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https://www.readbyqxmd.com/read/28525648/the-role-of-omics-in-the-application-of-adverse-outcome-pathways-for-chemical-risk-assessment
#1
Erica K Brockmeier, Geoff Hodges, Thomas H Hutchinson, Emma Butler, Markus Hecker, Knut Erik Tollefsen, Natalia Garcia-Reyero, Peter Kille, Dörthe Becker, Kevin Chipman, John Colbourne, Timothy W Collette, Andrew Cossins, Mark Cronin, Peter Graystock, Steve Gutsell, Dries Knapen, Ioanna Katsiadaki, Anke Lange, Stuart Marshall, Stewart F Owen, Edward J Perkins, Stewart Plaistow, Anthony Schroeder, Daisy Taylor, Mark Viant, Gerald Ankley, Francesco Falciani
In conjunction with the second International Environmental Omics Symposium (iEOS) conference, held at the University of Liverpool (UK) in September 2014, a workshop was held to bring together experts in toxicology and regulatory science from academia, government and industry. The purpose of the workshop was to review the specific roles that high-content omics datasets (e.g., transcriptomics, metabolomics, lipidomics, and proteomics) can hold within the adverse outcome pathway (AOP) framework for supporting ecological and human health risk assessments...
May 19, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28486152/benzotriazole-ultraviolet-stabilizers-alter-the-expression-of-the-thyroid-hormone-pathway-in-zebrafish-danio-rerio-embryos
#2
Xuefang Liang, Jiajia Li, Christopher J Martyniuk, Juan Wang, Yufeng Mao, Huan Lu, Jinmiao Zha
Benzotriazole ultraviolet stabilizers (BUVSs) are widely used in industrial products as well as personal-hygiene products to protect the material or skin from harmful UV-radiation. Due to their persistence and bioaccumulation, BUVSs have been ubiquitously detected in aquatic environments. Although the toxicological effects of BUVSs in aquatic organisms have been previously examined, the effects of BUVSs on the thyroid system have not been adequately addressed. In this study, we assessed putative thyroid disrupting effects of BUVSs (UV-234, UV-326, UV-329 and UV-P) in zebrafish embryos at 1, 10 and 100 μg/L for 96 h...
May 3, 2017: Chemosphere
https://www.readbyqxmd.com/read/28478747/creation-of-a-virtual-antidotes-network-between-pharmacy-departments-of-catalan-hospitals
#3
Raquel Aguilar-Salmerón, Edurne Fernández de Gamarra-Martínez, Milagros García-Peláez, Antoni Broto-Sumalla, Lidia Martínez-Sánchez, Santiago Nogué-Xarau
Objetive: To design a virtual antidote network between hospitals that could help to locate on-line those hospitals that stocked those antidotes with the highest difficulty in terms of availability, and ensured that the medication was loaned in case of necessity. METHODS: The application was developed by four hospital pharmacists and two clinical toxicologists with the support of a Healthcare Informatics Consultant Company. RESULTS: The antidotes network in Catalonia, Spain, was launched in July 2015...
May 1, 2017: Farmacia Hospitalaria
https://www.readbyqxmd.com/read/28461781/zebrafish-as-an-in-vivo-model-for-sustainable-chemical-design
#4
Pamela D Noyes, Gloria R Garcia, Robert L Tanguay
Heightened public awareness about the many thousands of chemicals in use and present as persistent contaminants in the environment has increased the demand for safer chemicals and more rigorous toxicity testing. There is a growing recognition that the use of traditional test models and empirical approaches is impractical for screening for toxicity the many thousands of chemicals in the environment and the hundreds of new chemistries introduced each year. These realities coupled with the green chemistry movement have prompted efforts to implement more predictive-based approaches to evaluate chemical toxicity early in product development...
December 21, 2016: Green Chemistry: An International Journal and Green Chemistry Resource: GC
https://www.readbyqxmd.com/read/28433707/genetic-susceptibility-to-toxicologic-lung-responses-among-inbred-mouse-strains-following-exposure-to-carbon-nanotubes-and-profiling-of-underlying-gene-networks
#5
Evan A Frank, Vinicius S Carreira, Kumar Shanmukhappa, Mario Medvedovic, Daniel R Prows, Jagjit S Yadav
The risk of human exposure to fiber nanoparticles has risen in recent years due to increases in the manufacture and utilization of carbon nanotubes (CNTs). CNTs are present as airborne particulates in occupational settings and their hazard potential has been demonstrated in experimental lung exposure studies using inbred mouse strains. However, it is not known whether different inbred strains differ in lung responses to CNTs by virtue of their genetics. In this work, common inbred strains (BALB/c, C57Bl/6, DBA/2, and C3H/He) were exposed to CNTs via oropharyngeal aspiration and lung histology and bronchoalveolar lavage (BAL) samples were evaluated over 28days with the objective of evaluating sensitivity/resistance among strains...
