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https://www.readbyqxmd.com/read/27899995/systematic-tracking-of-disrupted-modules-identifies-significant-genes-and-pathways-in-hepatocellular-carcinoma
#1
Meng-Hui Zhang, Qin-Hai Shen, Zhao-Min Qin, Qiao-Ling Wang, Xi Chen
The objective of the present study is to identify significant genes and pathways associated with hepatocellular carcinoma (HCC) by systematically tracking the dysregulated modules of re-weighted protein-protein interaction (PPI) networks. Firstly, normal and HCC PPI networks were inferred and re-weighted based on Pearson correlation coefficient. Next, modules in the PPI networks were explored by a clique-merging algorithm, and disrupted modules were identified utilizing a maximum weight bipartite matching in non-increasing order...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27899317/neurotrophic-factor-mediated-neuronal-differentiation-of-human-cord-blood-mesenchymal-stem-cells-and-their-applicability-to-assess-the-developmental-neurotoxicity
#2
Sadaf Jahan, Dipak Kumar, Ashvini Kumar, Chetan Singh Rajpurohit, Shripriya Singh, Akriti Srivastava, Ankita Pandey, A B Pant
Plasticity and developmental capacity of stem cells have now been established as a promising tool to restore the degenerative disorders. The linearity differentiation of human mesenchymal stem cells (hMSCs) into adipogenic, chondrogenic, osteogenic and even in neuronal subtypes has been demonstrated. The number of xenobiotics such as dexamethasone, insulin, isobutyl 1-methyle xanthine and retinoic acid has been reported for the potential to differentiate hMSCs into neuronal subtypes. But, the applicability of indigenous neurotrphic factor-nerve growth factor (NGF) has not been explored for the purpose...
November 26, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27895264/sex-differences-in-human-and-animal-toxicology-toxicokinetics
#3
Michael Gochfeld
Sex, the states of being female or male, potentially interacts with all xenobiotic exposures, both inadvertent and deliberate, and influences their toxicokinetics (TK), toxicodynamics, and outcomes. Sex differences occur in behavior, exposure, anatomy, physiology, biochemistry, and genetics, accounting for female-male differences in responses to environmental chemicals, diet, and pharmaceuticals, including adverse drug reactions (ADRs). Often viewed as an annoying confounder, researchers have studied only one sex, adjusted for sex, or ignored it...
November 28, 2016: Toxicologic Pathology
https://www.readbyqxmd.com/read/27894940/changes-in-the-mrna-expression-of-structural-proteins-hormone-synthesis-and-secretion-from-bovine-placentome-sections-after-ddt-and-dde-treatment
#4
A Wojciechowska, J Mlynarczuk, J Kotwica
Disorders in the barrier function and secretory activity of the placenta can be caused by xenobiotics (XB) present in the environment and their accumulation in tissues of living organisms. Thus, the aim of this study was to investigate the effect of 1,1,1-trichloro-2,2,-bis-4-chlorophenyl-ethane (DDT) and its metabolite 1,1-dichloro-2,2-bis-4-chlorophenyl-ethene (DDE) (for 24 or 48h) at doses of 1, 10 or 100ng/ml on the function of cow placentome sections in the second trimester of pregnancy. DDT and DDE affected neither (P>0...
November 25, 2016: Toxicology
https://www.readbyqxmd.com/read/27894245/recent-advances-in-understanding-of-kinetic-interplay-between-phase-ii-metabolism-and-efflux-transport
#5
Shuai Wang, Huijie Xing, Mengjing Zhao, Danyi Lu, Zhijie Li, Dong Dong, Baojian Wu
Mechanistic understanding of the metabolism-transport interplay assumes great importance in pharmaceutical fields because the knowledge can help to interpret drug/xenobiotic metabolism and disposition studies as well as the drug-drug interactions in vivo. About 10 years ago, it started to recognize that cellular phase II metabolism is strongly influenced by the excretion (efflux transport) of generated metabolites, a kinetic phenomenon termed "phase II metabolism-transport interplay". This interplay is believed to have significant effects on the pharmacokinetics (bioavailability) of drugs/chemicals undergoing phase II metabolism...
