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https://www.readbyqxmd.com/read/29629838/a-genetic-polymorphism-in-the-cyp1b1-gene-in-patients-with-squamous-cell-carcinoma-of-the-esophagus-an-iranian-mashhad-cohort-study-recruited-over-10-years
#1
Azam Rastgar Moghadam, Mehrane Mehramiz, Malihe Entezari, Hamideh Aboutalebi, Fatemeh Kohansal, Parisa Dadjoo, Hamid Fiuji, Mohammadreza Nasiri, Seyed Amir Aledavood, Kazem Anvari, Saeideh Ahmadi Simab, Mohammad Sadegh Khorrami, Ali Moradi, Seyed Mahdi Hassanian, Gordon A Ferns, Soodabeh Shahid Sales, Amir Avan
AIM: Esophageal cancer is the eighth most common cancer globally and the seventh most common cause of cancer-related deaths in men. Recent studies have shown that CYP450, family 1, subfamily B, polypeptide 1, which plays a role in the metabolism of xenobiotics, is associated with several cancers. Therefore, in the present study we investigated the association between a genetic variant, CYP1B1-rs1056836 gene, with the clinical characteristics of patients with squamous cell carcinoma of the esophagus (ESCC)...
April 9, 2018: Pharmacogenomics
https://www.readbyqxmd.com/read/29626533/the-repurposing-of-ivermectin-for-malaria-a-prospective-pharmacokinetics-based-virtual-clinical-trials-assessment-of-dosing-regimen-options
#2
Raj Badhan, Zaril Zakaria, Olusola Olafuyi
Ivermectin has demonstrated many successes in the treatment of a range of nematode infections. Considering the increase in malaria resistance attention has turned towards ivermectin as a candidate for repurposing for malaria. This study developed and validated an ivermectin physiologically-based pharmacokinetic model in healthy adults (20-50 years) and paediatric (3-5 years/15-25 kg) subjects and in a representative adult malaria population group (Thailand). Dosing optimisation demonstrated a twice daily for 3- or 5-day regimens would provide a time above the LC50 of more than 7 days for adult and paediatric...
April 4, 2018: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29620484/proton-pump-inhibitors-from-cyp2c19-pharmacogenetics-to-precision-medicine
#3
Nihal El Rouby, John J Lima, Julie A Johnson
Introduction- Proton Pump inhibitors (PPIs) are commonly used for a variety of acid related disorders. Despite the overall effectiveness and safety profile of PPIs, some patients do not respond adequately or develop treatment related adverse events. This variable response among patients is in part due to genotype variability of CYP2C19, the gene encoding the CYP450 (CYP2C19) isoenzyme responsible for PPIs metabolism. Areas covered-This article provides an overview of the pharmacokinetics and mechanism of action of the currently available PPIs, including the magnitude of CYPC19 contribution to their metabolism...
April 5, 2018: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/29611126/mode-of-action-of-nanoparticles-against-insects
#4
Giovanni Benelli
The employment of nanoparticles obtained through various synthesis routes as novel pesticides recently attracted high research attention. An impressive number of studies have been conducted to test their toxic potential against a wide number of arthropod pests and vectors, with major emphasis on mosquitoes and ticks. However, precise information on the mechanisms of action of nanoparticles against insects and mites are limited, with the noteworthy exception of silica, alumina, silver, and graphene oxide nanoparticles on insects, while no information is available for mites...
April 3, 2018: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/29593545/the-cytochrome-p450-mediated-metabolism-alternation-of-four-effective-lignans-from-schisandra-chinensis-in-carbon-tetrachloride-intoxicated-rats-and-patients-with-advanced-hepatocellular-carcinoma
#5
Rongrong Wu, Zhiyong Xiao, Xiaorui Zhang, Feng Liu, Wenxia Zhou, Yongxiang Zhang
It is highly valuable to study the pharmacokinetics of herbal components under the pathological condition of liver dysfunction for safe and rational use of herbal medicines. In this study, the pharmacokinetic profiles of four effective lignans from Schisandra chinensis (SC) , schisandrin, schisantherin A, deoxyshisandrin and γ-schisandrin, were investigated in carbon tetrachloride (CCl4 )-intoxicated rats. The metabolism of the four lignans was also studied using microsomes from patients with advanced hepatocellular carcinoma...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29588194/using-chemical-bond-based-method-to-predict-site-of-metabolism-for-five-biotransformations-mediated-by-cyp-3a4-2d6-and-2c9
#6
XuYan Fu, ShuaiBing He, Li Du, ZhaoLei Lv, Yi Zhang, Qian Zhang, Yun Wang
Although it has been proposed for decades to predict site of metabolism (SOM) by in silico methods, identifying SOM correctly remains an unsolved fundamental problem and is an active area of research. In our prior works, we proposed a chemical bond-based approach to construction of SOM prediction models by integrating chemical bond descriptors and drug-metabolizing enzymes data. Although it has been evaluated with both 10-fold cross-validation and independent validation, we believe comparisons between this method and prior methods using publicly accessible external datasets are indispensable and more desirable...
