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OBJECTIVE: The transverse tibial transfer technique is employed primarily to treat diabetic foot ulcers (DFUs), aiming to enhance leg circulation and promote new blood vessel growth. This technique is also beneficial for various conditions associated with poor blood flow in the lower extremities. However, there is no clear molecular mechanism to explain the relationship between the transverse tibial transfer technique and angiogenesis in patients with diabetic foot. This study aims to preliminarily explore the change of IL-6 and related cytokines in promoting angiogenesis during transverse tibial transplantation, providing a direction for future research. METHODS: We retrospectively assessed a study from April 2022 to November 2023 on 76 patients with severe DFUs at Wagner stages 3-4. Flow cytometry was used to detect the levels of 12 cytokines in serum before the operation and 3, 7, 14, 21, and 35 days after the operation. Ankle-brachial index (ABI), transcutaneous oxygen tension (TcPO2), and glycosylated hemoglobin (Hba1c) were recorded at admission and discharge. We examined the variations in cytokine levels, wound healing duration, amputation rates, infection incidence, and other key outcomes. RESULTS: In our investigation, a total of 76 individuals participated, comprising 49 males and 27 females. These subjects had an average age of 64.7 years, with a standard deviation of 13 years. The mean ulcer healing time was 74 ± 31 days, amputation occurred in 3 patients, pin tract infection occurred in one patient (1.3%), and incision infection occurred in one patient (1.3%). By day 35 following the surgery, both the ABI and TcPO2 values showed a significant increase from their preoperative levels. HbA1c significantly improved compared with presurgery (p < 0.001), IL-6 levels were significantly increased compared with presurgery (p < 0.05), and then decreased. CONCLUSION: The transverse tibial transfer (TTT) technique is safe and efficient for managing DFUs. The wound healing time in patients who smoke or consume alcohol is statistically significant compared with that of nonsmoking and nondrinking patients. IL-6 exhibited substantial changes at various postoperative time points. Future research could investigate the role of IL-6 in tibial transverse translation.

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Multifunctional responsive hydrogels hold significant promise for diabetic foot ulcer (DFU) treatment, though their complex design and manufacturing present challenges. This study introduces a novel supramolecular guanosine-phenylboronic-chlorogenic acid (GBC) hydrogel developed using a dynamic covalent strategy. The hydrogel forms through guanosine quadruplex assembly in the presence of potassium ions and chlorogenic acid (CA) linkage via dynamic borate bonds. GBC hydrogels exhibit pH and glucose responsiveness, releasing more chlorogenic acid under acidic and high glucose conditions due to borate bond dissociation and G-quadruplex (G4) hydrogel disintegration. Experimental results indicate that GBC hydrogels exhibit good self-healing, shear-thinning, injectability, and swelling properties. Both in vitro and in vivo studies demonstrate the GBC hydrogel's good biocompatibility, ability to eliminate bacteria and reactive oxygen species (ROS), facilitate macrophage polarization from the M1 phenotype to the M2 phenotype (decreasing CD86 expression and increasing CD206 expression), exhibit anti-inflammatory effects (reducing TNF-α expression and increasing IL-10 expression), and promote angiogenesis (increasing VEGF, CD31, and α-SMA expression). Thus, GBC hydrogels accelerate DFU healing and enhance tissue remodeling and collagen deposition. This work provides a new approach to developing responsive hydrogels to expedite DFU healing.

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Diabetic foot ulcer (DFU) is a common and severe complication of diabetes characterized by wound neuropathy, ischemia, and susceptibility to infection, making its treatment difficult. Dressings are commonly used in treating diabetic wounds; however, they have disadvantages, including lack of flexibility and mechanical strength, lack of coagulation activity, resistance to biodegradation, and low drug delivery efficiency. Developing more effective strategies for diabetic wound treatment has become a new focus. Microneedles (MN) can be used as a drug delivery platform for DFU wounds, allowing safe, effective, painless and minimally invasive medication administration through the skin. Herein, PDA@Ag/SerMA microneedles were prepared by combining the photothermal properties of polydopamine (PDA), the antimicrobial properties of argentum (Ag), and the ability of sericin methacryloyl (SerMA) to promote cell mitosis to accelerate wound healing and treat diabetic ulcer wounds. The results revealed that PDA@Ag/SerMA microneedles exhibited approximately 100% antimicrobial efficacy against Staphylococcus aureus and Escherichia coli under 808 nm near-infrared (NIR) irradiation. Furthermore, the wound healing rate of mice reached 95% within 12 days, which demonstrated the excellent antibacterial properties and wound healing efficacy of PDA@Ag/SerMA microneedles at cellular and animal levels, providing a potential solution for treating DFU.

