Wound Healing In Diabetic Foot Ulcers Research Articles

Long noncoding RNA H19 acts as a miR-29b sponge to promote wound healing in diabetic foot ulcer.

Aberrant expression of long noncoding RNA (lncRNA) H19 and microRNA (miR)-29b has been implicated in the complications of diabetes mellitus (DM). As a common and important complication of DM, diabetic foot ulcer (DFU) is characterized by high incidence and poor prognosis. Herein, we explored the role of lncRNA H19 in wound healing of DFU. Differentially expressed DM-related lncRNAs were initially screened by microarray data analysis. DFU models were then induced in DM mouse models. The functional role and interaction of lncRNA H19, miR-29b and FBN1 in DFU were subsequently determined by examining the proliferation, migration, and apoptosis of fibroblasts after silencing H19, inhibiting or overexpressing miR-29b and FBN1. According to microarray-based analysis, lncRNA H19 was upregulated in DM. In the ulcerative edge tissues of DFU, high expression of lncRNA H19 and FBN1 and low expression of miR-29b were observed. FBN1 was identified to be a target gene of miR-29b. LncRNA H19 could competitively bind to miR-29b, and then, inhibited its expression, which consequently upregulating FBN1. Silencing of lncRNA H19 led to inhibited proliferation, migration, and enhanced apoptosis of fibroblasts, accompanied by downregulated FBN1 but upregulated miR-29b, which diminished the expression of TGF-β1, Smad3, FN, and Col-1 and reduced extracellular matrix accumulation. Altogether, upregulation of lncRNA H19 can elevate the expression of FBN1 through competitively binding to miR-29b, which enhances the proliferation, migration, and inhibits apoptosis of fibroblasts, thus facilitating the wound healing of DFU.

Photo-Optical Transcutaneous Oxygen Tension Measurement Is of Added Value to Predict Diabetic Foot Ulcer Healing: An Observational Study.

Currently, transcutaneous oxygen tension measurement (TCpO2) is the most favorable non-invasive test for diabetic foot ulcer (DFU) healing prognosis. Photo-optical TCpO2 is novel, less time-consuming and more practical in use compared to regular electro-chemical TCpO2. We prospectively investigated the clinical value of photo-optical TCpO2 to predict DFU healing. Patients with suspected DFU undergoing conservative treatment underwent an ankle pressure, toe-pressure and photo-optical TCpO2 test. The primary endpoint was DFU wound healing at 12 months. Based on their clinical outcome, patients were divided into a DFU healing and DFU non-healing group. Healing was defined as fully healed ulcers and non-healing as ulcers that deteriorated under conservative treatment or that required surgical amputation. Differences between groups were analyzed and an optimal TCpO2 cut-off value was determined. In total, 103 patients were included, of which 68 patients (66%) were classified as DFU healing. The remaining 35 patients (34%) had deteriorated ulcers, of which 29 (83%) eventually required surgical amputation. An optimal TCpO2 cut-off value of 43 mmHg provided a sensitivity, specificity and odds ratio of 0.78, 0.56 and 4.4, respectively. Photo-optical TCpO2 is an adequate alternative tool to validate the vascular status of the lower extremity indicating healing prognosis in patients with DFU. Therefore, we recommend that photo-optical TCpO2 can be safely coapplied in clinical practice to assist in DFU treatment strategy.

Antibacterial-Integrated Collagen Wound Dressing for Diabetes-Related Foot Ulcers: An Evidence-Based Review of Clinical Studies.

