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https://www.readbyqxmd.com/read/28818587/phenanthrene-responsive-micrornas-and-their-targets-in-wheat-roots
#1
Jinfeng Li, Le Yue, Yu Shen, Yu Sheng, Xinhua Zhan, Guohua Xu, Baoshan Xing
MicroRNAs (miRNAs) play key roles in plant growth, development and responses to abiotic stress. Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental pollutants. However, it is yet unknown how miRNAs work during PAH uptake by plant roots. Thus, in this study we ascertain phenanthrene (a model PAH)-responsive miRNAs using small RNA high-throughput deep sequencing and their target genes in wheat roots. We identified 108 conserved and non-conserved miRNA members belonging to 82 miRNA families and found 11 differentially expressed miRNAs, among which four miRNAs (miR156, miR164, miR171a and miR9678-3p) were up-regulated and the other seven miRNAs (miR398, miR531, miR1121, miR5048-5p, miR9653b, miR9773 and miR9778) were down-regulated...
August 8, 2017: Chemosphere
https://www.readbyqxmd.com/read/28808886/assessment-of-pharmacokinetic-interactions-between-obeticholic-acid-and-caffeine-midazolam-warfarin-dextromethorphan-omeprazole-rosuvastatin-and-digoxin-in-phase-1-studies-in-healthy-subjects
#2
Jeffrey E Edwards, Lise Eliot, Andrew Parkinson, Sharon Karan, Leigh MacConell
INTRODUCTION: Obeticholic acid (OCA), a potent and selective farnesoid X receptor agonist, is indicated for the treatment of primary biliary cholangitis (PBC). We investigated the potential drug-drug interaction effect of OCA on metabolic CYP450 enzymes and drug transporters. METHODS: Five phase 1 single-center, open-label, fixed-sequence, inpatient studies were conducted in healthy adult subjects to evaluate the effect of oral daily doses of 10 or 25 mg OCA on single-dose plasma pharmacokinetics of specific probe substrates for enzymes CYP1A2 (caffeine, R-warfarin), CYP3A (midazolam, R-warfarin), CYP2C9 (S-warfarin), CYP2D6 (dextromethorphan), CYP2C19 (omeprazole), and drug transporters, BCRP/OATP1B1/OATP1B3 (rosuvastatin), and P-gp (digoxin)...
August 14, 2017: Advances in Therapy
https://www.readbyqxmd.com/read/28777516/hyperbaric-oxygenation-affects-the-mechanisms-of-acetylcholine-induced-relaxation-in-diabetic-rats
#3
Sanela Unfirer, Martina Mihalj, Sanja Novak, Aleksandar Kibel, Ava Cavka, Zrinka Mijalevic, Mario Gros, Ivica Brizic, Danijela Budimir, Anita Cosic, Mladen Boban, Ines Drenjancevic
The effects of hyperbaric oxygenation (HBO₂) on acetylcholine-induced vasorelaxation (AChIR) were evaluated in male Sprague-Dawley (SD) rats randomized into four groups: healthy controls (Ctrl), diabetic rats (DM), and control and diabetic rats that underwent hyperbaric oxygenation (Ctrl+HBO₂ and DM+HBO₂). AChIR was measured in aortic rings, with L-NAME, indomethacin, or MS-PPOH and a combination of inhibitors. mRNA expression of eNOS, iNOS, COX-1 and COX-2 was assessed by qPCR, and protein expression of CYP4A(1-3) by Western blot...
