Therapeutic effect of ursolic acid on fetal development in pregnant rats with gestational diabetes mellitus via AGEs-RAGE signaling pathway.

To investigate the effect of ursolic acid on the fetal development of gestational diabetes mellitus (GDM) caused by streptozotocin (STZ) and explore the potential mechanism for it. For the current experimental research, SD rats (pregnant animal) were used. STZ has been used to cause the diabetes mellitus in pregnant rats. Rats with evolved GDM were randomly divided and ursolic acid was given to pregnant rats in the experimental period up to 19 days in a dose-dependent manner. Blood samples and fetal rats of all group rats were collected at 19 days (pregnant rats), fetal rats and placental rats were weighted and the blood glucose, plasma insulin, C-peptide, and lipid parameters of pregnant women were estimated prior to delivery. Advanced serum glycation end-products (AGEs) were estimated at regular intervals in the heart and brain of pregnant rats. Monocyte Chemoattractant Protein-1 (MCP-1), NADPH oxidase 2 (Nox2), Role of advanced glycation end product (RAGE), Vascular endothelial growth factor (VEGF), p65, and vascular cell adhesion molecule 1 (VCAM-1) mRNA expression were estimated in the placenta. STZ-induced GDM pregnant rats showed significantly decreased placental weight and weight of fetal rats and dose-dependent ursolic acid treatment (p < .001) improved placental weight and weight of fetal rats at dose-dependent levels. After the ursolic acid treatment, serum blood glucose and lipid level were improved especially fasting blood glucose (FBG), high density lipoprotein (HDL), hepatic glycogen, fasting insulin (FINS), and serum insulin level and reached near to the normal control group rats. The antioxidant level of pancreas and liver were significantly (p < .001) reduced by the dose-dependent treatment of ursolic acid. Treatment with Ursolic acid moderately but not significantly decreases the risk of fetal development defects relative to the GDM group. The potential effect on fetal development in Pregnant Rats with Gestational Diabetes Mellitus via AGEs-RAGE signaling pathway was shown by Ursolic acid. PRACTICAL APPLICATIONS: As we know that the gestational diabetes mellitus increases worldwide day by day. In the current experimental study, we try to examine the gestational diabetic effect of ursolic acid. The finding of the current study showed the gestational diabetic protective effect in the female rats via AGEs-RAGE signaling pathway. The result showed the antioxidant, anti-inflammatory, and biochemical parameters. On the basis of the result, we can say that the ursolic acid can be the protective drug for treatment of gestational diabetes mellitus.

Prognostic impact of TAZ and ß-catenin expression in adenocarcinoma of the esophagogastric junction.

BACKGROUND: TAZ is a downstream agent of Hippo signal pathway. ß-catenin is a cell adhesion molecule associated with the invasion and metastasis of carcinomas as well as a critical component of Wnt pathway. TAZ and ß-catenin have long been thought to play a vital role in tumour development and progression. This study aimed to detect expression of TAZ and ß-catenin in adenocarcinoma of the esophagogastric junction (AEG) and explore their clinicopathological significance. METHODS: The expression of TAZ and ß-catenin were detected by immunohistochemistry of 135 AEG samples, and analyzed with complete clinicopathological features. Overall survival rates were also calculated using the Kaplan-Meier method. Cox proportional hazard model was performed to assess the prognostic values. 37 normal mucosa and 41 dysplasia samples of esophagogastric junction (EGJ) were studied comparably. RESULTS: TAZ protein showed a strictly nuclear staining pattern in AEG and dysplasia with IHC. Expression of TAZ was higher in dysplasia and AEG compared with normal mucosa (P < 0.001, 0.008). The positive expression rate of nuclear ß-catenin was significantly higher in carcinoma and dysplasia than that in normal mucosa (P < 0.001, =0.046). Abnormal expression rate of membranous ß-catenin in AEG was significantly higher than that in normal mucosa tissues and dysplasia (P = 0.001, 0.002). In AEG, over expression of TAZ was directly correlated with abnormal nuclear ß-catenin expression (r = 0.298, P < 0.001) and membranous ß-catenin (r = 0.202, P = 0.019). Patients with abnormal TAZ or ß-catenin expression of AEG exhibited a shorter overall survival (OS) and lower overall survival rate than those with normal TAZ or ß-catenin expression (P < 0.05). In addition, patients with abnormal expression of both TAZ and ß-catenin exhibited worst overall survival. In multivariate survival analysis, abnormal expression of TAZ, TAZ & ß-catenin (nuclear and membranous) and tumour differentiation were found to be independent prognostic factors related to OS of AEG patients. CONCLUSIONS: Over expression of TAZ was associated with abnormal expression of ß-catenin, which is correlated with poor prognosis of patients with AEG. Abnormal expression of TAZ and TAZ & ß-catenin (nuclear and membranous) are independent prognostic factors, so targeting TAZ and ß-catenin could prove to be a promising therapeutic strategy for the treatment of AEG. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2558852841276335.