Among the identified thousands of circular RNAs (circRNA) in humans and animals, Cdr1as (also known as CiRS-7) was recently demonstrated to act as a powerful miR-7 sponge/inhibitor in developing midbrain of zebrafish, suggesting a novel mechanism for regulating microRNA functions. MiR-7 is abundantly expressed in islet cells, but overexpressing miR-7 in transgenic mouse β cells causes diabetes. Therefore, we infer that Cdr1as expression may inhibit miR-7 function in islet cells, which in turn improves insulin secretion. Here, we show the first characterization of Cdr1as expression in islet cells, which was upregulated by long-term forskolin and PMA stimulation, but not high glucose, indicating the involvement of cAMP and PKC pathways. Remarkably, both insulin content and secretion were significantly increased by overexpression of Cdr1as in islet cells. We further identified a new target Myrip in the Cdr1as/miR-7 pathway that regulates insulin granule secretion, and also another target Pax6 that enhances insulin transcription. Taken together, our findings revealed the effects of the strongly interacting pair of Cdr1as/miR-7 on insulin secretion, which may become a new target for improving β cell function in diabetes.
Abnormal gut microbiome has been associated with depression. The mechanism of probiotics against depression remains unclear. This study aimed to determine whether Clostridium butyricum (Cb) could attenuate chronic unpredictable mild stress-induced depressive-like behavior and its possible mechanisms. Male C57BL/6 mice were subjected to chronic unpredictable mild stress (CUMS) and were treated with Cb. Depressive-like behavior was evaluated by a series of behavioral tests. The levels of cerebral 5-hydroxytryptamine (5-HT), brain derived neurotrophic factor (BDNF), glucagon-like peptide-1 (GLP-1) receptor and intestinal were measured. Cb treatment significantly improved CUMS-induced depressive-like behavior in mice. Meanwhile, Cb treatment exhibited prominent effects, increasing 5-HT and GLP-1 and upregulating BDNF expression. Furthermore, Cb-treated mice showed increased secretion of GLP-1 and upregulated GLP-1R expression. Taken together, our results demonstrate an antidepressive effect of Cb in CUMS mice partially attributed to stimulation of intestinal GLP-1 secretion and activation of cerebral GLP-1R.
Gastric cancer is a leading cause of mortality due to neoplastic disease. Although early detection of gastric cancers can decrease the mortality rate, it remains a diagnostic challenge because of the lack of effective biomarkers. In this study, fifteen gastric cancer patients and ten healthy subjects were recruited to assess novel serum biomarkers for gastric cancer using antibody microarray technology. ELISA was utilized to validate the antibody array results. As a result, compared to the controls, eleven cytokines were found to be significantly increased in gastric cancer, including interferon gamma receptor 1 (IFNGR1), neurogenic locus notch homolog protein 3 (Notch‐3), tumor necrosis factor receptor superfamily member 19L (TNFRSF19L), growth hormone receptor (GHR), signaling lymphocytic activation molecule family 8 (SLAMF8), folate receptor beta (FR‐beta), integrin alpha 5, galectin‐8, erythropoietin‐producing hepatocellular A1 (EphA1), epiregulin, and fibroblast growth factor 12 (FGF‐12) with P < 0.05. ELISA validation supported the results of the antibody array. More importantly, most of these eleven cytokines, including IFNGR1, TNFRSF19L, GHR, SLAMF8, FR‐beta, and integrin alpha 5 were discovered to be elevated in gastric cancer serum samples for the first time in this study, suggesting that these proteins may serve as novel biomarkers for the early diagnosis and prognosis determination of gastric cancer.
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