ObjectiveTo investigate the effect and mechanism of gastric bypass surgery (GBP) on fasting bloo-glucose (FBG) in type 2 diabetic rats. MethodsThe models of type 2 diabetic rats were induced by stretozotocin and 20 diabetic rats were randomly divided into two groups: diabetes-operation group (DO group, n=10) and diabetes-control group (DC group, n=10). Another twenty normal rats were randomly divided into two groups: normaloperation group (NO group, n=10) and normal-control group (NC group, n=10). The rats underwent GBP in DO group and NO group and sham operation in DC group and NC group. The FBG levels, serum dipeptidyl peptidase Ⅳ (DPPⅣ), and glucagon-like peptide-1 (GLP-1) concentrations of rats in each group were detected before operation and at 72 h, on 1 week, 4 weeks, and 8 weeks after operation. ResultsThe FBG levels of rats before operation were not significantly different between DO group and DC group or between NO group and NCgroup (Pgt;0.05). After operation, the FBG levels of rats in DO group gradually declined, reached the bottom on 4 weeks after operation and rose slightly on 8 weeks; The FBG levels of rats in DO group were lower after operation than before operation (Plt;0.05); After operation the FBG levels of rats in DO group were higher than that in NO group and NC group at the same time point (Plt;0.05); In DC group, the difference of FBG levels of rats at different time point was not statistically significant (Pgt;0.05); The inter-group and intra-group difference of FPG levels of rats for NO group and NC group was not statistically significant (Pgt;0.05). The concentrations of serum DPP-Ⅳ of rats before operation were not significantly different in each group (Pgt;0.05). After operation, the concentrations of serum DPP-Ⅳ of rats in DO group and NO group gradually decreased and markedly lower than that before operation, respectively (Plt;0.05). The concentrations of serum DPP-Ⅳ of rats after operation in DO group and NO group were significantly lower than that at the same time point in DC group and NC group, respectively (Plt;0.05); The intragroup difference of serum DPP-Ⅳ concentrations of rats for DC group and NC group was not statistically significant (Pgt;0.05). The concentrations of serum GLP-1 of rats before operation were not significantly different between DO group and DC group or between NO group and NC group (Pgt;0.05). After operation, the concentrations of serum GLP-1 of rats in DO group and NO group gradually increased, reached the top on 4 weeks after operation and declined slightly on 8 weeks; The concentrations of serum GLP-1 of rats in DO group and NO group were higher after operation than before operation (Plt;0.05);After operation, the concentrations of serum GLP-1 of rats in NO group were higher than that in NC group (Plt;0.05), but the concentrations of serum GLP-1 of rats at different time point in NO group were not different (Pgt;0.05). The intragroup difference of serum GLP-1 concentrations of rats for DC group and NC group was not statistically significant (Pgt;0.05). ConclusionsThere is obvious hypoglycemic effect of GBP on FBG levels of type 2 diabetic rats other than normal rats, in which high secretion of GLP-1 and low secretion of DPP-Ⅳ may be play an important role.
