British Journal of Dermatology最新文献

{"title":"Novel therapeutic strategy for intractable keloids: suppression of intracellular mechanotransduction and actin polymerization via Rho-kinase pathway inhibition.","authors":"Sally Min, Ki-Myo Kim, Jun Ho Park, Mihyun Lee, Joseph Hwang, Ji-Ung Park","doi":"10.1093/bjd/ljae384","DOIUrl":"10.1093/bjd/ljae384","url":null,"abstract":"<p><strong>Background: </strong>Keloid is a dermal fibrotic disorder characterized by excessive extracellular matrix production by fibroblasts. Despite the significance of mechanostimulation in fibrotic diseases, its association with keloid pathophysiology or treatment remains unexplored.</p><p><strong>Objectives: </strong>To investigate the role of mechanical force in keloid formation and elucidate the significance of Rho-associated coiled-coil-containing kinase 1 (ROCK1) as a mechanoresponsive target for keloid treatment.</p><p><strong>Methods: </strong>Patient-derived keloid fibroblasts (KFs) were subjected to cyclic stretching ranging from 0% to 20% elongation using a cell-stretching system. We observed the inhibitory effects of the ROCK1 inhibitor Y27632 on KFs and keloid formation. Validation was performed using a keloid xenograft severe combined immune-deficient (SCID) mouse model.</p><p><strong>Results: </strong>ROCK1 was overexpressed in KFs isolated from patients. Cyclic stretching induced fibroblast proliferation and actin polymerization by activating Rho/ROCK1 signalling. Treatment with Y27632 downregulated fibrotic markers reduced the migration capacity of KFs and induced extensive actin cytoskeleton remodelling. In the keloid xenograft SCID mouse model, Y27632 effectively suppressed keloid formation, mitigating inflammation and fibrosis.</p><p><strong>Conclusions: </strong>The ROCK1 inhibitor Y27632 is a promising molecule for keloid treatment, exerting its effects through actin cytoskeleton remodelling and nuclear inhibition of fibrotic markers in keloid pathogenesis.</p>","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"458-467"},"PeriodicalIF":11.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The management of atopic dermatitis in women of childbearing age: confused terminology, lack of evidence and resulting clinical inertia.","authors":"Ruchika Kumari, Christian J Apfelbacher, Catherine Nelson-Piercy, Carsten Flohr","doi":"10.1093/bjd/ljae398","DOIUrl":"10.1093/bjd/ljae398","url":null,"abstract":"","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"530-532"},"PeriodicalIF":11.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142458456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging challenges in global health dermatology: measuring impact and sustainability.","authors":"Morvarid Zehtab, L Claire Fuller, Wendemagegn Enbiale, Karolyn A Wanat, Luca Borradori, Henry W Lim, Esther E Freeman","doi":"10.1093/bjd/ljae435","DOIUrl":"10.1093/bjd/ljae435","url":null,"abstract":"","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"532-534"},"PeriodicalIF":11.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatial proteomics reveals sirtuin 1 to be a determinant of T-cell infiltration in human melanoma.","authors":"Jan-Malte Placke, Jenny Bottek, Renata Váraljai, Batool Shannan, Sarah Scharfenberg, Christoph Krisp, Philippa Spangenberg, Camille Soun, Devon Siemes, Lars Borgards, Franziska Hoffmann, Fang Zhao, Anette Paschen, Hartmut Schlueter, Ferdinand von Eggeling, Iris Helfrich, Florian Rambow, Selma Ugurel, Alpaslan Tasdogan, Dirk Schadendorf, Daniel R Engel, Alexander Roesch","doi":"10.1093/bjd/ljae433","DOIUrl":"10.1093/bjd/ljae433","url":null,"abstract":"<p><strong>Background: </strong>The tumour microenvironment significantly influences the clinical response of patients to therapeutic immune checkpoint inhibition (ICI), but a comprehensive understanding of the underlying immune-regulatory proteome is still lacking.</p><p><strong>Objectives: </strong>To decipher targetable biologic processes that determine tumour-infiltrating lymphocytes (TiLs) as a cellular equivalent of clinical response to ICI.