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BACKGROUND: Vascular endothelial injury, a key factor in diabetic foot ulcers (DFUs) pathogenesis, is linked to the impaired proliferation and migration of vascular endothelial cells, modulated by hypoxia-inducible factor, growth factors, and inflammatory elements. OBJECTIVE: The present study assesses the role of SIKVAV (Ser-Ile-Lys-Val-Ala-Val), a peptide shown to enhance cell proliferation and migration, on mouse aortic endothelial cell (MAEC) and the corresponding molecular mechanisms. METHODS: MAEC were treated with SIKVAV at 0, 100, 200, 400, and 600 µg/mL for 0, 24, 48, and 72 h. Cell viability was tested using the CCK-8 assay. Proliferating cell nuclear antigen (PCNA), extracellular signal-regulated kinase 1/2 (ERK1/2), and protein kinase B (Akt) levels were measured by qRT-PCR and western blot. RESULTS: SIKVAV augmented PCNA mRNA expression and stimulated vascular endothelial cell proliferation in a concentration and time-dependent fashion. Furthermore, it amplified the expression of p-ERK1/2 and p-Akt, pivotal components of the mitogen-activated protein kinase (MAPK)/ERK1/2 and phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathways. The inhibition of these pathways suppressed PCNA mRNA expression, cell proliferation rate, and decreased p-ERK1/2 and p-Akt levels, highlighting SIKVAV's role in promoting vascular endothelial cell proliferation via these pathways. CONCLUSION: The results of this study confirmed that SIKVAV grafted onto scaffolds can accelerate the proliferation of vascular endothelial cells for the therapy of skin wounds, and provide a theoretical basis for its application in ischemic disease as synthesized biomaterials scaffolds of tissue engineering.

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Background: Nursing can effectively prevent and ameliorate diabetic foot ulcers (DFU). However, there is a lack of literature on the bibliometric analysis of DFU nursing. This study aimed to analyze the research hotspots and development trends in DFU nursing over the past 10 years to provide references for future related research. Methods: The Web of Science Core Collection was used to retrieve literature related to DFU nursing from 2013 to 2023. Analyses included the annual publication trends; author, institution, and country collaborations; journal and literature co-citation; and keyword co-occurrence, clustering, and bursting, performed using CiteSpace 5.8 R3. Results: A total of 229 papers were included, showing an upward trend in annual publications. American scholar David G Armstrong (n = 3) and King's College Hospital London (n = 4) were the most productive authors and institutions, respectively. The United States ranked first (n = 45) in national contributions, followed by China and Brazil. The overall research strength between authors and institutions was relatively scattered, and intensive cooperation has not yet been formed. National collaborations resulted in a core team dominated by Europe and North America with concentrated research strengths. The most frequently co-cited journal and co-cited reference were Diabetes Care (111 citations) and Armstrong DG (2017) (131 citations), separately. Research hotspots mainly focused on risk assessment, classification systems, protective measures, and clinical management of DFU. "Primary care" and "intervention efficacy" were identified as the research trends in the coming years. Conclusion: The field of DFU nursing requires more attention. Academic exchange and cooperation between authors, institutions, and countries should be strengthened. Our future research will focus on the latest hotspots and trends, conducting more in-depth and comprehensive studies on DFU management.

