Hiromichi Morita, Takuya Miyagawa, Kenta Oka, Okuto Iwasawa, Hinako Saito, Toko Mori, Hisao Kawashima, Jun Omatsu, Daisuke Yamada, Shinichi Sato
Nectin cell adhesion molecule 4 (Nectin-4) is overexpressed in the tissue of extramammary Paget disease (EMPD), and its potential role as a circulating biomarker remains poorly explored. We therefore investigated serum levels of Nectin-4 in EMPD patients and healthy controls by ELISA assay and analysed its clinical relevance. Serum Nectin-4 levels were significantly higher in patients than in controls (p = 0.0015), especially in advanced stages (IIIB–IV; p = 0.028). Serum Nectin-4 levels tended to decrease following effective treatment and increase upon disease progression. Serum Nectin-4 correlated strongly with CEA (r = 0.705) but not with CYFRA. Patients with high serum Nectin-4 levels (cut-off of 394.2 pg/mL) exhibited shorter overall survival (p = 0.012). Further research is needed to elucidate the role of Nectin-4 in EMPD; however, these findings suggest that serum Nectin-4 may serve as a single marker for prognosis and treatment monitoring in EMPD.
{"title":"Serum Nectin-4 as a Potential Prognostic Biomarker for Extramammary Paget Disease","authors":"Hiromichi Morita, Takuya Miyagawa, Kenta Oka, Okuto Iwasawa, Hinako Saito, Toko Mori, Hisao Kawashima, Jun Omatsu, Daisuke Yamada, Shinichi Sato","doi":"10.1111/exd.70172","DOIUrl":"https://doi.org/10.1111/exd.70172","url":null,"abstract":"<div>\u0000 \u0000 <p>Nectin cell adhesion molecule 4 (Nectin-4) is overexpressed in the tissue of extramammary Paget disease (EMPD), and its potential role as a circulating biomarker remains poorly explored. We therefore investigated serum levels of Nectin-4 in EMPD patients and healthy controls by ELISA assay and analysed its clinical relevance. Serum Nectin-4 levels were significantly higher in patients than in controls (<i>p</i> = 0.0015), especially in advanced stages (IIIB–IV; <i>p</i> = 0.028). Serum Nectin-4 levels tended to decrease following effective treatment and increase upon disease progression. Serum Nectin-4 correlated strongly with CEA (<i>r</i> = 0.705) but not with CYFRA. Patients with high serum Nectin-4 levels (cut-off of 394.2 pg/mL) exhibited shorter overall survival (<i>p</i> = 0.012). Further research is needed to elucidate the role of Nectin-4 in EMPD; however, these findings suggest that serum Nectin-4 may serve as a single marker for prognosis and treatment monitoring in EMPD.</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 10","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145341875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Meagan Doppegieter, Nick van der Beek, Maurice C. G. Aalders, Erik N. T. P. Bakker, Martino Neumann, Ton G. van Leeuwen
Emerging evidence supports the neurogenic origin of psoriasis, yet the morphology and distribution of nerve fibres in psoriatic skin remain poorly characterised due to methodological inconsistencies and limited 3D data. The aim of this study was to provide a comprehensive 3D quantification of nerve fibre morphology in psoriatic skin and assess its spatial relation to vasculature and clinical parameters. High-resolution confocal microscopy was used to analyse 69 (70 μm thick) skin sections from 23 psoriasis patients, capturing full-thickness epidermis and dermis. Nerve fibres were segmented by location (epidermal, papillary and reticular) and quantified volumetrically alongside vascular networks. The results show that nerve fibres occupied ~0.1% of total skin volume and predominantly localised near vasculature in the dermis, with epidermal nerves branching from perivascular plexuses. Epidermal nerve fibre volume negatively correlated with erythema, age and epidermal thickness (p < 0.05). No significant correlation was observed between dermal nerve fibre volumes and vascular density or clinical severity scores. This study presents a detailed 3D neurovascular map of psoriatic skin, revealing a distinct topography of nerve-vessel relationships. The findings highlight that epidermal nerve fibres (not total nerve density) show the strongest association with clinical markers. These results provide a critical baseline for evaluating nerve-targeted therapies and modelling neurovascular responses in laser-based psoriasis treatments.
