Global trends in publications regarding macrophages-related diabetic foot ulcers in the last two decades

BACKGROUND Diabetic foot ulcers(DFUs)are one of the most severe and popular complications of diabetes.The persistent non-healing of DFUs is the leading cause of amputation,which causes significant mental and financial stress to patients and their families.Macrophages are critical cells in wound healing and perform essential roles in all phases of wound healing.However,no studies have been carried out to systematically illustrate this area from a scientometric point of view.Although there have been some bibliometric studies on diabetes,reports focusing on the investigation of macrophages in DFUs are lacking.AIM To perform a bibliometric analysis to systematically assess the current state of research on macrophage-related DFUs.METHODS The publications of macrophage-related DFUs from January 1,2004,to December 31,2023,were retrieved from the Web of Science Core Collection on January 9,2024.Four different analytical tools:VOSviewer(v1.6.19),CiteSpace(v6.2.R4),HistCite(v12.03.07),and Excel 2021 were used for the scientometric research.RESULTS A total of 330 articles on macrophage-related DFUs were retrieved.The most published countries,institutions,journals,and authors in this field were China,Shanghai Jiao Tong University of China,Wound Repair and Regeneration,and Aristidis Veves.Through the analysis of keyword co-occurrence networks,historical direct citation networks,thematic maps,and trend topics maps,we synthesized the prevailing research hotspots and emerging trends in this field.CONCLUSION Our bibliometric analysis provides a comprehensive overview of macrophage-related DFUs research and insights into promising upcoming research.

Home-based Detection and Prediction of Diabetic Foot Ulcers at Early Stage Using Sensor Technology and Supervised Learning

For years,foot ulcers linked with diabetes mellitus and neuropathy have significantly impacted diabetic patients’ health-related quality of life(HRQoL). Diabetes foot ulcers impact15% of all diabetic patients at some point in their lives. The facilities and resources used for DFU detection and treatment are only available at hospitals and clinics,which results in the unavailability of feasible and timely detection at an early stage. This necessitates the development of an at-home DFU detection system that enables timely predictions and seamless communication with users,thereby preventing amputations due to neglect and severity. This paper proposes a feasible system consisting of three major modules:an IoT device that works to sense foot nodes to send vibrations onto a foot sole,a machine learning model based on supervised learning which predicts the level of severity of the DFU using four different classification techniques including XGBoost,K-SVM,Random Forest,and Decision tree,and a mobile application that acts as an interface between the sensors and the patient. Based on the severity levels,necessary steps for prevention,treatment,and medications are recommended via the application.

Impact of tibial transverse transport in tissue regeneration and wound healing with perspective on diabetic foot ulcers

In this editorial,we comment on an article by Liao et al published in the current issue of the World Journal of Diabetes.We focus on the clinical significance of tibial transverse transport(TTT)as an effective treatment for patients with diabetic foot ulcers(DFU).TTT has been associated with tissue regeneration,improved blood circulation,reduced amputation rates,and increased expression of early angiogenic factors.Mechanistically,TTT can influence macrophage polarization and growth factor upregulation.Despite this potential,the limitations and conflicting results of existing studies justify the need for further research into its optimal application and development.These clinical implications highlight the efficacy of TTT in recalcitrant DFU and provide lasting stimuli for tissue re-generation,and blood vessel and bone marrow improvement.Immunomodu-lation via systemic responses contributes to its therapeutic potential.Future studies should investigate the underlying molecular mechanisms to enhance our understanding and the efficacy of TTT.This manuscript emphasizes the potential of TTT in limb preservation and diabetic wound healing and suggests avenues for preventive measures against limb amputation in diabetes and peripheral artery disease.Here,we highlight the clinical significance of the TTT and its importance in healing DFU to promote the use of this technique in tissue regeneration.