Objective To evaluate the efficacy of recombinant human brain natriuretic peptide (rhBNP) on Chinese patients with congestive heart failure by meta analysis. Methods Both foreign language databases including PubMed, EMbase, The Cochrane Library (Issue 3, 2009) and Chinese databases involving CBM, VIP and CJFD were searched to identify randomized controlled trials (RCTs) that reported the effect of rhBNP on the heart function (left ventricular ejection fraction (LVEF) and the recent level of improvement in cardiac function) and its side effects of Chinese patients with congestive heart failure. Two reviewers assessed the quality of each trial and extracted data independently. The Cochrane Collaboration’s RevMan 4.2.8 software was used for statistical analysis. Results Nineteen RCTs were included, all of which came from internal. The methodological quality of the included studies was good. The baseline data of each trial were comparable. The results of meta-analyses showed: (1) the improvement of LVEF was higher in the rhBNP group than that in the blank control group (WMD=7.22, 95%CI 3.15 to 11.291, P=0.000 5). The level of improvement in cardiac function was better in the rhBNP group than those in the blank control group (OR=5.48, 95%CI 1.61 to 18.65, P=0.007), the nitroglycerin group (OR=3.60, 95%CI 2.02 to 6.41, Plt;0.000 1), and the sodium nitroprusside group (OR=3.21, 95%CI 0.12 to 85.20, P=0.49). The incidence of side effects was lower in the rhBNP group than that in the nitroglycerin group (OR=0.23, 95%CI 0.11 to 0.47, Plt;0.000 1), and the sodium nitroprusside group (OR=0.30, 95%CI 0.11 to 0.82, P=0.02). Moreover, the results of sensitivity analysis were also consistent with the above findings. Conclusion Recombinant human brain natriuretic peptide can effectively improve the hemodynamics and cardiac function level of Chinese population of patients with heart failure. The treatment doses are safe and tolerant, so it is recommended to clinical use.
Objective To investigate immunological therapeutic effect and safety of dendritic cells (DCs) combined with heat shock protein 70 (HSP70)-peptide complex (PC) derived from autogeneic hepatoma tissue. Methods Thirty patients with hepatocellular carcinoma from February 2010 to February 2015 in the Gaochun People’s Hospital of Nanjing and The Third Affiliated Hospital of Nantong University were studied, and subsequently were divided into an immunotherapy group (treated with HSP70-PC/DCs vaccine,n=15) and a chemotherapy group (n=15) according to the prescribed postoperative treatment methods. The levels of T lymphocyte subtypes were assayed by FACS. The toxicity adverse reactions, alpha-fetoprotein (AFP), CA19-9, hepatic tumor recurrence rate, survival rate, and KPS of two groups patients were evaluated and compared between these two groups. Results ① The values of CD3+, CD4+, CD4+/CD8+, and CD3CD56 had no significant differences between the immunotherapy group and the chemotherapy group before treatment (P>0.05), which in the immunotherapy group were significantly higher than those in the chemotherapy group after treatment (P<0.05), and which were significantly higher in the immunotherapy group after treatment as compared with the levels before treatment (P<0.05), and which had no significant differences in the chemotherapy group between after treatment and before treatment (P>0.05). ② Before treatment, the levels of AFP and CA19-9 had no significant differences between the immunotherapy group and the chemotherapy group (P>0.05), which in the immunotherapy group were significantly lower than those in the chemotherapy group after treatment (P<0.05). In the immunotherapy group, the levels of AFP and CA19-9 after treatment were significantly lower than those before treatment (t=2.564，P=0.021；t=2.011，P=0.041), which in the chemotherapy group before treatment were decreased as compared with the levels before treatment (t=2.221,P=0.036;t=2.487,P=0.066). ③ The patients treated with the HSP-PC/DCs vaccines was well tolerated and no obvious toxicity was appeared. ④ All the patients were followed up 5–19 months with median follow-up time of 9 months. The median survival time was 560 d and 436 d in the immunotherapy group and the chemotherapy group, respectively. After treatment, KPS score was significantly higher and recurrence rate was significantly lower in the immunotherapy group as compared with the chemotherapy group (P<0.05). The total survival had no significant difference between the immunotherapy group and the chemotherapy group (P>0.05). Conclusions The preliminary results of limited cases in this study show that HSP70-PC/DC vaccination is safe and effective in treatment of hepatocellular carcinoma, the pulsed DCs are effective in activating specific T-cell responses against hepatocellular carcinoma cells. HSP70-PC/DC vaccine might improve immunity and prevent postoperative recurrence of hepatocellular carcinoma.