{"title":"Nerve Fibres in Psoriatic Skin and Their Relation to Vasculature and Clinical Parameters","authors":"Meagan Doppegieter, Nick van der Beek, Maurice C. G. Aalders, Erik N. T. P. Bakker, Martino Neumann, Ton G. van Leeuwen","doi":"10.1111/exd.70166","DOIUrl":"10.1111/exd.70166","url":null,"abstract":"<p>Emerging evidence supports the neurogenic origin of psoriasis, yet the morphology and distribution of nerve fibres in psoriatic skin remain poorly characterised due to methodological inconsistencies and limited 3D data. The aim of this study was to provide a comprehensive 3D quantification of nerve fibre morphology in psoriatic skin and assess its spatial relation to vasculature and clinical parameters. High-resolution confocal microscopy was used to analyse 69 (70 μm thick) skin sections from 23 psoriasis patients, capturing full-thickness epidermis and dermis. Nerve fibres were segmented by location (epidermal, papillary and reticular) and quantified volumetrically alongside vascular networks. The results show that nerve fibres occupied ~0.1% of total skin volume and predominantly localised near vasculature in the dermis, with epidermal nerves branching from perivascular plexuses. Epidermal nerve fibre volume negatively correlated with erythema, age and epidermal thickness (<i>p</i> < 0.05). No significant correlation was observed between dermal nerve fibre volumes and vascular density or clinical severity scores. This study presents a detailed 3D neurovascular map of psoriatic skin, revealing a distinct topography of nerve-vessel relationships. The findings highlight that epidermal nerve fibres (not total nerve density) show the strongest association with clinical markers. These results provide a critical baseline for evaluating nerve-targeted therapies and modelling neurovascular responses in laser-based psoriasis treatments.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70166","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145137087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lei Li, Zhiwei Zeng, Tengxiao Ma, Bo Hu, Muye Guo, Qiaoxing Wang
Reactive oxygen species (ROS) are critical to cellular metabolism, signal transduction and apoptosis. Recent studies have revealed the dual role of ROS in malignant melanoma pathogenesis and progression, where they can both promote tumour proliferation and metastasis or inhibit tumour growth by inducing apoptosis. Mitochondria, often referred to as the energy factories of cells, are closely involved in ROS generation, and their dysfunction significantly affects cellular homeostasis. This review explores the mechanisms by which ROS-mediated mitochondrial dysfunction contributes to malignant melanoma, focusing on its effects within the tumour microenvironment and its potential as a therapeutic target. Understanding these interactions is essential for developing novel strategies to combat malignant melanoma.
{"title":"The Role of ROS-Mediated Mitochondrial Dysfunction in the Development of Malignant Melanoma","authors":"Lei Li, Zhiwei Zeng, Tengxiao Ma, Bo Hu, Muye Guo, Qiaoxing Wang","doi":"10.1111/exd.70168","DOIUrl":"10.1111/exd.70168","url":null,"abstract":"<p>Reactive oxygen species (ROS) are critical to cellular metabolism, signal transduction and apoptosis. Recent studies have revealed the dual role of ROS in malignant melanoma pathogenesis and progression, where they can both promote tumour proliferation and metastasis or inhibit tumour growth by inducing apoptosis. Mitochondria, often referred to as the energy factories of cells, are closely involved in ROS generation, and their dysfunction significantly affects cellular homeostasis. This review explores the mechanisms by which ROS-mediated mitochondrial dysfunction contributes to malignant melanoma, focusing on its effects within the tumour microenvironment and its potential as a therapeutic target. Understanding these interactions is essential for developing novel strategies to combat malignant melanoma.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70168","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145130380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Richard B. Warren, Anne Weiss, Jakob Felding, Morten O. A. Sommer, Sandra Garcet, James G. Krueger
