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https://www.readbyqxmd.com/read/27921136/penicillium-roqueforti-pr-toxin-gene-cluster-characterization
#1
Pedro I Hidalgo, Elisabeth Poirier, Ricardo V Ullán, Justine Piqueras, Laurence Meslet-Cladière, Emmanuel Coton, Monika Coton
PR toxin is a well-known isoprenoid mycotoxin almost solely produced by Penicillium roqueforti after growth on food or animal feed. This mycotoxin has been described as the most toxic produced by this species. In this study, an in silico analysis allowed identifying for the first time a 22.4-kb biosynthetic gene cluster involved in PR toxin biosynthesis in P. roqueforti. The pathway contains 11 open reading frames encoding for ten putative proteins including the major fungal terpene cyclase, aristolochene synthase, involved in the first farnesyl-diphosphate cyclization step as well as an oxidoreductase, an oxidase, two P450 monooxygenases, a transferase, and two dehydrogenase enzymes...
December 5, 2016: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/27920888/development-of-a-high-resolution-melting-analysis-method-for-cyp2c19-17-genotyping-in-healthy-volunteers
#2
Zahra Ghasemi, Mehrdad Hashemi, Mahsa Ejabati, Seyyed Meisam Ebrahimi, Hamidreza Kheiri Manjili, Ali Sharafi, Ali Ramazani
BACKGROUND: Genetic polymorphisms of drug metabolisms by cytochrome P450 (P450s) could affect drug response, attracting particular interest in the pharmacogenetics. Due to the importance of CYP2C19* 17 allele and its capability of super- fast metabolism and also lack of information about distribution of the alleles in Iranian population, this research aimed to use High Resolution Melting (HRM) method compared to PCR-RFLP for genotyping healthy Iranian population. METHODS: Blood samples were collected from 100 healthy Iranian volunteers...
October 2016: Avicenna Journal of Medical Biotechnology
https://www.readbyqxmd.com/read/27920817/pharmacological-characterization-of-liquiritigenin-a-chiral-flavonoid-in-licorice
#3
Samaa Alrushaid, Neal M Davies, Stephanie E Martinez, Casey L Sayre
Liquiritigenin is a chiral flavonoid present in plant based food, nutraceuticals, and traditional medicines. It is also an important ingredient present in licorice. The purpose of this study is to explore the pharmacological activity of racemic liquiritigenin utilizing several in vitro assays with relevant roles in colon cancer and diabetes. Where possible, the pure enantiomers were tested to identify the stereospecific contribution to the activity. In vitro antioxidant, anticancer, anti-inflammatory activities (cyclooxygenase inhibition), antidiabetic activities (alpha-amylase and alpha-glucosidase inhibition) as well as cytochrome P450 (CYP450) inhibitory activities were assessed...
October 2016: Research in Pharmaceutical Sciences
https://www.readbyqxmd.com/read/27920344/smad3-4-binding-to-promoter-ii-of-p450arom-so-as-to-regulate-aromatase-expression-in-endometriosis
#4
Juan Qu, Yuanyuan Zhu, Xiadi Wu, Juan Zheng, Zhen Hou, Yugui Cui, Yundong Mao, Jiayin Liu
Activin A can stimulate aromatase P450 (P450arom) expression in eutopic endometrial stromal cells (ESCs) of endometriosis by activin type I receptor-Smad pathway. In order to identify Smad3/4 binding to P450arom promoter II that mediates activin A response in ESCs, polymerase chain reaction (PCR) products of a serial truncated deletion of the P450arom promoter II region between -904 and +87 bp were inserted into the pGL3-basic vector to generate the promoter reporter plasmids. Luciferase reporter plasmids were cotransfected into cells with or without activin A (25 ng/mL)...
