keyword
MENU ▼
Read by QxMD icon Read
search

1A2

keyword
https://www.readbyqxmd.com/read/29775322/prediction-of-human-cytochrome-p450-inhibition-using-a-multi-task-deep-autoencoder-neural-network
#1
Xiang Li, Youjun Xu, Luhua Lai, Jianfeng Pei
Adverse side effects of drug-drug interactions induced by human cytochrome P450 (CYP450) inhibition is an important consideration in drug discovery. It is highly desirable to develop computational models that can predict the inhibitive effect of a compound against a specific CYP450 isoform. In this study, we developed a multi-task model for concurrent inhibition prediction of five major CYP450 isoforms, namely 1A2, 2C9, 2C19, 2D6, and 3A4. The model was built by training multi-task autoencoder deep neural network (DNN) on a large dataset containing more than 13000 compounds, extracted from PubChem BioAssay Database...
May 18, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29763690/the-citrus-flavonone-hesperetin-attenuates-the-nuclear-translocation-of-aryl-hydrocarbon-receptor
#2
Yan Qin Tan, Leo Clement Chiu-Leung, Shu-Mei Lin, Lai K Leung
The environmental polycyclic aromatic hydrocarbons (PAH) and dioxins are carcinogens and their adverse effects have been largely attributed to the activation of AhR. Hesperetin is a flavonone found abundantly in citrus fruits and has been shown to be a biologically active agent. In the present study, the effect of hesperetin on the nuclear translocation of AhR and the downstream gene expression was investigated in MCF-7 cells. Confocal microscopy indicated that 7, 12-dimethylbenz[α]anthracene (DMBA) or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) -induced nuclear translocation of AhR was deterred by hesperetin treatment...
May 16, 2018: Comparative Biochemistry and Physiology. Toxicology & Pharmacology: CBP
https://www.readbyqxmd.com/read/29744741/effect-of-naltrexone-hydrochloride-on-cytochrome-p450-1a2-2c9-2d6-and-3a4-activity-in-human-liver-microsomes
#3
Haitham AlRabiah, Abdul Ahad, Gamal A E Mostafa, Fahad I Al-Jenoobi
BACKGROUND AND OBJECTIVE: Cytochrome P450 (CYP) 1A2, 2C9, 2D6, and 3A4 are the most important phase I drug-metabolizing enzymes in the liver, but there is a dearth of literature available on the effects of naltrexone hydrochloride on these major enzymes present in the human liver. Thus, in the present study, the effect of naltrexone hydrochloride on the activity of CYP1A2, 2C9, 2D6, and 3A4 using human liver microsomes (HLM) was investigated. METHODS: A selective probe for CYP1A2, 2C9, 2D6, and 3A4 was incubated with HLM with or without naltrexone hydrochloride...
May 9, 2018: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/29731771/undifferentiated-adipose-tissue-stem-cell-transplantation-promotes-hepatic-regeneration-ameliorates-histopathologic-damage-of-the-liver-and-upregulates-the-expression-of-liver-regeneration-and-liver-specific-genes-in-a-rat-model-of-partial-hepatectomy
#4
Konstantinos G Apostolou, Ioannis G Papanikolaou, Charalampos Katselis, Themistoklis Feretis, Dimitrios Kletsas, Manousos M Konstadoulakis, Maria Lymperi, Angelica A Saetta, Spiros Tsikalakis, George Agrogiannis, Efstratios Patsouris, George C Zografos, Apostolos E Papalois
Objective: Adipose tissue stem cells (ADSCs) present a promising therapeutic method to alleviate liver failure (LF). The purpose of this prospective study was to evaluate the efficacy of undifferentiated ADSC transplantation on liver regeneration and on the expression of liver regeneration- and liver-specific genes, following 60% partial hepatectomy (PHx). Methods: Sixty female rats were subjected to PHx and were transplanted with 106 or 2 × 106 ADSCs, either into the portal vein (PV) or into the hepatic parenchyma...
