Yanyan Yuan

STAT3 stimulates adipogenic stem cell proliferation and cooperates with HMGA2 during the early stage of differentiation to promote adipogenesis

Signal transducer and activator of transcription 3 (STAT3) is abundantly expressed in the adipose tissue of obese mice and humans, but the role of STAT3 in adipogenesis is still not fully understood. In the present study, we discovered an activation of STAT3 during the early differentiation stage of mouse 3T3-L1 preadipocytes. Stat3 knockdown using siRNA blocked cell cycle progression of both preadipoctes and early differentiating cells. Moreover, accumulation of lipid droplets was inhibited by Stat3 knockdown. Importantly, in the nucleus of early differentiating cells, we demonstrated that STAT3 protein co-localized with high-mobility-group protein AT-hook 2 (HMGA2), which was reported to promote adipogenesis in a previous study. Taken together, our data indicate that STAT3 and HMGA2 cooperatively promote adipogenesis which highlight a more detail understanding of STAT3 related transcription factor network during adipogenesis.

Obesity-associated digestive cancers: A review of mechanisms and interventions:

The prevalence of obesity has steadily increased over the past few decades. Previous studies suggest that obesity is an oncogenic factor and that over 20% of all cancers are obesity-related. Among such cancers, digestive system malignancies (including esophageal adenocarcinomas, colorectal cancers, and cancers of the gastric cardia, liver, and pancreas) are reported most frequently. While the 5-year survival rates of cancers of the breast and prostate are 90%, that rate is only 45% for digestive cancers. In this review, the mechanisms of obesity-associated digestive cancers are discussed, with an emphasis on obesity-related gene mutations, insulin and insulin-like growth factor signaling pathways, chronic inflammation, and altered adipokine levels. Evidence that these factors often function interdependently rather than independently in carcinogenesis is presented. Recommended interventions that may reduce the burden of obesity-associated digestive cancers, such as participation in physical activity, diet modulation, and calorie restriction, are also described.

Cortex Mori Radicis extract attenuates myocardial damages in diabetic rats by regulating ERS

Diabetic cardiomyopathy (DCM) is diagnosed when patients with diabetes develop ventricular dysfunction but do not exhibit coronary atherosclerosis or hypertension. Cortex Mori (CM) Radicis,he epidermis of the root of Morus alba L, has been traditionally used for cough treatment in oriental medicine. In this study, we investigated the protection of myocardium by CM in streptozotocin (STZ)-induced diabetic rats and the underlying mechanisms. Diabetes was induced in rats by an injection of STZ at 25mg/kg. The animals were randomly divided into 4 groups: control, diabetes, diabetes with CM treatment, diabetes with CM preventative treatment. Pathological changes were examined by hematoxylin-eosin staining. Extracellular matrix content was assessed by Massons trichrome staining and Western blot. Endoplasmic reticulum (ER) stress-associated molecules and main components of the mitogen-activated protein kinase (MAPK) pathway were also measured by Western blot. Myocardial damages were induced by the injection of STZ as evidenced by abnormal blood glucose and pathological cardiac changes. Administration of CM markedly ameliorated myocardial damages such as cardiac hypertrophy and fibrosis. ER stress was down-regulated, and p38 and ERK were suppressed by CM. Thus, CM may have therapeutic potential in the treatment of DCM by attenuating ER stress and ERK and p38 MAPK activation.

Dipeptidyl peptidase-4 inhibitors and cancer risk in patients with type 2 diabetes: a meta-analysis of randomized clinical trials

Some recent studies have suggested that the use of dipeptidyl peptidase-4 inhibitors (DPP4i) is associated with cancer development. However, some other studies suggest no such association. The aim of the present study was to evaluate the effect of DPP4i on the risk of developing cancers. The electronic databases PubMed, Medline, EMBASE, Web of Science and Cochrane Library and the clinical trial registry were searched for published and unpublished randomized clinical trials on humans. Eligible studies were RCTs conducted in patients with type 2 diabetes mellitus, comparing DPP4i with a placebo or other active drugs. A total of 72 trials with 35,768 and 33,319 patients enrolled for DPP4i and the comparison drugs, respectively. Overall, no significant associations were detected between the use of DPP4i and cancer development, in comparison with the use of other active drugs or placebo. The results were consistent across pre-defined subgroups stratified by type of DPP4i, type of cancer, drug for comparison, trial duration, or baseline characteristics. The results of this meta-analysis suggest that patients with type 2 diabetes treated with DPP4i do not have a higher risk of developing cancers than patients treated with a placebo or other drugs.

Prevalence of Pre-Diabetes and Its Associated Risk Factors in Rural Areas of Ningbo, China

Objective: The aims of the study were to investigate the prevalence of pre-diabetes and explore its associated risk factors in rural areas of Ningbo, China. Methods: A cross-sectional survey was conducted with 4583 adult residents in rural areas of Ningbo, China between March and May 2013. The survey used a multi-stage, stratified, cluster sampling method. Data collected included demographics and medical history, anthropometric measurements, blood pressure, blood lipid, and plasma glucose. After at least 10 h of overnight fasting, participants underwent an oral glucose tolerance test (OGTT) to identify pre-diabetes. Univariate and multivariate logistic regression analyses were used to evaluate the associated risk factors for pre-diabetes, and to estimate the effect of interaction between the factors. Results: There were 1307 survey participants having pre-diabetes (28.52%) and the age-standardized prevalence was 30.53%. Multivariate logistic regression results showed that overweight/obesity, hypertension, and higher triglycerides were the risk factors for developing pre-diabetes. There were positive interactions between overweight/obesity and triglycerides, and also between hypertension and triglycerides on the multiplicative scale, suggesting that they synergistically influenced the development of pre-diabetes. Conclusions: The rural areas in Ningbo had a high prevalence of pre-diabetes. Overweight and obesity, hypertension, and elevated triglycerides were the major risk factors. There is a need of early intervention for preventing pre-diabetes.