November 2016: Undersea & Hyperbaric Medicine: Journal of the Undersea and Hyperbaric Medical Society, Inc
https://www.readbyqxmd.com/read/28768289/%C3%AE-adrenergic-receptor-stimulated-cardiac-myocyte-apoptosis-role-of-cytochrome-p450-%C3%AF-hydroxylase
#4
Shan Jiang, Dan Huo, Xueying Wang, Huan Zhao, Jiang Tan, Qinghua Zeng, Stephen T OʼRourke, Chengwen Sun
Prolonged or excessive β-adrenergic activation leads to cardiac myocyte loss and heart dysfunction; however, the underlying cellular mechanisms are still unclear. Therefore, we first confirmed the effect of isoproterenol (ISO), a β-adrenergic receptor agonist, on cardiac toxicity using TUNEL and caspase activity assays in cultured rat cardiomyocytes. ISO treatment significantly increased cardiomyocyte apoptosis. Persistent ISO stimulation of cardiomyocytes also increased the expression of CYP4A3, a major CYP450 ω-hydroxylase that produces 20-hydroxyeicosatetraenoic acid (20-HETE) in a time-dependent manner...
August 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28767146/a-randomised-trial-of-effects-of-alcohol-on-cytochrome-p450-eicosanoids-mediators-of-inflammation-resolution-and-blood-pressure-in-men
#5
Anne E Barden, Venus Chavez, Michael Phillips, Emilie Mas, Lawrence J Beilin, Kevin D Croft, Trevor A Mori, Ian B Puddey
BACKGROUND: Cardiovascular effects of alcohol consumption may be influenced by both pro- and anti-inflammatory mechanisms. We previously showed that chronic alcohol consumption increased blood pressure (BP), oxidative stress and 20-hydroxyeicosatetraenoic acid (20-HETE), a vasoconstrictor and pro-inflammatory eicosanoid synthesised by CYP450 enzymes from arachidonic acid. This study in men examined the effect of consuming red wine (RW) on BP in relation to changes in 20-HETE, oxidative stress (F2 -isoprostanes), markers of inflammation, anti-inflammatory CYP450 epoxyeicosatrienoic acids (EETs) and specialised pro-resolving mediators of inflammation (SPMs) derived from eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)...
August 2, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28766385/paracetamol-overdose-induced-oxidative-stress-toxicity-metabolism-and-protective-effects-of-various-compounds-in-vivo-and-in-vitro
#6
Xu Wang, Qinghua Wu, Aimei Liu, Arturo Anadón, José-Luis Rodríguez, María-Rosa Martínez-Larrañaga, Zonghui Yuan, María-Aránzazu Martínez
Paracetamol (APAP) is one of the most widely used and popular over-the-counter analgesic and antipyretic drugs in the world when used at therapeutic doses. APAP overdose can cause severe liver injury, liver necrosis and kidney damage in human beings and animals. Many studies indicate that oxidative stress is involved in the various toxicities associated with APAP, and various antioxidants were evaluated to investigate their protective roles against APAP-induced liver and kidney toxicities. To date, almost no review has addressed the APAP toxicity in relation to oxidative stress...
August 16, 2017: Drug Metabolism Reviews
https://www.readbyqxmd.com/read/28757214/vulnerability-of-marsh-frog-pelophylax-ridibundus-to-the-typical-wastewater-effluents-ibuprofen-triclosan-and-estrone-detected-by-multi-biomarker-approach
#7
Halina I Falfushynska, Lesya L Gnatyshyna, Oksana Horyn, Oksana B Stoliar
Pharmaceutical and personal care products (PPCPs) are the environmental pollutants of growing concern. The aim of this study was to indicate the effects of typical PPCPs on the marsh frog Pelophylax ridibundus. We treated male frogs with waterborne ibuprofen (IBU, 250ng·L(-1)), triclosan (TCS, 500ng·L(-1)), or estrone (E1, 100ng·L(-1)) for 14days. Common vulnerability of the frogs was detected from dramatic decrease of Zn, total and metalated metallothionein (MT) concentrations, Zn/Cu ratio, the elevation of activity of glutathione-S-transferase, cathepsin D and DNA instability in the liver, the depletion of cholinesterase in the brain and cortisol in the blood plasma in all exposures...
