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Effects of Hirudin on High Glucose-Induced Oxidative Stress and Inflammatory Pathway in Rat Dorsal Root Ganglion Neurons

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Chinese Journal of Integrative Medicine 2020年第3期26卷 197-204页

作者： LIU Wei LIANG Xiao-chun SHI Yue Department of Traditional Chinese Medicine Peking Union Medical College Hospital Peking Union Medical College Chinese Academy of Medical Sciences

Objective:To investigate protective effects of hirudin on oxidative stress and apoptosis of spinal dorsal root ganglion cells in high-glucose rats at the cellular and molecular ***:Dorsal root ganglion neurons(DRGn)were harvested from embryonic day in 15 SD rats,purified and identificated after primary *** were divided into the normal control group,high-glucose(HG)group,positive control(alpha-lipoic acid,ALA)group,low-dose hirudin group(H1),medium-dose hirudin group(H2)and high-dose hirudin group(H3).The control group was cultured by neuron specific culture medium,while the HG group was cultured by neuron specific culture medium and 20 mmol/L glucose(HG medium).The hirudin groups were cultured by HG medium+0.25 IU/mL hirudin(H1),HG medium+0.5 IU/mL hirudin(H2)and HG medium+1 IU/mL hirudin(H3).The ALA group was cultured by HG medium +100μmol/L ALA.3-(4,5-dimethylthiazol-2-yl)-2,5-diphenylt etrazolium bromide(MTT)assay was used to explore the optimum concentration and intervention *** cytometry assay was used to detect the level of reactive oxygen series(ROS).Western blot and quantificational realtime polymerase chain reaction(qRT-PCR)were used to detect the expression of protein and mRNA of nuclear factor erythroid 2-related factor 2(Nrf-2),hemeoxygence-1(HO-1),nuclear factor-κB(NF-κB)and *** assay was used to test the apoptosis rate of different ***:After 24 h of culture,the cell activity of hirudin and ALA groups were higher than that of HG group,and there was a statistical difference between the H1 group and HG group(P<0.05).In hirudin groups,the apoptosis rate of cells,the expression of activated Caspase-3 protein and Caspase-3 mRNA were lower than those of HG group(P<0.01),higher than those of ALA group(P<0.01 or P<0.05).The ROS level of hirudin groups was higher than that of ALA group(P<0.01),lower than that of HG group(P<0.01 or P<0.05).The expression of NF-κB(P65)protein in H3 group were lower than those of HG g

关键词： hirudin diabetic peripheral neuropathy oxidative stress apoptosis dorsal root ganglion neuron

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Factors Associated with peripheral neuropathy in Type 2 Diabetes： Subclinical versus Confirmed neuropathy

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2017年第3期37卷 337-342页

作者： Yogendranathsing Unmar Mohammad Ishraq Zafar 高峰 Department of Endocrinology Union Hospital Tongji Medical College Huazhong University of Science and Technology

This study determined the prevalence of diabetic peripheral neuropathy(DPN) and subclinical DPN(s DPN) in patients with type 2 diabetes mellitus(T2DM) using nerve conduction study(NCS) as a diagnostic tool. We also investigated the factors associated with the development of s DPN and compared factors between the sD PN and confirmed DPN(cDPN). This cross-sectional study involved 240 T2DM patients who were successively admitted to the endocrinology wards of Wuhan Union Hospital over the period of January to December 2014. Data on the medical history, physical and laboratory examinations were collected. DPN was diagnosed using NCS. One-way ANOVA with least significant difference(LSD) analysis or chi-square tests was used to compare parameters among DNP-free, s DPN and c DPN patients. Independent factors associated with s DPN were determined using logistic regression. The results showed that 50.8% of the participants had DPN, and among them, 17.1% had sDPN. sDPN showed significant independent associations with age, height, HbA1c, presence of atherosclerosis and diabetic retinopathy. Patients with DPN differed significantly from those without DPN with respect to age, duration of disease(DOD), HbA1c, presence of atherosclerosis, diabetic retinopathy, nephropathy and hypertension. Patients with cDPN, relative to those with sDPN, had significantly longer DOD and higher prevalence of peripheral artery disease(PAD) and coronary artery disease(CAD). Our study suggests that a significant number of T2DM patients are affected by s DPN, and the development of this condition is associated with advanced age, tall stature, poor glycaemic control, presence of diabetic retinopathy and atherosclerosis. On the other hand, patients with cDPN tend to have a longer DOD and are more likely to suffer from PAD and CAD.

