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https://www.readbyqxmd.com/read/29913064/synthesis-of-novel-3-4-chloroisothiazole-based-imidazoles-as-fungicides-and-evaluation-of-their-mode-of-action
#1
Lai Chen, Bin Zhao, Zhijin Fan, Xiumei Liu, Qifan Wu, Hongpeng Li, Haixia Wang
A molecular design approach was used in our laboratory to guide the development of imidazole-based fungicides. Based on homology modeling and molecular docking studies targeting the cytochrome P450-dependent sterol 14α-demethylase, 3,4-dichloroisothiazole-based imidazoles showed great potential. Several such compounds were then rationally designed, synthesized, characterized, and their antifungal activities were evaluated. Bioassay results showed that compounds such as (R)-11, (R)-12, and (S)-11 have commendable, broad-spectrum antifungal activities that are comparable to those of commercial products...
June 18, 2018: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/29912670/lycii-fructus-extract-ameliorates-hydrogen-peroxide-induced-cytotoxicity-through-indirect-antioxidant-action
#2
Wensi Xu, Shunya Saiki, Takumi Myojin, Yujia Liu, Beiwei Zhu, Yoshiyuki Murata, Hitoshi Ashida, Makoto Tsunenaga, Yoshimasa Nakamura
Lycii Fructus is the dried ripe fruits of Lycium chinense and L. barbarum, which has long been used as a traditional food material in East Asia. The purpose of this study was to investigate the role of the indirect antioxidative action in the Lycii fructus extract (LFE)-induced cytoprotective effect in vitro. LFE significantly enhanced the expression of the drug-metabolizing enzyme genes and intracellular glutathione level in mouse hepatoma Hepa1c1c7 cells. LFE stimulated the nuclear translocation of aryl hydrocarbon receptor as well as nuclear factor (erythroid-derived 2)-like 2...
June 18, 2018: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/29908721/time-dependent-expression-pattern-of-cytochrome-p450-epoxygenases-and-soluble-epoxide-hydrolase-in-normal-human-placenta
#3
K Cizkova, Z Tauber
CYP2C and CYP2 J enzymes, commonly named as cytochrome P450 (CYP) epoxygenases, convert arachidonic acid to four regioisomeric epoxyeicosatrienoic acids (EETs), biologically active eicosanoids with many functions in organism. EETs are rapidly hydrolysed to less active dihydroxyeicosatrienoic acids (DHETs) by soluble epoxide hydrolase (sEH). We investigated spatio-temporal expression pattern of CYP2C8, CYP2C9, CYP2 J2 and sEH in normal human placenta by immunohistochemical method. In the villous trophoblast, CYP2C8 was the most abundant protein...
June 13, 2018: Acta Histochemica
https://www.readbyqxmd.com/read/29906693/proteomic-response-of-gill-microsomes-of-crassostrea-brasiliana-exposed-to-diesel-fuel-water-accommodated-fraction
#4
Gabrielle do Amaral E Silva Müller, Karim Hahn Lüchmann, Guilherme Razzera, Guilherme Toledo-Silva, Maria João Bebianno, Maria Risoleta Freire Marques, Afonso Celso Dias Bainy
Diesel fuel water-accommodated fraction (diesel-WAF) is a complex mixture of organic compounds that may cause harmful effects to marine invertebrates. Expression of microsomal proteins can be changed by oil exposure, causing functional alterations in endoplasmic reticulum (ER). The aim of this study was to investigate changes in protein expression signatures in microsomes of oysterl Crassostrea brasiliana (=C.gasar) gill after exposure to 10% diesel-WAF for 24 and 72 h. Protein expression signatures of gills of oysters exposed to diesel-WAF were compared to those of unexposed oysters using two-dimensional electrophoresis (2-DE) to identify differentially expressed proteins...
June 6, 2018: Aquatic Toxicology
https://www.readbyqxmd.com/read/29906537/phenolic-acid-and-flavonoid-rich-fraction-of-sasa-quelpaertensis-nakai-leaves-prevent-alcohol-induced-fatty-liver-through-ampk-activation
#5
Kalahe Hewage Iresha Nadeeka Madushani Herath, Jinhee Cho, Areum Kim, Tae Kil Eom, Ju-Sung Kim, Jae-Bum Kim, Yang Hoi Doh, Youngheun Jee
ETHNOPHARMACOLOGICAL RELEVANCE: Sasa quelpaertensis Nakai is an edible dwarf bamboo cultivated mainly in Jeju Island, South Korea and its leaf displays various health-promoting properties including antioxidant scavenging. AIM OF THE STUDY: In this study, we aimed at elucidating its hepatoprotective effect against alcohol-induced fatty liver. METHODS: In in vitro study, we evaluated the cytotoxicity and hepatoprotective effect of different solvent fractions (aqua, butanol, chloroform, ethyl acetate and hexane) of 80% EtOH extract of S...