December 5, 2016: Reproductive Sciences
https://www.readbyqxmd.com/read/27919778/a-mutation-in-the-psst-homologue-of-complex-i-nadh-ubiquinone-oxidoreductase-from-tetranychus-urticae-is-associated-with-resistance-to-meti-acaricides
#5
Sabina Bajda, Wannes Dermauw, Rafaela Panteleri, Naoya Sugimoto, Vassilis Douris, Luc Tirry, Masahiro Osakabe, John Vontas, Thomas Van Leeuwen
The acaricidal compounds pyridaben, tebufenpyrad and fenpyroximate are frequently used in the control of phytophagous mites such as Tetranychus urticae, and are referred to as Mitochondrial Electron Transport Inhibitors, acting at the quinone binding pocket of complex I (METI-I acaricides). Because of their very frequent use, resistance evolved fast more than 20 years ago, and is currently wide-spread. Increased activity of P450 monooxygenases has been often associated with resistance, but target-site based resistance mechanisms were never reported...
December 2, 2016: Insect Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/27919191/phytotherapeutic-approach-a-new-hope-for-polycyclic-aromatic-hydrocarbons-induced-cellular-disorders-autophagic-and-apoptotic-cell-death
#6
Durgesh Nandini Das, Prashanta Kumar Panda, Prajna Paramita Naik, Subhadip Mukhopadhyay, Niharika Sinha, Sujit K Bhutia
Polycyclic aromatic hydrocarbons (PAHs) comprise the major class of cancer-causing chemicals and are ranked ninth among the chemical compounds threatening to humans. Moreover, interest in PAHs has been mainly due to their carcinogenic property, these compounds are genotoxic, teratogenic, mutagenic, and carcinogenic. Polymorphism in cytochrome P450 (CYP450) and aryl hydrocarbon receptor (AhR) have the capacity to convert procarcinogens into carcinogens, which is an imperative factor contributing to individual susceptibility to cancer development...
December 5, 2016: Toxicology Mechanisms and Methods
https://www.readbyqxmd.com/read/27919007/challenges-in-assignment-of-allosteric-effects-in-cytochrome-p450-catalyzed-substrate-oxidations-to-structural-dynamics-in-the-hemoprotein-architecture
#7
Peter Hlavica
Cytochrome P450s (CYP) represent a superfamily of b-type hemoproteins catalyzing NAD(P)H-dependent oxidative biotransformation of a vast array of natural and xenobiotic compounds. Many eu- and prokaryotic members of this class of monooxygenases display complex non-Michaelis-Menten saturation kinetics, suggestive of homo-/heterotropic cooperativity arising from substrate-/effector-induced allosteric interactions. Here, the paradigm of multiple-ligand occupancy of the catalytic pocket in combination with enzyme oligomerization provides the most favored explanations for the atypical kinetic patterns...
November 25, 2016: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/27918912/predicting-cyp2d6-phenotype-from-resting-brain-perfusion-images-by-gradient-boosting
#8
Giulio Napolitano, Julia C Stingl, Matthias Schmid, Roberto Viviani
The cytochrome P450 enzyme 2D6 is involved in the metabolism of 20% of all commonly used drugs, including many psychotropic drugs and CNS-active substances. CYP2D6 is among the CYP enzymes with the highest expression levels in the brain, suggesting a role in the local brain metabolism of psychotropic drugs and the existence of endogenous substrates. The genetic polymorphism of CYP2D6, which causes individual differences in activity levels of the enzyme, has also been characterized functionally in human brain imaging studies...
November 22, 2016: Psychiatry Research
https://www.readbyqxmd.com/read/27918126/versatile-trityl-spin-labels-for-nanometer-distance-measurements-on-biomolecules-in%C3%A2-vitro-and-within-cells
#9
J Jacques Jassoy, Andreas Berndhäuser, Fraser Duthie, Sebastian P Kühn, Gregor Hagelueken, Olav Schiemann
Structure determination of biomacromolecules under in-cell conditions is a relevant yet challenging task. Electron paramagnetic resonance (EPR) distance measurements in combination with site-directed spin labeling (SDSL) are a valuable tool in this endeavor but the usually used nitroxide spin labels are not well-suited for in-cell measurements. In contrast, triarylmethyl (trityl) radicals are highly persistent, exhibit a long relaxation time and a narrow spectral width. Here, the synthesis of a versatile collection of trityl spin labels and their application in in vitro and in-cell trityl-iron distance measurements on a cytochrome P450 protein are described...
