Effect of Semaglutide on High-Fat-Diet-Induced Liver Cancer in Obese Mice.

This study aims to investigate the impact of semaglutide on the expression of liver cancer proteins in obese mice induced by a high-fat diet. Sixteen obese mice were randomly divided into two groups: the high-fat diet group and the semaglutide group, each consisting of eight mice. Additionally, eight normal male mice were included as the control group. Serum samples were collected, and a differential expression analysis of total proteins in adipose tissue was performed using quantitative tandem mass spectrometry (TMT) in combination with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Significant differential proteins were identified and subjected to a bioinformatics analysis. The findings revealed that these differential proteins, namely, integrin αV (ITGAV), laminin γ1 (LAMC1), fatty acid-binding protein 5 (FABP5), and lipoprotein lipase (LPL), regulate the occurrence and development of liver cancer by participating in the extracellular matrix (ECM) signaling pathway and the peroxisome proliferator-activated receptor (PPAR) signaling pathway. Notably, semaglutide can decelerate the progression of liver cancer by inducing the expression of ITGAV, LAMC1, FABP5, and LPL in the adipose tissue of obese mice.

Semaglutide ameliorates obesity-induced cardiac inflammation and oxidative stress mediated via reduction of neutrophil Cxcl2, S100a8, and S100a9 expression.

Obesity, which is driven by inflammation and oxidative stress, is a risk factor for cardiovascular disease. Semaglutide, a glucagon-like peptide-1 receptor agonist, is an antidiabetic drug with major effects on weight loss. In this study, single-cell transcriptomics was used to examine non-cardiomyocytes to uncover the mechanism of obesity-induced myocardial damage and the cardioprotective impact of semaglutide. We constructed obese mouse models and measured Tumor Necrosis Factor-α (TNF-α), Interleukin-6 (IL-6), Reactive Oxygen Species (ROS), and Malonic dialdehyde (MDA) levels in serum and heart tissue to determine the levels of inflammation and oxidative stress in obesity and the effect of semaglutide on these levels. Then, utilizing single-cell transcriptomes to screen for key cell populations and differentially expressed genes (DEGs), we assessed the effects of obesity and semaglutide on non-cardiac cells. Finally, a DEG localization analysis was performed to explore DEGs as well as cell types associated with inflammation and oxidative stress. Semaglutide reduced increased TNF-α, IL-6, ROS, and MDA levels in serum and cardiac tissues in obese mouse. Several genes are closely associated with inflammation and oxidative stress. Chemokine (C-X-C motif) ligand 2 (Cxcl2), S100 calcium binding protein A8 (S100a8), and S100 calcium binding protein A9 (S100a9), which were elevated in obesity but decreased following semaglutide treatment, were also expressed particularly in neutrophils. Finally, by decreasing neutrophil Cxcl2, S100a8, and S100a9 expressions, semaglutide may help to reduce cardiac inflammation and oxidative stress. Semaglutide significantly reduced body weight in obese mice as well as exerted anti-inflammatory and antioxidant effects possibly by inhibiting the expression of S100a8, S100a9, and Cxcl2 in neutrophils. These discoveries are expected to reveal new molecular mechanisms underlying obesity-related heart damage and semaglutide's cardioprotective properties.

Triglyceride-glucose index and cervical vascular function: outpatient-based cohort study.

OBJECTIVES: The purpose of this study was to investigate the correlation between triglyceride-glucose (TyG) index and cervical vascular function parameters in the general population without cerebrovascular disease. MATERIALS AND METHODS: This was a cross-sectional study that recruited a total of 1996 participants without cerebrovascular disease. TyG index was calculated based on fasting triglycerides and glucose. All patients were divided into two groups based on the median TyG index: the high TyG group and the low TyG group. The differences in basic clinical characteristics and neck vascular function parameters between the two groups of participants were compared, and then the correlation between TyG index and neck vascular function parameters was investigated. RESULTS: Participants with a high TyG index had lower systolic, diastolic, and mean flow velocities in the basilar, vertebral, and internal carotid arteries compared with those with a low TyG index. Participants with a high TyG index had higher pulsatility index in the left vertebral artery and right internal carotid artery, but this difference was not observed in the basilar artery. In addition, TyG index was significantly negatively correlated with systolic, diastolic, and mean flow velocities in the basilar, vertebral, and internal carotid arteries, and the correlation remained after adjusting for confounding factors. CONCLUSION: In the general population, there was a well-defined correlation between TyG index and cervical vascular function parameters, and increased TyG index was independently associated with reduced cervical vascular blood flow velocity.

