ABSTRACT
BACKGROUND: The non-healing of DFU is a major cause of high disability, morbidity, and mortality. Thus, new therapeutic targets and methods to help healing in patients with DFUs are major research hotspots. OBJECTIVE: This study examined the molecular differences between healing and non-healing DFUs to identify genes associated with diabetic foot ulcers (DFU) healing. METHODS: Differentially expressed genes (DEGs) were identified by bioinformatics. Samples were collected from patients with healing(n=10) and non-healing(n=10) DFUs from September 2021 to September 2022. IL-34 expression was measured by ELISA and qRT-PCT. The fibroblasts from healing and non-healing DFU were divided according to their gene signatures and subdivided based on their gene expression profile differences. RESULTS: A comparison of fibroblast subpopulation characteristics revealed that the proportion of subpopulation 4 was significantly higher in non-healing DFUs than in healing DFUs. Subpopulation 4 had 254 upregulated genes and 2402 downregulated genes in the non-healing compared with the healing DFUs. The DEGs were involved in several biological functions, including cytokine activity, receptor-ligand activity, signaling receptor activator activity, and receptor regulator activity. IL-34 was downregulated in non-healing compared with healing DFUs, suggesting a possible role of IL-34 in DFU healing. In the clinical specimens, IL-34 was significantly downregulated in non-healing DFUs, consistent with the bioinformatics results. CONCLUSION: IL-34 expression is downregulated in non-healing DFU. IL-34 appears to be involved in DFU healing, but the exact causal relationship remains to be explored.
ABSTRACT
Objective: Intensive glycemic control and exosomal miRNAs have both been reported to improve wound repair in diabetic ulcers. In this study, we aimed to investigate the effects of intensive glycemic control on serum exosome microRNA-126-3p (miR-126-3p), microRNA-125b-1-3p (miR-125b-1-3p), and wound healing in patients with diabetic ulcers. Methods: Herein, 45 diabetic patients with an ulcer, aged 35-75 years old, were randomly assigned to the intensive glycemic control group (n = 21) and the conventional glycemic control group (n = 24). Serum exosomes were extracted in the laboratory and assessed by Western blotting, transmission electron microscopy, and nanoparticle tracking analysis. The expression of miR-126-3p and miR-125b-1-3p was validated using quantitative real-time polymerase chain reaction. The wound healing of each diabetic ulcer patient was measured and imaged; additionally, clinical and follow-up data were collected. Finally, the clinical and laboratory data were combined for statistical analysis. Results: Intensive glycemic control was significantly more conducive to wound healing and infection control than conventional glycemic control (P < 0.05). Serum exosomal miR-126-3p was negatively correlated with fasting plasma glucose levels (r = 0.34, P < 0.05) and positively associated with the wound healing rate (r = 0.45, P < 0.01). The level of miR-126-3p in the intensive glycemic control group was significantly higher than that in the conventional glycemic control group (P < 0.01). Serum exosomal miR-125b-1-3p was not correlated with blood glucose levels (r = 0.03, P > 0.05) and was positively associated with the wound healing rate (r = 0.33, P < 0.05). No significant difference was observed in the level of miR-125b-1-3p between the intensive and conventional glycemic control groups. Regarding the prognosis of diabetic ulcers, the intensive glycemic control group was better than the conventional group (Z = -2.02, P < 0.05). Conclusion: Serum exosome (miR-125b-1-3p and miR-126-3p) levels are correlated with wound healing in diabetic ulcers. Intensive glycemic control increases the serum exosomal miR-126-3p level, which might be one of the mechanisms that promotes wound healing in diabetic ulcers.
ABSTRACT
Context: Burn therapy (MEBT)/moist exposed burn ointment (MEBO) is an effective traditional Chinese medicine method to treat diabetic wound, but the mechanism is unclear. Autophagy has been proved to be closely related with wound healing, so MEBO/MEBT is hypothesized to promote diabetic wound healing by regulating autophagy.Objective: To explore the mechanism of moist exposed MEBT/MEBO promoting diabetic wound repair.Materials and methods: Eighty male Wistar rats were randomly assigned to control (n = 20) and diabetic group induced by intraperitoneal injection of STZ (n = 60), which were further randomly assigned to MEBO, Kangfuxin and model groups (n = 20 each). All rats underwent full-thickness skin resection in the back. Wound healing was dynamically observed and wound tissues were collected at five time points for pathological examination, autophagosome and the expression of PI3K, Akt and mTOR.Results: The healing time in the control group was the shortest, no statistically significant difference was found between the MEBO and the Kangfuxin group (p = 0.76). The morphology of autophagosomes ranged large to small, which was the most obvious in the MEBO group. The mRNA and protein expression of PI3K, Akt and mTOR in each group reached the peak on Day 5, the levels in the MEBO group were the highest (F = 18.43, 19.97, 15.36, p < 0.05). On Day 11, the expression levels in each group began to decline.Discussion and conclusions: In this study, we discussed the molecular mechanism of MEBT/MEBO promoting the repair of diabetic ulcer wounds through autophagy and PI3K-Akt-mTOR signalling pathway, which provides a new way for drug design in the future.
