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Objective:To investigate the role of protein phosphatase 4 catalytic subunit (PP4C) in regulating hepatitis B virus X protein (HBx) levels and its effects on the biological functions of HBx, thus to provide a potential therapeutic targets for hepatitis B virus (HBV)-related hepatocellular carcinoma.Methods:In vivo and in vitro interactions between HBx and PP4C were analyzed by co-immunoprecipitation (Co-IP) and GST pull-down assay. Recombinant plasmids of PP4C and HBx were co-transfected with Lipofectamine 3000 reagents into hepatoma cells to detect the protein levels of HBx by Western blot. The half-life of HBx in the transfected cells treated with cycloheximide (CHX) were detected. The phosphorylation assay was used to evaluate the effects of PP4C on HBx phosphorylation. CCK8 assay, wound healing assay and Matrigel invasion chamber assay were used to analyze the effects of PP4C on the biological functions of HBx. Results:PP4C interacted with HBx in vivo and in vitro. PP4C overexpression significantly increased the protein level and stability of HBx and the phosphorylation assay confirmed that PP4C overexpression decreased the serine phosphorylation of HBx in hepatoma cells. PP4C overexpression enhanced the migration and invasion of hepatoma cells, but had no significant effects on the proliferation. Conclusions:The interactions between HBx and PP4C promoted the stability of HBx and ultimately enhanced the migration and invasion of hepatoma cells, and the mechanisms might be related to the decrease of HBx serine phosphorylation by PP4C. This study provided a theoretical basis for further investigation of the pathogenic mechanisms of HBx, and targeting PP4C and HBx interaction might provide insights for developing novel treatment for HBV-related hepatocellular carcinoma.
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Objective To analyze the serum samples of young and middle-aged patients with hypertension of different syndromes and healthy patients by means of metabonomics; To confirm its biomarker; To reveal the nature of phlegm dampness retention syndrome in essential hypertension. Methods The syndrome types of 34 hypertension patients were differentiated into 14 cases of liver-fire hyperactivity syndrome group, 14 cases of phlegm dampness retention syndrome group and 6 cases of yin deficiency and yang hyperactivity syndrome group. 15 healthy volunteers were selected as control group. 1H-NMR technique combined with partial least squares-discriminate analysis (PLS-DA) method was used to look for the biomarkers. And the levels of UA, TC and TG were recorded. Results The level of UA in phlegm dampness retention syndrome group was significantly higher than the other three groups (P<0.05). The level of TC in yin deficiency and yang hyperactivity syndrome group was higher and had significantly difference with the control group (P<0.05). The level of TG in phlegm dampness retention syndrome group was higher and had significantly difference with control group (P<0.05). The metabonomics study based on the 1H-NMR method could distinguish the phlegm dampness retention syndrome group from the normal control group, liver-fire hyperactivity syndrome group and yin deficiency and yang hyperactivity syndrome group. Compared with the control group, the levels of acetone, VLDL, and LDL were significantly higher and the levels of lactate, serine, glucose, methionine, alanine were significantly lower in phlegm dampness retention syndrome group; compared with the liver-fire hyperactivity syndrome group, levels of citrate, alanine, VLDL, and LDL were significantly higher and the levels of glucose, lysine, glutamate, proline lactate were significantly lower; compared with yin deficiency and yang hyperactivity syndrome group, the level of creatinine was significantly higher. Conclusion There are lipoprotein metabolism, amino acid metabolism and glucose metabolism disorder in the young and middle-age hypertensive patients with phlegm dampness retention syndrome.