Diabetic foot ulcer (DFU) is a chronic wound frequently delayed from severe infection. Wound dressing provides an essential barrier between the ulcer and the external environment. This review aimed to analyse the effectiveness of antibacterial collagen-based dressing for DFU treatment in a clinical setting. An electronic search in four databases, namely, Scopus, PubMed, Ovid MEDLINE(R), and ISI Web of Science, was performed to obtain relevant articles published within the last ten years. The published studies were included if they reported evidence of (1) collagen-based antibacterial dressing or (2) wound healing for diabetic ulcers, and (3) were written in English. Both randomised and non-randomised clinical trials were included. The search for relevant clinical studies (n) identified eight related references discussing the effectiveness of collagen-based antibacterial wound dressings for DFU comprising collagen impregnated with polyhexamethylene biguanide (n = 2), gentamicin (n = 3), combined-cellulose and silver (n = 1), gentian violet/methylene blue mixed (n = 1), and silver (n = 1). The clinical data were limited by small sample sizes and multiple aetiologies of chronic wounds. The evidence was not robust enough for a conclusive statement, although most of the studies reported positive outcomes for the use of collagen dressings loaded with antibacterial properties for DFU wound healing. This study emphasises the importance of having standardised clinical trials, larger sample sizes, and accurate reporting for reliable statistical evidence confirming DFU treatment efficiency.

A Narrative Review on Modern Wound Dressing for Diabetes Mellitus Wound

Introduction: Diabetic foot is a wide-ranging term for foot disorders includes infection, ulceration, or destruction of deep tissue due to peripheral neuropathy and ischemia from peripheral vascular disease. Wound dressings play a significant part in the treatment of diabetic foot ulcer (DFU). Modern wound dressing which is commonly known as the moist wound dressing can be better optional than the conservative one for the DFU. Aim: This study aimed to review the available articles on modern wound dressing for diabetes mellitus wound. Method: A total of six articles were reviewed and explained under the findings and discussion part of this study. The published articles from the year 2008 onwards are included in this narrative review. Result: Overall, it is evident that using of modern wound dressing can make sure excellent wound surroundings, avoid complications, improvement of quality of life of patients and aid the healing of DFU providing that the patient’s glycemic level is controlled. Conclusion: The process of wound healing in DFU is not static and it requires an appropriate environment at each stage of the healing process. And also a reasonable approach to the selection of dressing for certain types of wounds should be clarified. However, further study needs to be carried out to prove the current finding.

Inhibition of miRNA-152-3p enhances diabetic wound repair via upregulation of PTEN.

Diabetic foot ulcer (DFU) is a major complication of diabetes in the elderly population. The aim of this study was to investigate the potential mechanism of DFU at the molecular level and explore a feasible therapy for it. Using data from the Gene Expression Omnibus (GEO) database, we found that phosphatase and tensin homolog (PTEN) is differentially expressed between diabetic patients and those without diabetes. We also found that PTEN expression is regulated by glucose stimulation. In addition, decreased function of human umbilical vein endothelial cells (HUVECs) was found to be associated with reduction of PTEN. We identified microRNA-152-3p (miR-152-3p) to be a putative upstream negative regulator of PTEN, and in vivo and in vitro results indicated that miR-152-3p antagonist could restore HUVEC function and accelerate wound repair. Thus, miR-152-3p-induced downregulation of PTEN appears responsible for the delayed wound healing in DFU, and miR-152-3p inhibition may effectively accelerate wound repair, thereby providing a potential target for DFU therapy.

Long non-coding RNA H19 contributes to wound healing of diabetic foot ulcer.

Diabetic foot ulcer (DFU) is a chronic and non-healing complication of diabetes that leads to high hospital costs and, in extreme cases, to amputation. Recent studies have reported that long non-coding RNAs (lncRNAs) are linked to various diabetes-related symptoms. Thus, we aim to explore the role of lncRNA H19 in the wound healing process following DFU. Fibroblasts were isolated from the ulcer margin tissues of DFU patients, with the expression of lncRNA H19, connective tissue growth factor (CTGF) or serum response factor (SRF) altered by lentivirus infection. Next, rat models of DFU induced by high glucose and lipid diet were established, which was also infected with corresponding lentivirus. The interaction among lncRNA H19, SRF and CTGF was determined. Afterwards, cell proliferation and apoptosis, angiogenesis, ECM remodeling and wound healing in DFU tissues were evaluated to explore the effects of lncRNA H19/SRF/CTGF and MAPK signaling pathway on DFU. CTGF was poorly expressed in ulcer tissues from DFU rats and patients. CTGF overexpression was shown to activate the MAPK signaling pathway to promote cell proliferation, ECM remodeling, angiogenesis and wound healing while inhibiting cell apoptosis. LncRNA H19 was validated to elevate CTGF expression by recruiting SRF to the promoter region of CTGF, thus accelerating cell proliferation, ECM remodeling and wound healing while repressing cell apoptosis. Furthermore, MAPK signaling pathway activation is confirmed to be the underlying mechanism behind lncRNA H19/CTGF/SRF-induced results. Thus, lncRNA H19 accelerated wound healing in DFU through elevation of CTGF and activation of the MAPK signaling pathway.

