The effects of bariatric surgery on cognition in patients with obesity: a systematic review and meta-analysis.

Obesity impairs cognition. Bariatric surgery can result in substantial weight loss in patients with severe obesity; however, the impact of bariatric surgery on cognitive function remains controversial. To quantify the effect of bariatric surgery on cognition in patients with severe obesity, we performed a meta-analysis of 20 studies retrieved from PubMed, Cochrane, and Embase. Of these, 6 cohort studies found that Roux-en-Y gastric bypass leads to better performance for immediate verbal memory function (standardized mean difference [SMD] = .56; 95% confidence interval [CI]: .30-.82, P < .0001; I2 = 0%) and delayed memory function (SMD = .64; 95% CI: .38-.90, P < .00001; I2 = 0%) during in the short term. Similarly, positive impacts on immediate verbal memory function (SMD = .46; 95% CI: .09-.83, P < .00001) and delayed memory function (SMD = .84; 95% CI: .46-1.22, P < .0001) were identified during a long-term follow-up. The Roux-en-Y gastric bypass group showed no improvements in attention, cognitive speed, and executive function compared with the control obese group. In 14 longitudinal studies (12 single-arm pre-post comparison studies and 2 cohort studies whose control group had no follow-up cognitive data), patients performed better postoperatively than preoperatively in all cognitive domains during repeated assessments. The analysis for the 20 operative groups showed that individuals treated with bariatric surgery had higher scores after repeated assessment of most neuropsychological tests except for animal fluency and letter fluency than baseline scores. These findings suggest that patients with severe obesity may obtain immediate verbal and delayed memory function benefits from Roux-en-Y gastric bypass.

The Association of Trp64Arg Polymorphism in the Beta-Adrenergic Receptor With Insulin Resistance: Meta-Analysis.

Background: Insulin resistance is a metabolic disorder that occurs in type 2 diabetes mellitus and obesity. Genetic factors such as ß3-adrenoceptor polymorphism (Trp64Arg) may be involved in IR and insulin secretion. However, their association is controversial. Therefore, the current meta-analysis was conducted to clarify the relationship between the Trp64Arg and IR. Methods: The literature search was performed in PubMed, Embase, and Web of Science using the keywords "Receptors, Adrenergic, beta-3, Receptors, Adrenergic, Insulin Resistance, Protein-Coupled Receptor Kinase 3" from 2005 to February 7, 2021. We used a random-effects model to calculate the pooled effect size. We conducted subgroup analysis and regression analysis to identify sources of heterogeneity; and Egger's test and funnel plot were used to test publication bias. Finally, we conducted a sensitivity analysis. Results: We included eight papers with 1,586 subjects. There was a positive correlation between Trp64Arg mutation and insulin level (standardized mean difference = 0.20, 95% confidence intervals: 0.00 to 0.39, I2 = 57.6%, p = 0.016). However, there was no association between Trp64Arg and the homeostasis model (HOMA-IR) assessment. Egger's tests showed no publication bias; the sensitivity analysis showed that our results were stable. Regression analysis revealed no source of heterogeneity. Conclusion: Trp64Arg may be associated with IR. European ancestry, obesity, plasma insulin level, and test status may be potential factors affecting the relationship between Trp64Arg and IR.

The effects of bariatric surgery on dyslipidemia and insulin resistance in overweight patients with or without type 2 diabetes: a systematic review and network meta-analysis.

Obesity has become an epidemic in several regions globally; it may lead to cardiovascular diseases, diabetes, and dyslipidemia. Despite many therapies, all bariatric procedures fail in some patients. There is a lack of literature comparing treatment effects on specific metabolic indexes. PubMed, Embase, and Cochrane Central Register of Controlled Trials were searched for relevant articles. GeMTC and R software were used to perform a network meta-analysis, draw forest plots, investigate the possibility of statistical heterogeneity, generate I2 statistics, rank probabilities, and evaluate relative effects of surgical procedures. All analyses were based on a Bayesian consistency model. We included 35 randomized controlled trials, comprising 2198 individuals and 13 interventions. For patients with high insulin resistance, single-anastomosis (mini-) gastric bypass (SAGB) and sleeve gastrectomy (SG) may be effective options, with mean differences (95% confidence intervals [CIs]) of -4.45 (-9.04 to -.34) and -4.23 (-6.74 to -2.22), respectively, compared with control groups. For patients with severe dyslipidemia, in addition to SAGB and SG, duodenal switch (DS) may be an effective surgery, with mean differences (95% CIs) of -.97 (-1.39 to -.55), -1.98 (-3.76 to -.19), .53 (.04 to 1.04), and -.94 (-1.66 to -.16) compared with control groups in terms of triglycerides, total cholesterol, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) concentrations, respectively. In adult overweight patients with or without diabetes, SAGB and SG are most effective at ameliorating insulin resistance. SAGB, Roux-en-Y gastric bypass + omentectomy, and DS are useful for reducing triglycerides, total cholesterol, and LDL-C. SG + omentectomy elevates HDL-C concentrations best. Adjustable gastric band and biliopancreatic diversion may not control insulin resistance or dyslipidemia well.

