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I Porreca, L Ulloa-Severino, P Almeida, D Cuomo, A Nardone, G Falco, M Mallardo, C Ambrosino
Several studies associate foetal human exposure to bisphenol A (BPA) to metabolic/endocrine diseases, mainly diabesity. They describe the role of BPA in the disruption of pancreatic beta cell, adipocyte and hepatocyte functions. Indeed, the complexity of the diabesity phenotype is due to the involvement of different endoderm-derived organs, all targets of BPA. Here, we analyse this point delineating a picture of different mechanisms of BPA toxicity in endoderm-derived organs leading to diabesity. Moving from epidemiological data, we summarize the in vivo experimental data of the BPA effects on endoderm-derived organs (thyroid, pancreas, liver, gut, prostate and lung) after prenatal exposure...
October 24, 2016: Obesity Reviews: An Official Journal of the International Association for the Study of Obesity
Mikyung Lee, Zhichao Liu, Ruili Huang, Weida Tong
BACKGROUND: All biological processes are inherently dynamic. Biological systems evolve transiently or sustainably according to sequential time points after perturbation by environment insults, drugs and chemicals. Investigating the temporal behavior of molecular events has been an important subject to understand the underlying mechanisms governing the biological system in response to, such as, drug treatment. The intrinsic complexity of time series data requires appropriate computational algorithms for data interpretation...
October 6, 2016: BMC Bioinformatics
Robim M Rodrigues, Olivier Govaere, Tania Roskams, Tamara Vanhaecke, Vera Rogiers, Joery De Kock
This data set is composed of transcriptomics analyses of (i) liver samples from patients suffering from acetaminophen-induced acute liver failure (ALF) and (ii) hepatic cell systems exposed to acetaminophen and their respective controls. The in vitro systems include widely employed cell lines i.e. HepaRG and HepG2 cells as well as a novel stem cell-derived model i.e. human skin-precursors-derived hepatocyte-like cells (hSKP-HPC). Data from primary human hepatocytes was also added to the data set "Open TG-GATEs: a large-scale toxicogenomics database" (Igarashi et al...
June 2016: Data in Brief
Luna Rahman, Dongmei Wu, Michael Johnston, Andrew William, Sabina Halappanavar
Titanium dioxide nanoparticles (TiO2NPs) induce lung inflammation in experimental animals. In this study, we conducted a comprehensive toxicogenomic analysis of lung responses in mice exposed to six individual TiO2NPs exhibiting different sizes (8, 20 and 300nm), crystalline structure (anatase, rutile or anatase/rutile) and surface modifications (hydrophobic or hydrophilic) to investigate whether the mechanisms leading to TiO2NP-induced lung inflammation are property specific. A detailed histopathological analysis was conducted to investigate the long-term disease implications of acute exposure to TiO2NPs...
October 19, 2016: Mutagenesis
Ying Peng, Pu Xia, Junjiang Zhang, Daniel L Villeneuve, Jiamin Zhang, Zhihao Wang, Si Wei, Hongxia Yu, Xiaowei Zhang
Hydroxylated polybrominated diphenyl ethers (OH-PBDEs) are analogs of PBDEs with hundreds of possible structures and are frequently detected in the environment. However, the in vivo evidence on the toxicity of OH-PBDEs is still very limited. Here the developmental toxicity of 6-OH-BDE47, a predominant congener of OH-PBDEs detected in the environment, in chicken embryos was assessed using a toxicogenomic approach. Fertilized chicken eggs were dosed via in ovo administration of 0.006 to 0.474 nmol 6-OH-BDE47/g egg followed by 18-days incubation...
October 17, 2016: Environmental Science & Technology
Paula Moyano, Javier Del Pino, María José Anadon, María Jesús Díaz, Gloria Gómez, María Teresa Frejo
Chlorpyrifos (CPF) is an organophosphate insecticide reported to induce, both after acute and repeated exposure, learning and memory dysfunctions, although the mechanism is not completely known. CPF produces basal forebrain cholinergic neuronal loss, involved on learning and memory regulation, which could be the cause of such cognitive disorders. This effect was reported to be induced through apoptotic process, partially mediated by AChE overexpression, although neuronal necrosis was also described after CPF exposure...
October 10, 2016: Neurotoxicology and Teratology
Mohamed Diwan M AbdulHameed, Danielle L Ippolito, Jonathan D Stallings, Anders Wallqvist
BACKGROUND: Acute kidney injury (AKI) caused by drug and toxicant ingestion is a serious clinical condition associated with high mortality rates. We currently lack detailed knowledge of the underlying molecular mechanisms and biological networks associated with AKI. In this study, we carried out gene co-expression analyses using DrugMatrix-a large toxicogenomics database with gene expression data from rats exposed to diverse chemicals-and identified gene modules associated with kidney injury to probe the molecular-level details of this disease...
