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Although the role of low-level laser therapy (LLLT) and human adipose-derived stem cells (hADSC) in accelerating diabetic wound healing has been proven, their synergistic effect is still debated. This study aimed to evaluate the individual and combined effects of LLLT and hADSC on wound healing and on biomechanical parameters in type 2 diabetic rabbits. In this experimental study, 40 rabbits with type 2 diabetes (induced by streptozotocin (STZ)) were included. Rabbits were randomly assigned with equal ratios to 4 groups, including the control group (group A), hADSCs alone (group B), the laser alone (group C), and the combined group of hADSCs cells with laser (group D). 30 days after diabetes, two wounds were created on the back of each rabbit. Immediately after creating a wound, hADSC was injected into two parts of the wound. In the laser groups, the wound site was treated with a low-power 660 nm laser for 4 weeks daily for 20–30 s. The number of closed wounds in the treatment group was evaluated 7, 15 and 30 days after the treatment. On the 15th and 30th days, a standard sample of each healing wound was sent for biomechanical evaluation. Thirty days after treatment, the combined effect of LLLT + hADSCs was superior to their individual effects on wound healing and biomechanical parameters (mean bending stiffness, maximum force, high-stress load, and energy absorption), while their individual effects were similar. Fifteen days after treatment, the effect of LLLT alone was superior to hADSCs alone for wound healing and improvement of biomechanical parameters. LLLT and hADSCs, individually and in combination, were superior in diabetic wound healing and biomechanical parameters compared to the control group in type 2 diabetic rabbits. The combined effect of LLLT with hADSCs was superior to their individual effects. [ABSTRACT FROM AUTHOR]

Background: Gelatin hydrogel nonwoven fabrics (Genocel) are three-dimensional gelatin scaffolds that provide cells with space for proliferation, migration, and differentiation. They are expected to be an effective wound healing modality to treat intractable wounds, such as diabetic foot ulcers, because they enhance early neovascularization when used as a skin substitute. In this study, we explored the healing process of Genocel applied to skin defects in diabetic mice and compared it with that of a conventional skin substitute, Pelnac. Methods: Genocel and Pelnac sheets were used to treat skin defects on the backs of diabetic mice. On days 7 and 14, the remaining wound area was evaluated and specimens were harvested for HE, Azan, anti-CD31, CD68, and CD163 staining to assess neoepithelialization, granulation tissue formation, capillary formation, and macrophage infiltration. Results: Wounds treated with Genocel showed a wound healing process comparable to that of wounds treated with Pelnac. No significant differences were observed in the remaining wound area, neoepithelial length, granulation formation, number of pan-macrophages, or M2 ratio on days 7 and 14. The only significant difference was the number of induced M2 macrophages, which was higher in Pelnac group than in the Genocel group on day 7 (p

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.

Abstract Skin microbiota plays an essential role in the development and function of the cutaneous immune system, in the maintenance of the skin barrier through the release of antimicrobial peptides, and in the metabolism of some natural products. With the aim of characterizing changes in the cutaneous microbiota specifically associated with wound healing in the diabetic condition, we performed a 16 S rRNA gene Next Generation Sequencing of skin swabs taken within the ulcer bed of ten diabetic patients before (t0) and after 20 days of therapy (t20) with a fluorescein-based galenic treatment. Considering the twenty most representative genera, we found at t20 an increase of Corynebacterium, Peptostreptococcus, and Streptococcus, and a decrease of Enterococcus, Finegoldia, and Peptoniphilus genera. However, differences were not significant due to the high variability among samples and the small patient cohort. S. aureus was the most abundant species at t0 and was reduced by therapy in four patients. Comparing the microbiome in the ulcer bed and in the perilesional tissue of the same patient at t0, no major differences were observed. Taken together, our data indicate that in the absence of antibiotic-based therapy the healing process of diabetic ulcers is accompanied by changes in the microbiome composition.

Skin microbiota plays an essential role in the development and function of the cutaneous immune system, in the maintenance of the skin barrier through the release of antimicrobial peptides, and in the metabolism of some natural products. With the aim of characterizing changes in the cutaneous microbiota specifically associated with wound healing in the diabetic condition, we performed a 16 S rRNA gene Next Generation Sequencing of skin swabs taken within the ulcer bed of ten diabetic patients before (t0) and after 20 days of therapy (t20) with a fluorescein-based galenic treatment. Considering the twenty most representative genera, we found at t20 an increase of Corynebacterium, Peptostreptococcus, and Streptococcus, and a decrease of Enterococcus, Finegoldia, and Peptoniphilus genera. However, differences were not significant due to the high variability among samples and the small patient cohort. S. aureus was the most abundant species at t0 and was reduced by therapy in four patients. Comparing the microbiome in the ulcer bed and in the perilesional tissue of the same patient at t0, no major differences were observed. Taken together, our data indicate that in the absence of antibiotic-based therapy the healing process of diabetic ulcers is accompanied by changes in the microbiome composition. [ABSTRACT FROM AUTHOR]

Diabetic ulcers are one of the common complications in diabetic patients. Delayed wound healing is associated with persistent pro-inflammatory M1 polarization, reduced angiogenesis and increased reactive oxygen species (ROS) in the microenvironment. Wound healing consists of multiple phases and therefore requires treatment tailored to each phase. In this study, a biphasic drug-releasing microneedle (MN) was fabricated to achieve early ROS scavenging and late accelerated angiogenesis to promote wound healing. Vascular endothelial growth factor (VEGF) was first encapsulated in methacryloylated sulfonated chitosan (SCSMA) microspheres (V@MP), and then V@MP was loaded into hyaluronic acid (HA) microneedles along with cerium dioxide nanoparticles (CONPs). Rapid dissolution of HA rapidly releases the CONPs to clear ROS, whereas the V@MP stays in the wound. SCSMA slow degradation prolongs the release of VEGF, thereby promoting angiogenesis. In vitro and in vivo studies have shown that this biphasic drug-releasing smart microneedle improves cell proliferation and migration, effectively scavenges ROS, promotes angiogenesis and tissue regeneration, and synergistically promotes M2 macrophage polarization. It provides a new delivery mode for nano-enzymes and growth factors that could be multifunctional and synergistic in the treatment of diabetic ulcers. In our study, we present a microneedle (V@MP/C@MN) that can release drugs biphasically, which showed good repair ability in diabetic ulcer model. Large amounts of CONPs were rapidly released to alleviate oxidative stress during the inflammation of the wound, and V@MP stayed in the wound for a long period of time to release VEGF and promote angiogenesis in the late stage of wound healing. The results indicated that V@MP/C@MN could promote cell proliferation and migration, effectively scavenge ROS, promote angiogenesis and tissue regeneration, and synergistically promote M2 macrophage polarization, which could play a multifunctional and synergistic role in the treatment of diabetic ulcers. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract Diabetic ulcers (DUs) usually suffer from severe infections, persistent inflammation, and excessive oxidative stress during the healing process, which led to the microenvironmental alternation and severely impede DU healing, resulting in a delayed wound healing. Therefore, it is particularly important to develop a medical dressing that can address these problems simultaneously. To this end, self-healing composite hydrogels were prepared in this study utilizing Bletilla striata polysaccharide (BSP) and Berberine (BER) with borax via borate ester bond. The chemical and mechanical properties of the BSP/BER hydrogels were characterized, and their wound healing performance was investigated in vivo and in vitro. The results showed that the BSP/BER hydrogel significantly accelerated wound healing in DU mice with the healing rate of 94.90 ± 1.81% on the 14th day by using BSP/BER5, and this outstanding performance was achieved by the multi-targeted biological functions of antibacterial, anti-inflammatory and antioxidant, which provided favorable microenvironment for orderly recovery of the wound. Aside from exhibiting the antibacterial rate of over 90% against both Escherichia coli and Staphylococcus aureus, the BSP/BER5 hydrogel could significantly reduce NO levels 4.544 ± 0.32 µmol/L to exert its anti-inflammatory effects. Additionally, it demonstrated a hemolysis rate and promotes cell migration capabilities at (34.92 ± 1.66%). With the above features, the developed BSP/BER hydrogel in this study could be the potential dressing for clinical treatment of DU wound.

