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Toxicogenomics

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https://www.readbyqxmd.com/read/28229968/cytotoxic-and-toxicogenomic-effects-of-silibinin-in-bladder-cancer-cells-with-different-tp53-status
#1
Daiane Teixeira DE Oliveira, Andre Luiz Ventura Savio, Joao Paulo DE Castro Marcondes, Tatiane Martins Barros, Ludmila Correia Barbosa, Daisy Maria Favero Salvadori, Glenda Nicioli DA Silva
Silibinin is a natural phenol found in the seeds of the milk thistle plant. Recent data have shown its effectiveness for preventing/treating bladder tumours. Therefore, in this study we investigated the cytotoxic and toxicogenetic activity of silibinin in bladder cancer cells with different TP53 statuses. Two bladder urothelial carcinoma cell lines were used: RT4 (wild-type TP53 gene) and T24 (mutated TP53 gene). Cell proliferation, clonogenic survival, apoptosis rates, genotoxicity and relative expression profile of FRAP/mTOR, FGFR3, AKT2 and DNMT1 genes and of miR100 and miR203 were evaluated...
March 2017: Journal of Biosciences
https://www.readbyqxmd.com/read/28217008/toxicogenomics-to-evaluate-endocrine-disrupting-effects-of-environmental-chemicals-using-the-zebrafish-model
#2
Karina Caballero-Gallardo, Jesus Olivero-Verbel, Jennifer L Freeman
The extent of our knowledge on the number of chemical compounds related to anthropogenic activities that can cause damage to the environment and to organisms is increasing. Endocrine disrupting chemicals (EDCs) are one group of potentially hazardous substances that include natural and synthetic chemicals and have the ability to mimic endogenous hormones, interfering with their biosynthesis, metabolism, and normal functions. Adverse effects associated with EDC exposure have been documented in aquatic biota and there is widespread interest in the characterization and understanding of their modes of action...
December 2016: Current Genomics
https://www.readbyqxmd.com/read/28208020/graphene-oxide-induced-perturbation-to-plasma-membrane-and-cytoskeletal-meshwork-sensitize-cancer-cells-to-chemotherapeutic-agents
#3
Jianqiang Zhu, Ming Xu, Ming Gao, Zhihong Zhang, Yong Xu, Tian Xia, Sijin Liu
The outstanding physicochemical properties endow graphene materials (e.g., graphene oxide, GO) with beneficial potentials in diverse biomedical fields such as bioimaging, drug delivery, and biomolecular detection. GO recently emerged as a chemosensitizer; however, the detailed molecular basis underlying GO-conducted sensitization and corresponding biological effects are still elusive. Based on our recent findings that GO treatment at sublethal concentrations could impair the general cellular priming state, including disorders of plasma membrane and cytoskeleton construction, we aimed here to explore the mechanism of GO as a sensitizer to make cancer cells more susceptible to chemotherapeutic agents...
February 20, 2017: ACS Nano
https://www.readbyqxmd.com/read/28179884/cellular-signaling-pathways-in-insulin-resistance-systems-biology-analyses-of-microarray-dataset-reveals-new-drug-target-gene-signatures-of-type-2-diabetes-mellitus
#4
Syed Aun Muhammad, Waseem Raza, Thanh Nguyen, Baogang Bai, Xiaogang Wu, Jake Chen
Purpose: Type 2 diabetes mellitus (T2DM) is a chronic and metabolic disorder affecting large set of population of the world. To widen the scope of understanding of genetic causes of this disease, we performed interactive and toxicogenomic based systems biology study to find potential T2DM related genes after cDNA differential analysis. Methods: From the list of 50-differential expressed genes (p < 0.05), we found 9-T2DM related genes using extensive data mapping. In our constructed gene-network, T2DM-related differentially expressed seeder genes (9-genes) are found to interact with functionally related gene signatures (31-genes)...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28176778/reconciled-rat-and-human-metabolic-networks-for-comparative-toxicogenomics-and-biomarker-predictions
#5
Edik M Blais, Kristopher D Rawls, Bonnie V Dougherty, Zhuo I Li, Glynis L Kolling, Ping Ye, Anders Wallqvist, Jason A Papin
The laboratory rat has been used as a surrogate to study human biology for more than a century. Here we present the first genome-scale network reconstruction of Rattus norvegicus metabolism, iRno, and a significantly improved reconstruction of human metabolism, iHsa. These curated models comprehensively capture metabolic features known to distinguish rats from humans including vitamin C and bile acid synthesis pathways. After reconciling network differences between iRno and iHsa, we integrate toxicogenomics data from rat and human hepatocytes, to generate biomarker predictions in response to 76 drugs...
