Experimental Dermatology最新文献

{"title":"Non-Genetic Biomarkers in Merkel Cell Carcinoma: Prognostic Implications and Predictive Utility for Response to Anti-PD-(L)1 Immune Checkpoint Inhibitors","authors":"David L. Drum,&nbsp;Anika G. Jallorina,&nbsp;Leo S. Wan,&nbsp;Victor T. Chang,&nbsp;Mary F. Lee-Wong","doi":"10.1111/exd.70030","DOIUrl":"10.1111/exd.70030","url":null,"abstract":"<p>Merkel cell carcinoma (MCC) is a skin cancer that arises due to either Merkel cell polyomavirus infection (MCPyV) or ultraviolet (UV) radiation exposure, presenting primarily in the head and neck region of fair-skinned males. The recent success of PD-(L)1 immune checkpoint inhibitors (ICIs) in locally advanced/metastatic MCC, with an objective response rate (ORR) around 50% and improved survival, as a first-line treatment has moved ICIs to the forefront of therapy for MCC and generated interest in identifying biomarkers to predict clinical response. The MCC tumour microenvironment (TME) contains various components of the adaptive and innate immune system. These components can contribute to tumour immune escape through immunosuppression by preventing entrance of other immune cells or by aiding in the cytotoxic clearance of tumour cells. We aim to combine information from studies of baseline and on-treatment monitoring of the TME to help predict the success of ICIs in MCC. This review enhances the understanding of how CD8 T cells, γδ T cells and macrophages may impact predictions of response rates to ICIs in MCC patients. These immune cells are non-genetic biomarkers that can also be used to determine prognosis in MCC treatment.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70030","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142947101","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":"Microplastics and Skin Aging: Disruption of Barrier Function and Induction of Fibroblast Senescence","authors":"Yujie Ouyang,&nbsp;Songjiang Wu,&nbsp;Yuanyuan Zhao,&nbsp;Yibo Hu,&nbsp;Ling Jiang,&nbsp;Chuhan Fu,&nbsp;Li Lei,&nbsp;Yushan Zhang,&nbsp;Xiaolei Duan,&nbsp;Jinhua Huang,&nbsp;Jing Chen,&nbsp;Qinghai Zeng","doi":"10.1111/exd.70027","DOIUrl":"https://doi.org/10.1111/exd.70027","url":null,"abstract":"<div>\u0000 \u0000 <p>Microplastics (MPs) have emerged as a major concern among contemporary pollutants, but there is still limited knowledge regarding their impact on skin function. To address this issue, we conducted a transcriptome analysis on skin tissue that had been exposed to polystyrene (PS), which is one of the most prevalent type of MPs that can be absorbed through the skin. The results of our study, obtained through functional enrichment analysis and the experiment of treating HaCaT with PS, revealed that PS may have an effect on skin barrier function, specifically the permeability barrier through inhibiting keratinocyte differentiation. Additionally, PS also induced dysfunction in the extracellular matrix (ECM). Mechanistically, we observed that PS induced fibroblasts senescence and increased the secretion of senescence-related characteristics. Furthermore, the expression of core genes related to the ECM, such as <i>COL1A1</i>, <i>COL1A2</i> and <i>SPP1</i>, was found to be down-regulated in PS-treated fibroblasts. Moreover, an in vitro experiment provided evidence of the involvement of PPARγ in PS-induced fibroblast senescence. In conclusion, our study has identified PS as a causal factor for skin barrier dysfunction. Additionally, PS induces fibroblast senescence, leading to ECM dysfunction and contributing to skin aging. These findings further strengthen the understanding and management of the effects of MPs on skin health.</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143120739","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":"A Potential Contribution of S100A11 to Skin Fibrosis and Pulmonary Involvement in Systemic Sclerosis","authors":"Takuya Takahashi,&nbsp;Takehiro Takahashi,&nbsp;Yuichiro Segawa,&nbsp;Tetsuya Ikawa,&nbsp;Hitoshi Terui,&nbsp;Toshiya Takahashi,&nbsp;Hayakazu Sumida,&nbsp;Ayumi Yoshizaki,&nbsp;Shinichi Sato,&nbsp;Yoshihide Asano","doi":"10.1111/exd.70026","DOIUrl":"https://doi.org/10.1111/exd.70026","url":null,"abstract":"<div>\u0000 \u0000 <p>Systemic sclerosis (SSc) is characterised by immune dysregulation, vasculopathy and fibrosis, driven by genetic and environmental factors. S100 proteins, which constitute a unique class of calcium-binding proteins, have been shown to be critically implicated in various inflammatory and fibrotic conditions. In this study, we investigated the possible involvement of S100A11 in SSc by examining its cutaneous expression and systemic serum levels, correlating them with key clinical