Maggot excretions/secretions promote diabetic wound angiogenesis via miR18a/19a – TSP-1 axis

AimsThe impaired angiogenesis is one of the main factors affecting the healing of diabetic foot ulcer (DFU) wounds. Maggot debridement therapy (MDT) promotes granulation tissue growth and angiogenesis during DFU wound healing. Non-coding microRNAs can also promote local angiogenesis in DFU wounds by regulating wound repairing related gene expression. The purpose of this study was to investigate the mechanism of microRNAs in MDT promoting DFU wound angiogenesis. MethodsIn this study, we applied MDT to treat DFU wound tissue and detect the expression of the miR-17–92 cluster. In vitro experiments, human umbilical vein endothelial cells (HUVECs) were treated with maggot excretions/secretions (ES), the miR-17–92 cluster and the predicted target gene expression were measured. Tube formation assay and cell scratch assay were performed when inhibition of miR-18a/19a or overexpression of thrombospondin-1 (TSP-1) were used in this study. ResultsmiR-18a/19a transcription significantly up-regulated and TSP-1 expression down-regulated in patients wound tissue and in HUVECs. Inhibition of miR-18a/19a or overexpression of TSP-1 partially blocked the migration and tube formation ability stimulated by ES. ConclusionTargeted activation of miR-18a/19a transcription levels and subsequent regulation of TSP-1 expression may be a novel therapeutic strategy for DFU.

Diyabetik Ayağın İyileşmesinde Beslenme Tedavisinin Rolü Var mı?

Tüm dünyada diyabetli hasta sayısı giderek artmakta ve buna eşlik eden komplikasyonların özellikle de diyabetik ayak ülseri (DAÜ) insidansı artmaktadır ki diyabet ile ilişkili ayak komplikasyonları en yaygın morbidite sebebidir. DAÜ’ye bağlı komplikasyonların yıllık insidansı %2’dir. DAÜ’nin tedavisi ve izlemi, hastanın yaşam kalitesinin arttırılması, infeksiyonun kontrol edilmesi, ampütasyon riskinin azaltılması ve ülkede ekonomik yükünün azaltması gibi sebeplerden dolayı önemlidir. Etkin diyabet yönetimi ile DAÜ komplikasyonlarını geciktirmek veya önlemek mümkündür. Tedavi ve önlemde ki hedefler; hasta eğitimi, iyi metabolik kontrol, risk faktörleri olan hastaların saptanması ve tedavisidir. Diyabetli bireyde yara iyileşmesi bozulmuştur. DAÜ, inflamatuvar cevabın uzaması, matriks yenilenmesinin gecikmesi ile karakterizedir. DAÜ’nün iyileşmesinin gecikmesi, tekrarlayan infeksiyonların varlığı, hastaneye yatış sıklığının artması morbidite ile ilişkilidir. Bu başarısızlığı önlemek için tedavide multidisipliner yaklaşım önemlidir. DAÜ’de yara iyileşmesinde glisemik kontrolü sağlamak için medikal tedavilerle birlikte tıbbı beslenme tedavisi gerekmektedir. Beslenme tedavisindeki önceliğin ve beslenme desteği gereksiniminin belirlenmesinde beslenme durumunun değerlendirilmesi önem taşımaktadır. Besin ögelerinin alımının yetersiz olması inflamatuvar sürecin uzamasına, fibroblast proliferasyonunun azalmasına ve kollajen sentezinin bozulmasına neden olarak yara iyileşmesini geciktirmektedir. Malnutrisyon varlığı da yara iyileşmesini olumsuz etkiler. DAÜ’lü hastaların %84.8’inde beslenme durumunun bozulmuş olduğu gösterilmiştir. DAÜ’nün şiddeti ve bununla ilişkili inflamatuvar yanıt, besin ögesi eksikliklerini şiddetlendiren negatif protein metabolizmasıyla ilişkilidir. Optimal beslenmedeki amaç yara iyileşmesinin sağlanmasıdır. Beslenme durumunun düzeltilmesinde enerji, makro ve mikro besin ögeleri eksiğinin tamamlanması yara iyileşme sürecini olumlu etkilemektedir. Besin ögesi takviyesi tamamlayıcı terapötik bir önlem olabilir. DAÜ’leri tedavi etmek için kanıta dayalı bir kılavuz bulunmamaktadır. Bağışıklık fonksiyonunu etkileyen, yetersiz beslenme ve kötü glisemik kontrole neden olan risk faktörleri beslenme tedavisi ile iyileştirilebilir. Sonuç olarak, yeterli enerji, protein, vitamin ve mineral alımı sağlayan beslenme tedavisi, bağışıklık fonksiyonunu en üst düzeye çıkarmaya yardımcı olabilir. DAÜ’lü hastalar sağlıklı beslenmeye teşvik edilmelidir.

