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Toxicogenomics

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https://www.readbyqxmd.com/read/28819918/network-analysis-of-se-and-zn-related-proteins-in-the-serum-proteomics-expression-profile-of-the-endemic-dilated-cardiomyopathy-keshan-disease
#1
Sen Wang, Yanyan Lv, Yingting Wang, Peiru Du, Wuhong Tan, Mikko J Lammi, Xiong Guo
Keshan disease (KD) is an endemic cardiomyopathy with high mortality. Selenium (Se) and zinc (Zn) deficiencies are closely related to KD. The molecular mechanism of KD pathogenesis is still unclear. There are only few studies on the interaction of trace elements and proteins associated with the pathogenesis of KD. In this study, isobaric tags for relative and absolute quantitation (iTRAQ)-coupled two-dimensional liquid chromatography tandem mass spectrometry (2DLC-MS/MS) technique analysis was used to analyze the differential expression of proteins from serum samples...
August 18, 2017: Biological Trace Element Research
https://www.readbyqxmd.com/read/28780348/integration-of-in-silico-approaches-to-determination-of-endocrine-disrupting-perfluorinated-chemicals-binding-potency-with-steroidogenic-acute-regulatory-protein
#2
K Kranthi Kumar, B Uma Devi, P Neeraja
A myriad of perfluorinated compounds (PFCs) have the ability to interfere with steroidogenic acute regulatory (StAR) protein. Consequently, PFCs breaches cholesterol biotransformation in mitochondria and cause fatal consequences in steroidogenesis however, these were poorly characterized. In the present study, we have evaluated toxic potencies, nuclear mediated probabilities and interaction profiles with StAR of PFCs using computational system biology tools. Toxicity endpoints revealed that PFCs contain high carcinogenicity, developmental toxicity, skin sensitization effects with low mutagenic activity...
August 2, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28733229/estrogen-signaling-through-both-membrane-and-nuclear-receptors-in-the-liver-of-fathead-minnow
#3
Natàlia Garcia-Reyero, B Sumith Jayasinghe, Kevin J Kroll, Tara Sabo-Attwood, Nancy D Denslow
Estradiol is a potent sex steroid hormone that controls reproduction and other cellular pathways in fish. It is known to regulate important proteins such as vitellogenin, the egg yolk precursor protein, and zona radiata proteins that form the eggshell for fish eggs. These proteins are made in the liver and transported out into the blood from where they are taken up into the ovary during oogenesis. Estradiol can exert its influence directly through soluble nuclear receptors (there are three in fish) or indirectly through membrane receptors and a phosphorylation cascade...
July 18, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28732062/a-drosophila-model-for-toxicogenomics-genetic-variation-in-susceptibility-to-heavy-metal-exposure
#4
Shanshan Zhou, Sarah E Luoma, Genevieve E St Armour, Esha Thakkar, Trudy F C Mackay, Robert R H Anholt
The genetic factors that give rise to variation in susceptibility to environmental toxins remain largely unexplored. Studies on genetic variation in susceptibility to environmental toxins are challenging in human populations, due to the variety of clinical symptoms and difficulty in determining which symptoms causally result from toxic exposure; uncontrolled environments, often with exposure to multiple toxicants; and difficulty in relating phenotypic effect size to toxic dose, especially when symptoms become manifest with a substantial time lag...
