It has been demonstrated that glutamine is a key player in boosting endothelial cell (EC) proliferation. However, despite its importance, the role of endothelial glutaminolysis in diabetes remains largely unexplored. Our research aimed to investigate the function of glutaminolysis in ECs within the context of diabetes and to evaluate the potential therapeutic effects of salvianolic acid B (SalB) and α-ketoglutarate (α-KG) on diabetic vascular complications. Histological analysis of skin wounds in diabetic patients revealed delayed restoration of vascularization and collagen synthesis during wound healing, accompanied by decreased glutaminase 1 (GLS1) expression and reduced colocalization with the EC marker platelet-endothelial cell adhesion molecule-1 (CD31). Additionally, a significant decline in GLS1 activity and expression was observed in ECs isolated from diabetic hearts. In vitro studies using cultured ECs demonstrated that exposure to high glucose and high fat (HGHF) reduced GLS1 expression and suppressed glutaminolysis, impairing EC proliferation and tube formation. These adverse effects were mitigated by treatment with SalB or supplementation with α-KG plus nonessential amino acids (NEAAs). Among diabetic mice subjected to myocardial ischemia/reperfusion (MI/R), SalB administration or α-KG supplementation promoted myocardial revascularization and improved cardiac dysfunction. Notably, endothelial-specific GLS1 deletion in mice blocked the beneficial effects afforded by SalB but not those afforded by α-KG. Furthermore, SalB administration accelerated angiogenesis and cutaneous wound healing in diabetic mice, and these influences were removed by pharmacological inhibition of GLS1 using bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl) ethyl sulfide (BPTES) or genetic deletion of endothelial GLS1. These findings indicate that defective endothelial glutaminolysis contributes to impaired angiogenesis and poor ischemic tissue repair in diabetes. Improving endothelial glutaminolysis by treatment with SalB or metabolic supplementation with α-KG promotes angiogenesis and ischemic tissue repair in diabetic mice, emphasizing the possibility of GLS1 as a treatment target.

This review article examines how stem cell therapies can cure various diseases and injuries while also discussing the difficulties and moral conundrums that come with their application. The article focuses on the revolutionary developments in stem cell research, especially the introduction of gene editing tools like CRISPR-Cas9, which can potentially improve the safety and effectiveness of stem cell-based treatments. To guarantee the responsible use of stem cells in clinical applications, it is also argued that standardizing clinical procedures and fortifying ethical and regulatory frameworks are essential first steps. The assessment also highlights the substantial obstacles that still need to be addressed, such as the moral dilemmas raised by the use of embryonic stem cells, the dangers of unlicensed stem cell clinics, and the difficulties in obtaining and paying for care for patients. The study emphasizes how critical it is to address these problems to stop exploitation, guarantee patient safety, and increase the accessibility of stem cell therapy. The review also addresses the significance of thorough clinical trials, public education, and policy development to guarantee that stem cell research may fulfill its full potential. The review concludes by describing stem cell research as a promising but complicated topic that necessitates a thorough evaluation of both the hazards and the benefits. To overcome the ethical, legal, and accessibility obstacles and eventually guarantee that stem cell treatments may be safely and fairly included in conventional healthcare, it urges cooperation between the scientific community, legislators, and the general public.

Background: To investigate the current situation of nosocomial infections in oral cancer patients after surgery, explore possible risk factors for nosocomial infections, screen high-risk populations for nosocomial infections after oral cancer surgery in the early stage, and provide scientific basis for the prevention and control of nosocomial infections in oral cancer patients after surgery.

Methods: 201 patients with oral cancer who underwent surgery in the Department of Oral and Maxillofacial Surgery of our hospital from January 2019 to December 2023 were collected, and their clinical data were observed. Statistics on the incidence of nosocomial infections, infection sites, and pathogenic bacteria in patients undergoing oral cancer surgery. Through univariate analysis and multivariate logistic regression analysis, identify the risk factors for nosocomial infections in oral cancer patients after surgery.

