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network toxicology

Olivier Taboureau, Karine Audouze
During the past decades, many epidemiological, toxicological and biological studies have been performed to assess the role of environmental chemicals as potential toxicants for diverse human disorders. However, the relationships between diseases based on chemical exposure have been rarely studied by computational biology. We developed a human environmental disease network (EDN) to explore and suggest novel disease-disease and chemical-disease relationships. The presented scored EDN model is built upon the integration on systems biology and chemical toxicology using chemical contaminants information and their disease relationships from the reported TDDB database...
October 21, 2016: ALTEX
Yongbo Bao, Xiao Liu, Weiwei Zhang, Jianping Cao, Wei Li, Chenghua Li, Zhihua Lin
Clam, a filter-feeding lamellibranch mollusk, is capable to accumulate high levels of trace metals and has therefore become a model for investigation the mechanism of heavy metal toxification. In this study, the effects of cadmium were characterized in the gills of Tegillarca granosa during a 96-hour exposure course using integrated metabolomic and proteomic approaches. Neurotoxicity and disturbances in energy metabolism were implicated according to the metabolic responses after Cd exposure, and eventually affected the osmotic function of gill tissue...
October 20, 2016: Scientific Reports
Johannes F Wentzel, Martani J Lombard, Lissinda H Du Plessis, Lizelle Zandberg
Mycotoxins are toxic secondary metabolites produced by a range of fungi and are common contaminants of agricultural crops. These toxins are chemically diverse and structurally stable, enabling them to enter the food chain which can lead to numerous adverse health effects in animals and humans. Although mycotoxin exposure is associated with the development of several cancers, it has proved challenging to show a direct connection between exposure and oncogenic change. This study investigates the in vitro cytotoxicity, molecular mechanisms and secondary signalling responses associated with the exposure to three major mycotoxins, fumonisin B1 (FB1), deoxynivalenol (Don) and zearalenone (Zea)...
October 18, 2016: Archives of Toxicology
Hiroshi Yamazaki
Research over the past 30 years has elucidated the roles of polymorphic human liver cytochrome P450 (P450) enzymes associated with toxicological and/or pharmacological actions. Thalidomide exerts its various pharmacological and toxic actions in primates through multiple mechanisms, including nonspecific modification of many protein networks after bioactivation by autoinduced human P450 enzymes. To overcome species-differences between rodents, currently, nonhuman primates and/or mouse models with transplanted human hepatocytes are used...
October 17, 2016: Chemical Research in Toxicology
Min Wu, Qingxiong Yu, Qingfeng Li
Alopecia is a dermatological condition with limited therapeutic options. Only two drugs, finasteride and minoxidil, are approved by FDA for alopecia treatment. However, little is known about the differences in adverse effects between these two drugs. We examined the clinical reports submitted to the FDA Adverse Event Reporting System (FAERS) from 2004 to 2014. For both female and males, finasteride was found to be more associated with reproductive toxicity as compared to minoxidil. Among male alopecia cases, finasteride was significantly more concurrent with several forms of sexual dysfunction...
October 12, 2016: Oncotarget
Daniel P Bondeson, Craig M Crews
Protein homeostasis networks are highly regulated systems responsible for maintaining the health and productivity of cells. Whereas therapeutics have been developed to disrupt protein homeostasis, more recently identified techniques have been used to repurpose homeostatic networks to effect degradation of disease-relevant proteins. Here, we review recent advances in the use of small molecules to degrade proteins in a selective manner. First, we highlight all-small-molecule techniques with direct clinical application...
October 12, 2016: Annual Review of Pharmacology and Toxicology
Narsis A Kiani, Ming-Mei Shang, Jesper Tegnér
Drug discovery is complex and expensive. Numerous drug candidates fail rather late in clinical trials or even after released to the market. This is due to not only commercial considerations and less optimal drug efficacies, but adverse reactions originating from toxic effects constitute a major challenge. During the last two decades significant advances has been made enabling early prediction of toxic effects using in silico techniques. Yet, these essentially statistical techniques have not by design taken the disease driving pathophysiological mechanisms into account...
October 3, 2016: Current Pharmaceutical Design
John F Carriger, Todd M Martin, Mace G Barron
The mode of toxic action (MoA) has been recognized as a key determinant of chemical toxicity, but development of predictive MoA classification models in aquatic toxicology has been limited. We developed a Bayesian network model to classify aquatic toxicity MoA using a recently published dataset containing over one thousand chemicals with MoA assignments for aquatic animal toxicity. Two dimensional theoretical chemical descriptors were generated for each chemical using the Toxicity Estimation Software Tool. The model was developed through augmented Markov blanket discovery from the dataset of 1098 chemicals with the MoA broad classifications as a target node...