Clinical comprehensive treatment protocol for managing diabetic foot ulcers:A retrospective cohort study

BACKGROUND Diabetic foot ulcers(DFUs)are a common complication of diabetes,often leading to severe infections,amputations,and reduced quality of life.The current standard treatment protocols for DFUs have limitations in promoting efficient wound healing and preventing complications.A comprehensive treatment approach targeting multiple aspects of wound care may offer improved outcomes for patients with DFUs.The hypothesis of this study is that a comprehensive treatment protocol for DFUs will result in faster wound healing,reduced amputation rates,and improved overall patient outcomes compared to standard treatment protocols.AIM To compare the efficacy and safety of a comprehensive treatment protocol for DFUs with those of the standard treatment protocol.METHODS This retrospective study included 62 patients with DFUs,enrolled between January 2022 and January 2024,randomly assigned to the experimental(n=32)or control(n=30)group.The experimental group received a comprehensive treatment comprising blood circulation improvement,debridement,vacuum sealing drainage,recombinant human epidermal growth factor and anti-inflammatory dressing,and skin grafting.The control group received standard treatment,which included wound cleaning and dressing,antibiotics administration,and surgical debridement or amputation,if necessary.Time taken to reduce the white blood cell count,number of dressing changes,wound healing rate and time,and amputation rate were assessed.RESULTS The experimental group exhibited significantly better outcomes than those of the control group in terms of the wound healing rate,wound healing time,and amputation rate.Additionally,the comprehensive treatment protocol was safe and well tolerated by the patients.CONCLUSION Comprehensive treatment for DFUs is more effective than standard treatment,promoting granulation tissue growth,shortening hospitalization time,reducing pain and amputation rate,improving wound healing,and enhancing quality of life.

Efficacy of Huangma Ding or autologous platelet-rich gel for the diabetic lower extremity arterial disease patients with foot ulcers

BACKGROUND Diabetes foot is one of the most serious complications of diabetes and an important cause of death and disability,traditional treatment has poor efficacy and there is an urgent need to develop a practical treatment method.AIM To investigate whether Huangma Ding or autologous platelet-rich gel(APG)treatment would benefit diabetic lower extremity arterial disease(LEAD)patients with foot ulcers.METHODS A total of 155 diabetic LEAD patients with foot ulcers were enrolled and divided into three groups:Group A(62 patients;basal treatment),Group B(38 patients;basal treatment and APG),and Group C(55 patients;basal treatment and Huangma Ding).All patients underwent routine follow-up visits for six months.After follow-up,we calculated the changes in all variables from baseline and determined the differences between groups and the relationships between parameters.RESULTS The infection status of the three groups before treatment was the same.Procalcitonin(PCT)improved after APG and Huangma Ding treatment more than after traditional treatment and was significantly greater in Group C than in Group B.Logistic regression analysis revealed that PCT was positively correlated with total amputation,primary amputation,and minor amputation rates.The ankle-brachial pressure and the transcutaneous oxygen pressure in Groups B and C were greater than those in Group A.The major amputation rate,minor amputation rate,and total amputation times in Groups B and C were lower than those in Group A.CONCLUSION Our research indicated that diabetic foot ulcers(DFUs)lead to major amputation,minor amputation,and total amputation through local infection and poor microcirculation and macrocirculation.Huangma Ding and APG were effective attreating DFUs.The clinical efficacy of Huangma Ding was better than that of autologous platelet gel,which may be related to the better control of local infection by Huangma Ding.This finding suggested that in patients with DFUs combined with coinfection,controlling infection is as important as improving circulation.

Portraying Diabetic Foot Ulcers: Comparative Evaluation of Diabetic Foot Infections versus Diabetic Foot Ulcers