Results: This study included 201 patients undergoing oral cancer surgery, with 24 cases of nosocomial infections and a nosocomial infection rate of 11.91%. Surgical incision infection is the most common site of infection, accounting for 45.83%, followed by pulmonary infection, accounting for 33.33%. Through pathogen examination, a total of 22 strains of pathogens were found, including 14 Gram negative bacteria (63.64%) and 7 Gram positive bacteria (31.82%). The univariate analysis found that 11 items included: smoking history, drinking history, diabetes, operation duration, skin flap repair, intraoperative bleeding, preventive use of antibiotics, tracheal intubation, gastric tube retention time, venous thromboembolism on the operation day, preoperative oral scaling, which may be the risk factors for nosocomial infection after oral cancer surgery. Logistic regression analysis showed that six independent risk factors of nosocomial infection after oral cancer surgery included: diabetes, skin flap repair, intraoperative bleeding, tracheal intubation, gastric tube retention time, and venous thromboembolism on the day of operation.

Conclusion: Oral cancer surgery patients are at high risk of infection, and targeted monitoring of oral cancer surgery patients should be strengthened. Preventive measures should be taken for risk factors to reduce nosocomial infection rates.

Diabetic foot ulcers (DFUs) are a severe diabetic complication, frequently resulting in infections and amputations. The current research focuses on the development and assessment of a synergistic nano-herbal formulation based on green-synthesized silver nanoparticles and a polyherbal gel for the efficient treatment of DFUs. Silver nanoparticles (AgNPs) were green-synthesized using aqueous extracts of Tagetes erecta (Marigold) and Portulaca oleracea (Purslane). They were further blended with a polyherbal gel formulation to improve antimicrobial and wound-healing activities. AgNPs were synthesized using aqueous plant extracts and characterized through UV-Visible spectrophotometry (SPR peaks: 439 nm for T. erecta, 427 nm for P. oleracea), FT-IR (O-H stretching at 3610 cm⁻¹, 3687 cm⁻¹), XRD (semi-crystalline structure), and DLS (particle sizes: 311 nm and 304 nm, zeta potentials: -19.7 mV and -20.1 mV, respectively). Antimicrobial studies showed strong inhibition against S. aureus (21 mm, 20 mm) and K. pneumoniae (22 mm) for AgNPs. The polyherbal gel, incorporating extracts of Ficus racemosa, Emblica officinalis, Curcuma longa, Carica papaya, Terminalia bellerica, Acacia catechu, and Aloe vera, achieved 85% wound closure in diabetic rats by day 16, compared to 60% (untreated) and 95% (povidone iodine). AgNP-antibiotic combinations reached 90% healing. HbA1c levels remained unchanged, indicating glucose-independent healing. These findings suggest that AgNP-polyherbal formulations could serve as a sustainable and effective DFU treatment, enhancing antimicrobial activity and promoting tissue regeneration.

Objective: While the prevailing practice for treating chronic limb threatening ischaemia (CLTI) is revascularisation, we have a limited understanding of disease progression in patients with CLTI who do not undergo this intervention. This study compared the prognosis of CLTI patients with tissue loss who underwent revascularisation with the prognosis of those who were managed with non-revascularisation treatment, investigating the efficacy of revascularisation in improving the outcome of CLTI patients.

Methods: Utilising the Shizuoka Kokuho Database, a regionally representative longitudinal cohort in Japan, this retrospective analysis examined CLTI patients with tissue loss (ulcer and gangrene), between April 2012 and September 2020, identifying two distinct cohorts: those receiving non-revascularisation treatment and those undergoing revascularisation. The primary endpoint was amputation free survival, evaluated in both cohorts after applying post-propensity score matching.

Results: Of the 3 160 CLTI patients with tissue loss, 559 received non-revascularisation treatment, and 589 underwent revascularisation. The non-revascularisation treatment predominantly involved prostaglandin E1 injections (99.1%). After one to one propensity score matching, the revascularisation cohort (372 patients) exhibited a markedly enhanced amputation free survival rate compared with their non-revascularisation counterparts (amputation free survival rate at one year: 58.0% vs. 45.7%, p = .014). Subgroup analyses underscored the greater efficacy of revascularisation across multiple categories, including male (hazard ratio [HR] 0.59, 95% confidence interval (CI) 0.47 - 0.75), diabetes mellitus (HR 0.67, 95% CI 0.50 - 0.89), and patients with severe wounds (HR 0.76, 95% CI 0.61 - 0.93). However, the analysis did not find differences between the revascularisation and non-revascularisation treatment groups among female patients (HR 1.06, 95% CI 0.78 - 1.45) and patients with non-severe wounds (HR 0.87, 95% CI 0.58 - 1.30).

