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In vivo evaluation and mechanism prediction of anti-diabetic foot ulcer based on component analysis of Ruyi Jinhuang powder

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World Journal of Diabetes 2022年第8期13卷 622-642页

作者： Xiu-Yan Li Xiao-Tong Zhang Yi-Cheng Jiao Hang Chi Ting-Ting Xiong Wen-Jing Zhang Mi-Nan Li Yan-Hong Wang Key Laboratory of Basic and Application Research of Beiyao Heilongjiang University of Chinese MedicineHarbin 150040Heilongjiang ProvinceChina College of Pharmacy Harbin Medical UniversityHarbin 150040Heilongjiang ProvinceChina Key Laboratory of Basic and Application Research of Beiyao Heilongjiang University of Chinese MedicineMinistry of EducationCollege of PharmacyHarbin 150040Heilongjiang ProvinceChina

BACKGROUND Diabetes is a metabolic disease with a high complication rate.diabetic foot ulcers(DFUs)seriously affect the quality of life of patients.A total of 15%-20%of diabetic patients develop DFUs,which heal with difficulty over a long time and can result in amputation and disability.Traditional Chinese medicine has a unique effect in the treatment of skin ulcerative diseases.Ruyi Jinhuang powder(RHP)is one of the classic prescriptions in traditional Chinese medicine and is widely used in clinical practice.AIM To verify the ability of RHP to promote wound healing by electron microscopy analysis in animal models and hematoxylin-eosin(HE)staining.The effective components of RHP were extracted and identified by gas chromatography-mass spectrometry(GC-MS),and the obtained chemical components were analyzed by network pharmacology methods to predict its therapeutic mechanism.METHODS Sprague Dawley rats were injected with streptozotocin to establish the DFU model.HE staining was used to observe the wound tissue under an electron microscope.The chemical constituents of RHP were extracted first by supercritical fluid extraction and alcohol extraction,and then,GC-MS and ultra-performance liquid chromatography–MS were used to separately identify the chemical constituents.In addition,the"herb-component-target"link was established through the Traditional Chinese Medicine Systems Pharmacology database to obtain the target information,and the molecular docking of important components and key targets was performed in Discovery Studio software.Cytoscape software was used to visualize and analyze the relationship between the chemical composition,targets and Traditional Chinese Medicine network.RESULTS RHP promoted DFU healing in rats by affecting fibroblasts and nerve cells.A total of 89 chemical components were obtained by GC-MS.Network pharmacological analysis revealed that RHP was associated with 36 targets and 27 pathways in the treatment of DFU,of which the important components were luteolin,trans caryophyllene,ar-turmeron

关键词： Ruyi Jinhuang powder diabetic foot ulcer Mass spectrometry-chromatography Network pharmacology Hematoxylin-eosin staining Components analysis

Mesenchymal stem cells-based drug delivery systems for diabetic foot ulcer:A review

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World Journal of Diabetes 2023年第11期14卷 1585-1602页

作者： Hong-Min Zhang Meng-Liu Yang Jia-Zhuang Xi Gang-Yi Yang Qi-Nan Wu Department of Endocrinology People’s Hospital of Chongqing Liangjiang New AreaChongqing 400030China Department of Endocrinology The Second Affiliated Hospital of The Chongqing Medical UniversityChongqing 400030China Department of Endocrinology Dazu Hospital of Chongqing Medical UniversityThe People’s Hospital of DazuChongqing 406230China

The complication of diabetes,which is known as diabetic foot ulcer(DFU),is a significant concern due to its association with high rates of disability and mortality.It not only severely affects patients’quality of life,but also imposes a substantial burden on the healthcare system.In spite of efforts made in clinical practice,treating DFU remains a challenging task.While mesenchymal stem cell(MSC)therapy has been extensively studied in treating DFU,the current efficacy of DFU healing using this method is still inadequate.However,in recent years,several MSCs-based drug delivery systems have emerged,which have shown to increase the efficacy of MSC therapy,especially in treating DFU.This review summarized the application of diverse MSCs-based drug delivery systems in treating DFU and suggested potential prospects for the future research.