The effect of statins on bone turnover biomarkers: a systematic review and meta-analysis of randomized controlled trials.

Few studies have considered the effect of statins on bone turnover biomarker levels and the results of these studies are inconsistent. Here we performed a meta-analysis of the effect of statins on bone turnover biomarker levels. We used keywords, free words, and related words that included the terms "hydroxymethylglutaryl-CoA reductase inhibitors," "statin," and "bone turnover biomarkers" to search PubMed, Cochrane Library, and Embase. The Cochrane Risk Bias Evaluation Tool was used to evaluate the risk of bias, and Review Manager 5.3 and Stata 13.0 were used for statistical analyses. Six randomized controlled trials involving a total of 382 subjects were included in the meta-analysis. The results showed that statins increased the osteocalcin (OC) [mean difference (MD) = 0.73 ng/mL, 95% CI: 0.12, 1.35, I2 = 23% and p = 0.26], and decreased cross-linked N-telopeptide (NTX) (MD = -1.14 nM BCE, 95% CI: -2.21, -0.07, I2 = 0%, p = 0.53) and C-terminal peptide of type I collagen (CTX) (MD = -0.03 ng/mL, 95% CI: -0.05, -0.01, I2 = 0% and p = 0.56). There was no effect on bone-specific alkaline phosphatase (MD = -1.37 U/L, 95% CI: -3.09, 0.34, I2 = 0% and p = 0.94) and intact parathyroid hormone (MD = -1.73 pg/mL, 95% CI: -4.35, 0.89, I2 = 0% and p = 0.77). Statins increase bone formation biomarker OC and decrease bone resorption biomarker NTX and CTX levels.

Independent and combined effects of liraglutide and aerobic interval training on glycemic control and cardiac protection in diabetic cardiomyopathy rats.

OBJECTIVE: This study intended to explore the hypoglycemic and cardioprotective effects of 8-week aerobic interval training combined with liraglutide and elucidate the underlying mechanisms. METHOD: Male Wistar rats were randomly divided into 5 groups - normal control group (CON), diabetic cardiomyopathy group (DCM), high-dose liraglutide group (DH), low-dose liraglutide group (DL), and aerobic interval training combined with liraglutide group (DLE). High-fat diet and streptozotocin (STZ) were used to induce the DCM model, and both the liraglutide administration group and combination therapy group allocated to 8 weeks of either liraglutide or liraglutide and exercise intervention. Cardiac functions were analyzed by electrocardiography. Blood biochemical parameters were measured to judge glycemic control conditions. Hematoxylin and eosin (HE) staining and Sirus red staining was used to identify cardiac morphology and collagen accumulation, respectively. Advanced glycation end products (AGEs) were determined by enzymatic methods. The mRNA expression of myocardial remodeling genes (BNP, GSK3ß, α-MHC, ß-MHC and PPARα) and the protein expression of GLP-1, GLP-1R were analyzed. RESULTS: DCM rats developed hyperglycemia, impaired cardiac function with accumulation of AGEs and collagen (P < 0.05). The development of hyperglycemia and cardiac dysfunction was significantly attenuated with all interventions, as reduced cardiac fibrosis and improved cardiac function (P < 0.05). Cardiac remodeling genes were normalized after all interventions, these positive modifications were due to increased GLP-1 and GLP-1R expression in DCM heart (P < 0.05). Liraglutide combined with AIT significantly increased the diameters of cardiomyocytes, increased the α-MHC expressionx, reduced PPARαexpression and reduced the fluctuation of blood glucose level, which showed the safety and effective of medicine combined with exercise. CONCLUSION: Liraglutide combined with AIT intervention normalized blood glucose alleviates myocardial fibrosis and improves cardiac contractile function in DCM rats, supporting the efficacy and safety of the combination therapy.

Single-cell transcriptomics identifies Col1a1 and Col1a2 as hub genes in obesity-induced cardiac fibrosis.