Conclusion: This regional Japanese cohort study reveals a potential enhancement in the amputation free survival rate post-revascularisation for CLTI patients with tissue loss compared with non-revascularisation treatment, except in female patients and patients with non-severe wounds. Additional studies are needed to further elucidate these results.

Hydrogel dressings have emerged as promising tools for wound healing applications. However, the complex chemical synthesis and high cost of components, such as cytokines and stem cells, in most existing designs challenge their practical application. In this study, we adopted a modular design approach and natural materials to overcome these limitations, dividing the hydrogels into three distinct functional modules. The base module consisted of an interpenetrating polymer network of gelatin and chitosan. The drug release module incorporated liposomes loaded with quercetin, while the auxiliary module utilized a complex of protocatechuic aldehyde and trivalent iron. The presence of Schiff base crosslinking and hydrogen bond formation between the three modules enhanced the self-healing properties and mechanical strength of the hydrogel. Notably, the modular hydrogel exhibited excellent antioxidant, antibacterial, macrophage differentiation, and collagen promotion capabilities. This multifunctional hydrogel demonstrated the potential to provide safe and effective treatment, accelerate wound repair processes, and serve as a promising dressing for diabetic wound management. By utilizing natural components and a modular design strategy, this hydrogel offers a practical and cost-effective solution for improving wound healing outcomes, particularly in drug-resistant and diabetic wounds.

Hypoxia, persistent inflammation, excessive reactive oxygen species (ROS), bacterial infection, immune regulation disorder, and impaired angiogenesis are critical factors hindering diabetic wound healing. So far, clinical treatment still lacks comprehensive solutions to address these challenges. The main objective of this study is to develop and evaluate a novel multifunctional nanomaterial (Gen-BioCa/i-ZnPPOPs@HA) for enhancing the treatment of bacterial-infected diabetic wounds through a combination of photodynamic therapy, oxygen self-supply, and acetate supplementation. When infection occurs, Hyaluronic Acid (HA) shells are initially decomposed by hyaluronidase (HAase) secreted by the bacteria, releasing Gen, biomass Calcium peroxide (BioCa) and ionic porphyrin-based polyporous organic polymer (i-ZnPPOPs). BioCa decomposes to oxygen and Ca(OH)₂, which alleviates the hypoxia in diabetes wounds and neutralize lactic acid released by the damaged blood vessels. Under NIR irradiation, cationic i-ZnPPOPs combined with Gen showed bacteria-targeting capacity, rapid and high-efficient microbicidal activity. The vitro/vivo experiments results revealed that Gen-BioCa/i-ZnPPOPs@HA could promote macrophages toward M2 polarization, accelerating angiogenesis, collagen deposition and tissues remodeling. In addition, further introduction of acetate supplement shorten the inflammatory period and accelerated wound healing process. This study provides a new strategy for the treatment of chronic bacterial infectious diseases, indicating the important potential of multifunctional nanomaterials in chronic wounds treatment.

Persistent excessive inflammatory response in diabetic wounds caused by the imbalance of the immune microenvironment leads to delayed or nonhealing of the wounds. Timely attenuation of inflammation through immunoregulation is a crucial strategy to accelerate diabetic wound closure. Here, the protocatechuic acid (PCA)- and deferoxamine (DFO)-loaded polysaccharide-based immunoregulatory hydrogel (POCP@D) was developed by the dual-cross-linking strategy of borate ester bonds and imine bonds to promote advanced healing of full-thickness diabetic wounds. The POCP@D hydrogel showed good tissue adhesiveness property, flexibility, mechanical strength, injectability, self-healing, and glucose-responsive drug release properties, besides strong broad-spectrum antibacterial and antioxidant activities. The POCP@D hydrogel acted as an immunoregulatory platform to remold the in vivo immune microenvironment of diabetic wounds by regulating the M2-type macrophage polarization and timely relieving wound inflammation, thus promoting collagen deposition, angiogenesis, and the development of diabetic wounds from the inflammatory stage to the proliferative stage and ultimately achieving high-quality skin tissue regeneration. Overall, our developed immunoregulatory hydrogel held great potential for refractory diabetic wound therapy in clinical settings.

Introduction: A systematic review was conducted to investigate the efficacy of acellular fish skin grafts (AFSGs) for the treatment of complicated wounds. AFSGs can be used as a regenerative and antimicrobial tool for healing complicated wounds, but clinical evidence remains unclear.

