Search Results (1,256)

The aim of this study was to analyze the effect of concomitant use of cannabigerol (CBG) and 3-O-ethylascorbic acid (EAA) on changes in the proteome of UVA-irradiated skin melanocytes, with particular emphasis on adduct formation between lipid peroxidation products and metabolically important proteins. Proteomic analysis allowed the identification of 1248 proteins with statistically significantly changed expression following melanocytes irradiation and/or incubation with CBG/EAA. The top 25 proteins with the most strongly differentially abundant expression included proteins involved in cell protection/antioxidant response, as well as pro-inflammatory and proapoptotic signalization. Moreover, in melanocytes irradiated with UVA, the levels of lipid peroxidation product, 4-hydroxynonenal (4-HNE) and its protein adducts were increased, as well as significant changes in the profile of proteins modified by 4-HNE were observed. CBG and EAA, especially when used together, largely reverse these effects. This study for the first time demonstrated the combined effect of CBG and EAA on the proteome of melanocytes after their exposure to UVA radiation, which applies to both changes in protein expression and intracellular signaling based on proteins modified by 4-HNE. It can be suggested that CBG and EAA may provide melanocytes with effective protection against the effects of oxidative stress and perhaps even protect the skin from carcinogenesis. Full article

Vitiligo is a chronic, acquired autoimmune disorder characterized by white skin patches resulting from the loss of epidermal melanocytes. Vitiligo may arise through multiple mechanisms, including genetic susceptibility, oxidative stress, autoimmune dysfunction, and environmental factors. Treatment strategies have focused on inhibiting melanocyte loss and stimulating repigmentation. Mitogen-activated protein kinase (MAPK) pathways regulate various cellular processes, including differentiation, survival, and inflammatory responses. The dysregulated MAPK pathways play distinct roles in the development of vitiligo through a complex interplay of melanogenesis, oxidative stress, and autoimmune responses within different cells, thereby leading to melanocyte damage. Thus, therapeutic targeting of MAPK pathways has the potential to mitigate oxidative stress-induced damage and inhibit the exaggerated autoimmunity, thereby controlling disease progression and supporting repigmentation. This review provides an overview of MAPK signaling across the multicellular network in vitiligo pathogenesis and summarizes agents that may provide new perspectives for therapeutic intervention. Full article

Background: Lentigo maligna (LM) represents melanoma in situ and predominantly affects elderly individuals, typically arising on chronically sun-exposed skin of the head and neck. Although LM is characterized by slow horizontal growth and generally favourable prognosis, progression to invasive lentigo maligna melanoma may occur, making timely and effective treatment essential. Surgical excision remains the standard of care; however, advanced age, comorbidities, lesion size, and cosmetic or functional considerations may limit surgical feasibility. Case presentation: We report the case of a 93-year-old woman with no prior history of skin cancer who presented with a gradually enlarging pigmented lesion on the forehead. Clinical examination revealed an irregularly pigmented macule measuring 25 × 27 mm. Multiple mapping biopsies confirmed melanoma in situ of the lentigo maligna type, with adnexal extension and no evidence of dermal invasion. Given the patient’s advanced age and lesion location, a non-surgical approach was selected. Topical imiquimod 5% cream was applied five times per week for 12 weeks to the visible lesion and to a 20 mm margin around it. The patient was monitored closely throughout the treatment. Local inflammatory reactions were mild to moderate, consisting mainly of erythema, crusting, and superficial erosion, without systemic adverse effects. At treatment completion, marked clinical improvement with near-complete resolution of pigmentation was observed. Follow-up dermoscopic evaluation demonstrated only minimal residual granular pigmentation. Post-treatment mapping biopsies confirmed complete histological clearance of atypical melanocytic cells. Conclusions: This case illustrates that topical imiquimod may serve as a safe and effective alternative to surgery in carefully selected elderly patients with lentigo maligna. Close clinical follow-up and histological confirmation of clearance are essential to ensure treatment success and durable outcomes. Full article

