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https://www.readbyqxmd.com/read/29666465/molecular-epidemiology-of-lung-cancer-in-iran-implications-for-drug-development-and-cancer-prevention
#1
REVIEW
Zahra Fathi, Nicholas L Syn, Jian-Guo Zhou, Raheleh Roudi
Epidemiological studies undertaken over the past decades reveal a gradual but progressive increase in the incidence and mortality attributable to lung cancer in the Islamic Republic of Iran, a sovereign state geographically situated at the crossroads of Central Eurasia and Western Asia. We identified references published in English and Persian through searches of PubMed, EMBASE, Web of Science, Scopus, and the Scientific Information Database (SID)-a specialized Iranian database, which indexes Iranian scientific journals-between inception and 15 September 2017...
April 18, 2018: Journal of Human Genetics
https://www.readbyqxmd.com/read/29666456/serotonin-is-an-endogenous-regulator-of-intestinal-cyp1a1-via-ahr
#2
Christopher Manzella, Megha Singhal, Waddah A Alrefai, Seema Saksena, Pradeep K Dudeja, Ravinder K Gill
Aryl hydrocarbon receptor (AhR) is a nuclear receptor that controls xenobiotic detoxification via induction of cytochrome P450 1A1 (CYP1A1) and regulates immune responses in the intestine. Metabolites of L-tryptophan activate AhR, which confers protection against intestinal inflammation. We tested the hypothesis that serotonin (5-HT) is an endogenous activator of AhR in intestinal epithelial cells. Treatment of Caco-2 monolayers with 5-HT induced CYP1A1 mRNA in a time- and concentration-dependent manner and also stimulated CYP1A1 activity...
April 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29666259/shared-epitope-aryl-hydrocarbon-receptor-crosstalk-underlies-the-mechanism-of-gene-environment-interaction-in-autoimmune-arthritis
#3
Jiaqi Fu, Sarah V Nogueira, Vincent van Drongelen, Patrick Coit, Song Ling, Edward F Rosloniec, Amr H Sawalha, Joseph Holoshitz
The susceptibility to autoimmune diseases is affected by genetic and environmental factors. In rheumatoid arthritis (RA), the shared epitope (SE), a five-amino acid sequence motif encoded by RA-associated HLA-DRB1 alleles, is the single most significant genetic risk factor. The risk conferred by the SE is increased in a multiplicative way by exposure to various environmental pollutants, such as cigarette smoke. The mechanism of this synergistic interaction is unknown. It is worth noting that the SE has recently been found to act as a signal transduction ligand that facilitates differentiation of Th17 cells and osteoclasts in vitro and in vivo...
April 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29665350/pxr-structure-specific-activation-by-hepatotoxic-pyrrolizidine-alkaloids
#4
Claudia Luckert, Albert Braeuning, Alfonso Lampen, Stefanie Hessel-Pras
Pyrrolizidine alkaloids (PAs) comprise a large group of more than 660 secondary metabolites found in more than 6000 plant species worldwide. Acute PA intoxication induces severe liver damage. Chronic exposure to sub-lethal doses may cause cumulative damage or cancer. Nuclear receptor activation often constitutes a molecular event for xenobiotic-induced toxicity. However, so far nothing is known about potential interactions of PAs with nuclear receptors as a toxicological mode of action. Thus, in the present study PA-dependent activation of a comprehensive panel of nuclear receptors (PPARs, LXRα, RARα, RXRα, FXR, CAR, PXR, ERα/β) was investigated using GAL4/UAS-based transactivation reporter gene assays...
April 14, 2018: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29659532/genetic-heterogeneity-of-slc22-family-of-transporters-in-drug-disposition
#5
REVIEW
Elisa Lozano, Oscar Briz, Rocio I R Macias, Maria A Serrano, Jose J G Marin, Elisa Herraez
An important aspect of modern medicine is its orientation to achieve more personalized pharmacological treatments. In this context, transporters involved in drug disposition have gained well-justified attention. Owing to its broad spectrum of substrate specificity, including endogenous compounds and xenobiotics, and its strategical expression in organs accounting for drug disposition, such as intestine, liver and kidney, the SLC22 family of transporters plays an important role in physiology, pharmacology and toxicology...
April 16, 2018: Journal of Personalized Medicine
https://www.readbyqxmd.com/read/29659152/cranial-pair-i-the-olfactory-nerve
#6
Carlos Crespo, Teresa Liberia, José Miguel Blasco-Ibáñez, Juan Nácher, Emilio Varea
The olfactory nerve constitutes the first cranial pair. Compared with other cranial nerves, it depicts some atypical features. First, the olfactory nerve does not form a unique bundle. The olfactory axons join other axons and form several small bundles or fascicles: the fila olfactoria. These fascicles leave the nasal cavity, pass through the lamina cribrosa of the ethmoid bone and enter the brain. The whole of these fascicles is what is known as the olfactory nerve. Second, the olfactory sensory neurons, whose axons integrate the olfactory nerve, connect the nasal cavity and the brain without any relay...