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Background Diabetic foot ulcers (DFUs) are a significant complication of diabetes mellitus and are often accompanied by various complications including hemolytic anemia. However, the clinical and hematological correlates of hemolytic anemia in patients with DFU remain poorly understood. This prospective observational study aimed to investigate the clinical and hematological correlates of hemolytic anemia in patients with DFU and to elucidate the potential mechanisms underlying this complication and its impact on wound healing. Methodology A total of 148 adult patients diagnosed with DFUs were enrolled in this study. Clinical and demographic data were collected, including age, sex, duration of diabetes, glycemic control status, presence of comorbidities, and foot ulcer characteristics. Hematological parameters, including complete blood counts, reticulocyte counts, and hemolysis markers, were measured at baseline and during the follow-up visits. Statistical analyses were conducted to assess the prevalence of hemolytic anemia, identify the demographic and clinical factors associated with its presence, and explore its relationship with wound healing outcomes. Results The prevalence of hemolytic anemia among patients with DFU was 41.9%. Patients with hemolytic anemia had a longer duration of diabetes (mean duration: 8.3 ± 2.1 years), higher glycated hemoglobin (HbA1c) levels (mean: 9.2% ± 1.5%), and a greater burden of comorbidities than those without hemolytic anemia. Hematological analysis revealed significant differences in hemoglobin levels, red blood cell indices (mean corpuscular volume: 89.6 ± 5.2 fL), and markers of hemolysis (mean lactate dehydrogenase level: 325 ± 45 U/L) between DFU patients with and without hemolytic anemia. Furthermore, correlations were observed between hematological parameters and wound healing outcomes, suggesting potential implications for clinical management. Conclusions This study provides valuable insights into the clinical and hematological correlates of hemolytic anemia in patients with DFU. These findings highlight the importance of recognizing and addressing hematological abnormalities in the management of DFU, with potential implications for optimizing wound healing and improving clinical outcomes.

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AIM: To determine whether there are differences in glycemia during wound and wound-free states among individuals with diabetes at a Multidisciplinary Diabetic Foot and Wound Clinic from 2012-2019. METHODS: We conducted a retrospective analysis of prospectively collected data over 7.4 years from the Johns Hopkins Multidisciplinary Diabetic Foot and Wound Clinic. Participants with diabetic foot ulcers (DFUs) were observed during at least one wound period and one wound-free period and had at least one hemoglobin A1C (A1C) measurement in both a wound and wound-free period. The A1C measurements were aggregated and summarized across wound and wound-free periods, and compared using the Wilcoxon matched-pairs signed rank test. RESULTS: 206 eligible participants with a total of 623 wounds were included in this analysis. Participants were followed for a median period of 2.4 years (876 days). There were no significant differences in mean, minimum, and maximum A1C between the aggregate wound and wound-free period, with median (interquartile range [IQR]) values of 7.6% (6.6%, 9.1%) and 7.5% (6.6%, 9.1%) for mean A1C (p = 0.43), 6.9% (6.0%, 8.0%) and 6.8% (6.0%, 8.1%) for minimum A1C (p = 0.78), and 8.6% (7.1%, 10.9%) and 8.5% (7.0%, 10.7%) for maximum A1C (p = 0.06) in the wound and wound-free period respectively. CONCLUSIONS: This retrospective study showed similar levels of A1C during wound and wound-free periods, but given limitations of missing A1C and small sample size, further studies leveraging continuous glucose monitoring (CGM) data are needed to understand whether glycemia worsens in the setting of a DFU.

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Diabetes represents a widely acknowledged global public health concern. Diabetic foot ulcer (DFU) stands as one of the most severe complications of diabetes, its occurrence imposing a substantial economic burden on patients, profoundly impacting their quality of life. Despite the deepening comprehension regarding the pathophysiology and cellular as well as molecular responses of DFU, the current therapeutic arsenal falls short of efficacy, failing to offer a comprehensive remedy for deep-seated chronic wounds and microvascular occlusions. Conventional treatments merely afford symptomatic alleviation or retard the disease's advancement, devoid of the capacity to effectuate further restitution of compromised vasculature and nerves. An escalating body of research underscores the prominence of mesenchymal stem cells (MSCs) owing to their paracrine attributes and anti-inflammatory prowess, rendering them a focal point in the realm of chronic wound healing. Presently, MSCs have been validated as a highly promising cellular therapeutic approach for DFU, capable of effectuating cellular repair, epithelialization, granulation tissue formation, and neovascularization by means of targeted differentiation, angiogenesis promotion, immunomodulation, and paracrine activities, thereby fostering wound healing. The secretome of MSCs comprises cytokines, growth factors, chemokines, alongside exosomes harboring mRNA, proteins, and microRNAs, possessing immunomodulatory and regenerative properties. The present study provides a systematic exposition on the etiology of DFU and elucidates the intricate molecular mechanisms and diverse functionalities of MSCs in the context of DFU treatment, thereby furnishing pioneering perspectives aimed at harnessing the therapeutic potential of MSCs for DFU management and advancing wound healing processes.