2018: Stem Cells International
https://www.readbyqxmd.com/read/29727961/pyrethroid-insecticide-lambda-cyhalothrin-induces-hepatic-cytochrome-p450-enzymes-oxidative-stress-and-apoptosis-in-rats
#5
María-Aránzazu Martínez, Irma Ares, José-Luis Rodríguez, Marta Martínez, David Roura-Martínez, Victor Castellano, Bernardo Lopez-Torres, María-Rosa Martínez-Larrañaga, Arturo Anadón
This study aimed to examine in rats the effects of the Type II pyrethroid lambda-cyhalothrin on hepatic microsomal cytochrome P450 (CYP) isoform activities, oxidative stress markers, gene expression of proinflammatory, oxidative stress and apoptosis mediators, and CYP isoform gene expression and metabolism phase I enzyme PCR array analysis. Lambda-cyhalothrin, at oral doses of 1, 2, 4 and 8mg/kg bw for 6days, increased, in a dose-dependent manner, hepatic activities of ethoxyresorufin O-deethylase (CYP1A1), methoxyresorufin O-demethylase (CYP1A2), pentoxyresorufin O-depentylase (CYP2B1/2), testosterone 7α- (CYP2A1), 16β- (CYP2B1), and 6β-hydroxylase (CYP3A1/2), and lauric acid 11- and 12-hydroxylase (CYP4A1/2)...
August 1, 2018: Science of the Total Environment
https://www.readbyqxmd.com/read/29721716/effect-of-gambogenic-acid-on-cytochrome-p450-1a2-2b1-and-2e1-and-constitutive-androstane-receptor-in-rats
#6
Jing Sun, Xiaozhu Tang, Qianqian Xu, Tao Ge, Daiyin Peng, Weidong Chen
BACKGROUND AND OBJECTIVES: Gambogenic acid (GNA), which possesses diverse antitumor activities both in vitro and in vivo, is regarded as a potential anticancer compound. Cytochrome P450 (CYP) enzymes play an important role in the metabolism of most xenobiotics; constitutive androstane receptor (CAR), a nuclear receptor that might be activated by xenobiotics and associated with the expression of some CYPs. In this study, we determined the effect of GNA on multiple rat liver CYP isoforms (CYP1A2, 2B1, and 2E1) and CAR as well as the potential of GNA to interact with co-administered drugs...
May 2, 2018: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/29698620/cytochrome-p450-mediated-metabolic-activation-of-chrysophanol
#7
Ying Sun, Xin Xin, Kehan Zhang, Tiantian Cui, Ying Peng, Jiang Zheng
Chrysophanol, a major anthraquinone component occurring in many traditional Chinese herbs, is accepted as important active component with various pharmacological actions such as antibacterial and anticancer activity. Previous studies demonstrated that exposure to chrysophanol induced cytotoxicity, but the mechanisms of the toxic effects remain unknown. In the present metabolism study, three oxidative metabolites (M1-M3, aloe-emodine, 7-hydroxychrysophanol, and 2-hydroxychrysophanol) and five GSH conjugates (M4-M8) were detected in rat and human liver microsomal incubations of chrysophanol supplemented with GSH, and the formation of the metabolites was NADPH dependent except M4 and M5...
April 23, 2018: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29667811/in-vitro-and-in-vivo-studies-of-the-electrophilicity-of-physcion-and-its-oxidative-metabolites
#8
Xiaotong Qin, Ying Peng, Jiang Zheng
Physcion (1,8-dihydroxy-3-methoxy-6-methyl-9,10-anthracenedione) is a bioactive component found in Polygoni Multiflori Radix (PMR) which has been widely used as traditional Chinese medicine. Unfortunately, studies showed hepatotoxicity of PMR during its clinical use. The mechanisms of its toxic action remain unknown. The major objectives of this study were to characterize oxidative metabolites of physcion in vitro and in vivo and to determine the electrophilicity of the parent compound and its oxidative metabolites...