April 16, 2018: Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology
https://www.readbyqxmd.com/read/29656515/comparative-cyp-omic-analysis-between-the-ddt-susceptible-and-resistant-drosophila-melanogaster-strains-91-c-and-91-r
#7
Keon Mook Seong, Brad S Coates, May R Berenbaum, John M Clark, Barry R Pittendrigh
BACKGROUND: Cytochrome P450 monooxygenases (P450s) are involved in the biosynthesis of endogenous intracellular compounds and the metabolism of xenobiotics, including chemical insecticides. We investigated the structural and expression level variance across all P450 genes with respect to the evolution of insecticide resistance under multigenerational DDT selection. RESULTS: RNA-seq and reverse transcriptase quantitative PCR indicated that the transcript levels of seven P450 genes were significantly up-regulated and three P450 genes were down-regulated in the DDT-resistant strain 91-R, as compared to the control strain 91-C...
April 15, 2018: Pest Management Science
https://www.readbyqxmd.com/read/29653076/e4bp4-regulates-carboxylesterase-2-enzymes-through-repression-of-the-nuclear-receptor-rev-erb%C3%AE-in-mice
#8
Mengjing Zhao, Tianpeng Zhang, Fangjun Yu, Lianxia Guo, Baojian Wu
Carboxylesterases (CES) are a family of phase I enzymes that plays an important role in xenobiotic clearance and lipid metabolism. Here, we investigate a potential role of E4 promoter-binding protein 4 (E4bp4) in regulation of Ces and CPT-11 (irinotecan, a first-line drug for treating colorectal cancer) pharmacokinetics in mice. Mouse hepatoma Hepa-1c1c7 cells were transfected with Rev-erbα expression plasmid or siRNA targeting E4bp4. The relative mRNA and protein levels of Ces enzymes in the cells or the livers of wild-type and E4bp4-deficient (E4bp4-/- ) mice were determined by qPCR and Western blotting, respectively...
April 10, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29650790/effect-of-endocannabinoid-oleamide-on-rat-and-human-liver-cytochrome-p450-enzymes-in-in-vitro-and-in-vivo-models
#9
Gabriela Dovrtelova, Ondrej Zendulka, Kristyna Noskova, Jan Jurica, Ondrej Pes, Jan Dusek, Alejandro Carazo, Iveta Zapletalova, Natasa Hlavacova, Petr Pavek
The endocannabinoid system is important for many physiological and pathological processes, but its role in the regulation of liver cytochromes P450 (CYPs) is still unknown. We studied the influence of the endocannabinoid oleamide on rat and human liver CYPs. Oleamide was administered i.p. to rats at doses of 0.1, 1 and 10 mg/kg/day for 7 days. The content and activity of key CYPs was evaluated in rat liver microsomes. Moreover, its interactions with nuclear receptors regulating CYP genes and serum levels of their ligands (prolactin, corticosterone, and free triiodothyronine) were tested in vitro CYP inhibition assays...
April 12, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29650557/sputum-proteomics-and-airway-cell-transcripts-of-current-and-ex-smokers-with-severe-asthma-in-u-biopred-an-exploratory-analysis
#10
Kentaro Takahashi, Stelios Pavlidis, Francois Ng Kee Kwong, Uruj Hoda, Christos Rossios, Kai Sun, Matthew Loza, Fred Baribaud, Pascal Chanez, Steve J Fowler, Ildiko Horvath, Paolo Montuschi, Florian Singer, Jacek Musial, Barbro Dahlen, Sven-Eric Dahlen, N Krug, Thomas Sandstrom, Dominic E Shaw, Rene Lutter, Per Bakke, Louise J Fleming, Peter H Howarth, Massimo Caruso, Ana R Sousa, Julie Corfield, Charles Auffray, Bertrand De Meulder, Diane Lefaudeux, Ratko Djukanovic, Peter J Sterk, Yike Guo, Ian M Adcock, Kian Fan Chung
Background: Severe asthma patients with a significant smoking history have airflow obstruction with reported neutrophilia. We hypothesise that multi-omic analysis will enable the definition of smoking and ex-smoking severe asthma molecular phenotypes. Methods: The U-BIOPRED severe asthma patients containing current-smokers (CSA), ex-smokers (ESA), non-smokers (NSA) and healthy non-smokers (NH) was examined. Blood and sputum cell counts, fractional exhaled nitric oxide and spirometry were obtained. Exploratory proteomic analysis of sputum supernatants and transcriptomic analysis of bronchial brushings, biopsies and sputum cells was performed...