February 8, 2017: Nature Communications
https://www.readbyqxmd.com/read/28174625/sex-and-age-differences-in-the-expression-of-liver-micrornas-during-the-life-span-of-f344-rats
#6
Joshua C Kwekel, Vikrant Vijay, Tao Han, Carrie L Moland, Varsha G Desai, James C Fuscoe
BACKGROUND: Physiological factors such as age and sex have been shown to be risk factors for adverse effects in the liver, including liver diseases and drug-induced liver injury. Previously, we have reported age- and sex-related significant differences in hepatic basal gene expression in rats during the life span that may be related to susceptibility to such adverse effects. However, the underlying mechanisms of the gene expression changes were not fully understood. In recent years, increasing evidence for epigenetic mechanisms of gene regulation has fueled interest in the role of microRNAs (miRNAs) in toxicogenomics and biomarker discovery...
2017: Biology of Sex Differences
https://www.readbyqxmd.com/read/28155709/the-extraction-of-drug-disease-correlations-based-on-module-distance-in-incomplete-human-interactome
#7
Liang Yu, Bingbo Wang, Xiaoke Ma, Lin Gao
BACKGROUND: Extracting drug-disease correlations is crucial in unveiling disease mechanisms, as well as discovering new indications of available drugs, or drug repositioning. Both the interactome and the knowledge of disease-associated and drug-associated genes remain incomplete. RESULTS: We present a new method to predict the associations between drugs and diseases. Our method is based on a module distance, which is originally proposed to calculate distances between modules in incomplete human interactome...
December 23, 2016: BMC Systems Biology
https://www.readbyqxmd.com/read/28137721/transcriptional-functional-and-mechanistic-comparisons-of-stem-cell-derived-hepatocytes-heparg-cells-and-3d-human-hepatocyte-spheroids-as-predictive-in-vitro-systems-for-drug-induced-liver-injury
#8
Catherine C Bell, Volker M Lauschke, Sabine U Vorrink, Henrik Palmgren, Roger Duffin, Tommy B Andersson, Magnus Ingelman-Sundberg
Reliable and versatile hepatic in vitro systems for the prediction of drug pharmacokinetics and toxicity are essential constituents of preclinical safety assessment pipelines for new medicines. Here, we compared three emerging cell systems, hepatocytes derived from induced pluripotent stem cells (hiPS-Hep), HepaRG cells and 3D primary human hepatocyte (PHH) spheroids at transcriptional and functional levels in a multi-center study to evaluate their potential as predictive models for drug-induced hepatotoxicity...
January 30, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28137640/barriers-to-the-use-of-toxicogenomics-data-in-human-health-risk-assessment-a-survey-of-canadian-risk-assessors
#9
Julien Vachon, Céline Campagna, Manuel J Rodriguez, Marc-André Sirard, Patrick Levallois
Regulatory agencies worldwide need to modernize human health risk assessment (HHRA) to meet challenges of the 21st century. Toxicogenomics is at the core of this improvement. Today, however, the use of toxicogenomics data in HHRA is very limited. The purpose of this survey was to identify barriers to the application of toxicogenomics data in HHRA by human health risk assessors. An online survey targeting Canadian risk assessors gathered information on their knowledge and perception of toxicogenomics, their current and future inclusion of toxicogenomics data in HHRA, and barriers to the use of such data...
January 27, 2017: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/28117354/identification-of-consensus-biomarkers-for-predicting-non-genotoxic-hepatocarcinogens
#10
Shan-Han Huang, Chun-Wei Tung
The assessment of non-genotoxic hepatocarcinogens (NGHCs) is currently relying on two-year rodent bioassays. Toxicogenomics biomarkers provide a potential alternative method for the prioritization of NGHCs that could be useful for risk assessment. However, previous studies using inconsistently classified chemicals as the training set and a single microarray dataset concluded no consensus biomarkers. In this study, 4 consensus biomarkers of A2m, Ca3, Cxcl1, and Cyp8b1 were identified from four large-scale microarray datasets of the one-day single maximum tolerated dose and a large set of chemicals without inconsistent classifications...