parameters. First, we performed immunohistochemical (IHC) staining to examine S100A11 localisation in skin specimens from SSc patients and controls, and found that S100A11 was robustly expressed in SSc dermal fibroblasts. Analysis on the publicly available single-cell RNA-sequencing (scRNA-seq) data of SSc skin samples further confirmed that S100A11 was highly expressed in SSc dermal fibroblasts along with several key genes associated with cellular senescence. Finally, we evaluated serum levels of S100A11 in SSc patients and HCs using enzyme-linked immunosorbent assay (ELISA), and found that serum S100A11 levels were significantly elevated in diffuse cutaneous SSc (dcSSc) patients compared to controls. S100A11 serum levels in SSc patients were significantly correlated with modified Rodnan total skin thickness score and key parameters of SSc-related interstitial lung disease. Our data collectively suggested a potential pathophysiological role of S100A11 in the cutaneous and lung fibrosis associated with SSc, warranting further investigation into its functional roles in this disease.</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143120459","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":"Characterisation and Profiling of Standard Atopic Dermatitis Therapies in a Chronic Dermatitis Murine Model Induced by Oxazolone","authors":"Elena Calama,&nbsp;Ana I. Blanco,&nbsp;Juan L. Trincado,&nbsp;Arsenio Nueda,&nbsp;Félix Gil,&nbsp;Gloria Aniorte,&nbsp;Nuria Godessart,&nbsp;Amadeu Gavaldà","doi":"10.1111/exd.70024","DOIUrl":"10.1111/exd.70024","url":null,"abstract":"<div>\u0000 \u0000 <p>Atopic dermatitis (AD) is a common inflammatory skin disorder characterised by hypersensitivity to allergens, eczematous lesions and pruritus. The aim of this study was to comprehensively characterise a murine model of dermatitis and assess the similarity with the human disease, as well as to profile clinically relevant AD therapies. Four repeated topical administrations of oxazolone in the auricular skin of sensitised mice induced morphological features compatible with AD, including redness and swelling, as well as histological changes typical of spongiotic (eczematous) dermatitis and increased plasmatic IgE. Additionally, key driver Type 2 cytokines involved in the pathophysiology of the disease, IL-4, IL-13 and IL − 31, were upregulated in the skin, along with cytokines related to Type 1, 17 and 22 responses, which have been reported to be relevant in the chronic stages of the disease. RNA-seq studies in OXA model mice samples validate expression changes obtained by q-PCR and suggest a greater significant similarity with the transcriptomic signature of human AD with respect to psoriasis studies. Oral (cyclosporine, prednisolone and baricitinib) and topical treatments (betamethasone, tacrolimus and crisaborole) were effective inhibiting the induced pathology, as well as modulating the cytokine gene signature of AD. In conclusion, our 4 oxazolone challenges model recapitulates many of the key features of the disease and is responsive to AD standard of care therapies in humans.</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"33 12","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881713","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":"Hybrid of Deep Feature Extraction and Machine Learning Ensembles for Imbalanced Skin Cancer Datasets","authors":"Neetu Verma,&nbsp; Ranvijay,&nbsp;Dharmendra Kumar Yadav","doi":"10.1111/exd.70020","DOIUrl":"10.1111/exd.70020","url":null,"abstract":"<div>\u0000 \u0000 <p>Skin cancer remains one of the most common and deadly forms of cancer, necessitating accurate and early diagnosis to improve patient outcomes. In order to improve classification performance on unbalanced datasets, this study proposes a distinctive approach for classifying skin cancer that utilises both machine learning (ML) and deep learning (DL) methods. We extract features from three different DL models (DenseNet201, Xception, Mobilenet) and concatenate them to create an extensive feature set. Afterwards, several ML algorithms are given these features to be classified. We utilise ensemble techniques to aggregate the predictions from several classifiers, significantly improving the classification's resilience and accuracy. To address the problem of data imbalance, we employ class weight updates and data augmentation strategies to ensure that the model is thoroughly trained across all classes. Our method shows significant improvements over recent existing approaches in terms of classification accuracy and generalisation. The proposed model successfully received 98.7%, 94.4% accuracy, 99%, 95%, precision, 99%, 96% recall, 99%, and 96% f1-score for the HAM10000 and ISIC datasets, respectively. This study offers dermatologists and other medical practitioners' valuable insights into the classification of skin cancer.