June 12, 2018: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29905956/population-pharmacokinetic-pharmacodynamic-analyses-of-avatrombopag-in-patients-with-chronic-liver-disease-and-optimal-dose-adjustment-guide-with-concomitantly-administered-cyp3a-and-cyp2c9-inhibitors
#6
Maiko Nomoto, Jim Ferry, Ziad Hussein
Avatrombopag, a c-Mpl agonist, has been developed to provide an alternative therapy to standard platelet transfusion care for the treatment of thrombocytopenia. The main objectives of this article were to describe the pharmacokinetics (PK) of avatrombopag, to characterize the pharmacokinetic/pharmacodynamic (PK/PD) relationship between plasma avatrombopag concentrations and platelet count, and to identify potential intrinsic and extrinsic factors affecting PK or PK/PD in patients with chronic liver disease (CLD)...
June 15, 2018: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29905808/pharmacokinetic-modelling-of-darunavir-ritonavir-dose-reduction-800-100-to-400-100-mg-once-daily-in-a-darunavir-ritonavir-containing-regimen-in-virologically-suppressed-hiv-infected-patients-anrs-165-darulight-sub-study
#7
Minh P Lê, Marie-Laure Chaix, Sylvie Chevret, Julie Bertrand, François Raffi, Sébastien Gallien, El Mountacer Billah El Abbassi, Christine Katlama, Pierre Delobel, Yazdan Yazdanpanah, Juliette Saillard, Jean-Michel Molina, Gilles Peytavin
Background: In the ANRS 165 DARULIGHT study (NCT02384967) carried out in HIV-infected patients, the use of a darunavir/ritonavir-containing regimen with a switch to a reduced dose of darunavir maintained virological efficacy (≤50 copies/mL) for 48 weeks with a good safety profile. Objectives: To assess the total and unbound blood plasma pharmacokinetics of darunavir and associated antiretrovirals, and their penetration into semen before and after dose reduction...
June 13, 2018: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29904078/deciphering-the-late-steps-of-rifamycin-biosynthesis
#8
Feifei Qi, Chao Lei, Fengwei Li, Xingwang Zhang, Jin Wang, Wei Zhang, Zhen Fan, Weichao Li, Gong-Li Tang, Youli Xiao, Guoping Zhao, Shengying Li
Rifamycin-derived drugs, including rifampin, rifabutin, rifapentine, and rifaximin, have long been used as first-line therapies for the treatment of tuberculosis and other deadly infections. However, the late steps leading to the biosynthesis of the industrially important rifamycin SV and B remain largely unknown. Here, we characterize a network of reactions underlying the biosynthesis of rifamycin SV, S, L, O, and B. The two-subunit transketolase Rif15 and the cytochrome P450 enzyme Rif16 are found to mediate, respectively, a unique C-O bond formation in rifamycin L and an atypical P450 ester-to-ether transformation from rifamycin L to B...
June 14, 2018: Nature Communications
https://www.readbyqxmd.com/read/29904063/biosynthetic-studies-on-teleocidins-in-streptomyces
#9
REVIEW
Ikuro Abe
Teleocidin B, with its unique indolactam-terpenoid scaffold, is a potent activator of protein kinase C. This short review summarizes our recent research progress on the biosynthesis of teleocidins in Streptomyces blastmyceticus NBRC 12747. We first identified the biosynthetic genes for teleocidin B, which include genes encoding a non-ribosomal peptide synthetase (tleA), a cytochrome P450 monooxygenase (tleB), an indol prenyltransferase (tleC), and a C-methyltransferase (tleD). Notably, the tleD gene is located outside the tleABC cluster...
June 14, 2018: Journal of Antibiotics
https://www.readbyqxmd.com/read/29902864/protective-effect-of-acidic-polysaccharide-from-schisandra-chinensis-on-acute-ethanol-induced-liver-injury-through-reducing-cyp2e1-dependent-oxidative-stress
#10
Rongshuang Yuan, Xue Tao, Shuang Liang, Yan Pan, Li He, Jinghui Sun, Ju Wenbo, Xiangyan Li, Jianguang Chen, Chunmei Wang
AIM: Schisandra chinensis is a well-known traditional Chinese medicine used mainly as a recipe for hepatoprotection. Modern researches have revealed that the hepatoprotection is related to its lignans and crude polysaccharide. In this study, we examined the effect and mechanism of Schisandra chinensis acidic polysaccharide (SCAP) on the liver injury induced by ethanol. MAIN METHODS: SCAP was extracted with water extraction and ethanol precipitation. Liver injury models of both mice and HepG2 cells were produced by ethanol...
