Wound healing in diabetic ulcers remains a significant clinical challenge,primarily due to bacterial infection and impaired angiogenesis.Periplaneta americana extract(PAE)has been widely used to treat diabetic wounds,...Wound healing in diabetic ulcers remains a significant clinical challenge,primarily due to bacterial infection and impaired angiogenesis.Periplaneta americana extract(PAE)has been widely used to treat diabetic wounds,yet its underlying mechanisms are not fully understood.This study aimed to elucidate these mechanisms by analyzing long non-coding RNA(lncRNA)expressions in the wound tissues from diabetic anal fistula patients treated with or without PAE,using high-throughput sequencing.Peripheral blood monocytes from patients were differentiated into M0 macrophages with human macrophage colony-stimulating factor(hMCSF)and subsequently polarized into M1 macrophages with lipopolysaccharide.The results indicated that LINC01133 and SLAMF9 were downregulated in wound tissues of patients treated with PAE.Furthermore,PAE suppressed M1 macrophage polarization and enhanced human umbilical vein endothelial cell(HUVEC)proliferation,migration,and angiogenesis.These effects were diminished when LINC01133 or SLAMF9 were overexpressed.Mechanistically,LINC01133 was shown to upregulate SLAMF9 through interaction with ELAVL1.Overexpression of SLAMF9 reversed the effects of LINC01133 silencing on macrophage polarization and HUVEC functions.In conclusion,PAE facilitates the healing of infected diabetic ulcers by downregulating the LINC01133/SLAMF9 pathway.展开更多
The incidence of diabetic ulcer is high, the disability and mortality are also high, and its treatment is difficult, and the healing mechanism is not clear. The main reason for the delayed healing of DU is that the ch...The incidence of diabetic ulcer is high, the disability and mortality are also high, and its treatment is difficult, and the healing mechanism is not clear. The main reason for the delayed healing of DU is that the chronic inflammation window period is too long, and macrophages play a key role in its healing process. The polarization of macrophages controls the length of the inflammatory phase, and autophagy is thought to be closely related to the tendency of macrophage polarization. Autophagy regulators have limited clinical application. Traditional Chinese medicine may become an ideal autophagy inducer and provide new ideas and strategies for clinical treatment of diabetic ulcers. This article summarizes the role of macrophage autophagic polarization in the healing of diabetic ulcers and the prospects of traditional Chinese medicine.展开更多
There are 422 million diabetic people in the world.25%of these individuals are diagnosed with diabetic foot ulcer(DFU).20%of patients with DFU will suffer amputation of the lower limbs.Following amputation procedures,...There are 422 million diabetic people in the world.25%of these individuals are diagnosed with diabetic foot ulcer(DFU).20%of patients with DFU will suffer amputation of the lower limbs.Following amputation procedures,the mortality rate of patients is over 70%in 5 years.Diabetes has no cure and,therefore,treatment aims to prevent and treat its complications.Autologous platelet-rich plasma(PRP)has been shown to be a therapeutic tool for many types of disorders,including the treatment of DFU.This manuscript aims to carry out a review to provide more knowledge about the efficacy and safety of autologous PRP for wound closure in patients with DFU.The majority of studies included in this review state that PRP promotes improvement of DFU lesions by accelerating tissue healing processes.However,many studies have a small sample size and thus require larger sample range in order to improve robustness of data in the literature.展开更多
BACKGROUND Diabetic foot ulcers(DFUs)present a significant clinical challenge due to their high prevalence and profound impact on morbidity.Ultrasound-assisted wound debridement(UAWD)has emerged as a potential therape...BACKGROUND Diabetic foot ulcers(DFUs)present a significant clinical challenge due to their high prevalence and profound impact on morbidity.Ultrasound-assisted wound debridement(UAWD)has emerged as a potential therapeutic modality to improve healing outcomes in DFU management.AIM To evaluate the efficacy of UAWD in treating DFUs on wound closure rates,treatment duration,and quality of life outcomes.METHODS This systematic review and meta-analysis followed PRISMA guidelines,systematically searching PubMed,Embase,Web of Science,and the Cochrane Library with no date restrictions.Randomized controlled trials(RCTs)that evaluated the efficacy of UAWD in DFU treatment were included.Data were independently extracted by two reviewers,with discrepancies resolved through consensus or third-party consultation.The risk of bias was assessed using the Cochrane tool.χ2 and I2 statistics assessed heterogeneity,informing the use of fixed or random-effects models for meta-analysis,supplemented by sensitivity analysis and publication bias assessment through funnel plots and Egger's test.RESULTS From 1255 articles,seven RCTs met the inclusion criteria.The studies demonstrated that UAWD significantly reduced DFU healing time(standardized mean difference=-0.78,95%CI:-0.97 to-0.60,P<0.001)and increased healing rates(odds ratio=9.96,95%CI:5.99 to 16.56,P<0.001)compared to standard care.Sensitivity analysis confirmed the stability of these results,and no significant publication bias was detected.CONCLUSION UAWD is a promising adjunctive treatment for DFUs,significantly reducing healing times and increasing healing rates.These findings advocate for the integration of UAWD into standard DFU care protocols.展开更多
Diabetic foot(DF)is a major public health concern.As evident from numerous previous studies,supervision of DF ulcer(DFU)is crucial,and a specific quality check-up is needed.Patients should be educated about glycaemic ...Diabetic foot(DF)is a major public health concern.As evident from numerous previous studies,supervision of DF ulcer(DFU)is crucial,and a specific quality check-up is needed.Patients should be educated about glycaemic management,DFUs,foot lesions,proper care for injuries,diet,and surgery.Certain reasonably priced treatments,such as hyperbaric oxygen and vacuum-assisted closure therapy,are also available for DFUs,along with modern wound care products and techniques.Nonetheless,DF care(cleaning,applying antimicrobial cream when wounded,and foot reflexology),blood glucose monitoring to control diabetes,and monthly or quarterly examinations in individuals with diabetes are effective in managing DFUs.Between 50%and 80%of DF infections are preventable.Regardless of the intensity of the lesion,it needs to be treated carefully and checked daily during infection.Tissue regeneration can be aided by cleaning,dressing,and application of topical medicines.The choice of shoes is also important because it affects blood circulation and nerve impulses.In general,regular check-ups,monitoring of the patient’s condition,measuring blood glucose levels,and providing frequent guidance regarding DFU care are crucial.Finally,this important clinical problem requires involvement of multiple professionals to properly manage it.展开更多
