Studies have highlighted the role of actin cables in embryonic scarless wound healing across various species. However, evidence for similar structures in adult animals remains lacking. Adult newts, known for their exceptional skin regeneration capabilities, are considered promising models for postnatal human studies. This study investigated actin fiber formation and alignment during re-epithelialization in the Japanese fire-bellied newt (Cynops pyrrhogaster).

Full-thickness skin excisions were performed, and actin structures were analyzed using immunohistochemistry and electron microscopy. The role of actin in re-epithelialization was assessed by inhibiting its formation with cytochalasin B. Myosin, an interacting cytoskeletal molecule, was examined through immunohistochemistry, while E-cadherin, an adhesion molecule, was analyzed using both immunohistochemistry and electron microscopy.

Rather than an actin cable a mesh-like actin structure, termed the "actin mesh," was identified via immunohistochemical analysis. The actin mesh developed alongside wound epidermis extension and disappeared following complete re-epithelialization. Inhibition of actin formation delayed re-epithelialization, although the overall healing process showed no significant difference from the control group. Immunohistochemistry revealed the presence of myosin II and E-cadherin alongside Filamentous actin. Electron microscopy further demonstrated actin-rich structures in the wound epidermis compared to normal skin and confirmed E-cadherin-mediated cell-cell adhesion in the wound area.

The actin mesh plays a critical role in facilitating rapid re-epithelialization in adult newts, presenting a valuable model for studying scarless wound healing in adult organisms. The involvement of interacting molecules such as myosin and E-cadherin provides insights into the underlying mechanisms of this process. This model offers potential applications for addressing intractable wounds in humans.

Chronic infected diabetic wounds are complex and often lead to severe clinical outcomes such as sepsis, gangrene, and amputation. To address these challenges, herein we developed a novel tri-layered scaffold to provide multi-functional therapeutic support. The bottom poly (lactic-co-glycolic acid) (PLGA) fibrous layer contains doxycycline loaded CuBDC nanosheets for rapid antibacterial action. The porous PLGA/gelatin middle layer offers mechanical support and γ-tocotrienol loaded ZIF-8 nanocrystals mitigates oxidative stress in the wound. The PLGA top sealing fibrous layer delivers insulin and Transforming growth factor beta (TGF-β1) from Zeolitic Imidazolate Framework-8 (ZIF-8) nanocrystals to promote epithelialization and modulate inflammation. Comprehensive in vitro and in vivo evaluations demonstrated that the scaffold effectively filled deep wounds, reduced bacterial load, controlled inflammation, and accelerated the tissue regeneration. Histopathological analyses showed enhanced epithelialization and partial granulation tissue remodeling. Biochemical assays indicated an increase in glutathione peroxidase (GPx) activity and a reduction in lipid peroxidation. Gene expression analysis revealed decreased levels of the pro-inflammatory TNF-α and increased levels of the anti-inflammatory IL-10, facilitating the transition to the proliferative phase. This multi-layered composite scaffold, with its antimicrobial, antioxidant, and anti-inflammatory activities, controlled release capabilities, presents a promising solution the healing process of deep, infected diabetic wounds.

Diabetes mellitus ranks as the eighth most prevalent cause of mortality and disability worldwide. It is a major challenge for clinics to treat diabetic-infected wounds. The hydrogel (referred to as NanoAg@QAC), which combines the advantages of nanosilver (NanoAg) and quaternary ammonium chitosan (QAC), possesses the characteristics of an ideal wound dressing, including proper mechanical properties, antimicrobial activity, anti-biofilm properties, and cytocompatibility. The NanoAg@QAC hydrogel proved to be efficacious in treating infections caused by S. aureus and P. aeruginosa in vivo, thereby promoting wound closure during the initial phase of healing. The application of the NanoAg@QAC hydrogel efficiently suppressed M1-type macrophage marker iNOS expression and simultaneously enhanced the M2-type macrophage marker CD206, which promoted the M1 to M2 transition. The hydrogel significantly reduced the pro-inflammatory cytokine interleukin-1β (IL-1β) and increased the levels of vascular endothelial growth factor A (VEGFA), which alleviated the inflammatory response of the wound and promoted neovascularization. Furthermore, the NanoAg@QAC hydrogel enhanced tissue regeneration and collagen deposition. Thisw study demonstrates that the NanoAg@QAC hydrogel exhibits significant potential for application in the treatment of diabetic-infected wounds.

The American Heart Association (AHA) proposed the concept of cardiovascular-kidney-metabolic (CKM) syndrome, underscoring the interconnectedness of cardiovascular, renal, and metabolic diseases. The stress hyperglycemia ratio (SHR) represents an innovative indicator that quantifies blood glucose fluctuations in patients experiencing acute or subacute stress, correlating with detrimental clinical effects. Nevertheless, the prognostic significance of SHR within individuals diagnosed with CKM syndrome in stages 0 to 3, particularly with respect to all-cause or cardiovascular disease (CVD) mortality risks, has not been fully understood yet.

The current study analyzed data from 9647 participants with CKM syndrome, covering stages 0 to 3, based on the NHANES (National Health and Nutrition Examination Survey) collected from 2007 to 2018. In this study, the primary exposure variable was the SHR, computed as fasting plasma glucose divided by (1.59 * HbA1c - 2.59). The main endpoints of study were all-cause mortality as well as CVD mortality, with death registration data sourced through December 31, 2019. The CHARLS database (China Health and Retirement Longitudinal Study) was utilized as validation to enhance the reliability of the findings.

This study included 9647 NHANES participants, who were followed for a median duration of 6.80 years. During this period, 630 all-cause mortality cases and 135 CVD-related deaths in total were recorded. After full adjustment for covariates, our results displayed a robust positive association of SHR with all-cause mortality (Hazard ratio [HR] = 1.09, 95% Confidence interval [CI] 1.04-1.13). However, the SHR exhibited no significant relationship with CVD mortality (HR = 1.00, 95% CI 0.91-1.11). The mediation analysis results suggested that the relationship between SHR and all-cause mortality risk is partially mediated by RDW, albumin, and RAR. Specifically, the mediating effects were - 17.0% (95% CI - 46.7%, - 8.7%), - 10.1% (95% CI - 23.9%, - 4.7%), and - 23.3% (95% CI - 49.0%, - 13.0%), respectively. Additionally, analyses of the CHARLS database indicated a significant positive correlation between SHR and all-cause mortality among individuals diagnosed with CKM across stages 0-3 during the follow-up period from 2011 to 2020.