November 28, 2016: Current Drug Metabolism
https://www.readbyqxmd.com/read/27894218/molecular-and-cellular-studies-on-the-absorption-function-and-safety-of-food-components-in-intestinal-epithelial-cells
#6
Hideo Satsu
The intestinal tract comes into direct contact with the external environment despite being inside the body. Intestinal epithelial cells, which line the inner face of the intestinal tract, have various important functions, including absorption of food substances, immune functions such as cytokine secretion, and barrier function against xenobiotics by means of detoxification enzymes. It is likely that the functions of intestinal epithelial cells are regulated or modulated by these components because they are frequently exposed to food components at high concentrations...
November 29, 2016: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/27892694/gene-polymorphism-profiles-of-drug-metabolising-enzymes-gstm1-gstt1-and-gstp1-in-an-argentinian-population
#7
Natalia Weich, Alejandro Roisman, Belén Cerliani, Hilda V Aráoz, Lilien Chertkoff, Silvina M Richard, Irma Slavutsky, Irene B Larripa, Ariela F Fundia
BACKGROUND: Glutathione S-transferases (GSTs) are drug-metabolising enzymes involved in biotransformation of carcinogens, drugs, xenobiotics and oxygen free radicals. Polymorphisms of GST genes contribute to inter-individual and population variability in the susceptibility to environmental risk factors, cancer predisposition and pharmacotherapy responses. However, data about GST variability in Argentina are lacking. AIM: The purpose was to determine the prevalence of GSTM1, GSTT1 and GSTP1 polymorphisms in the general population from a central region of Argentina and to perform inter-population comparisons...
November 28, 2016: Annals of Human Biology
https://www.readbyqxmd.com/read/27890585/cadmium-in%C3%A2-vivo-exposure-alters-stress-response-and-endocrine-related-genes-in-the-freshwater-snail-physa-acuta-new-biomarker-genes-in-a-new-model-organism
#8
Pedro Martínez-Paz, Mónica Morales, Paloma Sánchez-Argüello, Gloria Morcillo, José Luis Martínez-Guitarte
The freshwater snail Physa acuta is a sensitive organism to xenobiotics that is appropriate for toxicity testing. Cadmium (Cd) is a heavy metal with known toxic effects on several organisms, which include endocrine disruption and activation of the cellular stress responses. There is scarce genomic information on P. acuta; hence, in this work, we identify several genes related to the hormonal system, the stress response and the detoxification system to evaluate the effects of Cd. The transcriptional activity of the endocrine-related genes oestrogen receptor (ER), oestrogen-related receptor (ERR), and retinoid X receptor (RXR), the heat shock proteins genes hsp70 and hsp90 and a metallothionein (MT) gene was analysed in P...
November 24, 2016: Environmental Pollution
https://www.readbyqxmd.com/read/27890005/mechanism-based-inhibitors-from-phytomedicine-risks-of-hepatotoxicity-and-their-potential-hepatotoxic-substructures
#9
Lili Wang, Xin He, Chunhuan Jin, Gregory Ondieki
The adverse reactions and side effects associated with use of herbal medicines, especially their damaging effects on the liver have increasingly been reported worldwide. Some of the herbal ingredients have the potential risk of herb-induced liver injury but their hepatotoxicity mechanisms and associated risk factors are not well characterized until now. Xenobiotics are catalyzed by cytochrome P450 enzymes into highly reactive metabolites, which can covalently bind to the enzyme itself and subsequently cause mechanism-based inhibition (MBI)...
November 23, 2016: Current Drug Metabolism
https://www.readbyqxmd.com/read/27889639/sulforaphane-is-a-nrf2-independent-inhibitor-of-mitochondrial-fission
#10
Gary B O'Mealey, William L Berry, Scott M Plafker
The KEAP1-Nrf2-ARE antioxidant system is a principal means by which cells respond to oxidative and xenobiotic stresses. Sulforaphane (SFN), an electrophilic isothiocyanate derived from cruciferous vegetables, activates the KEAP1-Nrf2-ARE pathway and has become a molecule-of-interest in the treatment of diseases in which chronic oxidative stress plays a major etiological role. We demonstrate here that the mitochondria of cultured, human retinal pigment epithelial (RPE-1) cells treated with SFN undergo hyperfusion that is independent of both Nrf2 and its cytoplasmic inhibitor KEAP1...