BACKGROUND Pain often predisposes patients with diabetic foot ulcers(DFUs)to negative emotional states,such as anxiety and depression,which can significantly impair treatment outcomes and recovery.However,very few stu...BACKGROUND Pain often predisposes patients with diabetic foot ulcers(DFUs)to negative emotional states,such as anxiety and depression,which can significantly impair treatment outcomes and recovery.However,very few studies have explored the relationship between anxiety,depression,and pain in DFUs,as well as the associated risk factors.AIM To analyze the correlation between anxiety,depression,and pain in patients with DFUs and to identify the associated risk factors.METHODS This study included 106 patients diagnosed with DFUs who were admitted to Tiantai County People’s Hospital between March 2022 and March 2024.The patients’anxiety levels were evaluated using Zung’s self-rating anxiety scale(SAS),depression status was assessed using Zung’s self-rating depression scale(SDS),and pain intensity was assessed using the visual analog scale(VAS).Subsequently,correlations between SAS,SDS,and VAS scores were analyzed.Univariate and multivariate analyses were conducted to explore the risk factors that contributed to anxiety and depression in patients with DFUs.RESULTS Among the 106 patients,39.62%exhibited anxiety and 43.40%presented with depression.Most patients experiencing anxiety or depression exhibited mild symptoms,with no severe cases observed.Compared with asymptomatic patients,those with anxiety or depression had significantly higher VAS scores.Correlation analysis indicated a significant positive relationship between both SAS and SDS scores and the VAS score.Univariate analysis identified sex,age,Wagner’s grade,presence of other complications,and smoking history as factors significantly associated with anxiety and depression.Multivariate analysis further confirmed that younger age,higher Wagner’s grade,and higher VAS scores were independent predictors of anxiety and depression.CONCLUSION This study reveals a significant positive correlation between anxiety,depression,and pain in patients with DFUs.This finding suggests that timely and effective pain intervention may be beneficial in alleviating negative emotions such as anxiety and depression.In addition,younger age(<50 years),higher Wagner’s grade,and higher VAS scores increase the risk of developing anxiety and depression in this patient population.展开更多
Microneedle(MN)patches could be a promising treatment for diabetic foot ulcers that plague thousands of people worldwide.While reducing skin resistance or increasing driving force can accelerate the efficiency of tran...Microneedle(MN)patches could be a promising treatment for diabetic foot ulcers that plague thousands of people worldwide.While reducing skin resistance or increasing driving force can accelerate the efficiency of transdermal drug delivery with conventional MN patches,it can create toxic chemical residues or require the help of additional devices.Herein,a thermo-responsive microneedles patch(TMN)with high biocompatibility without additional equipment is proposed.The TMN consisted of a bilayer microneedles composed of sodium alginate(SA)-g-poly(N-isopropylacrylamide)layer(SA-g-PNIPAM)loaded with sucrose octasulfate sodium salt(SOS)and hyaluronic acid layer and a polycaprolactone/chitosan nanofiber membrane loading with tetracycline hydrochloride(TH)and SOS.PNIPAM accelerates drug release by extruding the drug through a volumetric phase transition in response to temperature changes,and TH and SOS promote wound healing by inhibiting bacterial growth and promoting vascular regeneration and epithelial formation.The results showed that the drug release of TMN was significantly faster,with the drug release rate of more than 80% in the 10th h,and the antibacterial rate of TMN could reach 800%.In addition,TMN had good biocompatibility and good healing effects in vivo,which may be helpful for the design of multifunctional dressings in the future.展开更多
BACKGROUND Diabetic foot ulcers(DFUs)are a significant challenge in diabetic care,and the efficacy of negative pressure wound therapy(NPWT)in treating them remains a subject of continuous investigation.AIM To provide ...BACKGROUND Diabetic foot ulcers(DFUs)are a significant challenge in diabetic care,and the efficacy of negative pressure wound therapy(NPWT)in treating them remains a subject of continuous investigation.AIM To provide a comprehensive meta-analysis of the role of NPWT in the manage-ment of DFUs.METHODS A systematic review was performed based on Preferred Reporting Items for Sys-tematic Reviews and Meta-Analyses guidelines,searching databases like PubMed,Embase,Web of Science,and the Cochrane Library.Randomized clinical trials(RCTs)were included to compare NPWT to other dressings for DFUs.Outcomes measured were wound healing time and rate,granulation tissue formation time,amputation rate,and adverse events.Study quality was evaluated using Coch-rane's risk of bias tool.Analyses utilizedχ2,I2,fixed or random-effects models via Stata v17.RESULTS Of the 1101 identified articles,9 RCTs were selected for meta-analysis.Studies spanned from 2005 to 2020 and originated from countries including the United States,Chile,Pakistan,Italy,India,and Germany.Meta-analysis demonstrated a significant improvement in wound healing rate[risk ratio(RR)=1.46,95%CI:1.22-1.76,P<0.01]and a reduction in amputation rate(RR=0.69,95%CI:0.50-0.96,P=0.006)with NPWT.Furthermore,the time for granulation tissue formation was significantly reduced by an average of 19.54 days.However,the incidence of adverse events did not significantly differ between NPWT and control treatments.CONCLUSION NPWT significantly improves wound healing rates and reduces amputation rates in DFUs.It also hastens the formation of granulation tissue.However,the therapy does not significantly alter the risk of adverse events compared to alternate treatments.展开更多
Diabetic foot ulcers are among the most severe complications of the lower limb in patients with diabetes.As the immune resistance decreases due to the long-term exposure to hyperglycemic microenvironment,the wound oft...Diabetic foot ulcers are among the most severe complications of the lower limb in patients with diabetes.As the immune resistance decreases due to the long-term exposure to hyperglycemic microenvironment,the wound often fails to heal,leading to a poor prognosis.Foot ulcers have a high risk of amputation and mortality rates making it a growing health concern.Recently,exosomes derived from adipose mesenchymal stem cells have been shown to promote tissue healing,making them a popular topic in cell-free therapies.This article focuses on the risk factors leading to the development of diabetic foot ulcers and the mechanisms of non-healing with the hope to provide new directions or targets for future diabetic foot ulcer treatment.Additionally,this article clarifies the potential mechanisms of action of exosomes from adipose-derived stem cells in promoting the healing of diabetic foot ulcers and discusses its clinical application and limitations.This review aims to provide effective scientific evidence for research on the mechanism and clinical application of exosomes from adipose-derived stem cells for the treatment of diabetic foot ulcers.展开更多
BACKGROUND Diabetic foot ulcers(DFUs)represent a common and serious complication of diabetes,characterized by impaired wound healing and an increased risk of infection.These infections severely impact patient health,n...BACKGROUND Diabetic foot ulcers(DFUs)represent a common and serious complication of diabetes,characterized by impaired wound healing and an increased risk of infection.These infections severely impact patient health,necessitating extensive medical intervention,and increasing the risk of amputation.Vitamin D(VD)plays a critical role in immune regulation and tissue repair.AIM To investigate the effects of VD supplementation on infection rates,wound healing,and immune function in patients with DFUs.METHODS A randomized controlled trial was conducted involving 120 patients with DFUs.Participants were randomly assigned to either a control group(n=60),which received standard care without VD supplementation,or an intervention group(n=60),which received 2000 IU of oral VD3(cholecalciferol)daily for 12 weeks.The primary outcomes included the incidence and severity of infections,whereas the secondary outcomes included wound healing rate,serum 25-hydroxyvitamin D level,levels of immune markers(cathelicidin,interleukin-6 and tumor necrosis factor-α),and adverse events,such as hypercalcemia.RESULTS The incidence of infection was significantly lower in the VD supplementation group(25%)compared with the control group(45%)(P=0.01).Severe infections requiring systemic antibiotics or hospitalization were also less frequent in the VD supplementation group.Wound healing was notably enhanced in the VD supplementation group,with a 60%reduction in ulcer size compared with a 35%reduction in the control group(P<0.01).Serum 25(OH)D level significantly increased in the VD supplementation group(from 16.5 ng/mL to 35.2 ng/mL),confirming the efficacy of VD supplementation.Immune function improved,as demonstrated by a 30%rise in cathelicidin level and a 20%decline in levels of pro-inflammatory cytokines.No adverse effects,including hypercalcemia,were reported.CONCLUSION The VD supplementation effectively reduced infection rate,promoted wound healing,and strengthened immune responses in patients with DFUs.These findings support the incorporation of VD as a safe and effective adjunctive therapy in the clinical management of DFUs.展开更多