July 27, 2017: Comparative Biochemistry and Physiology. Toxicology & Pharmacology: CBP
https://www.readbyqxmd.com/read/28756922/in%C3%A2-vitro-and-in%C3%A2-vivo-cytochrome-p450-3a-enzyme-inhibition-by-aframomum-melegueta-and-denniettia-tripetala-extracts
#8
Sunday O Nduka, Mathew J Okonta, Daniel L Ajaghaku, Chinwe V Ukwe
OBJECTIVE: To evaluate the in vitro and in vivo inhibitory effects of two commonly used herbs, Aframomum melegueta (A. melengueta) and Dennettia tripetala (D. tripetala) on CYP 3A enzymes. METHODS: In vitro inhibition of the enzymes were assessed with microsomes extracted from female albino rats using erythromycin-N-demethylation assay (EMND) method while their in vivo effects were measured by estimating simvastatin plasma concentrations in rats. Pharmacokinetic parameters were determined using non-compartmental analysis as implemented in WinNonlin pharmacokinetic program...
June 2017: Asian Pacific Journal of Tropical Medicine
https://www.readbyqxmd.com/read/28724942/physiological-oxygen-tension-reduces-hepatocyte-dedifferentiation-in-in-vitro-culture
#9
Ren Guo, Xinxiu Xu, Yuting Lu, Xin Xie
Primary hepatocytes cultured in vitro are a powerful tool to study the functions of hepatocytes and to evaluate the metabolism and toxicity of new drugs. However, in vitro culture of hepatocytes has proven to be very difficult. Ordinary culture conditions lead to dedifferentiation of hepatocytes, resulting in rapid change in cell morphology and significant reduction in specific cell functions. In the current study, we show that hepatocyte dedifferentiation is a rapid process under 21% O2 conditions. Hepatocytes cultured in 21% O2 undergo epithelial-to-mesenchymal transition (EMT), obtain fibroblast-like morphology, and show decreased hepatic functions...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28720324/synthesis-and-diabetic-neuropathic-pain-alleviating-effects-of-2n-pyrazol-3-yl-methylbenzo-d-isothiazole-1-1-dioxide-derivatives
#10
Jin Ri Hong, Young Jin Choi, Gyochang Keum, Ghilsoo Nam
A novel series of fused-benzensulfonamide 2-N-(pyrazol-3-yl)methylbenzo[d]isothiazole-1,1-dioxide derivatives was designed and synthesized as metabolically stable T-type calcium channel inhibitors. Several compounds, 9, 10, and 17, displayed potent T-type channel inhibitory activity. Among them, compounds 10 and 17 showed good metabolic stability in human liver microsomes, and low hERG channel and CYP450 inhibition. Compound 10 exhibited diabetic neuropathic pain-alleviating effects in a streptozotocin-induced peripheral diabetic neuropathy (PDN) model...
July 8, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28717048/rna-seq-of-rice-yellow-stem-borer-scirpophaga-incertulas-reveals-molecular-insights-during-four-larval-developmental-stages
#11
Renuka P, Maganti S Madhav, Padmakumari A P, Kalyani M Barbadikar, Sathendra K Mangrauthia, Vijaya Sudhakara Rao K, Soma S Marla, Ravindra Babu V
The yellow stem borer (YSB), Scirpophaga incertulas is a prominent pest in the rice cultivation causing serious yield losses. The larval stage is an important stage in YSB, responsible for maximum infestation. However, limited knowledge exists on biology and mechanisms underlying growth and differentiation of YSB. To understand and identify the genes involved in YSB development and infestation, so as to design pest control strategies, we performed de novo transcriptome at 1(st), 3(rd), 5(th) and 7(th) larval developmental stages employing Illumina Hi-seq...
July 17, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28706242/draft-whole-genome-sequence-of-groundnut-stem-rot-fungus-athelia-rolfsii-revealing-genetic-architect-of-its-pathogenicity-and-virulence
#12
M A Iquebal, Rukam S Tomar, M V Parakhia, Deepak Singla, Sarika Jaiswal, V M Rathod, S M Padhiyar, Neeraj Kumar, Anil Rai, Dinesh Kumar
Groundnut (Arachis hypogaea L.) is an important oil seed crop having major biotic constraint in production due to stem rot disease caused by fungus, Athelia rolfsii causing 25-80% loss in productivity. As chemical and biological combating strategies of this fungus are not very effective, thus genome sequencing can reveal virulence and pathogenicity related genes for better understanding of the host-parasite interaction. We report draft assembly of Athelia rolfsii genome of ~73 Mb having 8919 contigs. Annotation analysis revealed 16830 genes which are involved in fungicide resistance, virulence and pathogenicity along with putative effector and lethal genes...