An increased SHR value is positively associated with an elevated likelihood of all-cause mortality within individuals diagnosed with CKM syndrome across stages 0-3, yet it shows no significant association with CVD mortality. SHR is an important tool for predicting long-term adverse outcomes in this population. Cardiovascular-kidney-metabolic (CKM) syndrome emphasizes the interconnectedness of cardiovascular, kidney, and metabolic diseases. The stress hyperglycemia ratio (SHR) is a novel marker reflecting stress-induced glucose fluctuations, but its prognostic value in individuals with CKM syndrome (stages 0-3) remains uncertain. This study explores the association between SHR and all-cause and cardiovascular disease (CVD) mortality in this population. Our findings indicate that SHR is significantly associated with an increased risk of all-cause mortality (HR = 1.09, 95% CI 1.04-1.13), but not with CVD mortality (HR = 1.00, 95% CI: 0.91-1.11). Mediation analysis results suggested that the relationship between SHR and all-cause mortality risk is partially mediated by RDW, albumin, and RAR. Specifically, the mediating effects were - 17.0% (95% CI - 46.7%, - 8.7%), - 10.1% (95% CI - 23.9%, - 4.7%), and - 23.3% (95% CI - 49.0%, - 13.0%), respectively. Validation using the CHARLS database supports these findings. These results suggest that SHR could serve as a prognostic biomarker for long-term mortality risk in CKM patients, offering potential clinical utility in risk stratification and management.

Diabetic foot (DF) is a major public health concern. As evident from numerous previous studies, supervision of DF ulcer (DFU) is crucial, and a specific quality check-up is needed. Patients should be educated about glycaemic management, DFUs, foot lesions, proper care for injuries, diet, and surgery. Certain reasonably priced treatments, such as hyperbaric oxygen and vacuum-assisted closure therapy, are also available for DFUs, along with modern wound care products and techniques. Nonetheless, DF care (cleaning, applying antimicrobial cream when wounded, and foot reflexology), blood glucose monitoring to control diabetes, and monthly or quarterly examinations in individuals with diabetes are effective in managing DFUs. Between 50% and 80% of DF infections are preventable. Regardless of the intensity of the lesion, it needs to be treated carefully and checked daily during infection. Tissue regeneration can be aided by cleaning, dressing, and application of topical medicines. The choice of shoes is also important because it affects blood circulation and nerve impulses. In general, regular check-ups, monitoring of the patient's condition, measuring blood glucose levels, and providing frequent guidance regarding DFU care are crucial. Finally, this important clinical problem requires involvement of multiple professionals to properly manage it.

Diabetes is a widespread metabolic disorder that presents considerable challenges in its management. Recent advancements in biomaterial research have shed light on innovative approaches for the treatment of diabetes. This review examines the role of biomaterials in diabetes diagnosis and treatment, as well as their application in managing diabetic wounds. By evaluating recent research developments alongside future obstacles, the review highlights the promising potential of biomaterials in diabetes care, underscoring their importance in enhancing patient outcomes and refining treatment methodologies.

This study focused on the potential of Gliricidia sepium (Jacq.) Kunth. ex. Walp. leaves zinc oxide nanoparticles hydrogel (GSL ZnONPs HG) for diabetic wound healing. The major components identified through HPLC analysis in Gliricidia sepium (Jacq.) Kunth. ex. Walp. leaves ethanolic extract (GSL) were apigenin-7-O-glucoside, kaempferol, and protocatechuic acid. These compounds exhibited anti-inflammatory properties. The hydrogel loaded with GSL ethanolic extract and Gliricidia sepium (Jacq.) Kunth. ex. Walp. leaves ethanolic extract zinc oxide nanoparticles (GSL ZnONPs) displayed controlled release and favorable swelling behavior. GSL ZnONPs HG enhanced tissue regeneration, reduced apoptosis, and modulated inflammation in diabetic wounds as demonstrated by wound morphology and closure measurements, as well as histopathological and immunohistochemical evaluations. It is important to highlight the dose-dependent behavior of GSL ZnONPs, demonstrating their effectiveness in promoting diabetic wound healing even at lower concentrations. This was supported by their response to various biomarkers through a significant reduction in vascular cell adhesion molecule-1 (VCAM-1) and advanced glycation end products levels (AGEs), and a notable increase in interleukin-10 (IL-10) and platelet-derived growth factor concentrations (PDGF). Collectively, the study highlights the potential of GSL ZnONPs HG as a promising approach to enhance diabetic wound healing.

This study explored the effects of Moist Exposed Burn Ointment (MEBO) on the healing process of pressure-induced wounds. Using a stage IV pressure ulcer model established in 42 rats, divided equally into a control gel group and an MEBO group, we investigated the efficacy of MEBO through topical application. The control group received Carbomer gel, while the MEBO group was treated with MEBO until complete wound healing. Results showed that MEBO significantly accelerated wound healing compared to the control group. Histological analysis, including hematoxylin and eosin (HE) staining and Masson's trichrome staining, revealed enhanced epithelialization and collagen deposition in the MEBO group. Furthermore, 16S rRNA sequencing indicated that MEBO reduced microbial diversity at the wound site and reshaped the microbial composition. Notably, The increased abundance of Acinetobacter and Staphylococcus, coupled with a reduction in Pseudomonas, may reflect a shift in the wound microbiome that could be conducive to healing. However, the exact role of these microbial shifts in promoting wound healing requires further investigation, as microbial dynamics in wound environments are complex and context-dependent. These findings suggest that MEBO facilitates wound healing by optimizing the wound microbiome, thereby offering a promising therapeutic approach for managing pressure ulcers.

Bacterial infections are a significant obstacle to the healing of acute and chronic wounds, such as diabetic ulcers and burn injuries. Traditional antibiotics are the primary treatment for bacterial infections, but they present issues such as antibiotic resistance, limited efficacy, and potential side effects. This challenge leads to the exploration of nanozymes as alternative therapeutic agents. Nanozymes are nanomaterials with enzyme-like activities. Owing to their low production costs, high stability, scalability, and multifunctionality, nanozymes have emerged as a prominent focus in antimicrobial research. Among various types of nanozymes, metal-based nanozymes offer several benefits, including broad-spectrum antimicrobial activity and robust catalytic properties. Specifically, copper-based nanozymes (CuNZs) have shown considerable potential in promoting wound healing. They exhibit strong antimicrobial effects, reduce inflammation, and enhance tissue regeneration, making them highly advantageous for use in wound care. This review describes the dual functions of CuNZs in combating infection and facilitating wound repair. Recent advancements in the design and synthesis of CuNZs, evaluating their antimicrobial efficacy, healing promotion, and biosafety both in vitro and in vivo on the basis of their core components, are critically important.

Periprosthetic joint infection (PJI) is a major complication following hip arthroplasty, leading to prolonged hospital stays, increased health care costs, and major morbidity. Diabetes mellitus is a prevalent comorbidity among hip arthroplasty patients, contributing to an increased risk of surgical complications, including infections. However, limited evidence exists regarding the microbial profiles of PJIs in diabetic patients compared to nondiabetic counterparts.