BACKGROUND Chronic nonhealing wounds,such as diabetic foot ulcer(DFU),suffer from delayed healing.Identifying effective biomarkers or targets is crucial for managing these refractory wounds.While N7-methylguanosine(m7...BACKGROUND Chronic nonhealing wounds,such as diabetic foot ulcer(DFU),suffer from delayed healing.Identifying effective biomarkers or targets is crucial for managing these refractory wounds.While N7-methylguanosine(m7G)methylation is important in RNA modification,its connection to chronic nonhealing wounds is poorly understood.AIM To assess the potential m7G biomarkers in DFU and their underlying molecular mechanisms.METHODS Differential expression analysis and weighted gene coexpression network analysis identified key genes in DFU.Hub genes were determined through m7G-DFU intersection,and gene set enrichment analysis was conducted.Diagnostic potential of hub genes was assessed using receiver operating characteristic curves.The hub gene’s expression(decapping scavenger enzyme,DCPS)was confirmed using quantitative reverse transcription polymerase chain reaction and immunofluorescence.In vitro,normal human epidermal keratinocyte models were knocked down for DCPS,and the function was assessed through flow cytometry,western blotting,immunofluorescence,Transwell assays,and scratch assays.RESULTS Weighted gene coexpression network analysis and differential expression analysis revealed links between DFU datasets and methylation processes,identifying hub gene DCPS as a candidate biomarker.Notably,its diagnostic value was confirmed with a test set and receiver operating characteristic curve,achieving an area under the curve of 0.98 and 0.99.Quantitative reverse transcription polymerase chain reaction and immunofluorescence analyses showed significantly reduced expression of DCPS in the wound skin of DFU patients and streptozotocin-induced diabetic mice,indicating its role as a regulatory factor of m7G in diabetic wounds.Mechanistically,in vitro studies showed that DCPS knockdown significantly reduced cyclin-dependent kinase 6 and cyclin D1 expression,disrupted the epithelial cell cycle,inhibited cell proliferation and migration,and increased apoptosis rates.CONCLUSION DCPS was identified as a promising DFU biomarker and therapeutic target,regulating m7G to affect cell cycle,proliferation,and epithelial cell migration during DFU wound healing.展开更多
BACKGROUND Shifting from the inflammatory to the proliferative phase represents a pivotal step during managing diabetic foot ulcers(DFUs);however,existing medical interventions remain insufficient.MicroRNAs(miRs)highl...BACKGROUND Shifting from the inflammatory to the proliferative phase represents a pivotal step during managing diabetic foot ulcers(DFUs);however,existing medical interventions remain insufficient.MicroRNAs(miRs)highlight notable capacity for accelerating the repair process of DFUs.Previous research has demonstrated which miR-122-5p regulates matrix metalloproteinases under diabetic conditions,thereby influencing extracellular matrix dynamics.AIM To investigate the impact of miR-122-5p on the transition from the inflammatory to the proliferative stage in DFU.METHODS Analysis for miR-122-5p expression in skin tissues from diabetic ulcer patients and mice was analyzed using quantitative real-time polymerase chain reaction(qRT-PCR).A diabetic wound healing model induced by streptozotocin was used,with mice receiving intradermal injections of adeno-associated virus-DJ encoding empty vector or miR-122.Skin tissues were retrieved at 3,7,and 14 days after injury for gene expression analysis,histology,immunohistochemistry,and network studies.The study explored miR-122-5p’s role in macrophage-fibroblast interactions and its effect on transitioning from inflammation to proliferation in DFU healing.RESULTS High-throughput sequencing revealed miR-122-5p as crucial for DFU healing.qRT-PCR showed significant upregulation of miR-122-5p within diabetic skin among DFU individuals and mice.Western blot,along with immunohistochemical and enzyme-linked immunosorbent assay,demonstrating the upregulation of inflammatory mediators(hypoxia inducible factor-1α,matrix metalloproteinase 9,tumor necrosis factor-α)and reduced fibrosis markers(fibronectin 1,α-smooth muscle actin)by targeting vascular endothelial growth factor.Fluorescence in situ hybridization indicated its expression localized to epidermal keratinocytes and fibroblasts in diabetic mice.Immunofluorescence revealed enhanced increased presence of M1 macrophages and reduced M2 polarization,highlighting its role in inflammation.MiR-122-5p elevated inflammatory cytokine levels while suppressing fibrotic activity from fibroblasts exposed to macrophage-derived media,highlighting its pivotal role in regulating DFU healing.CONCLUSION MiR-122-5p impedes cutaneous healing of diabetic mice via enhancing inflammation and inhibiting fibrosis,offering insights into miR roles in human skin wound repair.展开更多
BACKGROUND Diabetic foot ulcers(DFUs)in patients with type 2 diabetes(T2D)are associated with heightened risks of infection and amputation and thus require effective surgical interventions to enhance outcomes.Free ant...BACKGROUND Diabetic foot ulcers(DFUs)in patients with type 2 diabetes(T2D)are associated with heightened risks of infection and amputation and thus require effective surgical interventions to enhance outcomes.Free anterolateral thigh(ALT)perforator flap is a promising reconstructive method;however,diabetic vasculopathy challenges optimal perfusion.This study analyzes factors influencing intraoperative blood perfusion in ALT flap repair for DFUs.AIM To identify key factors affecting intraoperative blood perfusion during free ALT perforator flap repair in patients with T2D and DFUs,thereby providing insights to improve surgical outcomes.METHODS This retrospective case-control study included 100 patients with T2D who underwent ALT flap repair at our institution between June 2016 and June 2024.Patients were categorized into normal(n=50)and abnormal(n=50)blood perfusion groups based on intraoperative perfusion assessments.Data on demographics,clinical characteristics,vascular status,metabolic control,and preoperative laboratory parameters were collected.Statistical analyses,including univariate and multivariate logistic regression,were conducted to identify significant predictive factors for perfusion outcomes.RESULTS Old age,high body mass index,long diabetes duration,and presence of diabetic peripheral neuropathy were associated with impaired perfusion.Abnormal perfusion was correlated with poor ankle-brachial index and elevated glycated hemoglobin(HbA1c),creatinine,triglycerides,and partial pressure of carbon dioxide.Conversely,high hemoglobin,albumin,and prealbumin levels and partial pressure of oxygen(PaO_(2))were protective.Multivariate analysis identified diabetes duration,HbA1c,PaCO_(2),PaO_(2),and albumin as independent predictors of perfusion,underscoring the roles of metabolic control and vascular health.CONCLUSION Optimizing metabolic control,vascular health,and nutritional status was crucial to enhance intraoperative blood perfusion in diabetic patients undergoing ALT perforator flap repair for DFUs.展开更多