Minimally invasive sampling of the skin using tape strips for conducting biomarker research is a growing research area in medical dermatology. The goal of this study was to utilise tape strip sampling to investigate changes in protein skin levels of psoriasis patients after oral treatment with orismilast (a PDE4B/D inhibitor). The proteins were measured in extracts of tape-strip samples taken from the skin of patients with moderate–severe psoriasis participating in a 16-week Ph2b study (IASOS). The proteins were measured using the Olink technology or an ELISA assay. Our results show that protein levels of multiple proteins (32/71) were upregulated at baseline in the lesional skin compared to non-lesional skin, including three key biomarkers of the psoriasis disease pathology (IL-17A, CCL20 and TNFα). The protein levels of these three biomarkers were significantly reduced at Week 16, reaching a percent reduction of 52% and 51% for IL-17A, 66% and 60% for TNFα, and 41% and 54% for CCL20 for the two doses analysed (20 and 30 mg bid, respectively). In addition, we observed that the clinical response of a 75% reduction in PASI (PASI75) was associated with a 98% reduction in IL-17A protein levels in lesional skin, irrespective of the orismilast dose. In summary, a significant reduction of key proteins related to the TH17 axis and TH1 axis was observed in the skin of psoriasis patients after treatment with oral orismilast, supporting the observed clinical effect. Finally, this constitutes the first report where protein levels from the skin of psoriasis patients are quantified using tape strips as a minimally invasive skin sampling technology in combination with the Olink technology.
{"title":"Orismilast, a Potent and Selective PDE4B/D Inhibitor, Reduces Protein Levels of Key Disease Driving Cytokines in the Skin of Patients With Plaque Psoriasis","authors":"Richard B. Warren, Anne Weiss, Jakob Felding, Morten O. A. Sommer, Sandra Garcet, James G. Krueger","doi":"10.1111/exd.70153","DOIUrl":"10.1111/exd.70153","url":null,"abstract":"<p>Minimally invasive sampling of the skin using tape strips for conducting biomarker research is a growing research area in medical dermatology. The goal of this study was to utilise tape strip sampling to investigate changes in protein skin levels of psoriasis patients after oral treatment with orismilast (a PDE4B/D inhibitor). The proteins were measured in extracts of tape-strip samples taken from the skin of patients with moderate–severe psoriasis participating in a 16-week Ph2b study (IASOS). The proteins were measured using the Olink technology or an ELISA assay. Our results show that protein levels of multiple proteins (32/71) were upregulated at baseline in the lesional skin compared to non-lesional skin, including three key biomarkers of the psoriasis disease pathology (IL-17A, CCL20 and TNFα). The protein levels of these three biomarkers were significantly reduced at Week 16, reaching a percent reduction of 52% and 51% for IL-17A, 66% and 60% for TNFα, and 41% and 54% for CCL20 for the two doses analysed (20 and 30 mg bid, respectively). In addition, we observed that the clinical response of a 75% reduction in PASI (PASI75) was associated with a 98% reduction in IL-17A protein levels in lesional skin, irrespective of the orismilast dose. In summary, a significant reduction of key proteins related to the T<sub>H</sub>17 axis and T<sub>H</sub>1 axis was observed in the skin of psoriasis patients after treatment with oral orismilast, supporting the observed clinical effect. Finally, this constitutes the first report where protein levels from the skin of psoriasis patients are quantified using tape strips as a minimally invasive skin sampling technology in combination with the Olink technology.</p><p><b>Trial Registration:</b> ClinicalTrials.gov identifier: NCT05190419</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70153","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Murine epidermal γδ T cells, known as dendritic epidermal T cells (DETCs), play critical roles in cutaneous wound healing by secreting chemokines, cytokines and growth factors. Although DETCs predominantly produce IL-13 early after activation, the specific role of DETC-derived IL-13 in wound repair remains unknown. Here, we show that periwound DETCs are the primary source of IL-13 at early wound sites (4 h after full-thickness skin wounding). The delayed wound closure in DETC-deficient Tcrd−/− mice was restored by the local application of IL-13 immediately after wounding. Previous studies have demonstrated that macrophages infiltrating the wound granulation tissue undergo a phenotypic shift from iNOS-positive, proinflammatory type to arginase-1-positive, anti-inflammatory type during the late inflammatory phase (3–5 days post injury). At 24 h post wounding, however, most macrophages infiltrating the periwound hypodermis expressed arginase-1. In Tcrd−/− mice, both the number of macrophages in the periwound hypodermis and their arginase-1 expression were significantly reduced. Local IL-13 administration restored arginase-1 expression in the hypodermal macrophages without altering their overall number in Tcrd−/− mice. These results indicate that IL-13 rapidly produced by DETCs upon skin injury plays a critical role in wound healing by inducing arginase-1-positive macrophages in the periwound hypodermis during the early inflammatory phase.