The MSC-Derived Exosomal lncRNA H19 Promotes Wound Healing in Diabetic Foot Ulcers by Upregulating PTEN via MicroRNA-152-3p

Mesenchymal stem cells (MSCs) have been reported to hold promise to accelerate the wound-healing process in diabetic foot ulcer (DFU) due to the multilineage differentiation potential. Hence, this study intended to explore the wound healing role of MSC-derived exosomes containing long noncoding RNA (lncRNA) H19 in DFU. lncRNA H19 was predicated to bind to microRNA-152-3p (miR-152-3p), which targeted phosphatase and tensin homolog (PTEN) deleted on chromosome ten. Fibroblasts in DFU samples exhibited highly expressed miR-152-3p and poorly expressed lncRNA H19 and PTEN, along with an activated phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/protein kinase B (Akt1) signaling pathway. The fibroblasts were cocultured with lncRNA H19-transfected MSCs and MSC-derived exosomes to assess the effect of the lncRNA H19/miR-152-3p/PTEN axis on the biological activities and inflammation in fibroblasts. Mouse models of DFU were developed by streptozotocin, which was injected with MSC-derived exosomes overexpressing lncRNA H19. lncRNA H19 in MSCs was transferred through exosomes to fibroblasts, the mechanism of which improved wound healing in DFU, corresponded to promoted fibroblast proliferation and migration, as well as suppressed apoptosis and inflammation. Wound healing in mice with DFU was facilitated following the injection of MSC-derived exosomes overexpressing lncRNA H19. Taken together, MSC-derived exosomal lncRNA H19 prevented the apoptosis and inflammation of fibroblasts by impairing miR-152-3p-mediated PTEN inhibition, leading to the stimulated wound-healing process in DFU.

