ABSTRACT
2',4'-Dihydroxy-6'-methoxy-3',5'-dimethylchalcone (DMC), which is isolated and purified from the dried flower buds of Cleistocalyx operculatus (Roxb.) Merr. et Perry (Myrtaceae), was investigated for its insulinotropic benefits against glucotoxicity using in vitro methods. When exposed to high glucose at the cytotoxicity level for 48 h, RIN-5F ß-cells experienced a significant viability loss and impaired insulin secretion function, whereas cotreating with DMC could protect ß-cells against glucotoxicity-induced decrease in glucose-stimulated insulin secretion in a dose-dependent manner without affecting basal insulin secretion. It was demonstrated that DMC increased insulin secretion against glucotoxicity by simulating the effect of GLP-1 and enhancing the expression of GLP-1R, followed by activating the signal pathway of PDX-1, PRE-INS, and GLUT2-GCK. Another mechanism was that DMC avoided the pancreatic islet dysfunction resulting from cellular damage by suppressing the production of nitric oxide (NO) by iNOS, and the expression of MCP-1. The results indicated the potential application of DMC in the intervention against glucotoxicity-induced hyperglycemia.
Subject(s)
Chalcones/pharmacology , Glucose/toxicity , Insulin-Secreting Cells/drug effects , Insulin/metabolism , Myrtaceae/chemistry , Plant Extracts/pharmacology , Protective Agents/pharmacology , Animals , Cell Line, Tumor , Gene Expression/drug effects , Glucose/metabolism , Glucose Transporter Type 2/genetics , Glucose Transporter Type 2/metabolism , Homeodomain Proteins/genetics , Homeodomain Proteins/metabolism , Insulin Secretion , Insulin-Secreting Cells/metabolism , Rats , Trans-Activators/genetics , Trans-Activators/metabolismABSTRACT
OBJECTIVE: To analyze the prognosis of rectal gastrointestinal stromal tumors (GIST). METHODS: Records of 40 patients diagnosed as rectal GIST at the Affiliated Chinese Traditional Medical Hospital of Xinjiang Medical University and the People's Hospital of Tianjin City between June 1979 and June 2010 were reviewed. Clinical features, treatment modalities and outcomes were analyzed. RESULTS: There were 23 males and 17 females with a median age of 54.5 years old (range, 28-81 years old). During the follow-up(median 52.5 months, range 1-300 months), 18 patients developed recurrence including 7 local recurrence, 6 metastasis and 5 local recurrence complicated with metastasis. The overall survival rates at 1, 3 and 5 years were 82.5%, 60.0%, and 42.5% respectively. On univariate analysis, tumor size(P<0.01), Fletcher classification(P<0.01), mitotic index(P<0.01), and post-operative distant metastasis were associated with survival. Multivariate analysis showed that tumor size(P<0.05), mitotic rate (P<0.01), and postoperative distant metastasis(P<0.01) were independent prognostic factors associated with survival. CONCLUSIONS: Surgery is the main treatment for rectal GIST. Tumor size, mitotic rate and metastasis are independent prognostic factors in patients with rectal GIST.