{"title":"IL-13 From Murine Epidermal γδ T Cells Promotes Wound Healing by Inducing Arginase-1-Positive Hypodermal Macrophages in the Early Inflammatory Phase","authors":"Atsuko Ibusuki, Kazuhiro Kawai, Akiko Ito, Gyohei Egawa, Takuro Kanekura","doi":"10.1111/exd.70169","DOIUrl":"10.1111/exd.70169","url":null,"abstract":"<div>\u0000 \u0000 <p>Murine epidermal γδ T cells, known as dendritic epidermal T cells (DETCs), play critical roles in cutaneous wound healing by secreting chemokines, cytokines and growth factors. Although DETCs predominantly produce IL-13 early after activation, the specific role of DETC-derived IL-13 in wound repair remains unknown. Here, we show that periwound DETCs are the primary source of IL-13 at early wound sites (4 h after full-thickness skin wounding). The delayed wound closure in DETC-deficient <i>Tcrd</i><sup>−/−</sup> mice was restored by the local application of IL-13 immediately after wounding. Previous studies have demonstrated that macrophages infiltrating the wound granulation tissue undergo a phenotypic shift from iNOS-positive, proinflammatory type to arginase-1-positive, anti-inflammatory type during the late inflammatory phase (3–5 days post injury). At 24 h post wounding, however, most macrophages infiltrating the periwound hypodermis expressed arginase-1. In <i>Tcrd</i><sup>−/−</sup> mice, both the number of macrophages in the periwound hypodermis and their arginase-1 expression were significantly reduced. Local IL-13 administration restored arginase-1 expression in the hypodermal macrophages without altering their overall number in <i>Tcrd</i><sup>−/−</sup> mice. These results indicate that IL-13 rapidly produced by DETCs upon skin injury plays a critical role in wound healing by inducing arginase-1-positive macrophages in the periwound hypodermis during the early inflammatory phase.</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
As hyperpigmentation can worsen with exposure to ultraviolet (UV) and visible light (VL), sunscreens with well-balanced UVB/UVA protection and VL-blocking pigments are recommended. Assessing efficiency against VL-induced pigmentation is then mandatory. Recently, an in vivo pigmentation assessment allowing a VL protection factor (pVL-PF) determination, and an in vitro predictive method based on transmittance measures were introduced. However, the number of volunteers, tested sunscreens, and protection range were limited. Moreover, no statistical assessment was associated. This study aimed at testing the robustness and improving these methodologies by conducting a series of 9 monocentric, double-blind, randomised controlled in vivo studies involving 188 volunteers and 30 products, alongside an in vitro approach, in 2 independent laboratories. Our results first allowed us to improve pVL-PF calculation by better fitting to VL-induced pigmentation dynamics. Based on the 30 established pVL-PF, we evidenced that VL-protection level strongly correlated with the amount of pigments in products. Second, a statistical Bayesian approach, accounting for kinetic and inter-individual response variability over time, was proposed. This enabled us to determine that 24 out of 30 products significantly reduced VL-induced pigmentation. Finally, we showed that in vitro transmittance reduction was highly predictive of in vivo results. In conclusion, through several independent studies involving a large number of products and volunteers, a refined pVL-PF calculation associated with statistical indicators was proposed together with a predictive in vitro assessment. These methodologies to assess the efficacy of tinted products against VL-induced pigmentation are complementary and could also be of interest for other pathologies induced or aggravated by VL.
