382 results on '"Zhao-Qian Liu"'
Search Results
352. Effect of Jianweiyuyang granule on gastric ulcer recurrence and expression of VEGF mRNA in the healing process of gastric ulcer in rats
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Cheng-Hui Huang, Jia-bang Li, Xing-Ping Dai, Zhao-Qian Liu, Bing Zhou, and Xiang Ding
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Male ,Vascular Endothelial Growth Factor A ,medicine.medical_specialty ,Pathology ,Angiogenesis ,Gene Expression ,Gastroenterology ,Rats, Sprague-Dawley ,Ranitidine ,chemistry.chemical_compound ,Recurrence ,Internal medicine ,Gene expression ,medicine ,Animals ,RNA, Messenger ,Stomach Ulcer ,Base Sequence ,business.industry ,Microcirculation ,digestive, oral, and skin physiology ,Interleukin ,General Medicine ,digestive system diseases ,Rats ,Reverse transcription polymerase chain reaction ,Vascular endothelial growth factor ,Vascular endothelial growth factor A ,Basic Research ,chemistry ,Immunohistochemistry ,Female ,business ,Drugs, Chinese Herbal ,Interleukin-1 ,Phytotherapy ,medicine.drug - Abstract
AIM: To investigate the effect of Jianweiyuyang (JWYY) granule on gastric ulcer recurrence and its mechanism in the treatment of gastric ulcer in rats. METHODS: Gastric ulcer in rats was induced according to Okeba’s method with minor modification and the recurrence model was induced by IL-1β. The expression of vascular endothelial growth factor mRNA (VEGF mRNA) was examined by reverse transcription polymerase chain reaction in gastric ulcer and microvessel density (MVD) adjacent to the ulcer margin was examined by immunohistochemistry. RESULTS: MVD was higher in the JWYY treatment group (14.0±2.62) compared with the normal, model and ranitidine treatment groups (2.2±0.84, 8.8±0.97, 10.4±0.97) in rats (P
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- 2005
353. JAZF1 regulates visfatin expression in adipocytes via PPARα and PPARβ/δ signaling.
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Guang-feng Ming, Xi Li, Ji-ye Yin, Yu-hang Ai, Dao-miao Xu, Xin-hua Ma, Zhi-yong Liu, Hui-xia Liu, Hong-hao Zhou, and Zhao-qian Liu
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ZINC-finger proteins ,ADIPOKINES ,PROTEIN expression ,PEROXISOME proliferator-activated receptors ,CELLULAR signal transduction ,TYPE 2 diabetes ,GLUCOSE metabolism ,LIPID metabolism - Abstract
Objective Current whole genome-wide association study has identified the association of JAZF1 with type 2 diabetes; its close relation with glucose and lipid metabolism has also been revealed. However, to date, JAZF1 remains a relatively new gene with unknown function. Materials/Methods We constructed JAZF1 overexpression vector and synthesized JAZF1 siRNA, then transfected them into 3T3-L1 adipocytes, investigated the relationship between the regulations of JAZF1, visfatin, and other adipokines, researched the specific function of JAZF1 in glucose and lipid metabolism. Results This study found that the expression of JAZF1 was gradually but significantly upregulated during the induced differentiation of 3T3-L1 preadipocytes, and that the trend of its expression was consistent with that of visfatin. Further studies indicated that JAZF1 promoted the expressions of visfatin, PPARα, and PPARβ/δ in adipocytes but simultaneously inhibited the expressions of TAK1 and PPARγ. Luciferase reporter assay revealed that JAZF1 activated the transcription of visfatin, but ChIP assay results indicated that JAZF1 did not directly bind to visfatin PPRE. Our results also showed that the JAZF1 overexpression-increased visfatin expression was abolished by the addition of PPARα antagonist GW 6471 and PPARβ/δ antagonist GSK 3787 respectively. And these results were further confirmed by the experiment with PPARα and PPARβ/δ siRNAs. Meanwhile, we also found that JAZF1 inhibited the lipid accumulation during the differentiation of 3T3-L1 into mature adipocyte. Conclusions Our results indicate that JAZF1 might firstly upregulated the expression of PPARα and PPARβ/δ, which in turn activated the transcription of visfatin. JAZF1 plays an important role in lipid metabolism and may thus provide a potential tool for the treatment of obesity and lipid metabolism disorders among other diseases. [ABSTRACT FROM AUTHOR]
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- 2014
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354. Huperzine A Ameliorates Cognitive Deficits in Streptozotocin-Induced Diabetic Rats.
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Xiao-Yuan Mao, Dan-Feng Cao, Xi Li, Ji-Ye Yin, Zhi-Bin Wang, Ying Zhang, Chen-Xue Mao, Hong-Hao Zhou, and Zhao-Qian Liu
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HUPERZINE A ,COGNITION disorders treatment ,STREPTOZOTOCIN ,TREATMENT of diabetes ,LABORATORY rats ,NEUROTROPHINS ,DRUG dosage ,PHYSIOLOGY - Abstract
The present study was designed to probe the effects of Huperzine A (HupA) on diabetes-associated cognitive decline (DACD) using a streptozotocin (STZ)-injected rat model. Diabetic rats were treated with HupA (0.05 and 0.1 mg/kg) for seven weeks. Memory functions were evaluated by the water maze test. Nissl staining was selected for detecting neuronal loss. Protein and mRNA levels of brain-derived neurotrophic factor (BDNF) were analyzed by ELISA and real-time PCR, respectively. The activities of choline acetylase (ChAT), Acetylcholinesterase (AChE), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), NF-κB p65 unit, TNF-α, IL-1β, IL-6 and caspase-3 were measured using corresponding kits. After seven weeks, diabetic rats exhibited remarkable reductions in: body weight, percentage of time spent in target quadrant, number of times crossing the platform, ChAT and BDNF levels, SOD, GSH-Px and CAT accompanied with increases in neuronal damage, plasma glucose levels, escape latency, mean path length, AChE, MDA level as well as CAT, NF-κB p65 unit, TNF-α, IL-1β, IL-6 and caspase-3 in cerebral cortex and hippocampus. Supplementation with HupA significantly and dose-dependently reversed the corresponding values in diabetes. It is concluded that HupA ameliorates DACD via modulating BDNF, oxidative stress, inflammation and apoptosis. [ABSTRACT FROM AUTHOR]
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- 2014
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355. Pharmacokinetic comparison of the vasorelaxant compound ferulic acid following the administration of Guanxin II to healthy volunteers and patients with angina pectoris.
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YUN-HUI LI, XI HUANG, YANG WANG, RONG FAN, HONG-MIN ZHANG, PING REN, YAO CHEN, HONG-HAO ZHOU, ZHAO-QIAN LIU, YI-ZENG LIANG, and HONG-MEI LU
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ANGINA pectoris ,ANGINA pectoris treatment ,CORONARY heart disease treatment ,PHARMACOKINETICS ,FERULIC acid ,CHINESE medicine - Abstract
Coronary heart disease (CHD) is the leading cause of mortality worldwide. The Chinese medicinal formula Guanxin II has been shown to have a favorable effect in the attenuation of angina. The aim of this study was to compare the pharmacokinetics of ferulic acid (FA), which is a vasorelaxant compound present in Guanxin II, in healthy volunteers and patients with angina pectoris following the administration of Guanxin II. Ex vivo experiments were performed in order to investigate the vasorelaxant effect of FA on the human internal mammary artery (IMA) to provide evidence that it is a bioactive component of Guanxin II. Following the oral administration of Guanxin II, the FA levels in the serum were quantified by a simple and rapid high-performance liquid chromatography (HPLC) method. Treatment with FA (10
-8 -10-3 M) caused a concentration-dependent relaxation of endothelial IMA rings following precontraction with KCl. Statistically significant differences were identified between the pharmacokinetic parameters Cmax , t1/2 α, t1/2 ß and t1/2 Ka of the healthy volunteers and the patients with angina pectoris following the oral administration of Guanxin II. FA is a bioactive compound absorbed from Guanxin II that attenuates angina pectoris, a condition that may modify the pharmacokinetics of FA. Not only do the pharmacokinetic parameters direct the clinical use of Guanxin II, but they may also be useful for exploring the pathology of angina pectoris. [ABSTRACT FROM AUTHOR]- Published
- 2013
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356. The rs1142345 in TPMT Affects the Therapeutic Effect of Traditional Hypoglycemic Herbs in Prediabetes.