April 19, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28362344/proactive-approach-for-safe-use-of-antimicrobial-coatings-in-healthcare-settings-opinion-of-the-cost-action-network-amici
#6
Merja Ahonen, Anne Kahru, Angela Ivask, Kaja Kasemets, Siiri Kõljalg, Paride Mantecca, Ivana Vinković Vrček, Minna M Keinänen-Toivola, Francy Crijns
Infections and infectious diseases are considered a major challenge to human health in healthcare units worldwide. This opinion paper was initiated by EU COST Action network AMiCI (AntiMicrobial Coating Innovations) and focuses on scientific information essential for weighing the risks and benefits of antimicrobial surfaces in healthcare settings. Particular attention is drawn on nanomaterial-based antimicrobial surfaces in frequently-touched areas in healthcare settings and the potential of these nano-enabled coatings to induce (eco)toxicological hazard and antimicrobial resistance...
March 31, 2017: International Journal of Environmental Research and Public Health
https://www.readbyqxmd.com/read/28362102/systems-toxicology-real-world-applications-and-opportunities
#7
Thomas Hartung, Rex E FitzGerald, Paul Jennings, Gary R Mirams, Manuel C Peitsch, Amin Rostami-Hodjegan, Imran Shah, Martin F Wilks, Shana J Sturla
Systems Toxicology aims to change the basis of how adverse biological effects of xenobiotics are characterized from empirical end points to describing modes of action as adverse outcome pathways and perturbed networks. Toward this aim, Systems Toxicology entails the integration of in vitro and in vivo toxicity data with computational modeling. This evolving approach depends critically on data reliability and relevance, which in turn depends on the quality of experimental models and bioanalysis techniques used to generate toxicological data...
April 17, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28333795/diagnostic-tests-for-evaluation-of-stillbirth-results-from-the-stillbirth-collaborative-research-network
#8
Jessica M Page, Lauren Christiansen-Lindquist, Vanessa Thorsten, Corette B Parker, Uma M Reddy, Donald J Dudley, George R Saade, Donald Coustan, Carol J Rowland Hogue, Deborah Conway, Radek Bukowski, Halit Pinar, Cara C Heuser, Karen J Gibbins, Robert L Goldenberg, Robert M Silver
OBJECTIVE: To estimate the usefulness of each diagnostic test in the work-up for potential causes of stillbirth. METHODS: A secondary analysis of 512 stillbirths enrolled in the Stillbirth Collaborative Research Network from 2006 to 2008 was performed. The Stillbirth Collaborative Research Network was a multisite, geographically, racially, and ethnically diverse, population-based study of stillbirth in the United States. Participants underwent standardized evaluations that included maternal interview, medical record abstraction, biospecimen collection, fetal autopsy, and placental pathology...
April 2017: Obstetrics and Gynecology
https://www.readbyqxmd.com/read/28277368/diagnostic-tests-for-evaluation-of-stillbirth-stillbirth-collaborative-research-network
#9
Jessica M Page, Lauren Christiansen-Lindquist, Vanessa Thorsten, Corette B Parker, Uma M Reddy, Donald J Dudley, George R Saade, Donald Coustan, Carol J Rowland Hogue, Deborah Conway, Radek Bukowski, Halit Pinar, Cara C Heuser, Karen J Gibbins, Robert L Goldenberg, Robert M Silver
OBJECTIVE: To estimate the usefulness of each diagnostic test in the work-up for potential causes of stillbirth. METHODS: A secondary analysis of 512 stillbirths enrolled in the Stillbirth Collaborative Research Network from 2006 to 2008 was performed. The Stillbirth Collaborative Research Network was a multisite, geographically, racially, and ethnically diverse, population-based study of stillbirth in the United States. Participants underwent standardized evaluations that included maternal interview, medical record abstraction, biospecimen collection, fetal autopsy, and placental pathology...