{"title":"Visible Light-Induced Pigmentation: Improved In Vivo Methodology for Measuring Efficacy of 30 Products in 9 Randomised Controlled Trials and Correlation With In Vitro Assessment","authors":"Pascale Renoux, Hussein Jouni, Clément Laloux, Rita Touti, Diane-Lore Vieu, François Lamarche, Silvia Morim Santos, Françoise Bernerd, Claire Marionnet","doi":"10.1111/exd.70167","DOIUrl":"https://doi.org/10.1111/exd.70167","url":null,"abstract":"<p>As hyperpigmentation can worsen with exposure to ultraviolet (UV) and visible light (VL), sunscreens with well-balanced UVB/UVA protection and VL-blocking pigments are recommended. Assessing efficiency against VL-induced pigmentation is then mandatory. Recently, an in vivo pigmentation assessment allowing a VL protection factor (pVL-PF) determination, and an in vitro predictive method based on transmittance measures were introduced. However, the number of volunteers, tested sunscreens, and protection range were limited. Moreover, no statistical assessment was associated. This study aimed at testing the robustness and improving these methodologies by conducting a series of 9 monocentric, double-blind, randomised controlled in vivo studies involving 188 volunteers and 30 products, alongside an in vitro approach, in 2 independent laboratories. Our results first allowed us to improve pVL-PF calculation by better fitting to VL-induced pigmentation dynamics. Based on the 30 established pVL-PF, we evidenced that VL-protection level strongly correlated with the amount of pigments in products. Second, a statistical Bayesian approach, accounting for kinetic and inter-individual response variability over time, was proposed. This enabled us to determine that 24 out of 30 products significantly reduced VL-induced pigmentation. Finally, we showed that in vitro transmittance reduction was highly predictive of in vivo results. In conclusion, through several independent studies involving a large number of products and volunteers, a refined pVL-PF calculation associated with statistical indicators was proposed together with a predictive in vitro assessment. These methodologies to assess the efficacy of tinted products against VL-induced pigmentation are complementary and could also be of interest for other pathologies induced or aggravated by VL.</p><p><b>Trial Registration:</b> NCT06827392, NCT06796192, NCT06803901, NCT06796140, NCT06796153, NCT06796010, NCT06796088, NCT06796205, NCT06796179</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70167","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145012266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Radiation dermatitis is a common side effect of radiotherapy, affecting up to 95% of cancer patients receiving radiation therapy and often leading to skin damage, inflammation, and ulceration. The pathogenesis of radiation dermatitis involves complex mechanisms, such as the production of reactive oxygen species (ROS) and sustained inflammatory responses. Current treatments, including topical steroids, moisturisers, and non-steroidal anti-inflammatory drugs (NSAIDs), often provide limited efficacy, primarily addressing symptoms rather than the underlying pathophysiological processes. In this study, we evaluated the therapeutic potential of rice bran extract (RBE) in mitigating radiation-induced skin injury. High-performance liquid chromatography (HPLC) analysis revealed that RBE is rich in bioactive compounds, including pyrogallol, gallic acid, and ferulic acid, known for their antioxidant and anti-inflammatory properties. In vitro assays demonstrated that RBE exhibited fair biocompatibility, reduced IL-6 production, enhanced 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, stimulated procollagen synthesis, and promoted fibroblast migration. In a murine dorsal skin irradiation model, topical RBE application alleviated dermatitis severity, reduced skin ulceration, minimised histological signs of inflammation and fibrosis, and promoted epithelial regeneration. Bulk RNA sequencing revealed that RBE modulated key pathways related to inflammation resolution, epidermal repair, and metabolic adaptation, with Pparg identified as a central upstream regulator. Overall, RBE demonstrates antioxidant, anti-inflammatory, and pro-regenerative activities that support its potential for preventing and treating radiation dermatitis.