July 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28717108/isoflurane-is-a-suitable-alternative-to-ether-for-anesthetizing-rats-prior-to-euthanasia-for-gene-expression-analysis
#5
Noriyuki Nakatsu, Yoshinobu Igarashi, Taiki Aoshi, Isao Hamaguchi, Masumichi Saito, Takuo Mizukami, Haruka Momose, Ken J Ishii, Hiroshi Yamada
Diethyl ether (ether) had been widely used in Japan for anesthesia, despite its explosive properties and toxicity to both humans and animals. We also had used ether as an anesthetic for euthanizing rats for research in the Toxicogenomics Project (TGP). Because the use of ether for these purposes will likely cease, it is required to select an alternative anesthetic which is validated for consistency with existing TGP data acquired under ether anesthesia. We therefore compared two alternative anesthetic candidates, isoflurane and pentobarbital, with ether in terms of hematological findings, serum biochemical parameters, and gene expressions...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28717101/mechanism-based-risk-assessment-strategy-for-drug-induced-cholestasis-using-the-transcriptional-benchmark-dose-derived-by-toxicogenomics
#6
Taisuke Kawamoto, Yuichi Ito, Osamu Morita, Hiroshi Honda
Cholestasis is one of the major causes of drug-induced liver injury (DILI), which can result in withdrawal of approved drugs from the market. Early identification of cholestatic drugs is difficult due to the complex mechanisms involved. In order to develop a strategy for mechanism-based risk assessment of cholestatic drugs, we analyzed gene expression data obtained from the livers of rats that had been orally administered with 12 known cholestatic compounds repeatedly for 28 days at three dose levels. Qualitative analyses were performed using two statistical approaches (hierarchical clustering and principle component analysis), in addition to pathway analysis...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28716510/evaluation-of-in-vivo-and-in-vitro-models-of-toxicity-by-comparison-of-toxicogenomics-data-with-the-literature
#7
Katerina Taškova, Jean-Fred Fontaine, Ralf Mrowka, Miguel A Andrade-Navarro
Toxicity affecting humans is studied by observing the effects of chemical substances in animal organisms (in vivo) or in animal and human cultivated cell lines (in vitro). Toxicogenomics studies collect gene expression profiles and histopathology assessment data for hundreds of drugs and pollutants in standardized experimental designs using different model systems. These data are an invaluable source for analyzing genome-wide drug response in biological systems. However, a problem remains that is how to evaluate the suitability of heterogeneous in vitro and in vivo systems to model the many different aspects of human toxicity...
July 14, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28714573/assessment-of-the-dna-damaging-potential-of-environmental-chemicals-using-a-quantitative-high-throughput-screening-approach-to-measure-p53-activation
#8
Kristine L Witt, Jui-Hua Hsieh, Stephanie L Smith-Roe, Menghang Xia, Ruili Huang, Jinghua Zhao, Scott S Auerbach, Junguk Hur, Raymond R Tice
Genotoxicity potential is a critical component of any comprehensive toxicological profile. Compounds that induce DNA or chromosomal damage often activate p53, a transcription factor essential to cell cycle regulation. Thus, within the US Tox21 Program, we screened a library of ∼10,000 (∼8,300 unique) environmental compounds and drugs for activation of the p53-signaling pathway using a quantitative high-throughput screening assay employing HCT-116 cells (p53(+/+) ) containing a stably integrated β-lactamase reporter gene under control of the p53 response element (p53RE)...
August 2017: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/28673184/toxicogenomics-of-iron-oxide-nanoparticles-in-the-nematode-c-elegans
#9
Laura Gonzalez-Moragas, Si-Ming Yu, Núria Benseny-Cases, Stephen Stürzenbaum, Anna Roig, Anna Laromaine
We present a mechanistic study of the effect of iron oxide nanoparticles (SPIONs) in Caenorhabditis elegans combining a genome-wide analysis with the investigation of specific molecular markers frequently linked to nanotoxicity. The effects of two different coatings were explored: citrate, an anionic stabilizer, and bovine serum albumin, as a pre-formed protein corona. The transcriptomic study identified differentially expressed genes following an exposure to SPIONs. The expression of genes involved in oxidative stress, metal detoxification response, endocytosis, intestinal integrity and iron homeostasis was quantitatively evaluated...
July 4, 2017: Nanotoxicology
https://www.readbyqxmd.com/read/28671182/a-transcriptomics-data-driven-gene-space-accurately-predicts-liver-cytopathology-and-drug-induced-liver-injury
#10
Pekka Kohonen, Juuso A Parkkinen, Egon L Willighagen, Rebecca Ceder, Krister Wennerberg, Samuel Kaski, Roland C Grafström
Predicting unanticipated harmful effects of chemicals and drug molecules is a difficult and costly task. Here we utilize a 'big data compacting and data fusion'-concept to capture diverse adverse outcomes on cellular and organismal levels. The approach generates from transcriptomics data set a 'predictive toxicogenomics space' (PTGS) tool composed of 1,331 genes distributed over 14 overlapping cytotoxicity-related gene space components. Involving ∼2.5 × 10(8) data points and 1,300 compounds to construct and validate the PTGS, the tool serves to: explain dose-dependent cytotoxicity effects, provide a virtual cytotoxicity probability estimate intrinsic to omics data, predict chemically-induced pathological states in liver resulting from repeated dosing of rats, and furthermore, predict human drug-induced liver injury (DILI) from hepatocyte experiments...