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Aim and objective Diabetic foot ulcers (DFUs) are a frequent complication of diabetes mellitus, impacting more than one in 10 diabetic patients, with roughly half of these ulcers progressing to infection. Existing literature indicates that these infections are predominantly polymicrobial, with gram-positive isolates being the most common. This microbial profile informs the empiric antibiotic strategies employed in first-world countries, often including highly potent nephrotoxic antibiotics. This retrospective cohort study aims to assess the microbial profile and antibiotic treatment practices in patients with infected DFUs at Ochsner LSU Health Shreveport Academic Medical Center in Shreveport, Louisiana, United States. Materials and methods A total of 115 patients diagnosed with infected DFUs were included in the study. Patient records were reviewed to identify bacterial pathogens cultured from foot wounds, antibiotic treatment regimens administered, and the prevalence of acute kidney injury (AKI). Results The study found a predominance of gram-negative isolates (199; 59.4%), facultative anaerobes (246; 73.4%), and polymicrobial infections (67; 78.8%) in infected DFUs. Vancomycin was administered to 95 patients (82.6%), with only a small number subsequently testing positive for methicillin-resistant Staphylococcus aureus (MRSA). Combination therapy with vancomycin and Zosyn was given to 71 patients (61.7%), which increased the potential risk of antibiotic-induced nephrotoxicity. AKI was prevalent, affecting 58 patients (50.4%). Conclusions This study highlights a discrepancy between the microbial profile of infected DFUs and empiric antibiotic treatment practices at Ochsner LSU Health Shreveport Academic Medical Center. The predominance of gram-negative bacteria underscores the need for a polymicrobial, gram-negative-focused empiric treatment approach. Alternative antibiotics with broad-spectrum coverage and minimal nephrotoxicity, such as ceftriaxone, clindamycin, metronidazole, amoxicillin-clavulanate, and linezolid, should be considered. Tailored antibiotic strategies, guided by local microbial profiles and patient-specific factors, are essential to optimize treatment outcomes in this high-risk population.

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Early indicators of healing provide valuable information on the potential benefit of treatment. In patients with hard-to-heal (chronic) diabetic foot ulcers (DFUs), timely intervention is critical. Ulcers that fail to show measurable progress within four weeks of treatment are considered recalcitrant. These ulcers increase the risk of soft tissue infection, osteomyelitis and lower extremity amputation. A prognostic indicator or surrogate marker allows for rapid evaluation of treatment efficacy and safety. An inverse correlation between a percentage area reduction (PAR) of ≤50% at week 4 and complete healing by week 12 has been previously established; however, the data were derived from a standard of care (SoC) arm of clinical trials that are over a decade old. In this post hoc analysis, data from a large multicentre prospective randomised controlled trial were reviewed to assess PAR at week 4 as a prognostic indicator in patients treated with SoC. Overall, 65.4% (17/26) of patients with PAR >50% at week 4 achieved complete closure at week 12. The receiver operating characteristic (ROC) curve for area reduction by week 4 showed strong discrimination for predicting non-healing (area under the ROC curve: 0.92; p<0.001; positive predictive value: 70.6%; negative predictive value: 87.2%). These findings are consistent with previous studies and support the use of four-week PAR as a prognostic indicator.

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Diabetic foot ulcer (DFU) is a common and serious complication among diabetic patients, and its incidence and difficulty in treatment have placed large burdens on patient health and quality of life. Diabetic foot tissue typically exhibits chronic wounds, ulcers, or necrosis that are difficult to heal, are prone to infection, and, in severe cases, may even lead to amputation. Recent studies have shown that microRNAs (miRNAs) play key roles in the development and healing of DFUs. miRNAs are a class of short noncoding RNA molecules that regulate gene expression to affect cellular functions and physiological processes. miRNAs may be involved in the development of DFUs by regulating cell growth, proliferation, differentiation and apoptosis. miRNAs can also participate in the healing and recovery of DFUs by regulating key steps, such as inflammation, angiogenesis, cell migration and proliferation, tissue repair and matrix remodeling. Therefore, altering the pathological processes of diabetic foot by modulating the expression of miRNAs could improve the recovery and treatment outcomes of patients. This review provides new insights and perspectives for the treatment of DFUs by summarizing the roles of miRNAs in the development and healing of DFUs and the mechanisms.