Obesity is a risk factor for cardiovascular disease, leading to ventricular dysfunction and cardiac fibrosis, in which non-cardiomyocytes (nonCMs) play an important role. Early detection and treatment of heart illness may help to limit its progression. We screened for key markers of obesity-induced cardiac fibrosis using single-cell transcriptomics techniques. To begin, an obese mouse model was constructed using a high-fat diet. From a pathogenic perspective, pathological alterations in the obesity-induced heart were found. Differentially expressed genes (DEGs) were identified and functional enrichment analysis was performed. Then, to look for hub genes, key modules of DEGs were built. Finally, the cellular location of the hub genes was investigated. In mice, a high-fat diet raised body weight, messed up myocardial shape, and increased cardiac collagen content. NonCMs transcriptome data revealed 15 different cell types, including fibroblasts, immunological cells, and endothelial cells. There were a total of 33 DEGs found, with 22 up-regulated genes and 11 down-regulated genes. DEGs have a high connection with collagen and extracellular matrix (ECM), according to functional enrichment analysis. Col1a1 and Col1a2 scored well in module analysis and hub gene screening, and were chosen as hub genes. Col1a1 and Col1a2 were shown to be mostly expressed by fibroblasts after localization study. As a result, we believe Col1a1 and Col1a2 may be important markers of obesity-induced cardiac fibrosis, in which fibroblasts play a critical role.

A metabonomics-based renoprotective mechanism analysis of empagliflozin in obese mice.

With an increasing prevalence of obesity related kidney disease, exploring the mechanisms of therapeutic method is of critical importance. Empagliflozin is a new antidiabetic agent with broad clinical application prospect in cardiovascular and renal diseases. However, a metabonomics-based renoprotective mechanism of empagliflozin in obesity remains unclear. Our results showed that empagliflozin significantly alleviated the deposition of lipid droplet, glomerular and tubular injury. The innovation lied in detection of empagliflozin-targeted differential metabolites in kidneys. Compared with normal control mice, obese mice showed higher levels of All-trans-heptaprenyl diphosphate, Biliverdin, Galabiose, Galabiosylceramide (d18:1/16:0), Inosine, Methylisocitric acid, Uric acid, Xanthosine, O-glutarylcarnitine, PG(20:3(8Z,11Z,14Z)/0:0), PG(20:4(5Z,8Z,11Z,14Z)/0:0), PE(O-16:0/0:0), PG(22:6(4Z,7Z,10Z,13Z,16Z,19Z)/0:0), and lower level of Adenosine. Empagliflozin regulated these metabolites in the opposite direction. Associated metabolic pathways were Phospholipids metabolism, Purine metabolism, and Biliverdin metabolism. Most of metabolites were associated with inflammatory response and oxidative stress. Empagliflozin improved the oxidative stress and inflammation imbalance. Our study revealed the metabonomics-based renoprotective mechanism of empagliflozin in obese mice for the first time. Empagliflozin may be a promising tool to delay the progression of obesity-related kidney disease.

Single-cell transcriptome reveals effects of semaglutide on non-cardiomyocytes of obese mice.

Non-cardiomyocytes (nonCMs) play an important part in cardiac fibrosis pathophysiology, but the underlying molecular pathways are unknown. Semaglutide has cardioprotective properties, but it is still unclear whether it helps with cardiac fibrosis and what the processes are. The goal of this study is to use single cell transcriptomics approaches to investigate the molecular mechanism of semaglutide's cardioprotective action in obese mice. We found 15 non-CMs, with fibroblasts making up the majority of them. We found eight DEGs that altered significantly following semaglutide treatment by screening for differentially expressed genes (DEGs). DEGs were shown to have biological activities primarily related to extracellular matrix and collagen synthesis and distribution, with Serpinh1 and Pcolce expression being the most dramatically altered. Serpinh1 and Pcolce were mostly found in fibroblasts, which play a key role in the fibrosis of the heart. Furthermore, we discovered that semaglutide lowered cardiac collagen content and alleviated obesity-induced ventricular wall hypertrophy. As a result, our findings show that Serpinh1 and Pcolce, which are expressed by fibroblasts, may play a role in the development of obese cardiac fibrosis. By reducing Serpinh1 and Pcolce expression and delaying cardiac fibrosis, semaglutide may have a cardioprotective effect.

Relationship between geriatric nutritional risk index and osteoporosis in type 2 diabetes in Northern China.