July 3, 2017: Nature Communications
https://www.readbyqxmd.com/read/28666766/toxicogenomic-responses-of-human-alveolar-epithelial-cells-to-tungsten-boride-nanoparticles
#11
Hasan Türkez, Mehmet Enes Arslan, Erdal Sönmez, Abdulgani Tatar, Metin Açikyildiz, Fatime Geyikoğlu
During the recent years, microarray analysis of gene expression has become an inevitable tool for exploring toxicity of drugs and other chemicals on biological systems. Therefore, toxicogenomics is considered as a fruitful area for searching cellular pathways and mechanisms including cancer, immunological diseases, environmental responses, gene-gene interactions and chemical toxicity. In this work, we examined toxic effects of Tungsten Borides NPs on gene expression profiling of the human lung alveolar epithelial cells (HPAEpiC)...
June 27, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28594076/the-future-of-safety-science-is-happening-now-the-modernization-of-the-benefit-risk-paradigm
#12
Fabio Lievano, Linda Scarazzini, Frank Shen, James Duhig, Jeremy Jokinen
The future of safety science is happening now and has the potential to improve patient outcomes through an evolving approach to benefit-risk assessment. Three building blocks for the future of safety science, cognitive and behavioral systems, medical assessment, and data science, individually and collaboratively advance and modernize the benefit-risk paradigm. Incorporating the patient perspective and patient experiences will help identify tools that are useful in real-world practice. Medical assessment teams will bring together the study of toxicity and toxicogenomics, biomarkers, and special populations to personalize the benefit-risk profile...
August 2017: Pharmacoepidemiology and Drug Safety
https://www.readbyqxmd.com/read/28575330/the-utility-of-gene-expression-profiling-from-tissue-samples-to-support-drug-safety-assessments
#13
Daniel P Stiehl, Elaine Tritto, Salah-Dine Chibout, André Cordier, Pierre Moulin
Originally conceptualized as an integrated approach combining conventional toxicology methods with genome-wide expression profiling, toxicogenomics has promised to provide unequivocal relationships between the molecular changes elicited by a compound or a target pathway and the lesions that appear subsequently in the tissues. However, the discipline has only partially delivered on this promise, and the number of publications and submissions related to toxicogenomics is stagnating. The purpose of this article is to outline key factors contributing to a successful implementation of toxicogenomics in the drug discovery and development process...
May 31, 2017: ILAR Journal
https://www.readbyqxmd.com/read/28550087/transcriptional-networks-in-rodent-models-support-a-role-for-gut-brain-communication-in-neurogenic-hypertension-a-review-of-the-evidence
#14
REVIEW
Jasenka Zubcevic, Ashley Baker, Christopher J Martyniuk
Hypertension (HTN) is the most prevalent condition observed in primary health care. Hypertension shows complex etiology, and neuroinflammation, overactive sympathetic drive, and the microbiome are each associated with the disease. To obtain mechanistic perspective into neurogenic HTN, we first constructed a framework for transcriptional regulators of the disease using the Comparative Toxicogenomics Database. This approach yielded a core group of 178 transcripts that are prevalent in studies of HTN, including leptin and neuropeptide Y...
July 1, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28545612/drug-repositioning-based-on-triangularly-balanced-structure-for-tissue-specific-diseases-in-incomplete-interactome
#15
Liang Yu, Jin Zhao, Lin Gao
Finding new uses for existing drugs has become a new strategy for decades to treat more patients. Few traditional approaches consider the tissue specificities of diseases. Moreover, disease genes, drug targets and protein interaction (PPI) networks remain largely incomplete and the relationships between drugs and diseases conform to the triangularly balanced structure. Therefore, based on tissue specificities of diseases, we apply the triangularly balanced theory and the module distance defined for incomplete interaction networks to build drug-disease associations...