{"title":"Rice Bran Extract Alleviates Inflammation and Promotes Wound Healing in Radiation Dermatitis","authors":"Chen-Hsiang Kuan, Takatori Hideki, Chun-Ho Wu, Pin-Jui Kung, Wei-Hung Wang, Sung-Jan Lin, Cherng-Kang Perng","doi":"10.1111/exd.70162","DOIUrl":"https://doi.org/10.1111/exd.70162","url":null,"abstract":"<div>\u0000 \u0000 <p>Radiation dermatitis is a common side effect of radiotherapy, affecting up to 95% of cancer patients receiving radiation therapy and often leading to skin damage, inflammation, and ulceration. The pathogenesis of radiation dermatitis involves complex mechanisms, such as the production of reactive oxygen species (ROS) and sustained inflammatory responses. Current treatments, including topical steroids, moisturisers, and non-steroidal anti-inflammatory drugs (NSAIDs), often provide limited efficacy, primarily addressing symptoms rather than the underlying pathophysiological processes. In this study, we evaluated the therapeutic potential of rice bran extract (RBE) in mitigating radiation-induced skin injury. High-performance liquid chromatography (HPLC) analysis revealed that RBE is rich in bioactive compounds, including pyrogallol, gallic acid, and ferulic acid, known for their antioxidant and anti-inflammatory properties. In vitro assays demonstrated that RBE exhibited fair biocompatibility, reduced IL-6 production, enhanced 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, stimulated procollagen synthesis, and promoted fibroblast migration. In a murine dorsal skin irradiation model, topical RBE application alleviated dermatitis severity, reduced skin ulceration, minimised histological signs of inflammation and fibrosis, and promoted epithelial regeneration. Bulk RNA sequencing revealed that RBE modulated key pathways related to inflammation resolution, epidermal repair, and metabolic adaptation, with <i>Pparg</i> identified as a central upstream regulator. Overall, RBE demonstrates antioxidant, anti-inflammatory, and pro-regenerative activities that support its potential for preventing and treating radiation dermatitis.</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145012267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hao Dai, Zihao Li, Jiahui Hu, Wanying Chen, Quan Wang, Kaibo Liu, Yucang He, Liqun Li
This study utilised NHANES data from 2003 to 2006 and 2009 to 2014 to explore the association between the non-high-density lipoprotein to high-density lipoprotein cholesterol ratio (NHHR) and psoriasis. A total of 15 437 U.S. adults were analysed using multivariable logistic regression models that adjusted for cardiovascular disease, medication use, glucocorticoid therapy, and other covariates. Subgroup analyses by age, sex, and income were conducted. In addition, severity-stratified analyses were performed using data from the 2003 to 2006 and 2011 to 2014 cycles, where psoriasis severity information was available. Additional regression models comparing NHHR with traditional lipid markers (HDL-C, TC, non-HDL-C) were performed. Subsequently, Mendelian randomisation (MR) using GWAS summary statistics across European, East Asian, African, and Middle Eastern populations was conducted, with meta-analysis applied to improve precision. The results showed that NHHR was significantly associated with psoriasis (OR = 1.08, 95% CI: 1.00–1.17, p = 0.039), and those in the highest NHHR quartile had a 48% higher likelihood of developing psoriasis compared to those in the lowest quartile (OR = 1.48, 95% CI: 1.09–2.00).
