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Potential utility of aldose reductase-deficient Schwann cells IKARS1 for the study of axonal degeneration and regeneration

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Neural Regeneration Research 2018年第6期13卷 979-980页

作者： Naoko Niimi Kazunori Sango Diabetic Neuropathy Project Department of Sensory and Motor Systems Tokyo Metropolitan Institute of Medical Science

diabetic peripheral neuropathy（DPN）is one of the most common and intractable complications of diabetes mellitus.Its irritating symptoms,such as paresthesia,hyperalgesia and allodynia,can be causes of insomnia and depression;whereas its progression to more advanced stages can result in serious consequences,such as lower limb amputations and lethal arrhythmias.

关键词： DPN Potential utility of aldose reductase-deficient Schwann cells IKARS1 for the study of axonal degeneration and regeneration NGF NCV AR PNS

Efficacy of glucagon-like peptide-1 mimetics for neural regeneration

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Neural Regeneration Research 2015年第11期10卷 1723-1724页

作者： Kazunori Sango Kazunori Utsunomiya Diabetic Neuropathy Project (Former ALS/neuropathy project) Department of Sensory and Motor Systems Tokyo Metropolitan Institute of Medical Science Division of Diabetes Metabolism & Endocrinology Department of Internal Medicine Jikei University School of Medicine

Glucagon-like peptide 1（GLP-1）is secreted from enteroendocrine L cells in response to nutrient ingestion and exhibits insulinotropic properties by stimulating specific G protein-linked receptors（GLP-1Rs）on pancreaticβcells.Several GLP-1 mimetics,such as exenatide（exendin-4（Ex-4））,liraglutide,and lixisenatide,have been developed and approved as treatments for patients with type 2 diabetes.These peptides show bioactiv-ities almost identical to those of GLP- 1 and have a substantially longer plasma half-life than GLP-1 because of their resistance to dipeptidyl peptidase-4, a GLP-1 degrading enzyme.

关键词： GLP DRG Efficacy of glucagon-like peptide-1 mimetics for neural regeneration

Association of high-density lipoprotein cholesterol and wound healing in patients with diabetic foot ulcers

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Chinese Medical Journal 2022年第1期135卷 110-112页

作者： Lihong Chen Wanxia Ma Dawei Chen Chun Wang Yun Gao Xingwu Ran Department of Endocrinology and Metabolism Diabetic Foot Care CenterWest China HospitalSichuan UniversityChengduSichuan 610041China

To the Editor:diabetic foot ulcers(DFUs)are an important cause of morbidity in patients with diabetes mellitus(DM).The prevalence of foot ulcers in patients with diabetes is 4%to 10%,with the lifetime incidence estimated to be between 19%and 34%.[1]DFUs have become a considerable burden on patients and the healthcare service system.However,the mechanism is not fully understood,and DFUs are still difficult to heal.High-density lipoproteins(HDL)are circulating particles composed of phospholipids,cholesterol,and proteins.HDL attracted lots of attention mainly because of its protective effect against the development of atherosclerosis.However,it has been shown that decreased HDL levels are correlated with an increased risk of DM and its complications.The association of HDL with DFUs has also received much attention.Lower levels of HDL cholesterol were associated with increased risk for foot ulceration in patients with diabetes(odds ratio 0.427,95%confidence interval[CI]0.228-0.799,P=0.008).[2]HDL cholesterol levels were also revealed to be an independent risk factor of lower-extremity amputation and wound-related death in patients with DFUs(hazard ratio[HR]0.30,95%CI 0.14-0.63,P=0.002).Therefore,there might be a potential correlation between HDL and wound healing.

关键词： wound healing patients

Dynamic changes of wound-related miRNAs after application of autologous platelet-rich gel in diabetic wounds

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Chinese Medical Journal 2022年第21期135卷 2644-2646页

作者： Yan Li Yujie Liang Yunyi Gao Dawei Chen Xingwu Ran Department of Endocrinology and Metabolism Innovation Center for Wound RepairDiabetic Foot Care CenterWest China HospitalSichuan UniversityChengduSichuan 610041China

To the Editor:diabetic chronic cutaneous ulcers(DCUs)are among the most common and serious complications of diabetes mellitus.diabetic foot ulcers are the most common type of DCU and are now considered a global epidemic.[1]The clinical prevention and treatment of DCUs are critical and have remained challenging for clinicians.With the exploration of topical treatment methods,autologous platelet-rich gel(APG)is regarded as an adjuvant therapy to promote wound healing,and it has been widely used for wound repair.[2]Some microRNAs that play a critical role in the whole wound healing process have been found in wound tissues,which we call wound-related miRNAs(wr-miRNAs).However,few studies have explored the dynamic changes of wr-miRNAs during APG treatment.Our study aimed to evaluate the efficacy of APG in treating diabetic wounds and explore the dynamic changes of wr-miRNAs during wound healing.