December 5, 2016: Angewandte Chemie
https://www.readbyqxmd.com/read/27918111/imatinib-accelerates-progenitor-cell-mediated-liver-regeneration-in-choline-deficient-ethionine-supplemented-diet-fed-mice
#10
András Rókusz, Edina Bugyik, Vanessza Szabó, Armanda Szücs, Sándor Paku, Péter Nagy, Katalin Dezső
Severe chronic hepatic injury can induce complex reparative processes. Ductular reaction and the appearance of small hepatocytes are standard components of this response, which is thought to have both adverse (e.g. fibrosis, carcinogenesis) and beneficial (regeneration) consequences. This complex tissue reaction is regulated by orchestrated cytokine action. We have investigated the influence of the tyrosine kinase inhibitor imatinib on a regenerative process. Ductular reaction was induced in mice by the widely used choline-deficient ethionine-supplemented diet (CDE)...
December 5, 2016: International Journal of Experimental Pathology
https://www.readbyqxmd.com/read/27916218/fenofibrate-attenuates-malignant-hypertension-by-suppression-of-the-renin-angiotensin-system-a-study-in-cyp1a1-ren-2-transgenic-rats
#11
Šárka Jíchová, Šárka Doleželová, Libor Kopkan, Elzbieta Kompanowska-Jezierska, Janusz Sadowski, Luděk Červenka
BACKGROUND: Malignant hypertension is a life-threatening condition, and its pathophysiology is still poorly understood. The present study was designed to evaluate the role of interaction of the renin-angiotensin system with 20-hydroxyeicosatetraenoic acid (20-HETE), a product of cytochrome P450 (CYP)-dependent ω-hydroxylase pathway, in the pathophysiology of angiotensin II (ANG II)-dependent malignant hypertension in Cyp1a1-Ren-2 transgenic rats. METHODS: Malignant hypertension was induced by 12 days׳ dietary administration of 0...
December 2016: American Journal of the Medical Sciences
https://www.readbyqxmd.com/read/27915193/metabolic-fate-and-detectability-of-the-new-psychoactive-substances-2-4-bromo-2-5-dimethoxyphenyl-n-2-methoxyphenyl-methyl-ethanamine-25b-nbome-and-2-4-chloro-2-5-dimethoxyphenyl-n-2-methoxyphenyl-methyl-ethanamine-25c-nbome-in-human-and-rat-urine-by-gc-ms
#12
Achim T Caspar, Simon D Brandt, Andreas E Stoever, Markus R Meyer, Hans H Maurer
25B-NBOMe and 25C-NBOMe are potent 5-HT2A receptor agonists that have been associated with inducing hallucinogenic effects in drug users and severe intoxications. This paper describes the identification of their metabolites in rat and human urine by liquid chromatography (LC)-high resolution (HR)-MS/MS, the comparison of metabolite formation in vitro and in vivo and in different species, the general involvement of human cytochrome-P450 (CYP) isoenzymes on their metabolism steps, and their detectability by standard urine screening approaches (SUSAs) using GC-MS, LC-MS(n), or LC-HR-MS/MS...
