Neutrophils extracellular traps and ferroptosis in diabetic wounds

Huang, Yumeng; Ding, Youjun; Wang, B.C.; Ji, Qian; Chen, Peng; Tan, Qian

doi:10.1111/iwj.14231

Cited by 6 publications

(7 citation statements)

References 114 publications

(236 reference statements)

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“…Conversely, nutritional and antioxidant indicators decreased in the same pattern. Our ndings support previous studies suggesting that DFU patients with impaired healing are closely linked to chronic in ammation [21][22][23] and coagulation abnormalities [24]. The anti brinolytic system can cause hemodynamic disorders [25] in the feet of diabetic patients, exacerbating endothelial dysfunctions in DFU [26].…”

Section: Discussionsupporting

confidence: 90%

Combined with dynamic serum proteomics and clinical follow-up to screen the serum proteins to promote the healing of diabetic foot ulcer

Zhao

Xie

Weng

et al. 2023

Preprint

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Objective Non-healing diabetic foot ulcers are a leading cause of disability and death in diabetic patients, which often results in lower limb amputation. This study aimed to investigate the impact of biomarkers on the healing of diabetic foot ulcers by utilizing dynamic serum proteomics and skin proteomic analysis, combined with clinical case follow-up studies. Methods To analyze dynamic serum proteomic changes in four groups, age-matched normal subjects, diabetic patients, pre-treatment diabetic foot ulcer patients, and healed diabetic foot ulcer patients were selected. The differential proteins were screened in conjunction with normal and diabetic foot ulcer skin proteomics. In this study, a total of 80 patients with diabetic foot ulcers were enrolled and monitored for 3–6 months during treatment. To verify the significance of the differential proteins, age-matched diabetic patients (240 patients) and healthy controls (160 patients) were included as controls. Results Dynamic serum proteomics trend showed that the level of negative regulatory proteins related to endothelial cell migration, angiogenesis, and vascular development was significantly decreased after treatment of diabetic foot ulcer. This study also found that there is an opposite trend of differential protein biological processes, which is mainly enriched in protein activation cascade, immunoglobulin production, and complement activation. The researchers identified the core proteins APOA1, LPA, and APOA2 through a convergence of serum and skin proteomics screening. Clinical cases further validated that APOA1 levels are decreased in diabetic foot ulcer patients and are correlated with disease severity. Conclusions Based on our dynamic proteomics and clinical case studies, our bioinformatic analysis suggests that APOA1 plays a critical role in linking coagulation, inflammation, angiogenesis, and wound repair, making it a key protein that promotes the healing of diabetic foot ulcers.

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Section: Discussionsupporting

confidence: 90%

Combined with dynamic serum proteomics and clinical follow-up to screen the serum proteins to promote the healing of diabetic foot ulcer

Zhao

Xie

Weng

et al. 2023

Preprint

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“…However, dysregulated NETs formation can contribute to tissue damage and impaired wound healing. [ 6 ] Studies have demonstrated that citrullinated histone 3 DNA (CitH3‐DNA) complex can serve as a marker of NETs. [ 14 ] When NETs are formed, they also release cfDNA outside the neutrophiles, which can be detected and measured as an indicator of NETs activity.…”

Section: Resultsmentioning

confidence: 99%

“…However, in a hyperglycemic environment of diabetic wounds, prolonged excessive activation and dysregulated apoptosis of neutrophils lead to enhanced susceptibility to NETosis, and formation progress of NETs, resulting in higher NETs release compared to healthy controls. NETs may aggravate inflammation and cause persistent injury to wound tissues [ 6 ] by promoting endothelial‐to‐mesenchymal transition in a Hippo‐dependent pathway, leading to reduced angiogenesis, [ 7 ] up‐regulating the inflammatory response through the cfDNA web or histone‐induced toll‐like receptor 9 (TLR‐9) / nuclear factor kappa‐B signaling pathway activation. [ 8 ]…”

Section: Introductionmentioning

confidence: 99%

“…Previous research has explored the disruption of NETs using deoxyribonuclease (DNase) in experimental models of diabetic wounds treatment—an approach approved by the US Food and Drug Administration (FDA) for treating inflammation‐related diseases. [ 6a ] However, its clinical application has been hindered by significant side effects, such as the liberation of bacteria trapped within NETs. [ 9 ] Considering that cfDNA webs are the dominant structure of NETs, the use of cationic nanoparticles for scavenging NETs by targeting cfDNA web through strong electrostatic interaction has gained prominence as a viable approach to attenuate the dysregulated inflammatory response in diabetic wounds.…”

