Wenqin Xie

Diabetic peripheral neuropathy (DPN) is a common complication of type 2 diabetes mellitus (T2DM) that causes peripheral and autonomic nervous system dysfunction. Dysregulation of miRNAs plays a crucial role in DPN development. However, the role of miR-503-5p in DPN remains unknown. Herein, T2DM mice (db/db) were used as a DPN model in vivo, and astrocytes isolated from db/db mice were induced with high glucose levels as a DPN model in vitro. MiR-503-5p expression was analyzed using qRT-PCR. GFAP, MCP-1, and SEPT9 protein levels were analyzed using western blotting and immunofluorescence. Luciferase assays were performed to investigate the interaction between miR-503-5p and SEPT9. We found that miR-503-5p expression decreased in the spinal cord of DPN model mice and astrocytes treated with high glucose (HG). The db/db mice displayed higher body weight and blood glucose, lower mechanical withdrawal threshold and thermal withdrawal latency, and higher GFAP and MCP-1 protein levels than db/m mice. However, tail vein injection of agomiR-503-5p remarkably reversed these parameters, whereas antigomiR-503-5p enhanced them. HG markedly facilitated GFAP and MCP-1 protein expression in astrocytes, whereas miR-503-5p mimic or inhibitor transfection markedly blocked or elevated GFAP and MCP-1 protein expression, respectively, in astrocytes with HG. SEPT9 was a target of miR-503-5p. In addition, SEPT9 protein levels were found to be elevated in db/db mice and astrocytes treated with HG. Treatment with agomiR-503-5p and miR-503-5p mimic was able to reduce SEPT9 protein levels, whereas treatment with antigomiR-503-5p and miR-503-5p inhibitor led to inhibition of the protein. Furthermore, SEPT9 overexpression suppressed the depressing effect of miR-503-5p overexpression in astrocytes subjected to HG doses. In conclusion, miR-503-5p was found to alleviate peripheral neuropathy-induced neuropathic pain in T2DM mice by regulating SEPT9 expression.

Objective: To investigate the effect of energy intake restriction on postoperative cognitive dysfunction (POCD) after internal fixation of tibial fractures in mice. Methods: Thirty mice were divided into model groups of internal fixation of tibial fractures with 0%, 20%, 30% and 40% energy intake restriction and sham operation group (n = 6). Novel object recognition task and elevated plus maze test were used to assess the ability of recognition memory and anxiety-related behavior before and one week after surgery. The blood samples were collected from mice on days 1, 3 and 7 after surgery, and the mice were euthanized on the 8th day after surgery. RT-PCR and Western blot were employed to detect the expression of AMPK-SIRT1 pathway-related genes and proteins in the hippocampus. ELISA was used to detect the levels of inflammatory factors in the peripheral blood of mice. Hematoxylin-eosin (H&E) staining and immunofluorescence (IF) staining were used to detect the proliferation, differentiation and injury of hippocampal cells. Results: The results showed that 20% and 30% energy intake restriction significantly improved the POCD after internal fixation of tibial fractures in mice. Significantly, 30% energy intake restriction reduced the expression of AP-1, NF-.B, CD45, IBA-1, and inflammatory factors IL-1 ss, IL-6, IL-8 and TNF-a, and increased the expression of AMPK and SIRT1 after the operation. H&E and IF staining showed that 30% energy intake restriction reduced postoperative hippocampal neuronal damage. Conclusion: Energy intake restriction can significantly improve POCD after internal fixation of tibial fractures in mice and may provide a new treatment paradigm for POCD patients.