</p><p><strong>Methods: </strong>We mapped the spatial distribution of proteins in TiL-enriched vs. TiL-low compartments in melanoma by combining microscopy, matrix-assisted laser desorption mass spectrometry imaging and liquid chromatography-mass spectrometry, as well as computational data mining. Pharmacological modulation of sirtuin 1 (SIRT1) activity in syngeneic mouse models was used to evaluate the efficacy of pharmacological SIRT1 activation in two syngeneic melanoma mouse models, one known to be α-programmed cell death protein 1 (PD-1) sensitive and the other α-PD-1 resistant.</p><p><strong>Results: </strong>Spatial proteomics and gene ontology-based enrichment analysis identified > 145 proteins enriched in CD8high tumour compartments, including negative regulators of mammalian target of rapamycin signalling such as SIRT1. Multiplexed immunohistochemistry confirmed that SIRT1 protein was expressed more in CD8high than in CD8low compartments. Further analysis of bulk and single-cell RNA sequencing data from melanoma tissue samples suggested the expression of SIRT1 by different lymphocyte subpopulations (CD8+ T cells, CD4+ T cells and B cells). Furthermore, we showed in vivo that pharmacological SIRT1 activation increased the immunological effect of α-PD-1 ICI against melanoma cells in mice, which was accompanied by an increase in T-cell infiltration and T-cell-related cytokines, including interferon (IFN)-γ, CCL4, CXCL9, CXCL10 and tumour necrosis factor-α. In silico analysis of large transcriptional data cohorts showed that SIRT1 was positively associated with the proinflammatory T-cell chemokines CXCL9, CXCL10 and IFN-γ, and prolonged overall survival of patients with melanoma.</p><p><strong>Conclusions: </strong>Our study deciphers the proteomics landscape in human melanoma, providing important information on the tumour microenvironment and identifying SIRT1 as having important prognostic and therapeutic implications.</p>","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"481-491"},"PeriodicalIF":11.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142909307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recently discovered roles for macrophages in human skin development.","authors":"John A McGrath","doi":"10.1093/bjd/ljae473","DOIUrl":"10.1093/bjd/ljae473","url":null,"abstract":"","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"371-372"},"PeriodicalIF":11.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Joint exposure to multiple air pollutants, genetic risk and incident psoriasis: a large-scale prospective cohort study.","authors":"Yan Xiong, Yuting Xia, Xinyue Zhang, Biling Jiang, Zeling Zhang, Chunhui Xie, Xiaoping Miao, Jiajia Lan, Juan Tao","doi":"10.1093/bjd/ljae391","DOIUrl":"10.1093/bjd/ljae391","url":null,"abstract":"<p><strong>Background: </strong>Air pollution and genetic risk have been found to contribute to the onset and development of psoriasis. However, the extent to which genetic susceptibility modifies the effects of air pollutants on the risk of incident psoriasis remains unknown.</p><p><strong>Objectives: </strong>To assess the association between joint exposure to multiple air pollutants and the risk of psoriasis, and its modification, according to genetic susceptibility.</p><p><strong>Methods: </strong>This prospective study included 451 064 participants from the UK Biobank who had complete air pollution data and were free of psoriasis at baseline. All participants were enrolled from 2006 to 2010 and followed up to 2022. An air pollution score (APS) was calculated to assess joint exposure to multiple air pollutants, including fine particulate matter (PM) with diameters ≤ 2.5 μm (PM2.5), between 2.5 and 10 μm (PM2.5-10) and ≤ 10 μm (PM10), as well as nitrogen dioxide (NO2) and nitrogen oxides (NOx). To evaluate the genetic risk, a polygenic risk score (PRS) for psoriasis was constructed. Cox proportional hazard models were used to assess the association of air pollution and genetic susceptibility with the risk of psoriasis. Stratified analyses were conducted based on the individual characteristics.