Yating Yang, Wen Zeng, Guangsu Chen, Wei Zhang, Yushen Su, Hongguang Lu
{"title":"OPN1SW Modulates UVB-Associated DHCR7 Reduction and Associated 25(OH)D3 and Sterol-Pool Responses in Keratinocytes","authors":"Yating Yang, Wen Zeng, Guangsu Chen, Wei Zhang, Yushen Su, Hongguang Lu","doi":"10.1111/exd.70285","DOIUrl":"10.1111/exd.70285","url":null,"abstract":"<div>\u0000 \u0000 <p>Ultraviolet B (UVB) irradiation initiates cutaneous vitamin D-related photochemistry from 7-dehydrocholesterol (7-DHC), which is also the immediate precursor of cholesterol via 7-dehydrocholesterol reductase (DHCR7). Thus, DHCR7 occupies a branch-point position linking cholesterol biosynthesis and UVB-associated vitamin D-related metabolism. How keratinocytes regulate this metabolic relationship under UVB remains unclear. We examined whether OPN1SW is associated with DHCR7 protein abundance, conditioned medium 25-hydroxyvitamin D3 [25(OH)D3] (a vitamin D-related readout) and sterol-pool responses in UVB-exposed keratinocytes. A UVB dose that preserved > 80% cell viability, 10 mJ/cm<sup>2</sup>, increased OPN1SW protein abundance and reduced DHCR7 protein abundance in human epidermal keratinocytes and HaCaT cells. These changes were accompanied by increased conditioned medium 25(OH)D3 and a reduced cellular sterol-pool readout. OPN1SW overexpression increased DHCR7 protein abundance under basal conditions. Under UVB exposure, OPN1SW overexpression attenuated UVB-associated DHCR7 reduction, attenuated the UVB-associated increase in conditioned medium 25(OH)D3 and partially preserved the sterol-pool readout. Conversely, OPN1SW knockdown exacerbated DHCR7 reduction under UVB and was accompanied by higher conditioned medium 25(OH)D3 and a lower sterol-pool readout. DHCR7 knockdown produced concordant shifts in these readouts, supporting a contributory role for DHCR7. Together, these findings support the presence of a UVB-responsive OPN1SW-DHCR7 module that may contribute to keratinocyte adaptation to UVB exposure.</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"35 6","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148137022","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}
Lin Shang, Di Zhang, Zixuan He, Yue Bai, Ansheng Tan, Fenglin Zhuo
{"title":"Integrated Analysis of Macrophage-Associated Necroptosis in Alopecia Areata.","authors":"Lin Shang, Di Zhang, Zixuan He, Yue Bai, Ansheng Tan, Fenglin Zhuo","doi":"10.1111/exd.70305","DOIUrl":"10.1111/exd.70305","url":null,"abstract":"<p><p>Necroptosis, a form of programmed cell death, promotes inflammation in immune-mediated diseases, but its role in alopecia areata (AA) remains unclear. In this study, we investigated necroptosis-related signatures in AA using integrated transcriptomic and histological analyses. Four bulk RNA-seq datasets from the GEO database, comprising 191 scalp samples from AA patients and healthy controls, were analysed by ssGSEA and GSEA to assess necroptosis-related signatures. To address the cellular heterogeneity inherent in bulk RNA data, we further performed single-cell RNA-sequencing (scRNA-seq) to investigate cell-specific mechanisms, and immunofluorescence staining of scalp biopsies was conducted to validate the expression and cellular localisation of key necroptosis-related markers. Necroptosis-related scores were significantly higher in AA than in controls, correlated with disease severity and decreased after JAK/TYK2 inhibitor therapy. At single-cell resolution, a macrophage subset (IL4I1<sup>+</sup> macrophages_1) showed the strongest necroptosis-related signal and was associated with enhanced macrophage-fibroblast communication involving TGFβ, ITGB2 and GAS6 signalling, suggesting perifollicular microenvironmental remodelling. Immunofluorescence further supported increased necroptosis-associated signalling and macrophage enrichment in AA lesions. Together, these findings suggest that macrophage-associated necroptosis-related programmes may represent a disease-associated inflammatory component in AA and support further mechanistic investigation of necroptosis-associated pathways in this disease.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"35 6","pages":"e70305"},"PeriodicalIF":3.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148294162","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}
Jose Maria Villa-Gonzalez, Johanna Ramirez-Romero, Patricia Andres-Ibarrola, Maria Rosario Gonzalez-Hermosa, Elena B. Hawryluk, Hensin Tsao, Salvador Gonzalez
{"title":"Clinical Applications of Reflectance Confocal Microscopy in Paediatric Dermatology: A Systematic Review","authors":"Jose Maria Villa-Gonzalez, Johanna Ramirez-Romero, Patricia Andres-Ibarrola, Maria Rosario Gonzalez-Hermosa, Elena B. Hawryluk, Hensin Tsao, Salvador Gonzalez","doi":"10.1111/exd.70274","DOIUrl":"10.1111/exd.70274","url":null,"abstract":"<p>This systematic review evaluates the clinical applications of reflectance confocal microscopy (RCM) in paediatric dermatology. The objective was to summarise evidence on the diagnostic and monitoring value of RCM in patients aged ≤ 18 years across dermatologic conditions. Eligible studies included original studies, observational studies, case series and case reports that used RCM in paediatric patients; non-original studies and those lacking extractable paediatric data were excluded. MEDLINE and Web of Science were searched on June 23, 2025. Risk of bias in observational studies was assessed using the modified published criteria. Data were synthesised narratively due to heterogeneity in study design, populations and outcomes. Seventy-three studies met the inclusion criteria which were classified across four condition groups: the ‘Neoplastic and related lesions’ category (25 studies), ‘Congenital anomalies’ (8), ‘Inflammatory conditions’ (30), and ‘Infections and infestations’ (14). Because some studies evaluated more than one condition, they were included in multiple categories; therefore, category-specific counts exceed the number of unique included studies. Across categories, RCM facilitated non-invasive diagnosis, differentiation of clinically similar conditions, and longitudinal monitoring, especially for melanocytic lesions, congenital pigmentary disorders, lichen sclerosus, vitiligo, acne, molluscum contagiosum, verruca plana, dermatophytosis and scabies. Several studies emphasised the advantages in sensitive regions, such as the genital area. Risk-of-bias assessment revealed variable methodological rigour, reflecting a predominance of observational designs and limited paediatric-specific data. Study heterogeneity, small sample sizes and frequent reliance on case reports or series limited evidence. Overall, findings support RCM as a safe, repeatable tool that reduces reliance on invasive procedures and aids diagnosis and treatment monitoring in paediatric dermatology.</p><p><b>Trial Registration:</b> PROSPERO CRD420251018599.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"35 6","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70274","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148053384","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}
Zasca-Aisha Ristianto, Mackenzie R. Martin, Camille Scandurro, Alisa N. Femia
{"title":"Divergent Hematologic Malignancy Risk in Morphea and Systemic Sclerosis: A Retrospective Cohort Study in the All of Us Database","authors":"Zasca-Aisha Ristianto, Mackenzie R. Martin, Camille Scandurro, Alisa N. Femia","doi":"10.1111/exd.70290","DOIUrl":"10.1111/exd.70290","url":null,"abstract":"","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"35 6","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148053436","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}