Experimental Dermatology最新文献

{"title":"An Acid-Oxidising Solution Containing Hypochlorous Acid Reduces Staphylococcus aureus and Improves Bacterial Diversity in Epidermolysis Bullosa Wounds","authors":"Xiaolong A. Zhou,&nbsp;Michael B. Burns,&nbsp;Ziyou Ren,&nbsp;Elise Stagaman,&nbsp;Stefan J. Green,&nbsp;Lok Yiu Ashley Wu,&nbsp;Lynna Yang,&nbsp;Stephanie Rangel,&nbsp;Lydia Rabbaa,&nbsp;Amy S. Paller","doi":"10.1111/exd.70147","DOIUrl":"https://doi.org/10.1111/exd.70147","url":null,"abstract":"<p>Epidermolysis bullosa (EB) is a group of rare genetic skin disorders characterised by skin fragility and chronic, painful wounds that are highly susceptible to bacterial infection, particularly by <i>Staphylococcus aureus</i> (SA). This study evaluated the efficacy of an acid-oxidising solution containing hypochlorous acid (HOCl) in reducing SA colonisation, promoting wound healing, and restoring a healthier microbiome in EB wounds. In a 12-week open-label pilot study, 15 EB patients applied the HOCl-based spray (APR-TD011) daily to chronic wounds for 8 weeks, with full-length 16S rRNA sequencing of wound swabs performed before, during, and after treatment. At baseline, 87% of patients were culture-positive for SA, and sequencing revealed that SA had the highest relative abundance (34%), followed by <i>Acinetobacter guillouiae</i> and <i>Pseudomonas poae</i>. SA relative abundance decreased precipitously by Weeks 4 (to 11%) and 8 (primary endpoint; to 10%, <i>p</i> &lt; 0.01), and this effect persisted at 4 weeks post-treatment (Week 12; to 9.7%), including for methicillin-resistant SA. Concurrently, bacterial diversity increased, and wound sizes diminished in correlation with reduced SA levels (<i>r</i> = 0.64). Younger patients exhibited greater SA reduction trends. The treatment was well-tolerated, with minimal adverse effects and high patient satisfaction. This study underscores the role of microbial dysbiosis in EB wounds and highlights HOCl-based solutions as a promising therapy to mitigate pathogenic burden and enhance wound healing.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 8","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70147","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144832450","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":"Sympathetic Nerves Are Dispensable for the Responses of Melanocyte Stem Cells to Ultraviolet B Exposure","authors":"Xiaoling Yu,&nbsp;Bing Zhang","doi":"10.1111/exd.70151","DOIUrl":"https://doi.org/10.1111/exd.70151","url":null,"abstract":"<div>\u0000 \u0000 <p>Sympathetic nerves are known to regulate stem cells in the skin. In mice, acute nociception stress activates sympathetic nerves to release noradrenaline, which acts on ADRB2 receptors in melanocyte stem cells (McSCs) to regulate their activation, differentiation and migration. Similarly, ultraviolet B (UVB) exposure induces McSCs behaviours comparable to those observed under acute stress. While epidermal keratinocytes are recognised as key regulators of McSCs responses through secreted factors encoded by genes such as Wnt7a, Col2a1 and Pomc during UVB exposure, the role of other niche components remains largely unexplored. In this study, we investigated whether sympathetic nerves influence McSCs responses to UVB exposure. Using 6-hydroxydopamine to ablate sympathetic nerves, we found no significant differences in McSCs migration, differentiation, or the expression of key keratinocyte-secreted factors between control and sympathetically denervated mice. Furthermore, beta-adrenergic receptor blockade with Nadolol did not affect McSCs responses to UVB. These findings suggest that sympathetic nerves are dispensable for the responses of McSCs to UVB exposure.</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 8","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144832764","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}

{"title":"Effect of Intradermal Morphine on Histaminergic and Non-Histaminergic Itch: A Randomised, Single-Blinded, Human Study","authors":"Silvia Lo Vecchio,&nbsp;Giulia Erica Aliotta,&nbsp;Hiroai Okutani,&nbsp;Nadia Ammitzbøll,&nbsp;Anne-Marie Wegeberg,&nbsp;Asbjørn Mohr Drewes,&nbsp;Lars Arendt-Nielsen","doi":"10.1111/exd.70149","DOIUrl":"https://doi.org/10.1111/exd.70149","url":null,"abstract":"<p>Itch can be a side-effect of drugs like opioids, with prevalence depending on the route of administration. This study aimed to investigate if morphine (1) induced itch and neurogenic inflammation after intradermal injection and (2) modulates the responses to locally experimentally induced histaminergic and non-histaminergic itch. Twenty-four healthy volunteers participated in this