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Refined-JQ (JQ-R) is a mixture of refined extracts from(Ranunculaceae),(Leguminosae) and(Caprifoliaceae), the three major herbs of JinQi-JiangTang tablet, a traditional Chinese medicine (TCM) formula. The mechanisms by which JQ-R regulates glucose metabolism and improves insulin sensitivity were studied in type 2 diabetic KKmice and insulin-resistant L6 myotubes. To investigate the mechanisms by which JQ-R improves insulin sensitivity, a model of insulin-resistant cells induced with palmitic acid (PA) was established in L6 myotubes. Glucose uptake and expression of factors involved in insulin signaling, stress, and inflammatory pathways were detected by immunoblotting. JQ-R showed beneficial effects on glucose homeostasis and insulin resistance in a euglycemic clamp experiment and decreased fasting insulin levels in diabetic KKmice. JQ-R also improved the plasma lipid profiles. JQ-R directly increased the activity of superoxide dismutase (SOD) and decreased malondialdehyde (MDA) as well as inducible nitric oxide synthase (iNOS) levels in insulin-resistant L6 cells, and elevated the insulin-stimulated glucose uptake with upregulated phosphorylation of AKT. The phosphorylation levels of nuclear factor kappa B (NF-B p65), inhibitor of NF-B (IB), c-Jun N-terminal kinase (JNK1/2) and extracellular-signal-regulated kinases (ERK1/2) were also changed after JQ-R treatment compared with the control group. Together these findings suggest that JQ-R improved glucose and lipid metabolism in diabetic KKmice. JQ-R directly enhanced insulin-stimulated glucose uptake in insulin-resistant myotubes with improved insulin signalling and inflammatory response and oxidative stress. JQ-R could be a candidate to achieve improved glucose metabolism and insulin sensitivity in type 2 diabetes mellitus.
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Autophagy is a cellular normal reaction to cope with the changes in internal and external environmental pressure, and a degradation process of the material composition. Recent studies have shown that autophagy is closely related to the growth and physiological and pathological events of podocytes in kidneys and it is a potential target for the treatment of diabetic nephropathy(DN) and a self-protection mechanism. Rregulation of autophagy can affect some signaling pathways in the development of DN. Thus ,we summarize the pathogenesis of DN,the role of autophagy in the intrinsic kidney cells,and the effect of autophagy on some signaling pathways in the development of DN in this review.
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The development of diabetes is associated with parasecretion of insulin resulting from the mass loss and dysfunction of β-cell in pancreas. Autophagy is a process of high conservation, which can improve β-cell function impaired by inflammation, oxidative stress, and endoplasmic reticulum stress. That is beneficial to delaying the progression of diabetes. Thus, in this review we summarize the definition of autophagy, autophagy related proteins and modulation of autophagy signaling pathways, the protection of autophagy on the structure and function of β-cells, as well as autophagy in β-cells with inflammation, oxidative stress and endoplasmic reticulum stress.
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Aim To investigate the effects of 3 ,5 ,2 ’ , 4’-tetrahydroxychalcone (P40) on urate excretion, as well as mRNA and protein expressions of renal URAT1 and GLUT9 in hyperuricemic mice. Methods Sixty Kunming mice were randomly divided into six groups:normal control group, hyperuricemic group ( model group), P40 2. 0, 4. 0, 8. 0 mg·kg-1 groups and positive control group. All drugs were administered in-tragastrically to mice for 5 doses. Hyperuricemic mice were induced by intraperitoneal injection of uric acid (0. 15 g·kg-1 body weight) for 3 times. The urate levels were assayed with the phosphotungstic acid method. The mRNA and protein expressions of GLUT9 and URAT1 were determined by RT-PCR and Western blot. Results P40 at a dose of 4. 0 and 8. 0 mg · kg-1 significantly reduced the serum urate levels in a dose-dependent manner, when compared with untreat-ed hyperuricemic mice ( P<0. 05 or 0. 01 ) . The he-patic urate contents decreased in untreated-and treated-hyperuricemic mice as compared with normal mice ( P<0. 01 ) . Furthermore, P40 had no influence on the renal URAT1 mRNA and protein expression levels, while it could down-regulate renal GLUT9 protein ex-pression but not mRNA expression in hyperuricemic mice. Conclusion P40 possesses potent uricosuric effects associated with urate reabsorption by down-regu-lating the protein expression of GLUT9 in kidney.