April 12, 2018: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/29649238/generation-of-multidrug-resistant-human-tissues-by-overexpression-of-the-abcg2-multidrug-transporter-in-embryonic-stem-cells
#11
Zsuzsa Erdei, Anita Schamberger, György Török, Kornélia Szebényi, György Várady, Tamás I Orbán, László Homolya, Balázs Sarkadi, Ágota Apáti
The ABCG2 multidrug transporter provides resistance against various endo- and xenobiotics, and protects the stem cells against toxins and stress conditions. We have shown earlier that a GFP-tagged version of ABCG2 is fully functional and may be used to follow the expression, localization and function of this transporter in living cells. In the present work we have overexpressed GFP-ABCG2, driven by a constitutive (CAG) promoter, in HUES9 human embryonic stem cells. Stem cell clones were generated to express the wild-type and a substrate-mutant (R482G) GFP-ABCG2 variant, by using the Sleeping Beauty transposon system...
2018: PloS One
https://www.readbyqxmd.com/read/29645305/evolution-of-a-xenobiotic-degradation-pathway-formation-and-capture-of-the-labile-phthaloyl-coa-intermediate-during-anaerobic-phthalate-degradation
#12
Mario Mergelsberg, Valentin Egle, Matthias Boll
Xenobiotic phthalates are industrially produced on the annual million ton scale. The oxygen-independent enzymatic reactions involved in anaerobic phthalate degradation have only recently been elucidated. In vitro assays suggested that phthalate is first activated to phthaloyl-CoA followed by decarboxylation to benzoyl-CoA. Here, we report the heterologous production and characterization of the enzyme initiating anaerobic phthalate degradation from 'Aromatoleum aromaticum': a highly specific succinyl-CoA:phthalate CoA transferase (SPT, class III CoA transferase)...
April 12, 2018: Molecular Microbiology
https://www.readbyqxmd.com/read/29642532/ursodeoxycholate-restores-biliary-excretion-of-methotrexate-in-rats-with-ethinyl-estradiol-induced-cholestasis-by-restoring-canalicular-mrp2-expression
#13
Min Ju Kim, Yun Ju Kang, Mihwa Kwon, Young A Choi, Min-Koo Choi, Hye-Young Chi, Hye Hyun Yoo, Chang-Koo Shim, Im-Sook Song
The in vivo relevance of ursodeoxycholate (UDCA) treatment (100 mg/kg/day, per oral tid for 5 days before cholestasis induction followed by the same dosing for 5 days) on hepatic function was investigated in rats with 17α-ethinylestradiol (EE, 10 mg/kg, subcutaneous for 5 days)-induced experimental cholestasis. The bile flow rate and the expression level of hepatic multidrug resistance-associated protein 2 (Mrp 2) that were decreased in cholestasis were restored after UDCA treatment. Consistent with this, the biliary excretion clearance (CLexc,bile ) of a representative Mrp2 substrate-methotrexate (MTX)-was decreased in cholestatic rats but was restored after UDCA treatment...
April 9, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29629838/a-genetic-polymorphism-in-the-cyp1b1-gene-in-patients-with-squamous-cell-carcinoma-of-the-esophagus-an-iranian-mashhad-cohort-study-recruited-over-10-years
#14
Azam Rastgar Moghadam, Mehrane Mehramiz, Malihe Entezari, Hamideh Aboutalebi, Fatemeh Kohansal, Parisa Dadjoo, Hamid Fiuji, Mohammadreza Nasiri, Seyed Amir Aledavood, Kazem Anvari, Saeideh Ahmadi Simab, Mohammad Sadegh Khorrami, Ali Moradi, Seyed Mahdi Hassanian, Gordon A Ferns, Soodabeh Shahid Sales, Amir Avan
AIM: Esophageal cancer is the eighth most common cancer globally and the seventh most common cause of cancer-related deaths in men. Recent studies have shown that CYP450, family 1, subfamily B, polypeptide 1, which plays a role in the metabolism of xenobiotics, is associated with several cancers. Therefore, in the present study we investigated the association between a genetic variant, CYP1B1-rs1056836 gene, with the clinical characteristics of patients with squamous cell carcinoma of the esophagus (ESCC)...