January 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28111205/carcinogenic-risk-and-bisphenol-a-exposure-a-focus-on-molecular-aspects-in-endoderm-derived-glands
#11
Danila Cuomo, Immacolata Porreca, Gilda Cobellis, Roberta Tarallo, Giovanni Nassa, Geppino Falco, Antonio Nardone, Francesca Rizzo, Massimo Mallardo, Concetta Ambrosino
Epidemiological and experimental evidence associates the exposure to Bisphenol A with the increase of cancer risk in several organs, including prostate. BPA targets different pathways involved in carcinogenicity including the Nuclear Receptors (i.e. estrogen and androgen receptors), stress regulated proteins and, finally, epigenetic changes. Here, we analyse BPA-dependent carcinogenesis in endoderm-derived glands, thyroid, liver, pancreas and prostate focusing on cell signalling, DNA damage repair pathways and epigenetic modifications...
January 19, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28108177/discriminating-between-adaptive-and-carcinogenic-liver-hypertrophy-in-rat-studies-using-logistic-ridge-regression-analysis-of-toxicogenomic-data-the-mode-of-action-and-predictive-models
#12
Shujie Liu, Taisuke Kawamoto, Osamu Morita, Kouichi Yoshinari, Hiroshi Honda
Chemical exposure often results in liver hypertrophy in animal tests, characterized by increased liver weight, hepatocellular hypertrophy, and/or cell proliferation. While most of these changes are considered adaptive responses, there is concern that they may be associated with carcinogenesis. In this study, we have employed a toxicogenomic approach using a logistic ridge regression model to identify genes responsible for liver hypertrophy and hypertrophic hepatocarcinogenesis and to develop a predictive model for assessing hypertrophy-inducing compounds...
March 1, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28087837/off-target-effects-of-neuroleptics-and-antidepressants-on-saccharomyces-cerevisiae
#13
M Caldara, S Graziano, M Gullì, S Cadonici, Nelson Marmiroli
Over the past years, the use of antidepressants and neuroleptics has steadily increased. Although incredibly useful to treat disorders like depression, schizophrenia, epilepsy, or mental retardation, these drugs display many side effects. Toxicogenomic studies aim to limit this problem by trying to identify cellular targets and off-targets of medical compounds. The baker yeast Saccharomyces cerevisiae has been shown to be a key player in this approach, as it represents an incredible toolbox for the dissection of complex biological processes...
January 13, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28073477/a-review-of-the-phylogeny-ecology-and-toxin-production-of-bloom-forming-aphanizomenon-spp-and-related-species-within-the-nostocales-cyanobacteria
#14
REVIEW
Samuel Cirés, Andreas Ballot
The traditional genus Aphanizomenon comprises a group of filamentous nitrogen-fixing cyanobacteria of which several memebers are able to develop blooms and to produce toxic metabolites (cyanotoxins), including hepatotoxins (microcystins), neurotoxins (anatoxins and saxitoxins) and cytotoxins (cylindrospermopsin). This genus, representing geographically widespread and extensively studied cyanobacteria, is in fact heterogeneous and composed of at least five phylogenetically distant groups (Aphanizomenon, Anabaena/Aphanizomenon like cluster A, Cuspidothrix, Sphaerospermopsis and Chrysosporum) whose taxonomy is still under revision...
April 2016: Harmful Algae
https://www.readbyqxmd.com/read/28073113/in-vitro-to-in-vivo-extrapolation-for-drug-induced-liver-injury-using-a-pair-ranking-method
#15
Zhichao Liu, Hong Fang, Jürgen Borlak, Ruth Roberts, Weida Tong
Preclinical animal toxicity studies may not accurately predict human toxicity. In light of this, in vitro systems have been developed that have the potential to supplement or even replace animal use. We examined in vitro to in vivo extrapolation (IVIVE) of gene expression data obtained from The Open Japanese Toxicogenomics Project-Genomics Assisted Toxicity Evaluation System (Open TG-GATEs) for 131 compounds given to rats for 28 days, and to human or rat hepatocytes for 24 hours. Notably, a Pair Ranking (PRank) method was developed to assess IVIVE potential with a PRank score based on the preservation of the order of similarity rankings of compound pairs between the platforms using a receiver operating characteristic (ROC) curve analysis to measure area under the curve (AUC)...