Objective: This systematic review aimed to summarize the efficacy of AFSGs on complicated wounds using evidence from existing published studies.

Methods: Electronic databases like PubMed, ScienceDirect, Google Scholar, and Clinicaltrials.gov were searched for relevant literature reporting on the efficacy of AFSGs for wound healing. Based on the inclusion and exclusion criteria, nine studies were selected for data extraction. The quality of the articles was evaluated using the RoB 2 and ROBINS-I tools.

Results: Existing evidence shows that AFSGs accelerate wound healing, reduce pain, prevent antibiotic administration, and cause no autoimmune reactions. The total re-epithelialization time for diabetic foot ulcers (DFUs) was observed as 15 ± 8 weeks, depending on the severity of the ulcers. Acute full thickness biopsy wounds healed within 3.75 ± 0.25 weeks. As reported in papers, AFSGs showed significantly better effects than standard-of-care therapy, collagen alginate dressings, dehydrated human AMNION/chorion membrane, and/ or porcine small-intestine submucosa. However, instances of rashes, erythema, pain, and hypergranulation were reported when AFSGs were applied to biopsy wounds.

Conclusion: Overall, the evidence obtained in this systematic review indicates that AFSGs represent a clinically and financially effective option for the treatment of wounds when compared with conventional alternatives.

Objective: Conditioned medium of umbilical cord mesenchymal cells is a rich environment in various growth factors and cytokines, the use of which causes self-improvement and self-renewal in damaged tissues.

Methods: Therefore, we investigated the effect of Wharton's umbilical cord mesenchymal cells on cytokines, growth factors expression, and skin wound healing in diabetic rats. Rats were divided into two groups of ten. In the treated diabetic group, 1 ml of conditioned medium was used intradermally, and in the diabetic control group, the same amount of physiological serum was used. The tissue samples were evaluated for histological studies. The expression level of inflammatory/anti-inflammatory cytokines and growth factors was investigated using RT-PCR and western blotting analysis.

Results: Our results showed that wound healing increased in the diabetic rat group with a pleasant environment compared to the control group. It was also found in molecular studies that the expression of anti-inflammatory cytokines and growth factors was significantly increased in the treated samples compared to the control group. In addition, a significant decrease in TGF-β expression as an important inflammatory cytokine observed compared to the control group.

Conclusions: The use of the conditioned environment of Wharton's jelly mesenchymal cells of the human umbilical cord improves the process of wound healing in terms of tissue and also increases the expression of the critical anti-inflammatory cytokines and growth factors. It can be considered a novel approach in wound healing treatment.

Mucormycosis is a rare, opportunistic, and life-threatening fungal infection caused by fungi of the order Mucorales, which includes Rhizopus, Mucor,and Rhizomucor. This disease occurs in immunocompromised patients such as those with uncontrolled diabetes mellitus, hematologic malignancies, transplants, trauma, burns, or receiving glucocorticoid therapy. Mucormycosis can present in various ways, including rhino-orbital-cerebral, pulmonary, cutaneous, gastrointestinal, and disseminated disease. Osteoarticular mucormycosis, with the exclusion of bone extension from rhinosinusitis, is an exceedingly rare manifestation. Here, we present a 48-year-old female with uncontrolled type 1 diabetes mellitus who presented with diabetic ketoacidosis. During her hospital course, it was discovered that she had fallen in the woods before presentation, which caused her to develop a left knee wound concerning for osteomyelitis. After symptomatic improvement with antibiotics, she was discharged home, only for us to find out afterwards that her wound biopsy culture grew Rhizopus; thus, diagnosing her osteoarticular mucormycosis. She unfortunately was lost to follow-up and was never able to get started on the appropriate treatment. We discuss the clinical manifestations, useful diagnostic tools, and treatment of osteoarticular mucormycosis. We also reflect on how our delay in diagnosis led to our patient being discharged without appropriate treatment in hopes of avoiding similar situations in the future.

Background: The diabetic foot ulcer (DFU) is a common and serious complication of diabetes mellitus, which occurs in 15-25% of diabetic patients at some point in their lives. However, most of the Diabetic foot ulcers (DFUs) do not heal with conventional methods of wound care and progress to become chronic, non-healing ulcers with high morbidity, mortality, and economic stakes. Some of the recent techniques in the management of ulcers include Systemic Hyperbaric Oxygen Therapy (s-HBOT), Platelet-Rich Plasma (PRP), Vacuum-Assisted Closure (VAC) Therapy, and Negative Pressure Wound Therapy (NPWT) that aim at improving the ulcer healing rate and minimize the risks of amputation.

