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Toxicogenomics

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https://www.readbyqxmd.com/read/29024780/toxicogenomics-of-the-flame-retardant-tris-2-butoxyethyl-phosphate-in-hepg2-cells-using-rna-seq
#1
Boris V Krivoshiev, Gerrit T S Beemster, Katrien Sprangers, Bart Cuypers, Kris Laukens, Ronny Blust, Steven J Husson
Tris (2-butoxyethyl) phosphate (TBOEP) is a compound produced at high volume that is used as both a flame retardant and a plasticizer. It is persistent and bioaccumulative, yet little is known of its toxicological modes of action. Such insight may aid risk assessment in a weight-of-evidence approach supplementing current testing strategies. We used an RNA sequencing approach as an unbiased and sensitive tool to explore potential negative health effects of sub-cytotoxic concentrations of TBOEP on the transcriptome of the human liver hepatocellular carcinoma cell line, HepG2, with the lowest concentration used potentially holding relevance to human physiological levels...
October 9, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28958213/ligand-based-virtual-screening-molecular-docking-qsar-and-pharmacophore-analysis-of-quercetin-associated-potential-novel-analogs-against-epidermal-growth-factor-receptor
#2
Uma Devi Bommu, Kranthi Kumar Konidala, Neeraja Pabbaraju, Suneetha Yeguvapalli
The present study was to explore expectation and examination of therapeutic potential quercetin analogs as efficient anticancer agents against human epidermal growth factor receptor (EGFR), which is a consistent hallmark for moderating the non-small-cell lung carcinoma (NSCLC). Here, ligand-based virtual screening, pharmacophore approach and molecular docking were established as rational strategies for recognition of small analogs against the ligand binding domain of EGFR (PDB code: 1XKK). Adverse effects, toxicogenomics and pharmacokinetics reported that 10 candidates showed reliable consequences with less side effects and more efficient for target receptor...
December 2017: Journal of Receptor and Signal Transduction Research
https://www.readbyqxmd.com/read/28954626/hlaprofiler-utilizes-k-mer-profiles-to-improve-hla-calling-accuracy-for-rare-and-common-alleles-in-rna-seq-data
#3
Martin L Buchkovich, Chad C Brown, Kimberly Robasky, Shengjie Chai, Sharon Westfall, Benjamin G Vincent, Eric T Weimer, Jason G Powers
BACKGROUND: The human leukocyte antigen (HLA) system is a genomic region involved in regulating the human immune system by encoding cell membrane major histocompatibility complex (MHC) proteins that are responsible for self-recognition. Understanding the variation in this region provides important insights into autoimmune disorders, disease susceptibility, oncological immunotherapy, regenerative medicine, transplant rejection, and toxicogenomics. Traditional approaches to HLA typing are low throughput, target only a few genes, are labor intensive and costly, or require specialized protocols...
September 27, 2017: Genome Medicine
https://www.readbyqxmd.com/read/28937306/biocompatibility-assessment-of-functionalized-magnetic-mesoporous-silica-nanoparticles-in-human-heparg-cells
#4
Cédric Pisani, Estelle Rascol, Christophe Dorandeu, Clarence Charnay, Yannick Guari, Joël Chopineau, Jean-Marie Devoisselle, Odette Prat
Magnetic mesoporous silica nanoparticles (M-MSNs) are a promising class of nanoparticles for drug delivery. However, a deep understanding of the toxicological mechanisms of action of these nanocarriers is essential, especially in the liver. The potential toxicity on HepaRG cells of pristine, pegylated (PEG), and lipid (DMPC) M-MSNs were compared. Based on MTT assay and real-time cell impedance, none of these NPs presented an extensive toxicity on hepatic cells. However, we observed by transmission electron microscopy (TEM) that the DMPC and pristine M-MSNs were greatly internalized...