March 2017: Artificial Intelligence in Medicine
https://www.readbyqxmd.com/read/28521615/comprehensive-evaluation-of-usnic-acid-induced-cardiotoxicity-in-rats-by-sequential-cross-omics-analysis
#16
Y Yokouchi, M Imaoka, N Niino, N Kiyosawa, K Kai
Two-week administration of (+)-usnic acid (UA) induces mitochondrial swelling of cardiomyocytes, and toxicogenomic analysis of the heart revealed upregulation of oxidative stress, amino acid limitation, and endoplasmic reticulum stress-related genes in rats. To analyze the pathogenesis, UA was orally administrated to rats for 1, 4, 7, and 14 days, and sequential histopathological, genomic, and metabolomic analyses were performed on the heart, liver, and plasma. As a result, mitochondrial swelling of cardiomyocytes was observed on day 15 preceded by genomic upregulation on days 5 and 8...
January 1, 2017: Toxicologic Pathology
https://www.readbyqxmd.com/read/28472532/high-throughput-screening-data-interpretation-in-the-context-of-in-vivo-transcriptomic-responses-to-oral-cr-vi-exposure
#17
Julia E Rager, Caroline L Ring, Rebecca C Fry, Mina Suh, Deborah M Proctor, Laurie C Haws, Mark A Harris, Chad M Thompson
The toxicity of hexavalent chromium [Cr(VI)] in drinking water has been studied extensively, and available in vivo and in vitro studies provide a robust dataset for application of advanced toxicological tools to inform the mode of action (MOA). This study aimed to contribute to the understanding of Cr(VI) MOA by evaluating high-throughput screening (HTS) data and other in vitro data relevant to Cr(VI), and comparing these findings to robust in vivo data, including transcriptomic profiles in target tissues. Evaluation of Tox21 HTS data for Cr(VI) identified 11 active assay endpoints relevant to the Ten Key Characteristics of Carcinogens (TKCCs) that have been proposed by other investigators...
May 2, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28469246/interactive-toxicogenomics-gene-set-discovery-clustering-and-analysis-in-toxygates
#18
Johan Nyström-Persson, Yayoi Natsume-Kitatani, Yoshinobu Igarashi, Daisuke Satoh, Kenji Mizuguchi
Toxygates was originally released as a user-friendly interface to enhance the accessibility of the large-scale toxicogenomics database, Open TG-GATEs, generated by the Japanese Toxicogenomics Project. Since the original release, significant new functionality has been added to enable users to perform sophisticated computational analysis with only modest bioinformatics skills. The new features include an orthologous mode for data comparison among different species, interactive clustering and heatmap visualisation, enrichment analysis of gene sets, and user data uploading...
May 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28448553/a-computational-toxicogenomics-approach-identifies-a-list-of-highly-hepatotoxic-compounds-from-a-large-microarray-database
#19
Héctor A Rueda-Zárate, Iván Imaz-Rosshandler, Roberto A Cárdenas-Ovando, Juan E Castillo-Fernández, Julieta Noguez-Monroy, Claudia Rangel-Escareño
The liver and the kidney are the most common targets of chemical toxicity, due to their major metabolic and excretory functions. However, since the liver is directly involved in biotransformation, compounds in many currently and normally used drugs could affect it adversely. Most chemical compounds are already labeled according to FDA-approved labels using DILI-concern scale. Drug Induced Liver Injury (DILI) scale refers to an adverse drug reaction. Many compounds do not exhibit hepatotoxicity at early stages of development, so it is important to detect anomalies at gene expression level that could predict adverse reactions in later stages...
2017: PloS One
https://www.readbyqxmd.com/read/28440344/toxicogenomic-module-associations-with-pathogenesis-a-network-based-approach-to-understanding-drug-toxicity
#20
J J Sutherland, Y W Webster, J A Willy, G H Searfoss, K M Goldstein, A R Irizarry, D G Hall, J L Stevens
Despite investment in toxicogenomics, nonclinical safety studies are still used to predict clinical liabilities for new drug candidates. Network-based approaches for genomic analysis help overcome challenges with whole-genome transcriptional profiling using limited numbers of treatments for phenotypes of interest. Herein, we apply co-expression network analysis to safety assessment using rat liver gene expression data to define 415 modules, exhibiting unique transcriptional control, organized in a visual representation of the transcriptome (the 'TXG-MAP')...
April 25, 2017: Pharmacogenomics Journal
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