November 21, 2016: Redox Biology
https://www.readbyqxmd.com/read/27889186/circadian-homeostasis-of-liver-metabolism-suppresses-hepatocarcinogenesis
#11
Nicole M Kettner, Horatio Voicu, Milton J Finegold, Cristian Coarfa, Arun Sreekumar, Nagireddy Putluri, Chinenye A Katchy, Choogon Lee, David D Moore, Loning Fu
Chronic jet lag induces spontaneous hepatocellular carcinoma (HCC) in wild-type mice following a mechanism very similar to that observed in obese humans. The process initiates with non-alcoholic fatty liver disease (NAFLD) that progresses to steatohepatitis and fibrosis before HCC detection. This pathophysiological pathway is driven by jet-lag-induced genome-wide gene deregulation and global liver metabolic dysfunction, with nuclear receptor-controlled cholesterol/bile acid and xenobiotic metabolism among the top deregulated pathways...
November 14, 2016: Cancer Cell
https://www.readbyqxmd.com/read/27889180/rapid-restoration-of-methanogenesis-in-an-acidified-uasb-reactor-treating-2-4-6-trichlorophenol-tcp
#12
María Consuelo Díaz-Báez, Juan Daniel Valderrama-Rincon
Anaerobic bioreactors are often used for removal of xenobiotic and highly toxic pollutants from wastewater. Most of the time, the pollutant is so toxic that the stability of the reactor becomes compromised. It is well known that methanogens are one of the most sensitive organisms in the anaerobic consortia and hence the stability of the reactors is highly dependant on methanogenesis. Unfortunately few studies have focused on recovering the methanogenic activity once it has been inhibited by highly toxic pollutants...
November 18, 2016: Journal of Hazardous Materials
https://www.readbyqxmd.com/read/27886581/a-multi-omic-approach-to-elucidate-low-dose-effects-of-xenobiotics-in-zebrafish-danio-rerio-larvae
#13
Susie S Y Huang, Jonathan P Benskin, Nik Veldhoen, Bharat Chandramouli, Heather Butler, Caren C Helbing, John R Cosgrove
Regulatory-approved toxicity assays such as the OECD Fish Embryo Toxicity Assay (TG236) allow correlation of chemical exposure to adverse morphological phenotypes. However, these assays are ineffective in assessing sub-lethal (i.e. low-dose) effects, or differentiating between similar phenotypes induced by different chemicals. Inclusion of multi-omic analyses in studies investigating xenobiotic action provides improved characterization of biological response, thereby enhancing prediction of toxicological outcomes in whole animals in the absence of morphological effects...
November 18, 2016: Aquatic Toxicology
https://www.readbyqxmd.com/read/27885867/protein-corona-modulation-of-hepatocyte-uptake-and-molecular-mechanisms-of-gold-nanoparticle-toxicity
#14
Kyoungju Choi, Jim E Riviere, Nancy A Monteiro-Riviere
Protein corona formation over gold nanoparticles (AuNP) can modulate cellular responses by altering AuNP physicochemical properties. The liver plays an essential role in metabolism, detoxification and elimination of xenobiotics and drugs as well as circulating NP clearance. We investigated human hepatic uptake of 40 and 80nm AuNP with branched polyethylenimine (BPEI), lipoic acid (LA) and polyethylene glycol (PEG) coatings as well as human plasma protein (HP) and human serum albumin (HSA) coronas. AuNP-mediated cytotoxicity, reactive oxygen/reactive nitrogen species (ROS/RNS), and CYP activity in human hepatocytes as well as molecular mechanisms with 40nm bare and HP BPEI-AuNP were investigated...
November 25, 2016: Nanotoxicology
https://www.readbyqxmd.com/read/27885582/biotransformation-of-herbicides-by-aquatic-microbial-communities-associated-to-submerged-leaves
#15
Louis Carles, Florent Rossi, Muriel Joly, Pascale Besse-Hoggan, Isabelle Batisson, Joan Artigas
Leaf microbial communities possess a large panel of enzymes permitting the breakdown of leaf polymers as well as the transformation of organic xenobiotic compounds present in stream waters. This study aims to assess the potential of leaf microbial communities, exhibiting different exposure histories to pesticides (upstream versus downstream), to biotransform three maize herbicides (mesotrione, S-metolachlor, and nicosulfuron) in single and cocktail molecule exposures. The results showed a high dissipation of nicosulfuron (sulfonylurea herbicide) (from 29...