关键词： diabetic peripheral neuropathy type 2 diabetes mellitus subclinical diabetic peripheral neuropathy nerve conduction study

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Guidelines on multidisciplinary approaches for the prevention and management of diabetic foot disease(2020 edition)

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Burns & Trauma 2020年第1期8卷 217-268页

作者： Aiping Wang Guozhong Lv Xingbo Cheng Xianghua Ma Wei Wang Jianchao Gui JiHu Meng Lu Guoping Chu Jin’an Chen Hao Zhang Yiqiu Jiang Yuedong Chen Wengbo Yang Lin Jiang Houfa Geng Rendong Zheng Yihui Li Wei Feng Boey Johnson Wenjuan Wang Dalong Zhu Yin Hu diabetic Foot Centre The Air Force Hospital From Eastern Theater of PLANanjing210002China Department of Burn and Plastic Surgery Affiliated Hospital of Jiangnan UniversityWuxi214062China Department of endocrinology the First Affiliated Hospital of Suzhou UniversitySuzhou215006China Department of endocrinology Jiangsu Province HospitalNanjing210029China Vascular Surgery Gulou HospitalNanjing210008China Department of orthopedics Nanjing First HospitalNanjing210006China Department of endocrinology The Second Affiliated Hospital of Suzhou UniversitySuzhou215004China Department of endocrinology Xuzhou Central HospitalXuzhou221009China Department of endocrinology Jiangsu Province Hospital on Traditional of Chinese and Western Medicine210028China Operating department Jiangsu Medical AssociationNanjing210008China diabetic Foot Centre The National University Hospital119077Singapore Department of Chronic Non-Communicable Diseases Chinese Center for Disease Control and PreventionBeijing102206China

In recent years,as living standards have continued to improve,the number of diabetes patients in China,along with the incidence of complications associated with the disease,has been *** these complications,diabetic foot disease is one of the main causes of disability and death in diabetic *** to the differences in economy,culture,religion and level of medical care available across different regions,preventive and treatment methods and curative results for diabetic foot vary *** multidisciplinary models built around diabetic foot,the timely assessment and diagnosis of wounds and appropriate methods of prevention and treatment with internal and external surgery are key to clinical practice for this *** 2019,under the leadership of the Jiangsu Medical Association and Chinese Diabetes Society,the writing group for the Guidelines on multidisciplinary approaches for the prevention and management of diabetic foot disease(2020 edition)was established with the participation of scholars from the specialist areas of endocrinology,burn injury,vascular surgery,orthopedics,foot and ankle surgery and *** lessons from diabetic foot guidelines from other countries,this guide analyses clinical practices for diabetic foot,queries the theoretical basis and grades and gives recommendations based on the characteristics of the pathology in *** paper begins with assessments and diagnoses of diabetic foot,then describes treatments for diabetic foot in detail,and ends with protections for high-risk feet and the prevention of *** manuscript covers the disciplines of internal medicine,surgical,nursing and rehabilitation and describes a total of 50 recommendations that we hope will provide procedures and protocols for clinicians dealing with diabetic foot.

关键词： diabetic foot disease diabetic peripheral neuropathy peripheral arterial disease diabetic foot osteomyelitis diabetic foot infection diabetic complication Ankle-brachial index Transcutaneous oxygen pressure Recommendation Randomized controlled trials

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Glycyrrhizic acid promotes sciatic nerves recovery in type 1 diabetic rats and protects Schwann cells from high glucose-induced cytotoxicity

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The Journal of Biomedical Research 2022年第3期36卷 181-194,I0003,I0004页

作者： Min Shi Xiangcheng Zhang Ridong Zhang Hong Zhang Dalong Zhu Xiao Han Key Laboratory of Human Functional Genomics of Jiangsu Province Department of Biochemistry and Molecular BiologyNanjing Medical UniversityNanjingJiangsu 211166China Department of Endocrinology Nanjing Drum Tower Hospital Clinical College of Nanjing Medical UniversityNanjingJiangsu 210008China Department of Endocrinology the Affiliated Huai'an No.1 People's Hospital of Nanjing Medical UniversityHuai'anJiangsu 223300China Department of Intensive Care Unit the Affiliated Huai'an No.1 People's Hospital of Nanjing Medical UniversityHuai'anJiangsu 223300China