April 18, 2018: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/29659506/in-vitro-inhibitory-effects-of-synthetic-cannabinoid-eam-2201-on-cytochrome-p450-and-udp-glucuronosyltransferase-enzyme-activities-in-human-liver-microsomes
#9
Tae Yeon Kong, Soon-Sang Kwon, Jae Chul Cheong, Hee Seung Kim, Jin Young Kim, Hye Suk Lee
EAM-2201, a synthetic cannabinoid, is a potent agonist of the cannabinoid receptors that is widely abused as an illicit recreational drug in combination with other drugs. To evaluate the potential of EAM-2201 as a perpetrator of drug–drug interactions, the inhibitory effects of EAM-2201 on major drug-metabolizing enzymes, cytochrome P450s (CYPs) and uridine 5′-diphospho-glucuronosyltransferases (UGTs) were evaluated in pooled human liver microsomes using liquid chromatography–tandem mass spectrometry (LC-MS/MS)...
April 16, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29623041/an-adaptogen-withaferin-a-ameliorates-in-vitro-and-in-vivo-pulmonary-fibrosis-by-modulating-the-interplay-of-fibrotic-matricelluar-proteins-and-cytokines
#10
Swarna Bale, Pooladanda Venkatesh, Manoj Sunkoju, Chandraiah Godugu
Pulmonary fibrosis (PF) is chronic lung disease with only two FDA approved clinically available drugs, with limited safety profile. Inadequate therapy motivated us to explore the effect of vimentin inhibitor Withaferin A, as an anti-fibrotic agent against TGF-β1-induced in vitro fibrotic events and Bleomycin induced in vivo fibrosis with an emphasis on epithelial to mesenchymal transition (EMT), extracellular matrix deposition (ECM), inflammation, and angiogenesis. In vitro EMT and fibrotic events were induced by TGF-β1 in alveolar epithelial cells and human fetal lung fibroblasts followed by treatment with Withaferin A (0...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29620427/blocking-oestradiol-synthesis-pathways-with-potent-and-selective-coumarin-derivatives
#11
Sanna Niinivehmas, Pekka A Postila, Sanna Rauhamäki, Elangovan Manivannan, Sami Kortet, Mira Ahinko, Pasi Huuskonen, Niina Nyberg, Pasi Koskimies, Sakari Lätti, Elina Multamäki, Risto O Juvonen, Hannu Raunio, Markku Pasanen, Juhani Huuskonen, Olli T Pentikäinen
A comprehensive set of 3-phenylcoumarin analogues with polar substituents was synthesised for blocking oestradiol synthesis by 17-β-hydroxysteroid dehydrogenase 1 (HSD1) in the latter part of the sulphatase pathway. Five analogues produced ≥62% HSD1 inhibition at 5 µM and, furthermore, three of them produced ≥68% inhibition at 1 µM. A docking-based structure-activity relationship analysis was done to determine the molecular basis of the inhibition and the cross-reactivity of the analogues was tested against oestrogen receptor, aromatase, cytochrome P450 1A2, and monoamine oxidases...
December 2018: Journal of Enzyme Inhibition and Medicinal Chemistry
https://www.readbyqxmd.com/read/29616291/the-role-of-hepatic-cytochrome-p450s-in-the-cytotoxicity-of-dronedarone
#12
Si Chen, Qiangen Wu, Baitang Ning, Matthew Bryant, Lei Guo
Dronedarone is used to treat patients with cardiac arrhythmias and has been reported to be associated with liver injury. Our previous mechanistic work demonstrated that DNA damage-induced apoptosis contributes to the cytotoxicity of dronedarone. In this study, we examined further the underlying mechanisms and found that after a 24-h treatment of HepG2 cells, dronedarone caused cytotoxicity, G1-phase cell cycle arrest, suppression of topoisomerase II, and DNA damage in a concentration-dependent manner. We also investigated the role of cytochrome P450s (CYPs)-mediated metabolism in the dronedarone-induced toxicity using our previously established HepG2 cell lines expressing individually 14 human CYPs (1A1, 1A2, 1B1, 2A6, 2B6, 2C8, 2C9, 2C18, 2C19, 2D6, 2E1, 3A4, 3A5, and 3A7)...