Abstract Background Mesenchymal stem cells (MSCs)-based treatment strategy has shown promise in bolstering the healing process of chronic wounds in diabetic patients, who are at risk of amputation and mortality. To overcome the drawbacks of suboptimal cell retention and diminished cell viability at the injury site, a novel nanofibrous biomaterial-based scaffold was developed by using a controlled extrusion of a polymeric solution to deliver the cells (human adipose-derived MSCs (ADMSCs) and placenta-derived MSCs (PLMSCs)) locally to the animal model of diabetic ulcers. Methods The physicochemical and biological properties of the nano-bioscaffold were characterized in terms of microscopic images, FTIR spectroscopy, tensile testing, degradation and swelling tests, contact angle measurements, MTT assay, and cell attachment evaluation. To evaluate the therapeutic efficacy, a study using an excisional wound model was conducted on diabetic rats. Results The SEM and AFM images of scaffolds revealed a network of uniform nanofibers with narrow diameters between 100-130 nm and surface roughness less than 5 nm, respectively. ADMSCs and PLMSCs had a typical spindle-shaped or fibroblast-like morphology when attached to the scaffold. Desired characteristics in terms of swelling, hydrophilicity, biodegradation rate, and biocompatibility were achieved with the CS70 formulation. The wound healing process was accelerated according to wound closure rate assay upon treatment with MSCs loaded scaffold resulting in increased re-epithelialization, neovascularization, and less inflammatory reaction. Our findings unequivocally demonstrated that the cell-loaded nano-bioscaffold exhibited more efficacy compared with its acellular counterpart. In summation, our study underscores the potential of this innovative cellular scaffold as a viable solution for enhancing the healing of diabetic ulcers. Conclusion The utilization of MSCs in a nanofibrous biomaterial framework demonstrates significant promise, providing a novel avenue for advancing wound care and diabetic ulcer management. Graphical Abstract

Diabetic patients with poor blood glucose control are highly susceptible to developing secondary infections, which can lead to the development of prolonged diabetic ulcers. Therefore, a suitable medication that may effectively prevent the occurrence of secondary infections is crucial to shorten the closure of diabetic ulcers. Red betel leaf (Piper crocatum Ruiz & Pav) is reported to possess antimicrobial activity due to the presence of flavonoids. This study aimed to evaluate the effect of ethanolic extract of red betel leaf (EERBL) ointments against the most prevalent bacteria associated with diabetic foot ulcers (DFU): Staphylococcus aureus and Pseudomonas aeruginosa. The EERBL was prepared by macerating powdered red betel leaf with 96% ethanol and was screened for the presence of flavonoids and the determination of total flavonoid content (TFC) by thin layer chromatography and UV-Vis spectrophotometry, respectively. This study examined three hydrophilicbased ointments containing 10%, 20%, and 30% EERBL, respectively, followed by characterization for pH, spreadability, adhesivity, and viscosity. The EERBL ointments' effect on the bacteria was evaluated using the well-diffusion method by observing inhibition zone formation after 24-hour incubation. The results showed that varying the EERBL concentrations in the formulations led to different spreadability, adhesivity and viscosity (p

The Wound Healing Society guidelines for the treatment of arterial insufficiency ulcers were originally published in 2006, with the last update in 2014. These guidelines provided recommendations, along with their respective levels of evidence, on seven categories: diagnosis, surgery, infection control, wound bed preparation, dressings, adjuvant therapy and long‐term maintenance. Over the last 9 years, additional literature regarding these aspects of arterial ulcer management has been published. An advisory panel comprised of academicians, clinicians and researchers was chosen to update the 2014 guidelines. Members included vascular surgeons, internists, plastic surgeons, anaesthesiologists, emergency medicine physicians and dermatologists, all with expertise in wound healing. The goal of this article is to evaluate relevant new findings upon which an updated version of the guidelines will be based. [ABSTRACT FROM AUTHOR]

Background: Mesenchymal stem cells (MSCs)-based treatment strategy has shown promise in bolstering the healing process of chronic wounds in diabetic patients, who are at risk of amputation and mortality. To overcome the drawbacks of suboptimal cell retention and diminished cell viability at the injury site, a novel nanofibrous biomaterial-based scaffold was developed by using a controlled extrusion of a polymeric solution to deliver the cells (human adipose-derived MSCs (ADMSCs) and placenta-derived MSCs (PLMSCs)) locally to the animal model of diabetic ulcers. Methods: The physicochemical and biological properties of the nano-bioscaffold were characterized in terms of microscopic images, FTIR spectroscopy, tensile testing, degradation and swelling tests, contact angle measurements, MTT assay, and cell attachment evaluation. To evaluate the therapeutic efficacy, a study using an excisional wound model was conducted on diabetic rats. Results: The SEM and AFM images of scaffolds revealed a network of uniform nanofibers with narrow diameters between 100-130 nm and surface roughness less than 5 nm, respectively. ADMSCs and PLMSCs had a typical spindle-shaped or fibroblast-like morphology when attached to the scaffold. Desired characteristics in terms of swelling, hydrophilicity, biodegradation rate, and biocompatibility were achieved with the CS70 formulation. The wound healing process was accelerated according to wound closure rate assay upon treatment with MSCs loaded scaffold resulting in increased re-epithelialization, neovascularization, and less inflammatory reaction. Our findings unequivocally demonstrated that the cell-loaded nano-bioscaffold exhibited more efficacy compared with its acellular counterpart. In summation, our study underscores the potential of this innovative cellular scaffold as a viable solution for enhancing the healing of diabetic ulcers. Conclusion: The utilization of MSCs in a nanofibrous biomaterial framework demonstrates significant promise, providing a novel avenue for advancing wound care and diabetic ulcer management. [ABSTRACT FROM AUTHOR]

