Project description:Diabetic foot ulcer (DFU) is a common complication of diabetes characterized by increased inflammation and a slowed healing process for wounds. Interleukin-37 (IL-37) may act as an alarm to alert the immune system when released by epithelial barrier tissues during trauma or infection, exerting a broad range of protective effects in several diseases. The objective of this study was to examine the regenerative capabilities of IL-37 in improving the healing of diabetic wounds. Using streptozotocin (STZ)-induced diabetic mice, we found that diabetic IL-37Tg mice showed a significantly accelerated healing process. In addition, IL-37 strongly suppressed MAPK signaling pathway by inhibiting phosphorylation of the P38 and ERK. Moreover, IL-37 reduced the expression of Nod-like receptor protein-3 (NLRP3) and mature IL-1β. These results thus indicated that IL-37 inhibition of IL-1β production is mediated by suppressing the initial priming step and by inhibiting the NLRP3 inflammasome activation. Taken together, our findings demonstrated the promising regulatory activity of IL-37 against IL-1β production and indicated that IL-37 has the potential to be effective as a novel therapeutic agent for treatment of wound. Our data indicate a beneficial effect of IL-37 in diabetic wounds, suggesting a therapeutic potential for this cytokine in diabetic ulcer management.
Project description:Before and after negative pressure treatment in 3 diabetic foot patients, the granulation tissue of foot ulcer was sampled and analyzed quantitatively by LC-MS /MS method.
Project description:Diabetic foot ulcer (DFU) is a serious complication of diabetes mellitus, which causes great health damage and economic burden to patients. The pathogenesis of DFU is not fully understood.We screened wound healing-related genes using bioinformatics analysis, and full-thickness skin injury mice model and cellular assays were used to explore the role of target genes in diabetic wound healing. SFRP2 was identified as a wound healing-related gene, and the expression of SFRP2 is associated with immune cell infiltration in DFU. In vivo study showed that suppression of SFRP2 delayed the wound healing process of diabetic mice, impeded angiogenesis and matrix remodeling, and increased macrophage infiltration in wound tissues. In addition, suppression of SFRP2 enhanced M1 polarization in both the early and later stage of wound healing, and decreased M2 polarization in the later stage, which impeded the transition of M1 to M2 polarization of wound healing. Moreover, suppression of SFRP2 affected the transcriptome signatures-related to inflammatory response and energy metabolism at the early stage of wound healing. Extracellular flux analysis (EFA) showed that suppression of SFRP2 decreased mitochondrial energy metabolism and increased glycolysis in injury-related macrophages. Furthermore, suppression of SFRP2 inhibited transcriptome signaturesrelated to carbohydrate metabolism, lipid metabolism and amino acid metabolism, which consists the three main components of energy metabolism of macrophages. In conclusions, SFRP2 may function as a wound healing-related gene in DFU, and suppression of SFRP2 impaired diabetic wound healing by compromising the M1-to-M2 transition of macrophages and modulating the balance between mitochondrial energy metabolism and glycolysis.
Project description:Objective: This study aims to investigate the diversity of fibroblasts present in diabetic ulcers and their impact on the wound healing process, as well as to evaluate the effectiveness of Platelet-Rich Plasma (PRP) therapy in the management of diabetic ulcers. Methodology: The single-cell dataset GSE165816 from the GEO database was utilized to analyze DFU-healer and DFU-nonhealer samples in order to evaluate variations in fibroblasts. Functional characteristics of fibroblasts were investigated through analyses of cell communication, transcription factors, and pseudotime analysis. Additionally, a diabetic ulcer rat model was established to compare the therapeutic effects of PRP, followed by histological and transcriptomic sequencing analyses. Result: Single-cell sequencing analysis identified a greater abundance of fibroblasts in the group of diabetic foot ulcer (DFU) patients who exhibited healing. The findings from biological informatics analysis emphasized the critical role of fibroblasts in the wound healing process. Treatment with PRP notably enhanced wound healing in diabetic ulcers in rats, and transcriptomic analysis indicated that gene expression levels post-PRP treatment resembled those of the non-diabetic ulcer group, with a strong association to fibroblasts. Conclusion: Fibroblasts are essential in the process of healing diabetic ulcers, as certain transcription factors have the potential to facilitate wound closure. PRP therapy has been shown to enhance the healing process in diabetic ulcer rat models, possibly through the modulation of gene expression and the promotion of extracellular matrix arrangement. This research offers novel insights and potential therapeutic approaches for managing diabetic ulcers.
Project description:The purpose of this study was to evaluate gene expression differences in debrided human venous ulcer tissue from patients treated with low-frequency (20 kHz), low-intensity (100 mW/cm2) ultrasound compared to a sham treatment in an effort to better understand the potential biological mechanisms.