September 13, 2016: Aquatic Toxicology
Daniel Simão, Ana P Terrasso, Ana P Teixeira, Catarina Brito, Ursula Sonnewald, Paula M Alves
The generation of human neural tissue-like 3D structures holds great promise for disease modeling, drug discovery and regenerative medicine strategies. Promoting the establishment of complex cell-cell interactions, 3D culture systems enable the development of human cell-based models with increased physiological relevance, over monolayer cultures. Here, we demonstrate the establishment of neuronal and astrocytic metabolic signatures and shuttles in a human 3D neural cell model, namely the glutamine-glutamate-GABA shuttle...
2016: Scientific Reports
Salil N Pendse, Alexandra Maertens, Michael Rosenberg, Dipanwita Roy, Rick A Fasani, Marguerite M Vantangoli, Samantha J Madnick, Kim Boekelheide, Albert J Fornace, Shelly-Ann Odwin, James D Yager, Thomas Hartung, Melvin E Andersen, Patrick D McMullen
The twenty-first century vision for toxicology involves a transition away from high-dose animal studies to in vitro and computational models (NRC in Toxicity testing in the 21st century: a vision and a strategy, The National Academies Press, Washington, DC, 2007). This transition requires mapping pathways of toxicity by understanding how in vitro systems respond to chemical perturbation. Uncovering transcription factors/signaling networks responsible for gene expression patterns is essential for defining pathways of toxicity, and ultimately, for determining the chemical modes of action through which a toxicant acts...
September 3, 2016: Archives of Toxicology
Sandip Mondal, Kiran Bobde, Kaustav Aikat, Gopinath Halder
The present study explores the use of steam activated mung bean husk biochar (SA-MBHB) as a potential sorbent for the removal of non-steroidal and anti-inflammatory drug ibuprofen from aqueous solution. SA-MBHB was characterized by SEM, FTIR, BET, TGA, point of zero charge (pHPZC) and UV-Vis spectrophotometer. The relation between removal percentages of ibuprofen and parameters such as adsorbent dose (0.05 g-250 g), contact time (5 min-210 min), pH (2-10), speed of agitation (40-280 rpm), temperature (293-308 K) and initial ibuprofen concentration (5-100 ppm) was investigated and optimized by a series of batch sorption experiments...
November 1, 2016: Journal of Environmental Management
Mark F Miller, William H Goodson, Masoud H Manjili, Nicole Kleinstreuer, William H Bisson, Leroy Lowe
BACKGROUND: The current "single chemical as carcinogen" risk assessment paradigm might underestimate or miss the cumulative effects of exposure to chemical mixtures, as highlighted in recent work from the Halifax Project. This is particularly important for chemical exposures in the low-dose range that may be affecting crucial cancer hallmark mechanisms that serve to enable carcinogenesis. OBJECTIVE: Could ongoing low-dose exposures to a mixture of commonly encountered environmental chemicals produce effects in concert that lead to carcinogenesis? A workshop held at the NIEHS in August, 2015, evaluated the scientific support for the Low-Dose Mixture Hypothesis of Carcinogenesis and developed a research agenda...
August 12, 2016: Environmental Health Perspectives
George D Loizou
The exponential growth of the Internet of Things and the global popularity and remarkable decline in cost of the mobile phone is driving the digital transformation of medical practice. The rapidly maturing digital, non-medical world of mobile (wireless) devices, cloud computing and social networking is coalescing with the emerging digital medical world of omics data, biosensors and advanced imaging which offers the increasingly realistic prospect of personalized medicine. Described as a potential "seismic" shift from the current "healthcare" model to a "wellness" paradigm that is predictive, preventative, personalized and participatory, this change is based on the development of increasingly sophisticated biosensors which can track and measure key biochemical variables in people...
2016: Frontiers in Pharmacology
Shu Dong, Qi-Long Chen, Ya-Nan Song, Yang Sun, Bin Wei, Xiao-Yan Li, Yi-Yang Hu, Ping Liu, Shi-Bing Su
The classic toxicity of carbon tetrachloride (CCl4) is to induce liver lesion and liver fibrosis. Liver fibrosis is a consequence of chronic liver lesion, which can progress into liver cirrhosis even hepatocarcinoma. However, the toxicological mechanisms of CCl4-induced liver fibrosis remain not fully understood. We combined transcriptomic and proteomic analysis and biological network technology, predicted toxicological targets and regulatory networks of CCl4 in liver fibrosis. Wistar rats were treated with CCl4 for 9 weeks...