Context Diabetes mellitus is associated with morbid complications such as diabetic foot ulcers (DFUs) that may lead to amputations or mortality if not managed adequately. Objective New adjunctive interventions to treat diabetic wounds include topical biologics and growth factors. This study aims to evaluate their efficacy in improving wound-healing outcomes and safety. Methods Comprehensive database searches of MEDLINE via PubMed, EMBASE, and Cochrane were performed from inception to December 2022. Three independent researchers selected the studies. Randomized controlled trials that compared the use of a topical biologic growth factor-containing regimen to other biologics or standard of care (SOC) were included. This review followed PRISMA guidelines. Risk of bias analysis was performed using the Jadad scale. Network meta-analysis was performed. Treatments were grouped into common nodes based on the type of biologic agent. Primary outcomes of interest were healing rate and time to wound closure. Secondary outcomes included wound infection, serious adverse events (AEs), and amputation rate. Results Human umbilical cord (HUC) was associated with the highest cure, followed by recombinant human epidermal growth factor (hEGF). A significantly greater reduction in the time to cure DFUs was seen in HUC, hEGF, and fibroblast growth factor (FGF). There was a significantly lower risk of AEs when platelet-rich plasma (PRP) was administered. Conclusion HUC, hEGF, and FGF are promising topical biologics with statistically significant primary outcomes compared to SOC, while PRP is effective in reducing ulcer-related AEs. HUC has been found to be the most effective in terms of cure rate and a reduction in time to cure. [ABSTRACT FROM AUTHOR]

Objectives: The increasing incidence of chronic wounds such as diabetic foot ulcers and pressure ulcers, often compounded by bacterial infections and biofilm formation, presents significant challenges in wound management. Despite advancements in wound care products and a better understanding of molecular wound repair mechanisms, the treatment of chronic ulcerating conditions remains incomplete. VG111, a novel natural product formulation, emerges as a promising therapeutic candidate addressing the need for an effective wound healing agent with antimicrobial and tissue regenerative properties. Materials and Methods: A thorough evaluation of VG111 included antimicrobial assays to determine its minimum inhibitory concentration against an array of pathogens, assessment of its biofilm disruption capabilities, investigation into its profibrogenic activity through scratch assays, and analysis of its immunomodulatory effects on macrophage-derived cytokines. Quality consistency was ensured by high-performance liquid chromatography fingerprinting, while clinical applicability was assessed through observations in canine and human wound healing cases. Statistical Analysis: The cytotoxic effects of VG111 were assessed using a Two-way ANOVA, indicating no significant cytotoxicity at the tested concentration (Column factor p<0.0001). Results: VG111 demonstrated potent antimicrobial action with effective concentrations ranging from 2.5% to 5.0% v/v, targeting resistant strains of Methicillin-resistant Staphylococcus aureus , colistin-resistant Escherichia coli, Acinetobacter baumannii , and other priority pathogens. It showed biofilm clearance, enhanced fibroblast migration, and a favorable immunomodulatory profile by reducing inflammatory cytokines in vitro. In vivo applications corroborated these findings, with significant wound healing observed in both veterinary and clinical settings, negating the need for additional antibiotics. Conclusions: The study emphasized on VG111 as a robust wound healing agent with significant antimicrobial and biofilm-disrupting properties. Its broad-spectrum efficacy against critical pathogens and ability to promote tissue regeneration mark it as a promising avenue in the management of complex chronic wounds, meriting further clinical exploration. [ABSTRACT FROM AUTHOR]

Abstract Chronic wounds, resulting from persistent inflammation, can trigger a cascade of detrimental effects including exacerbating inflammatory cytokines, compromised blood circulation at the wound site, elevation of white blood cell count, increased reactive oxygen species, and the potential risk of bacterial infection. The interleukin-17 (IL-17) signaling pathway, which plays a crucial role in regulating immune responses, has been identified as a promising target for treating inflammatory skin diseases. This review aims to delve deeper into the potential pathological role and molecular mechanisms of the IL-17 family and its pathways in wound repair. The intricate interactions between IL-17 and other cytokines will be discussed in detail, along with the activation of various signaling pathways, to provide a comprehensive understanding of IL-17’s involvement in chronic wound inflammation and repair.

Diabetic ulcers are defined as erosion of the skin that extends from the dermis layer to deeper tissue, resulting from various factors, namely neuropathy, ischemia and infection, resulting in damage to the patient's skin integrity. Bhayangkara Hospital Makassar Medical Records 2022 number of diabetic ulcer patients was 5,743 people, the number of inpatient diabetic ulcer patients was 586 people (2.70%), and the number of outpatients was 5,157 people (4.38%). This research aims to find out a general description of the application of wound cleaning using 0.9% NaCl to avoid damage to skin integrity in patients in the PMerak Room, Bhayangkara Hospital, Makassar. This research method uses descriptive research with a case study approach, using 4 effective methods for collecting data, namely Interview, Observation, Physical Examination and documentation methods. The results of applying wound cleaning with 0.9% NaCl to patients who had diabetic ulcers in the swallow room at Bhayangkara Makassar Hospital for 3 days showed that the nursing problem was that damage to skin integrity had not been resolved. After implementing the intervention, the result was that pus in the wound was reduced, and a new network emerged. Conclusion: After applying wound care using 0.9% NaCl liquid, "Skin integrity has not been resolved in diabetic ulcer wounds. On the last day of the study, the surgical wound on the little finger had dried, and the base of the second, third and fourth toes of the right toe looked scaly and dry and sore. In the ulcers, new tissue appears in the center of the wound.

In the present study, the efficiency of two formulations of maggot therapy: free-range larvae on the wounds and larvae in a special bag (larval-bag), was compared for healing diabetic ulcers with Wagner 2 diabetic ulcer. This study was conducted as a parallel randomized clinical trial. Out of 281 patients with Wagner grade 2 diabetic ulcers referred to the wound clinic, 54 patients who met the inclusion criteria were randomly assigned to intervention groups. The disinfected larvae of Lucilia sericata were put on the wounds with 2 methods, free-range larvae and larval-bag. Follow up was done at every 48 h interval until the full appearance of granulated tissues. The main measures were wound bed preparation, removing of necrotic tissues, appearing of granulated tissues, and removing of bacterial infections in the wounds. Statistical analysis based on the Kaplan–Meier curve and the Wilcoxon (Breslow) test showed a significant reduction in wound healing time by using free-range larvae in comparison with larval-bag (P =.03). The median time to debridement was 4 days in the free-range larval group (95% confidence interval: 3-9 days) while it was 9 days in the larval-bag group (95% confidence interval: 5-16 days). Debridement rate (proportion of removed necrotic tissue surfaces) at any time in the free-ranged larvae group was 1.78 times that of the bagged larvae group (95% confidence interval 1.01-3.15, P =.036). There was no significant difference between free-range larval use and larval-bag in the acceptability of maggot therapy by patients (P =.48). It can be concluded that both of two formulations of the larval therapy (free-range larvae and larval-bag) could be recommended for cleaning out and bed preparation of diabetic ulcers. However, using free-range larvae is hardly recommended on the wounds which are eligible to use. [ABSTRACT FROM AUTHOR]