Background: Confusion often arises in caring for diabetic foot infections and ulcers, especially with antimicrobials;we aim to shed light on this entity and alert healthcare workers to its stewardship. Methods: Records were reviewed between February 2016 and September 2023. Data for patients diagnosed with diabetes and foot ulcers, infected or not, were examined following ICD 9 search terms. Records for patients were included if they were prediabetic/diabetic adults with foot ulcers, more than 18 years old, and on antidiabetic treatment. Patients were excluded if they insulin resistant, with normal HgbA1c levels, wheel-chair dependent, bed-bound, non-diabetic patients, diabetic patients who had vascular lower limb surgery earlier to ulcers, diabetic patients who had aortocoronary bypass, deep venous thrombosis within six months, malignancy, and severe clinical depression. A modified IWGDF/IDSA guidelines definitions for DFI and DFU was considered. Statistical analysis was done using R programming. Statistical methods were employed as appropriate, and a significant P-value was considered for P Results: Most characteristics were well balanced between DFI and DFU, on imaging osteomyelitis and tissue swelling were significantly more in DFI. Endovascular radiological procedures showed angiograms to be considerably more in DFI, while angioplasty was more in DFU, in addition to smoking. Bacteremia was uncommon, and swab cultures were mostly polymicrobial in both ulcers;no clear association with blood bacteria was detected with the polymicrobial growth, though few were concordant. Antimicrobials prescribed for both ulcers were not statistically different except for carbapenems, which were more in DFI (P Conclusion: Attention should be paid to best practices while caring for diabetic ulcers. These include swab culture interpretations, the use of antimicrobials, and plan management according to DFI or DFU to utilize either local care or combination with antimicrobials.

Diabetic foot ulcers: A devastating complication of diabetes mellitus continues non-stop in spite of new medical treatment modalities

Diabetic foot ulcer is a devastating complication of diabetes mellitus and significant cause of mortality and morbidity all over the world and can be complex and costly.The development of foot ulcer in a diabetic patient has been estimated to be 19%-34%through their lifetime.The pathophysiology of diabetic foot ulcer consist of neuropathy,trauma and,in many patients,additional peripheral arterial disease.In particular,diabetic neuropathy leads to foot deformity,callus formation,and insensitivity to trauma or pressure.The standard algorithms in diabetic foot ulcer management include assessing the ulcer grade classification,surgical debridement,dressing to facilitate wound healing,offloading,vascular assessment(status and presence of a chance for interventional vascular correction),and infection and glycemic control.Although especially surgical procedures are sometimes inevitable,they are poor predictive factors for the prognosis of diabetic foot ulcer.Different novel treatment modalities such as nonsurgical debridement agents,oxygen therapies,and negative pressure wound therapy,topical drugs,cellular bioproducts,human growth factors,energy-based therapies,and systematic therapies have been available for patients with diabetic foot ulcer.However,it is uncertain whether they are effective in terms of promoting wound healing related with a limited number of randomized controlled trials.This review aims at evaluating diabetic foot ulcer with regard to all aspects.We will also focus on conventional and novel adjunctive therapy in diabetic foot management.

Current scenario of traditional medicines in management of diabetic foot ulcers:A review

Diabetic foot infections and diabetic foot ulcers(DFU)cause significant suffering and are often recurring.DFU have three important pathogenic factors,namely,microangiopathy causing local tissue anoxia,neuropathy making the foot prone to injuries from trivial trauma,and local tissue hyperglycaemia favouring infection and delaying the wound healing.DFU have been the leading cause for non-traumatic amputations of part or whole of the limb.Western medicines focus mainly on euglycaemia,antimicrobials,debridement and wound cover with grafts,and off-loading techniques.Advances in euglycaemic control,foot care and footwear,systemic antimicrobial therapy,and overall health care access and delivery,have resulted in an overall decrease in amputations.However,the process of wound care after adequate debridement remains a major cost burden globally,especially in developing nations.This process revolves around two basic concerns regarding control/eradication of local infection and promotion of faster healing in a chronic DFU without recurrence.Wound modulation with various dressings and techniques are often a costly affair.Some aspects of the topical therapy with modern/Western medicines are frequently not addressed.Cost of and compliance to these therapies are important as both the wounds and their treatment are“chronic.”Naturally occurring agents/medications from traditional medicine systems have been used frequently in different cultures and nations,though without adequate clinical base/relevance.Traditional Chinese medicine involves restoring yin-yang balance,regulating the‘chi’,and promoting local blood circulation.Traditional medicines from India have been emphasizing on‘naturally’available products to control wound infection and promote all the aspects of wound healing.There is one more group of chemicals which are not pharmaceutical agents but can create acidic milieu in the wound to satisfy the above-mentioned basic concerns.Various natural and plant derived products(e.g.,honey,aloe vera,oils,and calendula)and maggots are also used for wound healing purposes.We believe that patients with a chronic wound are so tired physically,emotionally,and financially that they usually accept native traditional medicine which has the same cultural base,belief,and faith.Many of these products have never been tested in accordance to“evidence-based medicine.”There are usually case reports and experience-based reports about these products.Recently,there have been some trials(in vitro and in vivo)to verify the claims of usage of traditional medicines in management of DFU.Such studies show that these natural products enhance the healing process by controlling infection,stimulating granulation tissue,antimicrobial action,promoting fibroblastic activity and collagen deposition,etc.In this review,we attempt to study and analyse the available literature on results of topical traditional medicines,which are usually advocated in the management of DFU.An integrated and‘holistic’approach of both modern and traditional medicine may be more acceptable to the patient,cost effective,and easy to administer and monitor.This may also nevertheless lead to further improvement in quality of life and decrease in the rates of amputations for DFU.

