ABSTRACT
Among the numerous complications of diabetes mellitus, diabetic wounds seriously affect patients' quality of life and result in considerable psychological distress. Promoting blood vessel regeneration in wounds is a crucial step in wound healing. Lonicerin (LCR), a bioactive compound found in plants of the Lonicera japonica species and other honeysuckle plants, exhibits anti-inflammatory and antioxidant activities, and it recently has been found to alleviate ulcerative colitis by enhancing autophagy. In this study we investigated the efficacy of LCR in treatment of diabetic wounds and the underlying mechanisms. By comparing the single-cell transcriptomic data from healing and non-healing states in diabetic foot ulcers (DFU) of 5 patients, we found that autophagy and SIRT signaling activation played a crucial role in mitigating inflammation and oxidative stress, and promoting cell survival in wound healing processes. In TBHP-treated human umbilical vein endothelial cells (HUVECs), we showed that LCR alleviated cell apoptosis, and enhanced the cell viability, migration and angiogenesis. Furthermore, we demonstrated that LCR treatment dose-dependently promoted autophagy in TBHP-treated HUVECs by upregulating Sirt1 expression, and exerted its anti-apoptotic effect through the Sirt1-autophagy axis. Knockdown of Sirt1 significantly decreased the level of autophagy, and mitigated the anti-apoptotic effect of LCR. In a STZ-induced diabetic rat model, administration of LCR significantly promoted wound healing, which was significantly attenuated by Sirt1 knockdown. This study highlights the potential of LCR as a therapeutic agent for the treatment of diabetic wounds and provides insights into the molecular mechanisms underlying its effects.
Subject(s)
Diabetes Mellitus, Experimental , Luteolin , Wound Healing , Animals , Humans , Rats , Autophagy/drug effects , Diabetes Mellitus, Experimental/complications , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/metabolism , Human Umbilical Vein Endothelial Cells/metabolism , Luteolin/pharmacology , Luteolin/therapeutic use , Quality of Life , Sirtuin 1/genetics , Sirtuin 1/metabolism , Wound Healing/drug effectsABSTRACT
OBJECTIVE: The aim of this study was to compare clinical outcomes of patients with femoral neck fractures treated with the dynamic hip system blade (DHS-BLADE) or cannulated compression screws. METHODS: Eighty-six patients with femoral neck fractures were treated by closed reduction internal fixation with a DHS-BLADE (n = 42; 18 males and 24 females; mean age: 56.3 years (37-87)) or cannulated compression screws (n = 44; 20 males and 24 females; mean age: 53.8 years (26-83)) between March 2011 and August 2013. The groups were compared with Harris hip score, operation time, surgical blood loss, incision size, hospital stay, and related complications. RESULTS: The average follow-up time was 27 months (range, 24-36 months). There was no significant difference for the operation time, incision size, hospital stay, and Harris hip score between the groups. Also, no statistically significant differences in the rates of nonunion (4.5% vs. 0) and avascular necrosis of the femoral head (9.1% vs. 7.1%) were observed. However, the screw group experienced significantly less surgical blood loss (32.4 ± 24.7 ml) than the blade group (87.2 ± 46.6 ml; P = 0.041). The incidence of femoral neck shortening above 10 mm in the screw group was significantly higher than that in the blade group (15.9% vs. 2.4%, P = 0.031). The blade group had a significantly lower incidence of screw migration than the screw group (4.8% vs. 22.7%, P = 0.016). CONCLUSION: The DHS-BLADE and cannulated compression screws might be equally effective in terms of postoperative fracture union. However, the DHS-BLADE has advantages over cannulated compression screws for preventing femoral neck shortening, screw migration, and cut-out. LEVEL OF EVIDENCE: Level III, Therapeutic study.