Chronic non‐healing ulcers are common among diabetic patients, posing significant therapeutic challenges. This study compared traditional therapies (TT) and emerging therapies (ET) for enhancing diabetic patients' wound healing. A total of 150 diabetic patients with chronic ulcers, ages 30–65, were randomly assigned to one of two groups: TT (n = 75) or ET (n = 75). ET included growth factors, bioengineered skin substitutes, and hyperbaric oxygen therapy, while TT for wound healing predominantly included debridement, saline‐moistened dressings, and off‐loading techniques. The primary outcome was the percentage of lesions that healed within 12 weeks, which was assessed at intervals. Secondary outcomes included time to wound recovery, pain using Visual Analogue Scale (VAS), and life quality via Wound‐QoL questionnaire. By the 12th week, the ET group had a repair rate of 81.33% compared to 57.33% in TT group (p < 0.05). ET exhibited superior pain reduction (VAS score: 4.7 ± 1.6 for ET vs. 6.2 ± 1.4 for TT, p < 0.05) and improved life quality (Wound‐QoL score: 61.8 ± 9.1 for ET vs. 44.3 ± 10.3 for TT, p < 0.05). However, there were slightly more cases of cutaneous irritation and hematomas among ET patients. ET have demonstrated significant efficacy in accelerating wound healing in diabetic patients, surpassing traditional methods, with additional advantages in pain management and life quality. Due to the observed minor complications, however, caution is required. [ABSTRACT FROM AUTHOR]

Objective To investigate whether shikonin can regulate autophagy and promote wound healing in diabetic rats by upregulating C-X-C chemokine receptor type 4 (CXCR4). Methods A total of 24 Sprague-Dawley (SD) rats were assigned to control, diabetic, diabetic+ Shikonin, and diabetic+Shikonin+sh-CXCR4 groups (6 rats in each group) using random number table method. A diabetic rat model was established by intraperitoneal injection of streptozotocin, and a 1 cm-diameter skin punch was used to create an ulcer model on the back of the rat. Wound healing rates were calculated on days 0, 7, 14, and 21 after wounding. On day 21 after wounding, skin tissues were collected for hematoxylin & eosin and Masson trichrome staining to analyze the pathological changes of the wound. CD31 immunohistochemistry was performed to analyze the microvascular density of the wound and Western blotting was used to detect the expression of CXCR4 and cell autophagy-related proteins microtubule-related proteins light chain 3 (LC3) II/ LC3 I, Beclin1, and soluble p62 in the wound tissue. Autophagosomes were observed by transmission electron microscopy. One-way analysis of variance was used for comparison between groups. Results Compared with the control group, the diabetic group had reduced wound healing rate (on day 21: 72.44%±6.21% vs. 93.71%±6.76%), neovascularization, collagen deposition, microvascular density, levels of CXCR4, LC3 II /LC3 I, and Beclin, and increased p62 levels in the wound tissue, as well as decreased autophagosomes (P<0.05). Compared with the diabetic group, wound healing rate (on day 21: 86.74%±4.86% vs. 72.44%±6.21%), neovascularization, collagen deposition, microvascular density, levels of CXCR4, LC3 II/LC3 I, and Beclin, and autophagosomes were increased, but p62 levels were decreased in the diabetic+Shikonin group (P<0.05). Compared with the diabetic+Shikonin group, the diabetic+Shikonin group had decreased wound healing rate (on day 21: 76.15%±3.85% vs. 86.74%±4.86%), neovascularization, collagen deposition, microvascular density, levels of CXCR4, LC3 II/LC3 I, and Beclin, and autophagosomes in the wound tissue, as well as increased p62 levels (P<0.05). Conclusion Shikonin promotes the healing of diabetic ulcer wounds by upregulating CXCR4 expression and activating cell autophagy. [ABSTRACT FROM AUTHOR]

Insulin is a hormone whose efficacy in wound healing was recognised in the late 1920s. Intensive research is currently underway to develop materials that will allow the effective stabilisation of insulin and control of its diffusion rate. The aim of this review was to bring together research on the development of innovative wound care strategies based on insulin-enriched bioactive dressings. An analysis of the literature contained in bibliographic databases and published up to 30 June 2023 was performed. The results of the included basic and preclinical studies confirm that engineered polymeric matrices/scaffolds with insulin show high efficacy and good tolerability in topical wound treatment. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) can lead to diabetic ulcers (DUs), which are the most severe complications. Due to the need for more accurate patient classifications and diagnostic models, treatment and management strategies for DU patients still need improvement. The difficulty of diabetic wound healing is caused closely related to biological metabolism and immune chemotaxis reaction dysfunction. Therefore, the purpose of our study is to identify metabolic biomarkers in patients with DU and construct a molecular subtype‐specific prognostic model that is highly accurate and robust. RNA‐sequencing data for DU samples were obtained from the Gene Expression Omnibus (GEO) database. DU patients and normal individuals were compared regarding the expression of metabolism‐related genes (MRGs). Then, a novel diagnostic model based on MRGs was constructed with the random forest algorithm, and classification performance was evaluated utilizing receiver operating characteristic (ROC) analysis. The biological functions of MRGs‐based subtypes were investigated using consensus clustering analysis. A principal component analysis (PCA) was conducted to determine whether MRGs could distinguish between subtypes. We also examined the correlation between MRGs and immune infiltration. Lastly, qRT‐PCR was utilized to validate the expression of the hub MRGs with clinical validations and animal experimentations. Firstly, 8 metabolism‐related hub genes were obtained by random forest algorithm, which could distinguish the DUs from normal samples validated by the ROC curves. Secondly, DU samples could be consensus clustered into three molecular classifications by MRGs, verified by PCA analysis. Thirdly, associations between MRGs and immune infiltration were confirmed, with LYN and Type 1 helper cell significantly positively correlated; RHOH and TGF‐β family remarkably negatively correlated. Finally, clinical validations and animal experiments of DU skin tissue samples showed that the expressions of metabolic hub genes in the DU groups were considerably upregulated, including GLDC, GALNT6, RHOH, XDH, MMP12, KLK6, LYN, and CFB. The current study proposed an auxiliary MRGs‐based DUs model while proposing MRGs‐based molecular clustering and confirmed the association with immune infiltration, facilitating the diagnosis and management of DU patients and designing individualized treatment plans. [ABSTRACT FROM AUTHOR]

Diabetic ulcers can progress into tissue death, or gangrene, which create a risk for amputation. Measures for preventing other complications and accelerating wound healing in diabetic ulcers include blood sugar level control, diet adjustment, wound care, antidiabetic drug administration, and comorbid therapy. This leads to the use of various drugs that can potentially trigger drug interactions. This study aimed to identify possible drug interactions in the therapeutic management of diabetic ulcer patients treated in Husada Utama Hospital Surabaya, Indonesia, from January 2020–June 2022. This was a descriptive observational study using retrospective data from medical records. Results showed that 103 types of drugs were administered to 48 research samples with 41 of them experienced drug interactions (n=263 cases). Based on the severity of drug interactions, 31 cases were categorized as major cases (11.79%), with drug-class antibiotic-antiemetic interactions as the most frequent interactions. This study proves that it is essential for doctors and pharmacists.

