Read by QxMD icon Read


John L Vahle, Ulf Anderson, Eric A G Blomme, Jean-Christophe Hoflack, Daniel P Stiehl
Toxicogenomics held great promise as an approach to enable early detection of toxicities induced by xenobiotics; however, there remain questions regarding the impact of the discipline on pharmaceutical nonclinical safety assessment. To understand the current state of toxicogenomics in the sector, an industry group surveyed companies to determine the frequency of toxicogenomics use in in vivo studies at various stages of drug discovery and development and to assess how toxicogenomics use has evolved over time...
April 18, 2018: Regulatory Toxicology and Pharmacology: RTP
Cristiana M M Freire, Mariana G Braz, João Paulo C Marcondes, Nayara M Arruda, José Reinaldo C Braz, Cláudia A Rainho, Leandro G Braz, Daisy M F Salvadori
Despite the widespread use of the anaesthetics propofol (PROP) and isoflurane (ISO), data about their toxicogenomic potential and interference in epigenetic events are unknown. This study evaluated the expression and methylation profile of two important DNA-repair genes (XRCC1 and hOGG1) in 40 patients undergoing elective and minimally invasive surgery (tympanoplasty and septoplasty) under ISO or PROP anaesthesia. The endpoints were examined at three sampling times: before anaesthesia (T0), 2 h after the beginning of anaesthesia (T2) and 24 h after the beginning of surgery (T24)...
April 13, 2018: Mutagenesis
Jiaqi Lan, Sheikh Mokhlesur Rahman, Na Gou, Tao Jiang, Michael J Plewa, Akram Alshawabkeh, April Z Gu
Genotoxicity is considered the major concern for drinking water disinfection by-products (DBPs). Of over 700 DBPs identified to date, only a small number of has been assessed with limited information for DBP genotoxicity mechanism(s). In this study we evaluated genotoxicity of 20 regulated and un-regulated DBPs applying a quantitative toxicogenomics approach. We used GFP-fused yeast strains that examine protein expression profiling of 38 proteins indicative of all known DNA damage and repair pathways. The toxicogenomics assay detected genotoxicity potential of these DBPs in consistent with conventional genotoxicity assays endpoints...
April 16, 2018: Environmental Science & Technology
Kurt A Gust, Guilherme R Lotufo, Jacob K Stanley, Mitchell S Wilbanks, Pornsawan Chappell, Natalie D Barker
Within the US military, new insensitive munitions (IMs) are rapidly replacing conventional munitions improving safety from unintended detonation. Toxicity data for IM chemicals are expanding rapidly, however IM constituents are typically deployed in mixture formulations, and very little is known about their mixture toxicology. In the present study we sought to characterize the mixture effects and toxicology of the two predominant IM formulations IMX-101 and IMX-104 in acute (48 h) larval fathead minnow (Pimephales promelas) exposures...
March 23, 2018: Aquatic Toxicology
Zhichao Liu, Brian Delavan, Ruth Roberts, Weida Tong
Toxicogenomics (TGx) is an important tool to gain an enhanced understanding of toxicity at the molecular level. Previously, we developed a pair ranking (PRank) method to assess in vitro to in vivo extrapolation (IVIVE) using toxicogenomic datasets from the Open Toxicogenomics Project-Genomics Assisted Toxicity Evaluation System (TG-GATEs) database. With this method, we investiagted three important questions that were not addressed in our previous study: (1) is a 1-day in vivo short-term assay able to replace the 28-day standard and expensive toxicological assay? (2) are some biological processes more conservative across different preclinical testing systems than others? and (3) do these preclinical testing systems have the similar resolution in differentiating drugs by their therapeutic uses? For question 1, a high similarity was noted (PRank score = 0...
2018: Frontiers in Genetics
Dongyan Chen, Huangyou Liu, Enting Wang, Haiyang Yan, Haiqing Ye, Yuan Yuan
In current studies, histopathologic method, Agilent GeneChip hybridization and Western blot were used to investigate the toxicity of acrylamide (AA) and glycidamide (GA) in male mouse livers. The histopathologic results demonstrated that AA and GA could cause oxidative damage to mouse liver. Middle dose of GA and AA (50 mg/kg b.w./day) could significantly up-regulate the expression of cytochrome P450, as well as genes related to oxidative injury, cancer and inflammation, and significantly down-regulate the expression of genes related to anti-apoptosis, antioncogene and fatty acid synthesis...
