1.Study of change in activity of hepatic drug metabolism enzymes in rat model of chronic unpredictable mild stress.
Yu-xin ZANG ; Bing-ting SUN ; Wen-zhu ZHAO ; Na RONG ; Guo-liang DAI ; Wen-zheng JU ; Heng-shan TAN
Acta Pharmaceutica Sinica 2015;50(3):319-325
This study aimed to explore the impact of depression caused by chronic unpredictable mild stress (CUMS) on in vivo activity of six kinds of CYP450 isoforms in rats. According to 'Katz' method, the model of CUMS was established. Tolbutamide, chlorzoxazone, theophylline, midazolam, omeprazole and dextromethorphan were chosen as probe substrates of CYP2C6, CYP2E1, CYP1A2, CYP3A2, CYP2D1 and CYP2D2 of rats. Plasma concentration of six kinds of CYP450 in control group and model group were determined by LC-MS/MS and computed pharmacokinetic parameters. Consequently, metabolism of theophylline and chlorzoxazone accelerated significantly (P < 0.01), but tolbutamide, dextromethorphan, omeprazole and midazolam had no significant difference. The present study proved that depression caused by CUMS had strong induction to CYP1A2 and medium induction to CYP2E1.
Animals
;
Chlorzoxazone
;
metabolism
;
Chromatography, Liquid
;
Cytochrome P-450 Enzyme System
;
metabolism
;
Depression
;
Dextromethorphan
;
metabolism
;
Liver
;
enzymology
;
Midazolam
;
metabolism
;
Omeprazole
;
metabolism
;
Rats
;
Stress, Physiological
;
Tandem Mass Spectrometry
;
Theophylline
;
metabolism
;
Tolbutamide
;
metabolism
2.Expression of osteopontin mRNA and its clinical significance in gastric cancer.
Xian-jun SUN ; Wen-shu ZUO ; Heng MA ; Wen-hong HOU ; Shu-Ping CAI ; Xi-hong JIANG
Chinese Journal of Oncology 2005;27(5):292-295
OBJECTIVETo investigate the expression of osteopontin mRNA and its correlation with clinicopathologic features of gastric cancer and elucidate its role in tumor invasion and distant metastasis.
METHODSThe expression of OPN mRNA was detected by semi-quantitive RT-PCR. The relationship between the relative content of OPN mRNA and clinicopathologic features of gastric cancer was analyzed.
RESULTSIn 66 cancer tissue samples, a 330 bp band was detected in 50 cases, the positive rate of OPN mRNA expression was 75.8% (50/66). The expression in all 20 cases of normal gastric mucosa was negative. The expression was associated with the depth of tumor invasion, diameter, lymph node metastasis and but had no correlation with differentiation grades. The 66 patients were followed up for 10 approximately 27 months (mean 16 months). The OPN mRNA expression positive group (50 cases) had recurrence in 15 patients and the negative group (16 cases) had only 1 case with recurrence (P = 0.05); 10 patients died in OPN mRNA expression positive group but no patient died in OPN staining negative group (P = 0.05).
CONCLUSIONOPN mRNA is over-expressed in gastric cancer. It reflects the progression of disease and association with poor prognosis of gastric cancer. OPN may play an important role in the process of distant metastasis in gastric cancer.
Adenocarcinoma ; metabolism ; pathology ; Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Osteopontin ; biosynthesis ; genetics ; Prognosis ; RNA, Messenger ; biosynthesis ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Stomach Neoplasms ; metabolism ; pathology
3.Development of a universal primers PCR-coupled liquid bead array to detect biothreat bacteria.
Hai-yan WEN ; Jing WANG ; Heng-chuan LIU ; Xiao-hong SUN ; Yu YANG ; Kong-xin HU ; Lin-jun SHAN
Chinese Journal of Preventive Medicine 2009;43(10):890-894
OBJECTIVETo develop a fast, high-throughput screening method with suspension array technique for simultaneous detection of biothreat bacteria.
METHODS16 S rDNA universal primers for Bacillus anthracis, Francisella tularensis, Yersinia pestis, Brucella spp.and Burkholderia pseudomallei were selected to amplify corresponding regions and the genus-specific or species-specific probes were designed. After amplification of chromosomal DNA by 16 S rDNA primers 341A and 519B, the PCR products were detected by suspension array technique. The sensitivity, specificity, reproducibility and detection power were also analyzed.
