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54. Regulation profile of the intestinal peptide transporter 1 (PepT1)

Author

Wang,Chun-Yang, Liu,Shu, Xie,Xiao-Nv, and Tan,Zhi-Rong

Subjects
Drug Design, Development and Therapy
Abstract

Chun-Yang Wang,1,2 Shu Liu,1,2 Xiao-Nv Xie,1,2 Zhi-Rong Tan1,2 1Department of Clinical Pharmacology, Xiangya Hospital, Xiangya School of Medicine, Central South University, 2Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha, Hunan, People’s Republic of China Abstract: The intestinal peptide transporter 1 (PepT1) was first identified in 1994. It plays a crucial role in the absorption of small peptides including not only >400 different dipeptides and 8,000 tripeptides digested from dietary proteins but also a repertoire of structurally related compounds and drugs. Owing to its critical role in the bioavailability of peptide-like drugs, such as the anti-cancer agents and anti-virus drug, PepT1 is increasingly becoming a striking prodrug-designing target. Therefore, the understanding of PepT1 gene regulation is of great importance both for dietary adaptation and for clinical drug treatment. After decades of research, it has been recognized that PepT1 could be regulated at the transcriptional and post-transcriptional levels by numerous factors. Therefore, the present review intends to summarize the progress made in the regulation of PepT1 and provide insights into the PepT1’s potential in clinical aspects of nutritional and drug therapies. Keywords: PepT1, dietary, regulation, transport activity, absorption, bioavailability

Published
2017

55. DNA hypermethylated status and gene expression of PAX1/SOX1 in patients with colorectal carcinoma

Author

Huang,Jin, Tan,Zhi-Rong, Yu,Jing, Li,He, Lv,Qiao-Li, Shao,Ying-Ying, and Zhou,Hong-Hao

Subjects
OncoTargets and Therapy
Abstract

Jin Huang,1,2 Zhi-Rong Tan,1,2 Jing Yu,1,2 He Li,1,2 Qiao-Li Lv,1,2 Ying-Ying Shao,3 Hong-Hao Zhou1,2 1Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, Hunan, 2Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, Hunan, 3Institute of Life Science, Chongqing Medical University, Yuzhong District, Chongqing, China Background: Colorectal cancer (CRC) is a widespread and aggressive carcinoma with poor prognosis. Hypermethylation of specific gene promoters is an important mechanism of CRC. In this study, we investigated the hypermethylation of paired boxed gene 1 (PAX1) and sex-determining region Y-related high-mobility group box 1 (SOX1) genes in CRC tissues. Methods: DNA methylation at cg2,09,07,471 PAX1 and cg0,66,75,478 SOX1 from 166 cancer tissues and 37 normal tissues from CRC patients were compared using datasets downloaded from The Cancer Genome Atlas. Quantitative methylation-specific polymerase chain reaction and assay of PAX1 and SOX1 were performed in dissected tumor and paracancerous tissues by surgery from 41 CRC patients. Quantitative reverse transcription polymerase chain reaction and immunohistochemistry assay were performed in both CRC and paired normal tissues to detect mRNA and protein expression, respectively.Results: Methylation levels of PAX1/SOX1 genes were significantly higher in cancer tissues than in paired normal tissues. PAX1 and SOX1 genes were methylated in 28 (68.3%) of the 41CRC samples but in 5 (12.2%) and 0 (0%) of the paired normal control samples (both P0.5). In addition, the methylation level of PAX1/SOX1 was significantly higher in CRC patients with high TNM stage (TNM stage III/IV, 3.11±2.43) than those with low TNM stage (TNM stageI/II, 1.26±2.94, P

Published
2017

60. The potent mechanism-based inactivation of CYP2D6 and CYP3A4 with fusidic acid inin vivobioaccumulation

Author

Lin, Xiu-Xian, primary, Lian, Guang-Hui, additional, Xu, Ying, additional, Zhao, Qing, additional, Xiao, Jian, additional, Peng, Shi-Fang, additional, Xiao, Mei-Fang, additional, Ouyang, Dong-Sheng, additional, Tan, Zhi-Rong, additional, Wang, Yi-Cheng, additional, Peng, Jing-Bo, additional, Zhang, Wei, additional, and Chen, Yao, additional

Published
2017
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64. Quantification of Teprenone in Human Plasma by HPLC Coupled to Mass Spectrometry: Application to a Bioequivalence Study

Author

Zhou Yan-bin, He Juan, Song Juan, Ding Jin-song, and Tan Zhi-rong

Subjects
Detection limit, Chemical ionization, Chromatography, Chemistry, Organic Chemistry, Clinical Biochemistry, Analytical chemistry, Atmospheric-pressure chemical ionization, Bioequivalence, Mass spectrometry, Biochemistry, High-performance liquid chromatography, Analytical Chemistry, Liquid chromatography–mass spectrometry, medicine, Teprenone, medicine.drug
Abstract

