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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
#1
Nivedita Chatterjee, Young-Ho 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)...
November 30, 2016: Nanotoxicology
https://www.readbyqxmd.com/read/27890000/reproductive-toxicity-of-t-cells-in-early-life-abnormal-immune-development-and-postnatal-diseases
#2
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
#3
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...
November 16, 2016: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/27848238/a-tractable-method-for-measuring-nanomaterial-risk-using-bayesian-networks
#4
Finbarr Murphy, Barry Sheehan, Martin Mullins, Hans Bouwmeester, Hans J P Marvin, Yamine Bouzembrak, Anna L Costa, Rasel Das, Vicki Stone, Syed A M Tofail
While control banding has been identified as a suitable framework for the evaluation and the determination of potential human health risks associated with exposure to nanomaterials (NMs), the approach currently lacks any implementation that enjoys widespread support. Large inconsistencies in characterisation data, toxicological measurements and exposure scenarios make it difficult to map and compare the risk associated with NMs based on physicochemical data, concentration and exposure route. Here we demonstrate the use of Bayesian networks as a reliable tool for NM risk estimation...
December 2016: Nanoscale Research Letters
https://www.readbyqxmd.com/read/27832950/the-chick-embryo-chorioallantoic-membrane-cam-assay
#5
Domenico Ribatti
During avian development the mesodermal layers of the allantois and chorion fuse to form the chorioallantoic membrane (CAM). This structure rapidly expands generating a rich vascular network that provides an interface for gas and waste exchange. The CAM allows to study tissue grafts, tumor growth and metastasis, drugs delivery and toxicologic analysis, and angiogenic and anti-angiogenic molecules. The CAM is relatively simple, quick, and low-cost model that allows screening of a large number of pharmacological samples in a short time; does not require administrative procedures for obtaining ethics committee approval for animal experimentation...
November 7, 2016: Reproductive Toxicology
https://www.readbyqxmd.com/read/27799056/toxicity-of-graphene-family-nanoparticles-a-general-review-of-the-origins-and-mechanisms
#6
REVIEW
Lingling Ou, Bin Song, Huimin Liang, Jia Liu, Xiaoli Feng, Bin Deng, Ting Sun, Longquan Shao
Due to their unique physicochemical properties, graphene-family nanomaterials (GFNs) are widely used in many fields, especially in biomedical applications. Currently, many studies have investigated the biocompatibility and toxicity of GFNs in vivo and in intro. Generally, GFNs may exert different degrees of toxicity in animals or cell models by following with different administration routes and penetrating through physiological barriers, subsequently being distributed in tissues or located in cells, eventually being excreted out of the bodies...
October 31, 2016: Particle and Fibre Toxicology
https://www.readbyqxmd.com/read/27793746/evaluation-of-the-tobacco-heating-system-2-2-part-4-90-day-oecd-413-rat-inhalation-study-with-systems-toxicology-endpoints-demonstrates-reduced-exposure-effects-compared-with-cigarette-smoke
#7
Ee Tsin Wong, Ulrike Kogel, Emilija Veljkovic, Florian Martin, Yang Xiang, Stephanie Boue, Gregory Vuillaume, Patrice Leroyb, Emmanuel Guedj, Gregory Rodrigo, Nikolai V Ivanov, Julia Hoeng, Manuel C Peitsch, Patrick Vanscheeuwijck
The objective of the study was to characterize the toxicity from sub-chronic inhalation of test atmospheres from the candidate modified risk tobacco product (MRTP), Tobacco Heating System version 2.2 (THS2.2), and to compare it with that of the 3R4F reference cigarette. A 90-day nose-only inhalation study on Sprague-Dawley rats was performed, combining classical and systems toxicology approaches. Reduction in respiratory minute volume, degree of lung inflammation, and histopathological findings in the respiratory tract organs were significantly less pronounced in THS2...
October 25, 2016: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/27772743/electrophysiological-characterization-of-nsc-34-cell-line-using-microelectrode-array
#8
K R Sabitha, D Sanjay, B Savita, T R Raju, T R Laxmi
Neurons communicate with each other through intricate network to evolve higher brain functions. The electrical activity of the neurons plays a crucial role in shaping the connectivity. With motor neurons being vulnerable to neurodegenerative diseases, understanding the electrophysiological properties of motor neurons is the need of the hour, in order to comprehend the impairment of connectivity in these diseases. NSC-34 cell line serves as an excellent model to study the properties of motor neurons as they express Choline acetyltransferase (ChAT)...
November 15, 2016: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/27768803/human-environmental-disease-network-a-computational-model-to-assess-toxicology-of-contaminants
#9
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
https://www.readbyqxmd.com/read/27760991/identification-of-a-regulation-network-in-response-to-cadmium-toxicity-using-blood-clam-tegillarca-granosa-as-model
#10
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
https://www.readbyqxmd.com/read/27757495/evaluation-of-the-cytotoxic-properties-gene-expression-profiles-and-secondary-signalling-responses-of-cultured-cells-exposed-to-fumonisin-b1-deoxynivalenol-and-zearalenone-mycotoxins
#11
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
https://www.readbyqxmd.com/read/27750412/differences-in-toxicological-and-pharmacological-responses-mediated-by-polymorphic-cytochromes-p450-and-related-drug-metabolizing-enzymes
#12
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
https://www.readbyqxmd.com/read/27738338/differences-in-reproductive-toxicology-between-alopecia-drugs-an-analysis-on-adverse-events-among-female-and-male-cases
#13
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
https://www.readbyqxmd.com/read/27732798/targeted-protein-degradation-by-small-molecules
#14
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
https://www.readbyqxmd.com/read/27697024/systems-toxicology-systematic-approach-to-predict-toxicity
#15
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
https://www.readbyqxmd.com/read/27640153/a-bayesian-network-model-for-predicting-aquatic-toxicity-mode-of-action-using-two-dimensional-theoretical-molecular-descriptors
#16
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
https://www.readbyqxmd.com/read/27619889/functional-metabolic-interactions-of-human-neuron-astrocyte-3d-in-vitro-networks
#17
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
https://www.readbyqxmd.com/read/27592001/information-dependent-enrichment-analysis-reveals-time-dependent-transcriptional-regulation-of-the-estrogen-pathway-of-toxicity
#18
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
https://www.readbyqxmd.com/read/27544645/biosorptive-uptake-of-ibuprofen-by-steam-activated-biochar-derived-from-mung-bean-husk-equilibrium-kinetics-thermodynamics-modeling-and-eco-toxicological-studies
#19
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
https://www.readbyqxmd.com/read/27517672/low-dose-mixture-hypothesis-of-carcinogenesis-workshop-scientific-underpinnings-and-research-recommendations
#20
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
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