{"title":"The Association Between Non-High-Density Lipoprotein Cholesterol to High-Density Lipoprotein Cholesterol Ratio With Psoriasis: A Cross-Sectional Survey and Genetic Approach","authors":"Hao Dai, Zihao Li, Jiahui Hu, Wanying Chen, Quan Wang, Kaibo Liu, Yucang He, Liqun Li","doi":"10.1111/exd.70165","DOIUrl":"https://doi.org/10.1111/exd.70165","url":null,"abstract":"<div>\u0000 \u0000 <p>This study utilised NHANES data from 2003 to 2006 and 2009 to 2014 to explore the association between the non-high-density lipoprotein to high-density lipoprotein cholesterol ratio (NHHR) and psoriasis. A total of 15 437 U.S. adults were analysed using multivariable logistic regression models that adjusted for cardiovascular disease, medication use, glucocorticoid therapy, and other covariates. Subgroup analyses by age, sex, and income were conducted. In addition, severity-stratified analyses were performed using data from the 2003 to 2006 and 2011 to 2014 cycles, where psoriasis severity information was available. Additional regression models comparing NHHR with traditional lipid markers (HDL-C, TC, non-HDL-C) were performed. Subsequently, Mendelian randomisation (MR) using GWAS summary statistics across European, East Asian, African, and Middle Eastern populations was conducted, with meta-analysis applied to improve precision. The results showed that NHHR was significantly associated with psoriasis (OR = 1.08, 95% CI: 1.00–1.17, <i>p</i> = 0.039), and those in the highest NHHR quartile had a 48% higher likelihood of developing psoriasis compared to those in the lowest quartile (OR = 1.48, 95% CI: 1.09–2.00).</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144998755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marine Delmas, Benjamin Chaussin, Nathan Harismendy, Aurore Dougé, Paul-Olivier Rouzaire, Christopher Montemagno, Jérôme Durivault, Emmanuel Moreau, Elisabeth Miot-Noirault, Mercedes Quintana, Sophie Besse, Michel D'Incan, Emmanuel Chautard, Elodie Jouberton, Jacques Rouanet
The combination of melanin-targeted radionuclide therapy (TRT) and immunotherapy offers potential in overcoming melanoma resistance to conventional therapies. Studying the potential abscopal effect induced by TRT is essential to evaluate such combination. We develop here a preclinical murine model comprising a target (pigmented) and non-target (non-pigmented) tumour to study the abscopal effect induced by melanin-TRT in melanoma. Murine melanoma cell lines were tested: two pigmented (B16-F10 and B16-OVA) and one non-pigmented (B16-G4F), inoculated in C57BL/6 mice to assess pigmentation levels and immune infiltration. Heterogeneous tumour growth and repigmentation of the B16-G4F tumour led us to develop a non-pigmented cell line (B16-OVAmTYR−/−) by tyrosinase invalidation using CRISPR/Cas9. A dual-tumour model comprising the B16-OVA tumour and the B16-OVAmTYR tumour was evaluated in terms of tumour growth, pigmentation, and immune infiltrate. The B16-OVA model displayed homogeneous tumour growth, pigmentation and high immune infiltrate (CD8+ T cells p < 0.001; CD4+ T cells p < 0.05, regulatory T cells p < 0.001). The new B16-OVAmTYR−/− cell line ensured a consistent genetic background for comparative studies. The B16-OVAmTYR−/− maintained a non-pigmented phenotype without repigmentation (no melanin expression) and demonstrated similar tumour growth characteristics to its pigmented counterpart (DT = 2.4 ± 0.5 days). Establishing a dual-tumour model using both B16-OVA and B16-OVAmTYR−/− cell lines enabled concurrent study of pigmented and non-pigmented tumours in a single host, closely mirroring clinical scenarios of metastatic melanoma. We have successfully developed a new dual-tumour pigmented and non-pigmented mouse melanoma model mimicking clinical observations to study the abscopal effect in metastatic melanoma.
{"title":"Targeting Melanin Heterogeneity in Metastatic Melanoma: A Dual-Tumour Mouse Melanoma Model","authors":"Marine Delmas, Benjamin Chaussin, Nathan Harismendy, Aurore Dougé, Paul-Olivier Rouzaire, Christopher Montemagno, Jérôme Durivault, Emmanuel Moreau, Elisabeth Miot-Noirault, Mercedes Quintana, Sophie Besse, Michel D'Incan, Emmanuel Chautard, Elodie Jouberton, Jacques Rouanet","doi":"10.1111/exd.70159","DOIUrl":"https://doi.org/10.1111/exd.70159","url":null,"abstract":"<p>The combination of melanin-targeted radionuclide therapy (TRT) and immunotherapy offers potential in overcoming melanoma resistance to conventional therapies. Studying the potential abscopal effect induced by TRT is essential to evaluate such combination. We develop here a preclinical murine model comprising a target (pigmented) and non-target (non-pigmented) tumour to study the abscopal effect induced by melanin-TRT in melanoma. Murine melanoma cell lines were tested: two pigmented (B16-F10 