BACKGROUND Diabetic foot ulcers(DFUs)are a severe complication of diabetes and a leading cause of lower limb amputation due to impaired wound healing.Adipose-derived mesenchymal stem cells(ADSCs)have emerged as a prom...BACKGROUND Diabetic foot ulcers(DFUs)are a severe complication of diabetes and a leading cause of lower limb amputation due to impaired wound healing.Adipose-derived mesenchymal stem cells(ADSCs)have emerged as a promising therapeutic option for DFUs because of their angiogenic,immunomodulatory,and regenerative properties.However,studies on the molecular mechanisms and regulatory pathways of ADSCs in DFUs are limited.AIM To investigate the dose-response relationship,the optimal administration route,persistence,and molecular mechanisms of ADSCs in DFU healing.METHODS In this study,human ADSCs were isolated and cultured,and their differentiation potential was characterized.A DFU mouse model was established to evaluate the dose-dependent effects and persistence of ADSCs administered subcutaneously or intramuscularly.Wound closure rate,angiogenesis,inflammation,and collagen deposition were assessed in the ADSC-treated and model groups.Additionally,in vitro experiments using human dermal fibroblasts and endothelial cells were conducted to elucidate the molecular mechanisms underlying ADSC-mediated wound healing.RESULTS ADSC treatment significantly enhanced wound closure,promoted angiogenesis,modulated inflammatory responses,and accelerated tissue regeneration in the DFU model.Notably,the therapeutic efficacy and retention of ADSCs were influenced by both dosage and administration route,with subcutaneous injection of 5×105 ADSCs yielding the most favorable outcomes,particularly when injected into the feet,which resulted in prolonged retention.In vitro experiments further revealed that ADSCs exert their therapeutic effects via multiple mechanisms,including phosphatidylinositol 3-kinase signaling pathway activation to enhance vascular endothelial growth factor secretion,thereby promoting angiogenesis and modulating the Notch signaling pathway in DFUs to suppress inflammation and facilitate tissue regeneration.CONCLUSION ADSCs effectively promote DFU healing and have clinical potential as a treatment for chronic non-healing diabetic wounds.These findings provide a foundation for optimizing ADSC-based therapies for treating DFUs.展开更多
BACKGROUND Negative pressure wound therapy(NPWT)is a potential treatment for diabetic foot ulcers(DFUs),although the mechanisms underlying its effectiveness remain unclear.This study posits that NPWT may improve wound...BACKGROUND Negative pressure wound therapy(NPWT)is a potential treatment for diabetic foot ulcers(DFUs),although the mechanisms underlying its effectiveness remain unclear.This study posits that NPWT may improve wound healing by promoting angiogenesis and activating the nuclear factor erythroid 2-related factor 2(Nrf2)/Kelch-like epichlorohydrin-associated protein 1(Keap1)signaling pathway,which is crucial for the body’s defense against oxidative stress.The hypothesis indicates that enhancing antioxidant defenses through NPWT may positively affect the healing process.There are still limited data on the roles of Nrf2,its downstream signaling molecules,and angiogenesis markers in patients undergoing NPWT.AIM To study the mechanism of NPWT in DFUs.METHODS This study included a total of 40 hospitalized patients with DFUs from Xuzhou Central Hospital,who were divided into Control group(n=21)and NPWT group(n=19).The levels of Nrf2 and Keap1 were analyzed in the granulation tissue 7 days after treatment.The wound condition,erythrocyte sedimentation rate(ESR),procalcitonin(PCT),interleukin 6(IL-6),tumor necrosis factor alpha(TNF-α),vascular endothelial growth factor(VEGF),basic fibroblast growth factor(b-FGF),cluster of differentiation 31(CD31),and levels of oxidative stress[malondialdehyde(MDA),superoxide dismutase(SOD),catalase(CAT),and total antioxidant capacity(T-AOC)]were analyzed before and 7 days after treatment by the Mann-Whitney U test.RESULTS The NPWT group demonstrated significant improvements in wound healing compared to the control group after 7 days of treatment.The levels of ESR,PCT,IL-6,and TNF-αwere significantly reduced in the NPWT group compared to the control group(P<0.05),while the levels of CD31,VEGF,and b-FGF showed significant increases(P<0.05).The NPWT group exhibited notable elevations in the levels of Nrf2 and its downstream targets(SOD,CAT,and T-AOC),accompanied by decreases in the levels of Keap1 and MDA(P<0.05).CONCLUSION NPWT may contribute to the healing of DFUs by potentially reducing levels of oxidative stress.Its effects could possibly be enhanced through the action of Nrf2.展开更多
Skin-nerve interaction plays an important role in promoting wound healing.However,in diabetic ulcers(DUs),the diabetic periphery neuropathy and excessive levels of reactive oxygen species(ROS)block skin-nerve interact...Skin-nerve interaction plays an important role in promoting wound healing.However,in diabetic ulcers(DUs),the diabetic periphery neuropathy and excessive levels of reactive oxygen species(ROS)block skin-nerve interaction and further impede the DUs healing.Herein,we developed a nanoscale metal-organic framework loaded with nerve growth factor(NGF/Ce-UiO-66,denoted NGF/CU)for the treatment of DUs.The Ce-UiO-66(CU)was applied as an antioxidant to scavenge ROS and reduce the inflammatory response while the NGF aided in the recovery of cutaneous nerves to further promote DUs healing.Both in vitro and in vivo experiments revealed the effective ability of NGF/CU for DUs healing.Subsequent RNA sequencing analysis revealed the mechanism that NGF/CU can improve wound healing by inhibiting the NF-κB signaling pathway and recovering the neuroendocrine system of the skin.This strategy of nerve regulation will provide more ideas for the treatment of DUs and other organ injuries.展开更多
Diabetic foot ulceration is a devastating complication of diabetes that is associated with infection,amputation,and death,and is affecting increasing numbers of patients with diabetes mellitus.The pathogenesis of foot...Diabetic foot ulceration is a devastating complication of diabetes that is associated with infection,amputation,and death,and is affecting increasing numbers of patients with diabetes mellitus.The pathogenesis of foot ulcers is complex,and different factors play major roles in different stages.The refractory nature of foot ulcer is reflected in that even after healing there is still a high recurrence rate and amputation rate,which means that management and nursing plans need to be considered carefully.The importance of establishment of measures for prevention and management of DFU has been emphasized.Therefore,a validated and appropriate DFU classification matching the progression is necessary for clinical diagnosis and management.In the first part of this review,we list several commonly used classification systems and describe their application conditions,scope,strengths,and limitations;in the second part,we briefly introduce the common risk factors for DFU,such as neuropathy,peripheral artery disease,foot deformities,diabetes complications,and obesity.Focusing on the relationship between the risk factors and DFU progression may facilitate prevention and timely management;in the last part,we emphasize the importance of preventive education,characterize several of the most frequently used management approaches,including glycemic control,exercise,offloading,and infection control,and call for taking into account and weighing the quality of life during the formulation of treatment plans.Multidisciplinary intervention and management of diabetic foot ulcers(DFUs)based on the effective and systematic combination of these three components will contribute to the prevention and treatment of DFUs,and improve their prognosis.展开更多
In this study the w/o/w extraction–evaporation technique was adopted to prepare poly(lactic-co-glycolic acid)(PLGA)microspheres loading recombinant human epidermal growth factor(rhEGF).The micro-spheres were characte...In this study the w/o/w extraction–evaporation technique was adopted to prepare poly(lactic-co-glycolic acid)(PLGA)microspheres loading recombinant human epidermal growth factor(rhEGF).The micro-spheres were characterized for morphology by transmission electron microscopy(TEM)and particle size distribution.The release performances,the proliferation effects and therapeutic effects of rhEGF-loaded PLGA microspheres were all studied.The results showed that these spherical micro-spheres had a narrow size distribution and a high drug encapsulation efficiency(85.6%).RhEGF-loaded microspheres enhanced the growth rate of fibroblasts and wound healing more efficiently than pure rhEGF.The number of the proliferating cell nuclear antigen(PCNA)in the epidermis layer with the mi-crosphere treatment was significantly larger than those of the control groups.Overall locally sustained delivery of rhEGF from biodegradable PLGA microspheres may serve as a novel therapeutic strategy for diabetic ulcer repair.展开更多
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 pati...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.展开更多
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 makin...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.展开更多
基金supported by the Natural Science Foundation of Hunan Province(No.2021JJ30516).
