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Objective:To investigate the relationship between autophagy and nuclear factor E2 related factor 2(Nrf2) signaling pathway during high glucose-induced damage to Schwann cells.Methods:RSC96 were cells cultured in vitro and seeded in 96-well plates (1×10 4 cells/ml, 200 μl/well) or in 6-well plates (1×10 6 cells/ml, 2 ml/well) for 48 h. The cells were divided into 3 groups ( n=25 each) using a random number table method: control group (group C), high glucose group (group H) and high glucose+ autophagy agonist rapamycin group ( group H+ RAP). The cells were cultured in the common culture medium in group C. In group H, 50 mmol/L of glucose was added to the culture medium.In group H+ RAP, 50 mmol/L of glucose and 5 μmol/L rapamycin were added to the culture medium.At 48 h of incubation, the growth of cells was observed with inverted phase contrast microscope, the cell viability was measured using MTT method, apoptosis rate was determined by flow cytometry, malondialdehyde (MDA) content was determined by thiobarbituric acid method, superoxide dismutase (SOD) activity was detected using xanthine oxidase method, and the expression of Nrf2, P62 and microtubule-associated protein 1 light chain 3 Ⅱ (LC3 Ⅱ) was determined by Western blot. Results:Compared with group C, the cell viability and SOD activity were significantly decreased, apoptotic rate and MDA content were increased, and expression of Nrf2, P62 and LC3Ⅱ was up-regulated in group H and group H+ RAP ( P<0.05). Compared with group H, the cell viability and SOD activity were significantly increased, apoptosis rate and MDA content were decreased, the expression of Nrf2 and LCII was up-regulated and P62 expression was down-regulated in group H+ RAP ( P<0.05). Conclusion:Enhanced autophagy can activate Nrf2 signaling pathway, which is the endogenous protective mechanism of Schwann cell injury induced by high glucose.
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Peripheral nerve injury (PNI) is an important clinical complication, which brings long-term physical and psychological pain and economic burden to patients. There is no satisfactory treatment plan for PNI. Although microsurgery technology has been greatly developed, some peripheral nerve defects or ruptures caused by external forces can be repaired by surgery or nerve transplantation. However, due to the weak ability of nerve cell regeneration and surgical operations may cause damage to the injured nerves, the patient's functional recovery may not be able to achieve the desired effect. Therefore, it is urgent to find a safe and effective method to treat PNI. Mesenchymal stem cells have special differentiation potential and can differentiate into a variety of cell types in vitro and in vivo, and have received widespread attention from researchers. In this paper, the research progress of mesenchymal stem cells in nerve injury repair was summarized, and the characteristics, functions of mesenchymal stem cells and the mechanism of action in peripheral nerve injury repair were reviewed.
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In recent years, with the wide use of antimicrobial agents, the adverse reactions related to antimicrobial agents have attracted more and more attention.Among them, the adverse reactions in hematological system induced by antibacterial agents seriously affect patient′s health and doctor′s selection for antibiotics.For example, some beta lactam antibiotics can cause dysfunction of coagulation and hemolytic anemia.Chloramphenicol and sulfonamides can cause aplastic anemia.Linezolid can cause thrombocytopenia and anemia.It is important to understand the adverse reactions in hematological system caused by antibiotics.In this paper, the antibiotic induced adverse reactions in hematological system and their mechanism were summarized in order to provide information for the rational use of antimicrobial agents.
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Objective To evaluate the effect of hydrogen?rich saline on nuclear factor erythroid 2?related factor 2 ( Nrf2)∕antioxidant response element ( ARE) pathway in the peripheral nerve in a rat model of diabetic neuropathic pain ( DNP ) . Methods Thirty?six healthy male Sprague?Dawley rats, aged 8 weeks, weighing 180-200 g, were randomly divided into 3 groups ( n=12 each) using a random number table: control group ( C group) , DNP group and hydrogen?rich saline group ( HRS group) . Diabetes melli?tus was produced by intraperitoneal 1% streptozocin ( STZ) 65 mg∕kg and confirmed by fasting blood glucose concentration>16?67 mmol∕L. Hydrogen?rich saline 5 ml∕kg was injected intraperitoneally once a day for 14 consecutive days starting from 14 days after STZ injection in group HRS, and the equal volume of normal saline was given in C and DNP groups. The mechanical paw withdrawal threshold ( MWT) and thermal paw withdrawal latency ( TWL) were measured at 2 days before STZ injection ( T0 ) , and 7, 14, 21 and 28 days after STZ injection ( T1?4 ) . After measurement of the pain threshold at T4 , the motor nerve conduction velocity ( MNCV) of the right hindlimb and distal motor latency were measured. The expression of Nrf2 in nucleoprotein and HO?1 and NQO1 in total protein was detected in the sciatic nerve by Western blot. Re?sults Compared with group C, the MWT was significantly decreased, and the TWL was shortened at T1?4 , and the expression of Nrf2 in nucleoprotein and HO?1 and NQO1 in total protein was up?regulated in DNP and HRS groups (P<0?05). Compared with group DNP, the MWT was significantly increased, and the TWL was prolonged at T3 and T4 , and the expression of Nrf2 in nucleoprotein and HO?1 and NQO1 in total protein was up?regulated in group HRS ( P<0?05) . Conclusion The mechanism by which hydrogen?rich saline mitigates DNP is related to activated Nrf2∕ARE pathway in the peripheral nerve of rats.
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Objective To evaluate the effect of hydrogen-rich saline on Toll-like receptor 4 (TLR4) /nuclear factor kappa B (NF-κB) signaling pathway in the sciatic nerve of rats with diabetic neuropathic pain (DNP).Methods Pathogen-free male Sprague-Dawley rats, aged 8 weeks, weighing 180-210 g, were used in the study.DPN model was established by intraperitoneal injection of 1％ streptozocin (STZ) 65 mg/kg.Twenty-four diabetic rats were randomly divided into 2 groups (n =12 each) using a random number table: DPN group and hydrogen-rich saline group (HRS group).Another 12 normal rats were randomly selected and served as control group (group C).At 14 days after STZ injection, hydrogenrich saline 5 ml/kg was injected intraperitoneally once a day for 14 consecutive days in group HRS, while the equal volume of normal saline was given in C and DNP groups.Mechanical paw withdrawal threshold to yon Frey stimuli (MWT) and thermal paw withdrawal latency (TWL) were measured at 2 days before STZ injection (T0) , and 7, 14, 21 and 28 days after STZ injection (T1-4).The motor nerve conduction velocity (MNCV) of the right hindlimb was measured after pain threshold was measured at T4.After measurement of neurological function was completed, the expression of TLR4 and NF-κB was detected in the sciatic nerve (by Western blot) , the tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) contents in sciatic nerves were measured by enzyme-linked immunosorbent assay, and the neuronal apoptosis was detected by TUNEL.The apoptosis index was calculated.Results Compared with group C, the MWT was significantly decreased at T1-4, TWL was shortened at T2-4, and MNCV was decreased at T4, the expression of TLR4 and NF-κB, contents of TNF-α and IL-6, and apoptosis index were increased in HRS and DNP groups (P＜0.05).Compared with group DNP, the MWT was significantly increased, and TWL was prolonged at T3,4 MNCV was increased T4, and the expression of TLR4 and NF-κB, contents of TNF-α and IL-6, and apoptosis index were decreased in group HRS (P＜ 0.05).Conclusion Hydrogen-rich saline can mitigate DNP through blocking TLR4/NF-κB signaling pathway in the sciatic nerve of rats.