Neutrophil Extracellular Traps Are Markers of Wound Healing Impairment in Patients with Diabetic Foot Ulcers Treated in a Multidisciplinary Setting

Yang, Shuofei; Z, Gu; Lü, Can; Zhang, Ting; Guo, Xiaojia; Xue, Guanhua; Zhang, Lan

doi:10.1089/wound.2019.0943

Cited by 70 publications

(76 citation statements)

References 37 publications

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“…While a full evaluation of DFU biomarkers is outside the scope of this review, briefly, some recent reports of wound exudate biomarkers for DFU wound healing include epithelial neutrophil-activating protein (ENA)-78 [ 254 ], c-x-c motif chemokine ligand 6 (CXCL6) [ 255 ], and MMP-9 [ 256 ]. A number of serum biomarkers have been identified, including albumin [ 257 ], PLR and NLR [ 122 , 258 ], angiopoietin-like 2 (ANGPTL2) [ 259 ], lipoprotein-associated phospholipase A2 and interleukin-18 (IL-18) [ 260 ], pentraxin 3 [ 261 ], T-cell differentiation markers [ 262 ], stem/progenitor cells [ 263 ], as well as neutrophil extracellular traps (NETs)-specific markers [ 264 ]. Recent genomic analyses of DFU have utilized circRNAs [ 265 , 266 , 267 ], lncRNAs [ 268 ], miRNAs [ 99 , 100 , 269 ], genetic polymorphisms [ 270 , 271 , 272 ], cytokine arrays [ 273 ], and network maps [ 274 ] for the identification of other potential biomarkers for DFU diagnosis and prognosis.…”

Section: Diagnostic Measuresmentioning

confidence: 99%

Diabetic Wound-Healing Science

et al. 2021

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Diabetes mellitus is an increasingly prevalent chronic metabolic disease characterized by prolonged hyperglycemia that leads to long-term health consequences. It is estimated that impaired healing of diabetic wounds affects approximately 25% of all patients with diabetes mellitus, often resulting in lower limb amputation, with subsequent high economic and psychosocial costs. The hyperglycemic environment promotes the formation of biofilms and makes diabetic wounds difficult to treat. In this review, we present updates regarding recent advances in our understanding of the pathophysiology of diabetic wounds focusing on impaired angiogenesis, neuropathy, sub-optimal chronic inflammatory response, barrier disruption, and subsequent polymicrobial infection, followed by current and future treatment strategies designed to tackle the various pathologies associated with diabetic wounds. Given the alarming increase in the prevalence of diabetes, and subsequently diabetic wounds, it is imperative that future treatment strategies target multiple causes of impaired healing in diabetic wounds.

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Section: Diagnostic Measuresmentioning

confidence: 99%

Diabetic Wound-Healing Science

et al. 2021

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“…This uptake of neutrophil-derived apoptotic bodies’ by infiltrating monocytes/macrophages helps resolve the inflammatory phase in a self-perpetuating manner by limiting inflammatory cell infiltration and shifting the production of eicosanoids from pro-inflammatory to anti-inflammatory mediators [ 22 , 23 , 24 ]. Unfortunately, however, in diabetic wounds the inflammatory phase is significantly prolonged by the disruption of mechanisms which both control the influx of neutrophils as well as regulate their inflammatory processes [ 12 , 21 , 25 ]. Interestingly, it seems that the cause of many observed dysregulations of the inflammatory phase is not directly associated with localized high glucose levels but rather the epigenetic polarization of innate immune cell pro-inflammatory function prior to wound infiltration, as in progenitor cell modification due to T2DM-related systemic complications such as hyperglycemia [ 26 ].…”

Section: Wound Inflammation Orchestrates Healing and Regenerationmentioning

confidence: 99%

Chronic Diabetic Wounds and Their Treatment with Skin Substitutes

Holl

Kowaléwski

Zimek

et al. 2021

Cells

166

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With the global prevalence of type 2 diabetes mellitus steeply rising, instances of chronic, hard-healing, or non-healing diabetic wounds and ulcers are predicted to increase. The growing understanding of healing and regenerative mechanisms has elucidated critical regulators of this process, including key cellular and humoral components. Despite this, the management and successful treatment of diabetic wounds represents a significant therapeutic challenge. To this end, the development of novel therapies and biological dressings has gained increased interest. Here we review key differences between normal and chronic non-healing diabetic wounds, and elaborate on recent advances in wound healing treatments with a particular focus on biological dressings and their effect on key wound healing pathways.

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“…The level of neutrophil NETs-specific markers, such as citrullinated histone H3 (citH3), is higher in DFU compared to DFU-deficient and healthy patients. It was reported that NETs, released by neutrophils, contributed to delaying wound healing [ 117 ]. Thus, the inhibition of NETs may facilitate ameliorated wound healing in diabetic mice.…”

Section: Chronic Wound Healingmentioning

confidence: 99%

Immunology of Acute and Chronic Wound Healing

et al. 2021

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Skin wounds greatly affect the global healthcare system, creating a substantial burden on the economy and society. Moreover, the situation is exacerbated by low healing rates, which in fact are overestimated in reports. Cutaneous wounds are generally classified into acute and chronic. The immune response plays an important role during acute wound healing. The activation of immune cells and factors initiate the inflammatory process, facilitate wound cleansing and promote subsequent tissue healing. However, dysregulation of the immune system during the wound healing process leads to persistent inflammation and delayed healing, which ultimately result in chronic wounds. The microenvironment of a chronic wound is characterized by high quantities of pro-inflammatory macrophages, overexpression of inflammatory mediators such as TNF-α and IL-1β, increased activity of matrix metalloproteinases and abundance of reactive oxygen species. Moreover, chronic wounds are frequently complicated by bacterial biofilms, which perpetuate the inflammatory phase. Continuous inflammation and microbial biofilms make it very difficult for the chronic wounds to heal. In this review, we discuss the role of innate and adaptive immunity in the pathogenesis of acute and chronic wounds. Furthermore, we review the latest immunomodulatory therapeutic strategies, including modifying macrophage phenotype, regulating miRNA expression and targeting pro- and anti-inflammatory factors to improve wound healing.

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Neutrophil Extracellular Traps Are Markers of Wound Healing Impairment in Patients with Diabetic Foot Ulcers Treated in a Multidisciplinary Setting

Cited by 70 publications

References 37 publications

Diabetic Wound-Healing Science

Diabetic Wound-Healing Science

Chronic Diabetic Wounds and Their Treatment with Skin Substitutes

Immunology of Acute and Chronic Wound Healing

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