October 10, 2016: BMC Genomics
Mi Zhou, Mei Feng, Ling-Ling Fu, Lin-Dan Ji, Jin-Shun Zhao, Jin Xu
Tributyltin (TBT) is one of the most widely used organotin biocides, which has severe endocrine-disrupting effects on marine species and mammals. Given that TBT accumulates at higher levels in the liver than in any other organ, and it acts mainly as a hepatotoxic agent, it is important to clearly delineate the hepatotoxicity of TBT. However, most of the available studies on TBT have focused on observations at the cellular level, while studies at the level of genes and proteins are limited; therefore, the molecular mechanisms of TBT-induced hepatotoxicity remains largely unclear...
September 24, 2016: Food and Chemical Toxicology
Florence Pagé-Larivière, Amélie Tremblay, Céline Campagna, Manuel J Rodriguez, Marc-André Sirard
Bromodichloromethane (BDCM) is one of the trihalomethanes present in chlorinated water. Humans are thus daily exposed. Previous contradictory results failed to clearly establish the adverse effects of low concentrations of BDCM. By using the porcine preimplantation embryo as a sensitive model, we showed that exposure to low concentrations of BDCM (10 and 100ppb) during the first week of embryo development induced adverse effect on the blastocyst rate and alteration of the estradiol pathway. Our results also suggest that blastocysts exposed to BDCM present transcriptomic and epigenomic adaptive modifications compatible with the cardiac anomalies observed by previous studies of newborns exposed to BDCM during gestation...
September 23, 2016: Reproductive Toxicology
Allan Peter Davis, Cynthia J Grondin, Robin J Johnson, Daniela Sciaky, Benjamin L King, Roy McMorran, Jolene Wiegers, Thomas C Wiegers, Carolyn J Mattingly
The Comparative Toxicogenomics Database (CTD; provides information about interactions between chemicals and gene products, and their relationships to diseases. Core CTD content (chemical-gene, chemical-disease and gene-disease interactions manually curated from the literature) are integrated with each other as well as with select external datasets to generate expanded networks and predict novel associations. Today, core CTD includes more than 30.5 million toxicogenomic connections relating chemicals/drugs, genes/proteins, diseases, taxa, Gene Ontology (GO) annotations, pathways, and gene interaction modules...
September 19, 2016: Nucleic Acids Research
Hyosil Kim, Ju-Hwa Kim, So Youn Kim, Deokyeon Jo, Ho Jun Park, Jihyun Kim, Sungwon Jung, Hyun Seok Kim, KiYoung Lee
[This corrects the article DOI: 10.1371/journal.pone.0136698.].
2016: PloS One
Hoang-Quynh Le, Mai-Vu Tran, Thanh Hai Dang, Quang-Thuy Ha, Nigel Collier
The BioCreative V chemical-disease relation (CDR) track was proposed to accelerate the progress of text mining in facilitating integrative understanding of chemicals, diseases and their relations. In this article, we describe an extension of our system (namely UET-CAM) that participated in the BioCreative V CDR. The original UET-CAM system's performance was ranked fourth among 18 participating systems by the BioCreative CDR track committee. In the Disease Named Entity Recognition and Normalization (DNER) phase, our system employed joint inference (decoding) with a perceptron-based named entity recognizer (NER) and a back-off model with Semantic Supervised Indexing and Skip-gram for named entity normalization...
July 2016: Database: the Journal of Biological Databases and Curation
Mohamed Diwan M AbdulHameed, Danielle L Ippolito, Anders Wallqvist
The pregnane X receptor (PXR) is a ligand-activated transcription factor that acts as a master regulator of metabolizing enzymes and transporters. To avoid adverse drug-drug interactions and diseases such as steatosis and cancers associated with PXR activation, identifying drugs and chemicals that activate PXR is of crucial importance. In this work, we developed ligand-based predictive computational models for both rat and human PXR activation, which allowed us to identify potentially harmful chemicals and evaluate species-specific effects of a given compound...
October 17, 2016: Chemical Research in Toxicology
Meike van der Zande, Anna K Undas, Evelien Kramer, Marco P Monopoli, Ruud J Peters, David Garry, Elsa C Antunes Fernandes, Peter J Hendriksen, Hans J P Marvin, Ad A Peijnenburg, Hans Bouwmeester
The mode of action of silver nanoparticles (AgNPs) is suggested to be exerted through both Ag(+) and AgNP dependent mechanisms. Ingestion is one of the major NP exposure routes, and potential effects are often studied using Caco-2 cells, a well-established model for the gut epithelium. MCF-7 cells are epithelial breast cancer cells with extensive well-characterized toxicogenomics profiles. In the present study, we aimed to gain a deeper understanding of the cellular molecular responses in Caco-2 and MCF-7 cells after AgNP exposure in order to evaluate whether epithelial cells derived from different tissues demonstrated similar responses...
