Objective To investigate the effect of peroxisome proliferator-activated receptor γ (PPARγ) agonist pioglitazone on white matter lesions and spatial memory function in chronic hypertensive rats.Methods Thirty-six male Sprague-Dawley rats were randomly divided into a sham operation group (n =6),a hypertensive group,(n =15),and a pinglitazone group (n =15).A model of stroke-prone renovascular hypertensive rat (RHRSP) was induced by the two-kidney two clip method in the hypertensive group and pioglitazone group.At 8 weeks after procedure,the rats were administered intragastrically.10 mg/(kg · d) pioglitazone was given in the pioglitazone group and an equal volume of saline was given in the hypertensive group.Blood pressure was monitored via caudal artery every 2 weeks before procedure,before administration,and after administration,respectively.After 12 weeks of continuous administration,Loyez staining was used to observe the degree of leukoaraiosis,and Morris water maze test was used to detect spatial memory function.Results After modeling,the blood pressure of RHRSP increased gradually.It was significantly higher than the sham operation group (all P =0.001).There was no significant difference in blood pressure between the hypertensive group and the pioglitazone group (P =0.897).The Morris water maze test showed that escape latencies of the sham operation group and the pioglitazone group were significantly shorter than the hypertensive group (all P ＜0.05).The numbers of crossing hidden platform in the 3 groups of rats were 5.200 ± 1.798,4.560 ± 1.592,and 2.333 ± 1.978 times,respectively.There were significantly differences (F =8.143,P =0.001).Both the sham operation group and the pioglitazone group were significantly more than the hypertensive group (all P ＜0.05).Loyez staining showed that the grades of white matter lesions in corpus callosum of the sham operation group,the hypertensive group,and the pioglitazone group were 0.333 ± 0.516,2.600 ± 0.507,and 0.500 ± 0.522,respectively.There were significantly differences among the 3 groups (F =25.652,P =0.000).The grade of the sham operation group and the pioglitazone group was significantly lower than the hypertensive group (all P＜ 0.05).Conclusions PPARγ agonist pioglitazone may protect the spatial memory function by relieving white matter lesions of the chronic hypertensive rats.

Heterotrimeric G proteins are classes of signal-transducing proteins that bind to guanine nucleotides and possess GTP hydrolase activity. G proteins are composed of three subunits α, β, and γ, and are considered as the "molecular switch" in the GPCR signaling pathway. The abnormal activation of G protein is strongly related to diseases such as uveal melanoma, asthma, et al., making directly targeting G protein as an promising strategy for combating diseases. In this review, the classification and physiological functions of G protein are briefly described, and the research progress of G proteins in diseases, G protein modulators are reviewed.

Arsenites ; toxicity ; Cell Cycle ; drug effects ; Cell Division ; drug effects ; Cell Proliferation ; drug effects ; Cells, Cultured ; Dose-Response Relationship, Drug ; Humans ; Keratinocytes ; cytology ; Skin ; cytology ; Sodium Compounds ; toxicity

Objective To compare the effects of clopidogrel with or without combined with CYP3A4-metabolized statin in treating coronary artery disease (CAD) among the elderly patients.Methods The study cohort was defined as all patients were over 60 years of age and hospitalized for CAD who were prescribed clopidogrel between January 2000 and February 201 1.A total of 1021 patients were enrolled,with 178 of them prescribed clopidogrel and 843 patients were administrated clopidogrel combined with statins (CYP3A4-metabolized statins 636 and non CYP3A4-metabolized statins 207).The primary endpoint was all cause of death and the second endpoint were non-fatal myocardial infarction (MI),but hospitalized for unstable angina,stroke,transient ischemic attack,or repeated revascularization (PCI or coronary artery bypass graft).Results Among the clopidogrel group and the clopidogrel plus statins group,the incidence density of death was 6.86/1000 and 3.18/ 1000 respectively,with crude RR as 2.15(95％CI:1.39-3.33) and statistically significant (x2=3.53,P＜0.01).The incidence density of composite thromboembolic events did not show statistical significance (P＞0.05).The two groups were 1∶1 matched,after propensity score matching,clopidogrel coadministrated with statins group showed significant decrease in all cause of death,with RR as 0.42 (95％ CI:0.19-0.93),x2=7.23,P＜0.01.No significant difference was observed in deaths or composite thromboembolic events between statins via different cytochrome P450 pathways.Conclusion Clopidogrel with statin could reduce the mortality of elderly CAD patients compared with clopidogrcl without statin.The result did not show statistical significance between CYP3A4-metabolized statins or non CYP3A4-metabolized statins regarding the mortality or composite endpoint events.

OBJECTIVETo investigate the fat decreasing effects of fenofibrate on alcoholic fatty liver and drug-induced fatty liver in rats.