The present study aims to investigate the therapeutic effect and mechanism of glycyrrhizic acid(GA)in diabetic peripheral neuropathy(DPN).GA significantly mitigated nerve conduction velocity(NCV)deficit and morphological abnormality and reduced high-mobility group box-1(HMGB1)expression in the sciatic nerves of diabetic rats independent of blood glucose and body ***,GA alleviated the increase of HMGB1 and the decrease of cell viability in high glucose-stimulated RSC96 ***,GA obviously reduced the concentration of inflammatory cytokines in the sciatic nerves of diabetic rats and supernatants of high glucose-exposed RSC96 cells,then restored the decreased expression levels of nerve growth factor(NGF)and neuritin-1,and the increased expression levels of cleaved caspase-3 and neuron-specific ***,GA markedly inhibited receptor for advanced glycation end products(RAGE)expression,p38MAPK phosphorylation,and the nuclear translocation of NF-κBp65 in diabetic rats and high glucose-exposed RSC96 *** promotional effect of high glucose in RSC96 cells was diminished following Hmgb1 siRNA *** findings indicate that GA may exert neuroprotection on DPN by suppressing HMGB1,which lead to extenuation of inflammation response,balance of NGF,neuritin-1 and caspase-3,as well as inactivation of RAGE/p38MAPK/NF-κBp65 signaling pathway.

关键词： diabetic peripheral neuropathy glycyrrhizic acid high-mobility group box-1 inflammation

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The correlation between insulin and OCT-6 transcription factor in Schwann cells and sciatic nerve of diabetic rats

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Genes & Diseases 2018年第2期5卷 130-136页

作者： Mallahalli S.Manu Kuruvanthe S.Rachana Gopal M.Advirao Department of Biochemistry Davangere UniversityDavangereKarnatakaIndia

Insulin signal is one of the vital signaling cascade required for Schwann cells to myelinate the axons of peripheral nervous system(PNS).Myelin formation of peripheral nerve is a complex molecular event controlled by different neurotrophic and transcription *** altered or failure in this signaling progression is one of the reasons behind the demyelination of peripheral neurons in diabetic peripheral neuropathy(DPN).The Schwann cell in PNS includes POU domain transcription factor OCT-6 *** factor is considered as crucial for the initiation and enhancement of myelination during nerve *** know the importance of OCT-6 gene,here we studied the long term expression of OCT-6 nuclear protein in sciatic nerve of normal and diabetic neuropathic *** for the first time we elucidated the role of insulin in controlling the expression of OCT-6 in hyperglycemic Schwann cells and sciatic nerve of diabetic neuropathic *** results shows that,there will be long term OCT-6 expression in sciatic nerve of adult rats and also their significant decrease is observed in the diabetic ***,addition of Insulin for primary Schwann cells and diabetic rats shows the increased OCT-6 expression in both in vivo and in *** these results indicate the failure of OCT-6 support in neuropathy and also the importance of insulin signaling cascade in the expression of OCT-6 transcription factor.

关键词： diabetic peripheral neuropathy Insulin OCT-6 Schwann cells Sciatic nerve

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Insulin inhibits the JNK mediated cell death via upregulation of AKT expression in Schwann cells grown in hyperglycemia

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Frontiers in Biology 2018年第2期13卷 137-144页

作者： Mallahalli S. Manu Kuruvanthe S. Rachana Gopal M. Advirao Department of Biochemistry Davangere University Davangere Karnataka India

BACKGROUND： Schwann cells （SCs） are the glial cells of the peripheral nervous system, which forms a thick insulating structure around the axons. Hyperglycemia is known physiologic conditions in both type Ⅰ and type Ⅱ diabetes which causes diabetic neuropathy. But the SC possesses insulin receptors even though glucose uptake is independent of insulin. Since the insulin level is highly altered in diabetes, it is of greater importance to evaluate their role in the Schwann cell survival and death. METHODS： Schwann cells were isolated from neonatal pups and grown with and without insulin in hyperglycemic medium to mimic diabetic condition for 24 and 48 h. We studied the cell viability using 3 （4,5-dimethylthiazol-2-yl） 2,5- diphenyltetrazolium bromide （MTT） and mitochondrial membrane potential （MMP） assay at different time interval on SCs. We also studied the protein and gene expression of Protein Kinase B （AKT） and Jun N-terminal kinase （JNK）, which are greatly involved in cell survival and cell death respectively. RESULTS： The result shows that, high glucose levels for 48 h decrease the SC viability. Hyperglycemic condition induces the SC death by increasing the JNK expression which in turn reduces the MMP of glial cells. However, insulin administration for SCs grown in high glucose condition can reduce the JNK expression by activating AKT signaling pathway. CONCLUSION： These observations demonstrate that the proper insulin balance is required for Schwann cells survival in hyperglycemic condition. Therefore, altered insulin signaling can be one of the reasons for demyelination of peripheral neurons in diabetic neuropathy.