We conducted a retrospective cohort study to investigate the microbial diversity of PJIs in diabetic and nondiabetic patients following hip arthroplasty. Medical records of patients who underwent hip arthroplasty procedures between 1996 and 2021 were reviewed. Patients diagnosed with PJI, based on the international consensus meeting, were included in the study. Microbiological data, including culture results, and risk factors were collected and analyzed. A total of 4,261 culture-positive patients diagnosed with PJI following hip arthroplasty were included in the analysis.

Microbiological analysis revealed a diverse spectrum of microbial pathogens, with Staphylococcus species being the most commonly isolated pathogen. Comparison between diabetic and nondiabetic patients revealed differences in the microbial profiles of PJIs, with diabetic patients more likely to be infected with specific pathogens, including Candida albicans (P = 0.01 odds ratio (OR) 2.8, confidence interval (CI) 1.2 to 6.2), Klebsiella pneumoniae (P = 0.03 OR 2.4, CI 1.0 to 5.6), Staphylococcus aureus (P = 0.04 OR 1.3, CI 1.0 to 1.8), Staphylococcus epidermidis (P < 0.001 (R 1.7, CI 1.4 to 2.2), Polymicrobial infections (P < 0.001 OR 1.5, CI 1.2 to 1.8), and Clostridium perfringens (P = 0.04 OR 5.9, CI 1.0 to 33.1).

Our study provides valuable insights into the microbial diversity of PJIs in diabetic and nondiabetic patients following hip arthroplasty. The identification of a tendency to different microbial profiles in diabetic patients underscores the need for tailored approaches to infection prevention and management in this high-risk population. Further research is needed to elucidate the underlying mechanisms and develop targeted interventions to improve patient outcomes.

Diabetic wounds, a significant complication of Type 2 Diabetes Mellitus (T2DM), face delayed healing due to impaired inflammation, angiogenesis, and collagen synthesis. This study explores Febuxostat, a xanthine oxidase inhibitor for its therapeutic potential in wound healing. Combining computational approaches and in-vitro assays, the study evaluates its effects on key wound healing pathways, cell viability, migration.

The potential of Febuxostat in diabetic wound healing was studied using in-silico tools for Molecular docking and ADMET profiling, alongside Molecular dynamics (MD) simulations. Toxicity was assessed with OSIRIS Explorer, and biological activity was predicted using the PASS tool. In-vitro MTT and scratch assays on L929 cells further validated cytotoxicity and wound healing efficacy.

Docking analysis revealed strong binding affinities to key wound healing targets, including VEGF (-9.11 kcal/mol) and NFKβ (-8.62 kcal/mol). Pharmacokinetic studies highlighted favorable skin permeability, supporting topical applications. Toxicity predictions indicated a safe profile. Molecular dynamics simulations demonstrated stable protein-ligand complexes, particularly with VEGF. Cytotoxicity studies on L929 cells revealed an IC50 of 6.08 μM and the scratch assay demonstrated significant wound healing activity, highlighting its effectiveness in promoting cell migration and closure.

Febuxostat shows remarkable potential in enhancing diabetic wound healing by promoting cell migration, targeting wound-healing proteins, as demonstrated through in-silico and in-vitro studies. This drug is poised to effectively treat diabetic wounds, accelerating healing and reducing complications. Rigorous pre-clinical and clinical evaluations are essential to validate its safety, efficacy, and therapeutic potential.

Wound healing is a central physiological process that restores the barrier properties of the skin after injury, comprising close coordination between several cell types (including fibroblasts and macrophages) in the wound bed. The complex mechanisms involved are executed and regulated by an equally complex, reciprocal signalling network involving numerous signalling molecules such as catabolic and anabolic inflammatory mediators (e.g., cytokines, chemokines). In chronic wound environments, the balance in the molecular signatures of inflammatory mediators is usually impaired. Thus, we compared the ability of a collagen-based wound matrix against a synthetic wound matrix to attract fibroblasts and macrophages that deliver these signalling molecules. In particular, the balance between pro- and anti- inflammatory cytokine secretion was assessed. We found that the natural collagen-based matrix was the most efficient adhesive substrate to recruit and activate fibroblasts and macrophages on its surface. These cells secreted a variety of cytokines, and the natural biomaterial exhibited a more balanced secretion of pro- and anti-inflammatory mediators than the synthetic comparator. Thus, our study highlights the ability of native collagen matrices to modulate inflammatory mediator signatures in the wound bed, indicating that such devices may be beneficial for wound healing in the clinical setting.

A novel strategy that has emerged in recent years involves the use of aerogels for anti-inflammatory treatment, which has been extensively studied for its powerful application prospects in wound healing, diabetic complications, and tissue regeneration. However, the therapeutic efficacy of aerogels alone is compromised due to bacterial infections at the wound site. Therefore, it is necessary to incorporate effective antibacterial systems onto the aerogels to enhance their efficacy against bacterial infections. For instance, the design of cascade reactions targeting specific disease biomarkers for diagnostic and therapeutic purposes holds promise for enhancing treatment efficacy and precision. In this study, we successfully achieved the immobilization of glucose oxidase within an aerogel prepared from nanozymes, demonstrating remarkable catalytic activity and high-temperature stability. The cascade catalytic system comprising nanozymes and glucose oxidase was applied to combat Methicillin-resistant Staphylococcus aureus (MASR) bacterial infections, exhibiting effective biofilm removal capabilities. In therapeutic experiments on ulcerated wounds in diabetic mice, the cascade catalytic system demonstrated outstanding efficacy with excellent biocompatibility. The therapeutic effects were primarily manifested in the rapid clearance of biofilms formed by MASR, achieved by locally depleting glucose in the wound area, thereby promoting the healing process of ulcerated wounds.

Jatyadi thailam, an Ayurvedic preparation, is renowned for its efficacy in diabetic wound healing and inflammation. This study aimed to validate and compare the diabetic wound-healing potential of two Jatyadi thailam formulations - Ayurvedic formulary of India Jatyadi thailam (JT-AFI) and Yogagrantha formulation of Jatyadi thailam (JT-YG), in a diabetic environment using L929 fibroblast cells in vitro.

The effects on cell survival, proliferation, migration, angiogenesis, cell cycle progression, apoptosis, ROS generation, and mitochondrial function were evaluated.

The formulations promoted cell proliferation, migration, angiogenesis, while also regulating cell cycle and apoptosis. They effectively suppressed ROS generation and modulated mitochondrial function. JT-AFI exhibited superior efficacy in accelerating diabetic wound healing compared to JT-YG.

These findings provide substantial support for the mechanistic role of Jatyadi thailam in diabetic wound healing.