April 3, 2018: Archives of Toxicology
https://www.readbyqxmd.com/read/29607154/decreased-expression-of-hepatic-cytochrome-p450-1a2-cyp1a2-in-a-chronic-intermittent-hypoxia-mouse-model
#13
Xiao-Bin Zhang, Yi-Ming Zeng, Xiao-Yang Chen, Yi-Xiang Zhang, Jin-Zhen Ding, Cheng Xue
Background: Hepatic cytochrome P450 (CYP) isoforms, CYP1A2, is one of important enzymes for many drugs metabolism. Studies have confirmed that sustained hypoxia can influence the expression of hepatic CYP, including CYP1A2. The impact of chronic intermittent hypoxia (CIH), a marked characteristic of sleep apnea, on CYP1A2 remains unclear. The aim of the present study was to evaluate the effect of CIH on the expression of hepatic CYP1A2 in a mouse model with sleep apnea. Methods: Twenty four old male (6-8 weeks) C57BL/6J mice (n=12 in each group) were randomly assigned to either normoxia group or CIH group...
February 2018: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/29572664/identification-of-cytochrome-p450-mediated-drug-drug-interactions-at-risk-in-cases-of-gene-polymorphisms-by-using-a-quantitative-prediction-model
#14
Nicolas Fermier, Laurent Bourguignon, Sylvain Goutelle, Nathalie Bleyzac, Michel Tod
BACKGROUND AND OBJECTIVE: The magnitude of drug-drug interactions mediated by cytochrome P450 (CYP) may depend on the genotype of polymorphic cytochromes. The objective of this study was to identify drug-drug interactions with greater magnitude in CYP variant groups than in extensive metabolizers. METHODS: The in-vivo mechanistic static model was used to predict the area under the curve ratio of drug-drug interactions. Five cytochromes (CYP3A4/5, 2D6, 2C9, 2C19, 1A2) and five groups of genotypes for each polymorphic cytochrome (CYP2D6, 2C9, 2C19) were considered...
March 23, 2018: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/29549185/identification-of-a-nf-%C3%AE%C2%BA-b-inhibition-site-on-the-proximal-promoter-region-of-human-organic-anion-transporting-polypeptide-1a2-coding-gene-slco1a2
#15
Zhaojian Xiang, Weike Li, Lixue Wang, Jicai Yi, Kaiwen Chen, Mei Hong
Organic anion transporting polypeptides (OATPs; gene symbol SLCO ) are membrane transporters that mediate the transport of wide ranges of compounds. The expression of different OATP members has been reported in the kidney, liver, placenta, brain, and intestine. Because of their broad substrate spectra and wide distribution within the human body, these transporters have been proposed to play key roles in the influx transport of many oral drugs. Inflammation is known to regulate the expression and functions of many drug-metabolizing enzymes and drug transporters...
May 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29527614/small-molecule-activation-of-nitriles-coordinated-to-the-re-6-se-8-2-core-formation-of-oxazine-oxazoline-and-carboxamide-complexes
#16
Colleen P Chin, YiXin Ren, Joan Berry, Stanley A Knott, Craig C McLauchlan, Lisa F Szczepura
Novel oxazine, oxazoline and carboxamide cluster complexes were prepared when different nucleophilic oxygen species reacted with nitriles coordinated to the Lewis acidic [Re6Se8]2+ cluster core. Reaction of ICH2CH2O- (generated in situ) with [Re6Se8(PEt3)5(NCR)]A2 (1A2 (R = Me) and 2A2 (R = Ph) where A = BF4-), leads to the formation of [Re6Se8(PEt3)5(2-methyloxazoline)]2+ (32+) and [Re6Se8(PEt3)5(2-phenyloxazoline)]2+ (42+). Similarly, reaction of BrCH2CH2CH2O- with the same nitrile complexes, 1A2 and 2A2 (where A = BF4- or SbF6-) leads to the corresponding oxazine complexes, [Re6Se8(PEt3)5(2-methyloxazine)]2+ (52+) and [Re6Se8(PEt3)5(2-phenyloxazine)]2+ (62+)...
