{"title":"Oxidative Stress and Generalised Pustular Psoriasis: Report of d-ROM Measurements in Nine Cases Including Three of Pustular Psoriasis of Pregnancy","authors":"Chisato Tawada, Yoko Ueda, Yoko Mizutani, Xiaoyu Zang, Kayoko Tanaka, Hiroaki Iwata","doi":"10.1111/exd.70076","DOIUrl":"https://doi.org/10.1111/exd.70076","url":null,"abstract":"<p>Reactive oxygen species (ROS) are involved in the pathogenesis of generalised pustular psoriasis (GPP), but this involvement has not been fully elucidated. We performed the diacron-reactive oxygen metabolite (d-ROM) test and the biological antioxidant potential (BAP) test on sera from nine patients with active GPP who were hospitalised and treated at our hospital, including three patients with pustular psoriasis of pregnancy (PPP). The serum d-ROM and BAP levels were evaluated before treatment and at 1 month of treatment. We also performed immunostaining of 4-hydroxy-2-nonenal (4-HNE) in skin tissues. In the GPP patients, the average d-ROM levels were significantly reduced at 1 month of treatment (reduced to 343.0 ± 82.1 U.Carr from 423.2 ± 95.0 U.Carr, <i>p</i> = 0.005). The Generalised Pustular Psoriasis Area and Severity Index (GPPASI) score correlated with d-ROM levels (<i>r</i> = 0.57, <i>p</i> = 0.10), suggesting that those levels reflect the disease severity. In normal pregnancy, d-ROM values are known to increase from mid-term to late-term. The d-ROM values increased when GPP worsened in the case of PPP. Immunohistochemical staining of 4-HNE was positive for subcorneal pustules, neutrophils, and for the cytoplasm of epidermal keratinocytes, especially in upper epidermal layers. Our findings indicate that 4-HNE may play an important role in GPP and PPP.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 3","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70076","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143581669","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}
John Ivarsson, Alessandra Pecorelli, Anna Guiotto, Mariaurea Matias Souza, Hina Choudhary, Patricia Brieva, Francesca Ferrara, Giuseppe Valacchi
{"title":"Comparing UV and Diesel Cutaneous Damage and Evaluating the Protective Role of a Topical Antioxidant Mixture Containing Vitamin C, E and Ferulic Acid","authors":"John Ivarsson, Alessandra Pecorelli, Anna Guiotto, Mariaurea Matias Souza, Hina Choudhary, Patricia Brieva, Francesca Ferrara, Giuseppe Valacchi","doi":"10.1111/exd.70069","DOIUrl":"https://doi.org/10.1111/exd.70069","url":null,"abstract":"<p>Cutaneous tissue is one of the main targets of outdoor stressors, and nowadays, the effect of pollution on skin conditions and premature skin ageing has been well correlated, although the exact effect that different pollutants have on the skin has not been well defined, especially when compared to other stressors. Among the air pollutants, UV radiation and particulate matter (PM) have been found among the most aggressive in terms of skin damage, inducing oxinflammatory responses, promoting degradation of extracellular matrix (ECM) components, and compromising the cutaneous defensive barrier. Topical application of technologies able to prevent oxidative damage is still one of the best approaches to protect our skin, and considering the well-known antioxidant network, application of an antioxidant mixture is more recommended than a single compound. In the present study, human skin explants were exposed every day for 4 days to diesel particles (DEE) or to UV after the daily pre-treatment with a topical application of a commercially available antioxidant mixture (AOX Mix), containing 15% ascorbic acid, 0.5% ferulic acid and 1% tocopherol. Oxidative stress markers such as 4-hydroxynonenal, skin barrier proteins such as involucrin, filaggrin, claudin-1 and desmocollin-1, resilience markers such as elastin and tropoelastin, and the levels of Type I and Type III collagens were assessed. Topical application was able to prevent most of the damage induced by the outdoor stressors, confirming that daily protection is needed to prevent cutaneous premature ageing.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 3","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70069","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143581671","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}