Innovative solutions are required for the intervention of implant associated infections (IAIs), especially for bone defect patients with chronic inflammatory diseases like diabetes mellitus (DM). The complex immune microenvironment of infections renders implants with direct antibacterial ability inadequate for the prolonged against of bacterial infections. Herein, a synergistic treatment strategy was presented that combined sonodynamic therapy (SDT) with adaptive immune modulation to treat IAIs in diabetes patients. A multifunctional coating was created on the surface of titanium (Ti) implants, consisting of manganese dioxide nanoflakes (MnO2 NFs) with cascade catalytic enzyme activity and a responsive degradable hydrogel containing a sonosensitizer. The reactive oxygen species (ROS) generated by glucose-hydrogen peroxide (H2O2) cascade catalysis and ultrasound (US) activation sonosensitizer helped kill bacteria and release bacterial antigens. Meanwhile, Mn2+ facilitated dendritic cells (DCs) maturation, enhancing antigen presentation to activate both cellular and humoral adaptive immunity against bacterial infections. This approach effectively eliminated bacteria in established diabetic IAIs model and activated systemic antibacterial immunity, providing long-term antibacterial protection. This study presents a non-antibiotic immunotherapeutic strategy for fighting IAIs in chronic diseases.

To utilize machine learning for identifying treatment response genes in diabetic foot ulcers (DFU).

Transcriptome data from patients with DFU were collected and subjected to comprehensive analysis. Initially, differential expression analysis was conducted to identify genes with significant changes in expression levels between DFU patients and healthy controls. Following this, enrichment analyses were performed to uncover biological pathways and processes associated with these differentially expressed genes. Machine learning algorithms, including feature selection and classification techniques, were then applied to the data to pinpoint key genes that play crucial roles in the pathogenesis of DFU. An independent transcriptome dataset was used to validate the key genes identified in our study. Further analysis of single-cell datasets was conducted to investigate changes in key genes at the single-cell level.

Through this integrated approach, SCUBE1 and RNF103-CHMP3 were identified as key genes significantly associated with DFU. SCUBE1 was found to be involved in immune regulation, playing a role in the body's response to inflammation and infection, which are common in DFU. RNF103-CHMP3 was linked to extracellular interactions, suggesting its involvement in cellular communication and tissue repair mechanisms essential for wound healing. The reliability of our analysis results was confirmed in the independent transcriptome dataset. Additionally, the expression of SCUBE1 and RNF103-CHMP3 was examined in single-cell transcriptome data, showing that these genes were significantly downregulated in the cured DFU patient group, particularly in NK cells and macrophages.

The identification of SCUBE1 and RNF103-CHMP3 as potential biomarkers for DFU marks a significant step forward in understanding the molecular basis of the disease. These genes offer new directions for both diagnosis and treatment, with the potential for developing targeted therapies that could enhance patient outcomes. This study underscores the value of integrating computational methods with biological data to uncover novel insights into complex diseases like DFU. Future research should focus on validating these findings in larger cohorts and exploring the therapeutic potential of targeting SCUBE1 and RNF103-CHMP3 in clinical settings.

A diabetic wound exemplifies the challenge of chronic, nonhealing wounds. Elevated blood sugar levels in diabetes profoundly disrupt macrophage function, impairing crucial activities such as phagocytosis, immune response, cell migration, and blood vessel formation, all essential for effective wound healing. Moreover, the persistent presence of pro-inflammatory cytokines and reactive oxygen species, coupled with a decrease in anti-inflammatory factors, exacerbates the delay in wound healing associated with diabetes. This review emphasizes the dysfunctional inflammatory responses underlying diabetic wounds and explores preclinical studies of inflammation-modulating bioactives and biomaterials that show promise in expediting diabetic wound healing. Additionally, this review provides an overview of selected clinical studies employing biomaterials and bioactive molecules, shedding light on the gap between extensive preclinical research and limited clinical studies in this field.

Background:After skin damage, a complicated set of processes occur for epidermal and dermal wound healing. This process is hindered under diabetic conditions, resulting in nonhealing diabetic ulcers. In diabetes there is an increase in inflammation and proinflammatory cytokines. Modulating cells using photobiomodulation (PBM) may have an effect on inflammation and cell viability, which are crucial for the healing of wounds. Objective: This study explored the impact of PBM in the near-infrared spectrum (830 nm; 5 J/cm2) on inflammation in diabetic wound healing. Materials and Methods: Five cell models, namely normal, wounded, diabetic, diabetic wounded, and wounded with d-galactose were used. Cell morphology and migration rate were assessed, while cellular response measures included viability (Trypan blue and adenosine triphosphate), apoptosis (annexin-V/PI), proinflammatory cytokines interleukin-6, tumor necrosis factor-alpha (TNF-α), and cyclooxygenase-2, nuclear translocation of nuclear factor kappa B (NF-κB), and gene expression of advanced glycation end product receptor (AGER). Results: PBM resulted in increased levels of TNF-α, supported by activation of NF-κB. PBM stimulated translocation of NF-κB and upregulation of AGER. Conclusions: PBM modulates diabetic wound healing in vitro at 830 nm through stimulated NF-κB signaling activated by TNF-α.

Bacteriophage (phage) has been reported to reduce the bacterial infection in delayed-healing wounds and, as a result, aiding in the healing of said wounds. In this study we investigated whether the presence of phage itself could help repair delayed-healing wounds in diabetic mice. Three strains of phage that target Salmonella enterica, Escherichia coli, and Pseudomonas aeruginosa were used. To prevent the phage liquid from running off the wound, the mixture of phage (phage-cocktail) was encapsulated in a porous hydrogel dressing made with three-dimensional printing. The phage-cocktail dressing was tested for its phage preservation and release efficacy, bacterial reduction, cytotoxicity with 3T3 fibroblast, and performance in repairing a sterile full-thickness skin wound in diabetic mice. The phage-cocktail dressing released 1.7%-5.7% of the phages embedded in 24 h, and reduced between 37%-79% of the surface bacteria compared with the blank dressing (p <.05). The phage-cocktail dressing exhibited no sign of cytotoxicity after 3 days (p <.05). In vivo studies showed that 14 days after incision, the full-thickness wound treated with a phage-cocktail dressing had a higher wound healing ratio compared with the blank dressing and control (p <.01). Histological analysis showed that the structure of the skin layers in the group treated with phage-cocktail dressing was restored in an orderly fashion. Compared with the blank dressing and control, the repaired tissue in the phage-cocktail dressing group had new capillary vessels and no sign of inflammation in its dermis, and its epidermis had a higher degree of re-epithelialization (p <.05). The slow-released phage has demonstrated positive effects in repairing diabetic skin wounds.

