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Cell metabolism pathways involved in the pathophysiological changes of diabetic peripheral neuropathy

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Neural Regeneration Research 2024年第3期19卷 598-605页

作者： Yaowei Lv Xiangyun Yao Xiao Li Yuanming Ouyang Cunyi Fan Yun Qian Department of Orthopedics Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina Shanghai Engineering Research Center for Orthopaedic Material Innovation and Tissue Regeneration ShanghaiChina Youth Science and Technology Innovation Studio of Shanghai Jiao Tong University School of Medicine ShanghaiChina College of Fisheries and Life Science Shanghai Ocean UniversityShanghaiChina

diabetic peripheral neuropathy is a common complication of diabetes *** the pathophysiological metabolic mechanism impels the generation of ideal ***,existing limited treatments for diabetic peripheral neuropathy expose the urgent need for cell metabolism *** the lack of comprehensive understanding of energy metabolism changes and related signaling pathways in diabetic peripheral neuropathy,it is essential to explore energy changes and metabolic changes in diabetic peripheral neuropathy to develop suitable treatment *** review summarizes the pathophysiological mechanism of diabetic peripheral neuropathy from the perspective of cellular metabolism and the specific interventions for different metabolic pathways to develop effective treatment *** metabolic mechanisms(e.g.,polyol,hexosamine,protein kinase C pathway)are associated with diabetic peripheral neuropathy,and researchers are looking for more effective treatments through these pathways.

关键词： cell metabolism diabetic peripheral neuropathy peripheral nerve injury protein kinase C pathway reactive oxygen species.

diabetic corneal neuropathy as a surrogate marker for diabetic peripheral neuropathy

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Neural Regeneration Research 2022年第10期17卷 2172-2178页

作者： Wei Zheng So Natalie Shi Qi Wong Hong Chang Tan Molly Tzu Yu Lin Isabelle Xin Yu Lee Jodhbir S.Mehta Yu-Chi Liu Yong Loo Lin School of Medicine National University of SingaporeSingaporeSingapore Singapore Eye Research Institute SingaporeSingapore Department of Endocrinology Singapore General HospitalSingaporeSingapore Department of Cornea and External Eye Disease Singapore National Eye CentreSingaporeSingapore Ophthalmology and Visual Sciences Academic Clinical Program Duke-NUS Medical SchoolSingaporeSingapore

diabetic neuropathy is a prevalent microvascular complication of diabetes mellitus,affecting nerves in all parts of the body including corneal nerves and peripheral nervous system,leading to diabetic corneal neuropathy and diabetic peripheral neuropathy,*** peripheral neuropathy is diagnosed in clinical practice using electrophysiological nerve conduction studies,clinical scoring,and skin ***,these diagnostic methods have limited sensitivity in detecting small-fiber disease,hence they do not accurately reflect the status of diabetic *** recently,analysis of alterations in the corneal nerves has emerged as a promising surrogate marker for diabetic peripheral *** this review,we will discuss the relationship between diabetic corneal neuropathy and diabetic peripheral neuropathy,elaborating on the foundational aspects of each:pathogenesis,clinical presentation,evaluation,and *** will further discuss the relevance of diabetic corneal neuropathy in detecting the presence of diabetic peripheral neuropathy,particularly early diabetic peripheral neuropathy;the correlation between the severity of diabetic corneal neuropathy and that of diabetic peripheral neuropathy;and the role of diabetic corneal neuropathy in the stratification of complications of diabetic peripheral neuropathy.

关键词： corneal nerve quantification corneal nerves diabetic cornea diabetic corneal neuropathy diabetic microvascular complications diabetic peripheral neuropathy in vivo confocal microscopy neurotrophic keratopathy ocular surface

Long-term efficacy and safety of Huangqi(Radix Astragali Mongolici)-based Traditional Chinese Medicine in diabetic peripheral neuropathy:a Meta-analysis of randomized controlled trials

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Journal of Traditional Chinese Medicine 2024年第2期44卷 229-242页

作者： PING Jing HAO Hongzheng WU Zhenqi ZOU Meijuan LI Zuojing CHENG Gang School of Life Sciences and Biopharmaceutics Shenyang Pharmaceutical UniversityShenyang 110000China Department of Endocrinology Affiliated Hospital of Liaoning University of Traditional Chinese MedicineShenyang 110000China Department of Research Administration Affiliated Hospital of Liaoning University of Traditional Chinese MedicineShenyang 110000China School of Pharmacy Shenyang Pharmaceutical UniversityShenyang 110000China

