High glucose induces myocardial cell injury through increasing reactive oxygen species production

Objective: To study the injury effect and molecular mechanism of high glucose on myocardial cells. Methods: Myocardial cells H9 c2 were cultured and divided into the control group treated with DMEM containing 5.5 mmol/L glucose, the high glucose group treated with DMEM containing 35 mmol/L glucose, and the N-acetylcysteine(NAC) group pre-treated with 1000μmol/L NAC and treated with DMEM containing 1000 μmol/L NAC and 35 mmol/L glucose.The production of ROS and the expression of mitochondria pathway apoptosis molecules in cells as well as the contents of collagen and collagen metabolism molecules were measured.Results: After 8 h, 16 h and 24 h of treatment, ROS RFU as well as Bax, CytC, Caspase-3 and Caspase-9 protein expression in cells and Col-I, Col-Ⅲ, PINP and PⅢNP protein levels in culture medium of high glucose group were higher than those of control group, Bcl-2 protein expression were lower than those of control group, but CTX-Ⅰ protein levels in culture medium were not significantly different from those of control group; after 24 h of treatment, Bax, CytC,Caspase-3 and Caspase-9 protein expression in cells as well as Col-Ⅰ, Col-Ⅲ, PINP and PIIINP protein levels in culture medium of NAC group were lower than those of high glucose group whereas Bcl-2 protein expression was higher than that of high glucose group. Conclusions:High glucose can induce myocardial cell apoptosis, increase collagen synthesis and accelerate interstitial fibrosis by increasing the production of reactive oxygen species.

Correlation of miR-29b expression level with oxidative stress mediators and inflammatory cytokines in diabetic foot wound

Objective:To study the correlation of miR-29b expression level with oxidative stress mediators and inflammatory cytokines in diabetic foot (DF) wound.Methods: The DF patients admitted to our hospital between February 2015 and October 2017 were selected as the DF group and wound tissues were collected;non-diabetic patients admitted to our hospital due to trauma during the same period were selected as the control group and normal skin tissues were collected. The expression level of miR-29b as well as the contents of oxidative stress mediators and inflammatory cytokines in the tissues was measured.Results: miR-29b expression as well as malondialdehyde (MDA), interleukin-1β (IL-1β), interleukin-18 (IL-18), tumor necrosis factor-α (TNF-α), vascular cell adhesion molecule-1 (VCAM-1) contents in the wounds of DF group was significantly higher than those of control group while superoxide dismutase (SOD) and glutathione peroxidase (GPX) contents were significantly lower than those of control group;miR-29b expression was positively correlated with MDA, IL-1β, IL-18, TNF-α and VCAM-1 contents, and negatively correlated with GPX and SOD contents. Conclusion: The high expression of miR-29b in diabetic foot wound is related to the over-activation of oxidative stress response and inflammatory response.

Correlation of substance P expression in diabetic foot ulcer tissue with oxidative stress and apoptosis

Objective: To study the correlation of substance P (SP) expression in diabetic foot ulcer tissue with oxidative stress and apoptosis. Methods: Patients with diabetic foot ulcer who were treated in the Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology between January 2016 and March 2017 were selected as the diabetic foot ulcer (DFU) group of the research, the diabetic foot ulcer tissue samples were collected, patients who received debridement surgery due to trauma in the Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology during the same period were selected as the control group of the research, and normal wound tissue samples were collected. The contents of SP, oxidative stress molecules and apoptosis molecules in the wound specimens were detected. Results: SP, Prdx6, GSHPX and SOD contents in diabetic foot ulcer wound specimens of DFU group were significantly lower than those in normal wound specimens of control group while MDA, AOPP, Cyto-C, Caspase-9, Fas, FasL, Caspase-8 and Caspase-3 contents were significantly higher than those in normal wound specimens of control group;Prdx6, GSHPX and SOD contents in wound of patients with high SP were significantly higher than those of patients with low SP while MDA, AOPP, Cyto-C, Caspase-9, Fas, FasL, Caspase-8 and Caspase-3 contents were significantly lower than those of patients with low SP. Conclusion: The low expression of SP in diabetic foot ulcer tissue can activate oxidative stress response and apoptosis to participate in the formation of ulcer wound.

Efficacy of autologous bone marrow mononuclear cell transplantation therapy in patients with refractory diabetic peripheral neuropathy

Background:Owing to the multifactorial nature of the pathogenesis of diabetic peripheral neuropathy (DPN),conventional drug therapies have not been effective.The application of stem cells transplantation may be useful for the treatment of DPN.This study was designed to assess the safety and therapeutic effects of autologous bone marrow mononuclear cells (BMMNCs) transplantation on the treatment of refractory DPN.Methods:One hundred and sixty-eight patients with refractory DPN were recruited and enrolled in the study.They received intramuscular injection of BMMNCs and followed at 1,3,6,12,18,24,and 36 months after the transplantation.Clinical data,Toronto Clinical Scoring System (TCSS),and nerve conduction studies (NCSs) were compared before and after the transplantation.Results:The signs and symptoms of neuropathy were significantly improved after BMMNCs transplantation.The values of the TCSS scores at 1 month (9.68 ± 2.49 vs.12.55 ± 2.19,P<0.001) and 3 months (8.47 ± 2.39 vs.12.55 ± 2.19,P<0.001) after the treatment reduced significantly compared with the baseline value.This decrement remained persistent until the end of the study.The conduction velocity and action potential and sensory nerves were significantly improved after transplantation (3 and 12 months after the treatment vs.the baseline:motor nerve conduction velocity,40.24 ± 2.80 and 41.00 ± 2.22 m/s vs.38.21 ± 2.28 m/s,P<0.001;sensory nerve conduction velocity,36.96 ± 2.26 and 39.15 ± 2.61 m/s vs.40.41 ± 2.22 m/s,P<0.001;compound muscle action potential,4.67 ± 1.05 and 5.50 ± 1.20 μV vs.5.68 ± 1.08 μV,P<0.001;sensory nerve action potential,4.29 ± 0.99 and 5.14 ± 1.26 μV vs.5.41 ± 1.14 μV,P<0.001).No adverse event associated with the treatment was observed during the follow-up period.Conclusions:Autologous transplantation of BMMNCs may be an effective and promising therapeutic strategy for the treatment of refractory DPN.