关键词： prevention treatment miRNAs

Nociception at the diabetic foot,an uncharted territory

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World Journal of Diabetes 2015年第3期6卷 391-402页

作者： Ernst A Chantelau diabetic Foot Clinic Heinrich-Heine-University Düsseldorf40001 DüsseldorfGermany

The diabetic foot is characterised by painless foot ulceration and/or arthropathy;it is a typical complication of painless diabetic neuropathy.neuropathy depletes the foot skin of intraepidermal nerve fibre endings of the afferent A-delta and C-fibres,which are mostly nociceptors and excitable by noxious stimuli only.However,some of them are cold or warm receptors whose functions in diabetic neuropathy have frequently been reported.Hence,it is well established by quantitative sensory testing that thermal detection thresholds at the foot skin increase during the course of painless diabetic neuropathy.Pain perception(nociception),by contrast,has rarely been studied.Recent pilot studies of pinprick pain at plantar digital skinfolds showed that the perception threshold was always above the upper limit of measurement of 512 m N(equivalent to 51.2 g) at the diabetic foot.However,deep pressure pain perception threshold at musculus abductor hallucis was beyond 1400 k Pa(equivalent to 14 kg;limit of measurement) only in every fifth case.These discrepancies of pain perception between forefoot and hindfoot,and between skin and muscle,demand further study.Measuring nociception at the feet in diabetes opens promising clinical perspectives.A critical nociception threshold may be quantified(probably corresponding to a critical number of intraepidermal nerve fibre endings),beyond which the individual risk of a diabetic foot rises appreciably.Staging of diabetic neuropathy according to nociception thresholds at the feet is highly desirable as guidance to an individualised injury prevention strategy.

关键词： Foot ulcer Neuroarthropathy Insensitivityto pain Pain perception Diabetes mellitus Amputation diabetic neuropathy

Charcot osteoarthropathy in diabetes: A brief review with an emphasis on clinical practice

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World Journal of Diabetes 2011年第5期2卷 59-65页

作者： Evanthia Gouveri Nikolaos Papanas Outpatient Clinic of the diabetic Foot Second Department of Internal Medicine Democritus University of Thrace

Charcot osteoarthropathy (COA) is a potentially limbthreatening condition that mainly affects diabetic patients with neuropathy. In everyday practice, it presents as a red, hot, swollen foot, usually painless, and is frequently trig gered by trivial injury. Its etiology is traditionally attributed to impairment of either the autonomic nervous system, leading to increased blood flow and bone resorption, or of the peripheral nervous system, whereby loss of pain and protective sensation render the foot susceptible to repeated injury. More recently, excessive local inflammation is thought to play a decisive role. Diagnosis is based on clinical manifestation and imaging studies (plain X-rays, bone scan, Magnetic Resonance Imaging). The mainstay of management is immediate off-loading, while surgery is usually reserved for chronic cases with irreversible deformities and/or joint instability. The aim of this review is to provide an overview of COA in terms of pathogenesis, classification and clinical presentation, diagnosis and treatment, with an emphasis on the high suspicion required by clinicians for timely recognition to avoid further complications.

关键词： Charcot osteoarthropathy Diabetes mellitus diabetic neuropathy diabetic foot

Sortilin-induced lipid accumulation and atherogenesis are suppressed by HNF1b SUMOylation promoted by flavone of Polygonatum odoratum

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2023年第11期24卷 998-1013页

作者： Fang LIU Shirui CHEN Xinyue MING Huijuan LI Zhaoming ZENG Yuncheng LV Guangxi Key Laboratory of diabetic Systems Medicine&Institute of Basic Medical Sciences Faculty of Basic Medical SciencesGuilin Medical UniversityGuilin541199China Hunan Mingshun Pharmaceutical Co. Ltd.Shaodong422800China