Modulatory effect of caffeic acid in alleviating diabetes and associated complications

Diabetes mellitus(DM)is one of the most common metabolic disorders characterized by elevated blood glucose levels.Prolonged uncontrolled hyperglycemia often leads to multi-organ damage including diabetic neuropathy,nephropathy,retinopathy,cardiovascular disorders,and diabetic foot ulcers.Excess production of free radicals causing oxidative stress in tissues is often considered to be the primary cause of onset and progression of DM and associated complications.Natural polyphenols can be used to induce or inhibit the expression of antioxidant enzymes such as glutathione peroxidase,heme oxygenase-1,superoxide dismutase,and catalase that are essential in maintaining redox balance,and ameliorate oxidative stress.Caffeic acid(CA)is a polyphenolderived from hydroxycinnamic acid and possesses numerous physiological properties including antioxidant,anti-inflammatory,anti-atherosclerotic,immune-stimulatory,cardioprotective,antiproliferative,and hepatoprotective activities.CA acts as a regulatory compound affecting numerous biochemical pathways and multiple targets.These include various transcription factors such as nuclear factor-B,tumor necrosis factor-α,interleukin-6,cyclooxygenase-2,and nuclear factor erythroid 2-related factor 2.Therefore,this review summarizes the pharmacological properties,molecular mechanisms,and pharmacokinetic profile of CA in mitigating the adverse effects of DM and associated complications.The bioavailability,drug delivery,and clinical trials of CA have also been discussed.

Effect of Bismuth Subgallate/Borneol Combined with Autologous Platelet-Rich Gel in the Treatment of Patients with Diabetic Foot Ulcers

Objective: To explore the effect of Bismuth Subgallate/Borneol (SuileTM BSB) healing dressing combined with autologous platelet-rich gel (APG) in the treatment of diabetic foot ulcer (DFU). Methods: A total of 120 patients with DFU hospitalized in the Changsha Central Hospital from August 2020 to September 2021 were selected and randomly divided into an experimental group (BSB + APG, n = 60) and a control group (BSB, n = 60) according to random number table method. The total therapeutic effect, healing time, hospital stay, level indexes of various inflammatory factors before and after treatment and ulcer area were observed in the two groups. Results: The total effect of the control group was worse than that of the experimental group, and the data between the two groups were significant (P 0.05);after treatment, the levels of inflammatory factors including WBC, CRP, IL-6 and TNF-α in the control group were higher than those in the experimental group, and there was significant difference between the two groups (P 0.05);after 14 days of treatment, the ulcer area in the control group was larger than that in the experimental group, and the data between the two groups were significant (P Conclusion: BSB combined with APG can achieve better therapeutic effect, reduce the inflammatory reaction of patients, and promote wound healing in the treatment of patients with diabetic foot ulcer.