Background: Baeckea frutescens L. (BF) has been reported as a potential natural source for skin-whitening agents. However, its antimelanogenic activity and mechanisms remain unclear. Methods: The antimelanogenic effects of BF were evaluated in α-melanocyte-stimulating hormone (α-MSH)-stimulated B16F10 cells and in zebrafish embryos. Cell viability, intracellular tyrosinase activity and melanin content were measured. Western blot (WB) analysis was used to examine melanogenesis-related proteins. Network pharmacology and molecular docking were performed to predict potential targets and interactions of BF-derived metabolites. Results: The ethanolic extract of BF reduced intracellular tyrosinase activity and melanin content in cells without cytotoxicity. Western blot analysis showed decreased expression of microphthalmia-associated transcription factor (MITF) and its downstream melanogenic enzymes, including tyrosinase (TYR), tyrosinase-related protein-1 (TRP-1), and dopachrome tautomerase (DCT). In addition, BF reduced phosphorylation of protein kinase A (PKA), cAMP responsive element-binding protein (CREB) and extracellular signal-regulated kinase (ERK), suggesting potential suppression of PKA/CREB and ERK signaling pathways. These regulatory effects may contribute to MITF downregulation and subsequent inhibition of melanogenesis. BF reduced melanin accumulation in zebrafish embryos. Network pharmacology and molecular docking analyses further suggested that BF-derived metabolites, particularly bayogenin, may interact with multiple melanogenesis-related targets. Conclusions: BF may inhibit melanogenesis through coordinated modulation of multiple signaling pathways and may represent a promising skin-whitening candidate. Full article

Objectives: Our objective was to evaluate the diagnostic accuracy of clinical diagnoses in patients with chronic conjunctival lesions (CCLs) in relation to prevalence data and to identify clinical features that improve diagnostic performance. Methods: Retrospective data were collected for all patients with CCLs at a tertiary eye clinic between 2006 and 2024. A total of 1304 patients were reviewed; 391 had available histopathological data. Results: Misclassification was the highest for clinically benign, non-melanocytic, non-degenerative CCLs (referral rates: 0.446; positive predictive value [PPV]: 0.289). The referral rates for histology assessment were comparable for malignant melanocytic and non-melanocytic CCLs (0.923 and 0.989, respectively) and for benign melanocytic and non-melanocytic CCLs (0.319 and 0.446, respectively). In contrast, the diagnostic agreement was double for melanocytic malignant CCLs (0.800 vs. 0.391) and triple for melanocytic benign CCLs (0.934 vs. 0.289) compared with non-melanocytic CCLs. However, the limbal involvement increased the odds ratio (OR) for proper diagnostic performance to 7.0 (95% confidence interval (CI): 2.7–19.1), whereas the limbal overlapping increased the OR to 11.2 (95% CI: 4.0–35.9) among malignant CCLs. Conclusions: The clinical diagnosis of non-melanocytic CCLs is less frequently and less accurately confirmed histologically. In this CCL subgroup, where the lesion involves or overlaps the limbus, the likelihood of malignancy is increased sevenfold to elevenfold. Full article

Inflammatory skin diseases are characterized by complex interactions between immune pathways, epidermal barrier function, and environmental triggers, leading to distinct clinical and histopathological features. This narrative review aims to integrate current knowledge on the cutaneous immune microenvironment across major inflammatory skin diseases, including atopic dermatitis, psoriasis, hidradenitis suppurativa, and vitiligo. A comprehensive literature search was conducted using PubMed, Web of Science, and Scopus, focusing on studies published between 2021 and early 2026. The findings highlight disease-specific immune signatures, such as Th2-driven inflammation in atopic dermatitis, IL-23/Th17 axis activation in psoriasis, neutrophil-dominated responses in hidradenitis suppurativa, and cytotoxic T-cell-mediated melanocyte destruction in vitiligo. These molecular pathways are closely reflected in histopathological patterns, emphasizing the link between morphology and immunopathogenesis. Advances in targeted therapies, including biologics and Janus kinase inhibitors, demonstrate the clinical relevance of these pathways and support a transition toward mechanism-based treatment strategies. Dermatopathology is increasingly contributing to precision medicine approaches by supporting correlations between tissue features, immune pathways, and potential therapeutic targets. This review provides a framework for improved disease stratification and for the development of personalized treatment strategies in inflammatory skin diseases. Full article