Diabetic wounds pose a significant challenge in healthcare due to their complex nature and the difficulties they present in treatment and healing. Impaired healing processes in individuals with diabetes can lead to complications and prolonged recovery times. However, recent advancements in wound healing provide reasons for optimism. Researchers are actively developing innovative strategies and therapies specifically tailored to address the unique challenges of diabetic wounds. One focus area is biomimetic hydrogel scaffolds that mimic the natural extracellular matrix, promoting angiogenesis, collagen deposition, and the healing process while also reducing infection risk. Copper nanoparticles and copper compounds incorporated into hydrogels release copper ions with antimicrobial, anti-inflammatory, and angiogenic properties. Copper reduces infection risk, modulates inflammatory response, and promotes tissue regeneration through cell adhesion, proliferation, and differentiation. Utilizing copper nanoparticles has transformative potential for expediting diabetic wound healing and improving patient outcomes while enhancing overall well-being by preventing severe complications associated with untreated wounds. It is crucial to write a review highlighting the importance of investigating the use of copper nanoparticles and compounds in diabetic wound healing and tissue engineering. These groundbreaking strategies hold the potential to transform the treatment of diabetic wounds, accelerating the healing process and enhancing patient outcomes.

Diabetes mellitus is a metabolic disorder, in which chronic systemic inflammation and oxidative stress contribute to the progression of this condition and its complications. Melatonin, a hormone known for its potent antioxidant and anti-inflammatory properties, has emerged as a potential therapeutic intervention in diabetes. This review aims to evaluate the effects of melatonin supplementation on markers of oxidative stress and inflammation in diabetic patients.

A thorough literature search of databases, including PubMed, Embase, Web of Science, Cochrane Central, CNKI, and Scopus, was conducted through October 2023. We included randomized controlled trials investigating the effects of melatonin on markers of inflammation and oxidative stress, compared to placebo in patients with diabetes. The data was analyzed using the random-effects model and the summary effect size was determined using the standardized mean difference (SMD) with 95% confidence interval (CI).

Fourteen studies with 823 participants were included. Our analysis indicates that melatonin can lead to significant reductions in levels of C-reactive protein (CRP) [SMD = -0.75; 95% CI: -1.37, -0.12; P = 0.018], tumor necrosis factor-alpha (TNF-α) [SMD = -0.40; 95% CI: -0.64, -0.15; P = 0.001], interleukin (IL)-1 [SMD = -0.75; 95% CI: -1.03, -0.47; P < 0.0001], IL-6 [SMD = -0.79; 95% CI: -1.07, -0.51; P < 0.0001], and malondialdehyde (MDA) [SMD = -0.61; 95% CI: -0.80, -0.43; P < 0.0001]. Furthermore, we found a significant increase in levels of total antioxidant capacity (TAC) [SMD = 0.81; 95% CI: 0.12, 1.51; P = 0.021], glutathione (GSH) [SMD = 0.66; 95% CI: 0.28, 1.03; P = 0.001], and superoxide dismutase (SOD) [SMD = 1.69; 95% CI: 0.80, 2.58; P < 0.0001] following melatonin consumption in patients with diabetes.

Melatonin supplementation is a promising complementary strategy to attenuate oxidative stress and inflammation in diabetic patients.

The purpose of this study is to conduct a comparative analysis of the microbiological profiles in periprosthetic joint infections (PJIs) after total knee arthroplasty (TKA) between diabetic and non-diabetic patients. The study aims to address what are the variations in microbial colonization and infection patterns between diabetic and non-diabetic patients undergoing total knee arthroplasty.

A retrospective analysis of 2,569 culture-positive cases of PJIs post-TKA was conducted, comparing outcomes between diabetic (n = 321) and non-diabetic (n = 2,248) patients. Demographic, clinical, and microbiological data were collected and analyzed using descriptive statistics, chi-squared tests, logistic regression, and other statistical tests.

Diabetic patients exhibited distinct microbial colonization patterns, with a higher prevalence of pathogens such as Staphylococcus aureus (p = 0.033), Pseudomonas aeruginosa (p < 0.001), Streptococcus spp. (Streptococcus agalactiae and Streptococcus dysgalactiae; p = 0.010, 0.016 respectively), Candida spp. (p = 0.010), and Corynebacterium spp. (p = 0.024). Additionally, diabetic patients were at increased risk of polymicrobial infections. Comorbidities associated with diabetes, including chronic pulmonary disease, renal insufficiency, and peripheral artery disease, were significantly more prevalent in diabetic patients and further complicated PJI outcomes.

This study underscores the importance of tailored perioperative antimicrobial strategies and vigilant infection control measures in diabetic patients undergoing TKA. Understanding the differential microbial profiles and associated comorbidities can inform targeted interventions to mitigate the risk of PJIs and improve outcomes in this high-risk population. Further research is warranted to elucidate the underlying mechanisms and optimize management strategies for diabetic patients undergoing TKA.

Diabetic foot ulcers (DFUs) are one of the most serious complications of diabetes, often leading to necrosis and amputation. DFU is caused by the intricate diabetic microenvironment, including ischemia, hypoxia, hyperinflammation, reduced angiogenesis, and persistent infection. Traditional wound dressings made of single or mixed materials often struggle to meet all the requirements for effective diabetic wound healing. In contrast, multilayer dressings comprising more than single layers have the potential to address these challenges by combining their diverse chemical and physical properties. In this study, we developed a bilayer hydrogel comprising a GelMA-ALG-nano-ZnO protective film and a COL1-PRP regenerative hydrogel for facilitating diabetic wound healing. We demonstrated the protective properties against bacterial infection of the protective film, while highlighting the regenerative potential of the COL1-PRP hydrogel in promoting fibroblast and MUVEC migration, extracellular matrix secretion and deposition, and angiogenesis. Importantly, the bilayer hydrogel exhibited superior efficacy in promoting full-thickness wound healing in a diabetic rat model compared to its single-layer hydrogel counterparts. This multi-layer approach offers a promising strategy for addressing the complexities of diabetic foot treatment and improving clinical outcomes.

Wound healing is a complex process orchestrated by interactions between a variety of cell types, including keratinocytes, fibroblasts, endothelial cells, inflammatory cells, and bioactive factors such as extracellular matrix (ECM) components, growth factors, and cytokines. Chronic wounds exhibit delayed proliferative phase initiation, reduced angiogenesis, impaired ECM synthesis, and persistent inflammatory response. Chronic wounds are one of the main challenges to the healthcare system worldwide, with a high cost for medical services. Hence, investigation of new approaches to accelerate wound healing is essential. Phytomedicines are considered as potential agents for improving the wound healing by accelerating epithelization, collagen synthesis, and angiogenesis. These natural compounds have various advantages including availability, ease of application, and high effectiveness in wound managment. This study aimed to investigate the biological effects of saffron or Crocus sativus L. (C. sativus) petal extract on cell survival, migration, and angiogenesis using MTT, scratch and in vitro tube formation assays. Moreover, the expression of collagen type I alpha 1 (COL1A1) and vascular endothelial growth factor (VEGF) were evaluated in human dermal fibroblasts (HDF)s and human umbilical vein endothelial cells (HUVEC)s, respectively. The effect of the C. sativus extract on the skin of diabetic mice was also monitored. The results showed that C. sativus petal extract promoted the viability and migration of HDFs and HUVECs. Moreover, C. sativus petal extract enhanced the formation of tube-like structures by HUVECs cultured on the Matrigel basement membrane matrix, indicating its potential to stimulate angiogenesis. Gene expression studies have shown the the C. sativus extract increases wound healing by upregulation of COL1A1 and VEGF, which are crucial factors involved in collagen deposition, epithelialization, and angiogenesis. Histological analysis revealed that C. sativus petal extract enhanced vascularity and increased the number of fibroblasts and collagen synthesis, ultimately accelerating wound closure compared to wounds treated with eucerin and commercial ointment in diabetic mice. Therefore, C. sativus petal extract has potential as a herbal treatment to improve the healing of diabetic wounds.