Objective To construct a new type of self-assembling peptide nanofiber scaffolds—RGDmx, and to study the cell compatibility of the new scaffolds and the proliferation and chondrogenic differentiation of precartilaginous stem cells(PSCs) in scaffolds. Methods PSCs were separated and purified from newborn Sprague Dawley rats by magnetic activated cell sorting and indentified by immunohistochemistry and immunofluorescent staining. The RGDmx were constructed by mixing KLD-12 and KLD-12-PRG at volume ratio of 1 ∶ 1. PSCs at passage 3 were seeded into the KLD-12 scaffold (control group) and RGDmx scaffold (experimental group). The proliferation of PSCs in 2 groups were observed with the method of cell counting kit (CCK) -8 after 1, 3, 7, and 14 days after culture. The RGDmx were constructed by mixing KLD-12-PRG and KLD-12 at different volume ratios of 0, 20%, 40%, 60%, 80%, and 100% and the prol iferation of PSCs was also observed. The complete chondrogenic medium (CCM) was used to induce chondrogenic differentiation of PSCs in different scaffolds. The differentiation of PSCs was observed by toluidine blue staining and RT-PCR assay. Results PSCs were separated and purified successfully, which were identified by immunohistochemistry and immunofluorescent staining methods. The results of CCK-8 showed that the absorbance (A) value in the experimental group increased gradually and reached the highest at 7 days; the A value in the experimental group was significantly higher than that in the control group at 7 days and 14 days (P lt; 0.05). Meanwhile, the A value in the RGDmx scaffold with a volume ratio of 40% was significantly higher than those in others (P lt; 0.05). After 14 days of induction culture with CCM, the toluidine blue staining results were positive in 2 groups; the results of RT-PCR showedthat the expression levels of collagen type II and the aggrecan in the experimental group were significantly higher than those in the control group (P lt; 0.05). Conclusion The self-assembling peptide nanofiber scaffold—RGDmx is an ideal scaffold for tissue engineer because it has good cell compatibility and more effective properties of promoting the differentiation of PSCs to chondrocytes.
Objective To explore and compare the diagnostic value of blood pressure, brain natriuretic peptide (BNP), pulmonary artery systolic pressure (PASP) in evaluating right ventricular dysfunction (RVD) in patients with acute pulmonary embolism (APE). Methods A retrospective study was conducted on 84 APE patients who were diagnosed by computed tomographic pulmonary angiography. The patients were divided into a RVD group and a non-RVD group by echocardiography. Eighteen clinical and auxiliary examination variables were used as the research factors and RVD as the related factor. The relationship between these research factors and RVD were evaluated by logistic regression model, the diagnostic value of BNP and PASP to predict RVD was analyzed by receiver-operating characteristic (ROC) curve analysis. Results The patients with RVD had more rapid heart rate, higher diastolic blood pressure, higher mean arterial pressure, higher incidence of BNP>100 pg/ml and higher incidence of PASP>40 mm Hg (allP<0 05="" upon="" logistic="" regression="" model="" bnp="">100 pg/ml (OR=4.904, 95%CI 1.431–16.806, P=0.011) and PASP>40 mm Hg (OR=6.415, 95%CI 1.509–27.261, P=0.012) were independent predictors of RVD. The areas under the ROC curve to predict RVD were 0.823 (95%CI 0.729–0.917) for BNP, and 0.798 (95%CI 0.700–0.896) for PASP. Conclusions Blood pressure related parameters can not serve as a predictor of RVD. Combined monitoring of BNP level and PASP is helpful for accurate prediction of RVD in patients with APE.