Vogt–Koyanagi–Harada syndrome (VKH) is a rare granulomatous autoimmune disease characterised by a systemic immune response directed against melanocytes. This multisystem condition primarily affects organs that are rich in melanocytes, such as the eyes, inner ear, meninges and skin. VKH might be responsible for the development of chronic uveitis and permanent visual impairment, particularly in cases where a diagnosis is delayed and treatment is not administered in a timely manner. A key factor in its pathogenesis is the loss of immune tolerance to melanocytes, driven by a T-cell–mediated immune response and genetic susceptibility, including the presence of HLA-DRB1*04 antigens. In recent years, immune checkpoint inhibitors (ICIs) have become the standard treatment in oncology, including non-small cell lung cancer and unresectable melanoma. However, it should be noted that their utilisation carries with it the potential for immune-related adverse events, including rare cases of VKH-like uveitis. The objective of this review is to outline the clinical features of VKH syndrome, examine current diagnostic and treatment approaches, and emphasise the immunopathological mechanisms associated with drug-induced forms of VKH, with a particular focus on programmed cell death protein 1 (PD-1) inhibitors. The article also includes an analysis of the genetic, epigenetic, and environmental factors that predispose individuals to the disease. This analysis facilitates a deeper understanding of the pathogenesis of the disease and assists in the identification of patients at increased risk of drug-induced VKH manifestations. Full article

UVA exposure elicits immediate and persistent pigment darkening of the skin, which is thought to result from the oxidation and polymerization of existing melanin and/or precursors. Melanocytes produce eumelanin and pheomelanin. Eumelanin consists of 5,6-dihydroxyindole (DHI) and 5,6-dihydroxyindole-2-carboxylic acid (DHICA), while pheomelanin consists of benzothiazine and benzothiazole units. Melanins can be analyzed by quantifying specific degradation products using HPLC. Specifically, eumelanin can be analyzed as pyrrole-2,3,5-tricarboxylic acid (PTCA) and pyrrole-2,3-dicarboxylic acid (PDCA), specific degradation products of DHICA and DHI, respectively. Benzothiazole pheomelanin can be analyzed as thiazole-2,4,5-tricarboxylic acid (TTCA), whereas benzothiazine pheomelanin is analyzed as 4-amino-3-hydroxyphenylalanine (4-AHP) and 3-amino-4-hydroxyphenylalanine (3-AHP). Upon UVA exposure, melanins undergo structural modifications. Eumelanin undergoes oxidative cleavage to free pyrrole-2,3,5-tricarboxylic acid (Free PTCA) and undergoes cross-linking to form pyrrole-2,3,4,5-tetracarboxylic acid (PTeCA). UVA exposure of pheomelanin induces oxidative conversion from the benzothiazine to the benzothiazole. Nevertheless, these structural modifications have never been previously characterized in human skin. In this study, we exposed ex vivo skin to increasing UVA1 doses (60, 90 and 120 J/cm²; n = 6 in triplicate) and characterized the induced pigment darkening before, immediately, and 2 h after exposure through colorimetry, HPLC and spectrophotometry. The results showed changes in the CIELAB colorimetric parameters, namely a decrease in Luminance L*, the yellow-blue component b* and the Individual Typology Angle (ITA) in UVA1-exposed samples, indicative of skin darkening. In parallel, UVA1 exposure induced significant modifications of the levels of absorbance at 500 nm (A500) and melanin markers PTCA, PTeCA, PDCA, TTCA, and 4-AHP, as well as in the ratios of various markers, such as PTeCA/PTCA, Free/Total PTCA, and TTCA/4-AHP, indicative of photooxidation/degradation of melanins. Our study provides the first evidence of UVA1-induced modifications of melanins associated with pigment darkening occurring in human skin. Full article

Canities results from a progressive decline in melanocyte activity and melanin synthesis and is commonly associated with aesthetic concerns that motivate the use of cosmetic products for hair color correction. Shampoo, due to its frequent use, represents a suitable vehicle for the gradual deposition of pigments on the hair fiber. This study aimed to design and develop a shampoo containing dark synthetic semi-permanent dyes for the gradual coverage of gray hair. Four shampoo formulations were developed and evaluated through in vitro tests using bleached hair tresses to assess color deposition and performance. The selected formulation was subsequently subjected to accelerated stability studies and color sustainability evaluation. The results showed that the formulation maintained organoleptic, physicochemical, microbiological, and functional stability. Color sustainability assays indicated that the gray–black coloration persisted on hair tresses containing approximately 90% canities after eight washing cycles. The formulation incorporating the semi-permanent dyes Basic Blue 124, Basic Yellow 87, Basic Orange 31, and Basic Red 51 achieved a gradual gray–black tonal effect. In conclusion, the developed shampoo demonstrated stability and effectiveness for the gradual cosmetic coverage of gray hair. Full article