</p><p><strong>Results: </strong>During a median follow-up of 13.79 years (range 0.00-16.81), 4414 cases of psoriasis were recorded. The hazard ratios (HRs) for psoriasis were 1.036 [95% confidence interval (CI) 0.936-1.147], 1.091 (95% CI 0.987-1.206), 1.159 (95% CI 1.048-1.283) and 1.163 (95% CI 1.052-1.286) in the higher APS quintile groups (Q2, Q3, Q4 and Q5, respectively) vs. the lowest APS quintile (Q1; P-value for trend < 0.05). When considering genetic susceptibility, participants with a high PRS and a high APS had the greatest risk of incident psoriasis (HR 1.962, 95% CI 1.630-2.362) vs. those with a low PRS and low APS. The HRs for PM2.5-10, NOx, PM2.5 absorbance, PM2.5, NO2 and PM10 in the group with the highest exposure level and genetic risk were 1.831 (95% CI 1.537-2.181), 1.722 (95% CI 1.431-2.073), 1.698 (95% CI 1.416-2.037), 1.619 (95% CI 1.353-1.938), 1.504 (95% CI 1.252-1.806) and 1.425 (95% CI 1.192-1.704), respectively.</p><p><strong>Conclusions: </strong>Long-term exposure to various air pollutants is positively associated with an increased risk of incident psoriasis, particularly in individuals with a high genetic risk of the disease. More comprehensive measures are needed to reduce the air pollution levels for better prevention of psoriasis.</p>","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"420-429"},"PeriodicalIF":11.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142458450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic value of three complete blood count abnormalities, hypereosinophilia, hyperlymphocytosis and basophilic lymphocytes, in Drug Reaction with Eosinophilia and Systemic Symptoms.","authors":"Patti Carmela Liccardo, Saskia Ingen-Housz-Oro, Pierre Wolkenstein, Orianne Wagner-Ballon, Bouchra Badaoui","doi":"10.1093/bjd/ljae378","DOIUrl":"10.1093/bjd/ljae378","url":null,"abstract":"","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"537-538"},"PeriodicalIF":11.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expanding phenotypic insights of palmoplantar keratodermas based on novel FAM83G variants.","authors":"Marike W van Gisbergen, S Vanya J Rossel, Tom E J Theunissen, Renske Janssen, Tariraishe Kaseke, Jasper J van der Smagt, Peter M Steijlen, Maaike Vreeburg, Antoni H Gostynski, Michel van Geel","doi":"10.1093/bjd/ljae419","DOIUrl":"10.1093/bjd/ljae419","url":null,"abstract":"","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"544-546"},"PeriodicalIF":11.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploration of the mutational landscape of cutaneous leiomyoma confirms FH as a driver gene and identifies targeting purine metabolism as a potential therapeutic strategy.","authors":"Louise van der Weyden, Martin Del Castillo Velasco-Herrera, Saamin Cheema, Kim Wong, Jacqueline M Boccacino, Ian Vermes, Victoria Offord, Alastair Droop, David R A Jones, Elizabeth Anderson, Claire Hardy, Nicolas de Saint Aubain, Peter M Ferguson, Carolin Mogler, Neil Rajan, Derek Frew, Paul W Harms, Steven D Billings, Désirée Schatton, Marc Segarra-Mondejar, Mark J Arends, Ingrid Ferreira, Thomas Brenn, Christian Frezza, David J Adams","doi":"10.1093/bjd/ljae432","DOIUrl":"10.1093/bjd/ljae432","url":null,"abstract":"","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"551-553"},"PeriodicalIF":11.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11833311/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: Single-cell RNA sequencing comparison of CD4+, CD8+ and T-cell receptor γδ+ cutaneous T-cell lymphomas reveals subset-specific molecular phenotypes.","authors":"","doi":"10.1093/bjd/ljae374","DOIUrl":"10.1093/bjd/ljae374","url":null,"abstract":"","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":" ","pages":"e2"},"PeriodicalIF":11.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11833310/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}