Infectious diabetic wounds present a substantial challenge, characterized by inflammation, infection, and delayed wound healing, leading to elevated morbidity and mortality rates. In this work, we developed a multifunctional lipid nanoemulsion containing quercetin, chlorine e6, and rosemary oil (QCRLNEs) for dual anti-inflammatory and antibacterial photodynamic therapy (APDT) for treating infectious diabetic wounds. The QCRLNEs exhibited spherical morphology with a size of 51 nm with enhanced encapsulation efficiency, skin permeation, and localized delivery at the infected wound site. QCRLNEs with NIR irradiation have shown excellent wound closure and antimicrobial properties in vitro, mitigating the nonselective cytotoxic behavior of PDT. Also, excellent biocompatibility and anti-inflammatory and wound healing responses were observed in zebrafish models. The infected wound healing properties in S. aureus-infected diabetic rat models indicated re-epithelization and collagen deposition with no signs of inflammation. This multifaceted approach using QCRLNEs with NIR irradiation holds great promise for effectively combating oxidative stress and bacterial infections commonly associated with infected diabetic wounds, facilitating enhanced wound healing and improved clinical outcomes.

Diabetes mellitus (DM) is a pervasive global health issue with substantial morbidity and mortality, often resulting in secondary complications, including diabetic wounds (DWs). These wounds, arising from hyperglycemia, diabetic neuropathy, anemia, and ischemia, afflict approximately 15% of diabetic patients, with a considerable 25% at risk of lower limb amputations. The conventional approaches for chronic and diabetic wounds management involves utilizing various therapeutic substances and techniques, encompassing growth factors, skin substitutes and wound dressings. In parallel, emerging cell therapy approaches, notably involving adipose tissue-derived mesenchymal stem cells (ADMSCs), have demonstrated significant promise in addressing diabetes mellitus and its complications. ADMSCs play a pivotal role in wound repair, and their derived exosomes have garnered attention for their therapeutic potential. This review aimed to unravel the potential mechanisms and provide an updated overview of the role of ADMSCs and their exosomes in diabetes mellitus and its associated complications, with a specific focus on wound healing.

This descriptive cross-sectional study focuses on the prevalence of hypertension (HTN) and type 2 diabetes mellitus (T2DM) amongst patients who visited the Conservative Dentistry and Endodontics department. Recognizing these incidence statistics is critical for improving endodontic therapy delivery and assuring high-quality dental care with positive treatment outcomes.

In advance of getting dental care, all patients visiting the department were advised to get their blood sugar and blood pressure levels checked at random. Measurements were taken with digital equipment, and individuals with high levels were encouraged to seek medical advice before undergoing dental procedures. The obtained data was imported into Excel and analyzed with IBM SPSS software (version 21).

The investigation had 1,100 participants (55.8% female and 44.2% male), with an average age of 44.58 ± 12.77 years. Of the individuals, 40.6% were referred for type 2 diabetes, 12.6% for hypertension, and 24.0% for both diseases. There was a significant correlation (p < 0.05) between referral status and gender. The average blood pressure and random blood sugar readings were 141.02 mmHg ± 56.28 mmHg (systolic), 79.83 mmHg ± 10.68 mmHg (diastolic), and 126.68 mg/dL ± 15.36 mg/dL, respectively. There was a substantial (p < 0.05) difference in mean systolic blood pressure between men and women. Furthermore, age was strongly connected with random blood sugar levels (p < 0.05) and systolic and diastolic blood pressure (p < 0.05). There were significant (p < 0.05) variations in mean blood pressure and blood sugar levels between referred and non-referred individuals.

Age had a relationship with higher random blood sugar levels, systolic blood pressure, and diastolic blood pressure. Dentists should consider patient age while planning treatment, as type 2 diabetes mellitus and hypertension require unique techniques to emphasize patient safety and produce excellent outcomes.

To assess the efficacy of a chitosan-based gel (ChitoCare) for the treatment of non-healing diabetic foot ulcers (DFUs).

Forty-two patients with chronic DFUs were randomized to the ChitoCare or placebo gel for a 10-week treatment period and 4-week follow-up. The primary study end point was the rate of complete wound closure at week 10, presented as relative rate.

Thirty patients completed the 10-week treatment and 28 completed the 4-week follow-up. The ChitoCare arm achieved 16.7% complete wound closure at week 10 vs 4.2% in the placebo arm (p=0.297), 92.0% vs 37.0% median relative reduction in wound surface area from baseline at week 10 (p=0.008), and 4.62-fold higher likelihood of achieving 75% wound closure at week 10 (p=0.012). Based on the results of the Bates-Jensen Wound Assessment Tool, the wound state at week 10 and the relative improvement from the baseline were significantly better (median 20 vs 24 points, p=0.018, and median 29.8% vs 3.6%, p=0.010, respectively).

ChitoCare gel increased the rate of the DFU healing process. Several secondary end points significantly favored ChitoCare gel.

NCT04178525.

Currently, the treatment of diabetic wounds in clinical practice is still unsatisfactory due to the risks of oxidative damage and bacterial infection during the healing process. An optimal wound dressing should exhibit robust capabilities in scavenging reactive oxygen species (ROS) and combatting bacterial growth. In this study, we utilized borax as a crosslinker and prepared a pH/glucose dual-responsive composite hydrogel based on poly(vinyl alcohol) (PVA), sodium alginate (SA), and tannic acid (TA). This hydrogel, loaded with cerium dioxide, serves as an effective ROS scavenger, promoting wound closure by reducing the level of ROS in the wound area. Additionally, the hydrogel can release the antibacterial drug ofloxacin in response to the low pH and high glucose microenvironment in infected wounds. Results from skin defect model in diabetic mice demonstrated this ROS-scavenging and antibacterial hydrogel can suppress inflammation and accelerate wound healing. In summary, our work provides a new perspective on a local and stimulus-responsive drug delivery strategy for treating diabetic wounds.