{"title":"Severe Darier's Disease by Mitochondrial DNA Insertion Causing Nonsense Mutations: In Silico Prediction of a Pathophysiological Mechanism to a Novel Mutation","authors":"Haruna Shintani, Yasuaki Ikuno, Hiraku Kokubu, Shino Fujimoto, Akihiko Yamaguchi, Toshifumi Takahashi, Akiko Arakawa, Yukie Kande, Hayato Naka-Kaneda, Noriki Fujimoto","doi":"10.1111/exd.70070","DOIUrl":"https://doi.org/10.1111/exd.70070","url":null,"abstract":"<p>Darier's disease (DD) is an autosomal dominant genetic disorder caused by mutations in <i>ATP2A2</i>. Several cases with nonsense <i>ATP2A2</i> mutations presented mild-to-moderate phenotypes despite the presumed larger deletion sizes of the ATP2A2 protein. Here, we report a case of severe DD caused by a nonsense mutation with a mitochondrial DNA (mtDNA) insertion despite the smaller presumed deletion size of the ATP2A2 protein. In silico analyses of genomic lesions forming non-B DNA structures and sequence homology indicated the contingency of this DNA insertion. Analysis of the three-dimensional structure of the protein predicted no structural disturbance by this insertion. However, the QGRS Mapper algorithm predicted ectopic G-quadruplex formation in the inserted genome, which may possibly reduce <i>ATP2A2</i> transcription. Consistent with this hypothetical mechanism and possible nonsense-mediated mRNA decay, we identified downregulation of the mtDNA-inserted <i>ATP2A2</i>, which may partially contribute to the severe phenotype in this case. The mtDNA insertions into the human genome are reported to rarely occur, especially in cancers, and only a handful of mtDNA insertions causing genetic diseases are described. This study is the first report to identify mtDNA insertion as a cause of genetic disease in dermatology and demonstrates its pathophysiological mechanism through in silico analyses.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 3","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70070","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143581581","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}
Omera Bi, David Caballero-Lima, Stephen Sikkink, Gill Westgate, Sobia Kauser, Jacobo Elies, M. Julie Thornton
{"title":"Do Melanocytes Have a Role in Controlling Epidermal Bacterial Colonisation and the Skin Microbiome?","authors":"Omera Bi, David Caballero-Lima, Stephen Sikkink, Gill Westgate, Sobia Kauser, Jacobo Elies, M. Julie Thornton","doi":"10.1111/exd.70071","DOIUrl":"https://doi.org/10.1111/exd.70071","url":null,"abstract":"<p>In addition to producing melanin to protect epidermal keratinocytes against DNA damage, melanocytes may have important roles in strengthening innate immunity against pathogens. We have developed a functional, pigmented, human full-thickness 3D skin equivalent to determine whether the presence of melanocytes impacts epidermal bacterial growth and regulates the expression of genes involved in the immune response. We introduced primary epidermal melanocytes to construct a 3-cell full-thickness skin equivalent with primary dermal fibroblasts and epidermal keratinocytes. Immunohistochemistry verified the appropriate ratio and spatial organisation of melanocytes. Alpha-MSH induced melanogenesis, confirming an appropriate physiological response. We compared this 3-cell skin equivalent with the 2-cell version without melanocytes in response to inoculation with 3 species of bacteria: <i>Staphylococcus epidermidis, Corynebacterium striatum</i>, and <i>Cutibacterium acnes.</i> There was a significant decrease in the colonisation of bacteria in the skin equivalents containing functional melanocytes. There was increased expression of immune-response genes (<i>S100A9, DEFB4A, IL-4R</i>) following microorganism exposure; however, there were marked differences between the unpigmented and pigmented skin equivalents. This physiologically relevant human 3D-skin equivalent opens up new avenues for studying complex skin pigmentation disorders, melanoma, and UV damage, as well as the rapidly evolving field of the skin microbiome and the balance between commensal and pathogenic species.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 3","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70071","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143565049","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}
Rebecca Diehl, Stefanie Hübner, Saskia Lehr, Marta Rizzi, Kilian Eyerich, Alexander Nyström