MiR-203 Acts as an Inhibitor for Epithelial-Mesenchymal Transition Process in Diabetic Foot Ulcers via Targeting Interleukin-8

Objectives: As a complication of diabetes mellitus (DM), one of the leading causes for death and disability for DM patients is diabetic foot ulcers (DFUs). Epithelial to mesenchymal transition (EMT) plays a critical role in wound healing of DFUs. miR-203 is specifically enriched in keratinocytes and has been shown to target interleukin 8 (IL-8), which acts as an activator for the EMT process. In this study, we explored the interaction between miR-203 and IL-8 in DFU rat models and human keratinocyte cells, underlying the mechanism of miR-203’s function in DFUs progression. Methods: DFU rat models were used to test gene expression in DFU progression. Diabetic keratinocyte cell lines were used to validate in vitro. Wound healing and Transwell assays were applied to evaluate cell migration and invasion abilities. The EMT process was estimated by testing expression of E-cadherin, Vimentin and Slug. The interaction between miR-203 and IL-8 was determined by Luciferase assay. Results: Our results demonstrated that the wound-healing process had been slowed in DFUs, and the advanced glycation end products (AGEs) and the receptor for advanced glycation end products (RAGEs) in wound tissue were of a higher expression than those in normal rat. miR-203 was increased in skin tissues from DFU rat models, while IL-8 was decreased. Through knock-down of miR-203 in AGE-treated keratinocyte cells, it had been shown that the downregulation of miR-203 could promote cell proliferation and migration, and facilitate the EMT process. Meanwhile, Luciferase assay proved that miR-203 could directly target and inhibit IL-8. The repression of IL-8 could rescue the outcomes brought about by miR-203 inhibition. Conclusions: The upregulation of miR-203 in DFU tissues impaired wound healing by the repress EMT process. Specific knock-down of miR-203 could promote wound healing through the reactivation of its target gene IL-8 and the downstream IL-8/AKT pathway.

Improved Healing of Diabetic Foot Ulcer upon Oxygenation Therapeutics through Oxygen-Loading Nanoperfluorocarbon Triggered by Radial Extracorporeal Shock Wave.

Diabetic foot ulcers (DFUs), the most serious complication of diabetes mellitus, can induce high morbidity, the need to amputate lower extremities, and even death. Although many adjunctive strategies have been applied for the treatment of DFUs, the low treatment efficiency, potential side effects, and high cost are still huge challenges. Recently, nanomaterial-based drug delivery systems (NDDSs) have achieved targeted drug delivery and controlled drug release, offering great promises in various therapeutics for diverse disorders. Additionally, the radial extracorporeal shock wave (rESW) has been shown to function as a robust trigger source for the NDDS to release its contents, as the rESW harbors a potent capability in generating pressure waves and in creating the cavitation effect. Here, we explored the performance of oxygen-loaded nanoperfluorocarbon (Nano-PFC) combined with the rESW as a treatment for DFUs. Prior to in vivo assessment, we first demonstrated the high oxygen affinity in vitro and great biocompatibility of Nano-PFC. Moreover, the rESW-responsive oxygen release behavior from oxygen-saturated Nano-PFC was also successfully verified in vitro and in vivo. Importantly, the wound healing of DFUs was significantly accelerated due to improved blood microcirculation, which was a result of rESW therapy (rESWT), and the targeted release of oxygen into the wound from oxygen-loaded Nano-PFC, which was triggered by the rESW. Collectively, the oxygen-saturated Nano-PFC and rESW provide a completely new approach to treat DFUs, and this study highlights the advantages of combining nanotechnology with rESW in therapeutics.

Amino acids and wound healing in people with limb-threatening diabetic foot ulcers

BackgroundAmino acids are associated with wound healing in traumatic wounds and burns, although their effects on healing in patients with diabetic foot ulcers (DFUs) are limited. This study aimed to evaluate and identify specific amino acids associated with healing outcomes of patients with DFUs. MethodsSixty-two out of 85 patients who completed the in-hospital treatment for limb-threatening DFUs were enrolled. All ulcers had epithelialization without clinical evidence of infection at discharge. The patients and their families were instructed on foot-care techniques and committed to regular follow-up for 1 year. Baseline characteristics, PEDIS wound classification, laboratory data and serum amino acid levels were used to analyze their predictive power. ResultsFifty-seven patients completed the study in which 38 had healed and 19 had unhealed ulcers. The unhealed group had higher incidence of coronary artery disease and larger wound size. Most patients received endovascular therapy (81.6% healed group; 78.9% unhealed group) before enrollment. Following adjustments for clinical factors, the serum levels of arginine (326.4 μmol/L vs. 245.0 μmol/L, P = 0.045), isoleucine (166.7 μmol/L vs. 130.1 μmol/L, P = 0.019), leucine (325.8 μmol/L vs. 248.9 μmol/L, P = 0.039), and threonine (186.7 μmol/L vs. 152.0 μmol/L, P = 0.019) were significantly higher in the healed group. ConclusionsThe amino acids associated with wound healing in DFUs differ from those reported for traditional traumatic wounds. These findings affirm the necessity for future large-scaled studies for the application of these amino acids in DFU healing, either as prognostic predictors or supplemented regimens.

