Experimental Dermatology最新文献

{"title":"Single cell transcriptomics reveals dysregulated immnue homeostasis in different stages in HPV-induced cutaneous squamous cell carcinoma","authors":"Liqing Ding,&nbsp;Lanyuan Peng,&nbsp;Kai Huang,&nbsp;Shunlin Qu,&nbsp;Dongjie Li,&nbsp;Jianhua Yao,&nbsp;Fan Yang,&nbsp;Honglin Zhu,&nbsp;Shuang Zhao","doi":"10.1111/exd.15178","DOIUrl":"10.1111/exd.15178","url":null,"abstract":"<p>In order to explore the huge impact of impaired immnue homeostasis on the occurrence and development of cutaneous squamous cell carcinoma (cSCC), and investigate characterization of the cellular components and their changes which is crucial to understanding the pathologic process of HPV-induced cSCC, we diagnosed and followed up on a very rare HPV-induced cSCC patient who progressed at a very fast rate and transferred to death quickly. We performed single-cell RNA sequencing (scRNA-seq) of 11 379 cells from the skin tissues of this patient with four different skin statuses after HPV infection. Immunofluorescence experiments were used for validation. scRNA-seq identified that CD52⁺ HLA-DOA^- macrophages only existed in paracancerous cutaneous squamous cell carcinoma (pc-cSCC) and cSCC tissue. Besides, immune cells including CD8⁺ exhausted T cells and CD4⁺ regulatory T cells as well as matrix cells like MMP1⁺, and MMP11⁺ fibroblasts were gradually increased. Meanwhile, COMP⁺ ASPN⁺ fibroblasts gradually decreased. Cell interaction analysis revealed enhancement in interactions between monocytes/macrophages, fibroblasts and tumour-specific keratinocytes. scRNA-seq was performed in HPV-induced cSCC for the first time, to explore the correlation between infection and tumour. It is the first time to study the development of tumours from different stages of infection in HPV-induced cSCC. In this study, the tumour itself and the tumour microenvironment were both analysed and explored. And it was validated in clinical samples from different patients. Our findings reveal the dynamic immnue homeostasis from normal skin to cSCC tissue, this alteration might drive HPV-induced cSCC.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"33 10","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142389149","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 Narrowband Ultraviolet B Phototherapy on Systemic Metabolome in Korean Patients With Psoriasis","authors":"Yufei Li,&nbsp;Yujin Lee,&nbsp;Howard Lee,&nbsp;Seong-Jin Jo,&nbsp;Joo-Youn Cho","doi":"10.1111/exd.15192","DOIUrl":"10.1111/exd.15192","url":null,"abstract":"&lt;p&gt;Dear Editor,&lt;/p&gt;&lt;p&gt;Psoriasis is a chronic skin disease that increases the risk of developing psoriatic arthritis, cardiovascular disease, and other metabolic disorders. Therefore, understanding the systemic impacts of psoriasis treatments is crucial beyond merely addressing skin lesions. Although phototherapy, particularly narrowband ultraviolet B (nbUVB), is recognised as a safe and effective treatment option for psoriasis, its mechanisms and effects on systemic metabolites are not fully understood. To investigate these potential systemic effects, we conducted an untargeted metabolomic analysis of plasma samples from adult patients with psoriasis who underwent nbUVB phototherapy at least twice a week for a minimum of 8 weeks.&lt;/p&gt;&lt;p&gt;In this single-centre, before-and-after study, 23 patients with moderate-to-severe psoriasis were treated with nbUVB phototherapy at Seoul National University Hospital between 2015 and 2018 (Table S1). Treatments were administered using TL-01 lamps in a UV 7001K cabin (Waldmann, Villingen-Schwenningen, Germany) twice or thrice a week, starting at 400 mJ/cm&lt;sup&gt;2&lt;/sup&gt; and increasing by 10%–20% of the previous dose, with adjustments based on side effects such as erythema, irritation, and itching. The mean duration of phototherapy, mean session count, and cumulative nbUVB dose were 12.0 weeks, 25.0, and 35 423.9 mJ/cm&lt;sup&gt;2&lt;/sup&gt;, respectively. Topical corticosteroids of moderate potency or higher were allowed as needed, whereas no concurrent systemic treatment was administered. For each patient, the psoriasis area and severity index (PASI) score and plasma samples were collected before treatment, as well as on the day of the last UV exposure or the following day. Metabolomic profiling of the plasma samples was performed using an Orbitrap Exploris 120 mass spectrometer, equipped with a Vanquish Flex ultra-high-performance liquid chromatography system (Thermo Fisher Scientific; Waltham, MA, USA).