Effect of folic acid and vitamin E on promoter DNA methylation and expression of TGF-ß1, ESR-1 and CDH-1 in the uterus of STZ-induced diabetic rats.

The present study is the first attempt made to investigate the effects of diabetes on expression and promoter DNA methylation of TGF-ß1, ESR-1, and CDH-1 genes and also the effects of folic acid (FA) and vitamin E (Vit E) supplementations on improving diabetes mellitus. STZ-induced diabetic rats were treated with Vit E (200 mg/kg/day) and FA (25 mg/kg/day) for 8 weeks and expression and DNA methylation of TGF-ß1, ESR-1, and CDH-1 genes in uterus were analysed. Data indicated that diabetes increases the expression of TGFß-1 and ESR-1 and decreases CDH-1 expression and TGFß-1 promoter methylation in the uterus of rats. Vit E and FA improved the negative effects of diabetes by decreasing the expression of TGFß-1 and ESR-1 and increasing that of CDH-1 in diabetic rats. In conclusion, these findings emphasise that Vit E and FA supplementations could improve negative effects caused by diabetes on uterus function and fertility in diabetic rats.

HLA-G Expression in Tumor Tissues and Soluble HLA-G Plasma Levels in Patients with Gastrointestinal Cancer

Background: Overexpression of human leukocyte antigen G (HLA-G) and increased plasma levels of soluble HLA-G (sHLA-G) have been reported in different human malignancies, and are believed to be involved in tumor immune evasion. Objectives: This study was designed to evaluate the expression of HLA-G in tumor tissues and the plasma levels of sHLA-G in patients with gastrointestinal cancer, and to determine their associations with clinicopathological factors. The link between Helicobacter pylori infection and increased HLA-G expression or sHLA-G levels was also investigated in patients with gastric cancer. Methods: HLA-G expression was investigated in tumor tissues from 100 patients with gastric and colorectal adenocarcinoma using immunohistochemistry test, and plasma levels of sHLA-G were measured in 82 patients with ELISA method. The presence of H. pylori genome was investigated in tumor tissues from 25 patients with gastric cancer by PCR method. Results: HLA-G expression was observed in 43% of colorectal cancers and 34.6% of gastric cancers, and was not related with any of the clinicopathological factors. There was a significant correlation between increased sHLA-G level and stage I tumors. Eight of 25 (32%) gastric cancer specimens were positive for H. pylori, of which 3 samples were positive for HLA-G. Soluble HLA-G levels were above the cut-off value in all H. pylori-positive patients. Conclusion: Plasma levels of sHLA-G were significantly increased in our patients with a sensitivity of 89% and a specificity of 62%. Soluble HLA-G level can be considered a useful indicator for the early diagnosis of gastric and colorectal adenocarcinoma.