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https://www.readbyqxmd.com/read/29679682/bitter-and-sweet-tasting-molecules-it-s-complicated
#1
REVIEW
Antonella Di Pizio, Yaron Ben Shoshan-Galeczki, John E Hayes, Masha Y Niv
"Bitter" and "sweet" are frequently framed in opposition, both functionally and metaphorically, in regard to affective responses, emotion, and nutrition. This oppositional relationship is complicated by the fact that some molecules are simultaneously bitter and sweet. In some cases, a small chemical modification, or a chirality switch, flips the taste from sweet to bitter. Molecules humans describe as bitter are recognized by a 25 member subfamily of class A G-protein coupled receptors (GPCRs) known as TAS2Rs...
April 18, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29679509/pharmacokinetic-properties-of-wogonin-and-its-herb-drug-interactions-with-docetaxel-in-rats-with-mammary-tumors
#2
Ting Wang, Fangyi Long, Gang Jiang, Hong Cai, Qian Jiang, Kai Cheng, Zhiqiang Hu, Yuxi Wang
Docetaxel, frequently used for the treatment of breast cancer, is mainly metabolized via hepatic cytochrome P450 (CYP) 3A in humans and is also a substrate of P-glycoprotein (P-gp). Wogonin has been shown to be able to modulate the activities of CYPs and P-gp, and it could be served as an adjuvant chemotherapeutic agent. However, the impacts of co-administration of wogonin and docetaxel on their pharmacokinetics have not been studied for lacking analytical method of their simultaneous measurement. In the present study, we established an HPLC-MS/MS method for simultaneous measurement of wogonin and docetaxel in rat plasma, and it was then utilized to explore the pharmacokinetics of wogonin and the herb-drug interactions between wogonin and docetaxel after the combined administration in rats with mammary tumors...
April 21, 2018: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/29679043/identification-and-heterologous-expression-of-the-actinoallolide-biosynthetic-gene-cluster
#3
Yuki Inahashi, Taro Shiraishi, Akira Také, Atsuko Matsumoto, Yōko Takahashi, Satoshi Ōmura, Tomohisa Kuzuyama, Takuji Nakashima
Actinoallolides are anti-trypanosomal macrolides isolated from the secondary metabolites of two endophytic actinomycete strains, Actinoallomurus fulvus MK10-036 and K09-0307. A putative actinoallolide biosynthetic gene cluster was predicted from the genome sequence of the strain K09-0307. The gene cluster spans a contiguous 53 kb DNA region that comprises seven genes encoding three PKSs (aalA1, aalA2, and aalA3), cytochrome P450 (aalB), acyl-CoA dehydrogenase (aalC), crotonyl-CoA reductase (aalD), and TetR family regulator (aalR)...
April 20, 2018: Journal of Antibiotics
https://www.readbyqxmd.com/read/29678659/association-of-cyp3a4-1b-genotype-with-cyclosporin-a-pharmacokinetics-in-renal-transplant-recipients-a-meta-analysis
#4
Cai-E Wang, Ke-Peng Lu, Zhao Chang, Meng-Li Guo, Hai-Ling Qiao
OBJECTIVE: Cyclosporine (CsA) is a substrate of cytochrome P450 (CYP) 3A4 with a narrow therapeutic index and large individual difference. CYP3A4*1B is reported to be associated with CsA pharmacokinetics parameters, but the relevance is still in dispute. Therefore, a meta-analysis was employed to evaluate the influence of CYP3A4*1B on CsA pharmacokinetics at different post-transplantation times in adult renal transplant recipients. METHODS: Studies on evaluating the CYP3A4*1B genotype and CsA pharmacokinetics were retrieved through a systematical search of relevant database including PubMed, Emabase, Web of science, the Cochrane Library, Clinical Trials...
April 17, 2018: Gene
https://www.readbyqxmd.com/read/29677600/interactions-of-2-phenyl-benzotriazole-xenobiotic-compounds-with-human-cytochrome-p450-cyp1a1-by-means-of-docking-molecular-dynamics-simulations-and-mm-gbsa-calculations
#5
Karel Mena-Ulecia, Desmond MacLeod-Carey
2-phenyl-benzotriazole xenobiotic compounds (PBTA-4, PBTA-6, PBTA-7 and PBTA-8) that were previously isolated and identified in waters of the Yodo river, in Japan (Nukaya et al., 2001; Ohe et al., 2004; Watanabe et al., 2001) were characterized as powerful pro-mutagens. In order to predict the activation mechanism of these pro-mutagens, we designed a computational biochemistry protocol, which includes, docking experiments, molecular dynamics simulations and free energy decomposition calculations to obtain information about the interaction of 2-phenyl-benzotriazole molecules into the active center of cytochrome P450-CYP1A1 (CYP1A1)...
