisms. Aggregation and accumulation of NPs into cell leads to their interaction with biological macromolecules including proteins, nucleic acids and cellular organelles, which eventually induce toxicological effects. Application of toxicogenomics to investigate molecular pathway-based toxicological consequences has opened new vistas in nanotoxicology research. Indeed, genomic approaches appeared as a new paradigm in terms of providing information at molecular levels and have been proven to be as a powerful tool for identification and quantification of global shifts in gene expression...
2018: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29445054/comparison-of-drug-metabolism-and-its-related-hepatotoxic-effects-in-heparg-cryopreserved-human-hepatocytes-and-hepg2-cell-cultures
#2
Yuichi Yokoyama, Yoshifumi Sasaki, Natsuko Terasaki, Taku Kawataki, Koji Takekawa, Yumiko Iwase, Toshinobu Shimizu, Seigo Sanoh, Shigeru Ohta
Differentiated HepaRG cells maintain liver-specific functions such as drug-metabolizing enzymes. In this study, the feasibility of HepaRG cells as a human hepatocyte model for in vitro toxicity assessment was examined using selected hepatotoxic compounds. First, basal drug-metabolizing enzyme activities (CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A4, uridine 5'-diphospho-glucuronosyltransferase [UGT], and sulfotransferases [SULT]) were measured in HepaRG, human hepatocytes, and HepG2 cells. Enzyme activities in differentiated HepaRG cells were comparable to those in human hepatocytes and much higher than those in HepG2 cells, except for SULT activity...
February 14, 2018: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/29434983/analysis-of-expression-profile-data-identifies-key-genes-and-pathways-in-hepatocellular-carcinoma
#3
Xuwei Jiang, Yuqing Hao
The aims of the present study were to identify key genes and pathways associated with hepatocellular carcinoma (HCC) progression and predict compounds potentially associated with this type of carcinogenesis. The gene expression profile data of the GSE49515 dataset was obtained from the Gene Expression Omnibus database. The limma software package was used to identify the differentially expressed genes (DEGs). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed using the Biological Networks Gene Ontology tool and the Database for Annotation, Visualization and Integrated Discovery, respectively...
February 2018: Oncology Letters
https://www.readbyqxmd.com/read/29423630/yeast-based-genotoxicity-tests-for-assessing-dna-alterations-and-dna-stress-responses-a-40-year-overview
#4
REVIEW
Toshihiko Eki
By damaging DNA molecules, genotoxicants cause genetic mutations and also increase human susceptibility to cancers and genetic diseases. Over the past four decades, several assays have been developed in the budding yeast Saccharomyces cerevisiae to screen potential genotoxic substances and provide alternatives to animal-based genotoxicity tests. These yeast-based genotoxicity tests are either DNA alteration-based or DNA stress-response reporter-based. The former, which came first, were developed from the genetic studies conducted on various types of DNA alterations in yeast cells...
February 8, 2018: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29411056/a-novel-genotoxin-specific-qpcr-array-based-on-the-metabolically-competent-human-heparg%C3%A2-cell-line-as-a-rapid-and-reliable-tool-for-improved-in-vitro-hazard-assessment
#5
Gamze Ates, Birgit Mertens, Anja Heymans, Luc Verschaeve, Dimiter Milushev, Philippe Vanparys, Nancy H C Roosens, Sigrid C J De Keersmaecker, Vera Rogiers, Tatyana Y Doktorova
Although the value of the regulatory accepted batteries for in vitro genotoxicity testing is recognized, they result in a high number of false positives. This has a major impact on society and industries developing novel compounds for pharmaceutical, chemical, and consumer products, as afflicted compounds have to be (prematurely) abandoned or further tested on animals. Using the metabolically competent human HepaRG™ cell line and toxicogenomics approaches, we have developed an upgraded, innovative, and proprietary gene classifier...