A rapid, sensitive, and specific method has been developed for quantification of teprenone (TEP) in human plasma. The analytes were isolated from plasma by liquid–liquid extraction with t-butyl methyl ether. The extracts were analyzed by high-performance liquid chromatography coupled to mass spectrometry (HPLC–MS); gefarnate was used as internal standard (IS). HPLC separation of the analytes was performed on a C18 column with 1:54:45 (v/v) 1% aqueous acetic acid–methanol–acetonitrile as mobile phase; the flow rate was 0.2 mL min−1. The compounds were ionized by atmospheric-pressure chemical ionization (APCI). Calibration plots for TEP were linear in the range 20.0–2000.0 ng mL−1; correlation coefficients were >0.9981. The average extraction efficiency for TEP was >67%, method recovery was >95%, the limit of detection (LOD) was 1.0 ng mL−1, and the intraday and interday coefficients of variation were

Published
2007
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65. Real-time colorimetric detection of DNA methylation of the PAX1 gene in cervical scrapings for cervical cancer screening with thiol-labeled PCR primers and gold nanoparticles

Author

Huang,Jin, Liou,Yu-Ligh, Kang,Ya-Nan, Tan,Zhi-Rong, Peng,Ming-Jing, Zhou,Hong-Hao, Huang,Jin, Liou,Yu-Ligh, Kang,Ya-Nan, Tan,Zhi-Rong, Peng,Ming-Jing, and Zhou,Hong-Hao

Abstract

Jin Huang,1,2 Yu-Ligh Liou,1,2 Ya-Nan Kang,3 Zhi-Rong Tan,1,2 Ming-Jing Peng,1,2 Hong-Hao Zhou1,2 1Department of Clinical Pharmacology, Xiangya Hospital, Central South University, 2Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, 3Department of Obstetrics and Gynecology, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China Background: DNA methylation can induce carcinogenesis by silencing key tumor suppressor genes. Analysis of aberrant methylation of tumor suppressor genes can be used as a prognostic and predictive biomarker for cancer. In this study, we propose a colorimetric method for the detection of DNA methylation of the paired box gene 1 (PAX1) gene in cervical scrapings obtained from 42 patients who underwent cervical colposcopic biopsy. Methods: A thiolated methylation-specific polymerase chain reaction (MSP) primer was used to generate MSP products labeled with the thiol group at one end. After bisulfite conversion and MSP amplification, the unmodified gold nanoparticles (AuNPs) were placed in a reaction tube and NaCl was added to induce aggregation of bare AuNPs without generating polymerase chain reaction products. After salt addition, the color of AuNPs remained red in the methylated PAX1 gene samples because of binding to the MSP-amplified products. By contrast, the color of the AuNP colloid solution changed from red to blue in the non-methylated PAX1 gene samples because of aggregation of AuNPs in the absence of the MSP-amplified products. Furthermore, PAX1 methylation was quantitatively detected in cervical scrapings of patients with varied pathological degrees of cervical cancer. Conventional quantitative MSP (qMSP) was also performed for comparison. Results: The two methods showed a significant correlation of the methylation frequency of the PAX1 gene in cervical scrapings with severity of cervical cancer (n=42, P<0.05). The results of the pr

Published
2016

70. The potent mechanism-based inactivation of CYP2D6 and CYP3A4 with fusidic acid in in vivo bioaccumulation.

Author

Lin, Xiu-Xian, Lian, Guang-Hui, Xu, Ying, Zhao, Qing, Xiao, Jian, Peng, Shi-Fang, Xiao, Mei-Fang, Ouyang, Dong-Sheng, Tan, Zhi-Rong, Wang, Yi-Cheng, Peng, Jing-Bo, Zhang, Wei, and Chen, Yao

Subjects
ENZYME inactivation, ENZYME regulation, METOPROLOL, CARDIOVASCULAR agents, HYDROXYLATION, THERAPEUTICS
Abstract