Hyperbaric oxygen therapy (HBOT) is an adjuvant novel non-invasive treatment technique in the field of plastic surgery for treating different wounds. This technique utilizes 100% oxygen at pressures above the atmospheric pressure. In our study, we are discussing about eight different cases in the field of plastic surgery. HBOT plays an important role in the treatment for different pathological conditions. It involves a hundred percent breathing of oxygen in a closed chamber for a certain period of time. HBOT main mechanism of action is hyper oxygenation but also enhances the immunity by antimicrobial properties and improves stem cell production.

Abstract Diabetic ulcers (DUs) are one of the most serious complications of diabetes mellitus. The application of a functional dressing is a crucial step in DU treatment and is associated with the patient's recovery and prognosis. However, traditional dressings with a simple structure and a single function cannot meet clinical requirements. Therefore, researchers have turned their attention to advanced polymer dressings and hydrogels to solve the therapeutic bottleneck of DU treatment. Hydrogels are a class of gels with a three-dimensional network structure that have good moisturizing properties and permeability and promote autolytic debridement and material exchange. Moreover, hydrogels mimic the natural environment of the extracellular matrix, providing suitable surroundings for cell proliferation. Thus, hydrogels with different mechanical strengths and biological properties have been extensively explored as DU dressing platforms. In this review, we define different types of hydrogels and elaborate the mechanisms by which they repair DUs. Moreover, we summarize the pathological process of DUs and review various additives used for their treatment. Finally, we examine the limitations and obstacles that exist in the development of the clinically relevant applications of these appealing technologies. Graphical Abstract This review defines different types of hydrogels and carefully elaborate the mechanisms by which they repair diabetic ulcers (DUs), summarizes the pathological process of DUs, and reviews various bioactivators used for their treatment.

Background: Impaired inflammation and vascularization are common reasons for delayed diabetic wound healing. Nanoparticles (NPs)-in-nanofibers composites can manage diabetic wounds. A multifunctional scaffold was developed based on tadalafil (TDF)-loaded NPs incorporated into polyvinyl alcohol/Withania somnifera extract nanofibers. Materials & methods: TDF-loaded NPs were prepared and fully characterized in terms of their physicochemical properties. Extract of ashwagandha was prepared and a blend composed of TDF-loaded NPs, herbal extract and polyvinyl alcohol was used to prepare the whole composite. Results: The whole composite exhibited improved wound closure in a diabetic rat model in terms of reduced inflammation and enhanced angiogenesis. Conclusion: Results suggest that this multifunctional composite could serve as a promising diabetic wound dressing. [ABSTRACT FROM AUTHOR]

Diabetic ulcers induced by multidrug‐resistant (MDR) bacteria have severely endangered diabetic populations. These ulcers are very challenging to treat because the local high glucose concentration can both promote bacterial growth and limit the immune system's bactericidal action. Herein, a glucose oxidase‐peroxidase (GOx‐POD) dual‐enzyme mimetic (DEM) bionanocatalyst, Au@CuBCats is synthesized to simultaneously control glucose concentration and bacteria in diabetic ulcers. Specifically, the AuNPs can serve as GOx mimics and catalyze the oxidation of glucose for the formation of H2O2; the H2O2 can then be further catalytically converted into OH via the POD‐mimetic copper single atoms. Notably, the unique copper single atoms coordinated by one oxygen and two nitrogen atoms (CuN2O1) exhibit better POD catalytic performance than natural peroxidase. Further DFT calculations are conducted to study the catalytic mechanism and reveal the advantage of this CuN2O1 structure as compared to other copper single‐atom sites. Both in vitro and in vivo experiments confirm the outstanding antibacterial therapeutic efficacy of the DEM bionanocatalyst. This new bionanocatalyst will provide essential insights for the next generation of antibiotic‐free strategies for combating MDR bacterial diabetic ulcers, and also offer inspiration for designing bionanocatalytic cascading medicines. [ABSTRACT FROM AUTHOR]

Diabetic chronic wounds cause massive levels of patient suffering and economic problems worldwide. The state of chronic inflammation arises in response to a complex combination of diabetes mellitus‐related pathophysiologies. Advanced treatment options are available; however, many wounds still fail to heal, exacerbating morbidity and mortality. This review describes the chronic inflammation pathophysiologies in diabetic ulcers and treatment options that may help address this dysfunction either directly or indirectly. We suggest that treatments to reduce inflammation within these complex wounds may help trigger healing. [ABSTRACT FROM AUTHOR]

Skin ulcers are the most prevalent consequence of diabetes mellitus, and people with diabetic ulcers have a substantially greater death risk than those who do not have ulcers. Herbal medications have gained wide concern in recent years due to their multi-component, multi-target, and multi-pathway synergistic therapeutic effects. Clinical trials have demonstrated the safety and efficacy of herbal treatments in diabetic refractory ulcers. To systematically evaluate the healing effect of herbs on diabetic wounds, a literature search was conducted, the mechanism of action of 15 herbal extracts in promoting diabetic wound healing were reviewed, and the classification based on traditional Chinese medicine theory was discussed, which could provide a reference for the precise treatment and exploitation of herbal medicines for diabetic ulcers [ABSTRACT FROM AUTHOR]

Diabetic foot infection (DFI) is an important cause of morbidity and mortality. Antibiotics are fundamental for treating DFI, although bacterial biofilm formation and associated pathophysiology can reduce their effectiveness. Additionally, antibiotics are often associated with adverse reactions. Hence, improved antibiotic therapies are required for safer and effective DFI management. On this regard, drug delivery systems (DDSs) constitute a promising strategy. We propose a gellan gum (GG)‐based spongy‐like hydrogel as a topical and controlled DDS of vancomycin and clindamycin, for an improved dual antibiotic therapy against methicillin‐resistant Staphylococcus aureus (MRSA) in DFI. The developed DDS presents suitable features for topical application, while promoting the controlled release of both antibiotics, resulting in a significant reduction of in vitro antibiotic‐associated cytotoxicity without compromising antibacterial activity. The therapeutic potential of this DDS was further corroborated in vivo, in a diabetic mouse model of MRSA‐infected wounds. A single DDS administration allowed a significant bacterial burden reduction in a short period of time, without exacerbating host inflammatory response. Taken together, these results suggest that the proposed DDS represents a promising strategy for the topical treatment of DFI, potentially overcoming limitations associated with systemic antibiotic administration and minimizing the frequency of administration. [ABSTRACT FROM AUTHOR]