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Objective To investigate the effect of Kangxin Capsule on the stability of atherosclerotic plaque in rabbits. Methods Forty purebred male New Zealand white rabbits were randomly divided into model group, atorvastatin group, Kangxin Capsule high and low dose groups, and normal control group, 8 rabbit for each group, and were given corresponding administration. Atherosclerosis model was made by intimal injury and high cholesterol diet except for normal control group. After 6 W, aortic vascular pathomorphology were observed, and immunohistochemical method was used to detect the expression of MMP-2 and VCAM-1 in atherosclerotic plaques. Results Compared with model group, the ratio of the thickness of wall to the area of lumina (W/L), average optical density, and the percentage of positive area of Kangxin Capsule groups were less, also, the expression of MMP-2 and VCAM-1 were reduced. The differences were significant (P<0.05 or P<0.01), especially in the high-dose group. Conclusion Kangxin Capsule can reduce the expression of MMP-2 and VCAM-1, which is the possible mechanism of stabilizing the atherosclerotic plaque.
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Objective To observe the effect of Ruanmailing Oral Liquid on angiogenesis in atherosclerosis plaque of Apolipoprotein E (ApoE) gene knock-out mice, and explore the mechanisms of plaque stabilizing. Methods Totally 30 mice 6-8 weeks old ApoE knockout mice were fed a high fat diet for 12 weeks until the formation of a mature atherosclerotic plaque. They were randomly divided into three groups-model group, Ruanmailing group, simvastatin group, with another 6 normal C57BL/6J mice as the control group, and were administered for 12 weeks. Blood was extracted from orbital venous to measure the lipid (TC, TG, LDL-C, HDL-C) variation. HE-stain was used to observe aortic pathomorphological changes, meanwhile, immunohistochemical method was adopted to determine the microvessel density of plagues which is marked by CD105, as well as the expression of CD105 in aorta. Results Compared with the model group, TC, LDL-C, TG of Ruanmailing group and simvastatin group decreased significantly, while HDL-C increased significantly (P0.05). Conclusion Ruanmailing Oral Liquid may reduce the expression of CD105 and inhibit the angiogenesis within the plaque, which is the possible mechanism of stabilizing the atherosclerotic plaque.
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Objectives To study the relationship between TCM syndromes and adiponectin (APN) level, carotid atherosclerosis plaque of hypertension complicated with carotid atherosclerosis, and provide evidence for clinical diagnosis and treatment. Methods One hundred patients of hypertension complicated with carotid atherosclerosis were divided into phlegm syndrome group, stasis syndrome group, and intermingled phlegm and blood stasis syndrome group, and compared with 30 healthy people as control. Carotid atherosclerosis plaque was detected with GE LOGIQ500 color ultrasound system. ELISA was used to determine the serum APN. Results APN of the intermingled phlegm and blood stasis syndrome group was obviously lower than other groups, and there were obvious differences among them. There were more plaques in the intermingled phlegm and blood stasis syndrome group. A negative correlationship was showed between carotid artery intima media thickness (IMT) and APN of hypertension complicated with carotid atherosclerosis. Conclusion There is correlation between TCM syndrome and APN level, carotid atherosclerosis plaque of hypertension complicated with carotid atherosclerosis. The anomalous change of APN and plaque formation of the patients can be preliminarily estimated with the syndrome of TCM.
