The role of quantitative changes in the epxression of insulin receptor substrate-1 and nuclear ubiquitin in abnormal glycometabolism in the livers of KKay mice and the relative therapeutic mechanisms of Astragalus polysaccharide.

Ubiquitin and the ubiquitination pathway are important regulators of insulin signaling. The insulin receptor substrate­1 (IRS-1), an ubiquitin-interacting adaptor protein, serves as the key docking protein in insulin signaling. The effects of this dynamic interaction and the changes in ubiquitin expression on hepatic insulin signaling, as well as the relative therapeutic effects of Astragalus polysaccharide (APS) have not yet been elucidated. In this study, we aimed to investigate the abnormal changes which occur in the levels of IRS-1 and ubiquitin in the livers of mice (mice with insulin resistance and diabetes), and to elucidate the possible mechanisms responsible for these changes. A control group (CG), an insulin resistance group (IG) and a diabetes group (DG) were respectively composed of 12-week-old C57BL/6J mice fed a normal diet, C57BL/6J mice fed a high­fat diet and KKay mice fed a high­fat diet, and treatment groups were composed of corresponding groups treated with APS (CG + A, IG + A, DG + A). All the mice were age-matched and grouped at random. After eight weeks, the mouse models were successfully established and the related physiological or biochemical indexes were detected using corresponding methods. Ubiquitin expression in the liver was detected by immunohistochemisty, and western blot analysis was used to detect the expression of IRS-1 and ubiquitin. The results revealed that the expression of IRS-1 in the DG was significantly lower compared to that in the CG and IG; however, the nuclear expression of ubiquitin and the ubiquitination levels of IRS-1, including body weight and blood glucose and triglyceride levels in the DG were significantly higher compared to those in the CG or IG (P<0.05). There was a significant improvement in the ubiquitination levels in DG + A, including the blood glucose and triglyceride levels compared with the DG (P<0.05). From the stage of insulin resistance to the stage of diabetes, the reduced expression of IRS-1 and its enhanced ubiquitination levels combined with the overexpression of nuclear ubiquitin contributed to the abnormal glycometabolism and the disruption of insulin signaling. APS showed beneficial effects, such as lowering body weight, as well as blood glucose and triglyceride levels, and these effects correlated with the downregulation of the ubiquitination levels of IRS-1 and the nuclear expression of ubiquitin.

Dietary methionine intake and risk of incident colorectal cancer: a meta-analysis of 8 prospective studies involving 431,029 participants.

BACKGROUND: Methionine is one of the key components of one carbon metabolism. Experimental studies indicate that methionine may reduce inflammation-induced colon cancer. However, epidemiologic findings as to whether dietary methionine intake influences colorectal cancer incidence in humans are inconsistent. OBJECTIVE: To investigate the relationship between dietary methionine intake and risk of colorectal cancer by performing a meta-analysis of prospective studies. METHODS: Eligible studies were identified by searching PubMed and Embase and by reviewing the bibliographies of the retrieved publications. The summary risk estimates were computed using both a random- effects and a fixed-effects model. RESULTS: Eight eligible prospective cohort studies involving 431,029 participants and 6,331 colorectal cancer cases were identified. According to the random-effects model, the summary relative risks (RRs) for the highest compared with the lowest intake of methionine were 0.89 (95% confidence interval [CI] = 0.77-1.03) for colorectal cancer, 0.77 (95% CI = 0.64-0.92) for colon cancer, and 0.88 (95% CI = 0.55-1.42) for rectal cancer. In the stratified analysis, a significant inverse association between dietary methionine intake and risk of colorectal cancer was observed in studies with longer follow-up time (RR=0.81, 95% CI= 0.70-0.95), in Western studies (RR= 0.83, 95% CI = 0.73-0.95) and in men (RR = 0.75, 95% CI= 0.57-0.99). We found no indication of publication bias. CONCLUSION: This meta-analysis indicates that dietary methionine intake may be associated with decreased risk of colorectal cancer, especially colon cancer. More prospective studies with long follow-up time are needed to confirm these findings.

Partial intestinal obstruction secondary to multiple lipomas within jejunal duplication cyst: a case report.

Lipoma within jejunal duplication presenting as abdominal bloating and partial intestinal obstruction is an exceptional clinical entity. We report a case of 68-year-old man complaining of abdominal bloating for 10 d due to multiple lipomas arising from jejunal duplication cysts. Only a few cases of a single lipoma within a Meckel's diverticulum giving rise to this clinical scenario have been reported in the English language literature. However, no case of multiple lipomas within jejunal duplication cysts has been reported. We present a case in which double-balloon endoscopy revealed a small intestinal structure changed into Meckel's diverticulum-like cavities containing several lipomas. This case highlights intestinal lipoma as an uncommon cause of adult intussusceptions, which should be included in the differential diagnosis of small intestinal obstruction and appropriate examinations should be chosen.

[Association of vascular endothelial growth factor 936C/T polymorphism and the susceptibility to colorectal adenoma].

OBJECTIVE: To examine the association between polymorphism of vascular endothelial growth factor(VEGF)1498 C/T,936 C/T and colorectal adenoma genetic susceptibility. METHODS: A case-control study of 224 colorectal adenomas and 200 controls was conducted and VEGF genotypes were determined based on TaqMan-probe assay. The epidemiological factors were collected through questionnaire. Accordingly, the clinicopathological data of each sample were also investigated. RESULTS: The carriage of 936 CT and CT+TT genotypes had significantly higher risk of colorectal adenoma (CT vs. CC, OR=2.00, 95% CI: 1.23-3.25, P=0.006; CT+TT vs. CC, OR=2.04, 95% CI:1.28-3.26, P=0.003). 936-T allele carriage had increased risk of colorectal adenoma (OR=1.91, 95% CI:1.25-2.91, P=0.003). The genotypes of 1498 C/T and the frequency of C/T allele showed no differences between healthy persons and patients (P>0.05). In patients with 936 CT+TT and 936-T allele implied a tendency of villous adenoma category (CT+TT vs. CC, OR=2.54, 95% CI:1.12-5.75, P=0.040; T allele vs. C allele, OR=3.08, 95% CI, 1.64-5.80, P=0.001). CONCLUSION: VEGF 936 C/T polymorphism can influence susceptibility to colorectal adenoma.