February 6, 2018: Archives of Toxicology
https://www.readbyqxmd.com/read/29408670/toxicogenomics-applied-to-in-vitro-cell-transformation-assay-reveals-mechanisms-of-early-response-to-cadmium
#6
Giulia Callegaro, Matilde Forcella, Pasquale Melchioretto, Annalisa Frattini, Laura Gribaldo, Paola Fusi, Marco Fabbri, Chiara Urani
Cadmium is a well recognized carcinogen, primarily released into the environment by anthropogenic activities. In the effort to understand the early events responsible for cadmium carcinogenesis, we have used an in vitro biological system (the Cell Transformation Assay, CTA), that has been shown to closely model some key stages of the conversion of normal cells into malignant ones. Cadmium-triggered early responses in CTA were analysed through microarray-based toxicogenomics. Metallothioneins represent the earliest cell response, together with Slc30a1 encoding for a ZnT-1 zinc exporter...
January 31, 2018: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29408497/a-transcriptomic-analysis-of-turmeric-curcumin-represses-the-expression-of-cholesterol-biosynthetic-genes-and-synergizes-with-simvastatin
#7
Linda Saxe Einbond, Fabiana Manservisi, Hsan-Au Wu, Michael Balick, Victoria Antonetti, Andrea Vornoli, Ilaria Menghetti, Fiorella Belpoggi, Stephen Redenti, Alan Roter
The spice turmeric (Curcuma longa L.) has a long history of use as an anti-inflammatory agent. The active component curcumin induces a variety of diverse biological effects and forms a series of degradation and metabolic products in vivo. Our hypothesis is that the field of toxicogenomics provides tools that can be used to characterize the mode of action and toxicity of turmeric components and to predict turmeric-drug interactions. Male Sprague-Dawley rats were treated for 4 days with turmeric root containing about 3% curcumin (comparable to what people consume in the fresh or dried root) or a fraction of turmeric enriched for curcumin (∼74%) and liver tissue collected for gene expression analysis...
February 2, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29402904/in-vitro-rna-seq-based-toxicogenomics-assessment-shows-reduced-biological-effect-of-tobacco-heating-products-when-compared-to-cigarette-smoke
#8
Linsey E Haswell, Sarah Corke, Ivan Verrastro, Andrew Baxter, Anisha Banerjee, Jason Adamson, Tomasz Jaunky, Christopher Proctor, Marianna Gaça, Emmanuel Minet
The battery of regulatory tests used to evaluate the risk of novel tobacco products such as heated tobacco products (THPs) presents some limitations including a bias towards the apical endpoint tested, and limited information on the mode of action. This is driving a paradigm shift to more holistic systems biology approaches. In this study, we used RNA-sequencing to compare the transcriptomic perturbations following acute exposure of a 3D airway tissue to the aerosols from two commercial THPs and a reference 3R4F cigarette...
February 5, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29393436/identification-of-methylated-genes-and-mirna-signatures-in-nasopharyngeal-carcinoma-by-bioinformatics-analysis
#9
Yingli Wang, Qun Zhao, Na Lan, Shuqian Wang
Nasopharyngeal carcinoma (NPC) is prevalent in several regions, including. Southern China and Southeast Asia, with high mortality. The present study aimed to explore the epigenetic mechanisms of NPC and to provide novel biomarkers for prognosis. Two methylation data sets (GSE52068 and GSE62336) were downloaded from the Gene Expression Omnibus database. Following pretreatment of the raw data, differentially methylated regions (DMRs) and differentially methylated CpG islands (DMCs) were identified between the NPC samples and normal tissue controls using COHCAP software...
January 25, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29385404/toxsign-a-cross-species-repository-for-toxicogenomic-signatures
#10
Thomas A Darde, Pierre Gaudriault, Rémi Beranger, Clément Lancien, Annaëlle Caillarec-Joly, Olivier Sallou, Nathalie Bonvallot, Cécile Chevrier, Séverine Mazaud-Guittot, Bernard Jégou, Olivier Collin, Emmanuelle Becker, Antoine D Rolland, Frédéric Chalmel
Motivation: At the same time that toxicologists express increasing concern about reproducibility in this field, the development of dedicated databases has already smoothed the path toward improving the storage and exchange of raw toxicogenomic data. Nevertheless, none provides access to analyzed and interpreted data as originally reported in scientific publications. Given the increasing demand for access to this information, we developed TOXsIgN, a repository for TOXicogenomic sIgNatures...