关键词： diabetic foot ulcer Mesenchymal stem cells Drug delivery systems Diabetes Wound healing

Single nucleotide variations in the development of diabetic foot ulcer: A narrative review

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World Journal of Diabetes 2022年第12期13卷 1140-1153页

作者： Yan-Jun Hu Chen-Sheng Song Nan Jiang Division of Orthopaedics and Traumatology Department of OrthopaedicsSouthern Medical University Nanfang HospitalGuangzhou 510515Guangdong ProvinceChina

Diabetes mellitus has become a global health problem,and the number of patients with diabetic foot ulcers(DFU)is rapidly increasing.Currently,DFU still poses great challenges to physicians,as the treatment is complex,with high risks of infection,recurrence,limb amputation,and even death.Therefore,a comprehensive understanding of DFU pathogenesis is of great importance.In this review,we summarized recent findings regarding the DFU development from the perspective of single-nucleotide variations(SNVs).Studies have shown that SNVs located in the genes encoding C-reactive protein,interleukin-6,tumor necrosis factor-alpha,stromal cell-derived factor-1,vascular endothelial growth factor,nuclear factor erythroid-2-related factor 2,sirtuin 1,intercellular adhesion molecule 1,monocyte chemoattractant protein-1,endothelial nitric oxide synthase,heat shock protein 70,hypoxia inducible factor 1 alpha,lysyl oxidase,intelectin 1,mitogen-activated protein kinase 14,toll-like receptors,osteoprotegerin,vitamin D receptor,and fibrinogen may be associated with the development of DFU.However,considering the limitations of the present investigations,future multi-center studies with larger sample sizes,as well as in-depth mechanistic research are warranted.

关键词： diabetic foot diabetic foot ulcer diabetic foot osteomyelitis Single nucleotide variations Narrative review

Adiponectin as a therapeutic target for diabetic foot ulcer

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World Journal of Diabetes 2023年第6期14卷 758-782页

作者： Mona Mohamed Ibrahim Abdalla Jaiprakash Mohanraj Sushela Devi Somanath Department of Physiology Human Biology DivisionSchool of MedicineInternational Medical UniversityKuala Lumpur 57000Malaysia Department of Biochemistry Human Biology DivisionSchool of MedicineInternational Medical UniversityKuala Lumpur 57000Malaysia Department of Microbiology School of MedicineInternational Medical UniversityKuala Lumpur 57000Malaysia

The global burden of diabetic foot ulcers(DFUs)is a significant public health concern,affecting millions of people worldwide.These wounds cause considerable suffering and have a high economic cost.Therefore,there is a need for effective strategies to prevent and treat DFUs.One promising therapeutic approach is the use of adiponectin,a hormone primarily produced and secreted by adipose tissue.Adiponectin has demonstrated anti-inflammatory and antiatherogenic properties,and researchers have suggested its potential therapeutic applications in the treatment of DFUs.Studies have indicated that adiponectin can inhibit the production of pro-inflammatory cytokines,increase the production of vascular endothelial growth factor,a key mediator of angiogenesis,and inhibit the activation of the intrinsic apoptotic pathway.Additionally,adiponectin has been found to possess antioxidant properties and impact glucose metabolism,the immune system,extracellular matrix remodeling,and nerve function.The objective of this review is to summarize the current state of research on the potential role of adiponectin in the treatment of DFUs and to identify areas where further research is needed in order to fully understand the effects of adiponectin on DFUs and to establish its safety and efficacy as a treatment for DFUs in the clinical setting.This will provide a deeper understanding of the underlying mechanisms of DFUs that can aid in the development of new and more effective treatment strategies.

关键词： diabetic foot ulcer Adiponectin Anti-inflammatory Adipose tissue Antioxidants Wound healing

Future applications of exosomes delivering resolvins and cytokines in facilitating diabetic foot ulcer healing

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World Journal of Diabetes 2023年第1期14卷 35-47页

作者： Joshua P B Littig Rebecca Moellmer Devendra K Agrawal Vikrant Rai Translational Research Western University of Health SciencesPomonaCA 91766United States College of Podiatry Western University of Health SciencesPomonaCA 91766United States

Type 2 diabetes mellitus(T2DM)increases the risk of many lethal and debilitating conditions.Among them,foot ulceration due to neuropathy,vascular disease,or trauma affects the quality of life of millions in the United States and around the world.Physiological wound healing is stalled in the inflammatory phase by the chronicity of inflammation without proceeding to the resolution phase.Despite advanced treatment,diabetic foot ulcers(DFUs)are associated with a risk of amputation.Thus,there is a need for novel therapies to address chronic inflammation,decreased angiogenesis,and impaired granulation tissue formation contributing to the non-healing of DFUs.Studies have shown promising results with resolvins(Rv)and anti-inflammatory therapies that resolve inflammation and enhance tissue healing.But many of these studies have encountered difficulty in the delivery of Rv in terms of efficiency,tissue targetability,and immunogenicity.This review summarized the perspective of optimizing the therapeutic application of Rv and cytokines by pairing them with exosomes as a novel strategy for targeted tissue delivery to treat non-healing chronic DFUs.The articles discussing the T2DM disease state,current research on Rv for treating inflammation,the role of Rv in enhancing wound healing,and exosomes as a delivery vehicle were critically reviewed to find support for the proposition of using Rv and exosomes in combination for DFUs therapy.The literature reviewed suggests the beneficial role of Rv and exosomes and exosomes loaded with antiinflammatory agents as promising therapeutic agents in ulcer healing.