BACKGROUND: Osteoporosis is a very common bone disease in the elderly population and can lead to fractures and disability. Malnutrition can lead to osteoporosis. The geriatric nutritional risk index (GNRI) is a tool used to assess the risk of malnutrition and complications associated with nutritional status in older patients and is a crucial predictor of many diseases. Hence, this study investigated the association between the GNRI and the presence of osteoporosis and assessed the value of this index for predicting osteoporosis in patients with type 2 diabetes mellitus (T2DM). METHODS: This cross-sectional study enrolled 610 elderly patients with T2DM. General and laboratory data of the patients were collected, along with their measurements of bone mineral density (BMD). The GNRI was calculated based on ideal body weight and serum albumin (ABL) levels. Correlation analysis was performed to determine the relationship between the GNRI and BMD and bone metabolism indices. The GNRI predictive value for osteoporosis development was analyzed through logistic regression analysis and by creating a receiver operating characteristic curve (ROC), calculating the area under the curve (AUC). RESULTS: All patients were divided into the no-nutritional risk and nutritional risk groups. Compared with the no-nutritional risk group, the nutritional risk group had a longer diabetes course, older age, higher HbA1c levels, higher prevalence of osteoporosis; lower BMI, ABL,triglyceride (TG),Calcium (Ca),25-hydroxy-vitamin-D(25(OH)D),and parathyroid hormone(PTH) and lower femoral neck BMD,total hip BMD (P < 0.05). All patients were also assigned to the non-osteoporosis and osteoporosis groups. The non-osteoporosis group had higher GNRI values than the osteoporosis group (P < 0.05). Correlation analysis revealed a positive correlation between the GNRI and lumbar BMD, femoral neck BMD, and total hip BMD (P < 0.05). After the adjustment for confounding factors, Spearman's correlation analysis revealed that the GNRI was positively correlated with Ca, 25(OH)D, and PTH and negatively correlated with alkaline phosphatase (ALP) and procollagen of type-1 N-propeptide (P1NP). Regression analysis exhibited that the GNRI was significantly associated with osteoporosis. The ROC curve analysis was performed using the GNRI as the test variable and the presence of osteoporosis as the status variable. This analysis yielded an AUC for the GNRI of 0.695 and was statistically significant (P < 0.05). CONCLUSIONS: A lower GNRI among T2DM patients in northern China is associated with a higher prevalence of osteoporosis.

Correlation between Cardiac Ultrasound Index and Cardiovascular Risk in Healthy Obese and Overweight Populations.

Objective: To investigate the correlation of obesity and overweight with cardiac ultrasound parameters and future cardiovascular risk among healthy populations. Methods: Basic clinical characteristics as well as cardiac ultrasound parameters were collected from healthy people. Firstly, all participants were divided into three groups: normal, overweight, and obese. Then the differences in cardiac ultrasound parameters between the three groups were calculated. Subsequently, those aged 35-60 years were screened to determine their cardiovascular risk according to the SCORE system. Finally, the correlation between cardiac ultrasound indices and cardiovascular risk was calculated. Results: A total of 1328 healthy participants were included, of whom 504 were normal, 580 were overweight and 244 were obese. Obesity and overweight significantly increased the aorta, left atrium, right atrium, right ventricle, the end-diastolic diameter of the left ventricle, main pulmonary artery, right ventricular outflow tract, interventricular septum, left ventricular posterior wall, and triglycerides and decreased E/A values and high-density lipoprotein-cholesterol. Ejection fraction, fractional shortening, low-density lipoprotein-cholesterol, and total cholesterol did not change between the three groups. A total of 781 participants were screened for SCORE scores. Obesity and being overweight significantly increased the incidence of future cardiovascular events, and lower E/A values were also associated with cardiovascular risk. All cardiac parameters were strongly associated with cardiovascular risk. Conclusion: Our research demonstrates that obesity and overweight can damage heart shape and function and raise the risk of future cardiovascular events in people that are healthy. Cardiovascular risk and cardiac structural and functional impairments are significantly positively correlated.

Impact of Metabolic Surgery on Gut Microbiota and Sera Metabolomic Patterns among Patients with Diabetes.