Carboxyethyltin and transition metal co-functionalized tungstoantimonates composited with polypyrrole for enhanced electrocatalytic methanol oxidation.

Carboxyethyltin and first-row transition metals (TMs) were firstly introduced into trivacant Keggin-type tungstoantimonate in an aqueous solution, leading to the formation of four crystalline organic-inorganic hybrid sandwich-type polyoxometalates (POMs), formulated as Na10-x-yKyHx[((TM)(H2O)3)2(Sn(CH2)2COO)2(SbW9O33)2]·nH2O (SbW9-TM-SnR, TM = Mn, Co, Ni, Zn; x = 1, 1, 0, 0; y = 0, 5, 5, 2; n = 18, 24, 24, 22, respectively). SbW9-TM-SnR exhibit high catalytic ability for the oxidation of cyclohexanol. Meanwhile, SbW9-TM-SnR were composited with polypyrrole (PPy) through an electropolymerization process, forming PPy-SbW9-TM-SnR, on which platinum (Pt) was further electro-deposited to prepare PPy-SbW9-TM-SnR/Pt for electrocatalytic methanol (CH3OH) oxidation in acid solution. The composition and morphology of PPy-SbW9-TM-SnR/Pt were determined by IR, scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS) and X-ray photoelectron spectroscopy (XPS). The electrochemical experimental results show that SbW9-TM-SnR and PPy obviously enhance the electrocatalytic and anti-intoxication abilities of Pt, and the highest peak current density of 0.87 mA cm-2, corresponding to 1.85 and 1.43 times higher than those of pure Pt and PPy/Pt electrodes respectively, is acquired for the PPy-SbW9-Ni-SnR/Pt composite electrode. These findings may enlarge the application of PPy and POMs in the electrocatalytic field.

Anticancer activity of sesquiterpenoids extracted from Solanum lyratum via the induction of mitochondria-mediated apoptosis.

Sesquiterpenoids are a major type of compound found in Solanum lyratum (S. lyratum). The present study aimed to investigate whether sesquiterpenoids from S. lyratum demonstrated cytotoxicity against the MCF-7, HCT-8, A-549, SGC-7901 and BEL-7402 cell lines, and the mechanism of solajiangxin H and lyratol D, which exhibited high cytotoxicity against SGC-7901 cells (half maximal inhibitory concentration, IC50=4.8 and 5.9 µg/ml), was associated with mitochondria-mediated apoptosis. The results of the Cell Counting Kit-8 assay indicated that 15 sesquiterpenoids had cytotoxicity against the aforementioned cultured cells. The results of DAPI staining and western blot analysis, used to study the anticancer mechanisms of solajiangxin H and lyratol D in SGC-7901 cells, suggested that solajiangxin H and lyratol D induced the apoptosis of SGC-7901 cells significantly (P<0.01), downregulated the expression of the antiapoptotic proteins B-cell lymphoma (Bcl)-2 and survivin, and upregulated the expression of the proapoptotic proteins Bcl-2-like protein 4, second mitochondria-derived activator of caspase, cleaved (c)-caspase-3 and c-caspase-9. The present study therefore demonstrated that 15 sesquiterpenoids from S. lyratum exhibited anticancer activity in MCF-7, HCT-8, A-549, SGC-7901 and BEL-7402 cells, and that the anticancer mechanisms of solajiangxin H and lyratol D may be associated with mitochondria-mediated apoptosis. Additionally, the present study provides evidence in support of the hypothesis that S. lyratum may be a promising candidate for the development of novel cancer therapies.

[HPLC specific chromatogram spectrum-effect relationship for Shuanghuanglian on MDCK cell injury induced by influenza A virus (H1N1)].