关键词： insulin schwann cells apoptosis JNK AKT diabetic peripheral neuropathy

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Continuous glucose monitoring defined time-in-range is associated with sudomotor dysfunction in type 2 diabetes

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World Journal of Diabetes 2020年第11期11卷 489-500页

作者： Qing-Yu Guo Bin Lu Zhan-Hong Guo Zhou-Qin Feng Yan-Yu Yuan Xu-Guang Jin Pu Zang Ping Gu Jia-Qing Shao Department of Endocrinology Jinling HospitalSchool of MedicineNanjing UniversityNanjing 210002Jiangsu ProvinceChina Department of Endocrinology Jinling HospitalNanjing Medical UniversityNanjing 210002Jiangsu ProvinceChina Department of Endocrinology Jinling HospitalSouthern Medical UniversityNanjing 210002Jiangsu ProvinceChina

BACKGROUND Time in range(TIR),as a novel metric for glycemic control,has robust relevance with diabetic *** peripheral neuropathy(DPN)is characterized by sudomotor *** To explore the relationship between TIR obtained from continuous glucose monitoring(CGM)and sudomotor function detected by SUDOSCAN in subjects with type 2 *** The research enrolled 466 inpatients with type 2 *** subjects underwent 3-d CGM and *** was assessed with electrochemical skin conductance in hands(HESC)and feet(FESC).Average feet ESC<60μS was defined as sudomotor dysfunction(+),otherwise it was sudomotor dysfunction(-).TIR refers to the percentage of time when blood glucose is between 3.9-10 mmol/L during 1 d *** Among the enrolled subjects,135(28.97%)presented with sudomotor *** with sudomotor dysfunction(+)showed a decreased level of TIR(P<0.001).Compared to the lowest tertile of TIR,the middle and the highest tertiles of TIR was associated with an obviously lower prevalence of sudomotor dysfunction(20.51%and 21.94%vs 44.52%)(P<0.001).In addition,with the increase of TIR,HESC and FESC increased(P<0.001).Regression analysis demonstrated that TIR was inversely and independently linked with the prevalence of sudomotor dysfunction after adjusting for confounding values(odds ratio=0.979,95%CI:0.971-0.987,P<0.001).CONCLUSION The tight glycemic control assessed by TIR is of vitally protective value for sudomotor dysfunction in type 2 diabetes mellitus.

关键词： Time in range Sudomotor dysfunction SUDOSCAN diabetic peripheral neuropathy Continuous glucose monitoring Diabetes mellitus Type 2

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diabetic foot ulcer: Challenges and future

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World Journal of Diabetes 2022年第12期13卷 1014-1034页

作者： Li Yang Gui-Chuan Rong Qi-Nan Wu Department of Endocrinology Dazu Hospital of Chongqing Medical UniversityThe People's Hospital of DazuChongqing 402360China Department of Gynaecology Dazu Hospital of Chongqing Medical UniversityThe People's Hospital of DazuChongqing 402360China

diabetic foot ulcers(DFUs)have become one of the important causes of mortality and morbidity in patients with diabetes,and they are also a common cause of hospitalization,which places a heavy burden on patients and *** prevention and treatment of DFUs requires multidisciplinary *** controlling various risk factors,such as blood glucose levels,blood pressure,lipid levels and smoking cessation,local management of DFUs should be strengthened,such as debridement,dressing,revascularization,stem cell decompression and oxygen *** necessary,systemic anti-infection treatment should be *** reviewed the progress in the clinical practice of treating DFUs in recent years,such as revascularization,wound repair,offloading,stem cell transplantation,and anti-infection *** also summarized and prospectively analyzed some new technologies and measurements used in the treatment of DFUs and noted the future challenges and directions for the development of DFU treatments.