1. The accumulation of fusidic acid (FA) after multiple doses of FA has been reported on in previous studies but the related mechanisms have not been clarified fully. In the present study, we explain the mechanisms related to the mechanism-based inactivation of CYP2D6 and CYP3A4. 2. The irreversible inhibitory effects of FA on CYP2D6 and CYP3A4 were examined via a series of experiments, including: (a) time-, concentration- and NADPH-dependent inactivation, (b) substrate protection in enzyme inactivation and (c) partition ratio with recombinant human CYP enzymes. Metoprolol α-hydroxylation and midazolam 1′-hydroxylation were used as marker reactions for CYP2D6 and CYP3A4 activities, and HPLC-MS/MS measurement was also utilised. 3. FA caused to the time- and concentration-dependent inactivation of CYP2D6 and CYP3A4. About 55.8% of the activity of CYP2D6 and 75.8% of the activity of CYP3A4 were suppressed after incubation with 10 μM FA for 15 min. KI and kinact were found to be 2.87 μM and 0.033 min−1, respectively, for CYP2D6, while they were 1.95 μM and 0.029 min−1, respectively, for CYP3A4. Inhibition of CYP2D6 and CYP3A4 activity was found to require the presence of NADPH. Substrates of CYP2D6 and CYP3A4 showed that the enzymes were protected against the inactivation induced by FA. The estimated partition ratio for the inactivation was 7 for CYP2D6 and 12 for CYP3A4. 4. FA is a potent mechanism-based inhibitor of CYP2D6 and CYP3A4, which may explain the accumulation of FA in vivo. [ABSTRACT FROM AUTHOR]

Published
2018
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72. Searching the Cytochrome P450 Enzymes for the Metabolism of Meranzin Hydrate: A Prospective Antidepressant Originating from Chaihu-Shugan-San

Author

Huang, Xi, primary, Guo, Ying, additional, Huang, Wei-hua, additional, Zhang, Wei, additional, Tan, Zhi-rong, additional, Peng, Jing-bo, additional, Wang, Yi-cheng, additional, Hu, Dong-li, additional, Ouyang, Dong-sheng, additional, Xiao, Jian, additional, Wang, Yang, additional, Luo, Min, additional, and Chen, Yao, additional

Published
2014
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77. Simultaneous determination of sulindac and its metabolites sulindac sulfide and sulindac sulfone in human plasma by a sensitive UPLC-PDA method for a pharmacokinetic study

Author

Huang, Wei-Hua, primary, Shao, Li, additional, Li, Shun-Xiang, additional, Guo, Dong, additional, Wang, Lian-Sheng, additional, Li, Zhi, additional, Peng, Xiang-Dong, additional, Chen, Yao, additional, Zhang, Wei, additional, Zhou, Hong-Hao, additional, and Tan, Zhi-Rong, additional

Published
2014
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79. Clinical application and importance of one-step human CYP2C19genotype detection

Author

Zheng, Ling-Jie, Liu, Ning, Yang, Kun, Wang, Ai-Feng, Tan, Zhi-Rong, and Li, Xiang

Abstract

Background To directly achieve cytochrome P450 2C19 gene (CYP2C19) classification using one-step real-time fluorescent PCR detection and to verify the capabilities of this method with nucleic acid extracted from whole blood samples.Methods A human CYP2C19genotyping kit based on one-step real-time fluorescent PCR detection was used to analyze whole blood or genomic DNA samples. This method was compared with pyrosequencing and another quantitative (q)PCR kit for its accuracy, repeatability, detection range analysis, sensitivity, specificity, and anti-interference analysis.Results The one-step real-time PCR method achieved a 100% accuracy rate compared with pyrosequencing and the other qPCR kit. When detecting different concentrations of known genes, concentrations of each sample ranging from 0.2 to 125 ng/µL could be correctly detected. The genotypes of samples treated with anticoagulants, including EDTA and sodium citrate, and chyle blood samples could be correctly detected.Conclusion The one-step detection method demonstrated high accuracy and a wide detection range. It also had high levels of repeatability, sensitivity, and specificity for the assessment of genomic DNA test samples.

Published
2018
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81. Polymorphism of ORM1 Is Associated with the Pharmacokinetics of Telmisartan

Author

Chen, Wang-Qing, primary, Shu, Yan, additional, Li, Qing, additional, Xu, Lin-Yong, additional, Roederer, Mary W., additional, Fan, Lan, additional, Wu, Lan-Xiang, additional, He, Fa-Zhong, additional, Luo, Jian-Quan, additional, Tan, Zhi-Rong, additional, He, Yi-Jing, additional, Zhou, Hong-Hao, additional, Chen, Xiang, additional, and Zhang, Wei, additional

Published
2013
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84. Influence of ORM1 polymorphisms on the maintenance stable warfarin dosage

Author

Wang, Lian Sheng, primary, Shang, Jing Jing, additional, Shi, Shu Ya, additional, Zhang, Yan Qing, additional, Lin, Jian, additional, Guo, Zhi Hua, additional, Wang, Yi Chen, additional, Tang, Jie, additional, Liu, Jie, additional, Liu, Ying Zi, additional, Li, Zhi, additional, Tan, Zhi Rong, additional, Zhou, Hong Hao, additional, Jiang, Hai He, additional, and Xie, Hai Tang, additional