RESULTSAfter PCR amplification by 16 S rDNA primers and specific probe hybridization, the target microorganisms could be identified at genus level, cross reaction was recognized in the same genus. The detection sensitivity of the assay was 1.5 pg/microl (Burkholderia pseudomallei), 20 pg/microl (Brucella spp.), 7 pg/microl (Bacillus anthracis), 0.1 pg/microl (Francisella tularensis), and 1.1 pg/microl (Yersinia pestis), respectively. The coefficient of variation for 15 test of different probes was ranged from 5.18% to 17.88%, it showed good reproducibility. The assay could correctly identify Bacillus anthracis and Yersinia pestis strains in simulated white powder samples.
CONCLUSIONThe suspension array technique could be served as an opening screening method for biothreat bacteria rapid detection.
Bacillus anthracis ; isolation & purification ; Bioterrorism ; prevention & control ; DNA Primers ; DNA, Bacterial ; analysis ; Francisella tularensis ; isolation & purification ; Oligonucleotide Array Sequence Analysis ; methods ; Polymerase Chain Reaction ; methods ; RNA, Ribosomal, 16S ; genetics ; Yersinia pestis ; isolation & purification
4.Influence of short-term high-fat diet on glucose and lipid metabolism in male Han Chinese with type 2 diabetes mellitus.
Wen-hui LI ; Xin-hua XIAO ; Kang YU ; Qi SUN ; Guo-hua YANG ; Heng WANG ; Schmitz OLE
Acta Academiae Medicinae Sinicae 2008;30(4):509-515
OBJECTIVETo investigate the influence of short-term high-fat diet (HFD) on glucose and lipid metabolism in male Han Chinese with type 2 diabetes mellitus (T2DM).
METHODSMiddle-aged T2DM men supported with solely diet or diet and metformin were enrolled into the study. The design was an unblinded crossover design. Each of the subjects randomly received one from two types of isocalorie (8786.4 kJ/d) standard diet for three consecutive days on two occasions, with a 6-week wash-out period in between. The component ratios of fat, carbohydrate, and protein were 50%, 35%, and 15% vs. 25%, 60%, and 15% in patients administered with HFD or high carbohydrate diet (HCD). The 24-hour blood samples during the third day were collected. On the morning of the forth day an intravenous glucose tolerance test (IVGTT) was conducted with 25g of glucose.
RESULTSAccording to the determination results of 24-hour profile samples, HFD resulted in a markedly increased circulating level of non-esterified fatty acid (NEFA) as compared to HCD (P < 0.001). Nearly significant higher (P = 0.056) FPG was observed 72 hours after the administration of HFD. Circulating insulin levels were comparable between the two diets. A significantly higher HDL-C was also observed after HFD administration (P < 0.05). As assessed by the IVGTT, acute insulin response of glucose (AIRg) tended to increase after the HFD administration (P = 0.06). Fasting plasma glucagons (GLG) level and AUC(Glucagon) during breakfast period (8:00-12:00) were significantly higher after HFD administration than that of after HCD administration.
CONCLUSIONSShort-term HFD induced the increase of NEFA with lower glucose exposure to the patietns. Fasting plasma glucose increased at the fourth day without remarkable changes of insulin levels which may be due to the increase of hepatic glucose output after HFD administration. The short-term HFD in our study induced early stage of insulin resistance. GLG seemed to play a role in this procedure. beta-cell dysfunction may need a longer high NEFA exposure.
Adult ; Blood Glucose ; metabolism ; China ; Diabetes Mellitus, Type 2 ; ethnology ; metabolism ; Dietary Carbohydrates ; administration & dosage ; Dietary Fats ; administration & dosage ; Fatty Acids, Nonesterified ; metabolism ; Humans ; Insulin ; metabolism ; Male ; Middle Aged
5.Study on biomarker of Tripterygium wilfordii in treatment of rheumatoid arthritis based on PK/PD.
Shi-jia LIU ; Guo-liang DAI ; Bing-ting SUN ; Chang-yin LI ; Lei WU ; Ma SHI-TANG ; Wen-zheng JU ; Heng-shan TAN ; Hai-yan FU
China Journal of Chinese Materia Medica 2015;40(2):334-338
To observe the serum samples and the anti-inflammatory effect of Tripterygium wilfordii in treating RA by using the pharmacokinetic-pharmacodynamic model, make a correlation analysis on concentration-time and effect-time curves, and explore RORγt, IL-17, STAT3, IL-6 mRNA transcriptional levels in rats by PCR. Methotrexate, tripterine and high-dose T. wilfordii could down-regulate RORγt, IL-17, STAT3, IL-6 mRNA transcriptional levels in AA rat lymph nodes. The study on PK-PD model showed correlations between inflammatory factors and blood concentration of T. wilfordii. T. wilfordii and its main active constituent tripterine could show the inflammatory effect and treat RA by inhibiting IL-17 cytokine.