March 2018: General Physiology and Biophysics
Yesol Bak, Hui-Joo Jang, Jong-Woon Shin, Soo-Jin Kim, Hyun Woo Chun, Ji-Hye Seo, Su-Hyun No, Jung-Il Chae, Dong Hee Son, Seung Yeoun Lee, Jintae Hong, Do-Young Yoon
The carcinogenicity of chemicalsin the environment is a major concern. Recently, numerous studies have attempted to develop methods for predicting carcinogenicity including rodent and cell-based approaches. However, rodent carcinogenicity tests for evaluating the carcinogenic potential of a chemical to humans are time-consuming and costly. This study focused on the development of an alternative method for predicting carcinogenicity using quantitative PCR (qPCR) and colon cancer stem cells.A toxicogenomic method,mRNA profiling, is useful for predicting carcinogenicity...
March 15, 2018: Journal of Microbiology and Biotechnology
Julien Vachon, Florence Pagé-Larivière, Marc-André Sirard, Manuel J Rodriguez, Patrick Levallois, Céline Campagna
Human health risk assessment (HHRA) must be adapted to the challenges of the 21st century, and the use of toxicogenomics data in HHRA is among the changes that regulatory agencies worldwide are trying to implement. However, the use of toxicogenomics data in HHRA is still limited. The purpose of this study was to explore the availability, quality and relevance to HHRA of toxicogenomics publications as potential barriers to their use in HHRA. We conducted a scoping review of available toxicogenomics literature, using trihalomethanes as a case study...
March 5, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
Jinmyung Jung, Mijin Kwon, Sunghwa Bae, Soorin Yim, Doheon Lee
BACKGROUND: Muscle atrophy, an involuntary loss of muscle mass, is involved in various diseases and sometimes leads to mortality. However, therapeutics for muscle atrophy thus far have had limited effects. Here, we present a new approach for therapeutic target prediction using Petri net simulation of the status of phosphorylation, with a reasonable assumption that the recovery of abnormally phosphorylated proteins can be a treatment for muscle atrophy. RESULTS: The Petri net model was employed to simulate phosphorylation status in three states, i...
March 5, 2018: BMC Systems Biology
Célia Ventura, António Sousa-Uva, João Lavinha, Maria João Silva
The widespread application of carbon nanotubes (CNT) on industrial, biomedical, and consumer products can represent an emerging respiratory occupational hazard. Particularly, their similarity with the fiber-like shape of asbestos have raised a strong concern about their carcinogenic potential. Several in vitro and in vivo studies have been supporting this view by pointing to immunotoxic, cytotoxic and genotoxic effects of some CNT that may conduct to pulmonary inflammation, fibrosis, and bronchioloalveolar hyperplasia in rodents...
February 26, 2018: Environmental and Molecular Mutagenesis
Halil Bisgin, Binsheng Gong, Yuping Wang, Weida Tong
MicroRNAs (miRNAs) are key post-transcriptional regulators that affect protein translation by targeting mRNAs. Their role in disease etiology and toxicity are well recognized. Given the rapid advancement of next-generation sequencing techniques, miRNA profiling has been increasingly conducted with RNA-seq, namely miRNA-seq. Analysis of miRNA-seq data requires several steps: (1) mapping the reads to miRBase, (2) considering mismatches during the hairpin alignment (windowing), and (3) counting the reads (quantification)...
2018: Frontiers in Genetics
Yong Ni, Chengrui Jiang
This study aimed to identify the potential target genes for the treatment of ankylosing spondylitis (AS).Dataset GSE25101 was downloaded from Gene Expression Omnibus, including 16 AS and 16 normal control blood samples. Differentially expressed genes (DEGs) were identified using unmatched t-test in limma package with adjusted P < .05. Gene ontology-biological process (GO-BP) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted using multifaceted analysis tool for human transcriptome...
February 2018: Medicine (Baltimore)
Sourabh Dwivedi, Quaiser Saquib, Bilal Ahmad, Sabiha M Ansari, Ameer Azam, Javed Musarrat
The wider applications of nanoparticles (NPs) has evoked a world-wide concern due to their possible risk of toxicity in humans and other organisms. Aggregation and accumulation of NPs into cell leads to their interaction with biological macromolecules including proteins, nucleic acids and cellular organelles, which eventually induce toxicological effects. Application of toxicogenomics to investigate molecular pathway-based toxicological consequences has opened new vistas in nanotoxicology research. Indeed, genomic approaches appeared as a new paradigm in terms of providing information at molecular levels and have been proven to be as a powerful tool for identification and quantification of global shifts in gene expression...