March 26, 2018: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/29517952/optimizing-stability-in-ao-ota-31-a2-intertrochanteric-fracture-fixation-in-older-patients-with-osteoporosis
#17
Chi Zhang, Bo Xu, Guanzhao Liang, Xianshang Zeng, Dan Zeng, Deng Chen, Zhe Ge, Weiguang Yu, Xinchao Zhang
Objectives To compare the functional and radiographic outcomes of InterTAN nail (IT) and proximal femoral nail anti-rotation (PFNA) for managing primary AO/OTA 31-A2 intertrochanteric hip fractures (IHFs) in older osteoporotic patients. Methods Patients aged 60 years or older who received surgical treatment for IHFs (AO/OTA 3.1A2.1-A2.3) with IT or PFNA were retrospectively evaluated. The primary outcome was the postoperative treatment failure rate. The secondary outcome was the Harris Hip Score (HHS). Results A total of 326 osteoporotic cases (326 hips: IT, n = 162; PFNA, n = 164) were assessed with a mean follow-up of 43...
May 2018: Journal of International Medical Research
https://www.readbyqxmd.com/read/29514185/mid-term-survival-outcome-of-single-port-video-assisted-thoracoscopic-anatomical-lung-resection-a-two-centre-experience
#18
Ching Feng Wu, Ricardo Fernandez, de la Torre Mercedes, Maria Delgado, Eva Fieira, Ching Yang Wu, Ming Ju Hsieh, Marina Paradela, Yun-Hen Liu, Diego Gonzalez-Rivas
OBJECTIVES: Single-port video-assisted thoracoscopic surgery (SPVATS) anatomical resection has been shown to be a feasible technique for lung cancer patients. Whether SPVATS has equivalent or better oncological outcomes for lung cancer patients remains controversial. The purpose of this study was to evaluate the perioperative and mid-term survival outcomes of SPVATS in 2 different medical centres. METHODS: We retrospectively reviewed patients who underwent SPVATS anatomical resections between January 2014 and February 2017 in Coruña University Hospital's Minimally Invasive Thoracic Surgery Unit (Spain) and Chang Gung Memorial Hospital (Taiwan)...
March 3, 2018: European Journal of Cardio-thoracic Surgery
https://www.readbyqxmd.com/read/29501585/cytochrome-p4501-inhibiting-chemicals-amplify-aryl-hydrocarbon-receptor-activation-and-il-22-production-in-t-helper-17-cells
#19
Chris Schiering, Anne Vonk, Srustidhar Das, Brigitta Stockinger, Emma Wincent
The aryl hydrocarbon receptor (AHR) controls interleukin 22 production by T helper 17 cells (Th17). IL-22 contributes to intestinal homeostasis but has also been implicated in chronic inflammatory disorders and colorectal cancer, highlighting the need for appropriate regulation of IL-22 production. Upon activation, the AHR induces expression of cytochrome P4501 (CYP1) enzymes which in turn play an important feedback role that curtails the duration of AHR signaling by metabolizing AHR ligands. Recently we described how agents that inhibit CYP1 function potentiate AHR signaling by disrupting metabolic clearance of the endogenous ligand 6-formylindolo[3,2-b]carbazole (FICZ)...
May 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29491713/effect-of-mrsa-on-cyp450-dynamic-changes-of-cytokines-oxidative-stress-and-drug-metabolizing-enzymes-in-mice-infected-with-mrsa
#20
Huaqiao Tang, Nana Long, Lin Lin, Yao Liu, Jianlong Li, Fenghui Sun, Lijuan Guo, Fen Zhang, Min Dai
Background: Methicillin-resistant Staphylococcus aureus (MRSA) is a very damaging and widespread pathogen, which is associated with many diseases and causes serious infections. MRSA infection can modulate the effects of drugs, which may occur through an influence on cytochrome P450 (CYP450), the drug-metabolizing enzyme in the liver. In this study, we evaluated the underlying mechanism of drug failure or poisoning in MRSA infection. Materials and methods: Mice were infected with three different doses of MRSA and the changes in CYP450 expression, cytokines, and oxidative stress markers were evaluated...
2018: Infection and Drug Resistance
keyword
keyword
83666
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"