randomised, single-blinded study. Two areas on the volar forearms of each participant were randomly treated with either intradermal morphine 0.05 mL (0.1 mg/mL) or saline (isotonic saline 0.05 mL), followed by assessment of itch intensity, wheal, and flare reactions. After injection, histamine and cowhage (non-histaminergic itch) were randomly applied intradermally and topically, respectively at the sites of morphine/saline injection, and the assessments were repeated. Before saline/morphine injections (baseline measurement), after injections (post-intervention measurement), and after pruritogen application (post-pruritogen measurement), superficial blood perfusions were measured using full-field laser perfusion imaging. Morphine induced increased peak itch intensity and itch area under the curve compared to saline, without further increase by the experimentally induced histaminergic and non-histaminergic itch. Morphine also caused a larger wheal area compared to saline. Morphine increased superficial blood perfusion compared to saline both after treatment and after pruritogens. This study confirmed that (1) intradermal morphine induces spontaneous itch, (2) morphine induced neurogenic inflammation which alone and in combination with the pruritogens caused larger responses (wheal and flare) when compared with saline and (3) the itch intensities provoked by experimentally induced histaminergic and non-histaminergic substances were not modulated when applied to the morphine-treated areas.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 8","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70149","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144814915","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":"Updated Psoriasis Prevalence and Risk Factors in the United States—Insights From the 2023 NHIS","authors":"Priya Engel,&nbsp;Jashin J. Wu","doi":"10.1111/exd.70146","DOIUrl":"https://doi.org/10.1111/exd.70146","url":null,"abstract":"","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 8","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144782726","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}

{"title":"Skin Microbiome Under Topical and Systemic Therapeutics in Atopic Dermatitis, a Cross-Sectional Analysis From ProRaD","authors":"Robin Rohayem,&nbsp;Matthias Reiger,&nbsp;Luise Rauer,&nbsp;Avidan Uriel Neumann,&nbsp;CK-CARE-study group,&nbsp;Claudia Traidl-Hoffmann,&nbsp;Claudia Hülpüsch","doi":"10.1111/exd.70141","DOIUrl":"https://doi.org/10.1111/exd.70141","url":null,"abstract":"<p>Atopic dermatitis is a common and chronically relapsing inflammatory skin disease. Long-term management of the heterogeneous disease entity challenges patients and physicians globally. In our exploratory cross-sectional study, we investigated the correlation of local and systemic therapies with skin microbial changes in patients with atopic dermatitis (AD). We cross-sectionally evaluated the ProRaD cohort's study data between 2017 and 2019 at the Augsburg and Bonn study centres. Our analysis encompassed lesional skin microbiome swabs and medication data from 464 participants between 0 and 84 years of age. For comparative analysis, patients were grouped by disease severity. Categorisation of treatment levels was performed based on the treatment guideline for atopic dermatitis. In moderate AD, we found systemic therapy associated with a significantly lower relative abundance of <i>S. aureus</i> compared with patients receiving local treatment. However, skin microbial diversity did not significantly differ between therapeutic regimens. Furthermore, we observed a strong correlation between AD severity and relative <i>S. aureus</i> abundance in lesional skin swabs. Treatment choice, however, did not always align with disease severity, with substantial proportions of severely affected individuals receiving basic treatment only. Across all disease severities, patients receiving dupilumab tended to show a reduced <i>S. aureus</i> abundance compared to those receiving conventional immunosuppressive treatment and systemic glucocorticoids. Our findings align with recent research indicating reduced <i>S. aureus</i> abundance after systemic treatment with dupilumab, while topical anti-inflammatory treatment alone does not seem to affect skin microbial composition. Further research is needed to elucidate the microbial–immunological interactions and their implications for AD treatment.