Hyperbaric oxygen therapy (HBOT) is an adjuvant novel non-invasive treatment technique in the field of plastic surgery for treating different wounds. This technique utilizes 100% oxygen at pressures above the atmospheric pressure. In our study, we are discussing about eight different cases in the field of plastic surgery. HBOT plays an important role in the treatment for different pathological conditions. It involves a hundred percent breathing of oxygen in a closed chamber for a certain period of time. HBOT main mechanism of action is hyper oxygenation but also enhances the immunity by antimicrobial properties and improves stem cell production. [ABSTRACT FROM AUTHOR]

Charcot arthropathy is an insidious condition affecting the lower limbs of diabetic patients. It is a complication of diabetic neuropathy resulting from subsequent Wallerian degeneration of the nerves. This complication may eventually lead to limb amputation and a poor patient prognosis if not diagnosed and treated successfully. Herein, we report the case of a 73‐year‐old female who presented with rapidly progressive bilateral Charcot foot over a 5‐week period, necessitating an exostectomy on the mid foot, specifically on the cuboid bone and the navicular cuneiform joint. Her presentation with rapidly progressing foot ulcers on the plantar aspect prompted initial treatment based on osteomyelitis. The report will therefore serve as a useful guide on how to properly treat Charcot foot, which may present in an atypical manner.

[Display omitted] • Identification of new biomarkers linked to ICD in DUs. • Development of a diagnostic model using a random forest algorithm. • Near-perfect ROC analysis scores indicating high accuracy in differentiating DU from normal tissue. • Categorization of DUs into molecular classifications for a deeper understanding of their pathophysiology. • Potential implications for transformative strategies in DU management and personalized medicine. In this study, we redefine the diagnostic landscape of diabetic ulcers (DUs), a major diabetes complication. Our research uncovers new biomarkers linked to immunogenic cell death (ICD) in DUs by utilizing RNA-sequencing data of Gene Expression Omnibus (GEO) analysis combined with a comprehensive database interrogation. Employing a random forest algorithm, we have developed a diagnostic model that demonstrates improved accuracy in distinguishing DUs from normal tissue, with satisfactory results from ROC analysis. Beyond mere diagnosis, our model categorizes DUs into novel molecular classifications, which may enhance our comprehension of their underlying pathophysiology. This study bridges the gap between molecular insights and clinical practice. It sets the stage for transformative strategies in DUs management, marking a significant step forward in personalized medicine for diabetic patients. [ABSTRACT FROM AUTHOR]

The comparative evaluation offered within the paper aligns with the broader theme of sustainable wound care by means of focusing on the efficacy and environmental concerns of wound dressing technology. The development of advanced biomaterials not most effective for scientific wound control but additionally for environmental sustainability. With the aid of leveraging biocompatible substances and modern technology, such as biodegradable polymers and eco-friendly nanoparticles, researchers goal to create wound care answers that no longer handiest sell green recovery however also limit environmental impact. Via analyzing the benefits, demanding situations, and future directions of hydrogel dressings, electrospun biopolymer nanofibers, and numerous polymeric substances, the study contributes to the discussion on sustainable wound care. It underscores the significance of developing wound care solutions that now not most effective reveal clinical efficacy but also consider their environmental effect. This holistic method resonates with the purpose of exploring the intersection of scientific efficacy and environmental sustainability in the context of biomedical substances for wound care.

The present review was conducted to determine the efficacy of high‐voltage monophasic pulsed current (HVMPC) in treating diabetic ulcers, assess its effect on skin lesions with each of the pathophysiologic factors potentially contributing to diabetic ulcers, evaluate its safety, and identify treatment parameters. Electronic search of PubMed, Scopus, PEDro and Google Scholar databases was conducted. The revised tool for assessing risk of bias in randomised trials (RoB 2), the risk of bias in non‐randomised studies‐of interventions (ROBINS‐I) and the Joanna Briggs Institute (JBI) critical appraisal tool were used to assess risk of bias and methodological quality. Overall quality of evidence was determined using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) principles. Thirty‐two studies matched the eligibility criteria, and included 1061 patients with 1103 skin lesions of selected aetiologies; 12 randomised controlled trials were included in quantitative synthesis. HVMPC plus standard wound care (SWC) likely increased the probability of complete wound healing of pressure ulcers (PrUs) compared with sham/no stimulation plus SWC; relative risk (RR) 2.08; 95% CI: [1.42, 3.04], p = 0.0002; I2 = 0%, p = 0.61; eight studies, 358 ulcers. Although conclusive evidence regarding the effect of HVMPC on diabetic ulcers was not found, collateral evidence might suggest a potential benefit. Direct evidence, with moderate certainty, may support its efficacy in treating PrUs, albeit few adverse reactions were reported. Other observations, moreover, might indicate that this efficacy may not be limited to PrUs. Nonetheless, several aspects remain to be clarified for safe and effective application of electrical stimulation for wound healing. [ABSTRACT FROM AUTHOR]

Diabetic ulcer refers to a complication of chronic hyperglycaemia. When treating hyperglycaemia, it is necessary to well and immediately monitor the average level of glucose, i.e. glycated albumin (GA) value. This study investigated the correlation between GA values and the improvement of diabetic ulcers. A clinical, cross-sectional study. Thirty patients with Diabetic Foot Ulcer (DFU) were involved as the subjects of this study and they were selected by accidental sampling with the following criteria: (1) patients with Type 2 DM with DFU according to grade 2 and 3 PEDIS degrees; (2) aged 30-60 years; (3) diagnosis criteria for DM and DM type 2 in accordance to the American Diabetes Association 2012; (4) IMT value: 18.5-22.9. Data collection technique was by checking GA levels, while monitoring the improvement of diabetic ulcers was by using PEDIS degrees. Meanwhile, data analysis used Spearman's rho. The results of this study showed that most of research subjects had the values of GA failure with PEDIS 2 degree, i.e. 8 (26.7%) and there was no normal GA value with the degree of PEDIS 1, 2 and 3. There was a significant correlation between GA values and PEDIS degree (p = 0.001, p < 0.05). The findings revealed a correlation of GA values and improvement in diabetes ulcers. GA control is needed for the improvement of diabetes ulcers under nursing care. [ABSTRACT FROM AUTHOR]