A novel herbal treatment reduces depressive-like behaviors and increases brain-derived neurotrophic factor levels in the brain of type 2 diabetic rats

Background Radix Puerariae and hawthorn fruit have been demonstrated to treat diabetes. They offer potential benefits for preventing depression in diabetes. Objective The aim of this study was to investigate whether the combination of Radix Puerariae and hawthorn fruit (CRPHF) could prevent depression in a diabetic rat model generated by feeding the rats with a high-fat diet and a low-dose streptozotocin (STZ). Methods The CRPHF was provided by the Shanghai Chinese Traditional Medical University. Twenty-four rats were randomly divided into four groups: normal control, normal-given-CRPHF (NC), diabetic control, and diabetic-given-CRPHF (DC) groups. The type 2 diabetic model was created by feeding the rats with a high-fat diet for 4 weeks followed by injection of 25 mg/kg STZ. CRPHF was given at 2 g/kg/d to the rats of NC and DC groups by intragastric gavage daily for 4 weeks after the type 2 diabetic model was successfully created. Body weight, random blood glucose (RBG), oral glucose tolerance test, total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were measured during the study. Depressive-like behavior was evaluated at the end of the treatment by using the open field test (OFT), the elevated plus-maze test (EPMT), locomotor activity test (LAT), and forced swimming test (FST). Levels of extracellular signal-regulated protein kinase (ERK) and brain-derived neurotrophic factor (BDNF) in the prefrontal cortex were evaluated by using Western blot. Results 1) CRPHF reduced RBG and improved glucose tolerance in diabetic rats; 2) CRPHF reduced TC and TG but did not significantly change HDL-C or LDL-C in diabetic rats; 3) CRPHF reversed the loss in body weights observed in diabetic rats; 4) CRPHF reduced depressive-like behavior as measured by OFT, EPMT, LAT, and FST; 5) BDNF was upregulated, and ERK was activated in the prefrontal cortex of diabetic rats treated with CRPHF. Conclusion CRPHF has the potential of preventing depression in patients with diabetes.

Mori Cortex extract ameliorates nonalcoholic fatty liver disease (NAFLD) and insulin resistance in high-fat-diet/streptozotocin-induced type 2 diabetes in rats

Nonalcoholic fatty liver disease (NAFLD) and type 2 Diabetes Mellitus (T2DM) are highly prevalent diseases and are closely associated, with NAFLD being present in the majority of T2DM patients. In Asian traditional medicine, Mori Cortex is widely used for the treatment of diabetes and hyperlipidemia. However, whether it has a therapeutic effect on T2DM associated with NAFLD is still unknown. The present study showed that the oral treatment with Mori Cortex extract (MCE; 10 g·kg-1·d-1) lowered the blood lipid levels and reversed insulin resistance (IR) in high fat-diet/streptozotocin-induced type 2 diabetes in rats. The expression levels of sterol receptor element-binding protein-1c (SREBP-1c) and carbohydrate-responsive element binding protein (ChREBP), which are involved in steatosis in NAFLD rats, were measured in the liver samples. MCE decreased the protein and mRNA expression levels of SREBP-1c and ChREBP. In conclusion, down-regulation of SREBP-1c and ChREBP might contribute to the protective effect of MCE on hepatic injury and IR in the rats with T2DM associated with NAFLD.

Author Correction: Dipeptidyl peptidase-4 inhibitors and cancer risk in patients with type 2 diabetes: a meta-analysis of randomized clinical trials

A correction to this article has been published and is linked from the HTML version of this paper. The error has been fixed in the paper.

Root bark of Morus alba ameliorates the depressive-like behaviors in diabetic rats

Diabetes-induced depression is one of the severe chronic complications of diabetes mellitus. Up to now, there are only a few effective medicines to prevent or manage the co-morbidity of diabetes and depression. The present study was to investigate the effect of root bark of Morus alba (RBM) on depressive-like behaviors in the diabetic rats established by a high fat diet and a low dose of streptozotocin. Depressive-like behaviors were measured by the open field test, locomotor activity test and forced swimming test. Plasma glucose and lipid parameters were also measured. Expression of Brain-derived neurotrophic factor (BDNF) and phosphorylation of extracellular signal-regulated kinase (ERK) and Akt in the prefrontal cortex (PFC) were assessed. The results showed that a 4-week administration of RBM (10g/kg, ig) significantly reversed the depressive-like behaviors. BDNF expression and phosphorylation of ERK and Akt were increased in the PFC following RBM treatment in the diabetic rats. The data demonstrated that RBM could improve the depressive-like behaviors induced by diabetes, suggesting a therapeutic potential of RBM for the diabetes-associated depression.