Metabolic surgery is a promising treatment for obese individuals with type 2 diabetes mellitus (T2DM), but the mechanism is not completely understood. Current understanding of the underlying ameliorative mechanisms relies on alterations in parameters related to the gastrointestinal hormones, biochemistry, energy absorption, the relative composition of the gut microbiota, and sera metabolites. A total of 13 patients with obesity and T2DM undergoing metabolic surgery treatments were recruited. Systematic changes of critical parameters and the effects and markers after metabolic surgery, in a longitudinal manner (before surgery and three, twelve, and twenty-four months after surgery) were measured. The metabolomics pattern, gut microbiota composition, together with the hormonal and biochemical characterizations, were analyzed. Body weight, body mass index, total cholesterol, triglyceride, fasting glucose level, C-peptide, HbA1c, HOMA-IR, gamma-glutamyltransferase, and des-acyl ghrelin were significantly reduced two years after metabolic surgery. These were closely associated with the changes of sera metabolomics and gut microbiota. Significant negative associations were found between the Eubacterium eligens group and lacosamide glucuronide, UDP-L-arabinose, lanceotoxin A, pipercyclobutanamide B, and hordatine B. Negative associations were identified between Ruminococcaceae UCG-003 and orotidine, and glucose. A positive correlation was found between Enterococcus and glutamic acid, and vindoline. Metabolic surgery showed positive effects on the amelioration of diabetes and metabolic syndromes, which were closely associated with the change of sera metabolomics, the gut microbiota, and other disease-related parameters.

Social interactions upregulate hemolymph tryptophan and tyrosine levels in the male lobster cockroach.

In the present study, we found that tryptophan (TRP) and tyrosine (TYR) levels are increased in hemolymph of male Nauphoeta cinerea after social contact with either male or female conspecifics. Hemolymph was collected from individual males before and after the social interactions, and samples were analyzed by HPLC-ECD; analyte identities were confirmed by UPLC/MS. After a male-male first encounter fight, hemolymph TRP and TYR levels were significantly increased in dominants compared with the levels before the encounter. Conversely, TRP and TYR in subordinates were maintained at levels similar to those before the encounter. While after-fight TRP and TYR levels were significantly higher in dominants than subordinates, no significant differences were found in the contestants before the fight. Moreover, contact with an isolated male antenna was sufficient to stimulate attack behavior and increase hemolymph TRP and TYR titers to levels similar to those seen in dominants. After a male-female interaction, two distinct outcomes could be observed. Either hemolymph TRP and TYR levels were increased in successfully mated males, or TRP and TYR levels were unchanged in males that only exhibited premating wing-raising behavior but failed in mating. After contacting the antenna of a socially naïve male with an isolated female antenna, three patterns of behavior and related amino acid response were observed: 1) only premating wing-raising behavior with significant increase of TRP and TYR levels, 2) only attack behavior with significant increase of TRP and TYR levels, and 3) mixed wing-raising and attack behaviors with no significant changes in TRP and TYR levels. The present results show a robust response of hemolymph TRP and TYR to social contact. In light of previously characterized responses in pheromone and juvenile hormone levels, these amine responses suggest that the physiological response of N. cinerea to social contact is multi-dimensional.

Meta-analysis of the effect of sodium-glucose cotransporter 2 inhibitors on hepatic fibrosis in patients with type 2 diabetes mellitus complicated with non-alcoholic fatty liver disease.

AIM: This study aimed to analyze the effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors on the indexes of liver fibrosis in patients with type 2 diabetes mellitus complicated with non-alcoholic fatty liver disease, and also to observe the effects on liver enzymes and liver fat. METHODS: This meta-analysis was performed using RevMan 5.3 statistical software. RESULTS: SGLT2 inhibitors could significantly reduce the level of hepatic fibrosis index: fibrosis-4 (mean difference [MD] 0.25, 95% CI -0.39 to -0.11, p = 0.0007); serum type â…£ collagen 7s (MD 0.32, 95% CI -0.59 to -0.04, p = 0.02); and ferritin (MD 26.7, 95% CI 50.64, 2.76, p = 0.03). SGLT2 inhibitors could significantly reduce the level of liver enzymes: alanine aminotransferase (MD 3.49, 95% CI -5.1 to 1.58, p < 0.0001); aspartate aminotransferase (MD 3.64, 95% CI -5.10 to -2.18, p < 0.00001); and glutamate aminotransferase (MD 7.13, 95% CI -12.95 to -1.32, p = 0.02). SGLT2 inhibitors could significantly reduce the level of liver fat: liver-to-spleen attenuation ratio (MD 0.16, 95% CI 0.10-0.22, p < 0.00001); magnetic resonance imaging proton density fat fraction (MD 1.97, 95% CI -3.49 to -0.45, p = 0.01); liver controlled attenuation parameter (MD 0.29, 95% CI -26.95 to -13.64, p < 0.00001); liver fat score (MD 0.55, 95% CI 1.04 to -0.05, p = 0.03); and liver fat index (MD 11.21, 95% CI -16.53 to -5.89, p < 0.0001). CONCLUSION: SGLT2 inhibitors could improve liver fibrosis, liver enzymes, liver fat, and metabolic indexes in patients with type 2 diabetes mellitus complicated with non-alcoholic fatty liver disease.