&lt;/p&gt;&lt;p&gt;Following nbUVB phototherapy, the mean PASI score of the patient cohort significantly decreased from 10.6 to 3.3 (&lt;i&gt;p&lt;/i&gt; &lt; 0.001, Table S1). Changes in the overall levels of plasma metabolome, including 150 endogenous metabolites annotated with level 2 confidence according to the Metabolomics Standards Initiative, between pre- and post-treatment were subtle (Figure 1A). Five metabolites were found to be significantly changed, which may reflect the mechanism of action of nbUVB phototherapy (Figure 1B). Levels of 4-hydroxy docosahexaenoic acid, an anti-inflammatory metabolite derived from docosahexaenoic acid, decreased after treatment, indicating reduced inflammation [&lt;span&gt;1&lt;/span&gt;]. Levels of creatine, which has been recognised as an antioxidant capable of preventing UVB-induced keratinocyte apoptosis, increased after treatment [&lt;span&gt;2&lt;/span&gt;]. Carnitine, previously reported to be associated with the integral membrane protein CD147 highly expressed in psoriatic skin lesions, showed a similar increasing trend afte","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"33 10","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.15192","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380406","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":"Proteomic Analysis Reveals Oxidative Phosphorylation and JAK-STAT Pathways Mediated Pathogenesis of Pemphigus Vulgaris","authors":"Yuqi Cheng,&nbsp;Mingming Zhao,&nbsp;CaiHong Zhu,&nbsp;Xianfa Tang,&nbsp;Wenjun Wang,&nbsp;Huayang Tang,&nbsp;Xiaodong Zheng,&nbsp;Zhengwei Zhu,&nbsp;Yujun Sheng,&nbsp;Zaixing Wang,&nbsp;Fusheng Zhou,&nbsp;Jinping Gao","doi":"10.1111/exd.15184","DOIUrl":"10.1111/exd.15184","url":null,"abstract":"<div>\u0000 \u0000 <p>Pemphigus vulgaris (PV) stands as a rare autoimmune bullous disease, while the precise underlying mechanism remains incompletely elucidated. High-throughput proteomic methodologies, such as LC-MS/MS, have facilitated the quantification and characterisation of proteomes from clinical skin samples, enhancing our comprehension of PV pathogenesis. The objective of this study is to elucidate the signalling mechanisms underlying PV through proteomic analysis. Proteins and cell suspension were extracted from skin biopsies obtained from both PV patients and healthy volunteers and subsequently analysed using LC-MS/MS and scRNA-seq. Cultured keratinocytes were treated with PV serum, followed by an assessment of protein expression levels using immunofluorescence and western blotting. A total of 880, 605, and 586 differentially expressed proteins (DEPs) were identified between the lesion vs. control, non-lesion vs. control, and lesion vs. non-lesion groups, respectively. The oxidative phosphorylation (OXPHOS) pathway showed activation in PV. Keratinocytes are the major cell population in the epidermis and highly expressed ATP5PF, ATP6V1G1, COX6B1, COX6A1, and NDUFA9. In the cellular model, there was a notable increase in the expression levels of OXPHOS-related proteins (V-ATP5A, III-UQCRC2, II-SDHB, I-NDUFB8), along with STAT1, p-STAT1, and p-JAK1. Furthermore, both the OXPHOS inhibitor metformin and the JAK1 inhibitor tofacitinib demonstrated therapeutic effects on PV serum-induced cell separation, attenuating cell detachment. Metformin notably reduced the expression of V-ATP5A, III-UQCRC2, II-SDHB, I-NDUFB8, p-STAT1, p-JAK1, whereas tofacitinib decreased the expression of p-STAT1 and p-JAK1, with minimal impact on the expression of V-ATP5A, III-UQCRC2, II-SDHB, and I-NDUFB8. Our results indicate a potential involvement of the OXPHOS and JAK-STAT1 pathways in the pathogenesis of PV.