April 7, 2018: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/29676772/functional-roles-of-eriocalyxin-b-in-zebrafish-revealed-by-transcriptome-analysis
#6
Xunian Zhou, Cyanne Ye Cao, Angel Tsz-Yau Wan, Grace Gar-Lee Yue, Frankie Hin-Fai Kwok, Kwok-Pui Fung, Handong Sun, Clara Bik-San Lau, Pema-Tenzin Puno, Stephen Kwok-Wing Tsui
BACKGROUND: Eriocalyxin B (EriB) is a natural ent-kaurane diterpenoid obtained from Isodon eriocalyx var. laxiflora (family Lamiaceae), which has multiple biological activities (e.g. anti-tumor and anti-inflammatory) via the alteration of gene expression and signaling transduction. Recently, RNA sequencing (RNA-seq) has been developed as a dynamic transcriptome approach to analyze the transcriptional profile and in addition use such gene expression profiles to identify novel candidate genes in a zebrafish model...
April 20, 2018: Molecular omics
https://www.readbyqxmd.com/read/29676195/in-vitro-inhibitory-effects-of-sophocarpine-on-human-liver-cytochrome-p450-enzymes
#7
Jingwei Zhang, Chuansheng Li, Jingfa Zhang, Fan Zhang
1. Sophocarpine is a biologically active component isolated from the foxtail-like sophora herb and seed that is often orally administered for the treatment of cancer and chronic bronchial asthma. However, whether sophocarpine affects the activity of human liver cytochrome P450 (CYP) enzymes remains unclear. 2. In this study, the inhibitory effects of sophocarpine on the eight human liver CYP isoforms (CYP1A2, 3A4, 2A6, 2E1, 2D6, 2C9, 2C19, and 2C8) were investigated in vitro using human liver microsomes (HLMs)...
April 20, 2018: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/29675188/porphyrinoids-as-a-platform-of-stable-radicals
#8
REVIEW
Daiki Shimizu, Atsuhiro Osuka
The non-innocent ligand nature of porphyrins was observed for compound I in enzymatic cycles of cytochrome P450. Such porphyrin radicals were first regarded as reactive intermediates in catabolism, but recent studies have revealed that porphyrinoids, including porphyrins, ring-contracted porphyrins, and ring-expanded porphyrins, display excellent radical-stabilizing abilities to the extent that radicals can be handled like usual closed-shell organic molecules. This review surveys four types of stable porphyrinoid radical and covers their synthetic methods and properties such as excellent redox properties, NIR absorption, and magnetic properties...
February 14, 2018: Chemical Science
https://www.readbyqxmd.com/read/29674492/11beta-hydroxysteroid-dehydrogenase-1-human-tissue-distribution-selective-inhibitor-and-role-in-doxorubicin-metabolism
#9
Xin Yang, Wenyi Hua, Sangwoo Ryu, Phillip Yates, Cheng Chang, Hui Zhang, Li Di
11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) is mainly distributed in the human liver with no detectable levels in the intestine or kidney based on a newly developed proteomic approach. 11β-HSD1 is mostly membrane bound and retained in the liver microsomal faction. Inter-individual variability of 11β-HSD1 is relatively low with about a three-fold difference. A significant correlation was not observed between various demographic variables (ethnicity, gender, age, weight, smoking, and alcohol use) and 11β-HSD1 protein expression or activity based on data from thirty-one donors...
April 19, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29674455/rapid-selection-of-a-pyrethroid-metabolic-enzyme-cyp9k1-by-operational-malaria-control-activities
#10
John Vontas, Linda Grigoraki, John Morgan, Dimitra Tsakireli, Godwin Fuseini, Luis Segura, Julie Niemczura de Carvalho, Raul Nguema, David Weetman, Michel A Slotman, Janet Hemingway
Since 2004, indoor residual spraying (IRS) and long-lasting insecticide-impregnated bednets (LLINs) have reduced the malaria parasite prevalence in children on Bioko Island, Equatorial Guinea, from 45% to 12%. After target site-based (knockdown resistance; kdr ) pyrethroid resistance was detected in 2004 in Anopheles coluzzii (formerly known as the M form of the Anopheles gambiae complex), the carbamate bendiocarb was introduced. Subsequent analysis showed that kdr alone was not operationally significant, so pyrethroid-based IRS was successfully reintroduced in 2012...