The relationship between vitamin D status and islet function in patients with type 2 diabetes mellitus.

BACKGROUND: The aim of the study was to explore the relationship between vitamin D status and islet function in patients with type 2 diabetes mellitus. METHODS: The participants were recruited from Hebei General Hospital. Basic characteristics and blood indicators were collected after fasting overnight. The data were analyzed statistically using SPSS 22.0. Analysis of variance, a nonparametric test, or a trend Chi-square test was used for the comparisons. The association between 25-hydroxy vitamin D and modified homeostasis model assessment-ß was assessed using multivariate ordinal logistic regression. RESULTS: One hundred seventy-four patients aged 26 to 79 years with type 2 diabetes mellitus were included in this study. Patients with vitamin D deficiency had a lower modified homeostasis model assessment-ß level compared with those without vitamin D deficiency. There were differences in body mass index, diabetes course, glycosylated hemoglobin, fasting blood glucose, fasting blood C-peptide, triglyceride, and 25-hydroxy vitamin D among different modified homeostasis model assessment-ß groups based upon the tertiles. 25-hydroxy vitamin D, as continuous or categorical variables, was positively related to modified homeostasis model assessment-ß whether or not cofounding factors were adjusted. CONCLUSION: There is an association between increased 25-hydroxy vitamin D levels and improvement in modified homeostasis model assessment-ß function in patients with type 2 diabetes mellitus. TRIAL REGISTRATION: Cross-sectional trails ChiCTR2000029391 , Registration Date: 29/01/2020.

A correlation study of the relationships between nonalcoholic fatty liver disease and serum triglyceride concentration after an oral fat tolerance test.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) has become one of the most common chronic liver diseases worldwide. Triglyceride (TG) accumulation is central to NAFLD development. People now spend most of their day in the postprandial state, and the measurement of postprandial blood lipid concentration can make up for the lack of simple detection of fasting blood lipids. Postprandial triglyceride (PTG) is commonly used as a surrogate for postprandial blood lipid concentrations, and many studies have shown that PTG is a risk factor for NAFLD. The aim of the present study was to investigate the relationship between PTG concentration during oral fat tolerance testing (OFTT) and NAFLD. METHODS: A total of 472 Chinese adults, aged 25 to 65 years, were enrolled in the study. All the participants underwent OFTT. The serum concentrations of TG and other lipids were measured, and their relationships with NAFLD were analyzed. RESULTS: Of the 472 participants, 155 were diagnosed with NAFLD. The fasting and postprandial TG concentrations of the participants with NAFLD were higher than those of healthy participants (P < 0.05). The TG concentrations of the healthy participants peaked 4 h postprandially, whereas those of the participants with NAFLD peaked 6 h postprandially and reached higher peak values. Postprandial TG concentration was significantly associated with a higher risk of NAFLD. CONCLUSIONS: High PTG is positively related to a higher risk of NAFLD, and the PTG concentrations of patients with NAFLD are higher than in healthy individuals, with a delayed peak. Therefore, 4-h PTG may represent a potential marker of NAFLD. TRIAL REGISTRATION: ChiCTR1800019514 .

Changes of serum pepsinogen level and ABC classification after bariatric surgery.