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 8","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70141","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144773818","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":"Mechanism Study on Inhibition of EPHA2 Expression Impaired Skin Barrier Function by Gefitinib","authors":"Jiang-Yuan Zhang,&nbsp;Xue-Kun Nie,&nbsp;Zi-Chun Chen,&nbsp;Su-Juan Zhou,&nbsp;Xiao-Hui Lin,&nbsp;Li Zhang,&nbsp;Di Zhong,&nbsp;Bing-Ying Xiao,&nbsp;Shi-Qing Jiang,&nbsp;Wei-Ying Huang,&nbsp;Min-Hua Lin,&nbsp;Yu-Jia Wang","doi":"10.1111/exd.70145","DOIUrl":"https://doi.org/10.1111/exd.70145","url":null,"abstract":"<div>\u0000 \u0000 <p>Previous studies have unequivocally established the efficacy of gefitinib, an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKIs), in the management of patients afflicted with advanced Non-Small Cell Lung Cancer (NSCLC). Nonetheless, the manifestation of cutaneous toxicities of varying severity has been observed to compromise patient survival outcomes and limit its clinical applicability. Elucidating the mechanistic underpinnings of gefitinib-induced dermal barrier dysfunction is imperative, as it holds the potential to inform future therapeutic strategies and facilitate the development of innovative pharmacological interventions. Utilising a multi-modal approach, this study employed network pharmacology and molecular docking techniques to identify potential etiological factors of gefitinib-induced dermal barrier dysfunction. Oral administration of gefitinib was conducted to establish a clinical model, followed by Haematoxylin and Eosin (HE) staining for epidermal and stratum corneum morphological assessment, and immunohistochemical quantification of Keratins 1 (K1) and K10 and Desmoglein-1 (DSG-1). Molecular expression levels of K10, K17, Claudin-4 (CLDN4), Interleukin-6 (IL-6), Tumour Necrosis Factor-α (TNF-α), and Ephrin Type-A Receptor 2 (EPHA2) were evaluated in HaCaT keratinocytes using Reverse Transcription Quantitative Polymerase Chain Reaction (RT-qPCR) and Western Blot assays. Additionally, EPHA2 mRNA and protein expression in murine cutaneous tissues were ascertained through RT-qPCR and Western Blot analyses. Network pharmacology and molecular docking implicated EPHA2 as a central mediator in gefitinib-induced epidermal barrier dysfunction pathways. In murine models, gefitinib administration resulted in palpebral desquamation and dorsal cutaneous erythema, accompanied by elevated expression of K1, K17, and DSG-1 and epidermal hyperplasia. Furthermore, gefitinib augmented K10, K17, IL-6, and TNF-α expression in HaCaT cells, significantly attenuated cellular viability, and suppressed CLDN4 expression. EPHA2 mRNA and protein expression were notably downregulated in both HaCaT cells and BALB/c murine models. Ephrin-A1 Fc, an EPHA2 agonist, effectively mitigated gefitinib-induced cutaneous damage and inflammation, while concurrently downregulating K10, K17, IL-6, and TNF-α expression in HaCaT cells and upregulating CLDN4 expression. Gefitinib appears to induce dermal barrier dysfunction via the downregulation of EPHA2 expression.</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 8","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144725373","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}

{"title":"Targeting XIAP and EGFR as an Approach for Treating Melanoma","authors":"Joy Steinkamp,&nbsp;Nadine Mersch,&nbsp;Hamid Kashkar,&nbsp;Paola Zigrino","doi":"10.1111/exd.70144","DOIUrl":"https://doi.org/10.1111/exd.70144","url":null,"abstract":"","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 8","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717013","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}

{"title":"Neutrophils- and Pyroptosis-Related Genes IL1B and PYCARD as Diagnostic Biomarkers for Systemic Lupus Erythematosus","authors":"Ying Li,&nbsp;Weibo Lian","doi":"10.1111/exd.70143","DOIUrl":"https://doi.org/10.1111/exd.70143","url":null,"abstract":"<div>\u0000 \u0000 <p>Systemic lupus erythematosus (SLE) is closely associated with neutrophils and pyroptosis, but the pyroptosis related genes (PRGs) with neutrophils in SLE have been less studied. Based on public databases, key genes associated with neutrophil pyroptosis in SLE were identified through immune infiltration analysis and differential analysis. Subsequently, three machine learning algorithms were utilised to derive biomarkers. Additionally, based on the logistic regression model, we constructed a weighted score formula and determined the optimal cut-off value through receiver operating characteristic (ROC) analysis. Gene set enrichment analysis (GSEA) and localization analysis were performed on the biomarkers. The expression of the biomarkers in SLE was verified by reverse transcription-quantitative PCR (RT-qPCR) and western blotting. Through a series of screenings, two biomarkers (PYCARD and