April 19, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29673999/ribociclib-shows-potential-for-pharmacokinetic-drug-drug-interactions-being-a-substrate-of-abcb1-and-potent-inhibitor-of-abcb1-abcg2-and-cyp450-isoforms-in-vitro
#11
Ales Sorf, Jakub Hofman, Radim Kučera, Frantisek Staud, Martina Ceckova
Ribociclib is a novel cyclin-dependent kinase (CDK) 4 and 6 selective inhibitor that recently gained breakthrough therapy status and global approval for advanced breast cancer treatment. ATP-binding cassette (ABC) transporters may become a site of severe drug interactions and a mechanism of multidrug resistance (MDR) development. With respect to rapid progress of ribociclib in the clinical field, we aimed to identify its interactions with ABC transporters and cytochrome P450 (CYP) isoenzymes and evaluate its potential to overcome transporter-mediated MDR using established in vitro methods...
April 16, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29672818/the-in-vitro-and-in-vivo-effects-of-hypoxis-hemerocallidea-on-indinavir-pharmacokinetics-modulation-of-efflux
#12
Kaylee Havenga, Efrem Abay, Lubbe Wiesner, Alvaro Viljoen, Dewald Steyn, Josias Hamman
Hypoxis hemerocallidea (African potato) is a popular medicinal plant that has been used traditionally for the treatment of various disorders. Some HIV/AIDS patients use this traditional medicine together with their antiretroviral therapy. This study aimed to determine the impact of selected H. hemerocallidea materials (i.e., a commercial product, an aqueous extract, and biomass reference plant material) on the bidirectional permeability of indinavir across Caco-2 cell monolayers as well as the bioavailability of indinavir during an acute, single administration study in Sprague-Dawley rats...
April 19, 2018: Planta Medica
https://www.readbyqxmd.com/read/29672606/a-practice-changing-culture-method-relying-on-shaking-substantially-increases-mitochondrial-energy-metabolism-and-functionality-of-human-liver-cell-lines
#13
Aziza A A Adam, Vincent A van der Mark, Joanne M Donkers, Manon E Wildenberg, Ronald P J Oude Elferink, Robert A F M Chamuleau, Ruurdtje Hoekstra
Practice-changing culturing techniques of hepatocytes are highly required to increase their differentiation. Previously, we found that human liver cell lines HepaRG and C3A acquire higher functionality and increased mitochondrial biogenesis when cultured in the AMC-Bioartificial liver (BAL). Dynamic medium flow (DMF) is one of the major contributors to this stimulatory effect. Recently, we found that DMF-culturing by shaking of HepaRG monolayers resulted in higher mitochondrial biogenesis. Here we further investigated the effect of DMF-culturing on energy metabolism and hepatic functionality of HepaRG and C3A monolayers...
2018: PloS One
https://www.readbyqxmd.com/read/29672568/rna-seq-transcriptome-analysis-of-amaranthus-palmeri-with-differential-tolerance-to-glufosinate-herbicide
#14
Reiofeli A Salas-Perez, Christopher A Saski, Rooksana E Noorai, Subodh K Srivastava, Amy L Lawton-Rauh, Robert L Nichols, Nilda Roma-Burgos
Amaranthus palmeri (Amaranthaceae) is a noxious weed in several agroecosystems and in some cases seriously threatens the sustainability of crop production in North America. Glyphosate-resistant Amaranthus species are widespread, prompting the use of alternatives to glyphosate such as glufosinate, in conjunction with glufosinate-resistant crop cultivars, to help control glyphosate-resistant weeds. An experiment was conducted to analyze the transcriptome of A. palmeri plants that survived exposure to 0.55 kg ha-1 glufosinate...