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Xi Li, Feng-Mei Lian, Dong Guo, Lan Fan, Jie Tang, Jing-Bo Peng, Hong-Wen Deng, Zhao-Qian Liu, Xin-Hua Xiao, Yan-Rong Wang, Ke-Yi Qu, Sheng Deng, Qi Zhong, Yi-Ling Sha, Yan Zhu, Yu-Jing Bai, Xin-Yan Chen, Qiang Zhou, Hong-Hao Zhou, and Xiao-Lin Tong
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BLOOD sugar analysis ,TYPE 2 diabetes prevention ,HYPOGLYCEMIC agents ,PREDIABETIC state ,DNA analysis ,GLUCOSE intolerance ,ALLELES ,ALTERNATIVE medicine ,GENES ,GENETICS ,GLUCOSE tolerance tests ,LONGITUDINAL method ,MEDICAL cooperation ,BOTANIC medicine ,CHINESE medicine ,HEALTH outcome assessment ,REGRESSION analysis ,RESEARCH ,RESEARCH funding ,STATISTICAL sampling ,STATISTICS ,LOGISTIC regression analysis ,DATA analysis ,STATISTICAL significance ,BODY mass index ,RANDOMIZED controlled trials ,TREATMENT effectiveness ,PRE-tests & post-tests ,BLIND experiment ,DATA analysis software ,DESCRIPTIVE statistics ,THERAPEUTICS - Abstract
Therapeutic interventions in prediabetes are important in the primary prevention of type 2 diabetes (T2D) and its chronic complications. However, little is known about the pharmacogenetic effect of traditional herbs on prediabetes treatment. A total of 194 impaired glucose tolerance (IGT) subjects were treated with traditional hypoglycemic herbs (Tianqi Jiangtang) for 12 months in this study. DNA samples were genotyped for 184 mutations in 34 genes involved in drug metabolism or transportation. Multinomial logistic regression analysis indicated that rs1142345 (A > G) in the thiopurine S-methyltransferase (TPMT) gene was significantly associated with the hypoglycemic effect of the drug (P = 0.001, FDR P = 0.043). The "G" allele frequencies of rs1142345 in the healthy (subjects reverted from IGT to normal glucose tolerance), maintenance (subjects still had IGT), and deterioration (subjects progressed from IGT to T2D) groups were 0.094, 0.214, and 0.542, respectively. Binary logistic regression analysis indicated that rs1142345 was also significantly associated with the hypoglycemic effect of the drug between the healthy and maintenance groups (P = 0.027, OR = 4.828) and between the healthy and deterioration groups (P = 0.001, OR = 7.811). Therefore, rs1142345 was associated with the clinical effect of traditional hypoglycemic herbs. Results also suggested that TPMT was probably involved in the pharmacological mechanisms of T2D. [ABSTRACT FROM AUTHOR]
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- 2013
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357. Meta-Analysis on Pharmacogenetics of Platinum-Based Chemotherapy in Non Small Cell Lung Cancer (NSCLC) Patients.
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Ji-Ye Yin, Qiong Huang, Ying-Chun Zhao, Hong-Hao Zhou, and Zhao-Qian Liu
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Aim: To determine the pharmacogenetics of platinum-based chemotherapy in Non Small Cell Lung Cancer (NSCLC) patients. Methods: Publications were selected from PubMed, Cochrane Library and ISI Web of Knowledge. A meta-analysis was conducted to determine the association between genetic polymorphisms and platinum-based chemotherapy by checking odds ratio (OR) and 95% confidence interval (CI). Results: Data were extracted from 24 publications, which included 11 polymorphisms in 8 genes for meta-analysis. MDR1 C3435T (OR = 1.97, 95% CI: 1.11-3.50, P = 0.02), G2677A/T (OR = 2.61, 95% CI: 1.44-4.74, P = 0.002) and GSTP1 A313G (OR = 0.32, 95% CI: 0.17-0.58, P = 0.0002) were significantly correlated with platinum-based chemotherapy in Asian NSCLC patients. Conclusion: Attention should be paid to MDR1 C3435T, G2677A/T and GSTP1 A313G for personalized chemotherapytreatment for NSCLC patients in Asian population in the future. [ABSTRACT FROM AUTHOR]
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- 2012
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358. Cytoprotective effects of albumin, nitrosated or reduced, in cultured rat pulmonary vascular cells.
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Hui-Hua Li, Jing Xu, Wasserloos, Karta J., Jin Li, Tyurina, Yulia Y., Kagan, Valerian E., Xiaorong Wang, Chen, Alex F., Zhao-Qian Liu, Stoyanovsky, Detcho, Pitt, Bruce R., and Li-Ming Zhang
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ALBUMINS ,ENZYME activation ,PULMONARY blood vessels ,ENDOTHELIAL growth factors ,ENDOTHELIAL seeding ,SMOOTH muscle inflammation ,LABORATORY rats - Abstract
S-nitrosoalbumin (SNO-Alb) has been shown to be an efficacious cytoprotective molecule in acute lung injury, as well as ischemia-reperfusion injury in heart and skeletal muscle. Nonetheless, limited information is available on the cellular mechanism of such protection. Accordingly, we investigated the protective effects of SNO-Alb [ and its denitrosated congener, reduced albumin (SH-Alb) ] on tert-butyl hydroperoxide (tBH)-mediated cytotoxicity in cultured rat pulmonary microvascular endothelial cells (RPMEC), as well as hydrogen sulfide (H2S)-mediated cytotoxicity in rat pulmonary artery smooth muscle cells (RPASMC). We noted that tBH caused a concentration-dependent necrosis in RPMEC, and pretreatment of RPMEC with SNO-Alb dose-dependently decreased the sensitivity of these cells to tBH. A component of SNO-Alb cytoprotection was sensitive to NG-nitro-l-arginine methyl ester and was associated with activation of endothelial nitric oxide synthase (eNOS), phenomena that could be reproduced with pretreatment with SH-Alb. Exogenous H2S caused concentration-dependent apoptosis in RPASMC due to activation of ERK1/2 and p38, as well as downregulation of Bcl-2. Pretreatment with SNO-Alb reduced H2S-mediated apoptosis in a concentration-dependent manner that was associated with SNO-Alb-mediated inhibition of activation of ERK1/2 and p38. Pretreatment with SNO-Alb reduced toxicity of 1 mM sodium hydrosulfide in an NG-nitro-l-arginine methyl ester-sensitive fashion in RPASMC that expressed gp60 and neuronal NOS and was capable of transporting fluorescently labeled SH-Alb. Therefore, SNO-Alb is cytoprotective against models of oxidant-induced necrosis (tBH) and inhibitors of cellular respiration and apoptosis (H2S) in both pulmonary endothelium and smooth muscle, respectively, and a component of such protection can be attributed to a SH-Alb-mediated activation of constitutive NOS. [ABSTRACT FROM AUTHOR]
- Published
- 2011
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359. Translational control gone awry: a new mechanism of tumorigenesis and novel targets of cancer treatments.
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Ji-Ye YIN, DONG, Zizheng, Zhao-Qian LIU, and ZHANG, Jian-Ting
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CARCINOGENESIS ,CELLULAR control mechanisms ,REGULATION of cell growth ,GENETIC regulation ,GENE expression - Abstract
Translational control is one of primary regulation mechanisms of gene expression. Eukaryotic translational control mainly occurs at the initiation step, the speed-limiting step, which involves more than ten translation initiation factors [eIFs (eukaryotic initiation factors)]. Changing the level or function of these eIFs results in abnormal translation of specific mRNAs and consequently abnormal growth of cells that leads to human diseases, including cancer. Accumulating evidence from recent studies showed that the expression of many eIFs was associated with malignant transformation, cancer prognosis, as well as gene expression regulation. In the present paper, we perform a critical review of recent advances in understanding the role and mechanism of eIF action in translational control and cancer as well as the possibility of targeting eIFs for therapeutic development. [ABSTRACT FROM AUTHOR]
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- 2011
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360. Toll-like Receptor 4-Myeloid Differentiation Factor 88 Signaling Contributes to Ventilator-induced Lung Injury in Mice.
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Huihua Li, Xiaoli Su, Xuebin Yan, Wasserloos, Karla, Wei Chao, Kaynar, Murat, Zhao-Qian Liu, Leikauf, George D., Pitt, Bruce R., and Li-Ming Zhang
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- 2010
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361. IGF2BP2 variations influence repaglinide response and risk of type 2 diabetes in Chinese population.