Corneal ulcer caused by nocardia brasiliensis in a patient with diabetes

Dear Sir,Iam Dr.Sheng-Li Mi,from the Biomanufacturing engineering laboratory,Graduate School at Shenzhen,Tsinghua University,Shenzhen,China.I write to present a case report of nocardia brasiliensis in a patient with diabetes.Nocardia is part of a group of aerobic actinomycetes,widely distributed in soil.Nocardia asteroids and nocardia brasiliensis are the most common human pathogens.Humans infected by nocardia asteroids through the respiratory tract mainly suffer from primary suppurative pulmonary conditions.Infection of nocardia brasiliensis often occurs in the advanced stages of a progressive disease or immune disorder,especially Cushing syndrome,diabetes,or in patients using corticosteroids,immunosuppressive agents and broad-spectrum antibiotics for long time[1].To our knowledge,the reports of nocardia keratitis was very rare

Nursing Effect of Standardized Nursing Intervention in Endoscopic Examination of Patients with Gastric Ulcer Complicated with Diabetes

Objective:To explore the nursing effect of standardized nursing interventions in endoscopic examination of patients with gastric ulcer complicated with diabetes.Methods:90 patients with gastric ulcer complicated with diabetes who were treated in our hospital from May 2018 to May 2019 were selected and randomly divided into 2 groups,each containing 45.The control group received routine nursing,and the observation group performed standardized nursing intervention on the basis of the control group.The control group received conventional nursing,and the observation group performed standardized nursing intervention on the basis of the control group.After nursing,the two groups of patients were compared for their psychological state and nursing satisfaction.Results:After nursing,the HAMD and HAMA scores of the two groups were lower than before the nursing,and the observation group was lower than the control group,the difference was statistically significant(P<0.05).Conclusion:Standardized nursing intervention can alleviate the negative emotion of endoscopic examination of patients with gastric ulcer complicated with diabetes,which is conducive to the smooth progress of the examination.

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

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.

Adiponectin as a therapeutic target for diabetic foot ulcer

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.

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

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.

Exploring the mechanism of moist exposed burn ointment for the treatment of diabetic ulcer based on network pharmacology and molecular docking

Objective:To discuss the main active components and potential mechanisms of moist burn ointment in the treat-ment of diabetic ulcer were discussed by network pharmacology and molecular docking technology.Methods:Based on the TC-MSP database,the main active components and targets of MEBO were screened.The targets related to diabetic ulcers were searched from GeneCards,OMIM,PharmGkb,TTD,and DrugBank databases.The STRING 11.5 database was used to con-struct a protein-protein interaction(PPI)network to screen the core targets.The'drug-target-disease'network diagram was made in Cytoscape 3.8.2 software to screen the core active components.GO enrichment analysis and KEGG pathway enrichment analysis were performed using R language software.Finally,molecular docking was used to preliminarily verify the screening results.Results:A total of 37 active components of MEBO were screened to map 100 targets,5527 targets for diabetic ulcer dis-ease,and 77 intersection targets.PPI network topology analysis suggested that TP53,TNF,HSP90AA1 and other targets were key targets;the network diagram of ‘drug-target-disease’showed that acacetin,wogonin,quercetin,and rutaecarpine were the core active ingredients.GO function analysis mainly involved angiogenesis,ion transport,diameter regulation,cytokine receptor binding,and other processes.KEGG enrichment analysis mainly included PI3K-Akt,AGE-RAGE,and other signaling pathways.Molecular docking showed that the core active ingredients and key targets had good docking activity.Conclusion:The treatment of diabetic ulcer with MEBO is the result of multi-component,multi-target,and synergistic regulation,which provides a theoretical basis for the clinical application of MEBO and the treatment of diabetic ulcer.

Advances in the efficacy and safety of nano-silver dressings for diabetic foot ulcers(DFU)healing

As a new antimicrobial material,nano-silver dressing has been widely used in the treatment of diabetic foot ulcer(DFU)wounds in recent years.It not only has achieved a satisfactory effect in promoting the healing of DFU,but also has the advantages in controlling wound infection,relieving pain and reducing the frequency of dressing change.In this review,the principle,efficacy and safety of DFU wound healing were reviewed,and the future research directions were prospected.