November 24, 2016: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/27884721/comparison-of-xenobiotic-metabolising-human-porcine-rodent-and-piscine-cytochrome-p450
#16
REVIEW
Viktoriia Burkina, Martin Krøyer Rasmussen, Nadezhda Pilipenko, Galia Zamaratskaia
Cytochrome P450 proteins (CYP450s) are present in most domains of life and play a critical role in the metabolism of endogenous compounds and xenobiotics. The effects of exposure to xenobiotics depend heavily on the expression and activity of drug-metabolizing CYP450s, which is determined by species, genetic background, age, gender, diet, and exposure to environmental pollutants. Numerous reports have investigated the role of different vertebrate CYP450s in xenobiotic metabolism. Model organisms provide powerful experimental tools to investigate Phase I metabolism...
November 21, 2016: Toxicology
https://www.readbyqxmd.com/read/27884472/impact-of-untreated-wastewater-on-a-major-european-river-evaluated-with-a-combination-of-in%C3%A2-vitro-bioassays-and-chemical-analysis
#17
Maria König, Beate I Escher, Peta A Neale, Martin Krauss, Klára Hilscherová, Jiří Novák, Ivana Teodorović, Tobias Schulze, Sven Seidensticker, Muhammad Arslan Kamal Hashmi, Jörg Ahlheim, Werner Brack
Complex mixtures of micropollutants, including pesticides, pharmaceuticals and industrial chemicals emitted by wastewater effluents to European rivers may compromise the quality of these water resources and may pose a risk to ecosystem health and abstraction of drinking water. In the present study, an integrated analytical and bioanalytical approach was applied to investigate the impact of untreated wastewater effluents from the city of Novi Sad, Serbia, into the River Danube. The study was based on three on-site large volume solid phase extracted water samples collected upstream and downstream of the untreated wastewater discharge...
November 21, 2016: Environmental Pollution
https://www.readbyqxmd.com/read/27883283/usefulness-of-transthoracic-echocardiography-parameters-and-brain-natriuretic-peptide-as-mortality-predictors-in-hospitalized-acutely-poisoned-patients-a-prospective-observational-study
#18
Catalina Lionte, Victorita Sorodoc, Cristina Bologa, Cristina Tuchilus, Elisabeta Jaba
Acute poisonings represent a common cause of morbidity and mortality worldwide. The prognostic utility of the transthoracic echocardiography (TTE) parameters combined with brain natriuretic peptide (BNP) in acute poisoning with different xenobiotics, upon admission in the hospital was not evaluated. This prospective observational cohort study included 229 acutely poisoned non-diabetic adults, with a median age of 44 years (range 18-90 years), 50.7% women, with an in-hospital mortality rate of 8.7%. Univariate logistic regression analysis showed that age, the left ventricle kinetic abnormalities, the E wave deceleration time (EDT) and BNP correlated significantly with mortality in acutely poisoned patients...
November 24, 2016: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/27883262/phytochemicals-enhance-antioxidant-enzyme-expression-to-protect-against-nsaid-induced-oxidative-damage-of-the-gastrointestinal-mucosa
#19
REVIEW
Yu-Ting Cheng, Chi-Cheng Lu, Gow-Chin Yen
The gastrointestinal mucosa provides the first protective barrier for digested food and xenobiotics, which are easily attacked by toxic substances. Non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin, diclofenac, indomethacin, and ketoprofen, are widely used in clinical medicine, but these drugs may cause oxidative stress, leading to gastrointestinal damage, such as ulcers. Lansoprazol, omeprazole, and other clinical drugs are widely used to treat duodenal and gastric ulcers and haven been shown to have multiple biological functions, such as antioxidant activity and the ability to upregulate antioxidant enzymes in vivo...
November 24, 2016: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/27879438/a-comparison-of-rodent-and-nonrodent-laryngeal-and-tracheal-bifurcation-sensitivities-in-inhalation-toxicity-studies-and-their-relevance-for-human-exposure
#20
Vasanthi Mowat, David J Alexander, Andrew M Pilling
In inhalation toxicity studies, drug-induced lesions are frequently reported in the larynx and sometimes at the tracheal bifurcation (carina) in the rat, but less so in the dog or monkey, bringing into question the relevance of these rodent findings for humans. The rat larynx is widely considered to be more sensitive than that of the dog and monkey in its response to inhaled xenobiotics, although we could find no published data to support this. In this review, data from 52 inhalation studies involving rodent and nonrodent species were collated and reviewed...
November 22, 2016: Toxicologic Pathology
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