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https://www.readbyqxmd.com/read/28230985/discovery-of-competitive-and-non-competitive-ligands-of-the-organic-cation-transporter-1-oct1-slc22a1
#1
Eugene C Chen, Natalia Khuri, Xiaomin Liang, Adrian Stecula, Huan-Chieh Chien, Sook Wah Yee, Yong Huang, Andrej Sali, Kathleen M Giacomini
Organic cation transporter 1 (OCT1) plays a critical role in the hepatocellular uptake of structurally diverse endogenous compounds and xenobiotics. Here, we identified competitive and noncompetitive OCT1 interacting ligands in a library of 1,780 prescription drugs by combining in silico and in vitro methods. Ligands were predicted by docking against a comparative model based a eukaryotic homolog. In parallel, high-throughput screening (HTS) was conducted using the fluorescent probe substrate ASP+ in cells overexpressing human OCT1...
February 23, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28230183/drosophila-imaginal-disc-growth-factor-2-is-a-trophic-factor-involved-in-energy-balance-detoxification-and-innate-immunity
#2
Vaclav Broz, Lucie Kucerova, Lenka Rouhova, Jana Fleischmannova, Hynek Strnad, Peter J Bryant, Michal Zurovec
Drosophila imaginal disc growth factor 2 (IDGF2) is a member of chitinase-like protein family (CLPs) able to induce the proliferation of imaginal disc cells in vitro. In this study we characterized physiological concentrations and expression of IDGF2 in vivo as well as its impact on the viability and transcriptional profile of Drosophila cells in vitro. We show that IDGF2 is independent of insulin and protects cells from death caused by serum deprivation, toxicity of xenobiotics or high concentrations of extracellular adenosine (Ado) and deoxyadenosine (dAdo)...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28228079/lipid-based-nanoparticles-as-carriers-for-dermal-delivery-of-antioxidants
#3
Lucia Montenegro
The skin, being the outermost layer of our body, is constantly exposed to oxidative stress induced by UV-radiation, pollutants, smoke and xenobiotics. To counteract the deleterious effects of such exposure, the skin is equipped with a complex anti-oxidation system, involving both exogenous and endogenous antioxidants. As low molecular weight antioxidants undergo depletion in counteracting oxidative stress occurring in the skin, topical supplementation with these agents is regarded as a suitable strategy to restore skin oxidative balance...
February 22, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/28224616/critical-cholangiocarcinogenesis-control-by-cryptochrome-clock-genes
#4
Ali Mteyrek, Elisabeth Filipski, Catherine Guettier, Malgorzata Oklejewicz, Gijsbertus T J van der Horst, Alper Okyar, Francis Lévi
A coordinated network of molecular circadian clocks in individual cells generates 24-hour rhythms in liver metabolism and proliferation. Circadian disruption through chronic jet lag or Per2 clock gene mutation was shown to accelerate hepatocarcinoma development in mice. Since divergent effects were reported for clock genes Per and Cry regarding xenobiotic toxicity, we questioned the role of Cry1 and Cry2 in liver carcinogenesis. Male WT and Cry1(-/-) Cry2(-/-) mice (C57Bl/6 background) were chronically exposed to diethylnitrosamine (DEN) at ZT11...
February 22, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28224477/genistein-alleviates-neuroinflammation-and-restores-cognitive-function-in-rat-model-of-hepatic-encephalopathy-underlying-mechanisms
#5
Ajaz Ahmad Ganai, Mohammad Husain
Hepatic encephalopathy (HE) is a neuropsychiatric syndrome resulting from acute liver failure. Previously, we demonstrated hepatoprotective effects of genistein in D-galactosamine (D-GalN)-induced fulminant hepatic failure (FHF). In this study, we evaluated behavioural and neuroprotective effects of genistein in rat model of HE. HE was induced by intraperitonial administration of D-GalN (250 mg/kg BW) twice a week for 30 days Genistein was given as co-treatment through oral gavage daily at dose of 5 mg/kg BW...
February 21, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28222448/acute-effects-of-viral-exposure-on-p-glyco-protein-function-in-the-mouse-fetal-blood-brain-barrier
#6
Enrrico Bloise, Sophie Petropoulos, Majid Iqbal, Alisa Kostaki, Tania Maria Ortiga-Carvalho, William Gibb, Stephen G Matthews
BACKGROUND/AIMS: Viral infection during pregnancy is known to affect the fetal brain. The toll-like receptor (TLR)-3 is a pattern recognition receptor activated by viruses known to elicit adverse fetal neurological outcomes. The P-glycoprotein (P-gp) efflux transporter protects the developing fetus by limiting the transfer of substrates across both the placenta and the fetal blood-brain barrier (BBB). As such, inhibition of P-gp at these blood-barrier sites may result in increased exposure of the developing fetus to environmental toxins and xenobiotics present in the maternal circulation...