and B16-OVA) and one non-pigmented (B16-G4F), inoculated in C57BL/6 mice to assess pigmentation levels and immune infiltration. Heterogeneous tumour growth and repigmentation of the B16-G4F tumour led us to develop a non-pigmented cell line (B16-OVAmTYR−/−) by tyrosinase invalidation using CRISPR/Cas9. A dual-tumour model comprising the B16-OVA tumour and the B16-OVAmTYR tumour was evaluated in terms of tumour growth, pigmentation, and immune infiltrate. The B16-OVA model displayed homogeneous tumour growth, pigmentation and high immune infiltrate (CD8+ T cells <i>p</i> < 0.001; CD4+ T cells <i>p</i> < 0.05, regulatory T cells <i>p</i> < 0.001). The new B16-OVAmTYR−/− cell line ensured a consistent genetic background for comparative studies. The B16-OVAmTYR−/− maintained a non-pigmented phenotype without repigmentation (no melanin expression) and demonstrated similar tumour growth characteristics to its pigmented counterpart (DT = 2.4 ± 0.5 days). Establishing a dual-tumour model using both B16-OVA and B16-OVAmTYR−/− cell lines enabled concurrent study of pigmented and non-pigmented tumours in a single host, closely mirroring clinical scenarios of metastatic melanoma. We have successfully developed a new dual-tumour pigmented and non-pigmented mouse melanoma model mimicking clinical observations to study the abscopal effect in metastatic melanoma.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70159","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144929777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Acral melanoma (AM) is a rare subtype of cutaneous melanoma mainly found in acral locations. The treatment of advanced AM remains challenging due to its rarity and the distinct features of this subtype compared with the other common types of melanomas. There is thus an urgent need to develop effective therapeutic approaches for AM. This study was established to screen and evaluate potential therapeutic targets for AM. DNA microarray analysis comparing normal epidermal melanocytes and AM cell lines (SM2-1 and MMG-1) showed that approximately 500 genes were highly expressed in the AM cell lines compared with the levels in normal melanocytes. Among them, melanoma cell adhesion molecule (MCAM) was selected for further analyses and was found to be significantly highly expressed in AM cell lines compared with the levels in melanocytes and keratinocytes. Knockdown of MCAM significantly inhibited the proliferation of AM cell lines with decreased expression of cyclin D1 and BCL2. The cytotoxicity of MCAM-targeted antibody-drug conjugate was further evaluated and it significantly decreased the viability of AM cell lines. In conclusion, MCAM is highly expressed in AM cell lines and affects their proliferation, likely through modulating the expression of cyclin D1 and BCL2. These findings highlight the potential of MCAM as a therapeutic target of AM.
{"title":"Targeting Melanoma Cell Adhesion Molecule as a Novel Therapeutic Approach for Acral Melanoma","authors":"Yuka Tanaka, Takamichi Ito, Kiichiro Nishio, Keiko Tanegashima, Takeshi Nakahara","doi":"10.1111/exd.70164","DOIUrl":"https://doi.org/10.1111/exd.70164","url":null,"abstract":"<p>Acral melanoma (AM) is a rare subtype of cutaneous melanoma mainly found in acral locations. The treatment of advanced AM remains challenging due to its rarity and the distinct features of this subtype compared with the other common types of melanomas. There is thus an urgent need to develop effective therapeutic approaches for AM. This study was established to screen and evaluate potential therapeutic targets for AM. DNA microarray analysis comparing normal epidermal melanocytes and AM cell lines (SM2-1 and MMG-1) showed that approximately 500 genes were highly expressed in the AM cell lines compared with the levels in normal melanocytes. Among them, melanoma cell adhesion molecule (MCAM) was selected for further analyses and was found to be significantly highly expressed in AM cell lines compared with the levels in melanocytes and keratinocytes. Knockdown of MCAM significantly inhibited the proliferation of AM cell lines with decreased expression of cyclin D1 and BCL2. The cytotoxicity of MCAM-targeted antibody-drug conjugate was further evaluated and it significantly decreased the viability of AM cell lines. In conclusion, MCAM is highly expressed in AM cell lines and affects their proliferation, likely through modulating the expression of cyclin D1 and BCL2. These findings highlight the potential of MCAM as a therapeutic target of AM.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 9","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70164","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144929775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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