</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"33 12","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881716","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":"Molecular Characteristics of Sweet Syndrome: A Systematic Review","authors":"Laura Calabrese,&nbsp;Maurizio Romagnuolo,&nbsp;Martina D'Onghia,&nbsp;Pietro Rubegni,&nbsp;Angelo V. Marzano,&nbsp;Chiara Moltrasio","doi":"10.1111/exd.70022","DOIUrl":"10.1111/exd.70022","url":null,"abstract":"<p>Sweet syndrome (SS), originally described as acute febrile neutrophilic dermatosis, is a rare inflammatory skin condition, considered the prototype of neutrophilic dermatoses. It is characterised by the sudden onset of well-defined tender papules, plaques and nodules often accompanied by fever, neutrophilia and elevated markers of inflammation. Several variants have been described both clinically and histopathologically. Classifications include idiopathic, malignancy-associated, and drug-induced SS. The exact pathogenesis of SS is still unclear; however, recent findings have shed light on the role of dermal infiltrating neutrophils—in the context of innate immunity, and signalling pathways related to adaptive immunity. To critically analyse the current molecular landscape of SS and discuss the recent evidence supporting novel potential immune mediators and biological signalling pathways involved in SS pathogenesis. The methodology followed PRISMA guidelines and included two bibliographical databases, searching articles published until 17 December 2023. Titles, abstracts and full text were reviewed independently by two assessors, while other two investigators resolved any opinion differences. Of 3303 records identified through database search, 22 articles met the eligibility criteria for inclusion. We considered experimental studies that performed molecular analysis, in terms of cytokines quantification, gene expression and/or immunofluorescence/immunohistochemistry. As for the latter, only studies aimed at characterising the nature of the inflammatory infiltrate and potential mechanisms leading to distinct forms of cutaneous inflammatory cell influx were included. Overall, we described research on 202 SS patients (177 skin biopsies and 25 blood specimens) revealing the predominant role of neutrophil activation and abnormal proliferation as unifying mechanisms in different SS subtypes. Interestingly, we found that hyperactivation of the IL-1 pathway might occur only in a subset of SS patients and adaptive immunity could also play a role in the pathogenic scenario of SS, with a potential significant role of IL-17 axis. This systematic review provides a wealth of evidence on the molecular landscape of SS, although further research is needed to a deeper understanding of the patho-mechanisms of this rare disease and hopefully lead to targeted therapeutic approaches.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"33 12","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70022","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863298","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":"CD4+ T Cells Occupy Perivascular and Perifollicular Niches in Healthy Human Skin","authors":"Courtney E. Macon,&nbsp;Annie Yang,&nbsp;Dhara Patel,&nbsp;Jeffrey P. North,&nbsp;Michael D. Rosenblum,&nbsp;Jarish N. Cohen","doi":"10.1111/exd.70023","DOIUrl":"10.1111/exd.70023","url":null,"abstract":"<div>\u0000 \u0000 <p>Regulatory T cells (Tregs) are specialised T lymphocytes that sit at the nexus of immune regulation and tissue repair. While it is appreciated that a substantial number of Tregs are present in healthy human skin, less is known about their microanatomic spatial localisation. Knowledge about the specialised niches that Tregs occupy may aid in rational drug development to treat dermatologic diseases. Thus, we performed multiplexed immunohistochemistry for CD4 and FOXP3 (the lineage-defining transcription factor of Tregs) on healthy skin sections obtained from eight different cutaneous sites, and quantified Tregs and Tcon in distinct regions. We found that Tregs (CD4⁺ FOXP3⁺) comprised roughly 20% of CD4⁺ T cells in skin and that Tregs and T-conventional cells (Tcon; CD4⁺ Foxp3⁻) are enriched in follicularly dense skin and show preferential accumulation in perivascular and perifollicular niches in the upper dermis. Additionally, male skin shows a significant increase in the numbers of Tregs and Tcon, while female skin shows a higher Tcon:Treg ratio. We also find that the frequency of skin Tregs declines over time. Overall, we conclude that the upper dermal perivascular region is a niche that supports the accumulation of CD4⁺ T cells in steady-state human skin.