Objective: To investigate the effects of glucagon-like peptide-1(GLP-1)on high glucose-induced apoptosis of human umbilical vein endothelial cells (HUVECs) and the mechanism involved. Methods: HUVECs were cultured under varying conditions for 48 h, and the cell viability was spectrophotometrically measured by MTT assay. Flow cytometry detected the ratio of cell apoptosis. Western blot detected the protein levels of p-Akt and p-eNOS, while NO assay kit detected the NO concentration.
Results: Treatment of high glucose (33 mmol/L) for 48 h signiifcantly decreased the HUVECs viability and induced the apoptosis of HUVECs, concomitant with decreased Akt and eNOS phosphorylation leves and subsequent NO production. Treatment with GLP-1 (3 nmol/L) for 48 h in the high glucose group increased the HUVECs viability (P<0.01), decreased the ratio of HUVECs early apoptosis (P<0.05), ameliorated the reduced protein levels of p-Akt and p-eNOS caused by high glucose, and increased the NO production (P<0.05). The anti-apoptotic effect and the increased NO production of GLP-1were inhibited by PI3K inhibitor wortmannine (100 nmol/L) or eNOS inhibitor L-NAME (100μmol/L). The effect on p-Akt, p-eNOS of GLP-1 was inhibited by wortmannine (100 nmol/L) while L-NAME (100μmol/L) did not have any influence on the expression of p-Akt.
Conclusion: GLP-1 can ameliorate high glucose-induced HUVECs apoptosis, which is probably related to the up-regulation of PI3K/Akt/eNOS pathway.

Objective To explore the relationship of apolipoprotein E(ApoE) and its gene polymorphism with phlegm and blood stasis syndrome in patients with coronary heart disease(CHD).Methods Ninety-seven qualified CHD patients involving phlegm syndrome(PS),blood-stasis syndrome(BSS),and phlegm and blood stasis syndrome(PBSS) were adopted.Thirty-five healthy volunteers were enrolled into the control group.Serum ApoE level was examined in all of the subjects,and their whole blood DNA were extracted for the detection of ApoE gene polymorphism by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP).Correlation analysis of the data was performed with SPSS11.0 software.Results The difference of diabetes mellitus,smoking,low-density lipoprotein cholesterol(LDL-C) and high-density lipoprotein cholesterol(HDL-C) was significant between CHD patients and healthy volunteers(P

Objective To explore the relationship between acute coronary syndrome(ACS) and inflammation , and to observe the short-term effect of Xiangdan Injection(XI) in treating ACS and on inflammatory markers.Methods One hundred and twenty cases of ACS were randomized into two groups: 90 cases in treatment group and 30 in control group. All of the patients received the routine treatment, and the treatment group treated with XI additionally. The therapeutic effect was observed and plasma contents of inflammatory markers such as C-reactive protein (CRP), interleukin 6 (IL-6) and tumor necrosis factor ?(TNF-?) were detected before and after treatment.Results The effect of treatment group was better than that of the control group(P

Objective To investigate the effect of erythropoietin on the proliferation,differentiation,and apoptosis of the cultured neonatal porcine islet cells in vitro.Methods Neonatal porcine islet cells were separated and pured from neonatal pigs with collagenase digestion and tissue culture,and their viability and purity were tested. The neonatal porcine islet cells were divided into a control group and an experimental group.The experimental group was treated with erythropoietin but not the control group,and the insulin secretion responsiveness induced by low and high glucose stimulation in the islet was tested after 5 days. Cells were counted and the activation of amplification was determined by MTT chromatometry. The rates of cell apoptosis were observed by ethidium bromide/acridine orange (EB/AO) of fluorescent light staining and flow cytometry,and the cell cycle was analyzed by flow cytometry. The expression of bcl-2,bax,caspase-3,glucose transporter 2 (GlUT-2),and pancreatic duodenal homeobox-1 (PDX-1) mRNA was tested by RT-PCR.Results After erythropoietin was treated in the cell culture,the neonatal porcine islet cells had normal morphology,function,and reaction of insulin secretion to the glucose stimulation. Cell count showed more cells in the experimental group than in the control group (P＜0.05). MTT chromatometry showed the optical absorbance tended to increase with time,and compared with the control group,the optical absorbance was higher in the experimental group (P＜0.05),the expression of PDX-1 mRNA was slightly up-regulated (P＜0.05). The expression of GLUT-2 mRNA had no difference in the 2 groups (P=0.34). In the experimental group,the apoptisis rate was lower than that in the control group by flow cytometry and EB/AO fluoscence staining (P＜0.01),and the expression of bcl-2 mRNA was higher. Howerer bax mRNA and caspase-3 mRNA were obviously lower than those in the control group (P＜0.01).Conclusion Erythropoietin can promote the proliferation but has no effect on the function of neonatal porcine islet cells in vitro. Erythropoietin can protect neonatal porcine islet cells from apoptosis through up-regulating bcl-2 mRNA and downreguling bax and caspase-3 mRNA.