OBJECTIVE:To assess the long-term effectiveness of Huangqi(Radix Astragali Mongolici,HQ)-based Traditional Chinese Medicine(TCM)in the treatment of diabetic peripheral neuropathy(DPN).METHODS:Nine databases were searched to retrieve available randomized controlled trials that compared HQbased TCM and Western Medicines in the treatment of *** methodological quality of the included studies was assessed using the Cochrane bias risk tool,and RevMan 5.4 was used for data *** effect estimates of interest were risk ratio(RR),mean difference(MD)or standardized mean difference(SMD)with 95%confidence interval(CI).RESULTS:The results from 48 available studies assessing 3759 patients demonstrated that cases administered HQ-based TCM[RR=1.30,95%CI(1.21,1.40),P<0.00001]or HQ-based TCM combined with Western Medicines[RR=1.25,95%CI(1.19,1.31),P<0.00001]exhibited higher total efficacy rates than individuals who received Western Medicine *** results showed that the HQ-based TCM group had decreased Toronto Clinical Scoring System scores[MD=-1.50,95%CI(-1.83,-1.17),P<0.00001],and reduced serum interleukin 6[SMD=-0.57,95%CI(-0.87,-0.27),P=0.0002]and tumor necrosis factors-αlevels[SMD=-0.60,95%CI(-0.95,-0.25),P=0.0009].In addition,both HQ-based TCM and HQbased TCM combined with Western Medicine increased nerve conduction velocity and decreased glycaemia compared with Western Medicine *** terms of blood lipids,oxidative stress and adverse drug reactions,there were no significant differences between the HQ-based TCM groups and the Western Medicine control ***:The current Meta-analysis revealed that HQ-based TCM yields higher efficacy and safety than Western Medicine alone for the treatment of DPN,although further well-designed RCTs are required to validate these findings.

关键词： Huangqi(Radix Astragali Mongolici) medicine Chinese traditional diabetic peripheral neuropathy Meta-analysis

Amplitude of sensory nerve action potential in early stage diabetic peripheral neuropathy:an analysis of 500 cases

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Neural Regeneration Research 2014年第14期9卷 1389-1394页

作者： Yunqian Zhang Jintao Li Tingjuan Wang Jianlin Wang Department of Neurology the Fourth Affiliated Hospital of Kunming Medical University Neuroscience Institute Kunming Medical University

Early diagnosis of diabetic peripheral neuropathy is important for the successful treatment of diabetes mellitus. In the present study, we recruited 500 diabetic patients from the Fourth Affiliated Hospital of Kunming Medical University in China from June 2008 to September 2013：221 cases showed symptoms of peripheral neuropathy （symptomatic group） and 279 cases had no symptoms of peripheral impairment （asymptomatic group）. One hundred healthy control subjects were also recruited. Nerve conduction studies revealed that distal motor latency was longer, sensory nerve conduction velocity was slower, and sensory nerve action potential and amplitude of compound muscle action potential were significantly lower in the median, ulnar, posterior tibial and common peroneal nerve in the diabetic groups compared with control subjects. Moreover, the alterations were more obvious in patients with symptoms of peripheral neuropathy. Of the 500 diabetic patients, neural conduction abnormalities were detected in 358 cases （71.6%）, among which impairment of the common peroneal nerve was most prominent. Sensory nerve abnormality was more obvious than motor nerve abnormality in the diabetic groups. The amplitude of sensory nerve action potential was the most sensitive measure of peripheral neuropathy. Our results reveal that varying degrees of nerve conduction changes are present in the early, asymptomatic stage of diabetic peripheral neuropathy.

关键词： nerve regeneration peripheral nerve injury diabetic peripheral neuropathy neural con-duction electrophysiology sensory nerve motor nerve early diagnosis neural regeneration

Huangqi Guizhi Wuwu Decoction for treating diabetic peripheral neuropathy：a meta-analysis of 16 randomized controlled trials

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Neural Regeneration Research 2016年第8期11卷 1347-1358页

作者： Bing Pang Tian-yu Zhao Lin-hua Zhao Fang Wan Ru Ye Qiang Zhou Feng Tian Xiao-lin Tong Guang'anmen Hospital of China Academy of Chinese Medical Sciences Beijing China Department of Endocrinology First Teaching Hospital of Tianjin University of Traditional Chinese Medicine Tianjin China Digestive Disease Diagnosis and Treatment Center Beijing Chinese Medicine Hospital Capital Medical University Beijing China Institute of Basic Research in Clinical Medicine China Academy of Chinese Medical Sciences Beijing China