2018: Advances in Experimental Medicine and Biology
Yuichi Yokoyama, Yoshifumi Sasaki, Natsuko Terasaki, Taku Kawataki, Koji Takekawa, Yumiko Iwase, Toshinobu Shimizu, Seigo Sanoh, Shigeru Ohta
Differentiated HepaRG cells maintain liver-specific functions such as drug-metabolizing enzymes. In this study, the feasibility of HepaRG cells as a human hepatocyte model for in vitro toxicity assessment was examined using selected hepatotoxic compounds. First, basal drug-metabolizing enzyme activities (CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A4, uridine 5'-diphospho-glucuronosyltransferase [UGT], and sulfotransferases [SULT]) were measured in HepaRG, human hepatocytes, and HepG2 cells. Enzyme activities in differentiated HepaRG cells were comparable to those in human hepatocytes and much higher than those in HepG2 cells, except for SULT activity...
February 14, 2018: Biological & Pharmaceutical Bulletin
Xuwei Jiang, Yuqing Hao
The aims of the present study were to identify key genes and pathways associated with hepatocellular carcinoma (HCC) progression and predict compounds potentially associated with this type of carcinogenesis. The gene expression profile data of the GSE49515 dataset was obtained from the Gene Expression Omnibus database. The limma software package was used to identify the differentially expressed genes (DEGs). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed using the Biological Networks Gene Ontology tool and the Database for Annotation, Visualization and Integrated Discovery, respectively...
February 2018: Oncology Letters
Toshihiko Eki
By damaging DNA molecules, genotoxicants cause genetic mutations and also increase human susceptibility to cancers and genetic diseases. Over the past four decades, several assays have been developed in the budding yeast Saccharomyces cerevisiae to screen potential genotoxic substances and provide alternatives to animal-based genotoxicity tests. These yeast-based genotoxicity tests are either DNA alteration-based or DNA stress-response reporter-based. The former, which came first, were developed from the genetic studies conducted on various types of DNA alterations in yeast cells...
February 8, 2018: Applied Microbiology and Biotechnology
Gamze Ates, Birgit Mertens, Anja Heymans, Luc Verschaeve, Dimiter Milushev, Philippe Vanparys, Nancy H C Roosens, Sigrid C J De Keersmaecker, Vera Rogiers, Tatyana Y Doktorova
Although the value of the regulatory accepted batteries for in vitro genotoxicity testing is recognized, they result in a high number of false positives. This has a major impact on society and industries developing novel compounds for pharmaceutical, chemical, and consumer products, as afflicted compounds have to be (prematurely) abandoned or further tested on animals. Using the metabolically competent human HepaRG™ cell line and toxicogenomics approaches, we have developed an upgraded, innovative, and proprietary gene classifier...
February 6, 2018: Archives of Toxicology
Giulia Callegaro, Matilde Forcella, Pasquale Melchioretto, Annalisa Frattini, Laura Gribaldo, Paola Fusi, Marco Fabbri, Chiara Urani
Cadmium is a well recognized carcinogen, primarily released into the environment by anthropogenic activities. In the effort to understand the early events responsible for cadmium carcinogenesis, we have used an in vitro biological system (the Cell Transformation Assay, CTA), that has been shown to closely model some key stages of the conversion of normal cells into malignant ones. Cadmium-triggered early responses in CTA were analysed through microarray-based toxicogenomics. Metallothioneins represent the earliest cell response, together with Slc30a1 encoding for a ZnT-1 zinc exporter...
January 31, 2018: Toxicology in Vitro: An International Journal Published in Association with BIBRA
Linda Saxe Einbond, Fabiana Manservisi, Hsan-Au Wu, Michael Balick, Victoria Antonetti, Andrea Vornoli, Ilaria Menghetti, Fiorella Belpoggi, Stephen Redenti, Alan Roter
The spice turmeric (Curcuma longa L.) has a long history of use as an anti-inflammatory agent. The active component curcumin induces a variety of diverse biological effects and forms a series of degradation and metabolic products in vivo. Our hypothesis is that the field of toxicogenomics provides tools that can be used to characterize the mode of action and toxicity of turmeric components and to predict turmeric-drug interactions. Male Sprague-Dawley rats were treated for 4 days with turmeric root containing about 3% curcumin (comparable to what people consume in the fresh or dried root) or a fraction of turmeric enriched for curcumin (∼74%) and liver tissue collected for gene expression analysis...
February 3, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Linsey E Haswell, Sarah Corke, Ivan Verrastro, Andrew Baxter, Anisha Banerjee, Jason Adamson, Tomasz Jaunky, Christopher Proctor, Marianna Gaça, Emmanuel Minet
The battery of regulatory tests used to evaluate the risk of novel tobacco products such as heated tobacco products (THPs) presents some limitations including a bias towards the apical endpoint tested, and limited information on the mode of action. This is driving a paradigm shift to more holistic systems biology approaches. In this study, we used RNA-sequencing to compare the transcriptomic perturbations following acute exposure of a 3D airway tissue to the aerosols from two commercial THPs and a reference 3R4F cigarette...
February 5, 2018: Scientific Reports
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"