[Objective] To observe the preventive effect and mechanism of heat-clearing and toxicity-removing therapy for the treatment of acute coronary syndrome (ACS), and to explore the relationship of ACS with inflammation. [Methods] Fifty five ACS patients were randomized into 2 groups:41 patients in group A were treated with Sanhuang Tablets (mainly composed of Radix et Rhizoma Rhei, Radix Scutellariae and Rhizoma Coptidis) p.o., 4 tablets one time, twice a day, and a routine treatment for anticoagulation, anti-platelet aggregation and anti-myocardial ischemia; 14 patients in group B were given routine treatment for anticoagulation, anti-platelet aggregation and anti-myocardial ischemia. The treatment course lasted 2 weeks. After treatment, improvement in symptoms such as chest pain, chest distension, short breath, palpitation, fever, spontaneous sweating, insomnia, lassitude, aversion to cold and cold limbs was compared between group A and group B by scoring method. Meanwhile, inflammatory indicators in the two groups were also observed before and after treatment. [Results] The decrease in symptom scores, as well as the decrease in blood C-reactive protein (CRP) , tumor necrosis factor a (TNF-?) and interleukin 6 (IL-6) , was obvious in group A than that in group B (P

Two patients with primary hypertrophic osteoarthropathy (PHO) and their available healthy family members were studied.All exons of the SLCO2A1 and HPGD gene and adjacent exonintron sequences were amplified by PCR and subsequently sequenced.To assess the damaging effects of missense mutations in silico,the online database,PolyPhen-2 and SIFT were used.We identified two homozygous mutations in SLCO2A1 gene:one was c.1106G＞A (p.G369D) in exon 9,the other was c.611C＞T (p.S204L) in exon 4.No HPGD mutation was found in the affected individuals.The two mutation were predicted in silico by the bioinformatic tools.Our study further supports the role of mutations in the SLCO2A1 gene in the pathogenesis of PHO.Identification of the genotype in PHO may not only help the clinical diagnosis of PHO but also help the interpretation of genetic information for prenatal diagnosis and genetic counseling.

OBJECTIVE: To investigate the effect and mechanism of glucagon like peptide 1(GLP-1)on the proliferation and differentiation of endothelial progenitor cells(EPCs)derived from the peripheral blood. METHODS: Mononuclear cells were isolated from human peripheral blood by density gradient centrifugation. After 7 days of culture,attached cells were stimulated with different cultures of 0.2% BSA,and GLP-1(1,10,and 20 nmol/L). Laser scanning confocal microscope was used to determine the EPCs from human peripheral blood.The activity of EPCs was observed under reverse microscope. MTT was used to determine the proliferation of EPCs. The expression of KDR,Flt-1,VE-cadherin,and eNOS mRNA was detected by RT-PCR.The concentration of serum VEGF was detected by ELISA. The expression of VEGF protein was detected by immunohistochemical SP method. The EPCs cultured in GLP-1 were intervened by VEGFmAb. RESULTS: EPCs was proliferated more in the GLP-1 group(1,10,and 20 nmol/L) than in the control group (P<0.05 or P<0.01). The expression of KDR,FLT-1,VE-cadherin,eNOS mRNA and VEGF protein was higher than that in the control group(P<0.05 or P<0.01). VEGFmAb(100 ng/mL)down-regulated the expression of KDR,Flt-1,VE-cadherin,and eNOS mRNA. CONCLUSION GLP-1 can promote the proliferation and differentiation of EPCs derived from the peripheral blood by up-regulating VEGF autocrine.
Cell Differentiation ; drug effects ; Cell Proliferation ; drug effects ; Endothelial Cells ; cytology ; Glucagon-Like Peptide 1 ; pharmacology ; Humans ; Leukocytes, Mononuclear ; cytology ; Stem Cells ; cytology ; metabolism ; Vascular Endothelial Growth Factor A ; genetics ; metabolism