关键词： diabetic foot ulcer Chronic inflammation Amputation Exosomes Cytokines Resolvins

Acknowledging the use of botanicals to treat diabetic foot ulcer during the 21st century:A systematic review

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World Journal of Clinical Cases 2023年第17期11卷 4035-4059页

作者： Illora Narzary Amit Swarnakar Mrinal Kalita Sushil Kumar Middha Talambedu Usha Dinesh Babu Banjai Mochahary Sudem Brahma Jangila Basumatary Arvind Kumar Goyal Department of Biotechnology Bodoland UniversityKokrajhar 783370AssamIndia Department of Zoology Baosi Banikanta Kakati CollegeBarpeta 781311AssamIndia Medical Unit Bodoland UniversityKokrajhar 783370AssamIndia Department of Biotechnology Maharani Lakshmi Ammanni College for WomenBengaluru 560012KarnatakaIndia Department of Biochemistry Maharani Lakshmi Ammanni College for WomenBengaluru 560012KarnatakaIndia Faculty of Pharmacy and Pharmaceutical Sciences University of AlbertaEdmontonAlberta T6G 2E1Canada

BACKGROUND diabetic foot ulcer(DFU) is a serious health issue of diabetes mellitus that affects innumerable people worldwide. Management and treatment of this complication are challenging, especially for those whose immune system is weak.AIM To discuss the plants and their parts used to heal DFU, along with the mode of their administration in diabetic patients.METHODS The original articles on “the plants for the treatment of DFU” studied in clinical cases only were obtained from various bibliographic databases using different keywords.RESULTS The search resulted in 22 clinical cases records with 20 medicinal plants belonging to 17 families on 1553 subjects. The fruits and leaves were the most preferentially used parts for DFU treatment, regardless of whether they were being administered orally or applied topically. Of the 20 medicinal plants, 19 reported their effectiveness in increasing angiogenesis, epithelialization, and granulation, thus hastening the wound-healing process. The efficacy of these botanicals might be attributed to their major bioactive compounds, such as actinidin and ascorbic acid(in Actinidia deliciosa), 7-O-(β-D-glucopyranosyl)-galactin(in Ageratina pichinchensis), omega-3-fatty acid(in Linum usitatissimum), isoquercetin(in Melilotus officinalis), anthocyanins(in Myrtus communis), and plantamajoside(in Plantago major).CONCLUSION The validation of mechanisms of action underlying these phytocompounds contributing to the management of DFU can aid in our better understanding of creating efficient treatment options for DFU and its associated problems.

关键词： diabetic foot ulcer Phytocompounds Wound healing Angiogenesis Medicinal plants

Effectiveness of topical oxygen therapy in wound healing for patients with diabetic foot ulcer

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Frontiers of Nursing 2023年第1期10卷 85-93页

作者： Marvin Queg Josephine De Leon Graduate School Centro Escolar UniversityManilaManila 1005Philippines School of Nursing Centro Escolar UniversityManilaManila 1005Philippines

Objectives:Non-healing wounds have been one of the major challenges in health care because of increased morbidity,especially for those who have diabetes mellitus.Numerous regimens are being innovated to produce an evidence-based practice that would minimize complications and promote healing.Topical oxygen therapy is an innovation in wound care that has been considered influential in the wound healing process.This intervention aims to increase the oxygen concentration in the affected limb to promote wound healing.Methods:This research applied an experimental design that targeted a total of 60 adult patients aged 45–64 years with diabetic foot ulcers.A randomized systematic sampling technique was used to allow equal chances and prevent bias.In total,30 patients in the control group received usual care for diabetic foot ulcers,and the remaining 30 patients in the experimental group received topical oxygen therapy together with standard care for diabetic foot ulcers.Subjects were assessed using the Wagner-Meggitt Wound Classification System.Results:The result proved that there was a significant difference in the wound grade of patients in the experimental group after the application of the usual wound care plus the topical oxygen therapy using Friedman's test.The control and experimental groups were compared using Mann–Whitney statistical analyses,and the results showed that there was a significant difference between the control and experimental groups after the application of topical oxygen therapy.Conclusions:Topical oxygen therapy was demonstrated to be effective to aid in the wound healing process of patients with diabetic foot ulcers.Fur ther research was recommended to improve the application of topical oxygen therapy to patients with chronic wounds and promote the wound healing process.