March 6, 2017: Obstetrics and Gynecology
https://www.readbyqxmd.com/read/28245982/comparative-analysis-of-microrna-and-mrna-expression-profiles-in-cells-and-exosomes-under-toluene-exposure
#10
Jung-Hee Lim, Mi-Kyung Song, Yoon Cho, Woong Kim, Sung Ok Han, Jae-Chun Ryu
Recent studies have illustrated the growing importance of exosomes (small extracellular vesicles) and their constituent microRNAs (miRNAs) in the fields of toxicology and pathology. The mechanism of toxicity of toluene, a highly-prevalent and volatile organic compound, is largely unknown. To examine the role of miRNAs in toluene-induced toxicity, we investigated miRNAs and toluene-induced gene expression in HL-60 human promyelocytic leukemia cells and exosomes using microarrays. A total of 54 miRNAs were differentially expressed in HL-60 cell lines exposed to toluene and exosomes from the cells...
February 27, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28239160/insights-into-the-molecular-mechanisms-of-polygonum-multiflorum-thunb-induced-liver-injury-a-computational-systems-toxicology-approach
#11
Yin-Yin Wang, Jie Li, Zeng-Rui Wu, Bo Zhang, Hong-Bin Yang, Qin Wang, Ying-Chun Cai, Gui-Xia Liu, Wei-Hua Li, Yun Tang
An increasing number of cases of herb-induced liver injury (HILI) have been reported, presenting new clinical challenges. In this study, taking Polygonum multiflorum Thunb (PmT) as an example, we proposed a computational systems toxicology approach to explore the molecular mechanisms of HILI. First, the chemical components of PmT were extracted from 3 main TCM databases as well as the literature related to natural products. Then, the known targets were collected through data integration, and the potential compound-target interactions (CTIs) were predicted using our substructure-drug-target network-based inference (SDTNBI) method...
May 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28214551/effect-of-benzalkonium-chloride-on-trabecular-meshwork-cells-in-a-new-in-vitro-3d-trabecular-meshwork-model-for-glaucoma
#12
Meryem Bouchemi, Christophe Roubeix, Karima Kessal, Luisa Riancho, Anne-Laure Raveu, Hayet Soualmia, Christophe Baudouin, Françoise Brignole-Baudouin
PURPOSE: To validate a new culture model of primary human trabecular meshwork cells (p-hTMCs) using Matrigel®, in order to mimic in vitro 3D-TM organization, and to investigate the proinflammatory effect of benzalkonium chloride (BAK) in 3D p-hTMC cultures. METHODS: p-hTMCs, seeded onto Matrigel®-coated inserts were stimulated with BAK (10(-4)%), dexamethasone (DEX) (10(-6)M) or transforming growth factor-beta 2 (TGF-β2) (5ng/ml) for 48h and observed with confocal microscopy...
February 16, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28192153/comparison-of-the-acute-inhibitory-effects-of-tetrodotoxin-ttx-in-rat-and-human-neuronal-networks-for-risk-assessment-purposes
#13
COMPARATIVE STUDY
Emma E J Kasteel, Remco H S Westerink
Tetrodotoxin (TTX) is an extremely toxic marine neurotoxin. TTX inhibits voltage-gated sodium channels, resulting in a potentially lethal inhibition of neurotransmission. Despite numerous intoxications in Asia and Europe, limited (human) toxicological data are available for TTX. Additionally, the degree of interspecies differences for TTX is not well established, hampering the use of available (animal) data for human risk assessment and establishing regulatory limits for TTX concentrations in (shell)fish. We therefore used micro-electrode array (MEA) recordings as an integrated measure of neurotransmission to demonstrate that TTX inhibits neuronal electrical activity in both primary rat cortical cultures and human-induced pluripotent stem cell (hIPSC)-derived iCell(®) neurons in co-culture with hIPSC-derived iCell(®) astrocytes, with IC50 values of 7 and 10nM, respectively...
March 15, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28191694/generalizability-of-findings-from-randomized-controlled-trials-application-to-the-national-institute-of-drug-abuse-clinical-trials-network
#14
Ryoko Susukida, Rosa M Crum, Cyrus Ebnesajjad, Elizabeth A Stuart, Ramin Mojtabai
AIMS: To compare randomized controlled trial (RCT) sample treatment effects with the population effects of substance use disorder (SUD) treatment. DESIGN: Statistical weighting was used to re-compute the effects from 10 RCTs such that the participants in the trials had characteristics that resembled those of patients in the target populations. SETTINGS: Multi-site RCTs and usual SUD treatment settings in the United States. PARTICIPANTS: A total of 3592 patients in 10 RCTs and 1 602 226 patients from usual SUD treatment settings between 2001 and 2009...