January 27, 2018: Bioinformatics
https://www.readbyqxmd.com/read/29369008/computational-screening-ensemble-docking-and-pharmacophore-analysis-of-potential-gefitinib-analogues-against-epidermal-growth-factor-receptor
#11
Uma Devi Bommu, Kranthi Kumar Konidala, Rishika Pamanji, Suneetha Yeguvapalli
The observable mutated isoforms of epidermal growth factor receptor (EGFR) are important considerable therapeutic benchmarks in moderating the non-small cell lung cancer (NSCLC). Recently, quinazoline-based ATP competitive inhibitors have been developed against the EGFR; however, these imply the mutation probabilities, which contribute to the discovery of high probable novel inhibitors for EGFR mutants. Therefore, SAR-based bioactivity analysis, molecular docking and computational toxicogenomics approaches were performed to identify and evaluate new analogs of gefitinib against the ligand-binding domain of the EGFR double-mutated model...
February 2018: Journal of Receptor and Signal Transduction Research
https://www.readbyqxmd.com/read/29351546/accessing-an-expanded-exposure-science-module-at-the-comparative-toxicogenomics-database
#12
Cynthia J Grondin, Allan Peter Davis, Thomas C Wiegers, Jolene A Wiegers, Carolyn J Mattingly
The Comparative Toxicogenomics Database (CTD; http://ctdbase.org) is a free resource that provides manually curated information on chemical, gene, phenotype, and disease relationships to advance understanding of the effect of environmental exposures on human health. Four core content areas are independently curated: chemical-gene interactions, chemical-disease and gene-disease associations, chemical-phenotype interactions, and environmental exposure data (e.g., effects of chemical stressors on humans). Since releasing exposure data in 2015, we have vastly increased our coverage of chemicals and disease/phenotype outcomes; greatly expanded access to exposure content; added search capability by stressors, cohorts, population demographics, and measured outcomes; and created user-specified displays of content...
January 18, 2018: Environmental Health Perspectives
https://www.readbyqxmd.com/read/29337256/microrna-regulatory-networks-reflective-of-polyhexamethylene-guanidine-phosphate-induced-fibrosis-in-a549-human-alveolar-adenocarcinoma-cells
#13
Da Young Shin, Mi Ho Jeong, In Jae Bang, Ha Ryong Kim, Kyu Hyuck Chung
Polyhexamethylene guanidine phosphate (PHMG-phosphate), an active component of humidifier disinfectant, is suspected to be a major cause of pulmonary fibrosis. Fibrosis, induced by recurrent epithelial damage, is significantly affected by epigenetic regulation, including microRNAs (miRNAs). The aim of this study was to investigate the fibrogenic mechanisms of PHMG-phosphate through the profiling of miRNAs and their target genes. A549 cells were treated with 0.75 μg/mL PHMG-phosphate for 24 and 48 h and miRNA microarray expression analysis was conducted...
January 11, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29244179/sedaxane-use-of-nuclear-receptor-transactivation-assays-toxicogenomics-and-toxicokinetics-as-part-of-a-mode-of-action-framework-for-rodent-liver-tumors
#14
Richard C Peffer, David E Cowie, Richard A Currie, Daniel J Minnema
Experimental data demonstrate a mode of action (MOA) for liver tumors in male rats and mice treated with sedaxane that starts with activation of CAR, followed by altered expression of CAR-responsive genes, increased cell proliferation, and eventually clonal expansion of preneoplastic cells, leading to the development of altered foci and tumors. This MOA is non-relevant to human risk assessments. Methods and results in the MOA work for sedaxane illustrate promising directions that future MOA studies may be able to employ, in the spirit of "Tox21" and reduction of in vivo animal use: 1) currently available in vitro CAR and PXR reporter assays demonstrated that sedaxane is a direct CAR activator in mice and rats, and a weak PXR activator in rats; 2) mouse liver microarray results compared to a published CAR biomarker signature (based on 83 genes) showed a clear, statistical match, and a lack of correlation to similar biomarker signatures for AhR, PPARα, and STAT5B; 3) Ki67 immunohistochemistry and zonal image analysis showed significant increases in this marker of cell proliferation in mouse liver, without the need to dose a DNA labelling agent; and 4) toxicokinetic analysis of Cmax levels of sedaxane in blood showed a marked species difference between mice and rats that helps to explain differences in sensitivity to sedaxane...