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Qiong HUANG, Ji-ye YIN, Xing-ping DAI, Qi PEI, Min DONG, Zhi-guang ZHOU, Xi HUANG, Min YU, Hong-hao ZHOU, and Zhao-qian LIU
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CARRIER proteins ,TYPE 2 diabetes risk factors ,GENETIC polymorphisms ,HYPOGLYCEMIC agents - Abstract
AbstractAim:To investigate whether the insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) rs1470579 and rs4402960 polymorphisms are associated with the development of type 2 diabetes mellitus (T2DM) and the repaglinide therapeutic efficacy in Chinese T2DM patients.Methods:A case-control study of a total of 350 patients with T2DM and 207 healthy volunteers was conducted to identify their genotypes for the IGF2BP2 rs1470579 and rs4402960 polymorphisms using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Forty-two patients were randomly selected to undergo an 8-week repaglinide treatment (3 mg/d). Fasting plasma glucose (FPG), postprandial plasma glucose (PPG), glycated hemoglobin (HbAlc), fasting serum insulin (FINS), postprandial serum insulin (PINS), homeostasis model assessment for insulin resistance (HOMA-IR), serum triglyceride, total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-c), and high-density lipoprotein-cholesterol (HDL-c) were determined before and after repaglinide treatment.Results:The frequencies of the IGF2BP2 rs1470579 C allele and the rs4402960 T allele were higher in T2DM patients than in healthy controls (P<0.05 and P<0.001, respectively). The effects of the repaglinide treatment on FPG (P<0.05) and PPG (P<0.05) were reduced in patients with the rs1470579 AC+CC genotypes compared with AA genotype carriers. Patients with the rs4402960 GT+TT genotypes exhibited an enhanced effect of repaglinide treatment on PINS (P<0.01) compared with GG genotype subjects.Conclusion:The IGF2BP2 rs1470579 and rs4402960 polymorphisms may be associated with the development of T2DM, and these polymorphisms may affect the therapeutic efficacy of repaglinide in Chinese T2DM patients. [ABSTRACT FROM AUTHOR]
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- 2010
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362. Pretreatment with a Traditional Chinese Formula, Guanxin II, Reduces Cardiac Apoptosis via the Akt Survival Pathway in Rats with Myocardial Ischemia.
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Xi Huang, Xue-Ya Zhang, Feng Qin, Xiao-Yu Wang, Ping Ren, Zhao-Qian Liu, and Hong-Hao Zhou
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Guanxin II (GXII) is a traditional Chinese formula to treat coronary heart disease in China. Previous studies indicate cardioprotection of GXII are related to cardiomyocyte apoptosis. Akt is necessary and sufficient for inhibition of apoptosis in cardiomyocytes. Our aim was to examine whether or not the antiapoptotic mechanisms of GXII are related to the Akt pathway. Male Sprague-Dawley rats were randomly assigned to four groups: GXII administered at 2.5 or 0.5 g raw materials/kg, the vehicle control and sham-operated oral 0.9% NaCl. They were pretreated once a day for 15 consecutive days by gavage. Thirty min after the last administration, the left anterior descending coronary artery was occluded to induce myocardial ischemia except for the sham-operated rats. Compared with rats receiving vehicle, those rats pretreated with GXII at 2.5 g/kg significantly reduced infarct size and decrease apoptosis. Furthermore, GXII (2.5 g/kg) significantly activated Akt kinase, increased the Bcl-2/Bax ratio, inhibited cytochrome c release, reduced caspase-9 activation, and attenuated subsequent caspase-3 activation. GXII at 0.5 g/kg have no noticeable effect on these parameters. Meanwhile, GXII at 2.5 g/kg did not change myocardial blood flow of ischemic zone, indicating a direct action on cardiomyocytes. These results suggest GXII at 2.5 g/kg ensures the survival of myocardium by enhancing the Akt-mediated antiapoptosis pathway. The findings provide new evidence of the effective and safe therapy with GXII for patients with chronic coronary heart disease. [ABSTRACT FROM AUTHOR]
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- 2010
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363. Effects of UCP2 –866 G/A and ADRB3 Trp64Arg on rosiglitazone response in Chinese patients with Type 2 diabetes.
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Min Yang, Qiong Huang, Jing Wu, Ji-Ye Yin, Hong Sun, Hai-Ling Liu, Hong-Hao Zhou, and Zhao-Qian Liu
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ROSIGLITAZONE ,TYPE 2 diabetes ,HUMAN genetic variation ,GENETIC polymorphisms ,PHARMACOLOGY - Abstract
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Rosiglitazone is one of the thiazolidinedione medicines that is widely used in patients with Type 2 diabetes (T2DM); it acts by activation of peroxisome proliferator-activated receptor-γ. • There are no reports on the influence of genetic variations of UCP2 and ADRB3 on rosiglitazone response in Chinese T2DM patients. • The current study was designed to evaluate the relationship between the genetic polymorphisms of UCP2 –866G/A and ADRB3 Trp64Arg with susceptibility to T2DM development and the therapeutic efficacy of multiple-dose rosiglitazone in Chinese patients with T2DM. WHAT THIS STUDY ADDS • The genetic polymorphisms of UCP2 –866G/A and ADRB3 Trp64Arg are associated with the therapeutic efficacy of multiple-dose rosiglitazone in Chinese T2DM patients. AIMS The aim of this study was to explore the impact of UCP2 and ADRB3 genetic polymorphisms on the therapeutic efficacy of rosiglitazone in Chinese Type 2 diabetes (T2DM) patients. METHODS A total of 199 T2DM patients and 155 healthy volunteers were enrolled to identify UCP2 –866 G/A genotypes, and 273 T2DM patients and 166 controls were genotyped for Trp64Arg of ADRB3 by polymerase chain reaction-restriction fragment length polymorphism assay. Nine patients with GG genotype and 27 with GA+ AA genotype of UCP2 –866 G/A, 11 with Trp64Trp genotype and 25 with Trp64Arg genotype of ADRB3 received oral rosiglitazone as a single-agent therapy (4 mg day
−1 ) for 12 weeks. Serum fasting plasma glucose, postprandial plasma glucose, glycated haemoglobin (HbA1c ), fasting serum insulin, postprandial serum insulin (PINS), triglycerol (TG), cholesterol, homeostasis model assessment for insulin resistance, leptin and adiponectin in all T2DM patients were determined before and after rosiglitazone treatment. RESULTS There were no differences in allele frequency of either ADRB3 Trp64Arg or UCP2 –866 G/A between T2DM patients and control subjects. The A allele carriers of UCP2 in the T2DM patients had significantly lower PINS (61.5 ± 34.3 vs. 41.6 ± 28.7 mU l−1 , P < 0.01) (37.57, 59.16 vs. 34.82, 49.39) and low-density lipoprotein (LDL)-cholesterol compared with GG genotypes (3.4 ± 1.1 vs. 2.7 ± 1.1 mmol l−1 , P < 0.05) (2.64, 3.52 vs. 2.66, 3.15). After rosiglitazone treatment for 12 consecutive weeks, we found that A allele carriers of UCP2 in the T2DM patients had smaller attenuated PINS (−3.82 ± 13.2 vs.−42.1 ± 30.7 mU l−1 , P < 0.01) (9.45, 51.31 vs. 0.48, 11.88) and greater attenuated HbA1c (−1.85 ± 1.62 vs.−0.61 ± 0.80, P < 0.05) (0.14, 1.37 vs. 1.10, 2.38) compared with GG genotypes, and ADRB3 Trp64Arg had greater attenuated serum TG (−3.88 ± 2.77 vs.−0.24 ± 1.16 mmol l−1 , P < 0.05) (−0.19, 2.74 vs. 1.19, 1.45) and smaller attenuated LDL-cholesterol (1.08 ± 1.36 vs.−0.36 ± 0.99, P < 0.01) (−1.26, 0.78 vs.−1.26, 0.79) as well as reduced enhanced adiponectin (1.57 ± 1.10 vs. 3.15 ± 2.12 mmol l−1 , P < 0.05) (1.68, 4.08 vs.−9.18, 11.40) compared with ADRB3 Trp64Trp. CONCLUSION UCP2 –866 G/A and ADRB3 Trp64Arg polymorphisms are associated with the therapeutic efficacy of multiple-dose rosiglitazone in Chinese T2DM patients. [ABSTRACT FROM AUTHOR]- Published
- 2009
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364. Effects of allicin on CYP2C19 and CYP3A4 activity in healthy volunteers with different CYP2C19 genotypes.