February 13, 2017: Addiction
https://www.readbyqxmd.com/read/28185575/integration-of-metabolomics-lipidomics-and-clinical-data-using-a-machine-learning-method
#15
Animesh Acharjee, Zsuzsanna Ament, James A West, Elizabeth Stanley, Julian L Griffin
BACKGROUND: The recent pandemic of obesity and the metabolic syndrome (MetS) has led to the realisation that new drug targets are needed to either reduce obesity or the subsequent pathophysiological consequences associated with excess weight gain. Certain nuclear hormone receptors (NRs) play a pivotal role in lipid and carbohydrate metabolism and have been highlighted as potential treatments for obesity. This realisation started a search for NR agonists in order to understand and successfully treat MetS and associated conditions such as insulin resistance, dyslipidaemia, hypertension, hypertriglyceridemia, obesity and cardiovascular disease...
November 22, 2016: BMC Bioinformatics
https://www.readbyqxmd.com/read/28146279/detecting-protein-sulfenylation-in-cells-exposed-to-a-toxicant
#16
Phillip A Wages
Protein sulfenylation is a post-translational modification that is linked to many cell signaling networks and specific protein functions, thus the detection of any sulfenylated protein after a toxicological exposure is of importance. Specifically, the detection of protein sulfenylation can provide multiple levels of mechanistic insight towards understanding the impact of a toxicological exposure. For instance, sulfenylation is caused by only a handful of reactive chemical species. Any altered sulfenylation suggests a change in cellular health, and the elucidation of the specific protein target that undergoes sulfenylation can help ascertain downstream targets and associated adverse outcomes...
February 1, 2017: Current Protocols in Toxicology
https://www.readbyqxmd.com/read/28088864/integrated-high-throughput-multiomics-platform-enables-data-driven-construction-of-cellular-responses-and-reveals-global-drug-mechanisms-of-action
#17
Jeremy L Norris, Melissa A Farrow, Danielle B Gutierrez, Lauren D Palmer, Nicole Muszynski, Stacy D Sherrod, James C Pino, Jamie L Allen, Jeffrey M Spraggins, Alex L R Lubbock, Ashley Jordan, William Burns, James C Poland, Carrie Romer, M Lisa Manier, Yuan-Wei Nei, Boone M Prentice, Kristie L Rose, Salisha Hill, Raf Van de Plas, Tina Tsui, Nathaniel M Braman, M Ray Keller, Stacey A Rutherford, Nichole Lobdell, Carlos F Lopez, D Borden Lacy, John A McLean, John P Wikswo, Eric P Skaar, Richard M Caprioli
An understanding of how cells respond to perturbation is essential for biological applications; however, most approaches for profiling cellular response are limited in scope to pre-established targets. Global analysis of molecular mechanism will advance our understanding of the complex networks constituting cellular perturbation and lead to advancements in areas, such as infectious disease pathogenesis, developmental biology, pathophysiology, pharmacology, and toxicology. We have developed a high-throughput multiomics platform for comprehensive, de novo characterization of cellular mechanisms of action...
February 9, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28088094/organ-on-a-chip-for-assessing-environmental-toxicants
#18
REVIEW
Soohee Cho, Jeong-Yeol Yoon
Man-made xenobiotics, whose potential toxicological effects are not fully understood, are oversaturating the already-contaminated environment. Due to the rate of toxicant accumulation, unmanaged disposal, and unknown adverse effects to the environment and the human population, there is a crucial need to screen for environmental toxicants. Animal models and in vitro models are ineffective models in predicting in vivo responses due to inter-species difference and/or lack of physiologically-relevant 3D tissue environment...
January 11, 2017: Current Opinion in Biotechnology
https://www.readbyqxmd.com/read/28073536/microelectrode-array-mea-platform-as-a-sensitive-tool-to-detect-and-evaluate-ostreopsis-cf-ovata-toxicity
#19
Susanna Alloisio, Valentina Giussani, Mario Nobile, Mariachiara Chiantore, Antonio Novellino
In the last decade, the occurrence of harmful dinoflagellate blooms of the genus Ostreopsis has increased both in frequency and in geographic distribution with adverse impacts on public health and the economy. Ostreopsis species are producers of palytoxin-like toxins (putative palytoxin and ovatoxins) which are among the most potent natural non-protein compounds known to date, exhibiting extreme toxicity in mammals, including humans. Most existing toxicological data are derived from in vivo mouse assay and are related to acute effects of pure palytoxin, without considering that the toxicity mechanism of dinoflagellates can be dependent on the varying composition of complex biotoxins mixture and on the presence of cellular components...
May 2016: Harmful Algae
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
#20
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
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