</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"33 10","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380408","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":"Nrf2 Activation in Keratinocytes: A Central Role in Diabetes-Associated Wound Healing","authors":"Srinivasan Kaussikaa,&nbsp;Murali Krishna Prasad,&nbsp;Kunka Mohanram Ramkumar","doi":"10.1111/exd.15189","DOIUrl":"10.1111/exd.15189","url":null,"abstract":"<p>Wound healing is a complex biological process crucial for tissue repair, wherein keratinocytes play a pivotal role in initiating, sustaining and completing the cascade. Various local and systemic factors, such as lifestyle, age metabolic disorders and vascular insufficiency, can influence this process, and in the context of diabetic wounds, disrupted biological mechanisms, including inflammation, tissue hypoxia, decrease in collagen production along with increased oxidative stress and keratinocyte dysfunction, contribute to delayed healing. During re-epithelialisation, keratinocytes undergo rapid multiplication and migration, forming a dense hyperproliferative epithelial layer that restores the epidermal barrier. Nuclear factor-erythroid 2-related factor (Nrf2), a vital transcription factor, emerges as a central regulator in managing antioxidant proteins and detoxifying enzymes, serving as a guardian against elevated reactive oxygen species (ROS) levels during stress. Nrf2 also orchestrates angiogenesis and anti-inflammatory responses crucial for wound repair. Studies demonstrate that under high-glucose conditions, Nrf2 activation promotes wound healing by enhancing cell proliferation and migration while reducing apoptosis. Nrf2 activators stimulate endogenous antioxidant production, thereby mitigating oxidative stress. Furthermore, Nrf2 upregulation is associated with decreased expression of cytokines such as TNF-α and IL- 6. Recent research underscores the potential of bioactive molecules, including dietary polyphenols, traditional medicinal compounds and pharmacological agents, in activating Nrf2 and preventing diseases such as diabetes due to their robust antioxidative properties. This review aims to investigate the activation of Nrf2 by these bioactive molecules in cultured keratinocytes and animal models, elucidating the key molecular regulatory mechanisms involved in alleviating oxidative stress and facilitating the diabetic wound healing process. Understanding these complex pathways may offer insights into novel therapeutic strategies for enhanced wound healing in diabetes-associated complications.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"33 10","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.15189","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380407","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":"Increased CRHR1 expression on monocytes from patients with AA enables a pro-inflammatory response to corticotrophin-releasing hormone","authors":"Hong-Wei Guo,&nbsp;Hui-Jun Lai,&nbsp;Bo-Quan Long,&nbsp;Li-Xin Xu,&nbsp;Eddy Hsi Chun Wang,&nbsp;Jerry Shapiro,&nbsp;Kevin J. McElwee","doi":"10.1111/exd.15182","DOIUrl":"10.1111/exd.15182","url":null,"abstract":"<p>Stress may play a key role in alopecia areata (AA), though the exact interactions of stress with AA remain undefined. Corticotropin-releasing hormone (CRH), the proximal regulator of the stress axis, has been recognized as an immunomodulatory factor in tissues and peripheral blood mononuclear cells (PBMCs). We used multicolour flow cytometry to identify receptor CRHR1 expression on PBMC subsets in AA patients (<i>n</i> = 54) and controls (<i>n</i> = 66). We found that CRHR1 was primarily expressed by circulating monocytes. CRHR1 expression on monocytes was enhanced in AA compared with controls (3.17% vs. 1.44%, <i>p</i> = 0.002, chi-squared test). AA incidence was correlated to elevated CD14⁺ monocyte numbers (<i>R</i> = 0.092, <i>p</i> = 0.036) and markedly independently correlated with increased CRHR1 expression (<i>R</i> = 