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Li-Jun Yang, Lan Fan, Zhao-Qian Liu, Yan-Mei Mao, Dong Guo, Li-Hui Liu, Zhi-Rong Tan, Liang Peng, Chun-Ting Han, Dong-Li Hu, Dan Wang, and Hong-Hao Zhou
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OMEPRAZOLE ,PHARMACEUTICAL encapsulation ,PHARMACOKINETICS ,PLACEBOS ,CHROMATOGRAPHIC analysis ,GENETIC polymorphisms - Abstract
To investigate the interaction between allicin and omeprazole and to observe the effects of allicin on CYP2C19 and CYP3A4 activity in healthy Chinese male volunteers with different CYP2C19 genotypes. Eighteen subjects (six CYP2C19*1/ CYP2C19*1, four CYP2C19*1/ CYP2C19*2, two CYP2C19*1/ CYP2C19*3, and six CYP2C19*2/ CYP2C19*2) were enrolled in a two-phase randomized crossover trial. In each phase, all subjects received placebo or a 180 mg allicin capsule once daily for 14 consecutive days. The pharmacokinetics of omeprazole (20 mg orally on day 15) was determined for up to 12 h following administration by high-performance liquid chromatography. In carriers of the CYP2C19*1/ CYP2C19*1 and CYP2C19*1/ CYP2C19*2 or *3 genotype, allicin treatment increased the peak plasma concentration (C
max ) of omeprazole by 49.7 ± 7.2 ( p < 0.001) and 54.2 ± 9.2% ( p < 0.001), and increased the area under the plasma time–concentration curve ( $${\text{AUC}}_{\left( {0 - \infty } \right)} $$ ) of omeprazole by 48.1 ± 9.0 ( p = 0.001) and 73.6 ± 26.7% ( p < 0.001), respectively. The ratio of $${\text{AUC}}_{\left( {0 - \infty } \right)} $$ of 5-hydroxyomeprazole to omeprazole (a marker for CYP2C19 activity) decreased significantly ( p < 0.001 and p = 0.001, respectively). However, no pharmacokinetic parameters were significantly changed by allicin in CYP2C19*2/ CYP2C19*2. The Cmax and $${\text{AUC}}_{\left( {0 - \infty } \right)} $$ of omeprazole sulfone were unchanged in all three genotypes. Allicin reduced the metabolism of omeprazole by inhibiting CYP2C19 activity in individuals with the CYP2C19*1/ CYP2C19*1 and CYP2C19*1/ CYP2C19*2 or *3 genotypes, but not in those with the CYP2C19*2/ CYP2C19*2 genotype. Allicin did not significantly affect the activity of CYP3A4 in all subjects. [ABSTRACT FROM AUTHOR]- Published
- 2009
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365. Impact of genetic polymorphisms of leptin and TNF-α on rosiglitazone response in Chinese patients with type 2 diabetes.
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Hai-Ling Liu, Yang-Gen Lin, Jing Wu, Hong Sun, Zhi-Cheng Gong, Ping-Cheng Hu, Ji-Ye Yin, Wei Zhang, Dan Wang, Hong-Hao Zhou, and Zhao-Qian Liu
- Subjects
HORMONES ,GENETIC polymorphisms ,BLOOD plasma ,LEPTIN ,TYPE 2 diabetes - Abstract
Leptin and tumor necrosis factor-α (TNF-α) play important role in homeostasis and insulin resistance in the treatment of Type 2 diabetes (T2DM). The aims of the present study were to investigate the association between leptin G-2548A and TNF-α G-308A polymorphisms and rosiglitazone response in T2DM patients. 245 patients with T2D and 122 health volunteers were enrolled to identify leptin G-2548A and TNF-α G-308A genotypes by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Forty-two T2D patients with different leptin G-2548A and TNF-α G-308A genotypes received orally rosiglitazone as a single-agent therapy (4 mg day
−1 p.o.) for 12 weeks. Serum triglyceride (TG), fasting plasma glucose (FPG), postprandial plasma glucose (PPG), fasting serum insulin (FINs), glycated hemoglobin (HbAlc), postprandial serum insulin (PINS), homeostasis model assessment for insulin resistance (HOMA-IR), low-density lipoprotein-cholesterol (LDL-c), and high-density lipoprotein-cholesterol (HDL-c) were determined before and after rosiglitazone treatment. A significant association between the variation of G-2548A allele with body mass index (BMI), serum leptin levels and FPG was observed in T2DM patients. Moreover, patients with G allele of leptin G-2548A had lower BMI and serum leptin concertration as well as bigger FPG than that in AA genotypes (P < 0.05). Moreover, we found an enhanced rosiglitazone effect in patients with AA genotype of leptin G-2548A on FINS and PINS compared with GG+GA genotype (P < 0.05). Finally, our results showed an attenuated rosiglitazone effect in patients with GA+AA genotype of TNF-α G-308A on FINS compared with GG genotype (P < 0.05). These data suggest there were not significantly differences in the frequencies of leptin G-2548A and TNF-α G-308A between patients with T2DM and health control. TNF-α G-308A polymorphism might be associated with the therapeutic efficacy of rosiglitazone in T2DM patients. [ABSTRACT FROM AUTHOR]- Published
- 2008
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366. The association of adiponectin allele 45T/G and − 11377C/G polymorphisms with Type 2 diabetes and rosiglitazone response in Chinese patients.
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Hong Sun, Zhi-Cheng Gong, Ji-Ye Yin, Hai-Ling Liu, Ying-Zi Liu, Zhi-Wei Guo, Hong-Hao Zhou, Jing Wu, and Zhao-Qian Liu
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TYPE 2 diabetes ,BLOOD sugar ,PEOPLE with diabetes ,HOMEOSTASIS ,SERUM - Abstract
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Rosiglitazone is able to increase serum adiponectin levels significantly in Type 2 diabetic patients. • The role of genetic factors that determine the marked interindividual variability in glucose-lowering efficacy of rosiglitazone in Chinese patients is not known. • The current study was designed to evaluate the impact of the adiponectin common allele 45T/G and − 11377C/G polymorphisms on the response to rosiglitazone monotherapy in Chinese patients with Type 2 diabetes (T2D). WHAT THIS STUDY ADDS • The genetic polymorphisms of adiponectin alleles 45T/G and − 11377C/G as well as their common diplotypes are significantly associated with an attenuated fasting plasma glucose, postprandial plasma glucose and homeostasis model assessment for insulin resistance as well as an enhanced adiponectin concentration in Chinese patients with T2D after rosiglitazone treatment. AIMS The aim of the present study was to evaluate the impact of adiponectin allele T45G and C-11377G genetic polymorphisms on efficacy of rosiglitazone in Chinese patients with type 2 diabetes (T2D). METHODS Patients with T2D (n = 255) and 120 healthy volunteers were enrolled to identify 45T/G and –11377C/G genotypes by polymerase chain reaction-restriction fragment length polymorphism assay. Forty-two T2D patients with different 45T/G or –11377C/G genotypes received orally rosiglitazone as a single-dose therapy (4 mg day-1 p.o.) for 12 weeks. Serum triglyceride, fasting plasma glucose (FPG), postprandial plasma glucose (PPG), glycated hemoglobin, fasting serum insulin, postprandial serum insulin, total cholesterol, homeostasis model assessment for insulin resistance (HOMA-IR), low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol (HDL-c) and adiponectin concentration were determined before and after rosiglitazone treatment. RESULTS We showed an attenuated rosiglitazone effect in patients with –11377CG+GG heterozygote genotype on FPG, PPG, HOMA-IR compared with –11377CC homozygote genotype. However, we found an enhanced rosiglitazone effect on serum adiponectin concentration in patients with –11377CC homozygote genotype compared with –11377CG+GG heterozygote genotype ( P = 0.000) and in patients with 45TG + GG heterozygote genotype compared with 45TT homozygote genotype ( P = 0.018). Finally, our results showed that there was an enhanced effect in patients with –11377/45 CGTT diplotype compared with other discovered diplotypes on FPG ( P = 0.001) and PPG ( P = 0.003) after rosiglitazone treatment. CONCLUSIONS These data suggest that the adiponectin allele 45T/G and – 11377C/G polymorphisms are significantly associated with the therapeutic efficacy of multiple-dose rosiglitazone in Chinese patients with T2D. [ABSTRACT FROM AUTHOR]
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- 2008
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367. OATP1B1 POLYMORPHISM IS A MAJOR DETERMINANT OF SERUM BILIRUBIN LEVEL BUT NOT ASSOCIATED WITH RIFAMPICIN-MEDIATED BILIRUBIN ELEVATION.