Section: Introductionmentioning

confidence: 99%

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Innovative Bio‐based Hydrogel Microspheres Micro‐Cage for Neutrophil Extracellular Traps Scavenging in Diabetic Wound Healing

Xiao,

Ding,

Fang

et al. 2024

Advanced Science

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Neutrophil extracellular traps (NETs) seriously impede diabetic wound healing. The disruption or scavenging of NETs using deoxyribonuclease (DNase) or cationic nanoparticles has been limited by liberating trapped bacteria, short half‐life, or potential cytotoxicity. In this study, a positive correlation between the NETs level in diabetic wound exudation and the severity of wound inflammation in diabetic patients is established. Novel NETs scavenging bio‐based hydrogel microspheres ‘micro‐cage’, termed mPDA‐PEI@GelMA, is engineered by integrating methylacrylyl gelatin (GelMA) hydrogel microspheres with cationic polyethyleneimine (PEI)‐functionalized mesoporous polydopamine (mPDA). This unique ‘micro‐cage’ construct is designed to non‐contact scavenge of NETs between nanoparticles and the diabetic wound surface, minimizing biological toxicity and ensuring high biosafety. NETs are introduced into ‘micro‐cage’ along with wound exudation, and cationic mPDA‐PEI immobilizes them inside the ‘micro‐cage’ through a strong binding affinity to the cfDNA web structure. The findings demonstrate that mPDA‐PEI@GelMA effectively mitigates pro‐inflammatory responses associated with diabetic wounds by scavenging NETs both in vivo and in vitro. This work introduces a novel nanoparticle non‐contact NETs scavenging strategy to enhance diabetic wound healing processes, with potential benefits in clinical applications.

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“…Wound repair is a complex, multistage, and highly coordinated process . The typical wound healing process includes the inflammatory phase, proliferative phase, and remodeling phase; however, in diabetes, the normal progression through these stages is impaired. − In DFU, the healing process is interrupted and replaced by a persistent inflammatory state and long-term microcirculation defects . Under normal circumstances, the body produces reactive oxygen species (ROS) to prevent bacterial invasion and guard against wound infection. , However, in the hyperglycemic microenvironment of diabetes, excessive oxidative stress can lead to enhanced inflammatory responses, cell damage, hematopoietic disorders, reduced immune system function, increased risk of bacterial infection in wounds, and further delays in wound healing .…”

Section: Introductionmentioning

confidence: 99%

A Glucose-Responsive Hydrogel Platform Based on Poly(vinyl alcohol) for Enhanced Diabetic Wound Healing

Pan,

Wang,

Mei

et al. 2024

ACS Appl. Polym. Mater.

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Diabetic foot ulcers (DFUs) represent a common and challenging wound in clinical practice. The treatment of DFUs is hindered by various factors, including increased inflammation, impaired cell migration and proliferation, and abnormal blood vessel formation due to oxidative stress in a hyperglycemic environment. To enhance the therapeutic outcomes of DFUs, we have developed an intelligent hydrogel through modification with catechol and phenylboronic ester grafts. This hydrogel exhibits high glucose responsiveness and adhesiveness. The experiments have demonstrated that the dissociation of boronic ester bonds enables dynamic regulation of the diabetic microenvironment, allowing controlled release of antidiabetic drugs, thereby effectively promoting wound healing. The hydrogel possesses excellent tissue adhesion, conforming seamlessly to the skin and offering effective protection against external stresses during the tissue repair process in diabetic wounds. Research findings indicate that the hydrogel efficiently scavenges free radicals, ameliorating the oxidative stress at the wound site. Simultaneously, it facilitates cell migration, propelling angiogenesis, improving the healing process of diabetic wounds, and enhancing collagen deposition and tissue remodeling. This adhesive and glucose-responsive antioxidant hydrogel holds immense potential in the treatment of DFUs.

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Neutrophils extracellular traps and ferroptosis in diabetic wounds

Cited by 6 publications

References 114 publications

Combined with dynamic serum proteomics and clinical follow-up to screen the serum proteins to promote the healing of diabetic foot ulcer

Combined with dynamic serum proteomics and clinical follow-up to screen the serum proteins to promote the healing of diabetic foot ulcer

Innovative Bio‐based Hydrogel Microspheres Micro‐Cage for Neutrophil Extracellular Traps Scavenging in Diabetic Wound Healing

A Glucose-Responsive Hydrogel Platform Based on Poly(vinyl alcohol) for Enhanced Diabetic Wound Healing

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