Diabetes mellitus is one of the most prominent metabolic disorders in the world, and insulin resistance in diabetic patients leads to several complications including increased inflammation and delayed wound healing. Fibroblast migration and reepithelialization play a significant role in wound healing. In this study, we explored the effects of IL‐1β signaling on proliferation and migration of human fibroblasts from diabetic wound tissues. We observed elevated levels of IL‐1β in samples from diabetic patients when compared to normal wound tissues. At high concentrations, IL‐1β inhibited cell proliferation and migration in ex vivo fibroblast cultures. Moreover, expression of matrix metalloproteinases (MMPs) was upregulated, and tissue inhibitor of metalloproteinases (TIMPs) was downregulated in diabetic wound tissues and cells. These effects were regulated by levels of IL‐1β. Furthermore, IL‐1β induced p38 phosphorylation thereby activating the p38 MAPK pathway that in turn regulated the expression of MMPs and TIMPs. Together, our study identifies a novel mechanism behind delayed wound closure in diabetes mellitus that involves IL‐1β‐dependent regulation of cell proliferation and migration.

Introduction. To investigate the contribution and mechanism of NLRP3 inflammasome expression in human wounds in diabetes mellitus and in high glucose induced macrophages. Methods. In the present study, we compared the expression of NLRP3 inflammasome in debridement wound tissue from diabetic and nondiabetic patients. We also examined whether high glucose induces NLRP3 inflammasome expression in cultures THP-1-derived macrophages and the influence on IL-1β expression. Results. The expressions of NLRP3, caspase1, and IL-1β, at both the mRNA and protein level, were significantly higher in wounds of diabetic patients compared with nondiabetic wounds (P<0.05). High glucose induced a significant increase in NLRP3 inflammasome and IL-1β expression in THP-1-derived macrophages. M1 macrophage surface marker with CCR7 was significantly upregulated after high glucose stimulation. SiRNA-mediated silencing of NLRP3 expression downregulates the expression of IL-1β. Conclusion. The higher expression of NLRP3, caspase1, and secretion of IL-1β, signaling, and activation might contribute to the hyperinflammation in the human diabetic wound and in high glucose induced macrophages. It may be a novel target to treat the DM patients with chronic wound.

We aimed to evaluate the association between vitamin D deficiency and diabetic foot ulcer (DFU) in patients with diabetes. Pubmed, EMBASE, BIOSIS, the Cochrane Library, and Web of Knowledge, last updated in July 2018, were searched. We assessed eligible studies for the association between vitamin D deficiency and DFU in diabetic patients. The mean difference (MD) or the odds ratio (OR) was calculated for continuous or dichotomous data respectively. Data were analyzed by using the Cochrane Collaboration’s RevMan 5.0 software. Seven studies that involved 1115 patients were included in this study. There were significantly reduced vitamin D levels in DFU (MD −13.47 nmol/L, 95%CI −16.84 to −10.10; P = 0.34, I² = 12%). Severe vitamin D deficiency was significantly associated with an increased risk of DFU (OR 3.22, 95%CI 2.42−4.28; P = 0.64, I² = 0%). This is the first meta-analysis demonstrating the association between serum vitamin D levels and DFU. Severe vitamin D deficiency is significantly associated with an increased risk of DFU.

Background: NLRP3 inflammasome is one of the key contributors to the impaired wound healing in diabetes. In this study, we assessed the role of rapamycin on high glucose-induced inflammation in THP-1-derived macrophages and investigated the underlying signaling mechanisms. Methods: THP-1-derived macrophages were treated with high glucose to induce NLRP3 inflammasome activation. The cells were pretreated with rapamycin, BAY 11-7082 or PDTC before exposure to HG. mTOR, NF-κB and NLRP3 inflammasome expression were measured by western blot. Results: In our experiment, we found rapamycin reduces NLRP3 inflammasome activation in macrophages. Rapamycin reduced NLRP3 inflammasome activation by inhibiting mTOR phosphorylation and NF-κB activation. Moreover, mTOR siRNA inhibited NF-κB activation, leading to the suppression of NLRP3 inflammasome activation. Conclusion: Rapamycin could ameliorate high glucose-induced NLRP3 inflammasome activation by attenuating the mTOR/NF-κB signaling pathway in macrophages. Rapamycin might act as a possible therapeutic option for high glucose-induced inflammatory response in impaired wound healing in the future.

Background: Vitamin D deficiency has been associated with an increased risk in several diabetic complications. We aimed to evaluate the association between vitamin D and diabetic foot ulcer (DFU) in patients with type 2 diabetes. Methods: Fifty one patients were included in the study and divided into two groups for study of vitamin D, cholesterol, and triglycerides in blood serum on DFU. The association between vitamin D and DFU was measured by binary logistic regression analysis. The cut point of vitamin D for DFU was assessed by the receiver operating characteristic curve. Results: Levels of 25-OH-vitamin D were lower in patients with DFU than in DM group (P < 0.0001). The AUC of 25-OH-vitamin D was 0.8254 and had an optimal cut point value (13.68 ng/ml) for the identification of DFU, with a sensitivity of 90% and a specificity of 66.67% in all patients. Multivariate logistic regression analysis indicated that the significant risk factors included 25-OH-vitamin D level (P = 0.001, OR = 0.618) and HDL-C level (P = 0.038, OR = 0.012). Conclusion: Low serum 25-OH-vitamin D level was associated with DFU. This indication was more specific than cholesterol and triglycerides levels.

Background: In this study, we try to investigate the effect of antibiotic bone cement in patients with infected diabetic foot ulcer (DFU).Methods: This is a retrospective study, including fifty-two patients with infected DFU who had undergone treated between June 2019 and May 2021. Patients were divided into Polymethylmethacrylate (PMMA) group and control group. 22 patients in PMMA group received antibiotic bone cement and regular wound debridement, and 30 patients in control group received regular wound debridement. Clinical outcomes include the rate of wound healing, duration of healing, duration of wound preparation, rate of amputation, and frequency of debridement procedures.Results: In PMMA group, twenty-two patients (100%) had complete wound healing. In control group, twenty-eight patients (93.3%) had wound healing. Compared with control group, PMMA group had fewer frequencies of debridement procedures and shorter duration of wound healing (35.32 ± 3.77 days vs 44.37 ± 7.44 days, P < 0.001). PMMA group had five minor amputation, while control group had eight minor amputation and two major amputation. Regarding the rate of limb salvage, there was no limb lose in PMMA group and two limb losses in control group.Conclusion: The application of antibiotic bone cement is an effective solution for infected DFU treatment. It can effectively decreased the frequency of debridement procedures and shorten the healing duration in patients with infected DFU.