Ang Li, Feilong Chen, Qingyue Xia, Baoyi Liu, Jingkai Xu, Xuejiao Song, Tao Xu, Yong Cui
{"title":"Riboflavin Deficiency Associated With Psoriasis: Insights From Population and Transcriptome","authors":"Ang Li, Feilong Chen, Qingyue Xia, Baoyi Liu, Jingkai Xu, Xuejiao Song, Tao Xu, Yong Cui","doi":"10.1111/exd.70106","DOIUrl":"https://doi.org/10.1111/exd.70106","url":null,"abstract":"<div>\u0000 \u0000 <p>Psoriasis is a chronic inflammatory skin disease characterised by oxidative stress in the epidermis. Riboflavin (vitamin B2), an essential vitamin with antioxidant properties, may play a role in modulating this condition. Using data from three cycles of the National Health and Nutrition Examination Survey (NHANES), we analysed 13 825 U.S. citizens, including 409 (2.96%) cases of psoriasis. A fully adjusted weighted logistic regression model revealed that psoriasis was associated with decreased riboflavin intake: for each natural-log unit increase in riboflavin intake, the risk of psoriasis decreased by an average of 16% (OR: 0.84, 95% CI: 0.73–0.96). This association was particularly significant among middle-aged and elderly people (> 40 years). Transcriptome analysis of data series GSE41662 and GSE121212 demonstrated upregulation of riboflavin metabolising genes (SLC52A2, SLC52A3, RFK, FLAD1 and SLC25A32) in psoriatic lesional skin. In an in vitro psoriatic keratinocyte model, riboflavin reduction induced upregulation of inflammatory cytokines, ROS response and delayed keratinisation. These findings indicate that psoriasis is significantly associated with decreased riboflavin intake, and riboflavin metabolism is activated in psoriasis. The protective effect of riboflavin on psoriasis merits further attention.</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 5","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143896813","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":"Evaluation of the Smoking Exposure Effects on Carcinogenesis Markers According to the Localization of Melanocytic Lesions","authors":"Laurine Batut, Stéphane Sanchez, Nathalie Lalun, Lynda Saber Cherif, Nicole Bouland, Anne Durlach, Valérian Dormoy","doi":"10.1111/exd.70111","DOIUrl":"https://doi.org/10.1111/exd.70111","url":null,"abstract":"<div>\u0000 \u0000 <p>Melanoma is considered to be the most lethal skin cancer, and smoking is one of the most important public health issues, but its potential carcinogenic role in melanoma is still discussed. Our study aims to determine whether direct tobacco smoke exposure has an impact on melanocytic lesions regarding atypia and proliferation by analysing three markers of interest: DNA ploidy index, MCM6 and the α5-nicotinic acetylcholine receptor (CHRNA5). 90 patients with surgically removed melanocytic lesions were selected. Their smoking exposure data were collected. The expression of all three markers was analysed in lesions directly exposed to tobacco smoke and compared with lesions protected from exogen contact. No difference was found between lesions chronically exposed to smoke and those protected. In the smoker group, CHRNA5 expression (<i>p</i> = 0.25) and MCM6 expression (<i>p</i> = 0.24) were not statistically different depending on the location of lesions. There was also no difference in the DNA ploidy index (<i>p</i> = 0.3). Therefore, tobacco smoke does not seem to have an impact on CHRNA5 expression, proliferation and atypia markers in melanocytic lesions.</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 5","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143896790","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 Role of Bile Acid in Immune-Mediated Skin Diseases","authors":"Huike Ma, Ruonan Li, Baoquan Qu, Yuchen Liu, Ping Li, Jingxia Zhao","doi":"10.1111/exd.70108","DOIUrl":"https://doi.org/10.1111/exd.70108","url":null,"abstract":"<p>Immune-mediated skin disorders arise from dysfunctional immune responses, instigating inflammatory dermatoses and a reduced quality of life. The complex pathogenesis likely involves genetic risks, environmental triggers and aberrant immune activation. An emerging body of evidence suggests that bile acid disturbances may critically promote immune pathology in certain skin conditions. Bile acids synthesised from cholesterol regulate nutrient metabolism and immune cell function via nuclear receptors and G protein-coupled receptors (GPCRs). Altered bile acid profiles and receptor expression have been identified in psoriasis, atopic dermatitis (AD) and autoimmune blistering diseases. Disruptions in bile acid signalling affect the inflammatory and metabolic pathways linked to these disorders. Targeting components of the bile acid axis represents a promising therapeutic strategy. This review elucidates the intricate links between bile acid homeostasis and immune dysfunction in inflammatory skin diseases, synthesising evidence that targeting bile acid pathways may unlock innovative therapeutic avenues. This study compiles clinical and experimental data revealing disrupted bile acid signalling and composition in various immune-mediated dermatoses, highlighting the emerging significance of bile acids in cutaneous immune regulation.