December 13, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29224359/a-reduced-transcriptome-approach-to-assess-environmental-toxicants-using-zebrafish-embryo-test
#15
Pingping Wang, Pu Xia, Jianghua Yang, Zhihao Wang, Ying Peng, Wei Shi, Daniel L Villeneuve, Hongxia Yu, Xiaowei Zhang
Omics approaches can monitor responses and alterations of biological pathways at genome-scale, which are useful to predict potential adverse effects by environmental toxicants. However, high throughput application of transcriptomics in chemical assessment is limited due to the high cost and lack of "standardized" toxicogenomic methods. Here, a reduced zebrafish transcriptome (RZT) approach was developed to represent the whole transcriptome and to profile bioactivity of chemical and environmental mixtures in zebrafish embryo...
December 11, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/29221149/prediction-on-the-risk-population-of-idiosyncratic-adverse-reactions-based-on-molecular-docking-with-mutant-proteins
#16
Hongbo Xie, Diheng Zeng, Xiujie Chen, Diwei Huo, Lei Liu, Denan Zhang, Qing Jin, Kehui Ke, Ming Hu
Idiosyncratic adverse drug reactions are drug reactions that occur rarely and unpredictably among the population. These reactions often occur after a drug is marketed, which means that they are strongly related to the genotype of the population. The prediction of such adverse reactions is a major challenge because of the lack of appropriate test models during the drug development process. In this study, we chose withdrawn drugs because the reasons why they were withdrawn and from which countries or regions is easily obtained...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29203277/transcriptomic-study-of-the-toxic-mechanism-triggered-by-beauvericin-in-jurkat-cells
#17
L Escrivá, D Jennen, F Caiment, L Manyes
Beauvericin (BEA), an ionophoric cyclic hexadepsipeptide mycotoxin, is able to increase oxidative stress by altering membrane ion permeability and uncoupling oxidative phosphorylation. A toxicogenomic study was performed to investigate gene expression changes triggered by BEA exposure (1.5, 3 and 5μM; 24h) in Jurkat cells through RNA-sequencing and differential gene expression analysis. Perturbed gene expression was observed in a concentration dependent manner, with 43 differentially expressed genes (DEGs) overlapped in the three studied concentrations...
December 1, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/29179987/identification-of-genes-involved-in-the-four-stages-of-colorectal-cancer-gene-expression-profiling
#18
Guiling Shi, Yijia Wang, Chunze Zhang, Zhenying Zhao, Xiuying Sun, Shiwu Zhang, Jinling Fan, Cunxia Zhou, Jihong Zhang, Huijuan Zhang, Jun Liu
BACKGROUND: Colorectal cancer (CRC) is a common cancer with high morbidity and mortality. However, its molecular mechanism is not clear, nor the genes related to CRC stages. METHODS: Gene expression data in CRC and healthy colorectal tissues were obtained from gene expression omnibus. Limma package was used to identify the differentially expressed genes (DEGs) between control and CRC (stage I, II, III, and IV), obtaining 4 DEG sets. VennPlex was utilized to find all DEGs and intersection DEGs...
November 24, 2017: Molecular and Cellular Probes
https://www.readbyqxmd.com/read/29170679/frontiers-in-toxicogenomics-in-the-twenty-first-century-the-grand-challenge-to-understand-how-the-genome-and-epigenome-interact-with-the-toxic-environment-at-the-single-cell-whole-organism-and-multi-generational-level
#19
EDITORIAL
https://www.readbyqxmd.com/read/29163636/a-pipeline-for-high-throughput-concentration-response-modeling-of-gene-expression-for-toxicogenomics
#20
John S House, Fabian A Grimm, Dereje D Jima, Yi-Hui Zhou, Ivan Rusyn, Fred A Wright
Cell-based assays are an attractive option to measure gene expression response to exposure, but the cost of whole-transcriptome RNA sequencing has been a barrier to the use of gene expression profiling for in vitro toxicity screening. In addition, standard RNA sequencing adds variability due to variable transcript length and amplification. Targeted probe-sequencing technologies such as TempO-Seq, with transcriptomic representation that can vary from hundreds of genes to the entire transcriptome, may reduce some components of variation...
2017: Frontiers in Genetics
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