Vitiligo is characterized by epidermal melanocyte destruction, with autoreactive CD8⁺ T cells playing a central pathogenic role, yet the mechanisms driving their hyperactivation remain unclear. Lactate has emerged as a key immunometabolite that functions as both a signaling molecule and an epigenetic modulator via protein lactylation. Nevertheless, the role of lactate in vitiligo pathogenesis has not been explored. Here, we report that serum lactate levels are significantly elevated in vitiligo patients and correlate positively with disease activity. In a mouse model, lactate administration accelerated vitiligo progression, accompanied by increased CD8⁺ T cell infiltration and melanocyte destruction in lesional skin. In vitro, lactate enhanced CD8⁺ T cell effector molecule expression (granzyme B, perforin, IFN-γ, CD107a) and cytotoxic function. Mechanistically, lactate increased global protein lactylation in CD8⁺ T cells, with marked enrichment at histone H3 lysine 9 (H3K9). H3K9 lactylation (H3K9la) was associated with enhanced chromatin accessibility and transcriptional activation of effector genes, as revealed by RNA sequencing and CUT&Tag analyses. Pharmacological inhibition of lactate production or lactylation abrogated these effects. Collectively, our findings identify lactate as a critical driver of CD8⁺ T cell pathogenicity in vitiligo through H3K9la-mediated epigenetic reprogramming, highlighting lactate metabolism and lactylation as potential therapeutic targets. Full article

Objective: To investigate the method and clinical outcomes of employing plantar propeller perforator flaps for the repair of defects in the plantar region. Methods: This was a retrospective case series of 40 patients (20 males, 20 females; age range 20–75 years) who underwent plantar defect reconstruction using the horn-shaped perforator flap technique between January 2020 and October 2025. Defect etiologies included malignant melanoma (n = 24), melanocytic nevus (n = 3), and refractory wounds (n = 13). Defect sizes ranged from 2 cm × 1.5 cm to 5 cm × 5 cm. The primary outcome was flap survival; secondary outcomes included functional recovery (American Orthopaedic Foot and Ankle Society AOFAS score), sensory recovery (Semmes–Weinstein monofilaments), and time to full weight-bearing. Results: Complete flap survival was achieved in 38/40 patients (95%). Two patients (5%) experienced minor distal wound dehiscence and necrosis, successfully managed with full-thickness skin grafting and dressing changes without compromising final outcomes. Mean follow-up was 14.2 ± 6.8 months (range 3–24 months). Mean AOFAS score was 91.3 ± 5.6, with 80% achieving excellent functional recovery. Protective sensation was present in 87.1% of the tested patients. Mean time to full weight-bearing was 6.4 ± 1.8 weeks. No local tumor recurrence occurred in melanoma patients during follow-up. Conclusions: The horn-shaped perforator flap provides a reliable source of homologous glabrous skin for reconstructing small-to-medium-sized plantar defects while avoiding skin grafting at the donor site. Its combined rotation–advancement mechanism, flexible triangular leading-edge strategies, and preservation of multiple perforators contribute to favorable functional and aesthetic outcomes. Prospective comparative studies with standardized plantar-specific outcome measures are warranted. Full article

Vitiligo is a chronic autoimmune disease characterized by the destruction of epidermal melanocyte, resulting in well-demarcated white patches on the skin. Despite the established use of corticosteroids and calcineurin inhibitors and the recent introduction of Janus kinase (JAK) inhibitors, a breakthrough targeted therapy that interrupts the IFN-γ signaling pathway, stable repigmentation remains a major clinical challenge, necessitating deeper investigation into its pathogenesis. Among the factors contributing to vitiligo, including genetic predisposition and autoimmunity, oxidative stress is a central driver of melanocyte damage and the subsequent autoimmune response. Chronic oxidative disequilibrium (high ROS level and impaired mitochondrial activity) and reduced antioxidant capacity (Nrf2/ARE pathway and catalase deficiency) function as triggering factors upstream of most other pathogenic pathways. Consequently, targeting oxidative stress, either as a monotherapy or in synergy with emerging targeted treatments, remains a pivotal area of therapeutic interest even in the current era of targeted therapies. Still, a significant gap remains the lack of standardized oxidative biomarkers to monitor disease activity and therapeutic response. Identifying these indicators is essential for personalized clinical management in vitiligo. This review examines how chronic oxidative disequilibrium and a reduced antioxidant capacity initiate and sustain the autoimmune cascade, leading to disease onset and progression. Full article