November 27, 2016: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/27914545/potential-mode-of-action-of-a-novel-plumbagin-as-a-mosquito-repellent-against-the-malarial-vector-anopheles-stephensi-culicidae-diptera
#13
Venkatraman Pradeepa, Sengottayan Senthil-Nathan, Subbiah Sathish-Narayanan, Selvaraj Selin-Rani, Prabhakaran Vasantha-Srinivasan, Annamalai Thanigaivel, Athirstam Ponsankar, Edward-Sam Edwin, Muthiah Sakthi-Bagavathy, Kandaswamy Kalaivani, Kadarkarai Murugan, Veeramuthu Duraipandiyan, Naif Abdullah Al-Dhabi
Plumbagin was isolated and characterized from the roots of Plumbago zeylanica using chromatography: TLC, Column chromatogram, HPLC, FTIR and (1)H NMR. The isolated pure compounds were assayed for potency as inhibitors of: acetylcholine esterase (AchE), glutathione S-transferases (GST), superoxide dismutase (SOD), cytochrome P450 and α, β-esterase, and for repellency with Anopheles stephensi at four different concentrations (25, 50, 75 and 100ppm). The enzyme assay against the pure compound reveals that the level of esterase and SOD was decreased significantly in contrast the level of GST and cytochrome P450 was increased significantly...
November 2016: Pesticide Biochemistry and Physiology
https://www.readbyqxmd.com/read/27914535/indoxacarb-biotransformation-in-the-german-cockroach
#14
Ameya D Gondhalekar, Ernesto S Nakayasu, Isabel Silva, Bruce Cooper, Michael E Scharf
Insecticides that are used for pest control undergo physical and biological (enzymatic) degradation. Indoxacarb is an oxadiazine class sodium channel blocker insecticide used for German cockroach (Blattella germanica L.) control. At present, no information is available on enzymatic biotransformation or metabolism of indoxacarb in this important urban pest. We studied the biotransformation pathways of indoxacarb in one susceptible and three field strains with varying susceptibility levels using liquid chromatography and high-resolution mass spectrometry...
November 2016: Pesticide Biochemistry and Physiology
https://www.readbyqxmd.com/read/27914530/isochlorogenic-acid-a-affects-p450-and-ugt-enzymes-in-vitro-and-in-vivo
#15
Jing Wang, Hong Wang, Ying Peng, Guang-Ji Wang, Hai-Ping Hao
Isochlorogenic acid A (ICQA), which has anti-inflammatory, hepatoprotective, and antiviral properties, is commonly presented in fruits, vegetables, coffee, plant-based food products, and herbal medicines. These herbal medicines are usually used in combination with other medicines in the clinic. However, little is known about the regulatory effects of ICQA on drug-metabolizing enzymes and the herb-drug interactions. In the present study, we evaluated the inhibitory potentials of ICQA on CYP1A2, CYP2C9, CYP2C19, CYP3A4, CYP2D6, and CYP2E1 in vitro based on a cocktail approach...
November 2016: Chinese Journal of Natural Medicines
https://www.readbyqxmd.com/read/27913826/partial-gene-sequencing-of-cyp1a-vitellogenin-and-metallothionein-in-mosquitofish-gambusia-yucatana-and-gambusia-sexradiata
#16
Roberto Vázquez-Euán, Karla S Escalante-Herrera, Gabriela Rodríguez-Fuentes
Ground characteristics in the Yucatan Peninsula make recovery and treatment of wastewater very expensive. This situation has contributed to an increase of pollutants in the aquifer. Unfortunately, studies related to the effects of those pollutants in native organisms are scarce. The aim of this work was to obtain partial sequences of widely known genes used as biomarkers of pollutant effect in Gambusia yucatana and Gambusia sexradiata. The studied genes were: cytochrome P450 1A (CYP1A); vitellogenin (VTG); metallothionein (MT), and two housekeeping genes, 18S and β-actin...
