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https://www.readbyqxmd.com/read/28277368/diagnostic-tests-for-evaluation-of-stillbirth-stillbirth-collaborative-research-network
#1
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
#2
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
#3
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...
February 27, 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
#4
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
#5
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
#6
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 ten 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 USA. PARTICIPANTS: A total of 3,592 patients in ten 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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
https://www.readbyqxmd.com/read/28028702/field-evidence-of-bird-poisonings-by-imidacloprid-treated-seeds-a-review-of-incidents-reported-by-the-french-sagir-network-from-1995-to-2014
#13
Florian Millot, Anouk Decors, Olivier Mastain, Thomas Quintaine, Philippe Berny, Danièle Vey, Romain Lasseur, Elisabeth Bro
The large-scale use of neonicotinoid insecticides has raised growing concerns about their potential adverse effects on farmland birds, and more generally on biodiversity. Imidacloprid, the first neonicotinoid commercialized, has been identified as posing a risk for seed-eating birds when it is used as seed treatment of some crops since the consumption of a few dressed seeds could cause mortality. But evidence of direct effects in the field is lacking. Here, we reviewed the 103 wildlife mortality incidents reported by the French SAGIR Network from 1995 to 2014, for which toxicological analyses detected imidacloprid residues...
December 27, 2016: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28005974/bibliometrics-for-social-validation
#14
Daniel J Hicks
This paper introduces a bibliometric, citation network-based method for assessing the social validation of novel research, and applies this method to the development of high-throughput toxicology research at the US Environmental Protection Agency. Social validation refers to the acceptance of novel research methods by a relevant scientific community; it is formally independent of the technical validation of methods, and is frequently studied in history, philosophy, and social studies of science using qualitative methods...
2016: PloS One
https://www.readbyqxmd.com/read/27979774/gene-regulatory-networks-in-differentiation-and-direct-reprogramming-of-hepatic-cells
#15
REVIEW
Claude Gérard, Janne Tys, Frédéric P Lemaigre
Liver development proceeds by sequential steps during which gene regulatory networks (GRNs) determine differentiation and maturation of hepatic cells. Characterizing the architecture and dynamics of these networks is essential for understanding how cell fate decisions are made during development, and for recapitulating these processes during in vitro production of liver cells for toxicology studies, disease modelling and regenerative therapy. Here we review the GRNs that control key steps of liver development and lead to differentiation of hepatocytes and cholangiocytes in mammals...
December 12, 2016: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/27978797/prediction-of-chemical-multi-target-profiles-and-adverse-outcomes-with-systems-toxicology
#16
Henri Wathieu, Abiola Ojo, Sivanesan Dakshanamurthy
The field of systems biology, termed systems toxicology when applied to the characterization of adverse outcomes following chemical exposure, seeks to develop biological networks to explain phenotypic responses. Ideally, these are qualitatively and quantitatively similar to the actual network of biological entities that have functional consequences in living organisms. In this review, we outline computational tools for predicting chemical-protein interactions of multi-target compounds. Then, we discuss how the methods of systems toxicology currently draw on those interactions to predict resulting adverse outcomes which include diseases, adverse drug reactions, and toxic endpoints...
December 14, 2016: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/27933809/development-and-validation-of-a-computational-model-for-androgen-receptor-activity
#17
Nicole C Kleinstreuer, Patricia Ceger, Eric D Watt, Matthew Martin, Keith Houck, Patience Browne, Russell S Thomas, Warren M Casey, David J Dix, David Allen, Srilatha Sakamuru, Menghang Xia, Ruili Huang, Richard Judson
Testing thousands of chemicals to identify potential androgen receptor (AR) agonists or antagonists would cost millions of dollars and take decades to complete using current validated methods. High-throughput in vitro screening (HTS) and computational toxicology approaches can more rapidly and inexpensively identify potential androgen-active chemicals. We integrated 11 HTS ToxCast/Tox21 in vitro assays into a computational network model to distinguish true AR pathway activity from technology-specific assay interference...
December 9, 2016: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/27901397/a-systems-toxicology-approach-reveals-the-wnt-mapk-crosstalk-pathway-mediated-reproductive-failure-in-caenorhabditis-elegans-exposed-to-graphene-oxide-go-but-not-to-reduced-graphene-oxide-rgo
#18
Nivedita Chatterjee, Youngho Kim, Jisu Yang, Carlos P Roca, Sang-Woo Joo, Jinhee Choi
The potential hazards of graphene nanomaterials were investigated by exposing the nematode Caenorhabditis elegans to graphene oxide (GO) and reduced graphene oxide (rGO). The underlying mechanisms of the nano-bio interaction were addressed with an integrated systems toxicology approach using global transcriptomics, network-based pathway analysis, and experimental validation of the in-silico-derived hypotheses. Graphene oxide was found to reduce the worms' reproductive health to a greater degree than rGO, but it did not affect survival (24 h endpoint)...
December 20, 2016: Nanotoxicology
https://www.readbyqxmd.com/read/27890000/reproductive-toxicity-of-t-cells-in-early-life-abnormal-immune-development-and-postnatal-diseases
#19
Han-Xiao Liu, Aifang Jiang, Ting Chen, Wen Qu, Hui-Yi Yan, Jie Ping
Immunity is a balanced status with adequate biological defenses to recognize and fight "non-self", as well as adequate tolerance to recognize "self". To maintain this immune homeostasis, a well-organized T cell immune network is required, which in part depends on the well-controlled development of alternative effector T cells, with different cytokine repertoires. Recent research has pointed that developing fetal T cells network is a remarkably sensitive toxicological target for adverse factors in early life...
November 24, 2016: Current Drug Targets
https://www.readbyqxmd.com/read/27865774/a-systems-toxicology-approach-for-comparative-assessment-biological-impact-of-an-aerosol-from-a-candidate-modified-risk-tobacco-product-and-cigarette-smoke-on-human-organotypic-bronchial-epithelial-cultures
#20
Anita R Iskandar, Carole Mathis, Walter K Schlage, Stefan Frentzel, Patrice Leroy, Yang Xiang, Alain Sewer, Shoaib Majeed, Laura Ortega-Torres, Stephanie Johne, Emmanuel Guedj, Keyur Trivedi, Gilles Kratzer, Celine Merg, Ashraf Elamin, Florian Martin, Nikolai V Ivanov, Manuel C Peitsch, Julia Hoeng
This study reports a comparative assessment of the biological impact of a heated tobacco aerosol from the tobacco heating system (THS) 2.2 and smoke from a combustible 3R4F cigarette. Human organotypic bronchial epithelial cultures were exposed to an aerosol from THS2.2 (a candidate modified-risk tobacco product) or 3R4F smoke at similar nicotine concentrations. A systems toxicology approach was applied to enable a comprehensive exposure impact assessment. Culture histology, cytotoxicity, secreted pro-inflammatory mediators, ciliary beating, and genome-wide mRNA/miRNA profiles were assessed at various time points post-exposure...
March 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
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