METHODSAlcoholic fatty liver and drug-induced fatty liver rats models were established. The two kinds of rats with fatty liver were seperatedly divided into fenofibrate treatment group (80 mg/kg daily) and control group without treatment. Rats were killed after four weeks, then the levels of serum triglycerides (TG), total cholesterol (TC), high density lipoprotein (HDL) and malondialdehyde (MDA), hepatic lipase (HL), lipoprotein lipase (LPL) both in serum and liver tissue were measured according to the Test Kits. Histopathological changes in liver was dyed with HE and observed under light microscope.

RESULTSAfter treatment by fenofibrate, in the serum of rats with alcoholic fatty liver, the level of TG decreased significantly (1.07 mmol/L 0.06 mmol/L vs 1.56 mmol/L 0.29 mmol/L, t=5.115, p<0.001), while the level of TC had no alteration. The levels of MDA both in serum and liver tissue decreased (1.10 nmol/L 0.22 nmol/L vs 1.26 nmol/L 0.21 nmol/L, t=0.592, p<0.05; 5.92 nmol/g 1.24 nmol/g vs 7.42 nmol/g 1.22 nmol/g, t=3.477, p<0.05, respectively), while the levels of HL, LPL in serum and liver tissue increased significantly (Serum: 0.053muEq/ml/h 0.006muEq/ml/h vs 0.037 muEq/ml/h 0.006muEq/ml/h, t=-5.086, p<0.001; 0.018 muEq/ml/h 0.004 muEq/ml/h vs 0.014muEq/ml/h 0.004muEq/ml/h, t=-2.485, p<0.05. Liver tissue: 0.075muEq/ml/h 0.010muEq/ml/h vs 0.065muEq/ml/h 0.007muEq/ml/h, t=-2.437, p<0.05; 0.022 muEq/ml/h 0.014 muEq/ml/h vs 0.008 muEq/ml/h 0.002 muEq/ml/h, t=-2.876, p<0.05). Fat content in liver decreased (26.01 mg/g 1.69 mg/g vs 71.45 mg/g 2.66 mg/g, t=-43.224, p<0.001). The pathological changes of liver in fenofibrate-treated rats with alcoholic fatty liver were improved. For the drug-induced fatty liver rats, fenofibrate treatment group had no difference from the untreated control group.

CONCLUSIONFenofibrate can significantly decrease the fat content in liver tissue of rats with alcoholic fatty liver, as well as ameliorating liver pathological changes. But fenofibrate has no effect on drug-induced fatty liver.

Animals ; Carbon Tetrachloride ; toxicity ; Fatty Liver ; chemically induced ; drug therapy ; pathology ; Fatty Liver, Alcoholic ; blood ; drug therapy ; pathology ; Fenofibrate ; therapeutic use ; Hypolipidemic Agents ; therapeutic use ; Lipids ; blood ; Liver ; pathology ; Male ; Rats ; Rats, Wistar

OBJECTIVETo evaluate the effect of irbesartan on the proliferation, apoptosis, and VEGF mRNA expression of human umbilical vein cell line EA.hy926 in vitro.

METHODSThe human umbilical vein cell line EA.hyY926 were treated with various concentrations of irbesartan for 24 h. The cell proliferation after the treatment was detected by CCK8 assay, flow cytometry and FITC Annexin V/PI kit were used to detect changes in the cell apoptosis. RT-PCR was used to evaluate the expression of VEGF mRNA.

RESULTSThere were no changes in cell shape with various concentration of irbesartan. CCK-8 assay showed a greater rate of the cell proliferation in irbesartan group than that in control group with a dose-independent manner after 24 h treatment. After incubation with irbesartan, cell proliferation rate was significant (P < 0.05). FCM analysis showed no significantly changes in the cell apoptosis. Irbesartan increased the proliferation of EA.hy926 cells. At concentration of 1 x 10(-4), 1 x 10(-5), 1 x 10(-6) mol/L, VEGF mRNA expression enhanced either (P < 0.05).

CONCLUSIONIrbesartan could promote the proliferation and up-regulated VEGFmRNA expression in EA.hy926 cell line. This result suggested that in addition to antihypertensive effect, angiotensin receptor antagonist might be a novel therapeutic approach to chronic ischemic heart disease as heart failure.

Apoptosis ; drug effects ; Biphenyl Compounds ; pharmacology ; Cell Line ; Cell Proliferation ; drug effects ; Humans ; RNA, Messenger ; genetics ; Tetrazoles ; pharmacology ; Umbilical Veins ; cytology ; metabolism ; Vascular Endothelial Growth Factor A ; metabolism

OBJECTIVETo analyze the relationship between the expression of FasL, Perforin and Granzyme B and the development of acute graft versus host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).

METHODSThe peripheral blood mRNA expression of granzyme B, perforin, fasL from 17 patients after allo-HSCT was detected by competitive quantitative RT-PCR and the relationship between FasL, Granzyme B and Perforin expressions and clinical symptom of aGVHD was analyzed.