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Wei Zhang, Yi-Jing He, Zhou Gan, Lan Fan, Qing Li, An Wang, Zhao-Qian Liu, Sheng Deng, Yuan-Fei Huang, Lin-Yong Xu, and Hong-Hao Zhou
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BILIRUBIN ,SERUM ,LIVER diseases ,LIVER cells ,CHROMOSOME polymorphism - Abstract
1. Elevated serum bilirubin levels are caused mainly by liver diseases, haematolysis, genetic defects and drug intake. Unconjugated bilirubin (UCB) is taken up into hepatocytes by human organic anion transporting polypeptide 1B1 (OATP1B1; encoded for by the SLCO1B1 gene). The present study was performed to determine the association between SLCO1B1 gene polymorphisms and serum bilirubin levels in vivo. Moreover, the effects of administration of low-dose rifampicin on serum bilirubin levels in different SLCO1B1 genotypes was examined. 2. Serum bilirubin levels were examined in 42 healthy volunteers who had been analysed for SLCO1B1 genotype (seven, 13, 14 and eight with SLCO1B1 genotypes * 1a/* 1a, * 1b/* 1b, * 1b/* 15 and * 15/* 15, respectively). Among them, 24 subjects (seven, seven, eight and two with SLCO1B1 genotypes * 1a/* 1a, * 1b/* 1b, * 1b/* 15 and * 15/* 15, respectively) were selected to participate in an open-label, two-phase clinical trial. Each was given 450 mg rifampicin orally once daily at 2000 hours for 5 consecutive days. Serum bilirubin concentrations at 0800 hours on the 1st and 6th days were compared between the different SLCO1B1 genotypes. 3. In the 42 volunteers, the mean (±SD) serum UCB in both SLCO1B1* 1b/* 15 and * 15/* 15 groups was significantly higher than that in the SLCO1B1* 1b/* 1b group (11.07 ± 2.31, 13.01 ± 3.87 and 8.21 ± 2.68 µmol/L, respectively; P = 0.009 and P < 0.001). Total bilirum (T.BIL) in both the SLCO1B1* 1b/* 15 and * 15/* 15 groups was significantly higher than that in the SLCO1B1* 1b/* 1b group (16.69 ± 4.09, 20.71 ± 5.12 and 13.06 ± 5.12 µmol/L, respectively; P = 0.029 and P < 0.001). The direct bilirubin (D.BIL) in the SLCO1B1* 15/* 15 group was significantly higher than that in the SLCO1B1* 1b/* 1b group (7.69 ± 1.81 vs 4.85 ± 1.81 µmol/L, respectively; P = 0.001). Rifampicin significantly increased UCB, T.BIL and D.BIL concentrations in 24 healthy volunteers (17.68 ± 5.96 vs 13.95 ± 4.44 µmol/L ( P = 0.040), 5.72 ± 2.01 vs 4.35 ± 1.50 µmol/L ( P = 0.028) and 12.00 ± 4.26 vs 9.61 ± 3.15 µmol/L ( P = 0.035), respectively). However, the extent of the increase in serum bilirubin caused by 450 mg rifampicin for 5 days was not affected by SLCO1B1 genotype. 4. Genetic polymorphism in SLCO1B1 is a major determinant of interindividual variability in the serum bilirubin level. SLCO1B1* 15 carriers had higher baseline serum UCB, T.BIL and D.BIL levels compared with subjects with the SLCO1B1* 1a/* 1a and SLCO1B1* 1b/* 1b genotypes. SLCO1B1* 15/* 15 homozygotes are more susceptible to hyperbilirubinaemia. Serum bilirubin levels could be increased by low-dose rifampicin administration, but the extent of the increase was not associated with SLCO1B1 genotype. [ABSTRACT FROM AUTHOR]
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- 2007
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368. Impact of rosiglitazone on the expression of β3-AR in the stable cell lines expressed β3-AR gene.
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Xin Zhao, Min-Yu Hu, Qiong Huang, Zhong-Yang Tang, Xing-Ping Dai, Ji-Ye Yin, Feng Zhang, Hong-Hao Zhou, and Zhao-Qian Liu
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HYPOGLYCEMIC agents ,PEROXISOMES ,GENE expression ,NUCLEOTIDE sequence ,GENE transfection ,REVERSE transcriptase - Abstract
Background: The aim of the present study was to investigate the effect of rosiglitazone, a peroxisome proliferator-activated receptor γ2 (PPAR-γ2) agonist, on the expression of β
3 -adrenergic receptor (β3 -AR) at transcriptional and translational level. Methods: We cloned the cDNA sequences of human PPAR-γ2 (hPPAR-γ2) gene and human wild type and mutant β3 -adrenergic receptor ( hβ3 -AR) genes and established their eukaryotic expression vectors. The pcDNA3.1/hβ3 -AR (mutant and wild type) was transfected into SH-SY5Y cells using electroporation method. The expression level of β3 -AR protein was determined by Western blot analysis. Results: Our results showed that the reverse transcription-PCR products were consistent with theoretical fragment sizes of human PPAR-γ2 (1544 bp) and human β3 - AR genes (1578 bp). The sequence analysis of PPAR-γ2 and β3 -AR genes showed that the fragment sizes were the same as that of human PPAR-γ2 and human β3 - AR genes in Genebank. The pcDNA3.1/hβ3 -AR (mutant and wild type) was successfully cloned to SH-SY5Y cells. We found that the expression of β3 -AR protein was significantly inhibited by rosiglitazone in a concentration-dependent manner in SH-SY5Y cell lines stably expressed β3 - AR genes. Conclusions: The results suggest that rosiglitazone has a concentration-dependent inhibitory effect on the expression of β3 -AR protein, and this inhibitory effect may be due to activation of PPAR-γ2 receptor. Clin Chem Lab Med 2007;45:1511–6. [ABSTRACT FROM AUTHOR]- Published
- 2007
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369. The genetic polymorphisms of β3-adrenergic receptor (AR) Trp64Arg and β2-AR Gln27Glu are associated with obesity in Chinese male hypertensive patients.
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Wei Mo, Guang-Gan Zhang, Tian-Lun Yang, Xing-Ping Dai, Hui-Hua Li, Hui Zeng, Jie Liu, Yuan-Ming Tan, Hong-Hao Zhou, and Zhao-Qian Liu
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GENETIC polymorphisms ,BETA adrenoceptors ,ADRENERGIC receptors ,OBESITY ,HYPERTENSION ,CHINESE people ,POLYMERASE chain reaction ,CLINICAL chemistry - Abstract
Background: Genetic polymorphisms of β3-adrenergic receptor (AR) Trp64Arg and β2-AR Gln27Glu may result in significant change in the functions of these receptors. The aims of the present study were to investigate the association between Trp64Arg, Arg16Gly and Gln27Glu polymorphisms and the susceptibility to obesity and hypertension in a Chinese population. Methods: A total of 437 Chinese subjects including 149 obese hypertensive patients, 139 non-obese essential hypertensive patients, and 149 non-obese normotensive healthy controls were enrolled in the study. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and allele-specific (AS)-PCR assays were used to identify Trp64Arg, Arg16Gly, and Gln27Glu genotypes. Results: The allele frequencies of 64Arg and 27Glu in the obese hypertensive group were 0.178 and 0.128, respectively. Both were significantly higher than in the non-obese hypertensive and the control groups (p<0.05). Further analysis showed that this association existed only in male hypertensive patients. Conclusions: These data reveal that frequencies of β3-AR 64Arg and β2-AR 27Glu were significantly higher in our obese hypertensive patients than in the non-obese hypertensive population and healthy controls. β3-AR Trp64Arg and β2-AR Gln27Glu genetic polymorphisms are associated with obesity in Chinese male hypertensive patients. Clin Chem Lab Med 2007;45:493–8. [ABSTRACT FROM AUTHOR]
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- 2007
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370. β1-Adrenergic receptor polymorphisms influence the response to metoprolol monotherapy in patients with essential hypertension*.