XB130 inhibits healing of diabetic skin ulcers through the PI3K/Akt signalling pathway

BACKGROUND Diabetic skin ulcers,a significant global healthcare burden,are mainly caused by the inhibition of cell proliferation and impaired angiogenesis.XB130 is an adaptor protein that regulates cell proliferation and migration.However,the role of XB130 in the development of diabetic skin ulcers remains unclear.AIM To investigate whether XB130 can regulate the inhibition of proliferation and vascular damage induced by high glucose.Additionally,we aim to determine whether XB130 is involved in the healing process of diabetic skin ulcers,along with its molecular mechanisms.METHODS We conducted RNA-sequencing analysis to identify the key genes involved in diabetic skin ulcers.We investigated the effects of XB130 on wound healing using histological analyses.In addition,we used reverse transcription-quantitative polymerase chain reaction,Western blot,terminal deoxynucleotidyl transferasemediated dUTP nick end labeling staining,immunofluorescence,wound healing,and tubule formation experiments to investigate their effects on cellular processes in human umbilical vein endothelial cells(HUVECs)stimulated with high glucose.Finally,we performed functional analysis to elucidate the molecular mechanisms underlying diabetic skin ulcers.RESULTS RNA-sequencing analysis showed that the expression of XB130 was up-regulated in the tissues of diabetic skin ulcers.Knockdown of XB130 promoted the healing of skin wounds in mice,leading to an accelerated wound healing process and shortened wound healing time.At the cellular level,knockdown of XB130 alleviated high glucose-induced inhibition of cell proliferation and angiogenic impairment in HUVECs.Inhibition of the PI3K/Akt pathway removed the proliferative effects and endothelial protection mediated by XB130.CONCLUSION The findings of this study indicated that the expression of XB130 is up-regulated in high glucose-stimulated diabetic skin ulcers and HUVECs.Knockdown of XB130 promotes cell proliferation and angiogenesis via the PI3K/Akt signalling pathway,which accelerates the healing of diabetic skin ulcers.

Network pharmacology-based approach for exploring the biotargets and mechanisms of vitamin A for the treatment of diabetic foot ulcers

Background:In some developing countries,people have little knowledge about the causes of diabetic foot ulcers.Therefore,public health education for patients on these conditions is a prerequisite for effective pharmacological treatment.Diabetic foot ulcers are a complex symptom of diabetes and are hard to cure due to the lack of efficacious medicine and alternative treatment approaches.Vitamin A(VA)is known to have potent biological functions,including skin repair and immunoregulation.However,the potential pharmacological effects and molecular mechanisms of VA on foot ulcers are still to be discovered.Methods:By using bioinformatic/computational analyses,including network pharmacology,gene ontology and the Kyoto Encyclopedia of Genes and Genomes enrichment analysis,we aimed to identify and reveal the pharmacological targets,molecular mechanisms,biological functions,and signaling pathways of VA in the treatment of diabetic foot ulcers.Results:A total of 66 intersection genes were identified as candidate targets of VA,which are related to diabetic foot ulcers.Therein,18 core genes/targets,namely JUN,MAPK1,THRB,MAPK14,MTNR1B,CXCR3,ESR1,AR,HDAC1,IL-10,CNR1,DRD2,EGFR,ADRA2A,CCND1,RXRB,RARA,and RXRA,were further identified.Furthermore,the biological processes,cell components,and molecular functions which may underlie the effects of VA against diabetic foot ulcers were characterized.Conclusion:Based on our findings,we concluded that the pharmacological effects of VA on diabetic foot ulcers primarily involve the promotion of cellular regeneration and proliferation and the inhibition of inflammatory response.The core genes/targets may potentially serve as promising biomarkers for the diagnosis of diabetic foot ulcers.

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

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.