April 9, 2018: Pharmacogenomics
https://www.readbyqxmd.com/read/29627441/amentoflavone-induced-oxidative-stress-activates-nf-e2-related-factor-2-via-the-p38-map-kinase-akt-pathway-in-human-keratinocytes
#15
Lilik Duwi Wahyudi, Jiwon Jeong, Heejung Yang, Jung-Hwan Kim
Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key transcription factor that responds to oxidative stress and xenobiotics. Multiple lines of evidence suggest that Nrf2 activation protects against aging, inflammation, and many diseases, including cancer. Nrf2 activators derived from natural sources have been widely studied. In this study, we investigated the effect of amentoflavone (AFN), a biflavonoid found in many plants, on Nrf2 signaling in human keratinocytes (HaCaT cells). AFN significantly increased ARE luciferase activity by Nrf2 accumulation in the nucleus...
April 5, 2018: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29626534/pharmacokinetics-pharmacodynamics-and-drug-transport-and-metabolism-nonlinear-protein-binding-not-what-you-think
#16
REVIEW
Amelia N Deitchman, Ravi Shankar Prasad Singh, Hartmut Derendorf
Nonlinear protein binding is traditionally thought of as an increasing fraction unbound with increasing total drug concentration. In the past several years, research into the protein binding of several tetracyclines has shown that an unexpected and counterintuitive phenomenon has been observed. Specifically, that of decreasing unbound drug fraction with increasing total concentrations of drug over certain concentration ranges. While several studies of tigecycline have shown the importance calcium and its chelation may play in the protein-drug interaction, the potential clinical implications and relevance have not been explored...
April 4, 2018: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29626198/aryl-hydrocarbon-receptor-and-intestinal-immunity
#17
REVIEW
Bruno Lamas, Jane M Natividad, Harry Sokol
Aryl hydrocarbon receptor (AhR) is a member of the basic helix-loop-helix-(bHLH) superfamily of transcription factors, which are associated with cellular responses to environmental stimuli, such as xenobiotics and oxygen levels. Unlike other members of bHLH, AhR is the only bHLH transcription factor that is known to be ligand activated. Early AhR studies focused on understanding the role of AhR in mediating the toxicity and carcinogenesis properties of the prototypic ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)...
April 7, 2018: Mucosal Immunology
https://www.readbyqxmd.com/read/29626075/sulfotransferase-4a1-sult4a1-increases-its-expression-in-mouse-neurons-as-they-mature
#18
Takuyu Hashiguchi, Sawako Shindo, Shih-Heng Chen, Jau-Shyong Hong, Masahiko Negishi
Cytosolic sulfotransferases (SULTs) catalyze sulfation and play essential roles in detoxification of xenobiotics as well as inactivation of endo-biotics. Sulfotransferase 4A1 (SULT4A1) which was originally isolated as a brain-specific sulfotransferase, is the most highly conserved isoform among SULTs in vertebrates. Here, expression of SULT4A1 was examined neuron enriched and neuron-glia mixed cells derived from mouse embryo brains at day 14 gestation and mixed glia from 2 days-old neonate brains. Western blots showed an increase of SULT4A1 expression as neurons maturated...
April 6, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29626056/methylindoles-and-methoxyindoles-are-agonists-and-antagonists-of-human-aryl-hydrocarbon-receptor-ahr
#19
Martina Stepankova, Iveta Bartonkova, Eva Jiskrova, Radim Vrzal, Sridhar Mani, Sandhya Kortagere, Zdenek Dvorak
Novel methyl-indoles were identified as endobiotic and xenobiotic ligands of human aryl hydrocarbon receptor (AhR). We examined the effects of 22 methylated and methoxylated indoles on the transcriptional activity of AhR. Employing reporter gene assays in AZ-AHR transgenic cells, we determined full agonist, partial agonist or antagonist activities of tested compounds, having substantially variable EC50 , IC50 and relative efficacies. The most effective agonists (EMAX relative to 5 nM dioxin) of AhR were 4-Me-indole (134%), 6-Me-indole (91%) and 7-MeO-indole (80%), respectively...
April 6, 2018: Molecular Pharmacology
https://www.readbyqxmd.com/read/29623833/new-therapeutic-drugs-from-bioactive-natural-molecules-the-role-of-gut-microbiota-metabolism-in-neurodegenerative-diseases
#20
Francesco Di Meo, Stella Donato, Alba Di Pardo, Vittorio Maglione, Stefania Filosa, Stefania Crispi
The gut-brain axis is considered a neuroendocrine system, which connects brain and gastrointestinal tract and plays an important role in stress response. The homeostasis of gut-brain axis is important for healthy conditions and its alterations are associated to neurological disorders and neurodegenerative diseases. Gut microbiota is a dynamic ecosystem that can be altered by external factors such as diet composition, antibiotics or xenobiotics. Recent advances in gut microbiota analyses indicate that the gut bacterial community plays a key role in maintaining normal brain functions...
April 3, 2018: Current Drug Metabolism
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