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 5","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70108","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143888996","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}
Nermeen Ibrahim Bedair, Mohamed H. M. EL-Komy, Nouran Elhamy, Vanessa Hafez
{"title":"Nail Involvement Among Psoriasis Patients: A Comparative Retrospective Cohort Analysis of 2888 Egyptian Patients","authors":"Nermeen Ibrahim Bedair, Mohamed H. M. EL-Komy, Nouran Elhamy, Vanessa Hafez","doi":"10.1111/exd.70105","DOIUrl":"https://doi.org/10.1111/exd.70105","url":null,"abstract":"<div>\u0000 \u0000 <p>Nail involvement in psoriasis was reported in 10%–55% of psoriasis patients. Nail psoriasis treatment can be more challenging than treating skin lesions for lack of adequate absorption of topical agents plus the slower nail turnover. To study the demographic and clinical characteristics of psoriasis patients with nail involvement compared to psoriasis patients without nail involvement. Retrospective analysis of all patients attending the psoriasis unit between 2015 and 2020 was performed. Patients with and without nail involvement were compared accordingly. A total of 2888 patients were included in the analysis, 2363 of which had no nail involvement and 525 had clinical involvement of nails (18%). Nail involvement was significantly higher among male patients, smokers, patients with longer disease duration, patients with evidence of psoriatic arthritis and those on metformin. Patients with nail involvement did not show a significant association with diabetes or the manual nature of occupations. The retrospective nature of the study carries the risk of poor registration and has little control over the potential confounders. The involvement of nails in psoriasis was associated with severe disease and was a risk factor for other comorbidities including psoriatic arthritis.</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 5","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143880120","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":"Scaling Autologous Epidermal Cell Therapies: iPSC-Derived Keratinocytes and In Vivo Chimerism for Skin Regeneration","authors":"Sina Kardeh, Mohsen Mazloomrezaei, Ahmad Hosseini","doi":"10.1111/exd.70107","DOIUrl":"https://doi.org/10.1111/exd.70107","url":null,"abstract":"<p>Severe skin injuries and genetic disorders such as epidermolysis bullosa present significant clinical challenges due to limitations in current epidermal replacement therapies. While promising, cultured epithelial autografts (CEAs) suffer from prolonged culture times, cellular senescence, and low-quality clinical outcomes, limiting their widespread application. Recent advancements in iPSC-derived keratinocytes (iKeratinocytes) and in vivo chimerism offer transformative potential for scalable and personalised skin regeneration. Advances in understanding transcriptional networks, mRNA delivery, CRISPR-based genome editing, and automated biomanufacturing processes can enable improved and efficient protocols for generating iKeratinocytes. Despite these advances, there are still challenges for scaling iKeratinocytes, including optimising xeno-free culture systems and developing reproducible methods for generating multilayered skin with appendages. Interspecies chimerism utilising lineage-specific ablation systems and targeted in utero delivery of organ progenitor cells can enable human epidermal tissue development within animal hosts, offering an alternative novel platform for scaling epidermal cell and skin generation. This method, however, requires further refinements for complete ablation and detachment of target cells in the animal hosts and improved human cell integration in chimeric models. Together, iKeratinocytes and in vivo chimerism hold great promise for advancing autologous epidermal cell therapies and enabling broader clinical adoption and improved outcomes for patients with severe skin injuries and genetic disorders.