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Jie Liu, Zhao-Qian Liu, Bang-Ning Yu, Fang-Hua Xu, Wei Mo, Gan Zhou, Ying-Zi Liu, Qing Li, and Hong-Hao Zhou
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GENETIC polymorphisms ,CARDIOVASCULAR diseases ,HYPERTENSION ,THERAPEUTICS ,PHYSIOLOGICAL effects of chemicals ,PHARMACOLOGY - Abstract
Objectives: The human β
1 -adrenergic receptor, an important therapeutic target in cardiovascular diseases, has 2 common functional polymorphisms (Ser49Gly and Gly389Arg). Our study aimed to confirm that β1 -adrenergic receptor polymorphisms affect the blood pressure response to metoprolol monotherapy in the Chinese population with hypertension.Methods: β1 -Adrenergic receptor genotype was determined by polymerase chain reaction–restriction fragment length polymorphism assay for 223 patients with essential hypertension. Sixty-one patients with certain β1 -adrenergic receptor diplotypes, 18 for 49Ser389Arg/49Ser389Arg, 15 for 49Ser389Arg/49Gly389Arg, 19 for 49Ser389Gly/49Gly389Arg, and 9 for 49Ser389Gly/49Ser389Gly, were selected from those 61 for measurement of the antihypertensive effect of metoprolol. Patients were given 25 mg metoprolol every 12 hours for 4 weeks. Heart rate and blood pressure were measured weekly for the duration of metoprolol therapy.Results: The descent of systolic blood pressure after metoprolol administration was significantly different among genotype groups (10.4% ± 4.0%, 2.8% ± 4.7%, and 1.1% ± 1.5% for Arg389Arg, Gly389Arg, and Gly389Gly patients, respectively; P < .001). We also found a similar difference in changes of diastolic blood pressure (6.1% ± 4.3%, 2.2% ± 4.2%, and 0.9% ± 4.0%, respectively; P < .001) and mean arterial pressure (8.1% ± 3.5%, 2.5% ± 3.0%, and 1.0% ± 2.5%, respectively; P > .001) for Arg389Arg, Gly389Arg, and Gly389Gly patients. Ser49Gly variance exhibited a smaller contribution to the antihypertensive effect of metoprolol. Systolic blood pressure decreased significantly in Ser49 homozygous patients compared with Ser49Gly patients (8.4% ± 3.2% versus 5.3% ± 5.2%, P = .047). There was a highly significant relationship between diplotype and blood pressure during treatment. Systolic blood pressure significantly decreased in 49Ser389Arg/49Ser389Arg (12.0% ± 3.8%, P < .001) and 49Ser389Arg/49Gly389Arg (8.4% ± 5.5%, P < .001) patients, with the decrease in the former being more pronounced (P = .023). We also found a significant decrease in diastolic blood pressure (6.5% ± 4.7% versus 5.7% ± 3.2%, respectively; both P < .001) and mean arterial pressure (8.8% ± 3.2% versus 6.9% ± 3.7%, respectively; both P < .001) in 49Ser389Arg/49Ser389Arg and 49Ser389Arg/49Gly389Arg patients. However, blood pressure did not change significantly in 49Ser389Gly/49Gly389Arg and 49Ser389Gly/49Ser389Gly patients (all P > .05).Conclusions: β1 -Adrenergic receptor polymorphism was associated with different blood pressure responses to metoprolol therapy in patients with essential hypertension. 49Ser389Arg/49Ser389Arg and 49Ser389Arg/49Gly389Arg patients were good responders to metoprolol therapy; 49Ser389Arg/49Ser389Arg patients had a larger systolic blood pressure reduction than 49Ser389Arg/49Gly389Arg patients did. 49Ser389Gly/49Gly389Arg and 49Ser389Gly/49Ser389Gly patients were nonresponders to metoprolol antihypertensive therapy.Clinical Pharmacology & Therapeutics (2006) 80, 23–32; doi:10.1016/j.clpt.2006.03.004 [ABSTRACT FROM AUTHOR]- Published
- 2006
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371. Distributive characteristics of Ser49Gly and Gly389Arg genetic polymorphisms of β1-adrenoceptor in Chinese Han and Dai populations.
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Zhao-qian Liu, Jie Liu, Zhi-hua Xiang, Min-yu Hu, Wei Mo, Lian-sheng Wang, Dong-sheng Ou-Yang, Nan He, Dan Wang, and Hong-hao Zhou
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GENETIC polymorphisms ,ADRENERGIC receptors ,ETHNIC groups ,DNA ,LEUCOCYTES ,POLYMERASE chain reaction - Abstract
Aim: Genetic polymorphisms causing Ser49Gly and Gly389Arg mutants of β
1 - adrenoceptor may result in significant changes in the function of this receptor. The aim of the present study was to investigate the frequencies of the Ser49Gly and Gly389Arg mutant alleles in healthy Chinese populations and to investigate the differences between 2 Chinese ethnic groups (Han and Dai populations) with respect to the frequencies of these alleles. Methods: A total of 225 Han Chinese and 175 Dai Chinese unrelated healthy volunteers were recruited for this study. Genomic DNA was extracted from peripheral blood leukocytes by using a standard manual chloroform-phenol extraction. Fragments spanning the 2 polymorphisms were amplified by using polymerase chain reaction with template genomic DNA and relevant primers. The DNA products including the polymorphic loci were subjected to restriction endonuclease digestion with Eco0109I and BcgI. Digested fragments were detected with an ultraviolet detector after electrophoresis (100 V for approximately 1.5 h). Results: The frequencies of the Gly49 and Arg389 alleles were, respectively, 16.2% and 76.4% in the Han population and 14.6% and 75.7% in the Dai population. Conclusion: The polymorphisms causing the Ser49Gly and Gly389Arg mutations of the β1 -adrenoceptor existed in both healthy Han and Dai Chinese populations. The frequencies of the Ser49Gly and Gly389Arg mutant alleles were not significantly different in the Han and Dai populations. However, the frequency of the Gly389 variant seems to be significantly lower in these 2 populations than in an African-American population. [ABSTRACT FROM AUTHOR]- Published
- 2006
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372. CYP2C19 genotype and S-mephenytoin 4′-hydroxylation phenotype in a Chinese Dai population.
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Nan He, Feng-Xiang Yan, Song-Lin Huang, Wei Wang, Zhou-Sheng Xiao, Zhao-Qian Liu, and Hong-Hao Zhou
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CYTOCHROMES ,GENETIC polymorphisms ,HYDROXYLATION ,PHENOTYPES ,GENOTYPE-environment interaction ,CHEMICAL reactions ,POPULATION genetics ,CHINESE people - Abstract
Aims: To investigate the incidence of the CYP2C19 polymorphism in the Chinese Dai population. Methods: One hundred and ninety-three healthy Chinese Dai volunteers were identified with respect to CYP2C19 by genotype and phenotype analyses. A polymerase chain reaction–restriction fragment length polymorphism method was performed for genotyping procedures. The 4′-hydroxymephenytoin (4′-OH-MP) and S/R-mephenytoin (S/R-MP) excreted in the urine were determined by high-performance liquid chromatography and gas chromatography, respectively. Results: Eighteen subjects were identified as poor metabolisers (PMs). The frequency of PMs in the Chinese Dai subjects was 9.3% (95% confidence interval 5.2, 13.4), which is lower than that in the Chinese Han population (P<0.05). Chinese Dai subjects had a higher frequency of the mutant CYP2C19*2 allele (0.303) and a lower frequency of the mutant CYP2C19*3 allele (0.034). These two mutant alleles could explain all deficiencies of CYP2C19 activity in the Chinese Dai subjects. The frequency of the CYP2C19*3 allele is significantly lower than that in the Chinese Han population (P<0.05). The mean S/R ratio was lower in the homozygous extensive metabolisers (EMs) compared with that in heterozygous EMs (P<0.01), and the latter was lower than that in the PMs (P<0.01). Furthermore, the mean S/R ratio in CYP2C19*3/CYP2C19*2 heterozygous PMs was possibly lower than that in the CYP2C19*2/CYP2C19*2 homozygous PMs (P<0.05). Conclusion: The frequencies of PMs and CYP2C19*3 allele in the Chinese Dai population are significantly lower than those in the Han population. The CYP2C19 genotype analysis is largely consistent with the mephenytoin phenotype analysis. The variability of S/R ratios in EMs and PMs shows a gene–dosage effect. [ABSTRACT FROM AUTHOR]
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- 2002
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373. Pharmacokinetics of citalopram in relation to genetic polymorphism of CYP2C19.
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Bang-Ning, Yu, Guo-Lin, Chen, Nan, He, Dong-Sheng, Ouyang, Xiao-Ping, Chen, Zhao-Qian, Liu, and Hong-Hao, Zhou
- Abstract
The study was designed to define the contribution of cytochrome p450 2C19 (CYP2C19) and cytochrome p450 3A4 (CYP3A4) to citalopram N-demethylation and to evaluate the relationship between the disposition of citalopram and CYP2C19 genotype. A single oral 40-mg dose of citalopram was administered to eight extensive metabolizers and five poor metabolizers recruited from 77 healthy Chinese volunteers whose genotypes and phenotypes were predetermined. The plasma concentrations of citalopram and desmethylcitalopram were determined by high-performance liquid chromatography. It was found that the genotype of CYP2C19 had a significant effect on the N-demethylation of citalopram. Poor metabolizers with m1 mutation had higher area under the plasma concentration versus time curve (AUC0--> infinity ) values than did extensive metabolizers. Terminal elimination half-life (t1/2) values of citalopram in poor metabolizers were significantly higher than the values in extensive metabolizers who were either homozygous or heterozygous with CYP2C19*1. The oral clearance (CLoral) of citalopram in poor metabolizers was significantly lower than that of extensive metabolizers. The AUC0--> infinity and maximum plasma concentration (Cmax) of desmethylcitalopram in poor metabolizers were significantly lower than the values of extensive metabolizers. The results show that CYP3A4 is not the major enzyme in the N-demethylation of citalopram among extensive metabolizers. The polymorphism of CYP2C19 plays an important role in the N- demethylation of citalopram in vivo. The extensive metabolizers and poor metabolizers of CYP2C19 had significant difference in disposition of citalopram in vivo.
