Background Obesity is a major health problem worldwide, and non-alcoholic fatty pancreas disease (NAFPD) and non-alcoholic fatty liver disease (NAFLD) are obesity-associated complications. Liraglutide, a glucagon-like peptide-1 (GLP-1) agonist, has been approved for treatment of obesity. We aimed to evaluate the therapeutic effects of liraglutide on the complications through its regulation of endoplasmic reticulum (ER) stress. Methods A high-fat diet mouse model was established in C57BL/6J mice. Two groups of mice were fed a high-fat diet with 60% fat for 16 weeks and control mice were fed standard chow. A four-week 0.6 mg/kg/day liraglutide treatment was started in one high-fat diet group after 12 weeks of the high-fat diet. After sacrificing the mice, pancreatic and hepatic tissues were prepared for western blot and immunohistochemistry for ER stress proteins, including activating transcription factor 4 (ATF4), caspase 12, C/EBP homologous protein (CHOP) eukaryotic initiation factor 2 α (eIF2α), glucose regulated protein (GRP) 78 and protein kinase RNA-like endoplasmic reticulum kinase (PERK). Results Liraglutide significantly decreased body weight gained by mice consuming a high-fat diet (27.6 g vs. 34.5 g, P<0.001), and levels of all ER proteins increased significantly in both the pancreas and liver (all P<0.05). Expression of most ER stress proteins in pancreatic tissue correlated with disease scores of NAFLD (all P<0.05). However, no significant differences were found in pancreatic ATF 4 expression between mice without NAFLD, and those with early non-alcoholic steatohepatitis (NASH) and fibrotic NASH (P=0.122). Conclusion Liraglutide reduces the severity of NAFPD and NAFLD may through regulating the ER stress pathway and downstream apoptosis signaling.

Background Long noncoding RNAs (lncRNAs) have been shown to play an important role in the development and progression of esophageal carcinoma (EC). Recently, lncRNA LOC441178 was shown to be dysregulated in many cancer types; however, the role of LOC441178 in EC remains unclear. Materials and Methods Flow cytometry, transwell and wound healing assays were used to measure the apoptosis and migration in esophageal squamous cell carcinoma (ESCC) cells. RT-qPCR was used to detect the level of miR-182 in LOC441178-overexpressed EC cells. In addition, DNA methylation status of miR-182 promoter in LOC441178-overexpressed ESCC cells was detected by methylation-specific PCR (MSP) and bisulfite sequencing PCR. Results In this study, we found that LOC441178 negatively regulated miR-182 expression in ESCC cells. In addition, overexpression of LOC441178 inhibited the proliferation and migration and induced apoptosis in ESCC cells via downregulation of miR-182. Moreover, overexpression of LOC441178 markedly inhibited the phosphorylation of Akt and phosphorylation FOXO3a and increased the expression of FOXO3a in ESCC cells via downregulation of miR-182. Mechanistically, LOC441178 overexpression epigenetically suppressed miR-182 expression via DNA methylation. In vivo experiments revealed that overexpression of LOC441178 inhibited ESCC tumor growth in mouse xenograft model. Conclusion Collectively, our data suggested that LOC441178 overexpression epigenetically inhibited tumorigenesis of ESCC via DNA methylation of miR-182. These data indicated that the LOC441178/miR-182 axis might represent a novel therapeutic option for the treatment of ESCC.

Esophageal carcinoma (EC) is a highly malignant type of tumor. In a previous study, the authors found that long non-coding RNA (lncRNA) LOC441178 inhibited the tumorigenesis of EC. Moreover, exosomes derived from tumor cells containing lncRNAs were found to play a key role in the tumor environment; however, whether exosomes can affect the tumor microenvironment by carrying LOC441178 remains unclear. Thus, the present study aimed to clarify this. In order to assess the effects of exosomal LOC441178 in EC, cell invasion and migration were examined using the Transwell assay. Exosomes were identified using transmission electron microscopy, western blot analysis and nanoparticle tracking analysis. Furthermore, macrophage surface makers (CD206 and CD86) were analyzed using flow cytometry. Moreover, a subcutaneous xenograft mouse model was constructed to assess the role of TE-9 cells-derived exosomal LOC441178 in EC. The results revealed that LOC441178 overexpression notably suppressed the metastasis of EC cells. In addition, exosomes were successfully isolated from EC cells, and LOC441178 level was upregulated in exosomes derived from LOC441178-overexpressed EC cells. Exosomal LOC441178 also suppressed macrophage M2 polarization, and the polarized macrophages decreased EC cell invasion. Exosomes containing LOC441178 notably inhibited the growth of EC in mice. On the whole, the present study demonstrated that the delivery of LOC441178 by EC cell-secreted exosomes inhibited the tumorigenesis of EC by suppressing the polarization of M2 macrophages. These findings may provide a new theoretical basis for discovering new strategies against EC.

Background The pathophysiology and treatment of non-alcoholic fatty pancreas disease (NAFPD) have not been well established. Thus, the aim is to prove hypotheses that endoplasmic reticulum (ER)stress may take part in the pathogenesis of NAFPD. Methods The mice were randomly grouped into normal-group, model-group and experimental-group. The normal-group was fed with regular-diet, while model-group and experimental-group were fed with high-fat-diet for 16 weeks. After the NAFPD model was established successfully, the experimental-group began to give liraglutide 0.6 mg·kg -1 ·d -1 for 4 weeks. The normal-group and model-group were received saline only, total pancreatectomy was performed and pancreas samples were divided for western-blot and immunohistochemical, to detect the expression of GRP78、PERK、eLF2α、ATF4、CASPASE12 and CHOP. Results Western-blot and immunohistochemistry both revealed that the expression of above proteins of model-group were significantly increased compared with normal-group and were also obviously increased compared with experimental-group. (all P ≤0.05). The weight of body and the pancreas of the model-group was markedly higher than that of normal-group, and was also dramatically higher than that of experimental-group (all P ≤0.01). Conclusion Those results show ER stress may be one of the pathogenesis of NAFPD and liraglutide have the effect on regulating ER stress in NAFPD. Those findings have great significance in figuring out the pathophysiology of NAFPD.