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 5","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70107","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143880125","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":"Changes in the Immune Profile and Chromatin Accessibility of Peripheral Regulatory T Cells in Psoriasis Patients Before and After Treatment With Biologics","authors":"Yuxi Zhang, Xiaoqing Xu, Xiaojing Zhang, Shuangying Ni, Donger Chen, Yuqi Cheng, Xiaonan Liu, Niannian Cui, Lili Tang, Hui Cheng, Fusheng Zhou","doi":"10.1111/exd.70079","DOIUrl":"https://doi.org/10.1111/exd.70079","url":null,"abstract":"<div>\u0000 \u0000 <p>Psoriasis is a chronic inflammatory skin disease. The excessive activation of proinflammatory cytokines interleukin-17 (IL-17), IL-23 and T helper cell 17(Th17) is the main pathogenic factor. In addition, the dysfunction of suppressor cells such as regulatory T cells (Tregs) and the imbalance of the Th17/Treg ratio also play important roles in the pathogenesis of psoriasis. By testing the immune function of peripheral Tregs in psoriasis, psoriasis treated with anti-IL-17 biologics, and healthy controls, we found that the number and function of psoriatic peripheral Tregs were abnormal, and Tregs differentiated from ‘inhibitory’ to ‘inflammatory’ cells in the inflammatory environment, which may be the cause of Tregs dysfunction in psoriasis. We also found through the assay for targeting accessible chromatin with high-throughput sequencing (ATAC-seq) analysis that the chromatin accessibility of psoriatic peripheral Tregs was significantly higher than that of healthy controls and decreased after treatment, which may be related to <i>INO80</i>, a gene that controls changes in chromatin tightness or relaxation status. In addition, the differentially expressed genes (DEGs) of three groups, such as <i>NCAM2</i>, <i>CDH18</i>, <i>ZEB1</i> and <i>CCDC22</i>, were mainly concentrated in the signalling pathways related to effector T(Teff) cell aggregation and Tregs dysfunction. This study provides an important basis for the study of peripheral Tregs dysfunction in psoriasis.</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 4","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143865790","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}
Tae-Ryong Riew, Ji-Won Hwang, Tae Keun Kim, Yoon-Seob Kim
{"title":"RNA Sequencing Revealed Distinct Expression Profiles and Temporal Expression Dynamics in Murine Model of Foreign Body Reaction","authors":"Tae-Ryong Riew, Ji-Won Hwang, Tae Keun Kim, Yoon-Seob Kim","doi":"10.1111/exd.70104","DOIUrl":"https://doi.org/10.1111/exd.70104","url":null,"abstract":"<div>\u0000 \u0000 <p>Foreign body reaction (FBR) is an inflammatory and fibrotic reaction to degradation-resistant foreign materials characterised by the temporal cascade of cellular and molecular dynamics, which remains not fully elucidated. The aim of our study was to elucidate the temporal gene expression profiles of FBR. An FBR model was generated by implanting polycaprolactone into the abdominal subcutaneous layer of C57BL/6 mice. RNA sequencing was performed using established FBR tissues at various time points after implantation (FBR group; 2, 4, 8 and 12 weeks, <i>n</i> = 4 for each time points), and normal dorsal skin of mice as the control group (<i>n</i> = 3). We identified distinct gene expression profiles between the control group and the FBR group. Extracellular matrix (ECM), immune, and epigenetics-related genes were significantly enriched in the FBR group compared to normal skin. Within the FBR groups, expression profiles did not show definitive segregation across time points. We observed the highest expression of ECM-related genes (<i>Adamts4</i>, <i>Col9a3</i>, <i>Col6a2</i>, and <i>Furin</i>) and pathways in the 2-week samples, followed by a gradual down-regulation thereafter. In conclusion, our study elucidated distinct expression profiles of FBR in comparison to normal skin, as well as the temporal expression dynamics of FBR.</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 4","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143865788","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":"Lichen Planus Pemphigoides as an Adverse Reaction to Medication Use: A Retrospective Analysis of Commonly Implicated Medication Triggers Using the FDA Adverse Events Reporting Database","authors":"Gaurav N. Pathak, Priya Agarwal, Babar K. Rao","doi":"10.1111/exd.70103","DOIUrl":"https://doi.org/10.1111/exd.70103","url":null,"abstract":"","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 4","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143849197","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}