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OBJECTIVE: To observe the effects of Shenqi Fuzheng injection on the expression of MMP-3 and TIMP-1 in congestive heart failure model rats.METHODS: The experimental rats were randomly divided into 6 groups,i.e.normal group,model group,captopril(10 mg?kg-1)group,Shenqi Fuzheng injection low dosage(2 mL)group,Shenqi Fuzheng injection medium dosage(4 mL)group,and Shenqi Fuzheng injection high dosage(6 mL)group.All except the normal group were intraperitoneally injected with adriamycin on the first experimental day.After drug intervention for 8 weeks,the rats were anesthetized and sacrificed,with heart specimen sampled rapidly for pathological examination and semi-quantitative analysis of myocardial MMP-3 and TIMP-1 mRNA by RT-PCR method.RESULTS:In the model group compared with the normal group,MMP-3 mRNA were significantly increased(P
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BACKGROUND: Adriamycin is anthracycline-based drugs of anti-cancer and inhibits many malignant tumors. But due to the large toxicity, it will induce dose-dependent cardiac toxicity, resulting in heart failure in severe case. Compound huangjing oral lipid is against the injury of free radial and is expected to be applied as an assistant therapy for heart failure.OBJECTIVE: To probe into the therapeutic effect of compound huangjing oral lipid and its mechanism on heart failure.DESIGN: Randomized controlled observation was designed.SETTING: Department of Traditional Chinese Medicine , First Affiliated Hospital of Fujian University of Medical Science, Fujian College of Traditional Chinese Medicine.MATERIALS: The experiment was performed in Fujian Research Institute of Hypertension from August 2000 to May 2001, in which, 66 rats were employed and randomized into 6 groups, 11 rats in each one.METHODS: In normal group, physiological saline of equal volume was injected abdominally. In adriamycin group, adriamycin 1mg/kg was injected abdominally on the 2nd and 4th days after experiment, 2 mg/kg was injected on the 6th and 8th days, 3 mg/kg was on the 10th and 12th days and 4 mg/kg was on the 14th and 16th days. The dose was accumulated up to 20 mg/kg in 16 days. In adriamycin+compound huangjing oral liquid 2 mL (small-dose group), adriamycin +compound huangjing oral liquid 4 mL (moderate-dose group) and adriamycin+compound huangjing oral liquid 6ml (large-dose group), the oral lipid of various doses was applied for gastric perfusion everyday successively from the beginning of experiment, in which, the dose of adriamycin was same as adriamycin group. In adriamycin+tebonin group (tebonin group), tebonin 450 mg/kg was administrated once every two days, totally for 8 days, in which, the dose of adriamycin was same as adriamycin group.MAIN OUTCOME MEASURES: To observe the changes of Left ventricular weight and body weight (LVW/BW), α-MHC (myosin heavy-chain)and β-MHC.RESULTS: In the whole experiment, of 66 experimental animals, 5 rats in adriamycin group, 4 rats in small-dose group, 2 rats in moderate-dose group, 3 rats in large-dose group were died from obvious congestive heart failure, finally, 47 rats entered result analysis. Compared with normal group, in adriamycin group, α-MHC was reduced by 20.88% (P ＜ 0.01), β-MHC was increased by 50.93% (P ＜ 0.01) and LVW/BW was increased by 33.83% (P ＜ 0.01). After medication, myocardial β-MHC was transformed to α-MHC; compared with adriamycin group, α-MHC in every medical group was increased (P ＜ 0.01), β-MHC was decreased (P ＜ 0.01) and LVW/BW was decreased of different degrees (P ＜ 0.01 or P ＜ 0.05); among the above-changes, the results in moderate group were the best.CONCLUSION: Compound huangjing oral liquid alleviates toxicity of heart failure induced by adriamycin, probably due to the dose-dependence improvement of the oral liquid in myocardial α-MHC transformation.
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Objectives:To evaluate the use of needle catheter jejunostomy for early enteral nutrition in liver transplant recipients . Methods:Five liver transplant recipients who had indication were performed with needle catheter jejunostomy before abdominal wall closure.The Flocare jejunokath was inserted on the small bowel at the point 20 cm distal to the ligament of Treitz,continued to go ahead in the wall of the bowel for a distance of about 4～5 cm,and then pierced into bowel lumen.Enteral nutrition was given through jejunostic tube at postoperative 1st day. Results:The time for placing needle catheter jejunostomy during operation was (9.2?2.3)min.The jejunostic tube was used well and pulled out from 14 to 46 days after operation.One patient occurred with jejunostic tube obstruction, and the tube was reused after treatment.No other complication occurred associated with needle catheter jejunostomy. Conclusions:Needle catheter jejunostomy may become the preferable method for early enteral nutrition in indicated liver transplant recipients.