Published
2012
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86. Pharmacokinetic interactions between ilaprazole and clarithromycin following ilaprazole, clarithromycin and amoxicillin triple therapy

Author

Cao, Shan, primary, Zhou, Gan, additional, Ou-YANG, Dong-sheng, additional, Wu, Hui-zi, additional, Xiao, Kui, additional, Chen, Yao, additional, Guo, Dong, additional, Fan, Lan, additional, Tan, Zhi-rong, additional, Hu, Hai-tang, additional, Qin, Xiang-hong, additional, Zhou, Hong-hao, additional, and Zhang, Wei, additional

Published
2012
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89. Genistein alters caffeine exposure in healthy female volunteers

Author

Chen, Yao, primary, Xiao, Chang-Qiong, additional, He, Yi-Jing, additional, Chen, Bi-Lian, additional, Wang, Guo, additional, Zhou, Gan, additional, Zhang, Wei, additional, Tan, Zhi-Rong, additional, Cao, Shan, additional, Wang, Li-Ping, additional, and Zhou, Hong-Hao, additional

Published
2010
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99. A high-throughput inhibition screening of major human cytochrome P450 enzymes using an in vitro cocktail and liquid chromatography-tandem mass spectrometry.

Author

Qin, Chong‐Zhen, Ren, Xian, Tan, Zhi‐Rong, Chen, Yao, Yin, Ji‐Ye, Yu, Jing, Qu, Jian, Zhou, Hong‐Hao, and Liu, Zhao‐Qian

Abstract

ABSTRACT A sensitive and high-throughput inhibition screening liquid chromatography-mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous quantification of five probe metabolites (7-hydroxycoumarin, CYP2A6; 4-hydroxytolbutamide, CYP2C9; 4′-hydroxymephenytoin, CYP2C19; α-hydroxymetoprolol, CYP2D6; and 1-hydroxymidazolam, CYP3A4) for in vitro cytochrome P450 activity determination in human liver microsome and recombinant. All the metabolites and the internal standard, tramadol, were separated on a Waters 2695 series liquid chromatograph with a Phenomenex Luna C18 column (150 × 2.0 mm, 5 µm). Quality control samples and a positive control CYP inhibitor were included in the method. The IC50 values determined for typical CYP inhibitors were reproducible and in agreement with the literature. The method was selective and showed good accuracy (99.13-103.37%), and inter-day (RSD < 6.20%) and intra-day (RSD < 6.13%) precision. Also, the incubation extracts of the sample were stable at room temperature (20 °C) for 48 h and for 96 h in the autosampler (4 °C). The presented method is the first HPLC-MS/MS method of this combination for simultaneous detection of the five metabolites 7-hydroxycoumarin, 4-hydroxytolbutamide, 4′-hydroxymephenytoin, α-hydroxymetoprolol and 1-hydroxymidazolam in a single-run process. It is possible that the high-quality and -throughput cocktail provides suitable information in drug discovery and screening for new drug entities. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Published
2014
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100. Assessment of a pharmacokinetic and pharmacodynamic interaction between simvastatin and Ginkgo biloba extracts in healthy subjects.

Author

Dai, Ling-Ling, Fan, Lan, Wu, Hui-Zi, Tan, Zhi-Rong, Chen, Yao, Peng, Xiang-Dong, Shen, Min-Xue, Yang, Guo-Ping, and Zhou, Hong-Hao

Subjects
PHARMACOKINETICS, PHARMACODYNAMICS, SIMVASTATIN, GINKGO, HERBAL medicine
Abstract

1. Ginkgo biloba extract (GBE) is one of the most commonly used herbal remedies worldwide. It is usually concomitantly administrated with statins to treat diseases in geriatric patients. We aim to determine the influence of GBE on the pharmacokinetics (PK) and pharmacodynamics of simvastatin, which is currently unknown. 2. An open-label, randomized, two-period, two-treatment, balanced, crossover study was performed in 14 healthy volunteers. Subjects received simvastatin 40 mg once daily, co-treated with placebo or GBE 120 mg twice daily. Each treatment was administered for 14 d, separated by a wash-out period of 1 month. Simvastatin, simvastatin acid and lipoprotein concentrations were assessed. 3. GBE administration reduced mean simvastatin area under the curve (AUC)0-24, AUC0-∞ and Cmax by 39% ( p = 0.000), 36%( p = 0.001) and 32% ( p = 0.002), respectively, but did not cause significant differences in simvastatin acid PK or its cholesterol-lowering efficacy. 4. GBE consumption decreased simvastatin system exposure, but did not affect simvastatin acid PK. However, we cannot rule out the possibility for a pharmacodynamic interaction between GBE and simvastatin in vivo. [ABSTRACT FROM AUTHOR]

Published
2013
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