Adipose tissue presents a comparably easy source for obtaining stem cells, and more studies are increasingly investigating the therapeutic potential of adipose-derived stem cells. Wound healing, especially in chronic wounds, and treatment of skin diseases are some of the fields investigated. In this narrative review, the authors give an overview of some of the latest studies concerning wound healing as well as treatment of several skin diseases and concentrate on the different forms of application of adipose-derived stem cells. [ABSTRACT FROM AUTHOR]

Stem cells have demonstrated values in diabetic ulcer (DU) treatments. Challenges in this area are focused on enhancing the localized curative effects of stem cells and improving diabetic wound healing efficiently. Herein, a novel living microneedle (MN) patch is presented as a localized delivery system of bioactive platelet derived growth factor D (PDGF‐D) and human adipose‐derived stem cells (ADSCs) for DU wound treatment. Compared with traditional complicated stem cell carriers, the MN patch can keep stem cell viability for ADSCs encapsulation and delivery, and possesses good mechanical strengths to penetrate the local skin wounds noninvasively. It is demonstrated that the delivery ADSCs are with the abilities of angiogenesis promotion during the DU wound healing; while the additive PDGF‐D can contribute significantly to the proliferation of ADSCs, strengthening the cell function of ADSCs and further facilitating the healing processes. Thus, living MN patches accelerate vascularization, tissue regeneration, and collagen deposition in a wounded diabetic mouse model, suggesting their potential application to DU wound healing and other therapeutic applications. [ABSTRACT FROM AUTHOR]

The outbreak of the coronavirus disease 2019 (COVID‐19) led to events that significantly impaired the treatment and management of patients with chronic diabetes. Therefore, elective treatments at hospitals were cancelled and patients with chronic ailments were instructed to stay at home and minimise the time spent in public areas. The second was due to COVID‐19‐induced anxiety that deterred many patients from seeking care and adhering to periodic out‐patient visits. In this study, we examined the short‐term effects of the COVID‐19 pandemic on patients with chronic diabetes who suffered from contaminated diabetic ulcers. We conducted a retrospective study with patients who had undergone amputations following diabetic ulcers during 2019‐2020. The research group included diabetic amputees during the COVID‐19 outbreak period ranging from March 2020 to December 2020. The control group included diabetic amputees from the corresponding period in 2019. Using the Wagner Scale, we measured the difference in the severity of ulcers upon the patient's initial admission. Additionally, we examined patient survival rates based on the size of amputations, by specifically focusing on the period between 1‐ and 6‐months post‐surgery. The results failed to suggest a clear and statistically significant worsening trend in the condition of patients in the research and control groups. Due to public lockdowns, transportation restrictions, scarcity of healthcare staff, and reduced adherence to exposure anxiety, patients with diabetic foot ulcers received inferior medical care during the COVID‐19 pandemic. However, this study could not find a statistically significant difference in the mortality and major amputation rates in patients with diabetic ulcer before and during the pandemic. The health system should incorporate the existing institutional and technological recommendations to facilitate care and follow‐up of patients with diabetic foot ulcers during the current and future pandemics. [ABSTRACT FROM AUTHOR]

Diabetic ulcers (DUs) are characterized by a microenvironment with high oxidative stress, high blood glucose levels, and recalcitrant bacterial infections. This microenvironment is accompanied by long-term suppression of endogenous antioxidant systems, which makes their clinical management extremely challenging. To address this issue, a hybridized novel gold-palladium (AuPd) nanoshell of the injectable/injectable hydrogel system UiO/AuPd shells /BNN6/PEG@Gel (UAPsBP@Gel) is developed. The system is capable of acting as a nitric oxide (NO) reactor utilizing synergistic therapy that harnesses NIR-II light-triggered photothermal effects and controlled release of NO gas for synergistic treatment to eradicate biofilm infections at different depths. The AuPd nanoshells exhibits superoxide dismutase (SOD)-, glucose oxidase (GOx)-, and catalase (CAT)-like activities, enabling self-cascade process for scavenging both reactive oxygen species (ROS) and glucose. This activity reshapes the DUs microenvironment, switches on the endogenous antioxidant Nrf2/HO-1 pathway and inhibits the NF-κB pathway, promotes macrophage polarization toward the anti-inflammatory M2 phenotype, and reduces oxidative stress, resulting in efficient immunomodulation. In vitro/in vivo results demonstrate that the UAPsBP@Gel can multifacetedly enhance the epithelial rejuvenation process through wound hemostasis, pro-cellular migration and vascularization. These results highlight that a programmed therapeutic based on UBAPsP@Gel tailored to the different stages of infected DUs can meet complex clinical needs., (© 2025 Wiley‐VCH GmbH.)

Diabetic ulcers (DUs) are a common and severe complication of diabetes, characterized by impaired wound healing due to a complex pathophysiological mechanism. Elevated levels of 11β-hydroxysteroid dehydrogenase type I (11β-HSD1) in wounds have been demonstrated to modulate glucocorticoid activity, leading to delayed skin cell proliferation and restricted angiogenesis, ultimately hindering wound healing. In this study, we propose an electrospun poly(ε-caprolactone) (PCL) nanofiber scaffold doped with the 11β-HSD1 inhibitor BVT2733 (BPs) to prevent 11β-HSD1 activity during the diabetic wound healing process. The electrospun scaffold loaded with BVT2733 is designed to achieve localized inhibition of 11β-HSD1 in DUs. This scaffold exhibited a porous morphology and desirable drug-loading capacity, meeting the requirements for wound coverage and effective delivery of BVT2733 BPs. In vitro studies demonstrated that the sustained release of BVT2733 from the scaffold promoted skin cell proliferation and migration while stimulating angiogenesis by upregulating HIF1-α/VEGF expression. The therapeutic effect of the scaffold was further confirmed in a full-thickness wound model using diabetic mice. The mice treated with the scaffolds exhibited an accelerated wound healing rate, increased neovascularization, enhanced collagen deposition, and regeneration of skin appendages within 2 weeks postinjury. The findings here provide evidence for the use of 11β-HSD1 inhibitor-integrated biomaterials in treating DUs and represent a novel biological platform for modulating dysregulated mechanisms in DUs.

Mitochondrial dynamics is the process of mitochondrial fusion and division to maintain dynamic balance. In recent years, it has been found that this dynamic change plays an important role in regulating mitochondrial morphology and quantity, mitochondrial oxidative metabolism, membrane potential and energy production. In diabetes, hyperglycemia significantly interferes with the dynamic balance of mitochondrial fusion and division process, and affects the quantity, morphology and function of mitochondria. And ultimately, the dynamic change of mitochondria is closely related to many chronic complications of diabetes, but the specific mechanism remains unclear. Our research group has long been committed to exploring the roles and mechanisms of mitochondrial dynamics in a variety of diabetic complications. This review summarizes the research progress and potential mechanisms of mitochondrial dynamics in diabetic ulcers, diabetic nephropathy and diabetic cardiomyopathy.

