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Toxicogenomics

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https://www.readbyqxmd.com/read/28594076/the-future-of-safety-science-is-happening-now-the-modernization-of-the-benefit-risk-paradigm
#1
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...
June 8, 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
#2
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
#3
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 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 HTN, including leptin and neuropeptide Y...
May 26, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28545612/drug-repositioning-based-on-triangularly-balanced-structure-for-tissue-specific-diseases-in-incomplete-interactome
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
https://www.readbyqxmd.com/read/28420881/reduced-biological-effect-of-e-cigarette-aerosol-compared-to-cigarette-smoke-evaluated-in-vitro-using-normalized-nicotine-dose-and-rna-seq-based-toxicogenomics
#10
Linsey E Haswell, Andrew Baxter, Anisha Banerjee, Ivan Verrastro, Jessica Mushonganono, Jason Adamson, David Thorne, Marianna Gaça, Emmanuel Minet
Electronic cigarettes (e-cigarettes) use has increased globally and could potentially offer a lower risk alternative to cigarette smoking. Here, we assessed the transcriptional response of a primary 3D airway model acutely exposed to e-cigarette aerosol and cigarette (3R4F) smoke. Aerosols were generated with standard intense smoking regimens with careful consideration for dose by normalizing the exposures to nicotine. Two e-cigarette aerosol dilutions were tested for equivalent and higher nicotine delivery compared to 3R4F...
April 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28399865/toxicity-of-nano-and-ionic-silver-to-embryonic-stem-cells-a-comparative-toxicogenomic-study
#11
Xiugong Gao, Vanessa D Topping, Zachary Keltner, Robert L Sprando, Jeffrey J Yourick
BACKGROUND: The widespread application of silver nanoparticles (AgNPs) and silver-containing products has raised public safety concerns about their adverse effects on human health and the environment. To date, in vitro toxic effects of AgNPs and ionic silver (Ag(+)) on many somatic cell types are well established. However, no studies have been conducted hitherto to evaluate their effect on cellular transcriptome in embryonic stem cells (ESCs). RESULTS: The present study characterized transcriptomic changes induced by 5...
April 11, 2017: Journal of Nanobiotechnology
https://www.readbyqxmd.com/read/28392987/profiling-transcriptomes-of-human-sh-sy5y-neuroblastoma-cells-exposed-to-maleic-acid
#12
Chia-Chi Wang, Yin-Chi Lin, Yin-Hua Cheng, Chun-Wei Tung
BACKGROUND: Maleic acid is a multi-functional chemical widely used in the field of industrial chemistry for producing food additives and food contact materials. As maleic acid may contaminate food by the release from food packages or intentional addition, it raises the concern about the effects of excessive dietary exposure to maleic acid on human health. However, the influence of maleic acid on human health has not been thoroughly studied. In silico toxicogenomics approaches have found the association between maleic acid and nervous system disease in human...
2017: PeerJ
https://www.readbyqxmd.com/read/28388477/parental-diuron-exposure-alters-offspring-transcriptome-and-fitness-in-pacific-oyster-crassostrea-gigas
#13
Evelyne Bachère, Audrey Barranger, Roman Bruno, Julien Rouxel, Dominique Menard, David Piquemal, Farida Akcha
One of the primary challenges in ecotoxicology is to contribute to the assessment of the ecological status of ecosystems. In this study, we used Pacific oyster Crassostrea gigas to explore the effects of a parental exposure to diuron, a herbicide frequently detected in marine coastal environments. The present toxicogenomic study provides evidence that exposure of oyster genitors to diuron during gametogenesis results in changes in offspring, namely, transcriptomic profile alterations, increased global DNA methylation levels and reduced growth and survival within the first year of life...
August 2017: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/28382281/predictive-and-prognostic-biomarkers-of-respiratory-diseases-due-to-particulate-matter-exposure
#14
REVIEW
Hyo Jeong Kim, Min Gi Choi, Moo Kyun Park, Young Rok Seo
Air pollution is getting severe and concerns about its toxicity effects on airway and lung disease are also increasing. Particulate matter (PM) is major component of air pollutant. It causes respiratory diseases, such as asthma, chronic obstructive pulmonary disease, lung cancer, and so on. PM particles enter the airway and lung by inhalation, causing damages to them. Especially, PM2.5 can penetrate into the alveolus and pass to the systemic circulation. It can affect the cardiopulmonary system and cause cardiopulmonary disorders...
March 2017: Journal of Cancer Prevention
https://www.readbyqxmd.com/read/28361664/network-based-analysis-of-transcriptional-profiles-from-chemical-perturbations-experiments
#15
Francesca Mulas, Amy Li, David H Sherr, Stefano Monti
BACKGROUND: Methods for inference and comparison of biological networks are emerging as powerful tools for the identification of groups of tightly connected genes whose activity may be altered during disease progression or due to chemical perturbations. Connectivity-based comparisons help identify aggregate changes that would be difficult to detect with differential analysis methods comparing individual genes. METHODS: In this study, we describe a pipeline for network comparison and its application to the analysis of gene expression datasets from chemical perturbation experiments, with the goal of elucidating the modes of actions of the profiled perturbations...