文摘Wound healing in diabetic ulcers remains a significant clinical challenge,primarily due to bacterial infection and impaired angiogenesis.Periplaneta americana extract(PAE)has been widely used to treat diabetic wounds,yet its underlying mechanisms are not fully understood.This study aimed to elucidate these mechanisms by analyzing long non-coding RNA(lncRNA)expressions in the wound tissues from diabetic anal fistula patients treated with or without PAE,using high-throughput sequencing.Peripheral blood monocytes from patients were differentiated into M0 macrophages with human macrophage colony-stimulating factor(hMCSF)and subsequently polarized into M1 macrophages with lipopolysaccharide.The results indicated that LINC01133 and SLAMF9 were downregulated in wound tissues of patients treated with PAE.Furthermore,PAE suppressed M1 macrophage polarization and enhanced human umbilical vein endothelial cell(HUVEC)proliferation,migration,and angiogenesis.These effects were diminished when LINC01133 or SLAMF9 were overexpressed.Mechanistically,LINC01133 was shown to upregulate SLAMF9 through interaction with ELAVL1.Overexpression of SLAMF9 reversed the effects of LINC01133 silencing on macrophage polarization and HUVEC functions.In conclusion,PAE facilitates the healing of infected diabetic ulcers by downregulating the LINC01133/SLAMF9 pathway.
基金National Natural Science Foundation of China(81774310)National Natural Science Foundation of China Youth Project(81804095)Shanghai Traditional Chinese Medicine Health Service Collaborative Innovation Center Project(ZYJKFW201701002)
文摘The incidence of diabetic ulcer is high, the disability and mortality are also high, and its treatment is difficult, and the healing mechanism is not clear. The main reason for the delayed healing of DU is that the chronic inflammation window period is too long, and macrophages play a key role in its healing process. The polarization of macrophages controls the length of the inflammatory phase, and autophagy is thought to be closely related to the tendency of macrophage polarization. Autophagy regulators have limited clinical application. Traditional Chinese medicine may become an ideal autophagy inducer and provide new ideas and strategies for clinical treatment of diabetic ulcers. This article summarizes the role of macrophage autophagic polarization in the healing of diabetic ulcers and the prospects of traditional Chinese medicine.
文摘There are 422 million diabetic people in the world.25%of these individuals are diagnosed with diabetic foot ulcer(DFU).20%of patients with DFU will suffer amputation of the lower limbs.Following amputation procedures,the mortality rate of patients is over 70%in 5 years.Diabetes has no cure and,therefore,treatment aims to prevent and treat its complications.Autologous platelet-rich plasma(PRP)has been shown to be a therapeutic tool for many types of disorders,including the treatment of DFU.This manuscript aims to carry out a review to provide more knowledge about the efficacy and safety of autologous PRP for wound closure in patients with DFU.The majority of studies included in this review state that PRP promotes improvement of DFU lesions by accelerating tissue healing processes.However,many studies have a small sample size and thus require larger sample range in order to improve robustness of data in the literature.
基金Hubei Province Top Medical Youth Talent Program,Wuhan Knowledge Innovation Special Basic Research Project,No.2023020201020558Clinical Research Project of Affiliated Hospital of Guangdong Medical University,No.LCYJ2021B004 and No.LCYJ2019B010Science and Technology Plan Project of Zhanjiang,No.2022A01191.
文摘BACKGROUND Diabetic foot ulcers(DFUs)present a significant clinical challenge due to their high prevalence and profound impact on morbidity.Ultrasound-assisted wound debridement(UAWD)has emerged as a potential therapeutic modality to improve healing outcomes in DFU management.AIM To evaluate the efficacy of UAWD in treating DFUs on wound closure rates,treatment duration,and quality of life outcomes.METHODS This systematic review and meta-analysis followed PRISMA guidelines,systematically searching PubMed,Embase,Web of Science,and the Cochrane Library with no date restrictions.Randomized controlled trials(RCTs)that evaluated the efficacy of UAWD in DFU treatment were included.Data were independently extracted by two reviewers,with discrepancies resolved through consensus or third-party consultation.The risk of bias was assessed using the Cochrane tool.χ2 and I2 statistics assessed heterogeneity,informing the use of fixed or random-effects models for meta-analysis,supplemented by sensitivity analysis and publication bias assessment through funnel plots and Egger's test.RESULTS From 1255 articles,seven RCTs met the inclusion criteria.The studies demonstrated that UAWD significantly reduced DFU healing time(standardized mean difference=-0.78,95%CI:-0.97 to-0.60,P<0.001)and increased healing rates(odds ratio=9.96,95%CI:5.99 to 16.56,P<0.001)compared to standard care.Sensitivity analysis confirmed the stability of these results,and no significant publication bias was detected.CONCLUSION UAWD is a promising adjunctive treatment for DFUs,significantly reducing healing times and increasing healing rates.These findings advocate for the integration of UAWD into standard DFU care protocols.
基金Supported by the King Salman Center for Disability Research,No.KSRG-2023-407.
文摘Diabetic foot(DF)is a major public health concern.As evident from numerous previous studies,supervision of DF ulcer(DFU)is crucial,and a specific quality check-up is needed.Patients should be educated about glycaemic management,DFUs,foot lesions,proper care for injuries,diet,and surgery.Certain reasonably priced treatments,such as hyperbaric oxygen and vacuum-assisted closure therapy,are also available for DFUs,along with modern wound care products and techniques.Nonetheless,DF care(cleaning,applying antimicrobial cream when wounded,and foot reflexology),blood glucose monitoring to control diabetes,and monthly or quarterly examinations in individuals with diabetes are effective in managing DFUs.Between 50%and 80%of DF infections are preventable.Regardless of the intensity of the lesion,it needs to be treated carefully and checked daily during infection.Tissue regeneration can be aided by cleaning,dressing,and application of topical medicines.The choice of shoes is also important because it affects blood circulation and nerve impulses.In general,regular check-ups,monitoring of the patient’s condition,measuring blood glucose levels,and providing frequent guidance regarding DFU care are crucial.Finally,this important clinical problem requires involvement of multiple professionals to properly manage it.
文摘BACKGROUND Pain often predisposes patients with diabetic foot ulcers(DFUs)to negative emotional states,such as anxiety and depression,which can significantly impair treatment outcomes and recovery.However,very few studies have explored the relationship between anxiety,depression,and pain in DFUs,as well as the associated risk factors.AIM To analyze the correlation between anxiety,depression,and pain in patients with DFUs and to identify the associated risk factors.METHODS This study included 106 patients diagnosed with DFUs who were admitted to Tiantai County People’s Hospital between March 2022 and March 2024.The patients’anxiety levels were evaluated using Zung’s self-rating anxiety scale(SAS),depression status was assessed using Zung’s self-rating depression scale(SDS),and pain intensity was assessed using the visual analog scale(VAS).Subsequently,correlations between SAS,SDS,and VAS scores were analyzed.Univariate and multivariate analyses were conducted to explore the risk factors that contributed to anxiety and depression in patients with DFUs.RESULTS Among the 106 patients,39.62%exhibited anxiety and 43.40%presented with depression.Most patients experiencing anxiety or depression exhibited mild symptoms,with no severe cases observed.Compared with asymptomatic patients,those with anxiety or depression had significantly higher VAS scores.Correlation analysis indicated a significant positive relationship between both SAS and SDS scores and the VAS score.Univariate analysis identified sex,age,Wagner’s grade,presence of other complications,and smoking history as factors significantly associated with anxiety and depression.Multivariate analysis further confirmed that younger age,higher Wagner’s grade,and higher VAS scores were independent predictors of anxiety and depression.CONCLUSION This study reveals a significant positive correlation between anxiety,depression,and pain in patients with DFUs.This finding suggests that timely and effective pain intervention may be beneficial in alleviating negative emotions such as anxiety and depression.In addition,younger age(<50 years),higher Wagner’s grade,and higher VAS scores increase the risk of developing anxiety and depression in this patient population.
