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Toxicogenomics

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https://www.readbyqxmd.com/read/29224359/a-reduced-transcriptome-approach-to-assess-environmental-toxicants-using-zebrafish-embryo-test
#1
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
#2
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 In this study, we chose withdrawn drugs because the reasons why they were withdrawn and from which countries or regions is easily obtained...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
#3
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
#4
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
#5
EDITORIAL
https://www.readbyqxmd.com/read/29163636/a-pipeline-for-high-throughput-concentration-response-modeling-of-gene-expression-for-toxicogenomics
#6
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
https://www.readbyqxmd.com/read/29143341/a-toxicogenomics-approach-to-screen-chlorinated-flame-retardants-tris-2-chloroethyl-phosphate-and-tris-2-chloroisopropyl-phosphate-for-potential-health-effects
#7
Boris V Krivoshiev, Gerrit T S Beemster, Katrien Sprangers, Ronny Blust, Steven J Husson
Tris(2-chloroethyl) phosphate (TCEP) is a pervasive flame retardant that has been identified as a chemical of concern given its health effects and therefore its use has since been tightly regulated. Tris(2-chloroisopropyl) phosphate (TCIPP), an analogue of TCEP, is believed to be its replacement. However, compared to TCEP, little is known of the toxicological impacts of TCIPP. We used RNA sequencing as unbiased and sensitive tool to identify and compare effects on a transcriptome level of TCEP and TCIPP in the human hepatocellular carcinoma cell line, HepG2...
November 16, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/29126055/estrogen-responsive-gene-networks-in-the-teleost-liver-what-are-the-key-molecular-indicators
#8
April Feswick, Kelly R Munkittrick, Christopher J Martyniuk
An overarching goal of environmental genomics is to leverage sensitive suites of markers that are robust and reliable to assess biological responses in a range of species inhabiting variable environments. The objective of this study was to identify core groups of transcripts and molecular signaling pathways that respond to 17alpha-ethylinestadiol (EE2), a ubiquitous estrogenic contaminant, using transcriptome datasets generated from six independent laboratories. We sought to determine which biomarkers and gene networks were those most robust and reliably detected in multiple laboratories...
October 31, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/29105401/bioinformatic-analysis-identifies-three-potentially-key-differentially-expressed-genes-in-peripheral-blood-mononuclear-cells-of-patients-with-takayasu-s-arteritis
#9
Renping Huang, Yang He, Bei Sun, Bing Liu
OBJECTIVES: This study aimed to identify several potentially key genes associated with the pathogenesis of Takayasu's arteritis (TA). This identification may lead to a deeper mechanistic understanding of TA etiology and pave the way for potential therapeutic approaches. MATERIALS AND METHODS: In this experimental study, the microarray dataset GSE33910, which includes expression data for peripheral blood mononuclear cell (PBMC) samples isolated from TA patients and normal volunteers, was downloaded from the publicly accessible Gene Expression Omnibus (GEO) database...
January 2018: Cell Journal
https://www.readbyqxmd.com/read/29101769/computational-approaches-to-chemical-hazard-assessment
#10
Thomas Luechtefeld, Thomas Hartung
Computational prediction of toxicity has reached new heights as a result of decades of growth in the magnitude and diversity of biological data. Public packages for statistics and machine learning make model creation faster. New theory in machine learning and cheminformatics enables integration of chemical structure, toxicogenomics, simulated and physical data in the prediction of chemical health hazards, and other toxicological information. Our earlier publications have characterized a toxicological dataset of unprecedented scale resulting from the European REACH legislation (Registration Evaluation Authorisation and Restriction of Chemicals)...
2017: ALTEX
https://www.readbyqxmd.com/read/29074841/a-network-pharmacology-approach-to-determine-the-active-components-and-potential-targets-of-curculigo-orchioides-in-the-treatment-of-osteoporosis
#11
Nani Wang, Guizhi Zhao, Yang Zhang, Xuping Wang, Lisha Zhao, Pingcui Xu, Dan Shou
BACKGROUND Osteoporosis is a complex bone disorder with a genetic predisposition, and is a cause of health problems worldwide. In China, Curculigo orchioides (CO) has been widely used as a herbal medicine in the prevention and treatment of osteoporosis. However, research on the mechanism of action of CO is still lacking. The aim of this study was to identify the absorbable components, potential targets, and associated treatment pathways of CO using a network pharmacology approach. MATERIAL AND METHODS We explored the chemical components of CO and used the five main principles of drug absorption to identify absorbable components...
October 27, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29024780/toxicogenomics-of-the-flame-retardant-tris-2-butoxyethyl-phosphate-in-hepg2-cells-using-rna-seq
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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