December 2, 2016: Bulletin of Environmental Contamination and Toxicology
https://www.readbyqxmd.com/read/27913210/trpv4-activation-of-endothelial-nitric-oxide-synthase-resists-nonalcoholic-fatty-liver-disease-by-blocking-cyp2e1-mediated-redox-toxicity
#17
Ratanesh K Seth, Suvarthi Das, Diptadip Dattaroy, Varun Chandrashekaran, Firas Alhasson, Gregory Michelotti, Mitzi Nagarkatti, Prakash Nagarkatti, Anna Mae Diehl, Darwin P Bell, Wolfgang Liedtke, Saurabh Chatterjee
NAFLD is a clinically progressive disease with steatosis, inflammation, endothelial dysfunction and fibrosis being the stages where clinical intervention becomes necessary. Lack of early biomarkers and absence of a FDA approved drug obstructs efforts for effective treatment. NAFLD progression is strongly linked to a balance between liver injury, tissue regeneration and the functioning of endogenous defense mechanisms. The failure of the defense pathways to resist the tissue damage arising from redox stress, one of the "multiple hits" in disease progression, give rise to heightened inflammation and occasional fibrosis...
November 29, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27913146/effects-of-high-fat-diet-on-plasma-profiles-of-eicosanoid-metabolites-in-mice
#18
Weicang Wang, Jun Yang, Haixia Yang, Katherine Z Sanidad, Bruce D Hammock, Daeyoung Kim, Guodong Zhang
Obesity is a serious health problem in the US and is associated with increased risks of various human diseases. To date, the mechanisms by which obesity increases the risks of a wide range of human diseases are not well understood. Here we used a LC-MS/MS-based lipidomics, which can analyze >100 bioactive lipid mediators produced by cyclooxygenase, lipoxygenase, and cytochrome P450 enzymes, to analyze plasma profiles of lipid mediators in high-fat diet induced obesity in C57BL/6 mice. Our results show that the plasma concentrations of epoxyoctadecenoic acids (EpOMEs, also termed as leukotoxins) are significantly increased in plasma of high-fat diet-fed mice, in addition, EpOMEs are among the most abundant lipid mediators detected in mouse plasma...
November 30, 2016: Prostaglandins & Other Lipid Mediators
https://www.readbyqxmd.com/read/27910907/micrornas-modulate-adaption-to-multiple-abiotic-stresses-in-chlamydomonas-reinhardtii
#19
Xiang Gao, Fengge Zhang, Jinlu Hu, Wenkai Cai, Ge Shan, Dongsheng Dai, Kaiyao Huang, Gaohong Wang
MicroRNAs play an important role in abiotic stress responses in higher plants and animals, but their role in stress adaptation in algae remains unknown. In this study, the expression of identified and putative miRNAs in Chlamydomonas reinhardtii was assessed using quantitative polymerase chain reaction; some of the miRNAs (Cre-miR906-3p) were up-regulated, whereas others (Cre-miR910) were down-regulated when the species was subjected to multiple abiotic stresses. With degradome sequencing data, we also identified ATP4 (the d-subunit of ATP synthase) and NCR2 (NADPH: cytochrome P450 reductase) as one of the several targets of Cre-miR906-3p and Cre-miR910, respectively...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27910036/evaluation-of-the-pharmacokinetic-interaction-between-venetoclax-a-selective-bcl-2-inhibitor-and-warfarin-in-healthy-volunteers
#20
Ahmed Hamed Salem, Beibei Hu, Kevin J Freise, Suresh K Agarwal, Dilraj S Sidhu, Shekman L Wong
BACKGROUND AND OBJECTIVE: Venetoclax is a selective, B-cell lymphoma-2 inhibitor that has demonstrated clinical efficacy in a variety of hematological malignancies. In vitro data indicated weak cytochrome P450 (CYP) 2C9 inhibition by venetoclax; however, it is not predicted to cause clinically relevant inhibition due to high plasma protein binding. A Phase 1 study was conducted in healthy volunteers to evaluate the effect of venetoclax on warfarin pharmacokinetics. METHODS: Subjects received a single oral dose of 5 mg warfarin on day 1 of both periods 1 and 2, separated by a 14 days washout...
December 2, 2016: Clinical Drug Investigation
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