OBJECTIVE：This meta-analysis was performed to systematically assess the efficacy and safety of the Chinese herbal medicine Huangqi Guizhi Wuwu Decoction（HGWWD） for treating diabetic peripheral *** SOURCES：Six electronic databases,including the Cochrane Library,MEDLINE database,Chinese Biomedical Database,Chinese National Knowledge Infrastructure Database,Chinese Science and Technique Journals Database,and the Wanfang Database,were search ed on the internet for randomized controlled trials published up until 1 December *** search terms included ＂Chinese herbal medicine＂,＂diabetic peripheral neuropathy＂ and ＂randomized controlled trials＂ in Chinese and in *** SELECTION：We included randomized controlled trials using HGWWD/modified HGWWD for the treatment group,without restriction for the control *** assessed literature quality in accordance with the Cochrane Review Handbook.A random or a fixed effects model was used to analyze outcomes using Rev Man 5.2 *** MEASURES：The primary outcomes were changes in symptoms and nerve conduction *** secondary outcomeswere fasting blood glucose and hemorheological ***：Sixteen randomized controlled trials,with a total of 1,173 patients,were ***-analysis revealed that the efficacy of HGWWD for diabetic peripheral neuropathy was significantly superior compared with the control treatment（i.e.,control group）（risk ratio = 0.36,95% confidence interval（CI）：0.29–0.46,Z =8.33,P 〈 0.00001） Compared with the control group,there was an increase in median motor nerve conduction velocity（mean difference（MD） = 3.46,95%CI：1.88–5.04,Z = 4.30,P 〈 0.01） and median sensory nerve conduction velocity（MD = 3.30,95%CI：2.04–4.56,Z = 5.14,P 〈 0.01）.There was also an increase in peroneal motor nerve conduction velocity（MD = 3.22,95%CI：2.45–3.98,Z = 8.21,P 〈 0.01） and peroneal sensory nerve conduction velocity（MD = 3.05,95%CI：2.01–4.09,Z = 5.75,P 〈 0.01） in the treatment *** signi

关键词： nerve regeneration meta-analysis diabetic peripheral neuropathy randomized controlled trials Huangqi Guizhi Wuwu Decoction traditional Chinese medicine mecobalamin efficacy nerve conduction velocities fasting blood glucose hemorheology neural regeneration

The circ_0002538/miR-138-5p/plasmolipin axis regulates Schwann cell migration and myelination in diabetic peripheral neuropathy

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Neural Regeneration Research 2023年第7期18卷 1591-1600页

作者： Yu-Tian Liu Zhao Xu Wei Liu Sen Ren He-Wei Xiong Tao Jiang Jing Chen Yu Kang Qian-Yun Li Zi-Han Wu Hans-GüNther Machens Xiao-Fan Yang Zhen-Bing Chen Department of Hand Surgery Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei ProvinceChina Department of Geriatrics Renmin Hospital of Wuhan UniversityWuhanHubei ProvinceChina Department of Plastic and Hand Surgery Technical University of MunichMunichGermany

Circular RNAs(circRNAs)play a vital role in diabetic peripheral ***,their expression and function in Schwann cells in individuals with diabetic peripheral neuropathy remain poorly ***,we performed protein profiling and circRNA sequencing of sural nerves in patients with diabetic peripheral neuropathy and *** profiling revealed 265 differentially expressed proteins in the diabetic peripheral neuropathy *** Ontology indicated that differentially expressed proteins were mainly enriched in myelination and mitochondrial oxidative phosphorylation.A real-time polymerase chain reaction assay performed to validate the circRNA sequencing results yielded 11 differentially expressed ***_0002538 was markedly downregulated in patients with diabetic peripheral *** in vitro experiments showed that overexpression of circ_0002538 promoted the migration of Schwann cells by upregulating plasmolipin(PLLP)***,overexpression of circ_0002538 in the sciatic nerve in a streptozotocin-induced mouse model of diabetic peripheral neuropathy alleviated demyelination and improved sciatic nerve *** results of a mechanistic experiment showed that circ_0002538 promotes PLLP expression by sponging miR-138-5p,while a lack of circ_0002538 led to a PLLP deficiency that further suppressed Schwann cell *** findings suggest that the circ_0002538/miR-138-5p/PLLP axis can promote the migration of Schwann cells in diabetic peripheral neuropathy patients,improving myelin sheath structure and nerve ***,this axis is a potential target for therapeutic treatment of diabetic peripheral neuropathy.