Corinne I. Stoffel, Ossia Eichhoff, Phil F. Cheng, Luzia Seiler, Flavia Tellenbach, Andreas Dzung, Francesca Chiovaro, Reinhard Dummer, Mitchell P. Levesque
{"title":"Protein Kinase C Inhibition Overcomes Targeted Therapy Resistance in Cutaneous Melanoma","authors":"Corinne I. Stoffel, Ossia Eichhoff, Phil F. Cheng, Luzia Seiler, Flavia Tellenbach, Andreas Dzung, Francesca Chiovaro, Reinhard Dummer, Mitchell P. Levesque","doi":"10.1111/exd.70093","DOIUrl":"https://doi.org/10.1111/exd.70093","url":null,"abstract":"<div>\u0000 \u0000 <p>WNT5a expression is associated with a MAPK inhibitor resistant phenotype in melanoma driving cell polarity and invasion. No small molecules specifically targeting WNT5a are available. Promising results of targeting non-canonical WNT5a-dependent WNT signalling with a pan-PKC inhibitor in uveal melanoma prompted us to investigate the relevance of PKC inhibition in cutaneous melanoma. We revealed PKC signalling and WNT5a expression to be associated in a positive feedback loop, suggesting pan-PKC inhibitor as a potent inhibitor of WNT5a in cutaneous melanoma. Combinatorial PKC and MAPK pathway inhibition significantly reduced proliferation and invasion by induction of apoptosis in targeted therapy-resistant melanoma in vitro. In in vivo xenograft studies, we found less proliferation and apoptosis induction in the PKC inhibitor single and combination treatment group with MAPK pathway inhibitors than in the standard of care treatment group. Thus, targeting the non-canonical WNT signalling pathway via combinatorial PKC and MAPK pathway inhibition is beneficial for therapy-resistant cutaneous melanoma combating tumour heterogeneity in vivo. With our study, we are providing an alternate treatment strategy we think is worth investigating as future clinical interventions in cutaneous melanoma.</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 4","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143840927","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":"Topical Application of Fluoxetine Improves DNCB-Induced Atopic Dermatitis in Mice","authors":"Xue Jiang, Xiaobin Wu, Fujin Yang, Yanxi Li","doi":"10.1111/exd.70096","DOIUrl":"https://doi.org/10.1111/exd.70096","url":null,"abstract":"<div>\u0000 \u0000 <p>This study aimed to assess the therapeutic effects and underlying mechanisms of topical fluoxetine application in an atopic dermatitis (AD)-like mouse model. An AD-like mouse model was established using 2,4-dinitrochlorobenzene (DNCB) and treated with topical applications of fluoxetine on skin lesions. The therapeutic efficacy was evaluated by measuring the number of scratches, skin thickness, trans-epidermal water loss (TEWL), and skin moisture levels. Histopathological changes were examined through haematoxylin and eosin staining and toluidine blue staining to assess the local inflammatory state. Quantitative PCR (qPCR) was used to measure the expression of Th2-related cytokines (IL-5, IL-13, and IL-31) in skin lesions. Serum levels of IgE and thymus- and activation-regulated chemokine (TARC) were measured by enzyme-linked immunosorbent assay (ELISA). Topical fluoxetine significantly alleviated lesion symptoms in AD-like mice, reducing skin thickness and the number of scratching incidents. The treatment enhanced skin barrier recovery and reduced the infiltration of inflammatory cells, especially mast cells. Levels of Th2-related cytokines (IL-5, IL-13, and IL-31), indicative of local immune status, were also decreased. Serum concentrations of IgE and TARC showed a downward trend, with a more pronounced decrease in TARC levels. Our findings support the therapeutic role of topical fluoxetine in an AD-like mouse model through the repair of the skin barrier and inhibition of the Th2 inflammatory response in skin lesions, while also alleviating pruritus. These results suggest that fluoxetine may be a potential therapeutic candidate for AD.</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 4","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143840926","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}