0.215, <i>p</i> = 0.027). High CRHR1 expression was significantly related to chronic AA (disease duration &gt;1 year; <i>p</i> = 0.003, chi-squared test), and large lesion area (AA area &gt;25%; <i>p</i> = 0.049, chi-squared test). We also observed enhanced percentages of active monocytes and reduced CD16⁺ CD3− NK cell numbers in AA patients' PBMCs (<i>p</i> = 0.010; 0.025, respectively). In vitro CRH treatment of PBMCs and human monocyte cell line THP-1 promoted CD86 upregulation. The findings imply that stress-related factors CRH and CRHR1 contribute to AA development and progression where higher CRHR1 expression is associated with chronic AA and larger lesions.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"33 10","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.15182","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375364","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":"Inhibition of Ubiquitin C-Terminal Hydrolase L1 Facilitates Cutaneous Wound Healing via Activating TGF-β/Smad Signalling Pathway in Fibroblasts","authors":"Huihui Pan,&nbsp;Jinru Song,&nbsp;Qing An,&nbsp;Junyi Chen,&nbsp;Wenyue Zheng,&nbsp;Litian Zhang,&nbsp;Jingjing Gu,&nbsp;Chengcheng Deng,&nbsp;Bin Yang","doi":"10.1111/exd.15186","DOIUrl":"10.1111/exd.15186","url":null,"abstract":"<div>\u0000 \u0000 <p>Ubiquitin C-terminal hydrolase L1 (UCHL1) plays vital roles in cell proliferation, angiogenesis, inflammation and oxidative stress. Nevertheless, it is unclear whether UCHL1 could regulate the biologic behaviour of cells and ultimately influences wound healing. We aim to illustrate the roles and the underlying mechanism of UCHL1 in cutaneous wound healing. Murine full-thickness excisional wound model was utilised to study the effects of UCHL1 on wound healing through topical administration of the UCHL1 inhibitor LDN57444, followed by assessment of wound areas and histological alterations. Subsequently, ethynyldeoxyuridine, scratch and transwell assays were performed to examine fibroblast migration and proliferation. The extracellular matrix (ECM)-related genes expression and transforming growth factor-β (TGF-β)/Smad signalling pathways activation were investigated by immuno-fluorescent staining, Western blots and quantitative reverse transcription polymerase chain reaction. We identified elevated UCHL1 expression in non-healing wound tissues. The UCHL1 expression displayed a dynamic change and reached a peak on Day-7 post-wounding during the healing process in mice. Cutaneous administration of LDN57444 promoted wound healing by facilitating collagen deposition, myofibroblast activation and angiogenesis. In vitro experiments demonstrated that UCHL1 concentration dependently inhibited migration, ECM synthesis and activation of human dermal fibroblasts, which was mechanistically related to downregulation of TGF-β/Smad signalling. Furthermore, these effects could be reversed by TGF-β inhibitor SB431542. Our findings reveal that UCHL1 is a negative regulator of cutaneous wound healing and considered as a novel prospective therapeutic target for effective wound healing.</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"33 10","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375365","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":"Lentigo Maligna and Lentigo Maligna Melanoma of the External Ear: Clinical and Dermoscopic Features of 19 Patients","authors":"Emi Dika,&nbsp;Federico Venturi,&nbsp;Giulia Veronesi,&nbsp;Leonardo Veneziano,&nbsp;Biagio Scotti","doi":"10.1111/exd.15188","DOIUrl":"10.1111/exd.15188","url":null,"abstract":"<p>External ear lentigo maligna/lentigo melanoma (LM/LMM) represents approximately 1%–4% of all primary cutaneous melanomas. Over the past 20 years, dermoscopy has proven highly effective in early detection of LM/LMM, with recent studies identifying perifollicular linear projections (PLP) as a specific diagnostic criterion for early LM. However, in clinical practice, LM and LMM turn out to be very difficult to distinguish based on dermoscopic findings. Therefore, our retrospective