</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"33 12","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824075","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":"Advances in Microbiome-Based Therapeutics for Dermatological Disorders: Current Insights and Future Directions","authors":"Tushar Madaan,&nbsp;Kyla Doan,&nbsp;Alexandra Hartman,&nbsp;Dominick Gherardini,&nbsp;Alec Ventrola,&nbsp;Yuhang Zhang,&nbsp;Nalinikanth Kotagiri","doi":"10.1111/exd.70019","DOIUrl":"10.1111/exd.70019","url":null,"abstract":"<p>The human skin hosts an estimated 1000 bacterial species that are essential for maintaining skin health. Extensive clinical and preclinical studies have established the significant role of the skin microbiome in dermatological disorders such as atopic dermatitis, psoriasis, diabetic foot ulcers, hidradenitis suppurativa and skin cancers. In these conditions, the skin microbiome is not only altered but, in some cases, implicated in disease pathophysiology. Microbiome-based therapies (MBTs) represent an emerging category of live biotherapeutic products with tremendous potential as a novel intervention platform for skin diseases. Beyond using established wild-type strains native to the skin, these therapies can be enhanced to express targeted therapeutic molecules, offering more tailored treatment approaches. This review explores the role of the skin microbiome in various common skin disorders, with a particular focus on the development and therapeutic potential of MBTs for treating these conditions.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"33 12","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70019","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142785084","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":"Bactogram: Spatial Analysis of Bacterial Colonisation in Epidermal Wounds","authors":"Karl Wallblom,&nbsp;Fredrik Forsberg,&nbsp;Sigrid Lundgren,&nbsp;Jane Fisher,&nbsp;José Cardoso,&nbsp;Ganna Petruk,&nbsp;Ann-Charlotte Strömdahl,&nbsp;Karim Saleh,&nbsp;Manoj Puthia,&nbsp;Artur Schmidtchen","doi":"10.1111/exd.70018","DOIUrl":"https://doi.org/10.1111/exd.70018","url":null,"abstract":"<p>Skin barrier damage and subsequent development of harmful microbiota contribute to conditions such as wound infections, atopic dermatitis and chronic wounds, which impact millions of people globally and pose a significant economic burden on healthcare systems. Established microbial sampling methods, such as swabs and tissue biopsies, provide limited information on the spatial distribution of bacteria. We here describe a new method that produces a visual map of the distribution of cultivable bacteria, denoted ‘Bactogram’, across the whole wound and surrounding skin, suitable for image-based quantification. As part of an exploratory endpoint in a clinical trial we applied the Bactogram method to 48 suction blister wounds in 24 healthy volunteers. Bacteria developed in all wounds, predominantly on the skin under the dressing and near wound edges. Two quantification methods, based on visual scoring and image analysis, demonstrated high inter-, and intra-rater agreement and were used to characterise bacterial re-colonisation during epidermal wound healing. We also demonstrated proof of concept that the method can be used with chromogenic agar to enable spatial identification of pathogenic bacterial species, such as <i>Staphylococcus aureus</i>. In conclusion, this study introduces a simple method for sampling bacteria over large areas and generating a bacterial map that can identify spatial variations in bacterial composition and abundance in skin and wound conditions.</p><p><b>Trial Registration:</b> ClinicalTrials.gov identifier: NCT05378997</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"33 12","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70018","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142762234","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":"Evidence of a Dose-Dependent Phenotypic Effect of the Desmoplakin (DSP) c.273+5G > A Variant in a Child With Palmoplantar Keratoderma and Woolly Hair Association","authors":"Giulia Pascolini,&nbsp;Giovanni Luca Scaglione,&nbsp;Feliciana Mariotti,&nbsp;Paola Concolino,&nbsp;Angelo Minucci,&nbsp;Biagio Didona,&nbsp;Daniele Castiglia,&nbsp;Giovanni Di Zenzo","doi":"10.1111/exd.70012","DOIUrl":"https://doi.org/10.1111/exd.70012","url":null,"abstract":"","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"33 11","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142708352","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}