BACKGROUND: Very few studies have explored the changes of serum pepsinogen after bariatric surgery and no research has evaluated the feasibility of ABC classification to predict gastric cancer risk after bariatric surgery. METHODS: We enrolled 94 obese subjects that received bariatric surgery, including 41 sleeve gastrectomy (SG) and 53 Roux-en-Y gastric bypass (RYGB). The serum pepsinogen I (PGI), pepsinogen II (PGII), PGI/II ratio and seropositivity of Helicobacter pylori ( H. pylori ) were measured before and one year after surgery. Patients were classified according to ABC classification and post-operative change was evaluated. RESULTS: Preoperatively, four (4.2%) patients were classified into high risk group (classification C and D) for gastric cancer. Significant reduction of PGI, PGII and decrease of PGI/II ratio were noted after bariatric surgery. H. pylori seropositive patients had a greater postoperative change of PGI (-38.6µg/L vs -22.1µg/L, p=0.003) and PGII (-8.0µg/L vs -2.5µg/L, p <0.001) but a less postoperative change of PGI/II ratio (-0.6 vs -2.1, p =0.04) than H. pylori seronegative patients. One year after surgery, the portion of high risk group of ABC classification for gastric cancer increased markedly from 4.2% to 23.7%. CONCLUSION: Both of SG and RYGB resulted in significant reduction of serum PGI and PGII after bariatric surgery, and significantly influenced the ABC classification. The application of ABC classification for gastric cancer screening was limited after bariatric surgery.

Winner and loser effects in lobster cockroach contests for social dominance.

In the context of animal aggression, the winner/loser effect is a cross-taxa phenomenon. In the present study, the effect of social contest experience on winning and losing subsequent encounters was investigated in the furious male lobster cockroach, Nauphoeta cinerea. Dominant and subordinate individuals were generated as the result of an encounter between two socially naïve males (SNMs); the winner and loser were designated as 1st encounter dominants and 1st encounter subordinates, respectively. With these dominants and subordinates, three experiments were conducted: (I) the original pair met in a re-encounter, (II) the 1st encounter dominants and subordinates were paired with an inexperienced SNM, (III) the 1st encounter dominants and subordinates were paired with an experienced individual of the same rank. Each experiment was conducted at 1 week, 2 weeks, 3 weeks, 4 weeks and 5 weeks after the 1st encounter fight. Juvenile hormone (JH) III titer was monitored in all individuals before and after each subsequent encounter. Our results showed that, in the original pairing and in the pairing with SNMs, the probability that a 1st encounter dominant (or subordinate) would win (or lose) the subsequent encounter fit well with the 95% confidence interval of the theoretical criteria proposed by Begin et al. (1969), indicating the existence of the winning/losing effect. However, this effect was inconsistent along the five-week observation period. For all 1st encounter dominants, at each week after the 1st encounter, the before subsequent encounter JH III titers distribution was significantly different from that on the 1st encounter day; the distributions of before subsequent encounter JH III titers could be further clustered into two groups, the higher JH III group and the lower JH III group, which were significantly correlated with subsequent winning and losing, respectively. For the 1st encounter subordinates, the distributions of before subsequent encounter JH III titers were not significantly different from that of SNMs, but the titer distributions were significantly shifted to a higher level compared to the 1st encounter day. Compared with before subsequent encounter, the after subsequent encounter hemolymph JH III level was significantly increased in winners and significantly decreased in losers. From these data, we propose that instability of the winner and loser effects may occur due to physiological costs and recovery; this instability may partly explain why the social hierarchy is unstable in this cockroach species.

Photoperiod-dependent release of suppression pheromone in the male lobster cockroach Nauphoeta cinerea.

The complex agonistic repertoire between male lobster cockroaches (Nauphoeta cinerea) makes this species an excellent model for aggression studies. During the establishment of dominance hierarchies, 3-hydroxy-2-butanone (3H-2B) functions as a suppression pheromone, keeping the rivals in a submissive state. In the present study, we evaluated the release of 3H-2B by dominant individuals across four different time phases within the 24-h photoperiod, i.e., early scotophase (ES), late scotophase (LS), early photophase (EP), and late photophase (LP). For each time phase, we collected volatile pheromones during a 60-min first-encounter fight to measure the level of released 3H-2B. Subsequently, the amount of 3H-2B remaining in the sternal glands of dominant and subordinate individuals was measured and compared to socially naïve male controls. Release of 3H-2B was relatively high during ES or LP first-encounter fights, compared to LS or EP encounters. The attack duration and aggressive posture intensity in dominant males were positively correlated with the amount of 3H-2B release in all four phases. A similar statistical distribution was found between the amount of 3H-2B released by dominant males and the amount of 3H-2B in the sternal glands of naïve male sternal during LS, EP, and LP. However, during ES, the statistical distribution of 3H-2B released by the dominant was significantly greater than the distribution of 3H-2B content in socially naïve male sternal glands. The observed phase-dependence of 3H-2B release might be due to variations in 3H-2B biosynthesis or the scotophase-specific behavior of naïve males, wherein an aggressive posture is spontaneously adopted with concomitant 3H-2B release.

