Natural Biologics Accelerate Healing of Diabetic Foot Ulcers by Regulating Oxidative Stress

Song, Jianying; Liu, Aiai; Liu, Bo; Huang, Wei; Jiang, Zongxuan; Bai, Xue; Hu, Li‐Xin; Zheng, Silin; Guo, Shengming; Wu, Jianming; Chen, Qi

doi:10.31083/j.fbl2710285

Cited by 9 publications

(5 citation statements)

References 153 publications

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“…Numerous studies have attempted to highlight the role of ROS in delayed wound healing: the impairment of redox homeostasis due to increased production of ROS induces oxidative damage at the cellular level, which inhibits wound healing [23,24]. Moreover, the Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling pathway, involved in the transcription of antioxidant genes, is also impacted in diabetes [25]. It is, therefore, oxidative stress, which represents an increase in the level of ROS and/or a decrease in antioxidant defenses [22], which is involved when the healing defect [26].…”

Section: Introductionmentioning

confidence: 99%

Antioxidant Activities of Natural Compounds from Caribbean Plants to Enhance Diabetic Wound Healing

Accipe,

Abadie,

Neviere

et al. 2023

Antioxidants

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Diabetic wound healing is a global medical challenge. Several studies showed that delayed healing in diabetic patients is multifactorial. Nevertheless, there is evidence that excessive production of ROS and impaired ROS detoxification in diabetes are the main cause of chronic wounds. Indeed, increased ROS promotes the expression and activity of metalloproteinase, resulting in a high proteolytic state in the wound with significant destruction of the extracellular matrix, which leads to a stop in the repair process. In addition, ROS accumulation increases NLRP3 inflammasome activation and macrophage hyperpolarization in the M1 pro-inflammatory phenotype. Oxidative stress increases the activation of NETosis. This leads to an elevated pro-inflammatory state in the wound and prevents the resolution of inflammation, an essential step for wound healing. The use of medicinal plants and natural compounds can improve diabetic wound healing by directly targeting oxidative stress and the transcription factor Nrf2 involved in the antioxidant response or the mechanisms impacted by the elevation of ROS such as NLRP3 inflammasome, the polarization of macrophages, and expression or activation of metalloproteinases. This study of the diabetic pro-healing activity of nine plants found in the Caribbean highlights, more particularly, the role of five polyphenolic compounds. At the end of this review, research perspectives are presented.

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Section: Introductionmentioning

confidence: 99%

Antioxidant Activities of Natural Compounds from Caribbean Plants to Enhance Diabetic Wound Healing

Accipe,

Abadie,

Neviere

et al. 2023

Antioxidants

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“…Our analysis also demonstrated that the key genes identified were mainly related to the keratinization and differentiation of skin cells and inflammatory pathway-related receptors such as rage receptor binding and TLR4 receptor binding. On the one hand, the physiological environment of hyperglycemia in diabetic patients stimulates the AGE-RAGE pathway, thus triggering a persistent inflammatory response that inhibits the healing of ulcers in DFU patients (Song et al, 2022). The inflammatory damage caused by oxidative stress and the AGEs-RAGE pathway has also been detected in CLE patients (Martens et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Identification of a shared gene signature and biological mechanism between diabetic foot ulcers and cutaneous lupus erythemnatosus by transcriptomic analysis

Wu,

Wang,

Duan

et al. 2024

Front. Physiol.