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- 2003
374. Some studies on the resolving power of agarose-based high-performance liquid chromatographic media for the separation of macromolecules
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Stellan Hjertén, Zhao-Qian Liu, and Duan Yang
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Chromatography ,Resolution (mass spectrometry) ,Chemistry ,Organic Chemistry ,Analytical chemistry ,General Medicine ,Fractionation ,Biochemistry ,High-performance liquid chromatography ,Analytical Chemistry ,chemistry.chemical_compound ,Volume (thermodynamics) ,Compressibility ,Agarose ,SPHERES ,Macromolecule - Abstract
Columns packed with small cross-linked agarose beads (a mixture of gel spheres with diameters in the range 3–10 μm) for the fractionation of biopolymers are characterized by high plate numbers and large ratios (up to 2.8) between inner volume ( V i ) and void volume ( V o ) and therefore compete favourably with other high-performance liquid chromatographic (HPLC) packings in resolving power. Interestingly, some compressibility of the packing material decreases the void volume considerably, which means an enhancement in both the plate number and the V i / V o ratio, and, therefore, also in resolution.
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- 1984
375. Polyacrylamide gel electrophoresis: Recovery of non-stained and stained proteins from gel slices
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Zhao-Qian Liu, Stellan Hjertén, and Su-lian Zhao
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Free-flow electrophoresis ,Gel electrophoresis ,Two-dimensional gel electrophoresis ,Chromatography ,Staining and Labeling ,Gel electrophoresis of nucleic acids ,Chemistry ,Isoelectric focusing ,Difference gel electrophoresis ,Cell Membrane ,Electric Conductivity ,Biophysics ,Proteins ,Hydrogen-Ion Concentration ,Gel electrophoresis of proteins ,Biochemistry ,Isoelectric point ,Rosaniline Dyes ,Electrophoresis, Polyacrylamide Gel ,Acholeplasma laidlawii ,Isoelectric Focusing - Abstract
Following electrophoresis or isoelectric focusing in gels of polyacrylamide the protein band of interest is cut out and placed above a sucrose gradient column, containing carrier ampholytes (Pharmalyte). By electrophoresis, isoelectric focusing or displacement electrophoresis the proteins migrate out of the gel slice and into the isoelectric focusing column for concentration and further purification. From this column, the proteins can be withdrawn and their isoelectric points determined. Even after staining with Coomassie Brilliant Blue at least some proteins can be recovered by this technique and used for further analyses, for instance amino acid determinations. The focusing in a pH gradient by carrier ampholytes can be placed by an electrophoresis in a conductivity gradient column. However, in comparison with isoelectric focusing, this concentration technique has the drawback of not permitting further purification of the eluted protein.
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- 1983
376. O-Dealkylation of fluoxetine in relation to CYP2C19 gene dose and involvement of CYP3A4 in human liver microsomes.
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Zhao-Qian, Liu, Bing, Zhu, Yun-Fu, Tan, Zhi-Rong, Tan, Lian-Sheng, Wang, Song-Lin, Huang, Yan, Shu, and Hong-Hao, Zhou
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This work evaluated the kinetic behavior of fluoxetine O-dealkylation in human liver microsomes from different CYP2C19 genotypes and identified the isoenzymes of cytochrome P450 involved in this metabolic pathway. The kinetics of the rho-trifluoromethylphenol (TFMP) formation from fluoxetine was determined in human liver microsomes from three homozygous (wt/wt) and three heterozygous (wt/m1) extensive metabolizers (EMs) and three poor metabolizers (PMs) with m1 mutation (m1/m1) with respect to CYP2C19. The formation rate of TFMP was determined by gas chromatograph with electron-capture detection. The kinetics of TFMP formation was best described by the two-enzyme and single-enzyme Michaelis-Menten equation for liver microsomes from CYP2C19 EMs and PMs, respectively. The mean intrinsic clearance (V(max)/K(m)) for the high- and low-affinity component was 25.2 microl/min/nmol and 3.8 microl/min/nmol of cytochrome P450 in the homozygous EMs microsomes and 12.8 microl/min/nmol and 2.9 microl/min/nmol of cytochrome P450 in the heterozygous EMs microsomes, respectively. Omeprazole (a CYP2C19 substrate) at a high concentration and triacetyloleandomycin (a selective inhibitor of CYP3A4) substantially inhibited O-dealkylation of fluoxetine. Furthermore, fluoxetine O-dealkylation was correlated significantly with S-mephenytoin 4'-hydroxylation at a low substrate concentration and midazolam 1'-hydroxylation at a high substrate concentration in liver microsomes of 11 Chinese individuals, respectively. Moreover, there were obvious differences in the O-dealkylation of fluoxetine in liver microsomes from different CYP2C19 genotypes and in microsomal fractions of different human-expressed lymphoblast P450s. The results demonstrated that polymorphic CYP2C19 and CYP3A4 enzymes were the major cytochrome P450 isoforms responsible for fluoxetine O-dealkylation, whereas CYP2C19 catalyzed the high-affinity O-dealkylation of fluoxetine, and its contribution to this metabolic reaction was gene dose-dependent.
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- 2002
377. Assessment of Human Tribbles Homolog 3 Genetic Variation (rs2295490) Effects on Type 2 Diabetes Patients with Glucose Control and Blood Pressure Lowering Treatment
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Guojing Liu, Hong-Hao Zhou, Wei Zhang, Jie Tang, Zhenmin Wang, Zhao-Qian Liu, Fa-Zhong He, Zhangren Chen, Rong Liu, Xiao-Ping Chen, Xin Liu, Mou-Ze Liu, Xingyu Wang, and Jian-Quan Luo
- Subjects
0301 basic medicine ,medicine.medical_specialty ,lcsh:Medicine ,Type 2 diabetes ,General Biochemistry, Genetics and Molecular Biology ,Diabetic Eye Disease ,Individualized drug therapy ,03 medical and health sciences ,Internal medicine ,Genotype ,Medicine ,Allele ,Stroke ,lcsh:R5-920 ,business.industry ,Hazard ratio ,lcsh:R ,TRIB3 ,General Medicine ,medicine.disease ,030104 developmental biology ,Endocrinology ,Pharmacogenetics ,Hypertension ,business ,lcsh:Medicine (General) - Abstract
Effects of human tribbles homolog 3 (TRIB3) genetic variation (c.251 A > G, Gln84Arg, rs2295490) on the clinical outcomes of vascular events has not been evaluated in patients with type 2 diabetes after blood pressure lowering and glucose controlling treatment. We did an analysis of a 2 × 2 factorial (glucose control axis and blood pressure lowering axis) randomized controlled clinical trial at 61 centers in China, with a follow-up period of 5 years. The major vascular endpoints were the composites of death from cardio-cerebral vascular diseases, non-fatal stroke and myocardial infraction, new or worsening renal and diabetic eye disease. A total of 1884 participants were included in our research with a 4.8 years median follow-up. For glucose lowering axis, patients with TRIB3 (rs2295490) AA (n = 609) genotype exhibited significantly reduced risk of major vascular events compared with AG + GG (n = 335) genotype carriers (Hazard ratio 0.72, 95% CI 0.55–0.94, p = 0.016), Paradoxically, the risk of vascular events were significantly increased in patients with AA (n = 621) compared to AG + GG (n = 319) genotype for intensive glucose control (Hazard ratio 1.46, 95% CI, 1.06–2.17, 35 p = 0.018). For blood pressure lowering axis, marginally significant difference was found between TRIB3 variant and coronary events. Our findings suggest that good glucose and blood pressure control exhibited greater benefits on vascular outcomes in patients with TRIB3 (rs2295490) G allele.
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378. RECOVERY OF PROTEINS FROM GEL SLABS BY A COMBINATION OF DISPLACEMENT ELECTROPHORESIS AND ISOELECTRIC FOCUSING
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Su-lian Zhao, Stellan Hjerten, and Zhao-Qian Liu
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Electrophoresis ,Chromatography ,Materials science ,Isoelectric focusing ,Displacement (orthopedic surgery) - Published
- 1983
379. Genetic Polymorphism of rs13306146 Affects α2AAR Expression and Associated With Postpartum Depressive Symptoms in Chinese Women Who Received Cesarean Section
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Kai Ming Duan, Chao Fang, Si Qi Yang, Shu Ting Yang, Ji Dong Xiao, Huang Chang, Guo Xin Lin, Liang Bin Zhang, Ming Chao Peng, Zhao Qian Liu, and Sai Ying Wang
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α2-adrenoceptors ,postpartum depression ,single nucleotide polymorphism ,miRNA ,expression ,Genetics ,QH426-470 - Abstract
Postpartum depressive symptom (PDS) is a common psychological and mental disorder after giving birth. Our previous studies showing the application of dexmedetomidine, an α2-AR agonist, can significantly improve maternal sleep, as well as relieve and reduce the incidence of PDS. This study investigated the association between α2AAR gene polymorphisms and PDS. A total of 568 cesarean section patients were enrolled; the incidence of PDS is 18.13% (103 with PDS, 465 with non-PDS). The Edinburgh Postpartum Depression Scale score ≥10 was used to diagnose PDS at 42 days after delivery. The single-nucleotide polymorphisms of α2AR were sequenced by pyrosequencing. The effect of rs13306146 A > G polymorphism on α2AR transcription and the regulation of miR-646 on α2AR expression were assessed by dual luciferase reporter assays or gene transfection. Increased stress during pregnancy, poor relationship between mother-in-law and daughter-in-law, spousal relationship, domestic violence, antenatal depression, self-harm ideation, and stressful life events were all associated with increased PDS incidence (p < 0.05). The logistic regression analysis found that the α2AAR rs13306146 polymorphism was associated with PDS after adjusting confounding variables. The transcriptional function of the α2AAR rs13306146 A allele was decreased compared with the G allele, and the α2AAR expression level was correspondingly decreased (p < 0.05), as the strongest binding ability of miR-646 to the α2AAR rs13306146 AA genotype. The effect of α2AAR rs13306146 A > G polymorphism may change the binding ability of miR-646 at the 3′UTR of the α2AAR gene, affecting the expression of α2AAR. This study supports the involvement of the norepinephrine system in the pathogenesis of PDS. Genotypes of α2AAR may be novel and useful biomarkers for PDS.