January 11, 2017: ALTEX
https://www.readbyqxmd.com/read/28069986/mechanisms-involved-in-porcine-early-embryo-survival-following-ethanol-exposure
#16
Florence Pagé-Larivière, Céline Campagna, Marc-André Sirard
Alcohol consumption during pregnancy is still a cause of preventable birth defects and developmental disabilities. However, little is known about the impact of ethanol on preimplantation embryos and the molecular mechanisms involved. We aimed to determine the toxicogenomic impacts and the mechanisms involved in preimplantation embryonic survival following 0.2% ethanol exposure in porcine embryos. Gene expression changes were measured with a porcine embryo specific microarray and confirmed by RT-qPCR. Compared to control, ethanol exposure led to a 43% decrease in blastocyst rate and activated pathways associated with oxidative stress and nervous system damage, such as TP53 and TGF...
January 9, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28063342/linking-genomic-responses-of-gonads-with-reproductive-impairment-in-marine-medaka-oryzias-melastigma-exposed-chronically-to-the-chemopreventive-and-antifouling-agent-3-3-diindolylmethane-dim
#17
Lianguo Chen, Doris W T Au, Chenyan Hu, Weipeng Zhang, Bingsheng Zhou, Lin Cai, John P Giesy, Pei-Yuan Qian
3,3'-Diindolylmethane (DIM) has been promoted as an effective chemopreventive and antifouling additive. However, the concurrent risks or side effects of DIM are not fully understood, especially on tissues responsive to estrogen. Therefore, this study employed marine medaka (Oryzias melastigma) as a test model to evaluate relative safety and explore mechanisms of toxic action of DIM on development and function of gonad after chronic (28days) aqueous exposure to relatively low doses (0μg/L or 8.5μg/L). Integration of comprehensive toxicogenomic analysis at the transcriptome and proteome levels with apical endpoints, such as production of eggs and swimming performance of larvae, elucidated the molecular linkage in gonad from bottom up along the reproductive adverse outcome pathway...
February 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/28033256/identified-molecular-mechanism-of-interaction-between-environmental-risk-factors-and-differential-expression-genes-in-cartilage-of-kashin-beck-disease
#18
REVIEW
Fang-Fang Yu, Yan-Xiang Zhang, Lian-He Zhang, Wen-Rong Li, Xiong Guo, Mikko J Lammi
As environmental risk factors (ERFs) play an important role in the pathogenesis of Kashin-Beck disease (KBD), it is important to identify the interaction between ERFs and differentially expression genes (DEGs) in KBD. The environmental response genes (ERGs) were analyzed in cartilage of KBD in comparison to normal controls.We searched 5 English and 3 Chinese databases from inception to September 2015, to identify case-control studies that examined ERFs for KBD using integrative meta-analysis and systematic review...
December 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28032149/dtni-a-novel-toxicogenomics-data-analysis-tool-for-identifying-the-molecular-mechanisms-underlying-the-adverse-effects-of-toxic-compounds
#19
Diana M Hendrickx, Terezinha Souza, Danyel G J Jennen, Jos C S Kleinjans
Unravelling gene regulatory networks (GRNs) influenced by chemicals is a major challenge in systems toxicology. Because toxicant-induced GRNs evolve over time and dose, the analysis of global gene expression data measured at multiple time points and doses will provide insight in the adverse effects of compounds. Therefore, there is a need for mathematical methods for GRN identification from time-over-dose-dependent data. One of the current approaches for GRN inference is Time Series Network Identification (TSNI)...
December 28, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/28008973/disentangling-genetic-and-environmental-risk-factors-for-individual-diseases-from-multiplex-comorbidity-networks
#20
Peter Klimek, Silke Aichberger, Stefan Thurner
Most disorders are caused by a combination of multiple genetic and/or environmental factors. If two diseases are caused by the same molecular mechanism, they tend to co-occur in patients. Here we provide a quantitative method to disentangle how much genetic or environmental risk factors contribute to the pathogenesis of 358 individual diseases, respectively. We pool data on genetic, pathway-based, and toxicogenomic disease-causing mechanisms with disease co-occurrence data obtained from almost two million patients...
December 23, 2016: Scientific Reports
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