Efficacy of autologous bone marrow mononuclear cell transplantation therapy in patients with refractory diabetic peripheral neuropathy / 中华医学杂志(英文版)

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.

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 H9c2 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 1000 ?mol/L NAC and treated with DMEM containing 1000 ?mol/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.

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 H9c2 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 1 000 μmol/L NAC and treated with DMEM containing 1 000 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.