September 22, 2017: Nanotoxicology
https://www.readbyqxmd.com/read/28889778/genotoxicity-testing-progress-and-prospects-for-the-next-decade
#5
REVIEW
Hasan Turkez, Mehmet E Arslan, Ozlem Ozdemir
Genotoxicity and mutagenicity analyses have a significant role in the identification of hazard effects of therapeutic drugs, cosmetics, agrochemicals, industrial compounds, food additives, natural toxins and nanomaterials for regulatory purposes. To evaluate mutagenicity or genotoxicity, different in vitro and in vivo methodologies exert various genotoxicological endpoints such as point mutations, changes in number and structure of chromosomes. Areas covered: This review covered the basics of genotoxicity and in vitro/in vivo methods for determining of genetic damages...
October 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28888119/multiple-endpoints-gene-alteration-based-mega-assay-a-toxicogenomics-approach-for-water-quality-assessment-of-wastewater-effluents
#6
Toshikazu Fukushima, Hiroe Hara-Yamamura, Koji Nakashima, Lea Chua Tan, Satoshi Okabe
Wastewater effluents contain a significant number of toxic contaminants, which, even at low concentrations, display a wide variety of toxic actions. In this study, we developed a multiple-endpoints gene alteration-based (MEGA) assay, a real-time PCR-based transcriptomic analysis, to assess the water quality of wastewater effluents for human health risk assessment and management. Twenty-one genes from the human hepatoblastoma cell line (HepG2), covering the basic health-relevant stress responses such as response to xenobiotics, genotoxicity, and cytotoxicity, were selected and incorporated into the MEGA assay...
August 21, 2017: Chemosphere
https://www.readbyqxmd.com/read/28882690/toxicogenomic-and-bioinformatics-platforms-to-identify-key-molecular-mechanisms-of-a-curcumin-analogue-dm-1-toxicity-in-melanoma-cells
#7
Érica Aparecida de Oliveira, Diogenes Saulo de Lima, Lucas Esteves Cardozo, Garcia Ferreira de Souza, Nayane de Souza, Debora Kristina Alves-Fernandes, Fernanda Faião-Flores, José Agustín Pablo Quincoces, Silvia Berlanga de Moraes Barros, Helder I Nakaya, Gisele Monteiro, Silvya Stuchi Maria-Engler
Melanoma is a highly invasive and metastatic cancer with high mortality rates and chemoresistance. Around 50% of melanomas are driven by activating mutations in BRAF that has led to the development of potent anti-BRAF inhibitors. However resistance to anti-BRAF therapy usually develops within a few months and consequently there is a need to identify alternative therapies that will bypass BRAF inhibitor resistance. The curcumin analogue DM-1 (sodium 4-[5-(4-hydroxy-3-methoxy-phenyl)-3-oxo-penta-1,4-dienyl]-2-methoxy-phenolate) has substantial anti-tumor activity in melanoma, but its mechanism of action remains unclear...
September 4, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28870889/mir-194-as-predictive-biomarker-of-responsiveness-to-neoadjuvant-chemoradiotherapy-in-patients-with-locally-advanced-rectal-adenocarcinoma
#8
Edoardo D'Angelo, Carlo Zanon, Francesca Sensi, Maura Digito, Massimo Rugge, Matteo Fassan, Marco Scarpa, Salvatore Pucciarelli, Donato Nitti, Marco Agostini
AIMS: Curative surgery remains the primary form of treatment for locally advanced rectal cancer (LARC). Recent data support the use of preoperative chemoradiotherapy (pCRT) to improve the prognosis of LARC with a significant reduction of local relapse and an increase of overall survival. Unfortunately, only 20% of the patients with LARC present complete pathological response after pCRT, whereas in 20%-40%, the response is poor or absent. METHODS: We investigated the expression level of miR-194 in n=38 patients with LARC using our public microRNA (miRNA) expression dataset...
September 4, 2017: Journal of Clinical Pathology
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
#9
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
#10
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...
September 30, 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
#11
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
#12
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
#13
COMPARATIVE STUDY
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
#14
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
#15
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
#16
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
#17
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...
June 2017: Nanotoxicology
https://www.readbyqxmd.com/read/28671182/a-transcriptomics-data-driven-gene-space-accurately-predicts-liver-cytopathology-and-drug-induced-liver-injury
#18
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
#19
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)...
August 1, 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
#20
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
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