This study aims to investigate the impact of hepatocyte nuclear factor 1β(HNF1b)on macrophage sortilin-mediated lipid metabolism and aortic atherosclerosis and explore the role of the flavone of Polygonatum odoratum(PAOA-flavone)-promoted small ubiquitin-related modifier(SUMO)modification in the atheroprotective efficacy of HNF1b.HNF1b was predicted to be a transcriptional regulator of sortilin expression via bioinformatics,dual-luciferase reporter gene assay,and chromatin immunoprecipitation.HNF1b overexpression decreased sortilin expression and cellular lipid contents in THP-1 macrophages,leading to a depression in atherosclerotic plaque formation in low-density lipoprotein(LDL)receptor-deficient(LDLR−/−)mice.Multiple SUMO1-modified sites were identified on the HNF1b protein and co-immunoprecipitation confirmed its SUMO1 modification.The SUMOylation of HNF1b protein enhanced the HNF1b-inhibited effect on sortilin expression and reduced lipid contents in macrophages.PAOA-flavone treatment promoted SUMO-activating enzyme subunit 1(SAE1)expression and SAE1-catalyzed SUMOylation of the HNF1b protein,which prevented sortilin-mediated lipid accumulation in macrophages and the formation of atherosclerotic plaques in apolipoprotein E-deficient(ApoE−/−)mice.Interference with SAE1 abrogated the improvement in lipid metabolism in macrophage cells and atheroprotective efficacy in vivo upon PAOA-flavone administration.In summary,HNF1b transcriptionally suppressed sortilin expression and macrophage lipid accumulation to inhibit aortic lipid deposition and the development of atherosclerosis.This anti-atherosclerotic effect was enhanced by PAOA-flavone-facilitated,SAE1-catalyzed SUMOylation of the HNF1b protein.

关键词： Atherosclerosis Lipid accumulation Hepatocyte nuclear factor 1β(HNF1b) Flavone of Polygonatum odoratum SUMOylation

Mesenchymal stem cell-derived exosomes: The dawn of diabetic wound healing

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World Journal of Diabetes 2022年第12期13卷 1066-1095页

作者： Jing Wu Li-Hong Chen Shi-Yi Sun Yan Li Xing-Wu Ran Innovation Center for Wound Repair Diabetic Foot Care CenterDepartment of Endocrinology and MetabolismWest China HospitalSichuan UniversityChengdu 610041Sichuan ProvinceChina

Chronic wound healing has long been an unmet medical need in the field of wound repair,with diabetes being one of the major etiologies.diabetic chronic wounds(DCWs),especially diabetic foot ulcers,are one of the most threatening chronic complications of diabetes.Although the treatment strategies,drugs,and dressings for DCWs have made great progress,they remain ineffective in some patients with refractory wounds.Stem cell-based therapies have achieved specific efficacy in various fields,with mesenchymal stem cells(MSCs)being the most widely used.Although MSCs have achieved good feedback in preclinical studies and clinical trials in the treatment of cutaneous wounds or other situations,the potential safety concerns associated with allogeneic/autologous stem cells and unknown long-term health effects need further attention and supervision.Recent studies have reported that stem cells mainly exert their trauma repair effects through paracrine secretion,and exosomes play an important role in intercellular communication as their main bioactive component.MSC-derived exosomes(MSC-Exos)inherit the powerful inflammation and immune modulation,angiogenesis,cell proliferation and migration promotion,oxidative stress alleviation,collagen remodeling imbalances regulation of their parental cells,and can avoid the potential risks of direct stem cell transplantation to a large extent,thus demonstrating promising performance as novel"cell-free"therapies in chronic wounds.This review aimed to elucidate the potential mechanism and update the progress of MSC-Exos in DCW healing,thereby providing new therapeutic directions for DCWs that are difficult to be cured using conventional therapy.

关键词： diabetic wounds Wound and injuries Mesenchymal stem cells Exosomes Pre-conditioning Preclinical translation

Direct cellular reprogramming and transdifferentiation of fibroblasts on wound healing-Fantasy or reality?

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慢性疾病与转化医学:英文版 2023年第3期9卷 191-199页

作者： Juan Du Xuelai Liu Carol Wing Yan Wong Kenneth Kak Yuen Wong Zhixin Yuan diabetic Foot Diagnosis and Treatment Centre Jilin Province People HospitalChangchunJilinChina Department of Surgery Capital Institute of Pediatrics Affiliated Children HospitalBeijingChina Department of Surgery Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong SARChina Department of Emergency Surgery Jilin Province People HospitalChangchunJilinChina

Induced pluripotent stem cell(iPSC)technology is one of the de novo approaches in regeneration medicine and has led to new research applications for wound healing in recent years.Fibroblasts have attracted wide attention as the first cell line used for differentiation into iPSCs.Researchers have found that fibroblasts can be induced into different types of cells in variable mediums or microenvironments.This indicates the potential“stem”characteristics of fibroblasts in terms of direct cellular reprogramming compared with the iPSC detour.In this review,we described the morphology and biological function of fibroblasts.The stem cell characteristics and activities of fibroblasts,including transdifferentiation into myofibroblasts,osteogenic cells,chondrogenic cells,neurons,and vascular tissue,are discussed.The biological values of fibroblasts are then briefly reviewed.Finally,we discussed the potential applications of fibroblasts in clinical practice.

关键词： direct cellular reprogramming fibroblast wound healing