July 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28698613/transcriptome-and-metabolite-analyses-in-azadirachta-indica-identification-of-genes-involved-in-biosynthesis-of-bioactive-triterpenoids
#13
Sweta Bhambhani, Deepika Lakhwani, Parul Gupta, Ashutosh Pandey, Yogeshwar Vikram Dhar, Sumit Kumar Bag, Mehar Hasan Asif, Prabodh Kumar Trivedi
Azadirachta indica A. Juss, commonly known as Neem, is the reservoir of triterpenoids of economic importance. Metabolite analysis of different developmental stages of leaf and fruit suggests tissue-specific accumulation of the major triterpenoids in this important tree. Though biosynthesis of these complex molecules requires substrate flux from the isoprenoid pathway, enzymes involved in late biosynthetic steps remain uncharacterized. We established and analyzed transcriptome datasets from leaf and fruit and identified members of gene families involved in intermediate steps of terpenoid backbone biosynthesis and those related to secondary transformation leading to the tissue-specific triterpenoid biosynthesis...
July 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28696416/cytochrome-p450-interactions-are-common-and-consequential-in-massachusetts-hospital-discharges
#14
T H McCoy, V M Castro, A Cagan, L Snapper, A Roberson, R H Perlis
Despite the recognition that drug-drug interactions contribute substantially to preventable health-care costs, the prevalence of such interactions related to the cytochrome P450 system in clinical practice remains poorly characterized. This study drew retrospective hospital discharge cohorts from a large health claims data set and a large health system data set. For every hospital discharge, frequency of co-occurrence of substrates and inducers or inhibitors at cytochrome P450 2D6, 2C19, 3A4 and 1A2 were determined...
July 11, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28690379/competitive-rational-inhibitor-design-to-4-maleylaceto-acetate-isomerase
#15
Narges Zolfaghari
Tyrosinemia type I is the result of genetic disorder in fomaryl acetoacetase gene that leads to 4-fumaryl acetoacetate accumulation. The current treatment for tyrosinemia type I is nitisinone that inhibits 4-hydroxyphenyl pyruvic dioxygenase in competitive manner. In the present study, we have designed two theoretical chemicals, which could inhibit the direct enzyme responsible for fumarylacetoacetate formation. Subset 2_p.0.5 from Zinc database was screened by PyRx software using a Lamarckian genetic algorithm as the scoring function for docking...
2017: Bioinformation
https://www.readbyqxmd.com/read/28689442/drug-interactions-in-hiv-infected-patients-treated-for-hepatitis-c
#16
REVIEW
Vicente Soriano, Pablo Labarga, José V Fernandez-Montero, Carmen de Mendoza, Laura Benítez-Gutiérrez, José M Peña, Pablo Barreiro
The introduction of direct-acting antivirals (DAA) has revolutionized the hepatitis C field. Most hepatitis C patients can now be cured, including those coinfected with HIV. However, drug-drug interactions (DDI) between DAA and antiretrovirals (ARV) should be known to prevent either toxicity due to drug overexposure or treatment failures due to low drug concentrations. Areas covered: Clinically significant DDI may be classified as major (when co-administration should be contraindicated) or minor (when they require close monitoring, changes in drug dosage or in timing)...