To establish HPLC specific chromatogram and its correlation with the protection effect of Shuanghuanglian on MDCK (Madin-Darby canine kidney) cell injury induced by influenza A virus( H1N1). Nine recipes of Shuanghuanglian based on the official prescription were prepared according to orthogonal test for HPLC analysis and MDCK cells protection experiment separately (cytopathic effect (CPE) method was used for observing the virus infectivity and MTT staining results were used as the determining indexes for drug concentration selection and analyzing cell viability). The results suggested that all the other Shuang-Huang-Lian recipes except recipe1 demonstrate protecting effect on MDCK cell injury induced by influenza A virus (P < 0.01, P < 0.001). Stepwise regression analysis was used for analyzing the relationships between HPLC fingerprint and the protecting effect of Shuanghuanglian on influenza A virus induced MDCK cell injury. Peak 2, 3, 6, 8 and 12 were found to be strongly related with anti-influenza A virus efficacy. Stepwise regression analysis of recipes data and efficacy data showed that Lonicerae Japonicae Flos and Forsythiae Fructus were positively associated with the protecting effect of cells injury. From HPLC fingerprints, we found that peak 2, 3, 12 were from Lonicerae Japonicae Flos and peak 6, 8 were from Forsythiae Fructus. Four peaks were identified through comparing the retention time between the standard and Shuanghuanglian recipes, and they were chlorogenicacid, cryptochlorogenic acid, forsythoside B and 3,4-dicaffeoylquinic acid respectively. Caffeic acid derivatives in Lonicerae Japonicae Flos and Forsythiae Fructus were found to be greatly correlated with anti-influenza A virus efficacy and maybe the substance basis of Shuanghuanglian.

Effect of various absorption enhancers based on tight junctions on the intestinal absorption of forsythoside A in Shuang-Huang-Lian, application to its antivirus activity.

BACKGROUND: Forsythoside A (FTA), one of the main active ingredients in Shuang-Huang-Lian (SHL), possesses strong antibacterial, antioxidant and antiviral effects, and its pharmacological effects was higher than that of other ingredients, but the absolute bioavailability orally was approximately 0.72%, which was significantly low, influencing clinical efficacies of its oral preparations seriously. MATERIALS AND METHODS: In vitro Caco-2 cell and in vivo pharmacokinetics study were simultaneously performed to investigate the effects of absorption enhancers based on tight junctions: sodium caprate and water-soluble chitosan on the intestinal absorption of FTA, and the eventual mucosal epithelial damage resulted from absorption enhancers was evaluated by MTT test and morphology observation, respectively. The pharmacological effects such as antivirus activity improvement by absorption enhancers were verified by MDCK damage inhibition rate after influenza virus propagation. RESULTS: The observations from in vitro Caco-2 cell showed that the absorption of FTA in SHL could be improved by absorption enhancers. Meanwhile, the absorption enhancing effect of water-soluble chitosan may be almost saturable up to 0.0032% (w/v), and sodium caprate at concentrations up to 0.64 mg/mL was safe, but water-soluble chitosan at different concentrations was all safe for these cells. In pharmacokinetics study, water-soluble chitosan at dosage of 50 mg/kg improved the bioavailability of FTA in SHL to the greatest extent, and was safe for gastrointestine from morphological observation. Besides, treatment with SHL with water-soluble chitosan at dosage of 50 mg/kg prevented MDCK damage after influenza virus propagation better significantly than that of control. CONCLUSION: Water-soluble chitosan at dosage of 50 mg/kg might be safe and effective absorption enhancer for improving the bioavailability of FTA and the antivirus activity in vitro in SHL.

Benazepril inhibited the NF-κB and TGF-ß networking on LV hypertrophy in rats.

PURPOSE: Benazepril, an angiotensin-converting enzyme (ACE) inhibitor, has been used to treat hypertension, congestive heart failure, and chronic renal failure. However, its biological activity and mechanism of action in inflammation are not fully identified. The present study was designed to determine the in vivo anti-inflammatory effects of benazepril on LV hypertrophy in rats. METHODS: LV hypertrophy was produced in rats by abdominal aortic coarctation. They were then divided into the following groups: sham operation; LV hypertrophy; LV hypertrophy+benazepril (1mg/kg in a gavage, once a day for 4 weeks). Both morphological assays (hemodynamic and hemorheological measurement; LV hypertrophy assessment), and molecular assays (protein levels of Collagen type I/III, TNF-α and VCAM-1; TGF-ß gene expression; NF-κB or Smad activation; intracellular ROS production) were performed. RESULTS: The following effects were observed in rats treated with benazepril: (1) marked improvements in hemodynamic and hemorheological parameters; (2) significant reductions in LV hypertrophy, dilatation and fibrosis; (3) significantly attenuated protein levels of Collagen type I/III, TGF-ß, TNF-α and VCAM-1, NF-κB or Smad activation, as well as intracellular ROS production. CONCLUSIONS: These results suggest that the anti-inflammatory properties of benazepril may be ascribed to their down-regulation of both NF-κB and TGF-ß signaling pathways by acting on the intracellular ROS production in rats with LV hypertrophy, thus supporting the use of benazepril as an anti-inflammatory agent.