The polyamine metabolic pathway, an evolutionarily conserved nexus integrating nutrient sensing, translation control, and cellular proliferation, is fundamentally rewired in cancer. Melanoma, a malignancy of melanocytes notorious for its metastatic propensity and therapy resistance, exhibits a profound dependency on this pathway, extending beyond mere polyamine abundance to the specialized function of their derivative, hypusine. This review synthesizes cutting-edge insights into the deoxyhypusine synthase (DHPS)/eukaryotic initiation factor 5A (eIF5A) hypusination circuit as a critical amplifier of oncogenic signaling in melanoma. We dissect its role as a translational rheostat for pro-tumorigenic proteomes, a driver of phenotypic plasticity underpinning invasion and vasculogenic mimicry, and a modulator of the immunosuppressive tumor microenvironment. Moving beyond the classical inhibitor GC7, we explore the emergence of novel allosteric DHPS inhibitors with compelling preclinical efficacy. Finally, we propose a paradigm shift: targeting the DHPS/eIF5A axis represents a strategy to disrupt the “non-oncogene addiction” of melanoma—its reliance on hyperactive translation and adaptive survival mechanisms—offering a promising avenue alongside targeted therapies and immunotherapies. Full article

Cannabinoids (CBs) derived from Cannabis sativa have attracted growing interest for dermatological applications due to their anti-inflammatory, antiproliferative, antimicrobial, antifibrotic, and antipruritic properties. However, their clinical translation is significantly limited by physicochemical and pharmacokinetic challenges, including poor aqueous solubility, lipophilicity, instability, variable skin penetration, and inconsistent bioavailability. At the molecular level, CBs modulate keratinocyte proliferation, sebocyte activity, fibroblast function, melanocyte balance, and immune signalling through CB1/CB2 receptors, TRP channels, and PPARγ pathways. Evidence supports their potential in the treatment of psoriasis, atopic dermatitis, acne, allergic contact dermatitis, pruritus, scleroderma, and skin cancers. Clinical evidence remains preliminary: topical and oral formulations have demonstrated anti-inflammatory, antiproliferative, antibacterial, and antifibrotic effects, with improvements in pruritus, lesion severity, and quality of life in early-phase studies. However, most trials are small, uncontrolled, and lack placebo comparators, limiting generalisability. To overcome formulation barriers and enhance dermal delivery, advanced pharmaceutical strategies such as liposomes, nanoemulsions, polymeric nanoparticles, micelles, and transdermal systems have been investigated to improve stability, controlled release, and targeted skin deposition while minimising systemic exposure. This review integrates mechanistic insights, clinical evidence, and emerging nanotechnology-enabled delivery approaches, emphasising rational formulation design and translational considerations necessary for advancing CBs toward standardised and clinically reliable dermatological therapeutics. Full article

Extracellular vesicles (EVs) mediate intercellular communication by delivering proteins and RNAs, with their molecular cargo often reflecting the biological context of their source. Perinatal tissues are promising sources of EV-related biomaterials with potential dermatologic applications. In this study, we compared EV-related molecular cargo from two umbilical cord-associated sources, umbilical cord mesenchymal stem cell (UCMSC)-derived EVs and cord blood plasma (CBP), to investigate whether these materials exhibit distinct functional effects on melanogenesis. UCMSC-derived EVs were isolated from conditioned culture medium and characterized using nanoparticle tracking analysis (NTA), cryo-electron microscopy (cryo-EM), and canonical EV marker detection, while cord blood samples were processed to obtain plasma following centrifugation and filtration, containing EVs together with soluble plasma components. Functional assays in the murine melanocyte cell line B16F10 demonstrated that UCMSC-derived EVs suppressed melanin production, whereas CBP treatment enhanced melanogenesis. Integrative omics analyses combining microRNAs (miRNAs) microarray profiling and proteomic characterization revealed distinct molecular signatures between UCMSC-derived EVs and CBP samples. Functional validation using miRNA mimic assays showed that selected miRNAs, including miR-6862-5p, miR-3622b-5p, miR-7847-3p, miR-6774-5p, and miR-4685-5p, reduced melanin production, whereas others, including miR-203a-3p, miR-126-3p, miR-139-5p, and miR-15b-5p, increased melanin levels. Pathway analysis using Ingenuity Pathway Analysis (IPA) (QIAGEN Inc.) associated these miRNA subsets with signaling pathways involved in melanogenesis. Together, these findings indicate that UCMSC-derived EVs and CBP exhibit opposite functional effects on melanogenesis and possess distinct miRNA and protein cargo profiles, providing potential molecular targets for modulating pigmentation and supporting the development of EV-related therapeutic strategies for pigmentation disorders. Full article