O-linked β-D-N-acetylglucosamine (O-GlcNAc) modification represents a common form of posttranslational glycosylation orchestrated by two pivotal enzymes, namely, O-GlcNAc transferase and O-GlcNAcase. In recent years, emerging research has revealed a significant association between O-GlcNAc modification and the pathogenesis of diabetic foot ulcers (DFUs). Elevated O-GlcNAc levels under high-glucose conditions contribute to the pathogenesis of DFUs by modifying specific proteins, which are implicated in peripheral neuropathy, peripheral vascular disease, and impaired chronic wound healing. This process includes prolonged inflammation, compromised granulation tissue formation, disordered re-epithelialization, and blocked tissue remodelling. This review focuses on the pathogenesis of DFUs and on the correlation between protein O-GlcNAc modification and DFUs, offering potential new insights for the diagnosis and treatment of this condition.

Human umbilical cord mesenchymal stem cells (HUC-MSCs) are pluripotent and functional in many biological processes, by which releasing secretary factors to promote the self-repairing of damaged tissue or developing into functional cell at local organ. However, there is a high risk that oxidative stress would reduce the pluripotency and factor-secretion during the preparation and transplantation. Therefore, reducing oxidative stress is expected to improve the efficacy of HUC-MSCs therapy. Zinc (Zn) is an essential trace element which involves in the resistance of oxidative stress. To investigate Zn-regulated signaling pathways, we have profiled the gene expression at transcriptome level in primary HUC-MSCs treated with zinc sulfate, followed with GO and KEGG gene enrichment analysis. Zn treatment improved signal pathways for mineral absorption, cell growth, and cell death. Zn deficiency was mimicked by TPEN administration, which suppressed cell proliferation and reduced the expression of HUC-MSCs surface stem cell markers CD73, CD90 and CD105 by flow cytometry. Nuclear factor erythrocyte 2 related factor 2 (Nrf2) plays an important role in antioxidant biological processes. In vitro treatment of Zn significantly increased Nrf2 and Sirt3 expression at gene level and protein level respectively. Zn supplementation inhibited TPEN-induced failure of cell survival and reversed the reduction of Nrf2 and Sirt3 expression, which further reduced the production of ROS. Zn successfully presented its anti-oxidation effect by activating Nrf2/Sirt3 signaling pathway in HUC-MSCs. Zn supplementation may improve the efficacy of HUC-MSCs therapy with reduced oxidative stress.