[Effects of guanxinping tablet containing serum on H2O2-induced apoptosis and NF-kappaB expressions in vascular endothelial cells].

OBJECTIVE: To study the effects of Guanxinping Tablet (GT) containing serum on H2O2-induced apoptosis and the nuclear factor kappa B (NF-kappaB) expression in vascular endothelial cells (VECs). METHODS: Rabbits were randomly divided into the normal control group (treated with normal saline, 10 mL/kg), the verapamil group (0. 02 g/kg, 10 mL/kg), the small dose GT group (2; 8 g/kg, 10 mL/kg), the middle dose GT group (5.6 g/kg, 10 mL/kg), and the large dose GT group (11.2 g/kg, 10 mL/kg), 3 in each group. The medication was given to rabbits by gastrogavage for 3 successive days. The gastrogavage was performed twice on the last day with an interval of 2 h. One h after the last medication the peripheral blood was sampled from the vein of the ear edge. The blood was put for 1 h and centrifuged at 2 500 r/min for 30 min. The serum was extracted and deactivated at 56 degrees C for 30 min to prepare the drug containing serum. The apoptosis injury model was established using 100 micromol/L H2O2 induced VECs in the log phase growth. After modeling they were divided into 6 groups, 5 samples in each group, i. e., the normal group (10% vehicle serum culture solution), the model group (10% vehicle serum culture solution +100 micromol/L H2O2), the verapamil group (10% verapamil serum culture solution +100 micromol/L H2O2), the low dose GT group (10% low dose GT culture solution +100 micromol/L H2O2), the middle dose GT group (10% middle dose GT culture solution + 100 micromol/L H2O2), and the high dose GT group (10% high dose GT culture solution + 100 micromol/L H2O2). THE VEC apoptotic rate was detected using flow cytometry. The protein expression of NF-kappaB was detected using Western blot. RESULTS: The VEC apoptosis rate (9.00% +/- 1.18%) and the protein expression of NF-kappaB (0.39% +/- 0.06%) increased more in the model group than in the normal control group (P<0.01). Compared with the model group, the VEC apoptosis rate of the verapamil group (6.00% +/- 0.18%), the large dose GT group (5.30% +/- 0.08%), and the middle dose GT group (6.83% +/- 0.51%) were obviously lower. The expression of NF-kappaB of each treatment group significantly decreased (the verapamil group: 0.28% +/- 0.03%; the small dose GT group: 0.33% +/- 0.03%; the middle dose GT group: 0.30% +/- 0.03%; the large dose GT group: 0.28% +/- 0.04%, P<0.01, P<0.05). CONCLUSIONS: GT could fight against H2O2-induced VEC cell apoptosis. Its mechanism might be correlated with regulating the expression of NF-kappaB protein.

CDH1 germline mutation in hereditary gastric carcinoma.

This paper provides a bird's-eye view both in preclinical and clinical aspects of E-cadherin germline gene (CDH1) in gastric cancer patients and their families. E-cadherin, a product of CDH1 gene, belonging to the functionally related trans-membrane glycoprotein family, is responsible for the Ca(2+)-dependent cell-cell adhesion mechanism and contributes to dissociation followed by acquisition of cell motility, which usually occurs in the first step of cancer invasion and metastasis. CDH1 gene germline mutation is common in many types of carcinoma, and occurs very frequent in hereditary gastric carcinoma (HGC) patients and their families. Recently, more and more researches support that E-cadherin plays an important role in the differentiation, growth and invasion of HGC. So it is of great value to clarify its mechanisms both for understanding HGC pathogenesis and for clinical therapy, especially in China, where there are a high risk population of gastric cancer and a high HGC incidence rate. In this paper, recent researches on CDH1 gene mutation, especially its role in tumor genesis and progress of HGC, are reviewed, and advances in evaluation of its mutation status for HGC diagnosis, therapy and prognosis, are also discussed briefly.