Abstract Diabetes affects multiple systems in complex manners. Diabetic foot ulcers (DFUs) are a result of diabetes‐induced microarterial vessel disease and peripheral neuropathy. The presence of arteriosclerosis‐induced macroarterial disease can further complicate DFU pathophysiology. Recent studies suggest that mesenchymal stromal cell therapies can enhance tissue regeneration. This phase I study was designed to determine the safety and explore the efficacy of local injections of autologous adipose‐derived stromal vascular fraction (SVF) cells to treat nonhealing DFUs greater than 3 cm in diameter. Sixty‐three patients with type 2 diabetes with chronic DFU—all amputation candidates—were treated with 30 × 106 SVF cells injected in the ulcer bed and periphery and along the pedal arteries. Patients were seen at 6 and 12 months to evaluate ulcer closure. Doppler ultrasounds were performed in a subset of subjects to determine vascular structural parameters. No intervention‐related serious adverse events were reported. At 6 months, 51 subjects had 100% DFU closure, and 8 subjects had ≥75% closure. Three subjects had early amputations, and one subject died. At 12 months, 50 subjects had 100% DFU healing and 4 subjects had ≥85% healing. Five subjects died between the 6‐ and 12‐month follow‐up visits. No deaths were intervention related. Doppler studies in 11 subjects revealed increases in peak systolic velocity and pulsatility index in 33 of 33 arteries, consistent with enhanced distal arterial runoff. These results indicate that SVF can be safely used to treat chronic DFU, with evidence of efficacy (wound healing) and mechanisms of action that include vascular repair and/or angiogenesis.

[Display omitted] • Semaglutide was combined with electrospinning technology. • The membrane can inhibit the production of reactive oxygen species. • This fiber membrane accelerates angiogenesis. • This fiber membrane can rescue the cell damage induced by hyperglycemia. • Semaglutide fiber membrane accelerates diabetic wound healing. The healing of diabetic wounds is a difficult problem due to decreased proliferation, and migration of epidermal and endothelial cells. Here we reported semaglutide-loaded nanofiber membrane to promote diabetic wound healing through suppressing reactive oxygen species production and accelerating angiogenesis in a diabetic rat model. The fiber membrane was prepared by an electrostatic spinning technique. The fiber membrane consisted of thermalplastic polyurethane elastomer, polyvinyl butyral ester, zein and semaglutide (SMGT). The fiber membrane had a uniformly distributed diameter, suitable water vapor transmission rate, good water absorption and retention properties. In vivo data determined that the SMGT-loaded nanofiber membrane was able to promote normal skin pathological structure formation in regenerated tissue. In vitro experiments displayed that SMGT might facilitate HG-induced endothelial cell dysfunction by inhibiting ROS production. The present study provided a theoretical basis for the extensive application of SMGT in the treatment of diabetic ulcers and other wounds. [ABSTRACT FROM AUTHOR]

We tried to unveil the clinical significance of miR-146a as a bi omarker in M2 macrophage polarization in diabetic wound healing. Initially, we found reduced miR-146a in macrophages of diabetic patients. Next, dual-luciferase assay verified that toll-like receptor 4 (TLR4) was a target gene of miR-146 and was negative ly regulated by miR-146. Moreover, after ectopic expression and depletion experiments of miR-146 and/or TLR4, lipopolysaccharide-induced inflammatory response of macrophages was detected. The results revealed that overexpression of miR-146a promoted the M2 macrophage polarization by suppressing the TLR4/nuclear factor-kappaB (NF-κB) axis, so as to enhance wound healing in diabetic ulcers. Further, mouse models with diabetic ulcers were established to investigate the effects of miR-146a on diabetic wound healing in vivo, which revealed that miR-146a promoted wound healing in diabetic ulcers by inhibiting the TLR4/NF-κB axis. In conclusion, we demonstrate that miR-146a can induce M2 macrophage polarization to enhance wound healing in diabetic ulcers by inhibiting the TLR4/NF-κB axis. [ABSTRACT FROM AUTHOR]

Background: The study aimed at evaluating the plasmid profile and characterization of E. coli isolated from chronic diabetic foot ulcers among patients in Imo State, South East Nigeria. Methods: A total of 150 wound swab samples were collected and analyzed. Standard microbiological methods processed samples. Antibiogram was done by Kirby-Bauer disc diffusion method. Tests were conducted to determine biofilm potential, ESBL and AmpC production. Plasmid profiling was done by the alkaline lysis method and Gel electrophoresis. Results: Based on the results, out of the 150 swab samples, 61(40.6%) E. coli isolates were recovered. 57.8%, 32.8%, and 8.2% of the E. coli isolates were positive for biofilm formation, ESBL, and AmpC production, respectively. Further, the study revealed a pattern of multiple-drug resistance of E. coli to amoxicillin/clavulanic acid (96.7%), septrin (95.1%), and ampicillin (93.4%). Conclusion: Analysis of the multiple antibiotic resistance (MAR) index showed that the organism had MAR index values above the low-risk region (≤0.2) for all the tested antibiotics. Post-curring antibiogram tests revealed that nine isolates carried plasmids, suggesting that the mode of resistance may be plasmid-mediated. Findings could act as a therapeutic guide for antibiotic prescriptions in this environment. [ABSTRACT FROM AUTHOR]

Diabetic ulcers, a type of chronic and refractory wound, are the most common diabetic complication and their incidence is increasing. However, the specific mechanisms underlying the formation of diabetic ulcers have not been clarified and the current therapeutic methods are unsatisfactory. In this study, we found that asiaticoside facilitated the recovery of skin wounds in diabetic rats. Intensive studies demonstrated that asiaticoside promoted fibroblast proliferation and migration in a high-glycemic environment. Mechanistically, asiaticoside upregulated Wnt1 at the protein and immunohistochemistry levels and activated the Wnt/beta-catenin signaling cascade, thereby promoting fibroblast functions. Thus, asiaticoside promotes skin cell activities relevant to diabetic ulcers healing and thus may have therapeutic value. [ABSTRACT FROM AUTHOR]

Charcot arthropathy is an insidious condition affecting the lower limbs of diabetic patients. It is a complication of diabetic neuropathy resulting from subsequent Wallerian degeneration of the nerves. This complication may eventually lead to limb amputation and a poor patient prognosis if not diagnosed and treated successfully. Herein, we report the case of a 73‐year‐old female who presented with rapidly progressive bilateral Charcot foot over a 5‐week period, necessitating an exostectomy on the mid foot, specifically on the cuboid bone and the navicular cuneiform joint. Her presentation with rapidly progressing foot ulcers on the plantar aspect prompted initial treatment based on osteomyelitis. The report will therefore serve as a useful guide on how to properly treat Charcot foot, which may present in an atypical manner. [ABSTRACT FROM AUTHOR]