Animals
;
Arthritis, Rheumatoid
;
drug therapy
;
immunology
;
Biomarkers
;
Female
;
Interleukin-17
;
antagonists & inhibitors
;
genetics
;
Interleukin-6
;
genetics
;
Phytotherapy
;
Rats
;
Rats, Sprague-Dawley
;
Tripterygium
;
Triterpenes
;
pharmacokinetics
;
pharmacology
6.Clinical study on injected carbamide peroxide for treatment of respiratory failure complicated by lung infection in coal workers' pneumoconiosis.
Feng-rui ZHAO ; Jing ZHAO ; Hui ZHANG ; Wen-shou XU ; Chun-yan TIAN ; Dian-heng HAN ; Hong LI ; Li-an SUN ; Xiu-ying LI
Chinese Journal of Industrial Hygiene and Occupational Diseases 2006;24(2):121-122
Aged
;
Coal Mining
;
Drug Combinations
;
Humans
;
Male
;
Middle Aged
;
Peroxides
;
administration & dosage
;
therapeutic use
;
Pneumoconiosis
;
complications
;
drug therapy
;
Respiratory Insufficiency
;
drug therapy
;
etiology
;
Urea
;
administration & dosage
;
analogs & derivatives
;
therapeutic use
7.Effect of clopidogrel on plasma protein binding rate of ginsenosides: a liquid chromatography-mass spectrometry-based study.
Shi-Tang MA ; Guo-Liang DAI ; Wen-Zhu ZHAO ; Bing-Ting SUN ; Wen-Zheng JU ; Heng-Shan TAN
Journal of Southern Medical University 2015;35(1):109-112
OBJECTIVETo investigate the effect of clopidogrel on the binding rate of ginsenosides with rat serum proteins (RSA).
METHODSEquilibrium dialysis and liquid chromatography-mass spectrometry were employed to quantify the concentration of ginsenoside Rg1 and Rb1. The protein-binding rates of Rg1 and Rb1 in the presence or absence of clopidogrel (1.0 mg/L) were determined. A molecular simulation model (consisting of homology modeling and molecular docking interaction) was used to reveal the target protein-compound interactions.
RESULTSThe binding rates of ginsenosides Rg1 (0.4, 1.0, and 2.0 mg/L) with RSA were (30.16∓2.82)%, (33.42∓4.21)%, and (34.61∓3.42)%, and those of and Rb1 were (50.13∓2.34)%, (51.23∓3.23)%, and (53.11∓3.26)%, respectively. In the presence of clopidogrel, the binding rates of Rg1 decreased to (22.13∓2.72)%, (21.42∓3.22)%, and (25.45∓3.52)%, and those of Rb1 to (40.13∓3.24)%, (41.25∓4.15)%, and (43.11∓3.31)%, receptively. The molecular docking suggested that these compounds competed to bind with RSA.
CONCLUSIONClopidogrel can competitively bind to RSA with ginsenosides to lower the plasma protein binding rates of ginsenosides.
8.Quantitative study of diffusion weighted imaging on magnetic resonance imaging in focal hepatic lesions less than 3 cm.
Xi-Jie SUN ; Xian-Yue QUAN ; Wen LIANG ; Zhi-Bo WEN ; Sheng ZENG ; Fan-Heng HUANG ; Ming TANG
Chinese Journal of Oncology 2004;26(3):165-167
OBJECTIVETo evaluate the characteristics of MR imaging of hepatic lesions using measurement of apparent diffusion coefficient (ADC) value of hepatic lesions on diffusion weighted imaging.
METHODSMR diffusion weighted images were obtained in patients with 97 hepatic lesions (22 hepatocellular carcinomas, 21 metastatic tumors, 28 hemangiomas, 26 cysts). ADC values were evaluated with different sequences. The ADC ratio of lesion/liver was estimated.
RESULTSAverage ADC values of hepatic lesions were as follows: carcinomas (0.91 +/- 0.07) x 10(-3) mm(2)/s, metastatic tumors (1.13 +/- 0.27) x 10(-3) mm(2)/s, cavernous hemangiomas (1.94 +/- 0.37) x 10(-3) mm(2)/s, cysts (3.26 +/- 0.30) x 10(-3) mm(2)/s. The ADC ratio of lesion/liver was significantly different between primary carcinomas and metastatic tumors (P < 0.05).