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Autophagy is a cellular reaction to the changes of internal and external environmental pressure, and a degradation process of the material composition. Recent study has shown that autophagy is closely related to the quantity and insulin secretion of pan-creaticβcell. As a self-protection mechanism, the activation and regulation of autophagy are essential for maintaining the structure and function of pancreaticβcells in type 2 diabetes. Moreover, some drugs for type 2 diabetes were found to participate in the regulation of autophagy pathway in recent studies. Thus, in this review we summarize the importance of autophagy in protecting the structure and func-tion of pancreaticβcell, the regulation of autophagy pathway and the correlation between autophagy and drugs for type 2 diabetes.
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Aim To investigate the effect of dihydro-myricetin (DMY) on the insulin resistance in 3T3-L1 adipocytes and its mechanism. Methods The differ-entiated adipocytes were treated with 1 μmol · L-1 dexamethasone ( dex ) for 7 days to induce insulin re-sistance. With or without insulin, DMY (1 × 10 -6 ~ 1 × 10 -8 mol·L-1 ) was exposed to the normal and in-sulin-resistant 3 T3-L1 adipocytes for 48 hour and 72 hour, respectively. Rosiglitazone ( 1 × 10 -6 mol · L-1 ) was used as a positive control. The glucose up-take was evaluated by glucose consumption. The mR-NA expressions of glucose transporter 4 ( GLUT4 ) , protein kinase B ( PKB/Akt) and adiponectin were de-termined by RT-PCR analysis. Results DMY ( 5 × 10 -7 ~ 1 × 10 -8 mol·L-1 ) concentration-dependently increased the glucose uptake in insulin-resistant 3 T3-L1 adipocytes, similar to rosiglitazone. However, DMY did not affect the glucose consumption in normal 3T3-L1 cells. After treatment of DMY to insulin-resist-ant 3T3-L1 adipocytes for 72 hours, the expressions of GLUT4 , Akt2 and adiponectin mRNA were markedly increased, compared with the dexamethasone-treated group. Conclusion DMY could improve the insulin resistance in 3T3-L1 adipocytes, which is related to in-creasing the mRNA expression of GLUT4 , Akt2 and adiponectin.
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ObjectiveTo discuss the diagnosis and treatment of spontaneous carotid artery dissection (SCAD).Methods Clinical diagnosis and treatment data of 9 patients with SCAD were analyzed retrospectively.ResultsVascular ultrasound showed stenoses or occlusions of carotid artery.Angiography showed “flame-shaped ” sign in totally occluded proximal section and free intimal flap in stenoses section.One patient with total occlusion of bilateral internal carotid artery and 6 patients with total occlusion of unilateral internal carotid artery were treated with antiplatelet therapy.Two patients with incomplete occlusion of the carotid were operated with stent implantation in carotid arteries,and the clinical effect of both operations was satisfactory.ConclusionAngiography remains the gold standard in diagnosing SCAD,and stent implantation is an effective treatment of this disease.
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BACKGROUND:Bone marrow stem cell transplantation can improve heart function and prevent ventricle remodeling.At present,the adult bone marrow stem cells used for transplantation primarily included bone marrow mononuclear cells (BM-MNCs) and mesenchymal stem cells (MSCs),and endothelial progenitor cells.The curative effects and precise mechanisms of transplantation of various bone marrow stem cells remain unknown.OBJECTIVE:To compare the effects of transplantation of autologous BM-MNCs and MSCs via the coronary artery on ventricle remodeling subsequent to acute myocardial infarction (AMI). DESIGN,TIME AND SETTING:Randomized controlled animal experiment performed at the Center for Clinical Research,Hebei Provincial People's Hospital,Electron Microscope Room,Hebei Medical University between March 2005 and December 2006.MATERIALS:Thirty-six male Jizhong pigs,were randomly divided into 4 groups:control group (n = 6),infarct model group (n = 10),BM-MNC group (n = 10),and MSC group (n = 10).METHODS:Porcine autologous BM-MNCs were isolated by gradient density centrifugation,and MSCs were obtained by adherence method.Prior to transplantation,both BM-MNCs and MSCs were colloidal gold labeled.Except the infract model group,pigs in the other 3 groups were developed into AMI models by oppressing the left anterior descending branch with balloon catheter.Ninety minutes after modeling,(6.0±1.3)×107 autologous BM-MNCs and (4.5±2.1)x 107 MSCs were respectively transplanted into pigs in the BM-MNC group and the MSC group