March 24, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29588191/arachidonic-acid-metabolites-of-cyp4a-and-cyp4f-are-altered-in-women-with-preeclampsia
#7
Nicole L Plenty, Jessica L Faulkner, Joshua Cotton, Shauna-Kay Spencer, Kedra Wallace, Babbette LaMarca, Sydney R Murphy
Few studies exist on cytochrome P450 (CYP450) metabolites of arachidonic acid (AA) pertaining to the pathophysiological events in pregnancy. We hypothesized that metabolism of AA via the CYP450 pathways is altered within the placenta in women with preeclampsia (PE) and contributes to the pathophysiology of the disease. Thus, placental vascular CYP450 enzyme expression and activity were measured in normal pregnant (NP) and preeclamptic (PE) patients. CYP450 isoform expression (CYP4A11, CYP4A22, CYP4F2, and CYP4F3) was found to be elevated within the placenta of women with PE compared to normal pregnant (NP) women and chronic hypertensive (CHTN) pregnant women...
March 24, 2018: Prostaglandins & Other Lipid Mediators
https://www.readbyqxmd.com/read/29587600/anticancer-redox-activity-of-gallium-nanoparticles-accompanied-with-low-dose-of-gamma-radiation-in-female-mice
#8
Eman I Kandil, Sawsan M El-Sonbaty, Fatma Sm Moawed, Ola Ms Khedr
Guided treatments with nanoparticles and radiotherapy are a new approach in cancer therapy. This study evaluated the beneficial antitumor effects of γ-radiation together with gallium nanoparticles against solid Ehrlich carcinoma in female mice. Gallium nanoparticles were biologically synthesized using Lactobacillus helveticus cells. Transmission electron microscopy showed gallium nanoparticles with size range of 8-20 nm. In vitro study of gallium nanoparticles on MCF-7 revealed IC50 of 8.0 μg. Gallium nanoparticles (0...
March 2018: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/29577658/metabolism-study-for-cumyl-4cn-binaca-in-human-hepatocytes-and-authentic-urine-specimens-free-cyanide-is-formed-during-the-main-metabolic-pathway
#9
Anna Åstrand, Svante Vikingsson, Daniel Lindstedt, Gunilla Thelander, Henrik Green, Robert Kronstrand, Ariane Wohlfarth
To further elucidate the metabolism of CUMYL-4CN-BINACA, a new synthetic cannabinoid with a cyano group, and to evaluate biomarkers, we incubated the substance in human hepatocytes and analysed nine authentic urine specimens. We also quantified CUMYL-4CN-BINACA and cyanide in blood and provide comprehensive data on the seven autopsy cases, five determined CUMYL-4CN-BINACA intoxications. For metabolite elucidation, CUMYL-4CN-BINACA was incubated with pooled human hepatocytes up to 5 h, urine samples were analysed with and without enzymatic hydrolysis...
March 25, 2018: Drug Testing and Analysis
https://www.readbyqxmd.com/read/29574263/evaluation-of-joint-effects-of-cyprodinil-and-kresoxim-methyl-on-zebrafish-danio-rerio
#10
Yanhua Wang, Dejiang Dai, Yijun Yu, Guiling Yang, Weifeng Shen, Qiang Wang, Hongbiao Weng, Xueping Zhao
Aquatic organisms are usually exposed to a mixture of pesticides instead of individual chemicals. However, risk assessment of pesticides is traditionally based on toxicity data of individual compounds. In this study, we aimed to examine the joint toxicity of two fungicides cyprodinil (CYP) and kresoxim-methyl (KRM) to zebrafish (Danio rerio) using a systematic experimental approach. Results from 96-h semi-static test indicated that the LC50 values of KRM to D. rerio at multiple life stages (embryonic, larval, juvenile and adult stages) ranged from 0...