ObjectiveTo systematically evaluate the effects of weight-loss interventions on hormone levels and sexual function in patients with obesity. MethodsThis review was conducted in accordance with PRISMA guidelines. A systematic search of PubMed, Embase, and other databases was performed for studies published within the past decade that investigated the effects of bariatric surgery, glucagon-like peptide 1 (GLP-1) receptor agonists, and lifestyle interventions on sex hormones and sexual function. ResultsBariatric surgery (e.g., sleeve gastrectomy, gastric bypass) demonstrated the most pronounced improvements in hormonal balance and sexual function. In males, total testosterone levels doubled postoperatively, with marked increase in erectile function score. In females with polycystic ovary syndrome, androgen levels were reduced by 50%, with significant amelioration in the female sexual function index. GLP-1 receptor agonists (e.g., semaglutide, liraglutide) partially improved sperm quality and testosterone levels, but were also associated with a higher risk of erectile dysfunction (with a hazard ratio of approximately 4.5). Lifestyle interventions (e.g., low-calorie diet, exercise) could increase sex hormone-binding globulin levels and improve sexual function score, although their efficacy remained inferior to that of surgery. ConclusionsWeight-loss interventions can alleviate hormonal imbalances and sexual dysfunction in obesity, with bariatric surgery demonstrating the most significant effects. Pharmacological and lifestyle interventions have shown variable efficacy. Future research should further investigate mechanisms underlying effects of different weight-loss modalities on sexual health.
ObjectiveTo compare the effect of ileal transposition (IT) and Roux-en-Y gastric bypass (RYGBP) on blood glucose and expression of glucagon-like peptide-1 (GLP-1) in Goto-Kakizaki (GK) rats with non-obese type 2 diabetes mellitus (T2DM). MethodsThirty male GK rats were randomized divided into three groups:IT group (n=10), RYGBP group (n=10), and Sham group (n=10). The mortality and complication were observed after surgery. The levels of fasting blood glucose (FBG), fasting insulin (FINS), glycosylated hemoglobin (HbA1c), and GLP-1 were determined before operation, and 1 week, 2 weeks, 1 month, 2 months, 3 months, 6 months after operation in the GK rats of 3 groups. Results① Mortality and morbility. There was no death and complication occurred in IT group and Sham group, only 5 rats of RYGBP group suffered from complication, and 2 of them died. The mortality and morbility were higher in RYGBP group than those of IT group and Sham group (P < 0.05). ② FBG. Compared with before operation in the same group, the FBG levels of IT group and RYGBP group in 1 week, 2 weeks, 1 month, 2 months, 3 months, and 6 months after operation were all lower (P < 0.05). In 1 week, 2 weeks, 1 month, 2 months, 3 months, and 6 months after operation, FBG levels of IT group and RYGBP group were all lower than those of Sham group at the same time point (P < 0.05), but there was no significant difference between IT group and RYGBP group at the 6 time points (P > 0.05). ③ FINS and HbA1c. Compared with before operation in the same group, the FINS levels of IT group and RYGBP group in 3 months and 6 months after operation were higher than those of Sham group (P < 0.05), HbA1c levels of IT group and RYGBP group were both lower at the 2 time points (P < 0.05). In 3 months and 6 months after operation, FINS levels of IT group and RYGBP group were both higher, and HbA1c levels were both lower than corresponding indexes of Sham group at the same time point (P < 0.05), but there was no significant difference between IT group and RYGBP group at the 2 time points (P > 0.05). ④ GLP-1. Compared with before operation in the same group, the GLP-1 levels of IT group and RYGBP group in 1 week, 2 weeks, 1 month, 2 months, 3 months, and 6 months after operation were all higher (P < 0.05). In 1 week, 2 weeks, 1 month, 2 months, 3 months, and 6 months after operation, GLP-1 levels of IT group and RYGBP group were both higher than those of Sham group at the same time point (P < 0.05), but there was no significant difference between IT group and RYGBP group at the 6 time points (P > 0.05). ConclusionIT and RYGBP have a significant hypoglycemic effect on non-obese T2DM GK rats, but IT has lower mortality and morbility, which is more effective and safer, comparing with RYGBP.