March 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29902661/a-feasibility-study-of-the-toxic-responses-of-human-induced-pluripotent-stem-cell-derived-hepatocytes-to-phytochemicals
#11
Tomáš Smutný, Riina Harjumäki, Liisa Kanninen, Marjo Yliperttula, Petr Pávek, Yan-Ru Lou
Herbal medicines have been increasingly used in the last three decades. Despite their popularity, safety issues with herbal products need to be addressed. We performed a feasibility study of the toxic responses of human induced pluripotent stem cell-derived hepatocytes (iHep cells) to phytochemicals in comparison with hepatoblasoma-derived HepG2 cells and long-term human hepatocytes (LTHHs). The iHep cells expressed typical hepatocyte markers cytochrome P450 3A4 (CYP3A4), hepatocyte nuclear factor 4α, and albumin despite the expression of immature markers α-fetoprotein and cytokeratin 19...
June 11, 2018: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29901213/pbpk-modeling-strategy-for-predicting-complex-drug-interactions-of-letermovir-as-a-perpetrator-in-support-of-product-labeling
#12
Ying-Hong Wang, Dapeng Chen, Georgy Hartmann, Carolyn R Cho, Karsten Menzel
Letermovir is a human cytomegalovirus (CMV) terminase inhibitor for the prophylaxis of CMV infection in allogeneic hematopoietic stem-cell transplant (HSCT) recipients. In vitro, letermovir is a time-dependent inhibitor and an inducer of cytochrome P450 (CYP)3A, and an inhibitor of CYP2C8 and organic anion transporting polypeptide (OATP)1B. A stepwise approach was taken to qualify the interaction model of an existing letermovir physiologically-based pharmacokinetic (PBPK) model to predict letermovir interactions with CYP3A and OATP1B...
June 14, 2018: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29899137/retinoic-acid-receptor-signaling-is-necessary-in-steroidogenic-cells-for-normal-spermatogenesis-and-epididymal-function
#13
Estela J Jauregui, Debra Mitchell, Traci Topping, Cathryn A Hogarth, Michael D Griswold
Spermatogenesis in mammals is a very complex, highly organized process, regulated in part by testosterone and retinoic acid (RA). There is a significant amount known about how RA and testosterone signaling pathways independently regulate this process, but there is almost no information regarding whether these two signaling pathways directly interact and whether RA is critical for steroidogenic cell function. This study utilized a transgenic mouse line that expresses a dominant negative form of RA receptor α (RAR-DN) and the steroidogenic cell-specific Cre mouse line, Cyp17 iCre, to generate male mice with steroidogenic cells unable to perform RA signaling...
June 13, 2018: Development
https://www.readbyqxmd.com/read/29898636/effect-of-pretreatment-regimens-of-1-aminobenzotriazole-on-metabolism-and-gastric-emptying-of-probe-compounds-in-rat
#14
Shweta Padmanabhan, Harbeer Kaur, Abhijith Rao, Ajay Saxena, Yogesh Kumar Gupta, T Thanga Mariappan, Vinay K Holenarsipur
1. 1-Aminobenzotriazole (ABT) is a mechanism-based inactivator of major cytochrome P450 (CYP) enzymes, which is used in multiple mechanistic studies. 2. The purpose was to evaluate the effect of 2 h and 16 h pretreatment regimens of ABT on the exposures of triazolam in rat. Another objective was to evaluate the effect of ABT on gastric emptying of acetaminophen. 3. Plasma area under the curve (AUC) of triazolam was increased by 101-fold and 81-fold for the rats pre-treated with ABT at 2 h and 16 h, respectively, compared to control rats...
June 14, 2018: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/29897530/metabolism-and-toxicity-of-trichloroethylene-and-tetrachloroethylene-in-cytochrome-p450-2e1-knockout-and-humanized-transgenic-mice
#15
Yu-Syuan Luo, Shinji Furuya, Valerie Y Soldatov, Oksana Kosyk, Hong Sik Yoo, Hisataka Fukushima, Lauren Lewis, Yasuhiro Iwata, Ivan Rusyn
Trichloroethylene (TCE) and tetrachloroethylene (PCE) are structurally similar olefins that can cause liver and kidney toxicity. Adverse effects of these chemicals are associated with metabolism to oxidative and glutathione conjugation moieties. It is thought that CYP2E1 is crucial to the oxidative metabolism of TCE and PCE, and may also play a role in formation of nephrotoxic metabolites; however, inter-species and inter-individual differences in contribution of CYP2E1 to metabolism and toxicity are not well understood...