February 22, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28222028/expression-purification-and-characterization-of-human-cytosolic-sulfotransferase-sult-1c4
#7
Amber L Guidry, Zachary E Tibbs, Melissa Runge-Morris, Charles N Falany
Human cytosolic sulfotransferase 1C4 (hSULT1C4) is a dimeric Phase II drug-metabolizing enzyme primarily expressed in the developing fetus. SULTs facilitate the transfer of a hydrophilic sulfonate moiety from 3'-phosphoadenosine-5'-phosphosulfate (PAPS) onto an acceptor substrate altering the substrate's biological activity and increasing the compound's water solubility. While several of the hSULTs' endogenous and xenobiotic substrates have been identified, the physiological function of hSULT1C4 remains unknown...
February 21, 2017: Hormone Molecular Biology and Clinical Investigation
https://www.readbyqxmd.com/read/28220138/de-novo-transcriptome-assembly-of-phomopsis-liquidambari-provides-insights-into-genes-associated-with-different-lifestyles-in-rice-oryza-sativa-l
#8
Jun Zhou, Xin Li, Yan Chen, Chuan-Chao Dai
The mechanisms that trigger the switch from endophytic fungi to saprophytic fungi are largely unexplored. Broad host range Phomopsis liquidambari is established in endophytic and saprophytic systems with rice (Oryza sativa L.). Endophytic P. liquidambari promotes rice growth, increasing rice yield and improving the efficiency of nitrogen fertilizer. This species's saprophytic counterpart can decompose rice litterfall, promoting litter organic matter cycling and the release of nutrients and improving the soil microbial environment...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28219047/strategies-in-the-designing-of-prodrugs-taking-into-account-the-antiviral-and-anticancer-compounds
#9
REVIEW
Monika A Lesniewska-Kowiel, Izabela Muszalska
Prodrugs are a wide group of substances of low or no pharmacological activity. The search for prodrugs is aimed at obtaining drugs characterized by better pharmacokinetic properties, pharmaceutical availability and selective activity of the active substance. Prodrug strategies involve chemical modifications and syntheses of new structures as well as the establishment of systems that deliver active substances for therapeutic aims that is prodrug-based treatments. The paper describes decisive factors in prodrug designing, such as enzymes participating in their activation, concepts of chemical modifications in the group of antiviral drugs and new anticancer treatments based on prodrugs (ADEPT, GDEPT, LEAPT)...
February 9, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28218677/biologic-stress-oxidative-stress-and-resistance-to-drugs-what-is-hidden-behind
#10
REVIEW
Maria Pantelidou, Karyofyllis Tsiakitzis, Eleni A Rekka, Panos N Kourounakis
Stress can be defined as the homeostatic, nonspecific defensive response of the organism to challenges. It is expressed by morphological, biochemical, and functional changes. In this review, we present biological and oxidative stress, as well as their interrelation. In addition to the mediation in biologic stress (central nervous, immune, and hormonal systems) and oxidative stress, the effect of these phenomena on xenobiotic metabolism and drug response is also examined. It is concluded that stress decreases drug response, a result which seems to be mainly attributed to the induction of hepatic drug metabolizing enzymes...
February 17, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28218636/lobular-distribution-and-variability-in-hepatic-atp-binding-cassette-protein-b1-abcb1-p-gp-ontogenetic-differences-and-potential-for-toxicity
#11
Ngu Njei Abanda, Zoe Riches, Abby C Collier
The ATP Binding Cassette B1 (ABCB1) transporter has critical roles in endo- and xenobiotic efficacy and toxicity. To understand population variability in hepatic transport we determined ABCB1 mRNA and protein levels in total liver lysates sampled from 8 pre-defined sites (n = 24, 18-69 years), and in S9 from randomly acquired samples (n = 87, 7 days-87 years). ABCB1 levels did not differ significantly throughout individual livers and showed 4.4-fold protein variation between subjects. Neither mRNA nor protein levels varied with sex, ethnicity, obesity or triglycerides in lysates or S9 (that showed the same relationships), but protein levels were lower in pediatric S9 (p < 0...