Obesity is a chronic metabolic disease driven by multiple factors such as genetic susceptibility, environmental factors, and neuroendocrine system disorders. In recent years, the prevalence of obesity in China has been increasing year by year, and a series of obesity-induced diseases are a serious threat to public health. Glucagon-like peptide-1 receptor agonists, as a representative of the new weight loss drugs, have shown a therapeutic effect close to that of weight-loss metabolic surgery in clinical trials by targeting central appetite and metabolism and other synergistic effects, but they still face key problems such as significant differences in individual efficacy, limited evidence of the safety of long-term treatment, and regaining body weight after discontinuation of the drug. The mechanism of action and clinical evidence of several obesity drugs approved and listed in China are summarized, and the progress and challenges of obesity drug therapy in China in combination with recent advances in the development of multi-target agents internationally are discussed, with a view to providing a scientific basis for the clinical drug management of obesity and providing ideas for the research and development of obesity drugs in China as well as for the clinical transformation.
We present the binding ability of a new peptide (-CMPQVMPMC-) with dental enamel after being evaluated in the present study. Under a standard procedure, the recovery of M13 filamentous phage was greatly enhanced by displaying the peptide in phage coat protein pⅢ. Then the cyclic peptide was synthesized using a solid method. The effect of the cyclic peptide in vitro biomineralization was tested in a single-diffusion microtiter plate gel system. Absorbance at 405 nm of each sample was recorded for 24 h at every 6 h intervals. The relatively increased values of each sample were expressed as percentages relative to the blank group (100%). The cyclic peptide resulted in a concentration-dependent delayed nucleation. In addition, the overall values of peptide groups at the end of 24 h were lower than those in the control group but much higher than those in the BSA control group.
Objective To investigate and analyze the relationships among glucagon-like peptide-1 (GLP-1) level, chronic inflammation, and atherosclerosis in patients with non-alcoholic fatty liver disease (NAFLD). Methods From October 2016 to February 2017, using cross-sectional investigation, the GLP-1 level, chronic inflammation, and atherosclerosis were investigated in 80 subjects (40 NAFLD patients in NAFLD group, and 40 non-fatty liver disease participants in control group) who underwent physical examination at Xi’an Road Community Hospital. Results Compared with those in the control group, GLP-1 fasting level in patients with NAFLD [(9.09±1.03) vs. (9.15±1.06) pmol/L, P=0.807] and postprandial plasma GLP-1 [(15.96±3.37) vs. (17.46±4.76) pmol/L, P=0.108] had no changes. The correlations of GLP-1 level with chronic inflammation and insulin resistance (IR) were not significant either. The increased risk of carotid intima-media thickness related cardiovascular disease (CVD) in the NAFLD group was greater than that in the control group, and the difference was statistically significant [22 (55.0%)vs.13 (32.5%), P=0.043]. When the plasma lipoprotein-associated phospholipase A2 level increased, the risk of NAFLD increased [odd ratio (OR)=1.16, 95% confidence interval (CI) (1.02, 1.32), P=0.023]. Plasma ceramide kinase (CERK) in the NAFLD group was lower than that in the control group, and the difference was statistically significant [(12.36±2.45) vs. (18.33±3.71) ng/mL, P<0.001]. When the plasma CERK level of the fasting plasma was elevated, the risk of NAFLD decreased [OR=0.30, 95%CI (0.12, 0.78), P=0.014]. The homeostasis model assessment of insulin resistance (HOMA-IR) in the NAFLD group was higher than that in the control group, and the difference was statistically significant (2.46±2.53 vs. 1.11±0.66, P=0.002). The Matsuda index in the NAFLD group was less than that in the control group, and the difference was statistically significant (5.88±4.09 vs. 10.46±7.90, P=0.002). When HOMA-IR increased, the risk of NAFLD increased [OR=2.75, 95%CI (2.49, 3.12), P=0.036]. Conclusions Plasma GLP-1 level is not a sensitive indicator of chronic inflammation and IR in patients with NAFLD. Patients with NAFLD are in an increased risk of atherosclerosis and CVD. It suggests that NAFLD might be involved in chronic inflammation and IR. Chronic inflammation can cause IR, and then chronic inflammation and IR can cause NAFLD and subclinical atherosclerosis. In return for this, NAFLD increases chronic inflammation and IR.