Objective: This work intends to conduct a comprehensive meta-analysis of the effectiveness, healing time and effect on amputation of these advanced treatment modalities on management of DFUs.

Methods: The present study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for the reporting of systematic reviews and meta-analysis of randomized controlled trials. Information was obtained from 10 researches that considered different types of DFU treatment. The major end-points studied were rates of ulcer healing, time to heal and frequency of lower extremity amputations. The meta-analysis was conducted using R statistical software and the synthesis of results was done using forest and funnel plots.

Results: The pooled analysis showed that NPWT significantly improved ulcer healing rates (OR = 2.07, 95% CI: 1.09-3.05) and reduced time to healing (Mean Diff = -22 days, 95% CI: -41.60 to -2.40). HBOT, particularly s-HBOT, demonstrated a substantial reduction in amputation rates (OR = 0.08, 95% CI: -0.11-0.28). PRP also showed promise, especially in reducing healing time (Mean Diff = -25 days, 95% CI: -34.80 to -15.20), though with more variability across studies.

Conclusion: The results of NPWT were found to be significantly superior for ulcer closure and reduced healing time making it the treatment of choice for DFUs. Compared to controls, both HBOT and s-HBOT were strikingly effective in averting amputations. PRP had the possibility of being used as supplementary treatment especially in treatment with regard to the aspect of promotion of healing. Collectively, these results suggest that it is possible to use such advanced therapies to enhance the treatment of DFU; however, more effort is required to refine the protocols of such therapies and determine the sources of a differential response.

In modern society, the need for diabetic wound healing is increasing due to the increase in the number of diabetic patients. In particular, chronic inflammation is a major problem in diabetic wounds due to excessive accumulation of reactive oxygen species (ROS). Therefore, it is essential to remove ROS and promote angiogenesis for effective diabetic wound healing. In this study, we developed a thermo-responsive poly(organophosphazene) hydrogel system (TSP-TP) designed to deliver antioxidants and growth factors for a long period of time. The TSP-TP hydrogel stably loads and continuously releases tannic acid (TA) and platelet-derived growth factor (PDGF) through various physical interactions. Effective ROS scavenging induced macrophage polarization and alleviated chronic inflammation, while the sustained release of PDGF promoted angiogenesis, ultimately maximizing wound healing efficacy in a diabetic mouse model. Based on these results, the proposed TSP-TP hydrogel demonstrates synergistic effects through sustained delivery of antioxidants and growth factors, demonstrating a promising system with high applicability in diabetic wound treatment.

BackgroundChronic lower extremity ulcers (CLEU) are a significant health burden, often linked to complications such as diabetes and vascular diseases. Chronic kidney disease (CKD), a prevalent global health issue, has been increasingly associated with CLEU, though the nature of this relationship remains poorly understood. This study aimed to explore the association between CKD and CLEU in the US adult population.MethodsWe analyzed data from the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2004. The study included adults aged 20 years and older who completed interviews and examinations. CLEU was defined as self-reported ulcers or sores on the leg or foot lasting more than four weeks. CKD was diagnosed based on the 2012 KDIGO guidelines, using estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (UACR). Logistic regression models were used to assess the association between CKD and CLEU, adjusting for demographics, BMI, lifestyle factors, and comorbidities.ResultsAmong 8564 participants, individuals with CKD had a higher likelihood of developing CLEU, with an unadjusted odds ratio (OR) of 2.33 (95% CI: 1.86-2.91). After adjusting for confounders, the association remained significant, with adjusted ORs of 1.64 (95% CI: 1.26-2.12) and 1.57 (95% CI: 1.2-2.04) in Models 2 and 3, respectively. Stratified analyses showed no significant interactions across subgroups defined by age, sex, diabetes, hypertension, hyperlipidemia, and peripheral artery disease (PAD).ConclusionThis study demonstrates a robust association between CKD and CLEU in US adults, suggesting that CKD is an independent risk factor for CLEU. These findings highlight the need for integrated management strategies for CKD patients to reduce the risk of CLEU. Future longitudinal studies are needed to establish causality and inform targeted interventions.

