Objective To investigate the expression and significance of the adaptor protein epsin 3 (EPN3) in colorectal cancer in order to provide reference for further stud)' of EPN3. Methods GEPIA and GEDS were used to analyze the expression of EPN3 in colorectal cancer tissues and cells. SMART and cBioPortal databases were used to analyze the relationship between EPN3 gene metfrylation and cop)' number variation and its expression level. Metascape was used to complete analysis of gene ontology functional annotation and related pathways of EPN3 related genes and BioPlex was applied to construct a protein network in HCT116 cell. Thirteen pairs of colorectal cancer adjacent tissue and cancer tissue specimens were collected, and EPN3 mRNA expression were detected by Real-time PCR. The effect of abilities of cell proliferation, clone formation and migration via silencing EPN3 in HCT116 and HT29 were observed. Results GEPIA, GEDS, SMART and cBioPortal analyses showed that EPN3 was highly expressed in colorectal tumor tissues (P<0. 01), and was related to methylation and copy number variation. The enrichment result of EPN3 related genes showed that it was mainly related to cell adhesion. And a protein interaction network constructed by CCDC130, TNFAIP1, PHGDH, EPN2, etc. was related to protein ubiquitination. Real-time PCR result showed that EPN3 was highly expressed in tumor tissues (P<0. 05). Silencing EPN3 inhibited the proliferation, clony formation and migration abilities of HCT116 and HT29 cells. Conclusion EPN3 is highly expressed in colorectal cancer tissues and is related to cell adhesion and protein ubiquitination. Down-regulated EPN3 can inhibit abilities of proliferation, clony formation and migration of HCT116 and HT29 cells, and this could provide a reference for further research on EPN3.

OBJECTIVETo observe the protective effects of potassium channel opener nicorandil against cognitive dysfunction in mice with streptozotocin (STZ)-induced diabetes.

METHODSC57BL/6J mouse models of type 1 diabetes mellitus (T1DM) were established by intraperitoneal injection of STZ and received daily treatment with intragastric administration of nicorandil or saline (model group) for 4 consecutive weeks, with normal C57BL/6J mice serving as control. Fasting blood glucose level was recorded every week and Morris water maze was used to evaluate the cognitive behavior of the mice in the 4th week. At the end of the experiment, the mice were sacrificed to observe the ultrastructural changes in the hippocampus and pancreas under transmission electron microscopy; the contents of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) in the hippocampus and SOD activity and MDA level in the brain tissue were determined.

RESULTSCompared with the control group, the model group showed significantly increased fasting blood glucose (P<0.001), significantly prolonged escape latency (P<0.05) and increased swimming distance (P<0.01) with ultrastructural damage of pancreatic β cells and in the hippocampus; GIP and GLP-1 contents in the hippocampus (P<0.01) and SOD activity in the brain were significantly decreased (P<0.05) and MDA content was significantly increased in the model group (P<0.05). Compared with the model group, nicorandil treatment did not cause significant changes in fasting blood glucose, but significantly reduced the swimming distance (P<0.05); nicorandil did not improve the ultrastructural changes in pancreatic β cells but obviously improved the ultrastructures of hippocampal neurons and synapses. Nicorandil also significantly increased the contents of GIP and GLP-1 in the hippocampus (P<0.05), enhanced SOD activity (P<0.05) and decreased MDA level (P<0.01) in the brain tissue.

CONCLUSIONNicorandil improves cognitive dysfunction in mice with STZ-induced diabetes by increasing GIP and GLP-1 contents in the hippocampus and promoting antioxidation to relieve hippocampal injury.