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Objective: This study aimed to comprehensively analyze the incidence of amputation in Chinese patients with diabetic foot ulcers (DFUs). Methods: The Preferred Reporting Items for a Systematic Review and Meta-analysis (PRISMA) guidelines were used. The CNKI, Wanfang Data, VIP, PubMed, Web of Science, and Embase databases were searched to collect relevant literature on the incidence of amputation in Chinese patients with DFUs. Two researchers independently screened the literature, extracted data, and evaluated the risk of bias. The data were systematically analyzed using Stata 17.0 software to determine the incidence of amputation in this patient population. Results: A total of 25 papers were included in the study, revealing an incidence of amputation in Chinese patients with DFUs of 22.4% (95% confidence interval: 18.3-26.5%). The subgroup analysis revealed that a history of ulcers, Wagner grade >3, and diabetic peripheral vascular disease were the primary risk factors associated with a higher incidence of amputation in Chinese patients with DFUs (P<0.05). Among Chinese patients with DFUs, the amputation group and the non-amputation group showed significant differences in body mass index, duration of DFUs, total cholesterol, triglyceride, fasting blood glucose, white blood cell count, hemoglobin A1c, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, high-sensitivity C-reactive protein, and uric acid (P<0.05). Conclusion: The high incidence of amputation among Chinese patients with DFUs indicates that interventions should be implemented to prevent or minimize amputations. Systematic review registration: https://www.crd.york.ac.uk/prospero, identifier CRD42023463976.

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BACKGROUND: Diabetic foot ulcers (DFUs) are a common and serious complication of diabetes, often leading to amputation and decreased quality of life. Current treatment methods have limited success rates, highlighting the need for new approaches. This study investigates the potential of tibial transverse transport (TTT) to promote wound healing in DFUs. METHODS: To test this hypothesis, the study used New Zealand White rabbits to establish a diabetic model and simulate foot ulcers, followed by the treatment of unilateral TTT or bilateral TTT. The study employed histological analysis, flow cytometry, ELISA, and qPCR to assess the impact of TTT on tissue repair and endothelial progenitor cell (EPC) mobilization and homing, aiming to understand the underlying biological processes in wound healing. RESULTS: TTT significantly enhanced wound healing in diabetic rabbit foot ulcers. Specifically, bilateral TTT led to complete wound healing by day 19, faster than the unilateral TTT group, which healed by day 26, and the sham operation group, which nearly healed by day 37. Histological analysis showed improved tissue architecture, collagen deposition, and neovascularization in TTT-treated groups. Furthermore, TTT treatment resulted in a significant increase in VEGFR2 expression and VEGFR2/Tie-2 positive cells, particularly in the bilateral group. These findings were corroborated by qPCR results, which showed increased expression of VEGFA and CXCL12 by TTT. Conclusions: TTT may be a promising treatment for DFUs, significantly enhancing wound healing by stimulating EPC mobilization and homing mediated angiogenesis. This novel approach could substantially improve treatment outcomes for diabetic patients with chronic foot ulcers.

TTT accelerates wound healing in diabetic rabbit instep ulcers, with both unilateral and bilateral surgeries effective, and bilateral TTT showing enhanced efficacy.TTT boosts angiogenesis and collagen fiber formation, leading to increased granulation tissue and re-epithelialization of wounds.TTT induces the mobilization and homing of endothelial progenitor cells to promote angiogenesis and wound healing.