Diabetic foot patients frequently experience delayed wound healing due to compromised vascularity and oxygenation, which increases the risk of graft failure. Hyperbaric oxygen therapy (HBOT) has demonstrated potential in enhancing graft survival and accelerating wound healing in these patients. This study aimed to assess the efficacy of HBOT in improving graft success and wound healing rates in diabetic foot patients undergoing foot graft reconstruction. Forty-five diabetic patients with tissue defects requiring graft procedures were included. Among these, 28 patients received HBOT (2.4 ATA for 120 min daily), and 17 served as controls. Wound healing was assessed based on milestones of wound closure (25%, 50%, 75% and complete healing). The control group consisted of patients with adequate graft nutrition who did not require HBOT or were unable to undergo HBOT for other reasons. Statistical analyses were performed to compare healing times and graft retention rates between the two groups. Patients in the HBOT group exhibited significantly faster healing, with a median time to 50% healing of 18 days compared to 30.5 days in the control group (p < 0.05). A moderate negative correlation was observed between graft retention rates and time to complete healing (p < 0.05), indicating that higher graft retention was associated with shorter healing times. Despite higher HbA1c levels in the HBOT group, favourable healing outcomes were achieved. No adverse effects were reported in the HBOT group. HBOT significantly enhances graft survival and accelerates wound healing in diabetic foot patients, even in cases with poor glycaemic control. HBOT emerges as a valuable adjunctive treatment for patients with compromised vascular beds and hypoxic tissues. Future randomised controlled trials are needed to validate these results.

Tarsal tunnel syndrome (TTS) is elicited by compression of the tibial nerve in the tarsal tunnel. TTS in the absence of a lesion tends to be idiopathic, and most TTS is idiopathic. Patients complain of several plantar symptoms, and TTS affects their quality of life. The symptoms tend to worsen with walking, and ankle joint movement and arterial distortion may also be involved. Because TTS symptoms are similar to those of diabetic neuropathy and lumbar disease, clinical symptoms are diagnostically important. While magnetic resonance imaging reveals nerve compression, it is difficult to identify causative factors, and false-positive results are a concern. Wound-related complications after TTS surgery may be reduced by a zigzag skin incision. Surgery for carpal tunnel syndrome yields better outcomes and greater patient satisfaction than TTS surgery.

A young male patient presented with acute onset spastic quadriparesis. Clinically, he exhibited features of acromegaly alongside spastic quadriparesis. Neuroimaging revealed an osteophyte complex causing cord compression and canal stenosis. Biochemical and radiological assessments confirmed a growth hormone-secreting pituitary macroadenoma. He underwent anterior cervical discectomy with vertebral fusion of the cervical cord to relieve his neurological symptoms. His acromegaly was subsequently managed with surgery, followed by radiotherapy and medical therapy. While acromegaly may rarely present as a metabolic emergency, neurological emergencies are exceptionally rare. This is the first case report of acromegaly, which was recognised on presentation with an osteophyte complex causing quadriparesis.

A functional and biocompatible biomaterial is essential for accelerating the regeneration of skin tissue at the wound site. Hydrogel scaffolds in three dimensions show promising candidates for this purpose. This study was conducted to design a novel porous cross-linked alginate (Alg) hydrogel containing green tea (GT) and assess its morphology, swelling, weight loss, hemocompatibility, and cytocompatibility. Ultimately, the created hydrogel's therapeutic effectiveness was examined in a complete dermal diabetes wound model. The findings indicated that the hydrogel prepared had significant porosity, with interconnected pores around 75.821 µm in size. The weight loss evaluation indicated that the created hydrogel can be degraded naturally, with a weight loss ratio of about 74% for Alg/GT 80 mg after being incubated for 24 hours. Additionally, the study indicated that hydrogel dressings exhibited greater wound closure compared to gauze-treated wounds, which served as the control. The group with GT at a concentration of 80 mg showed the highest percentage of wound closure. The histopathological studies and IHC evaluation for TGF-β1 confirmed the in vivo finding. This study proposes utilizing 3D Alg hydrogels with GT as a wound dressing, but further studies are needed.