{"title":"Skin Deep and Beyond: Unravelling B Cell Extracellular Matrix Interactions in Cutaneous Immunity and Disease","authors":"Rebecca Diehl, Stefanie Hübner, Saskia Lehr, Marta Rizzi, Kilian Eyerich, Alexander Nyström","doi":"10.1111/exd.70068","DOIUrl":"https://doi.org/10.1111/exd.70068","url":null,"abstract":"<p>The extracellular matrix (ECM) is a crucial component in multicellular organisms, serving as both a structural scaffold and active signalling units. While the role of the ECM, namely, to maintain homeostasis and steer adaptive immunity, is well described in secondary lymphoid organs, it is underappreciated in the skin—despite remarkable molecular similarity. Here, we examine how the specialised organisation of the ECM influences B cell development and function in both skin and secondary lymphoid organs with a special focus on ECM–integrin signalling. We discuss the presence and function of B cells in healthy and diseased skin, including their role in wound healing, autoimmune responses and inflammatory conditions. Additionally, we explore the formation of tertiary lymphoid structures in chronic skin diseases as a window into studying B cell–ECM interactions. By integrating fundamental immunology with skin biology, we aim to identify key knowledge gaps and explore potential clinical implications of B cell–ECM interactions in dermatology and beyond.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 3","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70068","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143565048","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}
Yutong Ran, Xueting Peng, Yumin Xia, Hong Liu, Yale Liu
{"title":"Periostin in Bullous Pemphigoid: A Potential Biomarker of Disease Activity and Severity","authors":"Yutong Ran, Xueting Peng, Yumin Xia, Hong Liu, Yale Liu","doi":"10.1111/exd.70067","DOIUrl":"https://doi.org/10.1111/exd.70067","url":null,"abstract":"<div>\u0000 \u0000 <p>Elevated periostin levels are commonly observed in conditions characterised by increased IgE and eosinophilia, such as bullous pemphigoid (BP), which typically presents with eosinophil infiltration and elevated IgE levels. To explore the link between periostin levels and key clinical parameters in BP, serum periostin levels were assessed in 55 classic BP patients and 55 healthy controls using ELISA. Upon admission, the BP Disease Area Index (BPDAI) score, autoantibody levels, and peripheral blood immune cells of BP patients were evaluated. The investigation also employed the Olink proteomic platform to analyse circulating proinflammatory biomarkers. The results indicated significantly higher periostin levels in BP patients, showing a strong positive correlation with BPDAI scores, which was more pronounced compared to the correlation between BPDAI scores and BP 180 IgG or eosinophil counts. Correlation analysis revealed positive links between periostin levels in serum and attributes such as urticaria/erythema lesions, total IgE levels, serum BP180 IgG, BP180 IgE, BP230 IgE, and blood eosinophil counts. The findings from the Olink proteomic analysis provided additional evidence of the connection between periostin and type II inflammation in BP, which was further validated by the observed positive correlation between periostin and IL-13 using ELISA. Furthermore, it was observed that serum periostin levels decreased post-effective treatment. Overall, this study underscores a compelling association between periostin expression and the activity and severity of BP, as well as its reflection of type II inflammation.</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 2","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143475564","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}
Alan Santos-Mena, Oscar Gonzalez-Muñiz, Adrian Rodríguez-Carlos, Alejandro Rivas Guerrero, Crisol Rodriguez Mendieta, Yolanda M. Jacobo Delgado, Gerardo Sauceda Muñoz, Yvonne Rosenstein, Valentin Trujillo-Paez, Diana Portales-Perez, Luis A. de Jesus Gonzalez, Renato Calvillo, Irma Gonzalez-Curiel, Marlen Vitales-Noyola, Bruno Rivas-Santiago
{"title":"Wound Healing Effect of HDACi Repositioned Molecules in the Therapy for Chronic Wounds Models","authors":"Alan Santos-Mena, Oscar Gonzalez-Muñiz, Adrian Rodríguez-Carlos, Alejandro Rivas Guerrero, Crisol Rodriguez Mendieta, Yolanda M. Jacobo Delgado, Gerardo Sauceda Muñoz, Yvonne Rosenstein, Valentin Trujillo-Paez, Diana Portales-Perez, Luis A. de Jesus Gonzalez, Renato Calvillo, Irma Gonzalez-Curiel, Marlen Vitales-Noyola, Bruno Rivas-Santiago","doi":"10.1111/exd.70060","DOIUrl":"https://doi.org/10.1111/exd.70060","url":null,"abstract":"<div>\u0000 \u0000 <p>Globally, chronic wounds impact the health of millions of people, negatively affecting quality of life and healthcare budgets. Some of the crucial steps and pathways in healing mechanisms are the hypoxic response and the expression of host defence peptides, which are decreased in diseases related to chronic wounds such as diabetes mellitus and cardiovascular diseases. It has been shown that histone deacetylase inhibitors can induce the expression of Host Defence Peptides (HDP) by inducing the stabilisation and activation of hypoxia-inducible factor 1-α (HIF-1α), promoting wound healing pathways, although their high cost and side effects limit clinical research. With the help of bioinformatics tools, we found potential histone deacetylase inhibitor candidates in an FDA-approved drugs database. The candidates, 1,3-Diphenylurea (DiPU), 2'-Aminoacetanilide (Ace), and Tert-butyl (2-aminophenyl) carbamate (N-boc), show wound healing effects in HaCaT cells, increasing cell migration possibly via HIF-1α, inducing the expression of LL-37 and vascular endothelial growth factor (VEGF), while in a mouse ring angiogenesis model, Ace and N-boc have angiogenic effects. In a model of basal primary keratinocytes from donors with diabetes mellitus (DM), without DM, and from Diabetic Foot Ulcers (DFU), it was observed that only DiPU is capable of inducing LL-37 in all scenarios. There is limited information about histone deacetylase inhibitors and wound healing but in this paper, we observe promising results and a proposed mechanism that involved specifically Histone Deacetylase 1 inhibition (HDAC1).</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 2","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143475565","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}
Rui Zang, Chen-Chen Xu, Zhu Fan, Qing-Nan Wang, Zi-Jian Guo, Li Liu, Bing-Nan Cui, Yuan-Yuan Huang, Jiao Yang
{"title":"The Role of Fibroblasts in Chronic Inflammatory and Proliferative Skin Diseases","authors":"Rui Zang, Chen-Chen Xu, Zhu Fan, Qing-Nan Wang, Zi-Jian Guo, Li Liu, Bing-Nan Cui, Yuan-Yuan Huang, Jiao Yang","doi":"10.1111/exd.70066","DOIUrl":"https://doi.org/10.1111/exd.70066","url":null,"abstract":"<p>Fibroblasts (FBs) are crucial mesenchymal cells that preserve the skin's natural structure and physiological processes. They can build dense connective tissue by remodelling the extracellular matrix (ECM) and control immunological activity by secreting cytokines. This indicates that the development of chronic inflammatory and proliferative skin disorders is significantly influenced by fibroblasts. In order to provide new ideas for clinical research and treatment with a clearer perspective, this study thoroughly compiles the involvement of fibroblasts in various chronic inflammatory and proliferative skin diseases such as psoriasis, hypertrophic scar (HS), keloid, atopic dermatitis (AD), oral lichen planus (OLP), chronic eczema, and rosacea.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 2","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70066","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466202","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}
Sander Bekeschus, Debora Singer, Gishan Ratnayake, Klaus Ruhnau, Kostya Ostrikov, Erik W. Thompson
{"title":"Rationales of Cold Plasma Jet Therapy in Skin Cancer","authors":"Sander Bekeschus, Debora Singer, Gishan Ratnayake, Klaus Ruhnau, Kostya Ostrikov, Erik W. Thompson","doi":"10.1111/exd.70063","DOIUrl":"https://doi.org/10.1111/exd.70063","url":null,"abstract":"<p>Skin cancer affects millions of patients worldwide, and its incidence is increasing. Current therapies targeting skin tumour subtypes, such as basal cell carcinoma, cutaneous squamous cell carcinoma, melanoma and actinic keratosis, vary in their degree of effectiveness and tolerability, motivating new research avenues on complementing treatment strategies. Cold medical gas plasma is a partially ionised gas operated at about body temperature and generates various reactive oxygen and nitrogen species simultaneously. A range of medical gas plasma devices has proven safe in thousands of patients and is an approved medical product for dermatology conditions, such as nonhealing wounds, in Europe and, more broadly, for clinical trials. Extending potential gas plasma applications in the field of dermato-oncology is therefore plausible, especially in light of the strong preclinical evidence and early clinical data. This review summarises existing work on gas plasma treatment, focusing on approved jet plasmas in skin cancer and outlining central mechanisms and treatment concepts. It also provides a concrete perspective on integrating medical gas plasma treatment into existing skin cancer therapy schemes, encouraging translational scientists and clinicians to enable gas plasma-assisted cancer care through clinical research.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 2","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70063","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143447162","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}