Adipose-derived stem cells (ADSCs) hold promising application prospects in the treatment of diabetic wounds, although the underlying mechanisms of repair have not been fully elucidated. This research aimed to elucidate the mechanisms by which ADSCs promote wound healing.

Exosomes from ADSCs were isolated and circRps5 level was identified. To investigate the role of circRps5 in the regulation, exosomes from differently treated ADSCs were used. Different exosomes were injected into the edge of the wound in diabetic mice, and the effects on wound healing status, pathology, collagen, cytokines, and macrophage phenotype were assessed. Raw264.7 cells were co-treated with high glucose and exosomes, and then cell phenotype and autophagy were examined in vitro, followed by the evaluation of miR-124-3p's impact on cell phenotype.

Exosomes from ADSCs were isolated and identified using nanoparticle tracking analysis and exosome markers. Overexpression of circRps5 accelerated wound healing, reduced inflammatory response, enhanced collagen production, and promoted the M2 transformation of macrophages. In high glucose-induced macrophages, its overexpression also inhibited excessive autophagy. When macrophages overexpressed miR-124-3p, the induction of the M2 phenotype was suppressed. Luciferase reporter assay proved the combination of circRps5 and miR-124-3p.

This study identifies that circRps5 carried by ADSC-Exos promotes macrophage M2 polarization through miR-124-3p. These findings provide valuable insights into the mechanism of ADSC-Exos for treating refractory diabetic wounds, laying a solid theoretical groundwork for future clinical development.

Gram-negative bacteremia in hospitalized patients often leads to prolonged hospital stays, increased healthcare costs, and mortality rates. Simultaneously, the presence of comorbidities like chronic wounds increases the risk of severe infection and complicated hospital courses involving amputation, broad-spectrum antibiotic use, and repeat hospital admissions, after discharge. This case presents a 72-year-old male with a past medical history significant for chronic lower extremity cellulitis with multiple prior hospitalizations. On admission, the patient had a chief complaint of progressively worsening left lower extremity pain along with nausea, vomiting, and diarrhea. CT imaging of the left lower extremity suggested severe cellulitis without signs of osteomyelitis. Blood cultures initially suggested Corynebacterium jeikeium, but were sent to an outside facility due to ambiguity of results. The outside facility identified the pathogen as Ignatzschineria indica. After confirming the results, antibiotics were appropriately de-escalated to oral levofloxacin. The patient continued to show clinical improvement and was discharged with follow-up appointments scheduled for infectious disease and bi-weekly visits to wound care. Considering the increasing prevalence of chronic wounds in the United States, awareness and recognition of emerging pathogens are crucial for the timely diagnosis, treatment, and management of these complex patients. Our case adds to the growing body of reports on the management of I. indica bacteremia resulting from maggot-infested wounds.

With the increasing prevalence of diabetes, the healing of diabetic wounds has become a significant challenge for both healthcare professionals and patients. Recognizing the urgent need for effective solutions, it is crucial to develop suitable scaffolds specifically tailored for diabetic wound healing. In line with this objective, we have developed novel hybrid nanofibrous scaffolds by combining polyvinyl alcohol/chitosan (PVA/CS) and gelatin/poly(ε-caprolactone) (Gel/PCL) polymers through a double-nozzle electrospinning technique. In this study, we investigated the influence of the Gel/PCL blend ratio on the properties of the resulting nanofibers. Three different hybrid scaffold structures were examined: Gel/PCL (80:20)-PVA/CS (80:20), Gel/PCL (50:50)-PVA/CS (80:20), and Gel/PVA (20:80)-PVA/CS (80:20). Our findings demonstrate that the electrospun nanofibers of PVA/CS (80:20)-Gel/PCL (80:20) exhibited optimal mechanical performance, with a contact angle of approximately 54° and a diameter of 183 nm. Considering the crucial role of inhibiting bacterial adhesion in the success of implanted materials, we evaluated the cytocompatibility of the hybrid electrospun nanofibers using mouse fibroblast cells (L-929 cells). The in vitro cytotoxicity results obtained from L-929 fibroblast cell culture on the hybrid scaffolds revealed enhanced cell proliferation and appropriate cell morphology on the PVA/CS (80:20)-Gel/PCL (80:20) sample, indicating its capability to support tissue cell integration. Based on the information obtained from this study, the fabricated hybrid scaffold holds great promise for diabetic ulcer healing. Its optimal mechanical properties, suitable contact angle, and favorable cytocompatibility highlight its potential as a valuable tool in the field of diabetic wound healing. The development of such hybrid scaffolds represents a significant step forward in addressing the challenges associated with diabetic wound care.

Diabetic foot ulcers (DFUs) are chronic, difficult-to-heal wounds with a very high incidence of amputation. For patients with DFUs, prevention of amputation is crucial. However, the risk factors associated with DFU amputation and the extent to which different risk factors increase the risk of amputation are still uncertain. This study intends to provide a clinical basis for early intervention in DFU by retrospectively analysing the risk factors for DFU amputation. A retrospective analysis of 200 patients with DFUs admitted between October 2019 and October 2023 was conducted. Sixty-eight of the 200 underwent amputations. The overall amputation rate was 34%. Multiple logistic regression model showed that neutrophil/lymphocyte ratio (OR = 1.943; 95% CI:1.826-2.139), white blood cell (OR = 1.143; 95% CI:1.034-1.267), C-reactive protein (OR = 1.307; 95% CI:1.113-2.194) and Wagner grading (OR = 2.783; 95% CI: 1.751-4.302) were independent risk factors for amputation, while haemoglobin (OR = 0.742; 95% CI:0.638-0.965) and high density lipoprotein were independent protective factors for amputation (OR = 0.168; 95% CI:0.037-0.716), and further Receiver Operating Characteristic Curve curves showed that they showed high accuracy and were good predictors of amputation of DFUs.

The role of transforming growth factor β (TGF-β) in inflammation and immune response is established, but the mechanism of TGF-β signaling pathway-related genes (TRGs) in diabetic foot ulcer (DFU) is not fully understood. We aimed to investigate the contribution of TRGs in the identification, molecular categorization, and immune infiltration of DFU through bioinformatics analysis. TGF-β signaling pathway is activated in DFU. 33 TRGs were upregulated. Regression analysis revealed TGFBR1 and TGFB1 as significant differential expression core genes, validated by quantitative real-time PCR. The diagnostic model with core genes had high clinical validity (AUC = 0.909). Core gene expression was associated with immune cell infiltration. A total of 5672 genes showed differential expression in TGF-related patterns, with differences in biological functions and immune infiltration. TGF-β signaling pathway may be critical in DFU development.