2018: PloS One
https://www.readbyqxmd.com/read/29670361/identification-of-molecular-target-genes-and-key-pathways-in-hepatocellular-carcinoma-by-bioinformatics-analysis
#15
Lei Zhou, Yanyan Du, Lingqun Kong, Xingyuan Zhang, Qiangpu Chen
Background and aim: Hepatocellular carcinoma (HCC) is a major cause of cancer mortality and is increasing incidence worldwide. The aim of this study was to identify the key genes and microRNAs in HCC and explore their potential mechanisms. Methods: The gene expression profiles of GSE76427, GSE64041, GSE57957, and the microRNA dataset GSE67882 were downloaded from the Gene Expression Omnibus database. The online tool GEO2R was used to obtain differentially expressed genes (DEGs) and miRNAs (DEMs)...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29668912/ovine-placental-steroid-synthesis-and-metabolism-in-late-gestation
#16
Lawrence P Reynolds, Erin L Legacki, C Jo Corbin, Joel S Caton, Kimberly A Vonnahme, Scott Stanley, Alan J Conley
Steroid synthesis is required for pregnancy maintenance and for parturition but comparatively little is known about the major metabolic routes that influence circulating concentrations. Dietary intake changes progesterone and estradiol concentrations in pregnant ewes but whether this reflects placental synthesis is unknown. Progesterone metabolism by 5alpha-reduction is a major metabolic route in other species and can influence the onset of parturition. Therefore, studies were conducted to 1) determine placental enzyme activity, progesterone and estradiol measured by immuno-assay in late gestation ewes on low, moderate and high nutritional planes, 2) to assess the significance of 5alpha-reduction of progesterone in determining progesterone concentrations in late gestation ewes (gestation day 145) given finasteride to inhibit 5alpha-reductase metabolism...
April 14, 2018: Biology of Reproduction
https://www.readbyqxmd.com/read/29667657/unrivalled-diversity-the-many-roles-and-reactions-of-bacterial-cytochromes-p450-in-secondary-metabolism
#17
REVIEW
Anja Greule, Jeanette E Stok, James J De Voss, Max J Cryle
Covering: 2000 up to 2018The cytochromes P450 (P450s) are a superfamily of heme-containing monooxygenases that perform diverse catalytic roles in many species, including bacteria. The P450 superfamily is widely known for the hydroxylation of unactivated C-H bonds, but the diversity of reactions that P450s can perform vastly exceeds this undoubtedly impressive chemical transformation. Within bacteria, P450s play important roles in many biosynthetic and biodegradative processes that span a wide range of secondary metabolite pathways and present diverse chemical transformations...
April 18, 2018: Natural Product Reports
https://www.readbyqxmd.com/read/29667038/complex-drug-drug-gene-disease-interactions-involving-cytochromes-p450-systematic-review-of-published-case-reports-and-clinical-perspectives
#18
REVIEW
Flavia Storelli, Caroline Samer, Jean-Luc Reny, Jules Desmeules, Youssef Daali
Drug pharmacokinetics (PK) is influenced by multiple intrinsic and extrinsic factors, among which concomitant medications are responsible for drug-drug interactions (DDIs) that may have a clinical relevance, resulting in adverse drug reactions or reduced efficacy. The addition of intrinsic factors affecting cytochromes P450 (CYPs) activity and/or expression, such as genetic polymorphisms and diseases, may potentiate the impact and clinical relevance of DDIs. In addition, greater variability in drug levels and exposures has been observed when such intrinsic factors are present in addition to concomitant medications perpetrating DDIs...
April 17, 2018: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/29666456/serotonin-is-an-endogenous-regulator-of-intestinal-cyp1a1-via-ahr
#19
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/29663675/a-stable-artificial-multienzymatic-complex-using-a-heterotrimeric-protein-from-metallosphaera-sedula
#20
Fumiya Iwata, Hidehiko Hirakawa, Teruyuki Nagamune
Bacterial cytochrome P450 monooxygenases (P450s) are promising biocatalysts for chemical syntheses because they catalyze a variety of oxidations on non-activated hydrocarbons using O2 . However, the requirement of two auxiliary proteins, an electron transfer protein and a reductase, for the catalysis is a major bottleneck for in vitro applications of these monooxygenases. Our previous study showed that artificial assembly of a bacterial P450 with its auxiliary proteins using a heterotrimeric proliferating cell nuclear antigen (PCNA) from Sulfolobus solfataricus yields a self-sufficient P450, but partial dissociation of P450 from the complex at catalytic concentrations reduces the apparent specific activity of this self-sufficient P450...
April 16, 2018: Biotechnology Journal
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