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- 2021
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380. Genome-wide DNA methylation profiling reveals novel epigenetic signatures in squamous cell lung cancer.
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Yuan-Xiang Shi, Ying Wang, Xi Li, Wei Zhang, Hong-Hao Zhou, Ji-Ye Yin, and Zhao-Qian Liu
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DNA methylation , *CANCER invasiveness , *EPIGENETICS , *SQUAMOUS cell carcinoma , *NEOPLASTIC cell transformation , *CANCER risk factors - Abstract
Background: Epigenetic alterations are strongly associated with the development of cancer. The aim of this study was to identify epigenetic pattern in squamous cell lung cancer (LUSC) on a genome-wide scale. Results: Here we performed DNA methylation profiling on 24 LUSC and paired non-tumor lung (NTL) tissues by Illumina Human Methylation 450 K BeadArrays, and identified 5214 differentially methylated probes. By integrating DNA methylation and mRNA expression data, 449 aberrantly methylated genes accompanied with altered expression were identified. Ingenuity Pathway analysis highlighted these genes which were closely related to the carcinogenesis of LUSC, such as ERK family, NFKB signaling pathway, Hedgehog signaling pathway, providing new clues for understanding the molecular mechanisms of LUSC pathogenesis. To verify the results of high-throughput screening, we used 56 paired independent tissues for clinical validation by pyrosequencing. Subsequently, another 343 tumor tissues from the Cancer Genome Atlas (TCGA) database were utilized for further validation. Then, we identified a panel of DNA methylation biomarkers (CLDN1, TP63, TBX5, TCF21, ADHFE1 and HNF1B) in LUSC. Furthermore, we performed receiver operating characteristics (ROC) analysis to assess the performance of biomarkers individually, suggesting that they could be suitable as potential diagnostic biomarkers for LUSC. Moreover, hierarchical clustering analysis of the DNA methylation data identified two tumor subgroups, one of which showed increased DNA methylation. Conclusions: Collectively, these results suggest that DNA methylation plays critical roles in lung tumorigenesis and may potentially be proposed as a diagnostic biomarker. Trial registration: ChiCTR-RCC-12002830 Date of registration: 2012--12-17. [ABSTRACT FROM AUTHOR]
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- 2017
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381. Association of ABCB1 Polymorphisms With the Efficacy of Ondansetron in Chemotherapy-induced Nausea and Vomiting.
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Hui He, Ji-Ye Yin, Ya-Jing Xu, Xi Li, Yu Zhang, Zhuo-Gang Liu, Fan Zhou, Ming Zhai, Yan Li, Xiang-Ping Li, Ying Wang, Hong-Hao Zhou, and Zhao-Qian Liu
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ANTINEOPLASTIC agents , *ONDANSETRON , *TUMOR markers , *ACADEMIC medical centers , *CONFIDENCE intervals , *GENES , *GENETIC polymorphisms , *MULTIVARIATE analysis , *HEALTH outcome assessment , *RESEARCH funding , *SURVIVAL , *TUMORS , *LOGISTIC regression analysis , *GENOMICS , *ACUTE myeloid leukemia , *TREATMENT effectiveness , *DATA analysis software , *DESCRIPTIVE statistics , *ODDS ratio , *THERAPEUTICS - Abstract
Purpose: Resistance to the antiemetic ondansetron is still a major problem resulting in discomfort and poor compliance with chemotherapy in acute myeloid leukemia (AML) patients. Based on our hypothesis that this clinical resistance to ondansetron is associated with ABCB1 genetic polymorphisms, we investigated whether ABCB1 gene variations affect the efficacy of ondansetron in chemotherapy-induced nausea and vomiting. Methods: AML patients (n -- 215) treated for 3 days with high-dose cytarabine were enrolled in this study. Thirty minutes before the beginning of chemotherapy, 8 mg ondansetron was administered intravenously, followed by 24 mg by continuous infusion and 8 mg intravenously, once per day, until 2 days after chemotherapy. Chemotherapy-induced nausea and vomiting occurrence in the acute and delayed phases was calculated. ABCB1 and CYP2D6 polymorphisms were analyzed by allele-specific matrix-assisted laser desorption. Basic clinical characteristics of the AML patients were collected from medical records. Findings: No differences in genotype distribution frequencies of ABCB1 polymorphisms and haplotypes were observed in patients with different CYP2D6- predicted phenotypes. During the acute phase, patients with the CG haplotype (C3435T and G2677T) were associated with a high risk of grade 3/4 nausea and vomiting (P -- 0.003 and P -- 0.026, respectively). After adjustment for age, sex, smoking status, alcohol drinking status, body surface area, body mass index, and Eastern Cooperative Oncology Group--Performance Status, multivariate survival analysis implicated the CG haplotype as a predictive marker of the risk of grade 3/4 chemotherapy-induced nausea and vomiting in AML patients (P -- 0.003 and P -- 0.039, respectively). In addition, a significant association between the 3435CC genotype and grade 3/4 vomiting in AML patients was observed (P -- 0.016). However, no association between these ABCB1 gene polymorphisms and ondansetron efficacy was found in the delayed phase. Implications: These findings suggest that ABCB1 gene polymorphisms are associated with antiemetic efficacy of ondansetron in the acute phase after highdose cytarabine chemotherapy in AML patients. [ABSTRACT FROM AUTHOR]
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- 2014
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382. Pharmacogenetic analysis of the Programmed cell death 6-interacting protein in Chinese individuals
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Smieszkol, Kamila, Marques, Vera Ribeiro, and Zhao, Qian Liu
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Engenharia e Tecnologia::Outras Engenharias e Tecnologias [Domínio/Área Científica] - Abstract
Dissertação de Mestrado, Mestrado em Qualidade em Análises, Faculdade de Ciências e Tecnologia, Universidade do Algarve, 2015 Introduction: Pharmacogenetics is the study of germline genetic variation resulting in altered absorption, distribution, metabolism and excretion associated with the efficacy or toxicity of a drug, or affecting drug interaction with the target protein. Cancer is one of the top ten leading causes of death globally. Moreover lung cancer is one of the most commonly diagnosed cancer, most patients with NSCLC are being diagnose in a late stage and lost the opportunity of surgery. Platinum –based regimens in overall survival and quality of life shown meagre improvement. Study on single nucleotide polymorphism (SNP) showing significant improvement on detecting risk of lung cancer and overall survival by study and by measure and evaluate molecularly defined biomarkers. Results: A total of 335 lung cancer patients, the number of responders (CR or PR) were 100 and non-responders (PD or SD) were 235. All patients received platinum-based chemotherapy, cisplatin-based was 153(45.7%) and carboplatin-based was 182(44.3%). age (P-value 0.037), histology (0.022) and ECOG (0.033) may be considered statistically significant risk factors on platinum-based chemotherapy efficacy in all population. The rs31839825 SNP showed a significant association with chemotherapy response when considering the additive model (OR=0.67, P=0.033). The relationship of the SNP with response to chemotherapy showed significant associations with chemotherapy response: for stage I-II in additive (OR=1.89, P=0.017) and dominant (OR=2.1, P=0.014) models, for EAC in additive model (OR=0.83, P=0.041), for non-smoking (OR=0.47, P=0.048), and for cisplatin (OR=0.51, P=0.046) in recessive model. Conclusion: Results prove that there is a correlation between response and resistance to platinum based chemotherapy. It also suggests that there is a connection between resistance to a drug and the histology and association between the gene polymorphism and lung cancer risk or chemo sensitivity. More studies need to be performed to investigate the potential linking rs3183982 polymorphism in PDCD6IP encoding protein required for apoptosis with cancer progression and prognosis Erasmus Mundus
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- 2015
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