RESULTSThe expression level of Granzyme B, Perforin and FasL was 4.6 +/- 0.2, 4.5 +/- 0.1, 1.4 +/- 0.1 before aGVHD occurrence respectively, and was 98.7 +/- 2.5, 91.8 +/- 3.4, 61.5 +/- 2.2, after the occurrence in 14 patients (P < or = 0.05). Over expressions of Granzyme B, Perforin, and FasL during acute GVHD were detected in 13 of 14, 12 of 14, and 12 of 14 patients respectively. The upregulated expressions occurred prior to clinical symptom of aGVHD.

CONCLUSIONThe expressions of Granzyme B, Perforin, and FasL were significantly high in patients with acute aGVHD. Monitoring of the expressions, might predict the occurrence of clinical aGVHD and it severity and prognosis.

Acute Disease ; Adult ; Fas Ligand Protein ; genetics ; Female ; Gene Expression ; Graft vs Host Disease ; blood ; diagnosis ; etiology ; Granzymes ; genetics ; Hematopoietic Stem Cell Transplantation ; adverse effects ; methods ; Humans ; Male ; Perforin ; genetics ; Postoperative Complications ; blood ; diagnosis ; etiology ; Prognosis ; RNA, Messenger ; blood ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Transplantation, Homologous

This study was purposed to characterize the effect of carboxylic acid metabolite (SR26334) of clopidogrel bisulfate deprived of antiplatelet efficacy on the spectrum of gene expression in the cultured human umbilical vein endothelial cell (HUVEC) line (EA.hy926), and to explore the potential molecule mechanism of SR26334 impact on HUVEC. By using a Affymetrix HU133 plus 2.0 oligonucleotide microarray, the alteration of gene expression spectrum induced by SR26334 in HUVEC was detected, the real-time PCR was used to confirm the results of selected differentially expressing genes. The results indicated that total 235 including 176 up-regulated and 59 down-regulated genes were obtained with change more than 1.5-fold after SR26334 (10 µmol/L) acted on HUVEC for 48 h. SR26334 affected the expression levels of genes involved regulation of transcription, transcription, positive regulation of transcription from RNA polymerase II promoter, cell cycle, cell division, protein amino acid dephosphorylation in HUVEC. It is concluded that carboxylic acid metabolite SR26334 of clopidogrel bisulfate modulates function of endothelial cells through different pathway at gene level.
Cell Line ; Human Umbilical Vein Endothelial Cells ; cytology ; drug effects ; Humans ; Ticlopidine ; analogs & derivatives ; pharmacology ; Transcriptome ; drug effects

This study was purposed to investigate the effect of clopidogrel on gene expression profile of cultured human umbilical vein endothelial cell (HUVEC) line (EA.hy926), and explore its potential molecule mechanism. A Affymetrix U133 plus 2.0 oligonucleotide microarray was applied to detect the alteration of gene expression profile induced by clopidogrel in HUVEC. Real time RT-PCR was used to verify the result of selected differentially expressing genes. The results showed that total 508 genes (including 139 up-regulated and 369 down-regulated genes) were obtained with differential expression more than 1.5-fold after clopidogrel (10 µmol/L) acted on HUVEC for 48 h. Clopidogrel affected the expression levels of genes involved protein binding, transcription factor activity, zinc ion binding, regulation of DNA-dependent transcription, transcription, RNA splicing and so on. It is concluded that the clopidogrel modulate function of endothelial cells by regulating sets of genes through different pathway.
Cell Line ; Human Umbilical Vein Endothelial Cells ; drug effects ; metabolism ; Humans ; Oligonucleotide Array Sequence Analysis ; RNA, Messenger ; genetics ; Ticlopidine ; analogs & derivatives ; pharmacology ; Transcription, Genetic ; Transcriptome

UNLABELLEDOBJECTIVE To compare anti-oxidative effects of acupuncture at different Shichen (traditional twelve two-hour periods) accordin-17:00), You (17:00-19:00), Xu (19:00-21:00), Hui (21:00-23:00) periods according to the eight methods of the intelligent turtle, once each day, for 7 consecutive days. Changes of malondialdehyde (MDA) content and superoxide dismutase (SOD) activity after treatment were observed.

RESULTSSOD activities and MDA contents at the 12 periods were different in the healthy guinea pigs, SOD activity at Wu period was the highest and the lowest at Zi period; MDA content was the highest at Zi period and the lowest at Wu period. The needling method according to eight methods of the intelligent turtle could increase SOD activity in the guinea pigs. The increasing amplitude of SOD activity was the largest at Mao period and the smallest at the Wu period; it also could decreased MDA content, the decreasing amplitude of MDA was the largest at Wu period and the smallest at Hai period.

CONCLUSIONAcupuncture at different periods according to eight methods of intelligent turtle has different effects on serum SOD and MDA, which can increase SOD activity and decrease MDA content in the healthy guinea pig.

Acupuncture Therapy ; Animals ; Female ; Guinea Pigs ; Male ; Malondialdehyde ; blood ; Superoxide Dismutase ; blood ; Time Factors