Drug-resistant bacterial and biofilm infections, vascularization disorders, and inadequate hemostasis are the key factors that limit chronic diabetic wound healing. Here, we construct a microenvironment-responsive multifunctional platinum-armed iron-based MOF nanocomposite (Pt@FeMOF) to repair chronic wounds. Under acidic conditions (biofilm environment), Pt@FeMOF nanoparticles (NPs) produce reactive oxygen species via a synergistic Fenton reaction to eliminate both drug-resistant bacteria and their biofilms. Furthermore, based on transcriptomic results and ferroptosis marker evaluation, we reveal that the Pt@FeMOF NPs induce ferroptosis in bacteria via lipid peroxidation, GSH depletion, iron overload, and disruption of arginine metabolism. In addition, the Pt@FeMOF NPs promote vascular repair, possibly by inhibiting oxidative stress-mediated endothelial cell senescence in the microenvironment to restore angiogenesis. Finally, the Pt@FeMOF NPs are loaded into GelMA cryogels to further improve their hemostasis and exudate absorption. In vivo experiments demonstrate that Pt@FeMOF NPs-loaded cryogel dressings effectively promote MRSA- and P. aeruginosa-infected diabetic wounds. This ferroptosis-like antibacterial strategy may provide novel insights into the treatment of drug-resistant bacterial infections and fight against biofilm-associated infections. The proposed tactic provides a promising approach for the clinical treatment of diabetic wounds.

Background: Burn injuries can lead to severe complications across multiple organ systems, with kidney impairment being particularly common and clinically significant. Major adverse kidney events within 30 days post-surgery (MAKE30)-including death, initiation of new renal replacement therapy, or prolonged renal dysfunction-are increasingly used in clinical research to assess mid-term renal outcomes. However, studies on the incidence and risk factors of MAKE30 in burn patients remain limited.

Methods: We included burn patients admitted to a single-center burn intensive care unit between 2012 and 2022, excluding those with pre-existing kidney disease. The incidence of MAKE 30 was evaluated, and logistic regression analysis was performed to identify associated risk factors.

Results: Among 848 burn patients who underwent burn surgery during the study period, 286 (33.7 %) developed MAKE30. Postoperative acute kidney injury (AKI), age, diabetes mellitus, inhalation injury, deep burn area, intraoperative vasopressor use, fresh frozen plasma transfusion, and urine output were significantly associated with MAKE30. The incidence of MAKE30 was markedly higher in patients who developed postoperative AKI compared to those who did not (89.6 % vs. 18.3 %, p < 0.001). Additionally, chronic kidney disease (CKD) was significantly more prevalent in patients with MAKE30 than in those without (12.0 % vs. 1.7 %, p < 0.001).

Conclusion: Postoperative AKI is a significant risk factor for MAKE30 following burn surgery, and affected patients exhibit a substantially higher incidence of CKD. This study provides single-center data on incidence and its associated risk factors of MAKE30, underscoring the importance of early kidney function monitoring and intervention in this population.

Diabetic foot ulcer (DFU) is a prevalent and challenging clinical condition characterized by impaired microcirculation, chronic wound infections, and a hyperglycemic, high-reactive oxygen species (ROS) environment. These factors make treatment particularly complex, often requiring a multidisciplinary approach that yields suboptimal results. In this study, a novel therapeutic strategy was developed using metal-polyphenol nanoparticles synthesized from (-)-Epigallocatechin-3-gallate (EGCG) and ferric ions (Fe³⁺). These nanoparticles were further loaded with salvianolic acid B (SAB) and glucose oxidase (GOx) to enhance their multifunctional biological properties. Complementing these nanoparticles, a polysaccharide hydrogel was engineered using quaternized chitosan (QCS) and oxidized fucoidan (OFu), forming a robust and stable network through Schiff base linkages. This innovative platform demonstrated strong antibacterial activity against DFU-associated pathogens. Within the ulcer's hostile microenvironment, the hydrogel degraded via dynamic bond cleavage, releasing nanoparticles that boosted mitochondrial metabolism, induced M2 macrophage polarization, promoted angiogenesis and reduced ROS levels. These combined effects accelerated tissue regeneration and wound healing. The results suggest that this advanced hydrogel system holds significant promise as a therapeutic option for improving DFU management and addressing its multifaceted challenges.