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Diabetic Foot Ulcers (DFU) represent a grave complication often encountered in the advanced stages of diabetes mellitus. They frequently lead to recurrent hospitalizations and, in severe cases, can result in life-threatening conditions such as infections, gangrene, and even amputation Diabetic foot ulcers (DFU), as a serious complication in the late stage of diabetes mellitus, are prone to lead to repeated hospitalization, and in severe cases, infection, gangrene, and even amputation. Although there are many methods for treating diabetic foot, there is no clear and effective method to reduce the amputation rate of diabetic foot patients. In recent years, advancements in the understanding of stem cell therapy for the treatment of DFU have shed light on its potential as a novel therapeutic approach. In recent years, as the research on stem cell therapy for diabetic foot is gradually deepening, stem cells are expected to become a new therapeutic method for treating DFU in the future. Their therapeutic effects are through promoting angiogenesis, secreting paracrine factors, controlling inflammation, promoting collagen deposition, and regulating immunity, etc. Despite numerous studies confirming the efficacy of stem cell therapy in treating DFU, there is still a need for the establishment of standardized treatment protocols. Although numerous studies have shown that stem cell therapy for DFU is real and effective, there has not yet been a standardized treatment protocol. This article reviews studies related to stem cell therapy for DFU, looking at the mechanism of action, types of stem cells, and modes of administration.

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Diabetic foot ulcer (DFU) is a common chronic complication of diabetes. This complication is characterized by the formation of ulcers that are difficult to heal on the skin of the foot. Ulcers can negatively affect patients' quality of life, and improperly treated lesions can result in amputation and even death. Traditionally, the severity and type of foot ulcers are determined by doctors through visual observations and on the basis of their clinical experience; however, this subjective evaluation can lead to misjudgments. In addition, quantitative methods have been developed for classifying and scoring are therefore time-consuming and labor-intensive. In this paper, we propose a reconstruction residual network with a fused spatial-channel attention mechanism (FARRNet) for automatically classifying DFUs. The use of pseudo-labeling and Data augmentation as a pre-processing technique can overcome problems caused by data imbalance and small sample size. The developed model's attention was enhanced using a spatial channel attention (SPCA) module that incorporates spatial and channel attention mechanisms. A reconstruction mechanism was incorporated into the developed residual network to improve its feature extraction ability for achieving better classification. The performance of the proposed model was compared with that of state-of-the-art models and those in the DFUC Grand Challenge. When applied to the DFUC Grand Challenge, the proposed method outperforms other state-of-the-art schemes in terms of accuracy, as evaluated using 5-fold cross-validation and the following metrics: macro-average F1-score, AUC, Recall, and Precision. FARRNet achieved the F1-score of 60.81%, AUC of 87.37%, Recall of 61.04%, and Precision of 61.56%. Therefore, the proposed model is more suitable for use in medical diagnosis environments with embedded devices and limited computing resources. The proposed model can assist patients in initial identifications of ulcer wounds, thereby helping them to obtain timely treatment.

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Diabetic foot ulcers (DFUs) are chronic wounds and one of the most common complications of diabetes, imposing significant physical and mental burdens on patients due to their poor prognosis and treatment efficacy. Adipose-derived stem cells (ADSCs) have been proven to promote wound healing, with studies increasingly attributing these beneficial effects to their paracrine actions. Consequently, research on ADSC secretome as a novel and promising alternative for DFU treatment has been extensively conducted. This article provides a comprehensive review of the mechanisms underlying refractory DFU wounds, the secretome of ADSCs, and its role in promoting wound healing in diabetes foot ulcers. And the review aims to provide reliable evidence for the clinical application of ADSC secretome in the treatment of refractory DFU wounds.