2016: Journal of Toxicological Sciences
Aishwarya Alex Namasivayam, Alejandro Ferreiro Morales, Ángela María Fajardo Lacave, Aravind Tallam, Borislav Simovic, David Garrido Alfaro, Dheeraj Reddy Bobbili, Florian Martin, Ganna Androsova, Irina Shvydchenko, Jennifer Park, Jorge Val Calvo, Julia Hoeng, Manuel C Peitsch, Manuel González Vélez Racero, Maria Biryukov, Marja Talikka, Modesto Berraquero Pérez, Neha Rohatgi, Noberto Díaz-Díaz, Rajesh Mandarapu, Rubén Amián Ruiz, Sergey Davidyan, Shaman Narayanasamy, Stéphanie Boué, Svetlana Guryanova, Susana Martínez Arbas, Swapna Menon, Yang Xiang
Biological network models offer a framework for understanding disease by describing the relationships between the mechanisms involved in the regulation of biological processes. Crowdsourcing can efficiently gather feedback from a wide audience with varying expertise. In the Network Verification Challenge, scientists verified and enhanced a set of 46 biological networks relevant to lung and chronic obstructive pulmonary disease. The networks were built using Biological Expression Language and contain detailed information for each node and edge, including supporting evidence from the literature...
2016: Gene Regulation and Systems Biology
Filippo Zanetti, Alain Sewer, Carole Mathis, Anita R Iskandar, Radina Kostadinova, Walter K Schlage, Patrice Leroy, Shoaib Majeed, Emmanuel Guedj, Keyur Trivedi, Florian Martin, Ashraf Elamin, Céline Merg, Nikolai V Ivanov, Stefan Frentzel, Manuel C Peitsch, Julia Hoeng
Cigarette smoke (CS) has been reported to increase predisposition to oral cancer and is also recognized as a risk factor for many conditions including periodontal diseases, gingivitis, and other benign mucosal disorders. Smoking cessation remains the most effective approach for minimizing the risk of smoking-related diseases. However, reduction of harmful constituents by heating rather than combusting tobacco, without modifying the amount of nicotine, is a promising new paradigm in harm reduction. In this study, we compared effects of exposure to aerosol derived from a candidate modified risk tobacco product, the tobacco heating system (THS) 2...
August 15, 2016: Chemical Research in Toxicology
Deborah G Nguyen, Juergen Funk, Justin B Robbins, Candace Crogan-Grundy, Sharon C Presnell, Thomas Singer, Adrian B Roth
Modeling clinically relevant tissue responses using cell models poses a significant challenge for drug development, in particular for drug induced liver injury (DILI). This is mainly because existing liver models lack longevity and tissue-level complexity which limits their utility in predictive toxicology. In this study, we established and characterized novel bioprinted human liver tissue mimetics comprised of patient-derived hepatocytes and non-parenchymal cells in a defined architecture. Scaffold-free assembly of different cell types in an in vivo-relevant architecture allowed for histologic analysis that revealed distinct intercellular hepatocyte junctions, CD31+ endothelial networks, and desmin positive, smooth muscle actin negative quiescent stellates...
2016: PloS One
Paul Brownbill, Igor Chernyavsky, Barbara Bottalico, Gernot Desoye, Stefan Hansson, Gerry Kenna, Lisbeth E Knudsen, Udo R Markert, Nicola Powles-Glover, Henning Schneider, Lopa Leach
The human placenta is a critical life-support system that nourishes and protects a rapidly growing fetus; a unique organ, species specific in structure and function. We consider the pressing challenge of providing additional advice on the safety of prescription medicines and environmental exposures in pregnancy and how ex vivo and in vitro human placental models might be advanced to reproducible human placental test systems (HPTSs), refining a weight of evidence to the guidance given around compound risk assessment during pregnancy...
September 2016: Reproductive Toxicology
Silvia Cirillo, Donatella Canistro, Fabio Vivarelli, Moreno Paolini
Drinking water (DW) disinfection represents a milestone of the past century, thanks to its efficacy in the reduction of risks of epidemic forms by water micro-organisms. Nevertheless, such process generates disinfection by-products (DBPs), some of which are genotoxic both in animals and in humans and carcinogenic in animals. At present, chlorination is one of the most employed strategies but the toxicological effects of several classes of DBPs are unknown. In this investigation, a multidisciplinary approach foreseeing the chemical analysis of chlorinated DW samples and the study of its effects on mixed function oxidases (MFOs) belonging to the superfamily of cytochrome P450-linked monooxygenases of Cyprinus carpio hepatopancreas, was employed...
September 2016: Environmental Science and Pollution Research International
Luca Pagano, Alia D Servin, Roberto De La Torre-Roche, Arnab Mukherjee, Sanghamitra Majumdar, Joseph Hawthorne, Marta Marmiroli, Elena Maestri, Robert E Marra, Susan M Isch, Om Parkash Dhankher, Jason C White, Nelson Marmiroli
Functional toxicology has enabled the identification of genes involved in conferring tolerance and sensitivity to engineered nanomaterial (ENM) exposure in the model plant Arabidopsis thaliana (L.) Heynh. Several genes were found to be involved in metabolic functions, stress response, transport, protein synthesis, and DNA repair. Consequently, analysis of physiological parameters, metal content (through ICP-MS quantification), and gene expression (by RT-qPCR) of A. thaliana orthologue genes were performed across different plant species of agronomic interest to highlight putative biomarkers of exposure and effect related to ENMs...
July 5, 2016: Environmental Science & Technology
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