Large full-thickness skin lesions have been one of the most challenging clinical problems in plastic surgery repair and reconstruction. To achieve in situ skin regeneration and perfect clinical outcomes, we must address two significant obstacles: angiogenesis deficiency and inflammatory dysfunction. Recently, black phosphorus has shown great promise in wound healing. However, few studies have explored the bio-effects of BP to promote in situ skin regeneration based on its nanoproperties. Here, to investigate whether black phosphorus nanosheets have positive bio-effects on in situ skin repair, we verified black phosphorus nanosheets' positive effects on angiogenic and anti-inflammatory abilities in vitro. Next, the in vivo evaluation performed on the rat large full-thickness excisional wound splinting model more comprehensively showed that the positive bio-effects of black phosphorus nanosheets are multilevel in wound healing, which can effectively enhance anti-inflammatory ability, angiogenesis, collagen deposition, and skin re-epithelialization. Then, multiomics analysis was performed to explore further the mechanism of black phosphorus nanosheets' regulation of endothelial cells in depth. Molecular mechanistically, black phosphorus nanosheets activated the JAK-STAT-OAS signaling pathway to promote cellular function and mitochondrial energy metabolism in endothelial cells. This study can provide a theoretical basis for applying two-dimensional black phosphorus nanosheets as nanomedicine to achieve in situ tissue regeneration in complex human pathological microenvironments, guiding the subsequent optimization of black phosphorus.

Introduction: Diabetic ulcers have become one of the major complications of diabetes mellitus (DM) and are a leading cause of death and disabling disease. However, current therapies are not effective enough to meet clinical needs. A traditional Chinese medicine (TCM) formula, Pien Tze Huang (PZH), is known as a medicine that is used to treat diabetic ulcers. Methods: In this study, PZH (0.05 g/cm2 and 0.15 g/cm2) and the positive drug-rhEGF were topically administered in a high-fat diet (HFD) and streptozotocin (STZ)-induced diabetic full-thickness incisional wounds, respectively. Wound healing was assessed by wound closure rate, two-photon microscope (SHG), staining with Hematoxylin and eosin (H&E), and Masson's trichrome (MTC). Then, RNA sequencing (RNA-seq) analysis, Enzyme-linked immunosorbent assay (ELISA), western blotting, and immunofluorescence (IF), network analysis, were performed. Results and discussion: The results showed that PZH significantly accelerated wound healing, as well as enhanced the expression of collagen. RNA-seq analysis showed that PZH has functions on various biological processes, one of the key biological processes is inflammatory response. Tlr9, Klrk1, Nod2, Tlr2, and Ifng were identified as vital targets and the NF-κB signaling pathway was identified as the vital pathway. Additionally, PZH profoundly reduced the levels of Cleaved caspase-3 and promoted the expression of CD31 and TGF-β1. Mechanically, PZH significantly decreased expression of NKG2-D, NOD2, and TLR2, and further inhibited the activation of downstream NF-κB signaling pathway and inhibited expression of inflammatory factors (IFN-γ and IL-1β). Importantly, we found that several active ingredients may play a significant role in diabetic wound healing, including Notoginsenoside R1, Deoxycorticosterone, Ursolic acid, and 4-Methoxyphenol. In summary, our study sheds light on the complicated mechanisms underlying the promising anti-diabetic wounds of PZH and provides the discovery of agents treating diabetic ulcers.

The aim of this study was to analyze the link between periodontal microbiota and obesity in humans. We conducted a cohort study including 45 subjects with periodontitis divided into two groups: normo-weighted subjects with a body mass index (BMI) between 20 and 25 kg/m2 (n = 34) and obese subjects with a BMI > 30 kg/m2 (n = 11). Our results showed that obesity was associated with significantly more severe gingival inflammation according to Periodontal Inflamed Surface Area (PISA index). Periodontal microbiota taxonomic analysis showed that the obese (OB) subjects with periodontitis were characterized by a specific signature of subgingival microbiota with an increase in Gram-positive bacteria in periodontal pockets, associated with a decrease in microbiota diversity compared to that of normo-weighted subjects with periodontitis. Finally, periodontal treatment response was less effective in OB subjects with persisting periodontal inflammation, reflecting a still unstable periodontal condition and a risk of recurrence. To our knowledge, this study is the first exploring both salivary and subgingival microbiota of OB subjects. Considering that OB subjects are at higher periodontal risk, this could lead to more personalized preventive or therapeutic strategies for obese patients regarding periodontitis through the specific management of oral microbiota of obese patients.

The current treatments for diabetic foot ulcers have disadvantages of slow action and numerous complications. Tibial cortex transverse transport (TTT) surgery is an extension of the Ilizarov technique used to treat diabetic foot ulcers, and can shorten the repair time of diabetic foot ulcers. This study assessed the TTT technique for its effectiveness in healing diabetic foot ulcer skin lesions and its related molecular mechanisms.

Diabetic rat models were established by injecting healthy Sprague-Dawley rats with streptozotocin (STZ). The effects of TTT surgery on the model rats were assessed by recording changes in body weight, analyzing skin wound pictures, and performing H&E staining to assess the recovery of wounded skin. The numbers of endothelial progenitor cells (EPCs) in peripheral blood were analyzed by flow cytometry, and levels of CXCR4 and SDF-1 expression were qualitatively analyzed by immunofluorescence, immunohistochemistry, qRT-PCR, and western blotting.

Both the histological results and foot wound pictures indicated that TTT promoted diabetic wound healing. Flow cytometry results showed that TTT increased the numbers of EPCs in peripheral blood as determined by CD34 and CD133 expression. In addition, activation of the SDF-1/CXCR4 signaling pathway and an accumulation of EPCs were observed in skin ulcers sites after TTT surgery. Finally, the levels of SDF-1 and CXCR4 mRNA and protein expression in the TTT group were higher than those in a blank or fixator group.

TTT promoted skin wound healing in diabetic foot ulcers possibly by activating the SDF-1/CXCR4 signaling pathway.

Infectious diabetic ulcers (IDU) require anti-infection, angiogenesis, and nerve regeneration therapy; however, the latter has received comparatively less research attention than the former two. In particular, there have been few reports on the recovery of mechanical nociception. In this study, a photothermal controlled-release immunomodulatory hydrogel nanoplatform is tailored for the treatment of IDU. Due to a thermal-sensitive interaction between polydopamine-reduced graphene oxide (pGO) and the antibiotic mupirocin, excellent antibacterial efficacy is achieved through customized release kinetics. In addition, Trem2+ macrophages recruited by pGO regulate collagen remodeling and restore skin adnexal structures to alter the fate of scar formation, promote angiogenesis, accompanied by the regeneration of neural networks, which ensures the recovery of mechanical nociception and may prevent the recurrence of IDU at the source. In all, a full-stage strategy from antibacterial, immune regulation, angiogenesis, and neurogenesis to the recovery of mechanical nociception, an indispensable neural function of skin, is introduced to IDU treatment, which opens up an effective and comprehensive therapy for refractory IDU.