April 20, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29896284/development-of-a-three-gene-prognostic-signature-for-hepatitis-b-virus-associated-hepatocellular-carcinoma-based-on-integrated-transcriptomic-analysis
#16
Yao Yang, Qian Lu, Xuejun Shao, Banghui Mo, Xuqiang Nie, Wei Liu, Xianhua Chen, Yuan Tang, Youcai Deng, Jun Yan
Integration of public genome-wide gene expression data together with Cox regression analysis is a powerful weapon to identify new prognostic gene signatures for cancer diagnosis and prognosis. Hepatitis B virus (HBV) is a major cause of hepatocellular carcinoma (HCC), however, it remains largely unknown about the specific gene prognostic signature of HBV-associated HCC. Using Robust Rank Aggreg (RRA) method to integrate seven whole genome expression datasets, we identified 82 up-regulated genes and 577 down-regulated genes in HBV-associated HCC patients...
2018: Journal of Cancer
https://www.readbyqxmd.com/read/29895770/resistance-to-permethrin-%C3%AE-cyfluthrin-and-diazinon-in-florida-horn-fly-populations
#17
Chris J Holderman, Daniel R Swale, Jeffery R Bloomquist, Phillip E Kaufman
Horn flies, Haematobia irritans , a major cattle pest in the USA, cause substantial economic losses and current control methods rely heavily on insecticides. Three horn fly populations were evaluated for insecticide susceptibility to permethrin, β-cyfluthrin, and diazinon. Susceptibility was variable by population, with the greatest resistance exhibited by a 66-fold resistance ratio (RR) to permethrin and >14-fold RR to diazinon. Mechanisms of resistance were determined using molecular techniques and enzymatic assays...
June 12, 2018: Insects
https://www.readbyqxmd.com/read/29894786/functional-characterization-of-phenylalanine-ammonia-lyase-and-cinnamate-4-hydroxylase-encoding-genes-from-lycoris-radiata-a-galanthamine-producing-plant
#18
Wei Li, Yun Yang, Chong Qiao, Guolin Zhang, Yinggang Luo
Galanthamine (GAL), the well-known Amaryllidaceae alkaloid, is a clinically used drug for the treatment of Alzheimer's disease. L-Phenylalanine (Phe) and trans-cinnamic acid (CA) were enzymatically transformed into the catechol portion of GAL. Herein, a Phe ammonia-lyase-encoding gene LrPAL3 and a cinnamate 4-hydroxylase-encoding gene LrC4H were cloned from Lycoris radiata, a GAL-producing plant. LrPAL3 was overexpressed in Escherichia coli and purified to homogeneity. LrPAL3 catalyzes the forward deamination conversion of L-Phe into trans-CA...
June 9, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29893080/-perillyl-alcohol-production-by-engineered-heterologous-mevalonate-pathway-in-escherichia-coli
#19
Zehua Qin, Rubing Zhang, Jianping Yu
Perillyl alcohol, [4-isopropylene-1-cyclohexene] methanol, is a monocyclic monoterpene alcohol with special odorous similar to that of linalool and terpineol. It has application potential in pharmaceutical, daily chemical and food industries. In this study, one method for the synthesis of perillyl alcohol through the MVA pathway was studied. First, the MVA metabolic pathway originated from Enterococcus faecalis was constructed in Escherichia coli to synthesize limonene. Limonene was further transformed to perillyl alcohol by the hydroxylation of cytochrome P450 alkane hydroxylase...
May 25, 2018: Sheng Wu Gong Cheng Xue Bao, Chinese Journal of Biotechnology
https://www.readbyqxmd.com/read/29891984/sublethal-effects-of-the-novel-cis-nitromethylene-neonicotinoid-cycloxaprid-on-the-cotton-aphid-aphis-gossypii-glover-hemiptera-aphididae
#20
Li Cui, Huizhu Yuan, Qiyuan Wang, Qinqin Wang, Changhui Rui
Cycloxaprid is a novel cis-configuration neonicotinoid insecticide that is effective against a wide range of insect pests, including those that are resistant to conventional neonicotinoids. In this study, life table parameters were applied to estimate the cycloxaprid-induced sublethal effects on Aphis gossypii. The results indicated that the LC20 (0.81 mg a.i. L-1 ) of cycloxaprid significantly decreased the pre-oviposition period in first-progeny adults. Additionally, the life expectancy of F1 generation adults was reduced...
June 11, 2018: Scientific Reports
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