Diabetic foot ulcer (DFU) is one of the major complications of diabetes mellitus and often results in persistent non-healing lesions, infections, and amputations. Recently, an iron-dependent form of programmed cell death, ferroptosis, has been shown to have an essential role in the poor regeneration of DFUs. This mini-review aims to study the role of ferroptosis in the pathophysiology of diabetic wounds, clinical biomarkers, and potential treatments by targeting ferroptotic pathways. Hence, PubMed-indexed studies on ferroptosis in relation to diabetic wound healing, including in vitro , animal, and clinical studies, were systematically reviewed. The research was evaluated based on molecular mechanisms, biomarkers, and preclinical and clinical evidence. Ferroptosis inhibits wound healing by promoting lipid peroxidation, oxidative stress, and cell death in fibroblasts, keratinocytes, and endothelial cells. Wound severity and healing are associated with tissue and circulation biomarkers such as Glutathione Peroxidase 4 (GPX4), Solute Carrier Family 7 Member 11 (SLC7A11), Acyl-CoA Synthetase Long-Chain Family Member 4 (ACSL4), Malondialdehyde (MDA), and 4-Hydroxynonenal (4-HNE). Several treatments, including small-molecule ferroptosis inhibitors, iron chelators, and extracellular vesicles from mesenchymal stem cells, have demonstrated therapeutic benefits in preclinical studies ( in vitro and animal models) and early-phase clinical assessments, although no randomized controlled trials are currently available. Inhibition of ferroptosis is a promising and rational therapeutic approach to improve DFU healing. It is essential to normalize these biomarkers, optimize therapeutic regimens, and perform extensive, robust clinical trials to translate the preclinical findings for chronic diabetic wounds into effective patient treatments.
Introduction The diagnosis of primary syphilis can be challenging, as direct inoculation at non-genital sites such as the lips may result in extragenital chancres, even though the disease typically presents as a genital ulcer. Case Presentation A 32-year-old man had a lower lip ulcer that was indurated and painless for three weeks. The patient reported a history of orogenital contact with a woman 17 days before the appearance of the lip ulcer. Initially, the lesion was misdiagnosed as a traumatic ulcer and was unsuccessfully treated with topical antibiotics. Examining the lower lip revealed a single, distinct, oval ulcer with a clean base and firm induration. The submental lymph nodes showed a slight non-tender enlargement. A confirmatory Treponema Pallidum Hemagglutination Assay (TPHA) and a positive Venereal Disease Research Laboratory (VDRL) test (1/64) were found through serological testing. Human Immunodeficiency Virus (HIV) and Herpes Simplex Virus immunoglobulins (HSV IgM, IgG) were not detected. After receiving a single intramuscular dose of 2.4 million units of benzathine penicillin G, the patient recovered completely in two weeks. Conclusion Chronic indurated ulcers of the lip may have various etiologies, and the possibility of a primary syphilitic chancre, though rare, should always be considered. Awareness of this presentation is essential, as early diagnosis and appropriate treatment are crucial to prevent disease progression and transmission.
Introduction/Background Annular lichen planus (ALP) is a rare morphological variant of lichen planus that can mimic other annular dermatoses and often poses diagnostic challenges. Although lichen planus has been sporadically linked to systemic diseases, its association with ulcerative colitis is exceedingly rare. This case highlights the coexistence of ALP and ulcerative colitis, suggesting a possible immunopathogenic connection between the two conditions. Case Presentation A 40-year-old woman with a three-year history of ulcerative colitis presented with a six-month history of intensely pruritic, violaceous, annular lesions affecting the dorsal feet, hands, wrists, and face. Examination revealed flat-topped papules, some forming plaques with Wickham striae and annular configurations. Histopathology confirmed the diagnosis of annular lichen planus. The patient had no other known triggers such as new medications, infections, or contact allergens. She was treated with topical corticosteroids and antihistamines, resulting in partial resolution of the lesions over a four-week period. Conclusion This case underscores the importance of considering systemic autoimmune diseases like ulcerative colitis in patients presenting with atypical forms of lichen planus. It adds to the limited literature documenting ALP as a possible cutaneous manifestation associated with inflammatory bowel disease.