Association of vascular endothelial growth factor gene +405 C>G and -460 C>T polymorphism with diabetic foot ulcer in Indonesia

Background, the greatest risk factor for Diabetic foot ulcer (DFU) is neuropathy. Vascular endothelial growth factor (VEGF) gene is a gene encodes a protein vascular endothelial growth factor (VEGF), which has a function of angiogenesis and neurogenesis. VEGF plays a role in neuropathy, angiopathy and wound healing in DFU. Methods: Case-control study, case is types 2 DM with DFU and control is type 2 DM without DFU, Polymerase Chain Reaction-Restriction Fragment length polymorphism was done to find genotype polymorphism of VEGF gene. Results: Genotype GG VEGF + 405C> G does not have a significant association with DFU in DM patients (GG + CG / CC; OR; 0.52, 95% CI; 0.15 to 1.73 p; 0.289). G allele is proposed as a protective factor in DFU (OR; 0.86, 95% CI 0.57 to 1.28, and p; 0.456). Genotype TT from VEGF gene -460 C> T; have no significant association with DFU (TT + CT / CC; OR; 0.97, 95% CI; 0.41 to 2.26 and p; 0.942). T allele is predicted as protective factor in DFU (OR; 0.90, 95% CI; 0.59 to 1.37 and p; 0,641). Conclusion: G alleles and T alleles are predicted as a protective factor in DM patients associated with DFU.

Effects of silver alginate dressing for diabetic foot ulcers

Objective To explore the effects of silver alginate dressing for wounds of diabetic foot ulcers (DFU) . Methods From April 2017 to April 2018, we selected 120 DFU patients of Peking Union Medical College Hospital as subjects by convenience sampling. All of the patients were divided into control group and observation group with the random number table, 60 cases in each group. Observation group received the treatment of silver alginate dressing, while control group was treated with alginate dressing. After treatment, we compared the score of visual analogue scale (VAS) before and after treatment, times of changing dressing, time of wound healing and the healing rate of ulcer of patients after treatment between two groups. Results After treatment, the score of VAS, time of wound healing and times of changing dressing was (2.5±0.6) , (42±3.9) d and (14.3±1.9) respectively of observation group lower than those of control group with significant differences (t=13.964, 22.241, 21.122; P<0.01) . The healing rate of ulcer of observation group and control group was 93.3% and 75.0% respectively with a significant difference (χ2=23.564, P<0.01) . Conclusions The silver alginate dressing can promote the wound healing of DFU, shorten the time of healing, reduce the times of changing dressing and ease patients' pain. Key words: Diabetic foot; Silver ion; Alginate; Pain; Wound healing

Epidermal Vascular Endothelial Growth Factor Improved Wound Healing of Patients with Diabetic Foot Ulcer

Diabetic foot ulcer (DFU) is a kind of chronic vascular complications in diabetes. Wound healing in DFU is a complex process where reduced proangiogenic growth factor is an important factor. We studied angiogenesis factors which may contribute to the healing of DFU. Twenty five type 2 diabetes patients with acute DFU were treated with hospital standard procedure and closely observed for 1 month. Biopsies from wound edges were subjected to histopathology assessment and immunohistochemical staining of CD34, bFGF and VEGF. All examination was performed two times consecutively. We observed that granulation tissues developed faster at proximal site of the foot. Weak tissue VEGF was expressed before treatment. Interestingly, VEGF expression in epidermis increased significantly after patients received treatment. Increased VEGF is consistent with increased number of CD34 positive endothelial cells. These data suggest that epidermal VEGF is an important angiogenesis factor and may improve healing in acute DFU receiving standard treatment.