基金supported by the Joint Funds of National Natural Science Foundation of China(No.U22A20162)the Natural Science Foundation of Hebei Province of China(No.C2021202002)+1 种基金the National Natural Science Foundation of China(No.52271245),the Natural Science Foundation of Tianjin(No.21JCQNJC01280)the financial support from the Danish Council for Independent Research(9040-00219B),European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement ENSIGN(Project ID:101086226),L4DNANO(Project ID:101086227).
文摘Microneedle(MN)patches could be a promising treatment for diabetic foot ulcers that plague thousands of people worldwide.While reducing skin resistance or increasing driving force can accelerate the efficiency of transdermal drug delivery with conventional MN patches,it can create toxic chemical residues or require the help of additional devices.Herein,a thermo-responsive microneedles patch(TMN)with high biocompatibility without additional equipment is proposed.The TMN consisted of a bilayer microneedles composed of sodium alginate(SA)-g-poly(N-isopropylacrylamide)layer(SA-g-PNIPAM)loaded with sucrose octasulfate sodium salt(SOS)and hyaluronic acid layer and a polycaprolactone/chitosan nanofiber membrane loading with tetracycline hydrochloride(TH)and SOS.PNIPAM accelerates drug release by extruding the drug through a volumetric phase transition in response to temperature changes,and TH and SOS promote wound healing by inhibiting bacterial growth and promoting vascular regeneration and epithelial formation.The results showed that the drug release of TMN was significantly faster,with the drug release rate of more than 80% in the 10th h,and the antibacterial rate of TMN could reach 800%.In addition,TMN had good biocompatibility and good healing effects in vivo,which may be helpful for the design of multifunctional dressings in the future.
基金Supported by the National Natural Science Foundation of China,No.82202454 and No.81873934the Wang Zhengguo Trauma Medicine Fund(Growth Factor Revival Plan)No.SZYZ-TR-09+1 种基金the Shandong Provincial Natural Science Foundation Youth Fund,No.ZR2020QH168the Jinan Science and Technology Plan Project,No.202225065。
文摘BACKGROUND Diabetic foot ulcers(DFUs)are a significant challenge in diabetic care,and the efficacy of negative pressure wound therapy(NPWT)in treating them remains a subject of continuous investigation.AIM To provide a comprehensive meta-analysis of the role of NPWT in the manage-ment of DFUs.METHODS A systematic review was performed based on Preferred Reporting Items for Sys-tematic Reviews and Meta-Analyses guidelines,searching databases like PubMed,Embase,Web of Science,and the Cochrane Library.Randomized clinical trials(RCTs)were included to compare NPWT to other dressings for DFUs.Outcomes measured were wound healing time and rate,granulation tissue formation time,amputation rate,and adverse events.Study quality was evaluated using Coch-rane's risk of bias tool.Analyses utilizedχ2,I2,fixed or random-effects models via Stata v17.RESULTS Of the 1101 identified articles,9 RCTs were selected for meta-analysis.Studies spanned from 2005 to 2020 and originated from countries including the United States,Chile,Pakistan,Italy,India,and Germany.Meta-analysis demonstrated a significant improvement in wound healing rate[risk ratio(RR)=1.46,95%CI:1.22-1.76,P<0.01]and a reduction in amputation rate(RR=0.69,95%CI:0.50-0.96,P=0.006)with NPWT.Furthermore,the time for granulation tissue formation was significantly reduced by an average of 19.54 days.However,the incidence of adverse events did not significantly differ between NPWT and control treatments.CONCLUSION NPWT significantly improves wound healing rates and reduces amputation rates in DFUs.It also hastens the formation of granulation tissue.However,the therapy does not significantly alter the risk of adverse events compared to alternate treatments.
文摘Diabetic foot ulcers are among the most severe complications of the lower limb in patients with diabetes.As the immune resistance decreases due to the long-term exposure to hyperglycemic microenvironment,the wound often fails to heal,leading to a poor prognosis.Foot ulcers have a high risk of amputation and mortality rates making it a growing health concern.Recently,exosomes derived from adipose mesenchymal stem cells have been shown to promote tissue healing,making them a popular topic in cell-free therapies.This article focuses on the risk factors leading to the development of diabetic foot ulcers and the mechanisms of non-healing with the hope to provide new directions or targets for future diabetic foot ulcer treatment.Additionally,this article clarifies the potential mechanisms of action of exosomes from adipose-derived stem cells in promoting the healing of diabetic foot ulcers and discusses its clinical application and limitations.This review aims to provide effective scientific evidence for research on the mechanism and clinical application of exosomes from adipose-derived stem cells for the treatment of diabetic foot ulcers.
基金Supported by Natural Science Foundation of Henan Province,No.202300410396the Young Talents Promotion Project of Henan Province,No.2021HYTP043.
文摘BACKGROUND Diabetic foot ulcers(DFUs)represent a common and serious complication of diabetes,characterized by impaired wound healing and an increased risk of infection.These infections severely impact patient health,necessitating extensive medical intervention,and increasing the risk of amputation.Vitamin D(VD)plays a critical role in immune regulation and tissue repair.AIM To investigate the effects of VD supplementation on infection rates,wound healing,and immune function in patients with DFUs.METHODS A randomized controlled trial was conducted involving 120 patients with DFUs.Participants were randomly assigned to either a control group(n=60),which received standard care without VD supplementation,or an intervention group(n=60),which received 2000 IU of oral VD3(cholecalciferol)daily for 12 weeks.The primary outcomes included the incidence and severity of infections,whereas the secondary outcomes included wound healing rate,serum 25-hydroxyvitamin D level,levels of immune markers(cathelicidin,interleukin-6 and tumor necrosis factor-α),and adverse events,such as hypercalcemia.RESULTS The incidence of infection was significantly lower in the VD supplementation group(25%)compared with the control group(45%)(P=0.01).Severe infections requiring systemic antibiotics or hospitalization were also less frequent in the VD supplementation group.Wound healing was notably enhanced in the VD supplementation group,with a 60%reduction in ulcer size compared with a 35%reduction in the control group(P<0.01).Serum 25(OH)D level significantly increased in the VD supplementation group(from 16.5 ng/mL to 35.2 ng/mL),confirming the efficacy of VD supplementation.Immune function improved,as demonstrated by a 30%rise in cathelicidin level and a 20%decline in levels of pro-inflammatory cytokines.No adverse effects,including hypercalcemia,were reported.CONCLUSION The VD supplementation effectively reduced infection rate,promoted wound healing,and strengthened immune responses in patients with DFUs.These findings support the incorporation of VD as a safe and effective adjunctive therapy in the clinical management of DFUs.