Introduction The use of Artificial Intelligence (AI) for image-based diagnosis in dermatology is increasing rapidly. The clinical accuracy of AI in diagnosing different skin conditions remains under evaluation. This study aimed to evaluate the diagnostic performance of an AI application in comparison to confirmed clinical diagnoses by dermatologists. Method A cross-sectional study was carried out on 400 patients with different skin conditions, including acne, alopecia, eczema, pigmentary disorders, psoriasis, immunological disorders, tumors, infections, and infestations. The study analyzed AI-based predictions using the Tibot AI application, comparing them against dermatologists’ diagnoses. Results The AI application demonstrated high diagnostic accuracy for certain dermatological conditions such as adnexal disorders (AUC 0.93–0.98), pigmentary disorders (AUC 0.88–0.94), and cutaneous tumors (AUC 0.87–0.95). Sensitivity for adnexal disorders was 88.9% (top one) and 94.4% (top three), and for Pigmentary disorders, it was 75.8% and 87.9% for top one and top-three predictions, respectively. However, AI performance was lower for immunological disorders (31.3% sensitivity) and cutaneous infestations (22.2%). Overall accuracy improved across all conditions when considering the top-three predictions. Discussion Tibot AI-application demonstrated high diagnostic accuracy for conditions with distinct morphological features such as adnexal, pigmentary disorders, and cutaneous tumors. It showed lower sensitivity for immunological disorders and infestations, indicating the need for further AI training with more diverse datasets. Conclusion AI-based diagnostic accuracy improved significantly when considering the top-three diagnoses, indicating its value as a differential diagnostic tool. It showed promising accuracy in adnexal, pigmentary disorders, and cutaneous tumors. However, it is less robust for immunological skin diseases and infections, highlighting the need for further refinement.
Background Mechanical stresses affect biological processes, cellular homeostasis, and skin wound healing. Objective We investigated the effects of mechanical stretching on epidermal keratinocytes, focusing on its role in wound healing and keloid formation. Methods Epidermal keratinocytes were stretched using a biochemical stretch device with or without a cyclooxygenase-2 inhibitor. Cells and supernatants were collected after 1−24 h of stimulation. Stretched keratinocytes were co-cultured with normal dermal or keloid-derived fibroblasts. Prostaglandin E2 and 12-hydroxyeicosatetraenoic acid were measured via enzyme-linked immunosorbent assay. Prostaglandin E2 receptor EP3 and transforming growth factor-β1 (TGF-β1) were analyzed using qRT-PCR. TGF-β1 was also examined using western blotting. Prostaglandin E2 synthase and TGF-β1 were also stained and analyzed using immunofluorescence microscopy. Results Mechanical stretching of keratinocytes increased the levels of prostaglandin E2, which stimulates keratinocyte proliferation and exerts antifibrotic effects, as well as those of prostaglandin E synthase 2 and prostaglandin E2 receptor 3. In contrast, mechanical stretching did not affect the levels of transforming growth factor-β1 in affected keratinocytes. However, co-culture with keloid-derived fibroblasts markedly increased the levels of transforming growth factor-β1 in mechanically stretched keratinocytes. Discussion These results suggest that the stretching stimulation of keratinocytes promotes epithelialization by increasing prostaglandin E2 production. Furthermore, stretching stimulation of keratinocytes in the presence of keloid-derived fibroblasts possibly promotes keloid formation via the upregulation of TGF-β1 levels in keratinocytes. Conclusion Mechanical stretching induced PGE2 production and increased the TGF-β1 levels in keratinocytes in the presence of keloid-derived fibroblasts. Our results suggest that stretch stimulation in the presence of keloid-derived fibroblasts promotes keloid development.