March 20, 2018: Journal of Hazardous Materials
https://www.readbyqxmd.com/read/29571132/ugt-mediated-metabolism-plays-a-dominant-role-in-the-pharmacokinetic-behavior-and-the-disposition-of-morusin-in-vivo-and-in-vitro
#11
Chuqi Hou, Wenqin Liu, Zhi Liang, Weichao Han, Jinqing Li, Ling Ye, Menghua Liu, Zheng Cai, Jie Zhao, Yi Chen, Shuwen Liu, Lan Tang
Morusin is a prenylated flavone isolated from mulberry, the branch and root bark of various Morus species, which possesses diverse pharmacological activities. However, it lacks extensive studies about its absorption and disposition. This study investigated the pharmacokinetic behavior of morusin in rat, and its first-pass metabolism in situ. The metabolic pathway of morusin was further investigated by 12 human recombinant UDP-glucuronosyltransferases (UGTs), 9 CYP450s, as well as liver and intestinal microsomes...
March 12, 2018: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/29562214/tissue-specific-molecular-and-cellular-toxicity-of-pb-in-the-oyster-crassostrea-gigas-mrna-expression-and-physiological-studies
#12
Jie Meng, Wen-Xiong Wang, Li Li, Guofan Zhang
Lead (Pb) is one of the ubiquitous and toxic elements in aquatic environment. In oysters, gills and digestive glands are the main target organs for Pb-induced toxicity, but there is limited information on the molecular mechanisms underlying its toxicity. The present study investigated the Pb-induced toxicity mechanisms in the Pacific oyster (Crassostrea gigas) based on transcriptome, phenotypic anchoring, and validation of targeted gene expression. Gene ontology and pathway enrichment analyses revealed the differential Pb toxicity mechanisms in the tissues...
March 13, 2018: Aquatic Toxicology
https://www.readbyqxmd.com/read/29556126/modulation-of-cyp450-als1-and-cox-2-signaling-pathways-induced-by-candida-albicans-infection-via-novel-antifungal-agents
#13
Rehab M Abdel Megeed, Dalia B Fayed, Amira Abood, Mai O Kadry
Although, fluconazole is widely used in clinical treatment as an antifungal drug, it recorded potential problems as resistance and intracellular accumulation. Female albino mice were injected with single ip dose of Candida albicans (1.5 × 106 CFU) . Three weeks post treatment with fluconazole and two novel synthesized compounds [(2-(4-(Pyridin-2-yl) aminosulfonylphenylamino)-6-(naphthalen-2-yl)-4-(pyridin-2-yl) pyridine-3carbonitrile) and (2-(4-(Pyrimidin-2-yl) aminosulfonylphenylamino)-6-(naphthalen-2-yl)-4-(pyridine-2-yl)pyridine-3-carbonitrile) (13b & 14b, respectively)] in both low and high doses (50 mg/kg & 200 mg/kg), liver function and vaginal inflammation were assessed...
March 2018: Saudi Pharmaceutical Journal: SPJ: the Official Publication of the Saudi Pharmaceutical Society
https://www.readbyqxmd.com/read/29552858/-effect-of-ophiopogonin-d-in-resisting-vascular-endothelial-cell-apoptosis-induced-by-ang%C3%A2-through-up-regulating-cyp2j2-eets
#14
Xiao-Yan Huang, Yu-Guang Wang, Yi Wang, Yue Gao
This study aimed to investigate the effect and mechanism of ophiopogonin D (OP-D) on Ang Ⅱ-induced HUVECs apoptosis, in order to provide a reliable basis for the safety and efficacy of traditional Chinese medicines. The effect of Ang Ⅱ on survival and total proteins content of HUVECs were measured by MTT and Western blotting. The effect of OP-D on Ang Ⅱ-induced lactate dehydrogenase (LDH) release rate in HUVECs was measured by enzyme standard instrument. The effects of OP-D and 11,12-EET on phosphorylation of JNK/c-Jun induced by Ang Ⅱ were measured by Western blot and RT-PCR with the help of JNK specific inhibitor SP600125 and CYP450 isozymes selective inhibitor 6-(2-propargyloxyphenyl) hexanoic acid (PPOH)...
January 2018: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/29552849/-cloning-and-functional-identification-of-a-new-nadph-cytochrome-p450-reductase-in-andrographis-paniculata
#15
Meng-Die Qi, Jian Wang, Xiao-Jing Ma, Quan Zhang, Fang-Fang Wang, Ying Kang, Hui-Xin Lin, Yong Liu
Andrographolide is a main active ingredient in traditional Chinese medicine Andrographis paniculata,with a variety of pharmacological activity,widely used in clinical practice. However its biosynthetic pathway has not been resolved. Cytochrome P450 reductase provides electrons for CYP450 and plays an important role in the CYP450 catalytic process. In this study,the coding sequence of A. paniculata CPR was screened and cloned by homologous alignment,named ApCPR4. The ApCPR4 protein was obtained by prokaryotic expression...