September 6, 2016: Nanotoxicology
Klara Piletič, Tanja Kunej
MicroRNAs (miRNAs) are short non-coding RNAs that act as important regulators of gene expression as part of the epigenetic machinery. In addition to posttranscriptional gene silencing by miRNAs, the epigenetic mechanisms also include DNA methylation, histone modifications and their crosstalk. Epigenetic modifications were reported to play an important role in many disease onsets and progressions and can be used to explain several features of complex diseases, such as late onset and fluctuation of symptoms. However, miRNAs not only function as a part of epigenetic machinery, but are also epigenetically modified by DNA methylation and histone modification like any other protein-coding gene...
October 2016: Archives of Toxicology
Lei Liu, Maria Tsompana, Yong Wang, Dingfeng Wu, Lixin Zhu, Ruixin Zhu
Drug discovery and development is a costly and time-consuming process with a high risk for failure resulting primarily from a drug's associated clinical safety and efficacy potential. Identifying and eliminating inapt candidate drugs as early as possible is an effective way for reducing unnecessary costs, but limited analytical tools are currently available for this purpose. Recent growth in the area of toxicogenomics and pharmacogenomics has provided with a vast amount of drug expression microarray data. Web servers such as CMap and LTMap have used this information to evaluate drug toxicity and mechanisms of action independently; however, their wider applicability has been limited by the lack of a combinatorial drug-safety type of analysis...
September 26, 2016: Journal of Chemical Information and Modeling
Chie Furihata, Takashi Watanabe, Takayoshi Suzuki, Shuichi Hamada, Madoka Nakajima
Toxicogenomics is a rapidly developing discipline focused on the elucidation of the molecular and cellular effects of chemicals on biological systems. As a collaborative study group of Toxicogenomics/JEMS·MMS, we conducted studies on hepatocarcinogens in rodent liver in which 100 candidate marker genes were selected to discriminate genotoxic hepatocarcinogens from non-genotoxic hepatocarcinogens. Differential gene expression induced by 13 chemicals were examined using DNA microarray and quantitative real-time PCR (qPCR), including eight genotoxic hepatocarcinogens [o-aminoazotoluene, chrysene, dibenzo[a,l]pyrene, diethylnitrosamine (DEN), 7,12-dimethylbenz[a]anthracene, dimethylnitrosamine, dipropylnitrosamine and ethylnitrosourea (ENU)], four non-genotoxic hepatocarcinogens [carbon tetrachloride, di(2-ethylhexyl)phthalate (DEHP), phenobarbital and trichloroethylene] and a non-genotoxic non-hepatocarcinogen [ethanol]...
2016: Genes and Environment: the Official Journal of the Japanese Environmental Mutagen Society
Pu Xia, Xiaowei Zhang, Yuwei Xie, Miao Guan, Daniel L Villeneuve, Hongxia Yu
There are thousands of chemicals used by humans and detected in the environment for which limited or no toxicological data are available. Rapid and cost-effective approaches for assessing the toxicological properties of chemicals are needed. We used CRISPR-Cas9 functional genomic screening to identify the potential molecular mechanism of a widely used antimicrobial triclosan (TCS) in HepG2 cells. Resistant genes at IC50 (the concentration causing a 50% reduction in cell viability) were significantly enriched in the adherens junction pathway, MAPK signaling pathway, and PPAR signaling pathway, suggesting a potential role in the molecular mechanism of TCS-induced cytotoxicity...
October 4, 2016: Environmental Science & Technology
Liang Cheng, Yue Jiang, Zhenzhen Wang, Hongbo Shi, Jie Sun, Haixiu Yang, Shuo Zhang, Yang Hu, Meng Zhou
The similarity of pair-wise diseases reveals the molecular relationships between them. For example, similar diseases have the potential to be treated by common therapeutic chemicals (TCs). In this paper, we introduced DisSim, an online system for exploring similar diseases, and comparing corresponding TCs. Currently, DisSim implemented five state-of-the-art methods to measure the similarity between Disease Ontology (DO) terms and provide the significance of the similarity score. Furthermore, DisSim integrated TCs of diseases from the Comparative Toxicogenomics Database (CTD), which can help to identify potential relationships between TCs and similar diseases...
2016: Scientific Reports
Zide Zhao, Yingying Zhang, Fengchun Gai, Ying Wang
Despite ongoing research into diabetes and its complications, the underlying molecular associations remain to be elucidated. The systematic identification of molecular interactions in associated diseases may be approached using a network analysis strategy. The biomarker-target interrelated molecules associated with diabetes and its complications were identified via the Comparative Toxicogenomics Database (CTD); the Search Tool for Recurring Instances of Neighboring Genes was utilized for network construction...
September 2016: Molecular Medicine Reports
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