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Background Diabetic foot ulcers (DFUs) are prevalent complications of diabetes mellitus, often leading to severe infections and adverse clinical outcomes. Klebsiella pneumoniae, a gram-negative bacterium, has emerged as a significant causative agent in DFU infections, raising concerns due to its increasing antibiotic resistance, particularly in extended-spectrum ß-lactamase (ESBL) and metallo-ß-lactamase (MBL) production. Aim This study aimed to comprehensively assess the prevalence, antibiotic resistance profiles, and clinical correlates of ESBL- and MBL-producing K. pneumoniae isolates specifically derived from DFUs. Methods A cross-sectional observational study was conducted at Krishna Vishwa Vidyapeeth from January 2023 to June 2023, involving 126 patients diagnosed with DFUs. Clinical and demographic data were collected, and wound swabs underwent microbiological analysis. Phenotypic detection methods were employed to identify ESBL and MBL production, followed by standardized antibiotic susceptibility testing. Results Among the 126 isolates tested, 36 (28.6%) were identified as ESBL-producing and 21 (16.7%) as MBL-producing strains. ESBL-producing isolates exhibited high resistance rates to antibiotics such as ampicillin (92.3%), amoxicillin-acid (84.6%), and cephalosporins, including ceftriaxone (76.9%), and cefepime (73.8%). MBL-producing isolates demonstrated even broader resistance profiles, including resistance to fluoroquinolones (ciprofloxacin, 60.0%; levofloxacin, 57.1%), aminoglycosides (gentamicin, 42.9%), and carbapenems (meropenem, 38.1%; imipenem, 35.7%). Conclusion This study identifies a significant prevalence of ESBL- and MBL-producing K. pneumoniae in DFUs, showcasing high antibiotic resistance rates. Comorbidities correlate significantly with the presence of resistant isolates, necessitating treatment strategies for effective management.

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Diabetic foot ulcers (DFUs) are a serious vascular disease. Currently, no effective methods are available for treating DFUs. Pro-protein convertase subtilisin/kexin type 9 (PCSK9) regulates lipid levels to promote atherosclerosis. However, the role of PCSK9 in DFUs remains unclear. In this study, we found that the expression of PCSK9 in endothelial cells (ECs) increased significantly under high glucose (HG) stimulation and in diabetic plasma and vessels. Specifically, PCSK9 promotes the E3 ubiquitin-protein ligase NEDD4 binding to vascular endothelial growth factor receptor 2 (VEGFR2), which led to the ubiquitination of VEGFR2, resulting in its degradation and downregulation in ECs. Furthermore, PCSK9 suppresses the expression and activation of AKT, endothelial nitric oxide synthase (eNOS), and ERK1/2, leading to decreased nitric oxide (NO) production and increased superoxide anion (O2._) generation, which impairs vascular endothelial function and angiogenesis. Importantly, using evolocumab to limit the increase in PCSK9 expression blocked the HG-induced inhibition of NO production and the increase in O2._ production, as well as inhibited the phosphorylation and expression of AKT, eNOS, and ERK1/2. Moreover, evolocumab improved vascular endothelial function and angiogenesis, and promoted wound healing in diabetes. Our findings suggest that targeting PCSK9 is a novel therapeutic approach for treating DFUs.

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

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Background: Diabetic foot ulcers (DFU) seriously threaten the health and quality of life of patients. The microbiota is the primary reason for the refractory and high recurrence of DFU. This study aimed to determine the wound microbiota at different DFU stages. Methods: Wound samples were collected from 48 patients with DFU and divided into three phases: inflammatory (I, n = 49), proliferation (P, n = 22), and remodeling (R, n = 19). The wound samples obtained at different stages were then subjected to 16S rRNA gene sequencing. The number of operational taxonomic units (OTUs) in the different groups was calculated according to the criterion of 97 % sequence similarity. The diversity of the microbiota differentially presented bacterial taxa at the phylum and genus levels, and important phyla and genera in the different groups were further explored. Results: After sequencing, 3351, 925, and 777 OTUs were observed in groups I, P, and R, respectively, and 175 OTUs overlapped. Compared with the inflammatory stage, the α-diversity of wound microbiota at proliferation and remodeling stages was significantly decreased (P < 0.05). At the phylum level, Firmicutes, Proteobacteria, Actinobacteriota, and Bacteroidota were the dominant phyla, accounting for more than 90 % of all the phyla. At the genus level, Random Forest and linear discriminant analysis effect size analyses showed that Peptoniphilus, Lactobacillus, Prevotella, Veillonella, Dialister, Streptococcus, and Ruminococcus were the signature wound microbiota for the inflammatory stage; Anaerococcus, Ralstonia, Actinomyces, and Akkermansia were important species for the proliferation stage; and the crucial genera for the remodeling stage were Enterobacter, Pseudomonas, Sondgrassella, Bifidobacterium, and Faecalibacterium. Conclusions: There were significant differences in the composition and structure of the wound microbiota in patients with DFU at different stages, which may lay a foundation for effectively promoting wound healing in DFU.