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Diabetic foot ulcers (DFU) and cutaneous lupus erythematosus (CLE) are both diseases that can seriously affect a patient’s quality of life and generate economic pressure in society. Symptomatically, both DLU and CLE exhibit delayed healing and excessive inflammation; however, there is little evidence to support a molecular and cellular connection between these two diseases. In this study, we investigated potential common characteristics between DFU and CLE at the molecular level to provide new insights into skin diseases and regeneration, and identify potential targets for the development of new therapies. The gene expression profiles of DFU and CLE were obtained from the Gene Expression Omnibus (GEO) database and used for analysis. A total of 41 common differentially expressed genes (DEGs), 16 upregulated genes and 25 downregulated genes, were identified between DFU and CLE. GO and KEGG analysis showed that abnormalities in epidermal cells and the activation of inflammatory factors were both involved in the occurrence and development of DFU and CLE. Protein-protein interaction network (PPI) and sub-module analysis identified enrichment in seven common key genes which is KRT16, S100A7, KRT77, OASL, S100A9, EPGN and SAMD9. Based on these seven key genes, we further identified five miRNAs(has-mir-532-5p, has-mir-324-3p,has-mir-106a-5p,has-mir-20a-5p,has-mir-93-5p) and7 transcription factors including CEBPA, CEBPB, GLI1, EP30D, JUN,SP1, NFE2L2 as potential upstream molecules. Functional immune infiltration assays showed that these genes were related to immune cells. The CIBERSORT algorithm and Pearson method were used to determine the correlations between key genes and immune cells, and reverse key gene-immune cell correlations were found between DFU and CLE. Finally, the DGIbd database demonstrated that Paquinimod and Tasquinimod could be used to target S100A9 and Ribavirin could be used to target OASL. Our findings highlight common gene expression characteristics and signaling pathways between DFU and CLE, indicating a close association between these two diseases. This provides guidance for the development of targeted therapies and mutual interactions.

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“…At this stage, the expression of anti-inflammatory markers, such as interleukin-12 (IL-12), IL-6, IL-1 or tumor necrosis factor-α, is enhanced, while the activity of anti-inflammatory cues, such as IL-10 and IL-4, is reduced [ 7 , 12 ]. This leads to an imbalance between angiogenic factors (promoters of new blood vessel formation) and angiostatic factors, impairing angiogenesis and leading to endothelial progenitor cell dysfunction aside from hindering the proliferation and migration of fibroblasts and keratinocytes [ 10 , 13 ]. This is exacerbated by the limited neuropeptide activity at the site, since in hyperglycemia conditions, neuropeptides such as Substance P, neuropeptide Y or neurotensin endowed with regenerative functions, have their activity reduced.…”

Section: Diabetic Ulcers: Healing Impairments and Classificationsmentioning

confidence: 99%

Emerging Antimicrobial and Immunomodulatory Fiber-Based Scaffolding Systems for Treating Diabetic Foot Ulcers

Felgueiras

2023

Pharmaceutics

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Diabetic foot ulcers (DFUs) are one of the main complications of diabetes and are characterized by their complexity and severity, which are frequently aggravated by overexpressed inflammatory factors and polymicrobial infections. Most dressing systems offer a passive action in the treatment of DFUs, being frequently combined with antibiotic or immunomodulatory therapies. However, in many instances due to these combined therapies' inability to properly fight microbial presence, and provide a suitable, breathable and moist environment that is also capable of protecting the site from secondary microbial invasions or further harm, aggravation of the wound state is unavoidable and lower limb amputations are necessary. Considering these limitations and knowing of the urgent demand for new and more effective therapeutic systems for DFU care that will guarantee the quality of life for patients, research in this field has boomed in the last few years. In this review, the emerging innovations in DFU dressing systems via fiber-based scaffolds modified with bioactive compounds have been compiled; data focused on the innovations introduced in the last five years (2017–2022). A generalized overview of the classifications and constraints associated with DFUs healing and the bioactive agents, both antimicrobial and immunomodulatory, that can contribute actively to surpass such issues, has also been provided.

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Natural Biologics Accelerate Healing of Diabetic Foot Ulcers by Regulating Oxidative Stress

Cited by 9 publications

References 153 publications

Antioxidant Activities of Natural Compounds from Caribbean Plants to Enhance Diabetic Wound Healing

Antioxidant Activities of Natural Compounds from Caribbean Plants to Enhance Diabetic Wound Healing

Identification of a shared gene signature and biological mechanism between diabetic foot ulcers and cutaneous lupus erythemnatosus by transcriptomic analysis

Emerging Antimicrobial and Immunomodulatory Fiber-Based Scaffolding Systems for Treating Diabetic Foot Ulcers

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