基金Supported by National Natural Science Foundation of China,No.82370903Noncommunicable Chronic Diseases-National Science and Technology Major Project,No.2023ZD0509400 and No.2023ZD0509402+1 种基金2023 Key Disciplines on Public Health Construction of Chongqing,the Natural Science Foundation of Chongqing Municipal Science and Technology Bureau,No.cstc2024ycjh-bgzxm0014Major Project of Science and Technology Research Program of Chongqing Education Commission of China,No.KJZD-M202400102.
文摘BACKGROUND Chronic nonhealing wounds,such as diabetic foot ulcer(DFU),suffer from delayed healing.Identifying effective biomarkers or targets is crucial for managing these refractory wounds.While N7-methylguanosine(m7G)methylation is important in RNA modification,its connection to chronic nonhealing wounds is poorly understood.AIM To assess the potential m7G biomarkers in DFU and their underlying molecular mechanisms.METHODS Differential expression analysis and weighted gene coexpression network analysis identified key genes in DFU.Hub genes were determined through m7G-DFU intersection,and gene set enrichment analysis was conducted.Diagnostic potential of hub genes was assessed using receiver operating characteristic curves.The hub gene’s expression(decapping scavenger enzyme,DCPS)was confirmed using quantitative reverse transcription polymerase chain reaction and immunofluorescence.In vitro,normal human epidermal keratinocyte models were knocked down for DCPS,and the function was assessed through flow cytometry,western blotting,immunofluorescence,Transwell assays,and scratch assays.RESULTS Weighted gene coexpression network analysis and differential expression analysis revealed links between DFU datasets and methylation processes,identifying hub gene DCPS as a candidate biomarker.Notably,its diagnostic value was confirmed with a test set and receiver operating characteristic curve,achieving an area under the curve of 0.98 and 0.99.Quantitative reverse transcription polymerase chain reaction and immunofluorescence analyses showed significantly reduced expression of DCPS in the wound skin of DFU patients and streptozotocin-induced diabetic mice,indicating its role as a regulatory factor of m7G in diabetic wounds.Mechanistically,in vitro studies showed that DCPS knockdown significantly reduced cyclin-dependent kinase 6 and cyclin D1 expression,disrupted the epithelial cell cycle,inhibited cell proliferation and migration,and increased apoptosis rates.CONCLUSION DCPS was identified as a promising DFU biomarker and therapeutic target,regulating m7G to affect cell cycle,proliferation,and epithelial cell migration during DFU wound healing.
基金Supported by the National Natural Science Foundation of China,No.82274528.
文摘BACKGROUND Shifting from the inflammatory to the proliferative phase represents a pivotal step during managing diabetic foot ulcers(DFUs);however,existing medical interventions remain insufficient.MicroRNAs(miRs)highlight notable capacity for accelerating the repair process of DFUs.Previous research has demonstrated which miR-122-5p regulates matrix metalloproteinases under diabetic conditions,thereby influencing extracellular matrix dynamics.AIM To investigate the impact of miR-122-5p on the transition from the inflammatory to the proliferative stage in DFU.METHODS Analysis for miR-122-5p expression in skin tissues from diabetic ulcer patients and mice was analyzed using quantitative real-time polymerase chain reaction(qRT-PCR).A diabetic wound healing model induced by streptozotocin was used,with mice receiving intradermal injections of adeno-associated virus-DJ encoding empty vector or miR-122.Skin tissues were retrieved at 3,7,and 14 days after injury for gene expression analysis,histology,immunohistochemistry,and network studies.The study explored miR-122-5p’s role in macrophage-fibroblast interactions and its effect on transitioning from inflammation to proliferation in DFU healing.RESULTS High-throughput sequencing revealed miR-122-5p as crucial for DFU healing.qRT-PCR showed significant upregulation of miR-122-5p within diabetic skin among DFU individuals and mice.Western blot,along with immunohistochemical and enzyme-linked immunosorbent assay,demonstrating the upregulation of inflammatory mediators(hypoxia inducible factor-1α,matrix metalloproteinase 9,tumor necrosis factor-α)and reduced fibrosis markers(fibronectin 1,α-smooth muscle actin)by targeting vascular endothelial growth factor.Fluorescence in situ hybridization indicated its expression localized to epidermal keratinocytes and fibroblasts in diabetic mice.Immunofluorescence revealed enhanced increased presence of M1 macrophages and reduced M2 polarization,highlighting its role in inflammation.MiR-122-5p elevated inflammatory cytokine levels while suppressing fibrotic activity from fibroblasts exposed to macrophage-derived media,highlighting its pivotal role in regulating DFU healing.CONCLUSION MiR-122-5p impedes cutaneous healing of diabetic mice via enhancing inflammation and inhibiting fibrosis,offering insights into miR roles in human skin wound repair.
文摘BACKGROUND Diabetic foot ulcers(DFUs)in patients with type 2 diabetes(T2D)are associated with heightened risks of infection and amputation and thus require effective surgical interventions to enhance outcomes.Free anterolateral thigh(ALT)perforator flap is a promising reconstructive method;however,diabetic vasculopathy challenges optimal perfusion.This study analyzes factors influencing intraoperative blood perfusion in ALT flap repair for DFUs.AIM To identify key factors affecting intraoperative blood perfusion during free ALT perforator flap repair in patients with T2D and DFUs,thereby providing insights to improve surgical outcomes.METHODS This retrospective case-control study included 100 patients with T2D who underwent ALT flap repair at our institution between June 2016 and June 2024.Patients were categorized into normal(n=50)and abnormal(n=50)blood perfusion groups based on intraoperative perfusion assessments.Data on demographics,clinical characteristics,vascular status,metabolic control,and preoperative laboratory parameters were collected.Statistical analyses,including univariate and multivariate logistic regression,were conducted to identify significant predictive factors for perfusion outcomes.RESULTS Old age,high body mass index,long diabetes duration,and presence of diabetic peripheral neuropathy were associated with impaired perfusion.Abnormal perfusion was correlated with poor ankle-brachial index and elevated glycated hemoglobin(HbA1c),creatinine,triglycerides,and partial pressure of carbon dioxide.Conversely,high hemoglobin,albumin,and prealbumin levels and partial pressure of oxygen(PaO_(2))were protective.Multivariate analysis identified diabetes duration,HbA1c,PaCO_(2),PaO_(2),and albumin as independent predictors of perfusion,underscoring the roles of metabolic control and vascular health.CONCLUSION Optimizing metabolic control,vascular health,and nutritional status was crucial to enhance intraoperative blood perfusion in diabetic patients undergoing ALT perforator flap repair for DFUs.
基金Supported by The Zhongguancun National Independent Innovation Demonstration Zone Industrial Ecosystem Cultivation Project,No.20220468089.