February 17, 2017: Pharmaceutics
https://www.readbyqxmd.com/read/28217095/endogenous-protein-interactome-of-human-udp-glucuronosyltransferases-exposed-by-untargeted-proteomics
#12
Michèle Rouleau, Yannick Audet-Delage, Sylvie Desjardins, Mélanie Rouleau, Camille Girard-Bock, Chantal Guillemette
The conjugative metabolism mediated by UDP-glucuronosyltransferase enzymes (UGTs) significantly influences the bioavailability and biological responses of endogenous molecule substrates and xenobiotics including drugs. UGTs participate in the regulation of cellular homeostasis by limiting stress induced by toxic molecules, and by controlling hormonal signaling networks. Glucuronidation is highly regulated at genomic, transcriptional, post-transcriptional and post-translational levels. However, the UGT protein interaction network, which is likely to influence glucuronidation, has received little attention...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28215799/comprehensive-understanding-of-pm2-5-on-gene-and-microrna-expression-patterns-in-zebrafish-danio-rerio-model
#13
Junchao Duan, Yang Yu, Yang Li, Li Jing, Man Yang, Ji Wang, Yanbo Li, Xianqing Zhou, Mark R Miller, Zhiwei Sun
PM2.5 is a major public health concern and some severe diseases have been attributed to exposure to PM2.5. However, a comprehensive understanding of gene and microRNA expression patterns induced by PM2.5 is missing. The objective of this study was to evaluate the toxicity of PM2.5 via genome-wide transcriptional analysis in the model teleost fish, zebrafish (Danio rerio). Gene ontology analysis revealed that the most impact gene functional categories induced by PM2.5 included oxidation-reduction process, transport, response to xenobiotic stimulus, response to chemical stimulus and metabolic process...
February 16, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28214915/evaluation-of-the-gard-assay-in-a-blind-cosmetics-europe-study
#14
Henrik Johansson, Robin Gradin, Andy Forreryd, Maria Agemark, Kathrin Zeller, Angelica Johansson, Olivia Larne, Erwin van Vliet, Carl Borrebaeck, Malin Lindstedt
Chemical hypersensitivity is an immunological response towards foreign substances, commonly referred to as sensitizers, which gives rise primarily to the clinical symptoms known as allergic contact dermatitis. For the purpose of mitigating risks associated with consumer products, chemicals are screened for sensitizing effects. Historically, such predictive screenings have been performed using animal models. However, due to industrial and regulatory demand, animal models for the purpose of sensitization assessment are being replaced by animal-free testing methods, a global trend that is spreading across industries and market segments...
February 17, 2017: ALTEX
https://www.readbyqxmd.com/read/28213243/multi-residue-analysis-of-36-priority-and-emerging-pollutants-in-marine-echinoderms-holothuria-tubulosa-and-marine-sediments-by-solid-liquid-extraction-followed-by-dispersive-solid-phase-extraction-and-liquid-chromatography-tandem-mass-spectrometry-analysis
#15
J Martín, A Zafra-Gómez, F Hidalgo, A J Ibáñez-Yuste, E Alonso, J L Vilchez
Marine echinoderms are filter-feeding invertebrates widely distributed along the coasts, and which are therefore extensively exposed to anthropogenic xenobiotics. They can serve as good sentinels for monitoring a large variety of contaminants in marine ecosystems. In this context, a multi-residue analytical method has been validated and applied to Holothuria tubulosa specimens and marine sediments for the determination of 36 organic compounds, which belong to some of the most problematic groups of emerging and priority pollutants (perfluoroalkyl compounds, estrogens, parabens, benzophenones, plasticizers, surfactants, brominated flame retardants and alkylphenols)...
May 1, 2017: Talanta
https://www.readbyqxmd.com/read/28212450/expression-and-activity-of-multidrug-resistance-proteins-in-mature-endothelial-cells-and-their-precursors-a-challenging-correlation
#16
Agnieszka Krawczenko, Aleksandra Bielawska-Pohl, Karolina Wojtowicz, Roksana Jura, Maria Paprocka, Elżbieta Wojdat, Urszula Kozłowska, Aleksandra Klimczak, Catherine Grillon, Claudine Kieda, Danuta Duś
Active cellular transporters of harmful agents-multidrug resistance (mdr) proteins-are present in tumor, stem and endothelial cells, among others. While mdr proteins are broadly studied in tumor cells, their role in non-tumor cells and the significance of their action not connected with removal of harmful xenobiotics is less extensively documented. Proper assessment of mdr proteins expression is difficult. Mdr mRNA presence is most often evaluated but that does not necessarily correlate with the protein level...