IL1B) were obtained. The weighted score based on biomarkers could better distinguish SLE patients from healthy individuals with high diagnostic accuracy. These two biomarkers were found to be involved in the same pathways, including ‘toll-like receptor signaling pathway’, ‘NOD-like receptor signaling pathway’ and ‘chemokine signaling pathway’. Subcellular localization analyses showed that both biomarkers were mainly localised in the cytoplasm. The results of RT-qPCR and western blotting showed that PYCARD and IL1B were highly expressed in SLE samples, which was consistent with our transcriptome results. In conclusion, we filled a knowledge gap in the area of central granulocyte-associated pyroptosis in SLE. These findings provide a reference for the potential targeting of neutrophil-associated pyroptosis genes in the treatment of patients with SLE.</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 7","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688223","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}

{"title":"The Skin Microbiome, Microbial Metabolites and the Epidermal Response to Ultraviolet Radiation—Towards Next Generation Suncare","authors":"Steven D. Mercer,&nbsp;Andrew J. McBain,&nbsp;Catherine O'Neill","doi":"10.1111/exd.70142","DOIUrl":"https://doi.org/10.1111/exd.70142","url":null,"abstract":"<p>Ultraviolet radiation (UVR) presents one of the greatest challenges to human skin, with numerous studies documenting its effects on skin physiology. Recently, growing recognition of the microbiome's crucial role in skin health has led to investigations on how UVR influences skin-microbiome interactions. Research in mice suggests that the microbiome plays a key role in regulating the skin's response to UVR, impacting inflammation, immune function, and keratinocyte differentiation. These effects may be mediated by microbial metabolites (MM), yet the impact of UVR on microbial metabolism and its subsequent effects on skin health remains poorly understood. Some studies suggest that UVR exposure may modify the composition of the microbiome, which could, in turn, alter the microbial metabolome. This viewpoint reviews the current literature regarding the interplay between the skin, its microbiome, and UVR, and speculates on how UVR-induced changes to microbial composition and metabolism might affect skin health. Furthermore, future areas of research that should be considered and the potential of MM in next generation suncare, cosmetics and therapeutics will be highlighted.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 7","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70142","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688216","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":"Interleukin-17A-Related Inflammation Mediates Cardiac Injury in Chronic Relapsing Psoriasis-Like Mouse Model","authors":"Mengyan Hu,&nbsp;Han Cao,&nbsp;Shimin Zhang,&nbsp;Li Zhang,&nbsp;Lihong Chen,&nbsp;Yuhan Xia,&nbsp;Jiayi Zhang,&nbsp;Qi Yang,&nbsp;Feng Xue,&nbsp;Xia Li,&nbsp;Jie Zheng","doi":"10.1111/exd.70139","DOIUrl":"https://doi.org/10.1111/exd.70139","url":null,"abstract":"<div>\u0000 \u0000 <p>Psoriasis is an inflammatory disease characterised by chronic recurrent relapses. Previous observational studies have shown that patients with psoriasis are predisposed to cardiovascular comorbidities, but few studies have investigated the impact of psoriasis-related chronic inflammation on cardiac function. In this study, we used imiquimod (IMQ) to establish psoriasis-like mouse models with short-term inflammation (IMQ-ST) or long-term repeated inflammation (IMQ-LT), to mimic acute or chronic recurrent pathophysiology of psoriasis inflammation. The inflammatory pattern in the hearts of IMQ-ST mice and IMQ-LT mice was similar to that in the skin, characterised by increased level of interleukin (IL)-17A and proportion of IL-17A-producing γδT cells. However, only IMQ-LT mice showed declined cardiac function, significant myocardial tissue necrosis, and decreased expression of genes encoding structural and functional proteins in cardiomyocytes. Furthermore, IL-17A neutralisation markedly alleviated myocardial injury and improved cardiac function in IMQ-LT mice. In conclusion, we demonstrated that IL-17A-mediated inflammation was present in the skin and heart of acute and chronic psoriasis-like mouse models. However, only IMQ-LT mice developed myocardial injury and declined cardiac function, which could be prevented by IL-17A neutralisation.</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 7","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144672010","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}