文摘BACKGROUND Diabetic foot ulcers(DFUs)are a severe complication of diabetes and a leading cause of lower limb amputation due to impaired wound healing.Adipose-derived mesenchymal stem cells(ADSCs)have emerged as a promising therapeutic option for DFUs because of their angiogenic,immunomodulatory,and regenerative properties.However,studies on the molecular mechanisms and regulatory pathways of ADSCs in DFUs are limited.AIM To investigate the dose-response relationship,the optimal administration route,persistence,and molecular mechanisms of ADSCs in DFU healing.METHODS In this study,human ADSCs were isolated and cultured,and their differentiation potential was characterized.A DFU mouse model was established to evaluate the dose-dependent effects and persistence of ADSCs administered subcutaneously or intramuscularly.Wound closure rate,angiogenesis,inflammation,and collagen deposition were assessed in the ADSC-treated and model groups.Additionally,in vitro experiments using human dermal fibroblasts and endothelial cells were conducted to elucidate the molecular mechanisms underlying ADSC-mediated wound healing.RESULTS ADSC treatment significantly enhanced wound closure,promoted angiogenesis,modulated inflammatory responses,and accelerated tissue regeneration in the DFU model.Notably,the therapeutic efficacy and retention of ADSCs were influenced by both dosage and administration route,with subcutaneous injection of 5×105 ADSCs yielding the most favorable outcomes,particularly when injected into the feet,which resulted in prolonged retention.In vitro experiments further revealed that ADSCs exert their therapeutic effects via multiple mechanisms,including phosphatidylinositol 3-kinase signaling pathway activation to enhance vascular endothelial growth factor secretion,thereby promoting angiogenesis and modulating the Notch signaling pathway in DFUs to suppress inflammation and facilitate tissue regeneration.CONCLUSION ADSCs effectively promote DFU healing and have clinical potential as a treatment for chronic non-healing diabetic wounds.These findings provide a foundation for optimizing ADSC-based therapies for treating DFUs.
文摘BACKGROUND Negative pressure wound therapy(NPWT)is a potential treatment for diabetic foot ulcers(DFUs),although the mechanisms underlying its effectiveness remain unclear.This study posits that NPWT may improve wound healing by promoting angiogenesis and activating the nuclear factor erythroid 2-related factor 2(Nrf2)/Kelch-like epichlorohydrin-associated protein 1(Keap1)signaling pathway,which is crucial for the body’s defense against oxidative stress.The hypothesis indicates that enhancing antioxidant defenses through NPWT may positively affect the healing process.There are still limited data on the roles of Nrf2,its downstream signaling molecules,and angiogenesis markers in patients undergoing NPWT.AIM To study the mechanism of NPWT in DFUs.METHODS This study included a total of 40 hospitalized patients with DFUs from Xuzhou Central Hospital,who were divided into Control group(n=21)and NPWT group(n=19).The levels of Nrf2 and Keap1 were analyzed in the granulation tissue 7 days after treatment.The wound condition,erythrocyte sedimentation rate(ESR),procalcitonin(PCT),interleukin 6(IL-6),tumor necrosis factor alpha(TNF-α),vascular endothelial growth factor(VEGF),basic fibroblast growth factor(b-FGF),cluster of differentiation 31(CD31),and levels of oxidative stress[malondialdehyde(MDA),superoxide dismutase(SOD),catalase(CAT),and total antioxidant capacity(T-AOC)]were analyzed before and 7 days after treatment by the Mann-Whitney U test.RESULTS The NPWT group demonstrated significant improvements in wound healing compared to the control group after 7 days of treatment.The levels of ESR,PCT,IL-6,and TNF-αwere significantly reduced in the NPWT group compared to the control group(P<0.05),while the levels of CD31,VEGF,and b-FGF showed significant increases(P<0.05).The NPWT group exhibited notable elevations in the levels of Nrf2 and its downstream targets(SOD,CAT,and T-AOC),accompanied by decreases in the levels of Keap1 and MDA(P<0.05).CONCLUSION NPWT may contribute to the healing of DFUs by potentially reducing levels of oxidative stress.Its effects could possibly be enhanced through the action of Nrf2.
基金the financial support from National Natural Science Foundation of China(Grant No.82372098 and 82104073)Opening Project of State Key Laboratory of High Performance Ceramics and Superfine Microstructure(SKL202212SIC)Shanghai Science and Technology Commission/General Project of Natural Science Foundation of Shanghai in 2021(21ZR1440600).
文摘Skin-nerve interaction plays an important role in promoting wound healing.However,in diabetic ulcers(DUs),the diabetic periphery neuropathy and excessive levels of reactive oxygen species(ROS)block skin-nerve interaction and further impede the DUs healing.Herein,we developed a nanoscale metal-organic framework loaded with nerve growth factor(NGF/Ce-UiO-66,denoted NGF/CU)for the treatment of DUs.The Ce-UiO-66(CU)was applied as an antioxidant to scavenge ROS and reduce the inflammatory response while the NGF aided in the recovery of cutaneous nerves to further promote DUs healing.Both in vitro and in vivo experiments revealed the effective ability of NGF/CU for DUs healing.Subsequent RNA sequencing analysis revealed the mechanism that NGF/CU can improve wound healing by inhibiting the NF-κB signaling pathway and recovering the neuroendocrine system of the skin.This strategy of nerve regulation will provide more ideas for the treatment of DUs and other organ injuries.
基金Supported by the National Natural Science Foundation of ChinaNo. 81873238 and 82074532+1 种基金the Open Projects of the Discipline of Chinese Medicine of Nanjing University of Chinese Medicine supported by the Subject of Academic Priority Discipline of Jiangsu Higher Education Institutions,No. ZYX03KF012the Postgraduate Research&Practice Innovation Program of Jiangsu Province,No. KYCX22_1963。
文摘Diabetic foot ulceration is a devastating complication of diabetes that is associated with infection,amputation,and death,and is affecting increasing numbers of patients with diabetes mellitus.The pathogenesis of foot ulcers is complex,and different factors play major roles in different stages.The refractory nature of foot ulcer is reflected in that even after healing there is still a high recurrence rate and amputation rate,which means that management and nursing plans need to be considered carefully.The importance of establishment of measures for prevention and management of DFU has been emphasized.Therefore,a validated and appropriate DFU classification matching the progression is necessary for clinical diagnosis and management.In the first part of this review,we list several commonly used classification systems and describe their application conditions,scope,strengths,and limitations;in the second part,we briefly introduce the common risk factors for DFU,such as neuropathy,peripheral artery disease,foot deformities,diabetes complications,and obesity.Focusing on the relationship between the risk factors and DFU progression may facilitate prevention and timely management;in the last part,we emphasize the importance of preventive education,characterize several of the most frequently used management approaches,including glycemic control,exercise,offloading,and infection control,and call for taking into account and weighing the quality of life during the formulation of treatment plans.Multidisciplinary intervention and management of diabetic foot ulcers(DFUs)based on the effective and systematic combination of these three components will contribute to the prevention and treatment of DFUs,and improve their prognosis.
基金the National Natural Science Foundation of China(Grant No.50373033)the Applied Foundational Research Key Fund of Tianjin(Grant No.05YFJZJC01001)the International Cooperative Fund of Tianjin(Grant No.05YFGHHZ20070)
文摘In this study the w/o/w extraction–evaporation technique was adopted to prepare poly(lactic-co-glycolic acid)(PLGA)microspheres loading recombinant human epidermal growth factor(rhEGF).The micro-spheres were characterized for morphology by transmission electron microscopy(TEM)and particle size distribution.The release performances,the proliferation effects and therapeutic effects of rhEGF-loaded PLGA microspheres were all studied.The results showed that these spherical micro-spheres had a narrow size distribution and a high drug encapsulation efficiency(85.6%).RhEGF-loaded microspheres enhanced the growth rate of fibroblasts and wound healing more efficiently than pure rhEGF.The number of the proliferating cell nuclear antigen(PCNA)in the epidermis layer with the mi-crosphere treatment was significantly larger than those of the control groups.Overall locally sustained delivery of rhEGF from biodegradable PLGA microspheres may serve as a novel therapeutic strategy for diabetic ulcer repair.
文摘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.
文摘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.
