The aim of this study was to investigate the syste-matic changes in ghrelin and leptin expression, as well as their correlation with insulin resistance (IR) during the development of type 2 diabetes mellitus (T2DM) in a rat model. T2DM was induced in rats fed a high-fat (HF)-diet followed by the intraperitoneal injection of low-dose streptozotocin (STZ, 35 mg/kg). Sixty male Sprague-Dawley rats were divided into 4 groups: the control, HF-4W (HF diet for 4 weeks), HF-8W (HF diet for 8 weeks) and the T2DM group. During the development of T2DM, the production of ghrelin in the stomach and leptin in adipose tissue, the blood levels of ghrelin and leptin, and the expression of leptin and ghrelin receptors (OB-Rb and GHS-R1a) in the hypothalamus were measured by enzyme-linked immunosorbent assay (ELISA), radioimmunology assay (RIA), immunohistochemistry (IHC) and real-time reverse transcription-polymerase chain reaction (real-time RT-PCR). IR was assessed using the hyperinsulinemic-euglycemic clamp technique. The production of ghrelin in the stomach, the plasma ghrelin levels and the expression of GHS-R1a in the hypothalamus were significantly reduced in the HF-4W and HF-8W rats compared with the control rats; however, no significant difference was found between the HF-8W and T2DM group rats. Comparing the control to the T2DM group, the production of leptin in the adipose tissue and the serum leptin levels increased, whereas the expression of OB-Rb in the hypothalamus decreased. At the same time, the glucose infusion rate (GIR), indicating the insulin sensitivity, decreased significantly; GIR positively correlated with plasma ghrelin and negatively correlated with serum leptin levels. In conclusion, increased leptin levels are associated with obesity and T2DM, while decreased ghrelin levels are associated with obesity/IR rather than T2DM.

No abstract

No abstract

No abstract

No abstract

Background Colorectal carcinoma, primarily colorectal adenocarcinoma (CRA), is one of the most common malignancies, ranking third, while contributing the second cause of cancer death in the world. MicroRNAs, a type of non-coding RNA, play an important role in regulating cancer-related cell biology. To simply and accurately predict survival risk for CRA patients, we identified a novel seven-miRNA signature. The microRNA (miRNA) expression profiles along with clinical data of 512 CRA patients were downloaded from The Cancer Genome Atlas (TCGA) database, and 415 patients with complete clinical information were further divided into training set and test set randomly. To construct the prognostic signature in the training set, a series of Cox regression analyses were performed, including univariate regression, least absolute shrinkage and selectionator operator (LASSO) - Cox regression, and multivariate regression. Results Seven predictive miRNAs (miR-153-2, miR-3199-2, miR-144, miR-887, miR-561, miR-3684, and miR-505) were ultimately screened. The ROC curves for 5-year survival in the training set, test set and entire set were 0.889, 0.742, and 0.816, respectively. Kaplan-Meier analysis results of the three sets all showed p <0.05. Further analyses demonstrated that the signature was an independent prognostic risk factor for CRA patients, and its predictive ability was superior to age and TNM stage. Functional enrichment analysis revealed that p53 and ErbB pathways were related to the prognostic regulation of miRNAs in the signature in CRA patients.Conclusion Our study demonstrated the potential of this novel seven-miRNA signature to independently predict overall survival in patients with CRA. Functional enrichment analysis further revealed the possible regulatory role of miRNAs in the signature in CRA-related cell biological processes and signaling pathways.