关键词： diabetic foot ulcer localize oxygenation neuro ischemic foot ulcer neuropathic ulcer oxygenation topical oxygen therapy wound healing

A Case Report of diabetic foot ulcer Treated by Herbal Food Homology Therapy

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Case Reports in Clinical Medicine 2023年第6期12卷 189-195页

作者： Lufei Wang Wei Jiang Hui Li State Key Laboratory of Genetic Engineering School of Life Sciences Fudan University Shanghai China Changhai Hospital Naval Medical University Shanghai China MOE Key Laboratory of Contemporary Anthropology School of Life Sciences Fudan University Shanghai China

diabetic foot ulcer (DFU) is a common and severe complication among patients with diabetes. There are hundreds of natural products derived from herbs that have been identified and proven to be effective for glucose-lowering and wound-healing effects, such as flavones. In this case study, we reported that a 76-year-old male patient with severe traumatic DFU was cured after drinking yellow tea (dehydrogenated Camellia sinensis) as a postprandial auxiliary treatment for six months. Previously, the patient was required to be hospitalized, but the wound deteriorated after five months. The patient drank yellow tea at approximately 12:30 pm (the active time of heart meridian) after lunch every day. Five grams of yellow tea were boiled in one liter of water and covered above 70°C for approximately 30 minutes. He experienced profuse sweating on his back after drinking yellow tea, with no other adverse effects. His lifestyle and healthcare remained constant except for replacing green tea with yellow tea. After six months, the ulcer had completely healed, and after one year of follow-up, no new abnormalities or side effects were found. This self-controlled case study indicates that flavone-enriched yellow tea or other herbs may be an auxiliary therapy for diabetes and its complications.

关键词： diabetic foot ulcer Auxiliary Treatment Yellow Tea Flavones

Therapeutic Effectiveness of Leukocyte-and Platelet-rich Fibrin for diabetic foot ulcers:A Retrospective Study

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Current Medical Science 2024年第3期44卷 568-577页

作者： Fen WANG Xiao-ling ZHANG Jing ZHANG Song GONG Jing TAO Hui XIANG Xiao-qing FU Xu-na BIAN Xue-feng YU An-hui XU Cheng-la YI Shi-ying SHAO Department of Endocrinology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Branch of National Clinical Research Center for Metabolic Diseases Wuhan430030China Department of Radiology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Department of Trauma Surgery Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China

Objective diabetic foot ulcer(DFU)is one of the most serious complications of diabetes.Leukocyte-and platelet-rich fibrin(L-PRF)is a second-generation autologous platelet-rich plasma.This study aims to investigate the clinical effects of L-PRF in patients with diabetes in real clinical practice.Methods Patients with DFU who received L-PRF treatment and standard of care(SOC)from 2018 to 2019 in Tongji Hospital were enrolled.The clinical information including patient characteristics,wound evaluation(area,severity,infection,blood supply),SOC of DFU,and images of ulcers was retrospectively extracted and analyzed.L-PRF treatment was performed every 7±2 days until the ulcer exhibited complete epithelialization or an overall percent volume reduction(PVR)greater than 80%.Therapeutic effectiveness,including overall PVR and the overall and weekly healing rates,was evaluated.Results Totally,26 patients with DFU were enrolled,and they had an ulcer duration of 47.0(35.0,72.3)days.The severity and infection of ulcers varied,as indicated by the Site,Ischemia,Neuropathy,Bacterial Infection,and Depth(SINBAD)scores of 2–6,Wagner grades of 1–4,and the Perfusion,Extent,Depth,Infection and Sensation(PEDIS)scores of 2–4.The initial ulcer volume before L-PRF treatment was 4.94(1.50,13.83)cm3,and the final ulcer volume was 0.35(0.03,1.76)cm3.The median number of L-PRF doses was 3(2,5).A total of 11 patients achieved complete epithelialization after the fifth week of treatment,and 19 patients achieved at least an 80%volume reduction after the seventh week.The overall wound-healing rate was 1.47(0.63,3.29)cm3/week,and the healing rate was faster in the first 2 weeks than in the remaining weeks.Concurrent treatment did not change the percentage of complete epithelialization or healing rate.Conclusion Adding L-PRF to SOC significantly improved wound healing in patients with DFU independent of the ankle brachial index,SINBAD score,or Wagner grade,indicating that this method is appropriate for DFU treatment under different clinical conditions

关键词： diabetic foot ulcer autologous platelet-rich plasma leukocyte-and platelet-rich fibrin standard of care percentage volume reduction