March 23, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28337249/cellular-homeostasis-and-antioxidant-response-in-epithelial-ht29-cells-on-titania-nanotube-arrays-surface
#16
Rabiatul Basria Smn Mydin, Srimala Sreekantan, Roshasnorlyza Hazan, Mustafa Fadzil Farid Wajidi, Ishak Mat
Cell growth and proliferative activities on titania nanotube arrays (TNA) have raised alerts on genotoxicity risk. Present toxicogenomic approach focused on epithelial HT29 cells with TNA surface. Fledgling cell-TNA interaction has triggered G0/G1 cell cycle arrests and initiates DNA damage surveillance checkpoint, which possibly indicated the cellular stress stimuli. A profound gene regulation was observed to be involved in cellular growth and survival signals such as p53 and AKT expressions. Interestingly, the activation of redox regulator pathways (antioxidant defense) was observed through the cascade interactions of GADD45, MYC, CHECK1, and ATR genes...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28329862/the-transcriptome-of-the-zebrafish-embryo-after-chemical-exposure-a-meta-analysis
#17
Andreas Schüttler, Kristin Reiche, Rolf Altenburger, Wibke Busch
Numerous studies have been published in the past years investigating the transcriptome of the zebrafish embryo (ZFE) upon being subjected to chemical stress. Aiming at a more mechanistic understanding of the results of such studies, knowledge about commonalities of transcript regulation in response to chemical stress is needed. Thus, our goal in this study was to identify and interpret genes and gene sets constituting a general response to chemical exposure. Therefore, we aggregated and reanalyzed published toxicogenomics data obtained with the ZFE...
June 1, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28329830/secondhand-smoke-prevalent-polycyclic-aromatic-hydrocarbon-binary-mixture-induced-specific-mitogenic-and-pro-inflammatory-cell-signaling-events-in-lung-epithelial-cells
#18
Ross S Osgood, Brad L Upham, Pierre R Bushel, Kalpana Velmurugan, Ka-Na Xiong, Alison K Bauer
Low molecular weight polycyclic aromatic hydrocarbons (LMW PAHs; < 206.3 g/mol) are prevalent and ubiquitous environmental contaminants, presenting a human health concern, and have not been as thoroughly studied as the high MW PAHs. LMW PAHs exert their pulmonary effects, in part, through P38-dependent and -independent mechanisms involving cell-cell communication and the production of pro-inflammatory mediators known to contribute to lung disease. Specifically, we determined the effects of two representative LMW PAHs, 1-methylanthracene (1-MeA) and fluoranthene (Flthn), individually and as a binary PAH mixture on the dysregulation of gap junctional intercellular communication (GJIC) and connexin 43 (Cx43), activation of mitogen activated protein kinases (MAPK), and induction of inflammatory mediators in a mouse non-tumorigenic alveolar type II cell line (C10)...
May 1, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28289583/microarray-technology-reveals-potentially-novel-genes-and-pathways-involved-in-non-functioning-pituitary-adenomas
#19
X Qiao, H Wang, X Wang, B Zhao, J Liu
Microarray data of non-functioning pituitary adenomas (NFPAs) were analyzed to disclose novel genes and pathways involved in NFPA tumorigenesis. Raw microarray data were downloaded from Gene Expression Omnibus. Data pre-treatment and differential analysis were conducted using packages in R. Functional and pathway enrichment analyses were performed using package GOs-tats. A protein-protein interaction (PPI) network was constructed using server STRING and Cytoscape. Known genes involved in pituitary adenomas (PAs), were obtained from the Comparative Toxicogenomics Database...
December 1, 2016: Balkan Journal of Medical Genetics: BJMG
https://www.readbyqxmd.com/read/28245982/comparative-analysis-of-microrna-and-mrna-expression-profiles-in-cells-and-exosomes-under-toluene-exposure
#20
Jung-Hee Lim, Mi-Kyung Song, Yoon Cho, Woong Kim, Sung Ok Han, Jae-Chun Ryu
Recent studies have illustrated the growing importance of exosomes (small extracellular vesicles) and their constituent microRNAs (miRNAs) in the fields of toxicology and pathology. The mechanism of toxicity of toluene, a highly-prevalent and volatile organic compound, is largely unknown. To examine the role of miRNAs in toluene-induced toxicity, we investigated miRNAs and toluene-induced gene expression in HL-60 human promyelocytic leukemia cells and exosomes using microarrays. A total of 54 miRNAs were differentially expressed in HL-60 cell lines exposed to toluene and exosomes from the cells...
February 27, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
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