OBJECTIVE: To investigate the change in serum visfatin level after laparoscopic Roux-en-Y gastric bypass surgery in patients with Type 2 diabetes mellitus (T2DM) and to explore the relationship between visfatin insulin resistance and diabetes. METHODS: Thirty-three patients with Type 2 diabetes were studied before and after the gastric bypass surgery. The level of fasting serum visfatin was measured by enzyme-linked immunosorbent assay. Fasting plasma glucose (FPG), glycated hemoglobin (HbA1c) and fasting insulin (FINS) were measured before and after the gastric bypass surgery. RESULTS: Compared with before the operation, the indicators of HbA1c, FINS, and insulin resistance index (HOMA-IR) were decreased after the laparoscopic Roux-en-Y gastric bypass surgery. The body mass index (BMI) [(24.53 ± 0.62) kg/m² vs (26.71 ± 0.69) kg/m2] was decreased, with significant difference (P<0.001). The serum visfatin level [(9.79 ± 0.64) ng/mL] was significantly lower than before the operation [(38.24 ± 5.32) ng/mL], with significant difference (P<0.001). CONCLUSION Serum level of visfatin is decreased in T2DM patients who undergo gastric bypass surgry, reflecting an improvement in insulin resistance and diabetes.
Diabetes Mellitus, Type 2 ; blood ; surgery ; Female ; Gastric Bypass ; Humans ; Insulin Resistance ; Laparoscopy ; Male ; Middle Aged ; Nicotinamide Phosphoribosyltransferase ; blood ; Postoperative Period

OBJECTIVE: To explore the eff ect of silibinin on β cells in C57BL/6J mice fed a high-fat diet and the possible mechanisms. METHODS: A total of 18 male C57BL/6J mice at 3 weeks old were divided into a normal chow group (n=6), a high-fat diet group (n=6) and a high-fat diet plus silibinin group (n=6). Aft er intervention for 10 weeks, fasting blood glucose (FBG), fasting insulin (FINS), triglycerides (TG), alanine aminotransferase (ALT), creatinine (Cr) and blood urea nitrogen (BUN), lipid metabolism, antioxidant enzyme activities and apoptosis were evaluated. Pancreatic tissues were isolated to examine insulin-induced gene-1 (Insig-1), sterol regulatory element binding protein-1c (SREBP-1c) and fatty acid synthetase (FAS) mRNA and protein expression. RESULTS: Compared with the high-fat diet group, the function of insulin secretion was improved, and the level of blood glucose was decreased in the high-fat diet plus silibinin group (P<0.05). The levels of lipid content and oxidative stress and the rates of β cell apoptosis were lower in high-fat diet plus silibinin group than those in the high-fat diet group (both P<0.05). Simultaneously, the silibinin could promote the expression of Insig-1 and depress the expression of SREBP-1c and FAS (all P<0.05). Moreover, there was no significant difference in the levels of serum ALT, Cr and BUN among the 3 groups (all P>0.05). CONCLUSION Silibinin can protect β cells of mice fed a high-fat diet, and this effect might be related to, at least partially, increase in its antioxidative ability through regulation of insig-1/SREBP-1c pathway. Moreover, silibinin is safe for long-term treatment.
Alanine Transaminase ; blood ; Animals ; Apoptosis ; Blood Glucose ; analysis ; Blood Urea Nitrogen ; Creatinine ; blood ; Diet, High-Fat ; Fatty Acid Synthases ; metabolism ; Insulin ; blood ; Insulin-Secreting Cells ; cytology ; drug effects ; Lipid Metabolism ; Lipids ; Male ; Membrane Proteins ; metabolism ; Mice ; Mice, Inbred C57BL ; Oxidative Stress ; Silybin ; Silymarin ; pharmacology ; Sterol Regulatory Element Binding Protein 1 ; metabolism ; Triglycerides ; blood

Tumor-induced osteomalacia(TIO)is a rare paraneoplastic syndrome in which tumor-induced osteochondrosis is a metabolic bone disease caused by increased renal excretion of phosphorus due to excessive secretion of fibroblast growth factor 23(FGF23)by tumor tissue.We report here a rare case of TIO in which the tumor was found in the hyoid body and the patient had tertiary hyperparathyroidism.The patient's symptoms did not improve after removal of the tumor from the hyoid body,and the patient's hypophosphatemia was gradually improved after subsequent removal of the left parathyroid gland.TIO derived from the tongue tumor is very rare,and also subsequent tertiary hyperparathyroidism is even rarer.This report helps to improve the understanding of TIO and provides reference in the diagnosis and treatment of TIO.