CONCLUSIONQuantitative study in hepatic lesions using ADC values and the ADC ratio of lesion/liver, would improve the accuracy in diagnosing hepatic lesions.
Cysts ; diagnosis ; Diagnosis, Differential ; Diffusion ; Hemangioma, Cavernous ; diagnosis ; Humans ; Liver ; pathology ; Liver Neoplasms ; diagnosis ; secondary ; Magnetic Resonance Imaging
9.Determination of the repair half-time of human nasopharyngeal carcinoma cell lines CNE1, CNE2, HONE1 and C666-1.
Wen-jun WANG ; Xiao-kang ZHENG ; Jia-bin LIU ; Ya-wei YUAN ; Long-hua CHEN ; Heng-wen SUN
Journal of Southern Medical University 2010;30(4):777-778
OBJECTIVETo determine the repair half-time (T1/2), a speed parameter of sub-lethal damage repair (SLDR), of human nasopharyngeal carcinoma (NPC) cell lines CNE1, HONE1, C666-1 and CNE2.
METHODSA total radiation dose of 8 Gy divided into 4+4 Gy was delivered to the cell lines at the interval of 0 s, 15 s, 30 s, 1 h, 2 h, 4 h or 6 h. The cell survival fractions were determined using the standard cell clonogenic assay. The curves of the changes in the surviving cell fraction after a total dose of 8 Gy, as a function of the interval between the two doses of 4 Gy, were fitted manually, and the T1/2 of each cell line was calculated according to the curves.
RESULTSThe T1/2 of CNE1, HONE1, C666-1 and CNE2 were 18 s, 22 s, 29 s and 27 s, respectively.
CONCLUSIONThe speed of SLDR of NPC cells is quite rapid, indicating that the fraction delivery time longer than 20 s might decrease the effect of radiotherapy.
Cell Line, Tumor ; Cell Survival ; radiation effects ; Dose-Response Relationship, Radiation ; Humans ; Nasopharyngeal Neoplasms ; pathology ; radiotherapy ; Radiation Injuries ; prevention & control ; Radiotherapy, Conformal ; Radiotherapy, Intensity-Modulated
10.Effects of glucagon on islet beta cell function in patients with diabetes mellitus.
Tong WANG ; Xin-Hua XIAO ; Wen-Hui LI ; Heng WANG ; Qi SUN ; Tao YUAN ; Guo-Hua YANG
Chinese Medical Sciences Journal 2008;23(2):117-120
OBJECTIVETo evaluate islet beta cell response to intravenous glucagon (a non-glucose secretagogue) stimulation in diabetes mellitus.
METHODSNineteen patients with type 1 diabetes (T1D) and 131 patients with type 2 diabetes (T2D) were recruited in this study. T2D patients were divided into two groups according to therapy: 36 cases treated with insulin and 95 cases treated with diet or oral therapy. The serum C-peptide levels were determined at fasting and six minutes after intravenous injection of 1 mg of glucagon.
RESULTSBoth fasting and 6-minute post-glucagon-stimulated C-peptide levels in T1D patients were significantly lower than those of T2D patients (0.76 +/- 0.36 ng/mL vs. 1.81 +/- 0.78 ng/mL, P < 0.05; 0.88 +/- 0.42 ng/mL vs. 3.68 +/- 0.98 ng/mL, P < 0.05). In T1D patients, the C-peptide level after injection of glucagon was similar to the fasting level. In T2D, patients treated with diet or oral drug had a significantly greater fasting and stimulated C-peptide level than those patients received insulin therapy (2.45 +/- 0.93 ng/mL vs. 1.61 +/- 0.68 ng/mL, P < 0.05; 5.26 +/- 1.24 ng/mL vs. 2.15 +/- 0.76 ng/mL, P < 0.05). The serum C-peptide level after glucagon stimulation was positively correlated with C-peptide levels at fasting in all three groups (r = 0.76, P < 0.05).
CONCLUSIONSThe 6-minute glucagon test is valuable in assessing the function of islet beta cell in patients with diabetes mellitus. It is helpful for diagnosis and treatment of diabetes mellitus.
Adult ; C-Peptide ; blood ; Diabetes Mellitus, Type 1 ; drug therapy ; Diabetes Mellitus, Type 2 ; drug therapy ; Female ; Glucagon ; pharmacology ; therapeutic use ; Glycated Hemoglobin A ; metabolism ; Humans ; Insulin ; therapeutic use ; Islets of Langerhans ; drug effects ; metabolism ; Male ; Middle Aged