1-(2,4-Dibromophenyl)-3,6,6-trimethyl-1,5,6,7-tetrahydro-4H-indazol-4-one: A Novel Opioid Receptor Agonist with Less Accompanying Gastrointestinal Dysfunction than Morphine.

BACKGROUND: The authors investigated the pharmacology and signaling pathways of the opioid receptors modulated by compound 1, 1-(2,4-dibromophenyl)-3,6,6-trimethyl-1,5,6,7-tetrahydro-4H-indazol-4-one. METHODS: In vitro studies of compound 1 were assessed by using a radioligand-binding assay (n = 3), a cyclic adenosine monophosphate assay (n = 3), a ß-arrestin assay (n = 3), an internalization assay (n = 3), and an immunohistochemistry (n = 8). In vivo studies of compound 1 were characterized using a tail-flick test (n = 5 to 6), tail-clip test (n = 7), von Frey hair test (n = 5), and charcoal meal test (n = 5). RESULTS: Compound 1 elicited robust effects in µ-opioid (mean ± SD; binding affinity: 15 ± 2 nM; cyclic adenosine monophosphate assay: 24 ± 6 nM), δ-opioid (82 ± 7 nM; 1.9 ± 0.1 µM), and κ-opioid (76 ± 9 nM; 1.4 ± 0.5 µM) receptor-expressing cells. Compound 1 acts as a full agonist of ß-arrestin-2 recruitment in µ-opioid (1.1 ± 0.3 µM) and δ-opioid (9.7 ± 1.9 µM) receptor-expressing cells. Compound 1 caused less gastrointestinal dysfunction (charcoal meal test: morphine: 82 ± 5%; compound 1: 42 ± 5%) as well as better antinociception in mechanical pain hypersensitivity (tail-clip test: morphine: 10 ± 3 s; compound 1: 19 ± 1 s) and in cancer-induced pain (von Frey hair test: morphine: 0.1 ± 0.1 g; compound 1: 0.3 ± 0.1 g) than morphine at equi-antinociceptive doses. CONCLUSIONS: Compound 1 produced antinociception with less gastrointestinal dysfunction than morphine.

Metabolic Surgery for Diabetes Treatment: Sleeve Gastrectomy or Gastric Bypass?

BACKGROUND: Bariatric surgery has gained reputation for its metabolic effect and is increasingly being performed to treat type 2 diabetes mellitus (T2DM). However, there is still a gray area regarding the choice of surgical procedure according to patient characteristics due to inadequate evidences, so far. We aim to compare the efficacy of two most commonly performed bariatric/metabolic surgeries, sleeve gastrectomy (SG) and gastric bypass (GB) with regard to remission of T2DM after surgery. METHODS: Outcomes of 579 (349 female and 230 male) patients who had undergone SG (109) or GB (470) for the treatment of T2DM with 1-year follow-up were assessed. The remission of T2DM after SG or GB surgery was evaluated in matched groups using the ABCD scoring system. The ABCD score is composed of the age, BMI, C-peptide levels and duration of T2DM (years). RESULTS: The weight loss of the SG patient at 1 year after surgery was similar to the GB patients [26.3 (1.1) vs. 32.6 (1.2) %; p = 0.258]. The mean BMI decreased from 35.7 (7.2) to 28.3 (3.7) Kg/m2 in SG patients at 1 year after surgery and decreased from 36.9 (7.2) to 26.7 (4.5) Kg/m2 in the GB patients. The mean HbA1c decreased from 8.8 to 6.1 % of the SG group and from 8.6 to 5.9 % of the GB group. Sixty-one (56.0 %) patients of the SG group and 300 (63.8 %) of the GB group achieved complete remission of T2DM (HbA1c < 6.0 %) at 1 year after surgery without statistical difference. However, GB exhibited significantly better glycemic control than the SG surgery in groups stratified by different ABCD score. At 5 year after surgery, GB had a better remission of T2DM than SG (53.1 vs. 35.3 %; p = 0.055). CONCLUSIONS: In conclusion, although both SG and GB are effective metabolic surgery, GB carries a higher power on T2DM remission than SG. ABCD score is useful in T2DM patient classification and selection for different procedures.