关键词： circ_0002538 circRNA sequencing competing endogenous RNAs demyelination diabetic peripheral neuropathy miR-138-5 myelination plasmolipin protein profiling Schwann cells

Strategies and Research Progress of Chinese Medicine in Prevention and Treatment of diabetic peripheral neuropathy

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Chinese Journal of Integrative Medicine 2018年第10期24卷 794-800页

作者： YANG Dan LIANG Xiao-chun Department of Traditional Chinese Medicine Peking Union Medical College Hospital Peking Union Medical CollegeTranslational Medicine Center Chinese Academy of Medical Sciences

diabetic peripheral neuropathy （DPN） seriously affects the quality of life in patients with type 2 diabetes mellitus. This paper reviews the role of Chinese medicine in the main treatment goal of DPN, including protecting pancreatic β-cells, in the use of antioxidation therapy to delay disease progression, and in the endpoint of neural repair and regeneration. We propose that protecting the body from injury caused by high glucose and oxidative stress, and promoting repair and regeneration of nerves should be the research direction for the prevention and treatment of DPN.

关键词： diabetic peripheral neuropathy pancreatic β-cell anti-oxidative stress neural repair and regeneration Chinese medicine

Targeted metabolomics reveals the aberrant energy status in diabetic peripheral neuropathy and the neuroprotective mechanism of traditional Chinese medicine JinMaiTong

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Journal of Pharmaceutical Analysis 2024年第2期14卷 225-243页

作者： Bingjia Zhao Qian Zhang Yiqian He Weifang Cao Wei Song Xiaochun Liang Department of Traditional Chinese Medicine Peking Union Medical College HospitalPeking Union Medical CollegeChinese Academy of Medical SciencesBeijing100730China Institute of Basic Medicine Sciences Chinese Academy of Medical SciencesBeijing100005China Medical Research Center Peking Union Medical College HospitalPeking Union Medical CollegeChinese Academy of Medical SciencesBeijing100730China

diabetic peripheral neuropathy (DPN) is a common and devastating complication of diabetes, for which effective therapies are currently lacking. Disturbed energy status plays a crucial role in DPN pathogenesis. However, the integrated profile of energy metabolism, especially the central carbohydrate metabolism, remains unclear in DPN. Here, we developed a metabolomics approach by targeting 56 metabolites using high-performance ion chromatography-tandem mass spectrometry (HPIC-MS/MS) to illustrate the integrative characteristics of central carbohydrate metabolism in patients with DPN and streptozotocin-induced DPN rats. Furthermore, JinMaiTong (JMT), a traditional Chinese medicine (TCM) formula, was found to be effective for DPN, improving the peripheral neurological function and alleviating the neuropathology of DPN rats even after demyelination and axonal degeneration. JMT ameliorated DPN by regulating the aberrant energy balance and mitochondrial functions, including excessive glycolysis restoration, tricarboxylic acid cycle improvement, and increased adenosine triphosphate (ATP) generation. Bioenergetic profile was aberrant in cultured rat Schwann cells under high-glucose conditions, which was remarkably corrected by JMT treatment. In-vivo and in-vitro studies revealed that these effects of JMT were mainly attributed to the activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK) and downstream peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). Our results expand the therapeutic framework for DPN and suggest the integrative modulation of energy metabolism using TCMs, such as JMT, as an effective strategy for its treatment.

关键词： diabetic peripheral neuropathy JinMaiTong Energy metabolism Targeted metabolomics Adenosine monophosphate-activated protein kinase

Angiogenin gene polymorphism A risk factor for diabetic peripheral neuropathy in the northern Chinese Han population?

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Neural Regeneration Research 2013年第36期8卷 3434-3440页

作者： Hongli Wang Dongsheng Fan Yingshuang Zhang Department of Neurology Peking University Third Hospital

Angiogenin is associated with the pathogenesis of diabetic peripheral neuropathy. Here, we se- quenced the coding region of the angiogenin gene in genomic DNA from 207 patients with type 2 diabetes mellitus （129 diabetic peripheral neuropathy patients and 78 diabetic non-neuropathy pa- tients） and 268 healthy controls. All subjects were from the Han population of northern China. No mutations were found. We then compared the genotype and allele frequencies of the angiogenin synonymous single nucleotide polymorphism rs11701 between the diabetic peripheral neuropathy patients and controls, and between the diabetic neuropathy and non-neuropathy patients, using a case-control design. We detected no statistically significant genetic associations. Angiogenin may not be associated with genetic susceptibility to diabetic peripheral neuropathy in the Han population of northern China.

关键词： neural regeneration angiogenin single nucleotide polymorphism type 2 diabetes mellitus diabetic peripheral neuropathy angiogenesis diabetic microvascular complications genetic susceptibility risk factor peripheral nerve injury grants-supported paper neuroregeneration