2017: PloS One
https://www.readbyqxmd.com/read/28209616/octn1-is-a-high-affinity-carrier-of-nucleoside-analogs
#17
Christina Drenberg, Alice A Gibson, Stanley Pounds, Lei Shi, Dena Rhinehart, Lie Li, Shuiying Hu, Guoqing Du, Anne T Nies, Matthias Schwab, Navjotsingh Pabla, William Blum, Tanja A Gruber, Sharyn D Baker, Alex Sparreboom
Resistance to xenobiotic nucleosides used to treat acute myeloid leukemia (AML) and other cancers remains a major obstacle to clinical management. One process suggested to participate in resistance is reduced uptake into tumor cells via nucleoside transporters, although precise mechanisms are not understood. Through transcriptomic profiling, we determined that low expression of the ergothioneine transporter OCTN1 (SLC22A4; ETT) strongly predicts poor event-free survival and overall survival in multiple cohorts of AML patients receiving treatment with the cytidine nucleoside analog cytarabine...
February 16, 2017: Cancer Research
https://www.readbyqxmd.com/read/28207188/polymorphism-in-the-abcb1-gene-is-associated-with-the-risk-of-bullous-pemphigoid-in-a-polish-population
#18
Mariola Rychlik-Sych, Małgorzata Barańska, Michał Dudarewicz, Jadwiga Skrętkowicz, Agnieszka Żebrowska, Jacek Owczarek, Elżbieta Waszczykowska
BACKGROUND AND OBJECTIVES: Polymorphisms in the P-glycoprotein-encoding ABCB1 gene may affect the intracellular concentration of xenobiotics, and thus contribute to the development of autoimmune diseases, including bullous pemphigoid (BP). The objective of the present study was to investigate whether there is an association between the C3435T and G2677T/A polymorphisms in the ABCB1 gene and the risk of BP in a Polish population. PATIENTS AND METHODS: The study included 71 patients with BP and 156 healthy volunteers...
February 16, 2017: Journal der Deutschen Dermatologischen Gesellschaft, Journal of the German Society of Dermatology: JDDG
https://www.readbyqxmd.com/read/28206856/effect-of-photoperiod-on-permethrin-resistance-in-aedes-aegypti
#19
O Karina Villanueva, Gustavo Ponce, Beatriz Lopez, Selene M Gutierrez, Iram P Rodriguez, Guadalupe Reyes, Karla J Saavedra, William C Black, Julian Garcia, Barry Beaty, Lars Eisen, Adriana E Flores
Living organisms have been exposed to light-dark cycles that allowed them to adapt to different ecological niches. Circadian cycles affect hormone release, metabolism, and response to xenobiotic compounds. Current studies have shown that insect susceptibility to toxic agents depends on circadian cycles, mainly because the biochemical processes involved in detoxification and responses to oxidative stress are modulated by this process. The goal of this study was to determine the effect of photoperiod on resistance to permethrin in Aedes aegypti ...
December 2016: Journal of the American Mosquito Control Association
https://www.readbyqxmd.com/read/28202360/lycopene-resveratrol-vitamin-c-and-feso4-increase-damage-produced-by-pro-oxidant-carcinogen-4-nitroquinoline-1-oxide-in-drosophila-melanogaster-xenobiotic-metabolism-implications
#20
I E Dueñas-García, M E Heres-Pulido, M R Arellano-Llamas, J De la Cruz-Núñez, V Cisneros-Carrillo, C S Palacios-López, L Acosta-Anaya, L F Santos-Cruz, L Castañeda-Partida, A Durán-Díaz
4-nitroquinoline-1-oxide (4-NQO) is a pro-oxidant carcinogen bioactivated by xenobiotic metabolism (XM). We investigated if antioxidants lycopene [0.45, 0.9, 1.8 μM], resveratrol [11, 43, 172 μM], and vitamin C [5.6 mM] added or not with FeSO4 [0.06 mM], modulate the genotoxicity of 4-NQO [2 mM] with the Drosophila wing spot test standard (ST) and high bioactivation (HB) crosses, with inducible and high levels of cytochromes P450, respectively. The genotoxicity of 4-NQO was higher when dissolved in an ethanol - acetone mixture...
February 12, 2017: Food and Chemical Toxicology
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