Study on the effect of ankle pump motion on wound healing of diabetic foot ulcer

Objective To explore the effect of ankle pump on wound healing of diabetic foot ulcer (DFU) . Methods Using convenience sampling method, patients hospitalized in Podiatry Department of Tianjin Medical University Metabolic Diseases Hospital from July to December 2015 and eligible for inclusion-exclusion criteria were recruited to control group, and patients who were hospitalized from May to October 2016 were recruited to observation group according inclusion-exclusion criteria. A total of 162 patients with DFU were recruited and 156 patients completed the whole study, with 72 cases in observation group and 84 cases in control group. Routine treatment and nursing care of DFU were given to both groups, and on the basis of that ankle pump motion therapy training was given to the observation group. After treatment for 9 weeks, the foot ulcer area, healing condition, transcutaneous arterial oxygen tension (TcPO2) , foot skin temperature and ankle brachial index (ABI) were compared. In addition, the adverse events throughout the process of the two groups were recorded. Results After 9-week treatment, the healing rate of observation group was higher than the control group, and the difference wasn't statistically significant (χ2=3.714, P=0.054) . The area of foot ulcer of both groups decreased, and the difference wasn't statistically significant before and after treatment (P 0.05) . There was no statistical difference of TcPO2, ABI and skin temperature between the two groups before treatment (P>0.05) . In observation group, Wagner grading Ⅱ patients' skin temperature and ABI, Wagner grading Ⅲ patients' TcPO2 and skin temperature, Wagner grading Ⅳ patients' TcPO2 were all higher than those of the control group, with statistical difference (P<0.01) . There were 4 cases of asymptomatic hypoglycemia in each group, and there was no statistical difference of adverse event in both groups. Conclusions The ankle pump motion has a positive effect on the wound healing of DFU, which has the advantage of high safety. Key words: Diabetic foot; Ulcer; Ankle pump motion

Naringin, a flavanone glycoside, promotes angiogenesis and inhibits endothelial apoptosis through modulation of inflammatory and growth factor expression in diabetic foot ulcer in rats

Chronic, unhealed diabetic foot ulcer (DFU) is one of the most severe complications of diabetes mellitus (DM). Naringin, a flavanone glycoside antioxidant, was reported to have antidiabetic and anti-apoptotic properties. In the present study DM was induced experimentally by streptozotocin (STZ, 55mg/kg, i.p.). In surgically introduced wounds on the dorsal surface of the hind paw of rats, the healing potential of naringin was investigated. Rats were treated with naringin (20, 40 and 80mg/kg, p.o.), insulin (10IU/kg, s.c.) and tetrachlorodecaoxide (TCDO) (1 drop, twice a day, topically) for 16days. The wound area was measured every second day, and on day 17 various biochemical parameters were determined in serum, wound tissue, and histopathological examination of the wound was performed. Naringin (40 and 80mg/kg) significantly (P<0.05) improved wound area, serum glucose level, glycated Hb and serum insulin. Naringin treatment at 40 and 80mg/kg resulted in significant (P<0.05) up-regulation of mRNA expression of growth factor (IFG-1, TGF-β and VEGF-c), Ang-1 and collagen-1 whereas mRNA expression of inflammatory mediators (TNF-α, IL-1β and IL-6) was down-regulated. Furthermore, naringin significantly (P<0.05) attenuated STZ-induced apoptosis and stimulated angiogenesis in the wound tissue. Further results suggest that angiogenesis was improved via naringin-mediated inhibition of hyperglycemia, oxidative stress, down-regulation of inflammatory mediator expression and up-regulation of growth factor expression, leading to improved wound healing of DFU.