118 I nternational Diabetes Foundation (IDF) considers that diabetic foot disease needs special awareness since it becomes a clinical and substantial problem for diabetic patients and becomes a major economic burden to health systems worldwide. 1 Diabetic foot ulcers (DFU) are the most common occurring problems throughout the globe, with a global prevalence of 6.3% 2 and a startle recurrence rate of about 40 % within a year, 60% within 3 years, and 65% within 5 years. 3 Comprehensive treatment strategies are needed to circumvent limb amputation risk which is reported to happen every 20 s. 4 Therefore, DFU becomes an overwhelming complex crisis not only for patients but also for families and society. 5 The magnitude of the DFU problem remains vast with a dramatic increase in global diabetes prevalence from 451 million in 2017 to 693 million by 2045. 6 A wound can be defined as a discontinuity of cellular, anatomical, and functional connection of a living tissue, which can be caused by various injuries including physical, chemical, thermal, microorganism, and immunological factors. 7 To restore its’ structural and functional integrity, the tissue will encounter sequential phases with overlapping phases of wound healing including coagulation (hemostasis), inflammation, proliferation, and remodeling phases. In skin tissue, these processes require vast interaction of various cells from different compartments of the skin and its extracellular matrix components. 8 At normal conditions, the acute wound healing mechanism is highly efficient, lasting for about three weeks to result in a complete repair of both the epidermis and superficial dermis. 9 The first phase, hemostasis, immediately starts upon injury resulting in the fibrin clot formation and constriction of blood vessels. Platelets, the fundamental contributor to hemostasis and coagulation, will be activated when encountering subendothelial connective tissue. Then it will express its receptors to interact with various proteins promoting adhesion to the blood vessel wall and will promote the formation of an insoluble clot (eschar). The eschar not only serves as a plug to prevent further bleeding but also prevents pathogen invasion and provides a scaffold for incoming immune cells and a source of cytokines and growth factors to recruit immunocompetent cells to migrate into the wound area. 10 Migration and extravasation of leucocytes to the site of the wound will induce an inflammatory reaction involving the release of inflammatory cytokines including interleukins (IL-1, IL6), Tumour Necrosis Factor-α (TNF-α), Platelet-Derived Growth Factor (PDGF), Fibroblast Growth Factor-2 (FGF2). The leucocyte activity also involved many other factors including histamine, kinins, leukotrienes, proteases, acid hydrolases, nitrogen oxide, and reactive oxygen species. The inflammatory phase is tightly regulated to localize inflammation and prevent excessive tissue destruction. 9 The subsequent event following inflammation is the proliferative phase, to contract the injured tissue and reduces the wound area. Various cytokines and molecules such as Transforming Growth Factor- beta (TGF-β), Vascular Endothelial Growth Factor (VEGF), Epidermal Growth Factor (EGF), and connective tissue growth factor (CTGF). 11 The fourth phase (remodeling phase), spans the entire process from the initial formation of fibrin clot to the formation of scar tissue. Principal contributors of the following two phases are fibroblasts, which are not only responsible for collagen and extracellular matrix synthesis, but also organize EDITORIAL ARTICLE INFO Evy Sulistyoningrum* 1 1 Histology Department, Faculty of Medicine, Universitas Islam Indonesia, Jl. Kaliurang 14,5 Ngemplak, Sleman, Yogya- karta, Indonesia, 55584 *Corresponding author: evy.sulistyoningrum@uii.ac.id DOI: 10.20885/JKKI.Vol14.Iss2.art1 Copyright @2023 Authors. JKKI: Jurnal Kedokteran dan Kesehatan Indonesia P-ISSN 2085-4145 | E-ISSN 2527-2950 Indonesian Journal of Medicine and Health Journal homepage: https://journal.uii.ac.id/JKKI Diabetic wound and oxidative stress