January 2018: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/29542427/evaluation-of-herb-drug-interaction-of-synacinntm-and-individual-biomarker-through-cytochrome-450-inhibition-assay
#16
Fadzilah Adibah Abd Majid, Nur Syukriah Ab Rahman, Effendy Abd Wahid, Ain Nabihah Zainudin, Siti Nurazwa Zainol, Hassan Fahmi Ismail, Tet Soon Wong, K Vijaya Bhargava, Nirbhay Kumar Tiwari, Sanjeev Giri
Drug interaction of SynacinnTM polyherbal with known diabetic drugs is unknown. SynacinnTM contains standardized extracts of five herbal against gallic acid, curcumin, rosmarinic acid, catechin and andrographolide. SynacinnTM and its five standard markers were analysed for its possible interaction with CYP450 enzymes assay. This study was conducted using liquid chromatography-tandem mass spectroscopy (LC-MS/MS) using probe substrates using human liver microsomes against CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4(Midazolam) and CYP3A4 (Testosteron)...
March 13, 2018: Drug Metabolism Letters
https://www.readbyqxmd.com/read/29534510/effects-of-honokiol-on-cyp450-activity-and-transporter-mrna-expression-in-type-2-diabetic-rats
#17
Junjun Wang, Ting Zhai, Yong Chen
This study was aimed to clarify the effect of honokiol (Hon) on the activity of Cytochrome P450 (CYP450) enzymes, and the level of mRNA expression of liver and kidney transporters in type 2 diabetic rats induced by high-fat diet and strepotozotocin. Rats were randomly divided into normal control (NC) group, diabetic control (DC) group and Hon groups ( n = 6). The activities of hepatic CYP1A2, CYP2E1, CYP2C, CYP2B, CYP3A and CYP4A, and the mRNA expression levels of hepatic and renal transporters, were determined...
March 12, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29521669/the-use-of-serum-methadone-metabolite-ratios-to-monitor-changing-perinatal-pharmacokinetics
#18
John J McCarthy, Ernest J Vasti, Martin H Leamon, Joseph Graas, Coburn Ward, Catherine Fassbender
OBJECTIVES: Pregnancy profoundly alters drug metabolism, accelerating clearance and confounding medication management, primarily through induction of CYP450 enzymes. Methadone is a CYP450 substrate with altered pharmacokinetics during pregnancy. We report on the use of serum methadone/metabolite ratios (MMRs) to monitor changes in methadone metabolism through the perinatal period and to objectively guide methadone dosing. Previous research found average MMRs in nonpregnant populations of between 11...
March 7, 2018: Journal of Addiction Medicine
https://www.readbyqxmd.com/read/29512903/tracking-down-a-novel-steroid-hydroxylating-promiscuous-cytochrome-p450-cyp154c8-from-streptomyces-sp-w2233-sm
#19
Bikash Dangi, Ki-Hwa Kim, Sang-Ho Kang, Tae-Jin Oh
CYP154C8 from Streptomyces sp. was identified as a novel cytochrome P450 with substrate flexibility to different sets of steroids. The in vitro reaction of these steroids with CYP154C8 revealed interesting product formation patterns with the same group of steroids. Nuclear magnetic resonance study revealed the major product of corticosterone hydroxylated at the C21 position; while progesterone, androstenedione, testosterone, and 11-ketoprogesterone were exclusively hydroxylated at 16α position. However, the 16α-hydroxylated product of progesterone was further hydroxylated to yield dihydroxylated products...
March 7, 2018: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/29500141/polymorphisms-in-cyp450-genes-and-the-therapeutic-effect-of-atorvastatin-on-ischemic-stroke-a-retrospective-cohort-study-in-chinese-population
#20
Chen Peng, Ying Ding, Xin Yi, Yupei Shen, Zhiqiang Dong, Limei Cao, Qiang Li, Haiyan Ren, Lin He, Daizhan Zhou, Xu Chen
PURPOSE: Ischemic stroke (IS) is one of the most common neurologic diseases and is the main cause of death and disability in the Chinese population. This retrospective cohort study was performed to elucidate the relationship between single nucleotide polymorphisms (SNPs) in cytochrome P450 genes and the therapeutic effect of atorvastatin. METHODS: A total of 192 cases of IS were enrolled in the study. All patients were treated with atorvastatin, and their lipid levels and proportions were measured...
February 27, 2018: Clinical Therapeutics
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