关键词： diabetic foot ulcer diabetic peripheral artery disease diabetic peripheral neuropathy

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Relationship of serum vitamin D levels with diabetic microvascular complications in patients with type 2 diabetes mellitus

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Chinese Medical Journal 2021年第7期134卷 814-820页

作者： Wei-Jing Zhao Xin-Yi Xia Jun Yin Department of Endocrinology and Metabolism Shanghai Clinical Center for Metabolic DiseasesShanghai Diabetes InstituteShanghai Key Laboratory of Diabetes MellitusShanghai Jiao Tong University Affiliated Sixth People’s HospitalShanghai200233China Shanghai Clinical Center for Metabolic Diseases Shanghai Key Laboratory of Diabetes MellitusShanghai Diabetes InstituteShanghai Jiao Tong University Affiliated Sixth People’s HospitalShanghai 200233China Department of Endocrinology and Metabolism Shanghai Eighth People’s HospitalShanghai 200235China.

Background:Vitamin D deficiency has been reported to be associated with diabetic microvascular complications,but previous studies have only focused on the relationship between vitamin D and specific ***,we aimed to explore the relationship between vitamin D level and diabetic microvascular complications in general,including diabetic retinopathy(DR),diabetic nephropathy(DN),and diabetic peripheral neuropathy(DPN).Methods:This was a cross-sectional study of 815 patients with type 2 diabetes mellitus(T2DM).Clinical information and laboratory results were collected from the medical *** relationship between vitamin D and the three diabetic microvascular complications was ***:The serum 25-hydroxyvitamin D(25[OH]D)level of patients with DPN and/or DN was significantly lower than that of T2DM patients without any microvascular complications(P<0.01).Univariate analysis showed that the 25(OH)D level was related to DPN and DN,but not *** adjustment,the 25(OH)D level was confirmed to be an independent protective factor for DPN(odds ratio[OR]:0.968,P=0.004)and DN(OR:0.962,P=0.006).The prevalence of DPN and DN increased significantly as the serum 25(OH)D levels ***,patients with both DPN and DN had the lowest concentration of serum 25(OH)D(P<0.001),and the prevalence of macroalbuminuria increased more abruptly than that of microalbuminuria across the 25(OH)D *** the patients with vitamin D insufficiency,those with DPN presented more comorbid macroalbuminuria than those without DPN(15.32%vs.4.91%;P=0.001).Conclusions:Vitamin D deficiency is independently associated with higher risk of DPN and DN,but not DR,in T2DM ***,it may be a potential predictor for both the occurrence and severity of DPN and DN.

关键词： Type 2 diabetes mellitus diabetic retinopathy diabetic nephropathy diabetic peripheral neuropathy Vitamin D

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Puerarin prevents high glucose-induced apoptosis of Schwann cells by inhibiting oxidative stress

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Neural Regeneration Research 2012年第33期7卷 2583-2591页

作者： Yingying Wu Bing Xue Xiaojin Li Hongchen Liu Institute of Stomatology Chinese PLA General Hospital Beijing 100853 China Department of Endocrinology General Hospital of Shenyang Military Region Shenyang 110016 Liaoning Province China Department of Endocrinology Chinese PLA General Hospital Beijing 100853 China

Oxidative stress may be the unifying factor for the injury caused by hyperglycemia in diabetic peripheral neuropathy. Puerarin is the major isoflavonoid derived from Radix puerariae and has been shown to be effective in increasing superoxide dismutase activity. This study sought to investigate the neuroprotective effect of puerarin on high glucose-induced oxidative stress and Schwann cell apoptosis in vitro. Intracellular reactive oxygen radicals and mitochondrial transmembrane potential were detected by flow cytometry analysis. Apoptosis was confirmed by TUNEL and oxidative stress was monitored using an enzyme-linked immunosorbent assay for the DNA marker 8-hydroxy-2-deoxyguanosine. The expression levels of bax and bcl-2 were analyzed by quantitative real-time reverse transcriptase-PCR, while protein expression of cleaved caspase-3 and -9 were analyzed by means of western blotting. Results suggested that puerarin treatment inhibited high glucose-induced oxidative stress, mitochondrial depolarization and apoptosis in a dose-dependent manner. Furthermore, puerarin treatment downregulated Bax expression, upregulated bcl-2 expression and attenuated the activation of caspase-3 and -9. Overall, our results indicated that puerarin antagonized high glucose-induced oxidative stress and apoptosis in Schwann cells.

关键词： puerarin diabetic peripheral neuropathy hyperglycemia Schwann cell apoptosis caspase mitochondrial transmembrane potential oxidative stress 8-hydroxy-2-deoxyguanosine reactive oxygen radical

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