August 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28684064/protective-role-of-vitamin-e-preconditioning-of-human-dermal-fibroblasts-against-thermal-stress-in-vitro
#17
Hira Butt, Azra Mehmood, Muhammad Ali, Saba Tasneem, Muhammad Sohail Anjum, Moazzam N Tarar, Shaheen N Khan, Sheikh Riazuddin
AIMS: Oxidative microenvironment of burnt skin restricts the outcome of cell based therapies of thermal skin injuries. The aim of this study was to precondition human dermal fibroblasts with an antioxidant such as vitamin E to improve their survival and therapeutic abilities in heat induced oxidative in vitro environment. MAIN METHODS: Fibroblasts were treated with 100μM vitamin E for 24h at 37°C followed by heat shock for 10min at 51°C in fresh serum free medium...
September 1, 2017: Life Sciences
https://www.readbyqxmd.com/read/28678150/metabolism-of-the-marine-phycotoxin-ptx-2-and-its-effects-on-hepatic-xenobiotic-metabolism-activation-of-nuclear-receptors-and-modulation-of-the-phase-i-cytochrome-p450
#18
Jimmy Alarcan, Estelle Dubreil, Antoine Huguet, Dominique Hurtaud-Pessel, Stefanie Hessel-Pras, Alfonso Lampen, Valérie Fessard, Ludovic Le Hegarat
PTX-2 is a marine biotoxin frequently found in shellfish that can lead to food intoxication in humans. Information regarding PTX-2 metabolism is scarce, and little is known of its effect on xenobiotic-metabolizing enzymes (XME) or its molecular pathways. The aim of this study was consequently to examine PTX-2 Phase I metabolism using rat and human liver S9 fractions, and also to assess the capability of PTX-2: (i) to modulate the gene expression of a panel of Phase I (CYP450) and II (UGT, SULT, NAT, and GST) enzymes, as well as the Phase III or 0 (ABC and SLCO) transporters in the human hepatic HepaRG cell line using qPCR; (ii) to induce specific CYP450 in HepaRG cells measured by immunolabeling detection and the measurement of the cells' activities; and (iii) to activate nuclear receptors and induce CYP promoter activities in HEK-T and HepG2 transfected cell lines using transactivation and reporter gene assay, respectively...
July 5, 2017: Toxins
https://www.readbyqxmd.com/read/28677033/preparation-and-evaluation-of-self-microemulsions-for-improved-bioavailability-of-ginsenoside-rh1-and-rh2
#19
Feifei Yang, Jing Zhou, Xiao Hu, Stephanie Kyoungchun Yu, Chunyu Liu, Ruile Pan, Qi Chang, Xinmin Liu, Yonghong Liao
Due to intestinal cytochrome P450 (CYP450)-mediated metabolism and P-glycoprotein (P-gp) efflux, poor oral bioavailability hinders ginsenoside-Rh1 (Rh1) and ginsenoside-Rh2 (Rh2) from clinical application. In this study, Rh1 and Rh2 were incorporated into two self-microemulsions (SME-1 and SME-2) to improve oral bioavailability. SME-1 contained both CYP450 and P-gp inhibitory excipients while SME-2 only consisted of P-gp inhibitory excipients. Results for release, cellular uptake, transport, and lymph node distribution demonstrated no significant difference between either self-microemulsions in vivo, but were elevated significantly in comparison to the free drug...
July 5, 2017: Drug Delivery and Translational Research
https://www.readbyqxmd.com/read/28674395/comparative-transcriptome-analysis-on-the-synthesis-pathway-of-honey-bee-apis-mellifera-mandibular-gland-secretions
#20
YuQi Wu, HuoQing Zheng, Miguel Corona, Christian Pirk, Fei Meng, YuFei Zheng, FuLiang Hu
Secretions from mandibular glands (MGs) have important caste-specific functions that are associated with the social evolution of honey bees. To gain insights into the molecular architecture underlying these caste differences, we compared the gene expression patterns of MGs from queens, queenright workers (WQRs) and queenless workers (WQLs) using high-throughput RNA-sequencing technology. In total, we identified 46 candidate genes associated with caste-specific biosynthesis of fatty acid pheromones in the MG, including members of cytochrome P450 (CYP450) family and genes involved in fatty acid β-oxidation and ω-oxidation...
July 3, 2017: Scientific Reports
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