The era of relying on antibiotics for curing bacterial infections is rapidly approaching an end, necessitating development of non-antibiotic-based infection-control strategies. Dispersal of infectious biofilms is a potential strategy but yields dispersed bacteria in blood that may cause sepsis. We report a bromide-loaded, core-shell ZnO₂-nanoparticle/Ce-based metal-organic framework (ZnO₂@CeMOF/Br) of which the ZnO₂ core degrades at pH ≤ 6.5, leaving the MOF's Ce node intact. ZnO₂-core degradation initially generates a nonradical, relatively stable, low-oxidative hydrogen peroxide that can cleave matrix DNA causing dispersal of Staphylococcus aureus biofilms and reacts with bromide ions to form transient hypobromous acid. Hypobromous acid modulates macrophage polarization toward an M1-like phenotype to clear dispersed bacteria from blood. Subsequently the Ce³⁺/Ce⁴⁺ redox couple forming the Ce node acts as an electron shuttle upon oxidation/reduction to faciltate two catalytic reactions, maintaining hydrolysis of phosphodiester bonds and associated cleavage of matrix DNA as well as modulation of macrophage polarization. Neither growth of tissue cells or macrophages nor hemolysis are negatively affected by exposure to ZnO₂@CeMOF/Br nanocatalysts at a ZnO₂ nanoparticle over CeMOFs weight ratio ≤ 1.2, up until CeMOF concentrations less than at least 180 μg/mL. Under biosafe, low-turnover catalytic conditions, irrigation of infected wounds in diabetic mice with ZnO₂@CeMOF/Br nanocatalysts (90 μg/mL) results in 100% survival, fast recovery of healthy body temperature and weight, lower numbers of CFUs in blood and wound and organ tissues, and macrophage polarization toward an M1-like phenotype, demonstrating potential of ZnO₂@CeMOF/Br nanocatalysts for non-antibiotic-based infection control.

Islet transplantation is a promising therapy for insulin-dependent diabetes. However, immune rejection and insufficient vascularization hinder the survival and function of transplanted islets. Here, we show effective engraftment of vascularized and functional mouse and rat islets transplanted into biomaterial-remodeled spleens of nonimmunosuppressed rodents and human islets transplanted into the remodeled spleens of nonhuman primates (NHPs) on varying degrees of immunosuppression. We found evidence that konjac glucomannan-modified silica nanoparticles (KSiNPs) remodeled the spleen into an extracellular matrix (ECM)-rich, immunosuppressive niche to support the survival of syngeneic or xenogeneic islets. Transplanted islets in the remodeled spleens showed improved engraftment, neovascularization, and functionality and restored normoglycemia in streptozotocin (STZ)-induced type 1 diabetic models in the mice and macaques, with stable insulin and C-peptide secretion in mice for 90 days and macaques for 28 days. KSiNP injection and islet transplantation into macaque spleens under B-ultrasound guidance were preclinically feasible. These findings highlight the safety and effectiveness of spleen tissue remodeling in supporting the survival and function of transplanted islets, providing a promising strategy for treating type 1 diabetes mellitus (T1DM).

Background: Although sternal surgical site infections (SSI) are an important complication after cardiac surgeries, predictors of treatment failure are poorly studied.

Objectives: The aim of this study is to assess the clinical and microbiology predictors of a sternal SSI therapeutic failure.

Methods: Patients who presented a sternal SSI were retrospectively analyzed. Data regarding demographic characteristics, clinical findings, initial laboratory and radiologic findings and treatment of index sternal SSI were evaluated. Primary outcome was treatment failure, comprising infection relapse (clinical sternal SSI after complete treatment) or infection persistence (outpatient antimicrobial treatment failure). The microbiology was assessed at the index infection and in the outcome. P-values < 0.05 were considered statistically significant.

Results: Among 489 included patients, mean age was 58 years, 265 (55%) were female, 185 (38%) had diabetes mellitus. The overall prevalence of therapeutic failure was 14% (67), occurring in a median of 174 days (±41) after index cardiac surgery. Most frequent etiologies were cocci Gram-positive and Klebsiella pneumoniae. None of laboratory or thoracic tomographic findings presented during the index sternal SSI was related to outcome. After multivariate analysis, Staphylococcus aureus, carbapenem-resistant Gram-negative bacilli (GNB), fungi, diabetes mellitus and presence of mediastinitis/osteomyelitis were positive predictors of therapeutic failure.

Conclusions: Emerging carbapenem-resistant GNB, fungi and S. aureus were etiologies associated with higher risk of therapeutic failure in sternal SSI. DM and deep sternal wound infections were also contributing factors. Its clinical implications and the exact role of multi-resistant microorganism itself are subject for more studies.