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Background The increased inflammation is closely correlated with post-operative delirium (POD). Mesencephalic astrocyte-derived neurotrophic factor (MANF) shows protective effect on inflammatory diseases. However, the relationship between MANF and POD is still undefined. This study aimed to explore the potential effect of MANF on POD. Methods Pre- and post-operative levels of MANF and inflammatory cytokines were measured in serum from POD and non-POD patients by ELISA, as well as endogenous MANF in serum from healthy individuals with different ages. Endogenous MANF in mice brain from different ages was also measured. Abdominal surgery was performed for POD mice model. POD-like behavior changes in mice were evaluated using buried food test, open field test and Y maze test. Results Endogenous MANF was decreased in age-dependent manner in both humans and mice. The pre-operative level of MANF in serum from POD patients was lower compared with that in non-POD patients (p=0.016). MANF increase in serum after surgery was less in POD patients than that in non-POD patients (p<0.001). In mice, recombinant human MANF reversed the surgery-induced elongation of latency to eat food, increase in latency to center and increase in time in center in open field test, and also increase in duration in novel arm in Y maze test. In addition, MANF inhibited surgery-induced inflammation, microglial activation and M1 polarization in mice. Conclusion The relative low MANF level may contribute to POD in the elderly. MANF has a protective role against POD-like behavior changes in mice.

Aim Glucagon‐like peptide‐1 receptor agonists (GLP‐1Ras) have been reported to prevent non‐alcoholic fatty liver disease (NAFLD), but the potential mechanisms are still debated. MicroRNAs (miRNAs) play a prominent role in the field of metabolic disorders, including NAFLD. Our study was designed to further evaluate the effect of GLP‐1Ra liraglutide on NAFLD in terms of miRNAs. Methods MicroRNA expression was evaluated by clustering analysis of microRNA arrays in high fat diet‐fed mice. The luciferase reporter assay was carried out to validate the cross‐talk between adipose triglyceride lipase (ATGL) and miR‐124a. MicroRNA‐124a mimics and inhibitor plasmids were transfected to study the role of miR‐124a in palmitate‐treated normal human liver cell line (HL‐7702). Liraglutide treatment was used to observe the effect of GLP‐1Ra on the miR‐124a/ATGL pathway. Results Expression of ATGL decreased and miR‐124a expression increased in hepatosteatosis in vivo and in vitro. Mechanistically, miR‐124a interacted with the 3′‐untranslated region of ATGL mRNA and induced its degradation. MicroRNA‐124a overexpression antagonized the effect of liraglutide on NAFLD by inhibiting ATGL expression, whereas miR‐124a knockdown led to elevated ATGL and sirtuin 1 (Sirt1) expression, and subsequently decreased lipid accumulation and inflammation in cells. Conclusions MicroRNA‐124a overexpression contributes to the progression of NAFLD through reduction of ATGL expression, whereas miR‐124a knockdown can reverse this trend, suggesting that miR‐124a and its downstream target ATGL can be novel therapeutic targets of NAFLD. We reveal a novel mechanism by which liraglutide attenuates NAFLD by the miR‐124a/ATGL/Sirt1 pathway.

Islet β cell dedifferentiation is one of the most important mechanisms in the occurrence and development of diabetes. We studied the possible effects of chemokine stromal cell‐derived factor‐1 (SDF‐1) in the dedifferentiation of islet β cells. It was noted that the number of dedifferentiated islet β cells and the expression of SDF‐1 in pancreatic tissues significantly increased with diabetes. In islet β cell experiments, inhibition of SDF‐1 expression resulted in an increase in the number of dedifferentiated cells, while overexpression of SDF‐1 resulted in a decrease. This seemed to be contradicted by the effect of diabetes on the expression of SDF‐1 in pancreatic tissue, but it was concluded that this may be related to the loss of SDF‐1 activity. SDF‐1 binds to CXCR4 to form a complex, which activates and phosphorylates AKT, subsequently increases the expression of forkhead box O1 (FOXO1), and inhibits the dedifferentiation of islet β cells. This suggests that SDF‐1 may be a novel target in the treatment of diabetes.

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