via the coronary artery and cultured for 28 days.MAIN OUTCOME MEASURES:Observation of pathological changes of cardiac muscle tissue by light and electron microscope;Examination of cardiac function by ultrasonograph;Detection of the number of blood vessels and apoptotic myocardial cells,and expression of nuclear factor-κB (NF-κB) and troponin Ⅰ and its correlation to cardiac function by immunohistochemistry;Detection of mRNA expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in the cardiac tissue as well as its correlation to cardiac function by reverse transcription-polymerase chain reaction (RT-PCR).RESULTS:In the MSC group,there was proliferation of a great deal of blood vessels as well as growth of abnormal cell masses around the coronary vessels,while the BM-MNC group exhibited the "budding" of many capillary vessels.Prior to transplantation,cardiac function indices were basically similar among each group (F = 1.550,P＞0.05).Twenty-eight days after transplantation,left ventricular ejection fraction was significantly lower in the control,BM-MNC,and MSC groups than in the infarct model group (F = 5.30,P＜0.05),while endocardial fractional shortening was significantly higher (F = 10.67,P＜0.01).Compared with the infarct model group,the number of blood vessels in the infarct zone and infarct border zone was increased in the BM-MNC group (F=29.56-34.87,P＜0.01) and had no apparent change in the MSC group.In the BM-MNC and MSC groups,apoptotic myocardial cells in the infarct zone and infarct border zone were significantly reduced (F=14.31-35.34,P＜0.01 ) and troponin I expression rate was significantly increased (F=19.05,P＜0.01 ),as compared with the infarct model group.In addition,NF-κB positive rate in the infarct border zone was significantly lower in the BM-MNC and MSC groups than in the infarct model group (F=19.05,P＜0.01).VEGF gene expression level in the infarct border zone was significandy higher in the BM-MNC group than in the infarct model group and MSC group (F = 49.41,P＜0.01).bFGF gene expression level in the infarct border zone was significantly higher in the MSC group than in the infarct model and BM-MNC groups (F=4.71,P＜0.01).LVEF was negatively correlated to myocardial cell apoptosis rate and NF-κB level (r=-0.441 1,P＜0.05;r=-0.579 6,P＜0.01 ).LVEF was positively correlated to number of blood vessels,VEGF and bFGF expression (r=0.775,P＜0.01;r=0.565 1,P＜0.05;r=0.573 5,P＜0.05).CONCLUSION:Transplantation of both autologous BM-MNC and MSC via coronary artery can improve the condition of left ventricular remodeling subsequent to myocardial infarction.The improvement of cardiac functions is related to the increase of blood vessels,VEGF and bFGF expression,the decrease of myocardial cell apoptosis and NF-κ B level in cardiac muscle tissues after stem cell transplantation.BM-MNC transplantation better promotes blood vessel proliferation and VEGF expression in the cardiac tissue but produces worse effects on bFGF gene expression than MSC transplantation.
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Objective To investigate the factors and rate of the forming of the collateral feeding arteries from inferior phrenic artery(IPA) in hepatocellular carinoma(HCC).Methods IPA was demonstrated on angiographs in 137 patients with HCC during transcatheter arterial chemoembolization(TACE),TACE was performed through diaphragmatic inferior artery(DIA) super setectively.Results Of 137 cases,21 cases underwent TACE through DIA(15.3%),of them 2 cases were recurrent after surgical operation(9.5%),3 cases had the tumor receive blood supply from IPA at first TACE(14.3%) and 16 cases were occured after TACE tow and more times(76.2%).Conclusion Collateral branches originated from IPA are important feeding arteries in HCC,TACE of IPA can be performed with a high success rate without major complications.
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Objective To find out the appropriate bedbound period after Coronary Arteriography (CAG) in order to reduce the complications and uncomfort caused by prolonged Bedbound period and affected limb immobilization.Methods 121 cases of CAG patients were randomly divided into the reduced period group (experiment group) and the conventional group (the control group),two ways of nursing and observation respectively.Result the rate of complication occurred in the experiment group much less than that of in the control group and the bedbound period were different as well.The above items showed statistics significance (P<0.005～0.05).Conclusion The reduced bedbound period decreases the suffering of CAG patients and provides the reliable clinical evidence for proper nursing approach in this field.