monocentric study aimed to investigate dermoscopic characteristics, as well as the epidemiological and clinical data of 19 patients diagnosed with the external ear (EE) LM/LMM at the Oncologic Dermatology Unit in Bologna. Dermoscopic images were obtained using the FotoFinder Medicam 800HD, and specific criteria validated by the International Dermoscopy Society (IDS) for atypical pigmented facial lesions were assessed. Fisher's exact test was primarily used for statistical comparisons. As results, most of the patients were male (74%) with an average age (± SD) at diagnosis of 69.8 (± 15.1) years old. LMM appeared more commonly observed in elderly patients as compared to LM (mean 71.6 vs. 66.7, <i>p</i> = 0.514), presenting as pigmented macule (89.5%) of the ear lobule (23.9%). A statistically significant difference (<i>p</i> = 0.01) of tumour’ diameter between LMM and LM was reported with the first resulting more than twice the size of the latter. Concerning dermoscopic findings, asymmetric pigmented follicles, obliteration of the follicular openings and grey circles were more frequently observed in LMM compared to LM (63.2% vs. 31.6%; 63.2% vs. 26.3%; 47.4% vs. 15.8%, respectively).</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"33 10","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.15188","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375366","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":"IL23R mutations associated with decreased risk of psoriasis lead to the differential expression of genes implicated in the disease","authors":"Shraddha S. Rane,&nbsp;Elan Shellard,&nbsp;Antony Adamson,&nbsp;Steve Eyre,&nbsp;Richard B. Warren","doi":"10.1111/exd.15180","DOIUrl":"https://doi.org/10.1111/exd.15180","url":null,"abstract":"<p>Psoriasis is an incurable immune-mediated skin disease, affecting around 1%–3% of the population. Various lines of evidence implicate IL23 as being pivotal in disease. Genetic variants within the IL23 receptor (IL23R) increase the risk of developing psoriasis, and biologic therapies specifically targeting IL23 demonstrated high efficacy in treating disease. IL23 acts via the IL23R, signalling through the STAT3 pathway, mediating the cascade of events that ultimately results in the clinical presentation of psoriasis. Given the essential role of IL23R in disease, it is important to understand the impact of genetic variants on receptor function with respect to downstream gene regulation. Here we developed model systems in CD4⁺ (Jurkat) and CD8⁺ (MyLa) T cells to express either the wild type risk or mutant (R381Q) protective form of IL23R. After confirmation that the model system expressed the genes/proteins and had a differential effect on the phosphorylation of STAT3, we used RNAseq to explore differential gene regulation, in particular for genes implicated with risk to psoriasis, at a single time point for both cell types, and in a time course experiment for Jurkat CD4⁺ T cells. These experiments discovered differentially regulated genes in the cells expressing wild type and mutant IL23R, including HLA-B, SOCS1, RUNX3, CCR5, CXCR3, CCR9, KLF3, CD28, IRF, SOCS6, TNFAIP and ICAM5, that have been implicated in both the IL23 pathway and psoriasis. These genes have the potential to define a IL23/psoriasis pathway in disease, advancing our understanding of the biology behind the disease.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"33 9","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.15180","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142276607","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":"Efficacy and safety of ritlecitinib in vitiligo patients across Fitzpatrick skin types with biomarker analyses","authors":"Elena Peeva,&nbsp;Yuji Yamaguchi,&nbsp;Zhan Ye,&nbsp;Brett King,&nbsp;Mauro Picardo,&nbsp;Abigail Sloan,&nbsp;Khaled Ezzedine,&nbsp;Ester Del Duca,&nbsp;Yeriel Estrada,&nbsp;Mina Hassan-Zahraee,&nbsp;Wen He,&nbsp;Craig Hyde,&nbsp;Johnathan Bar,&nbsp;Paola Facheris,&nbsp;Emma Guttman-Yassky","doi":"10.1111/exd.15177","DOIUrl":"https://doi.org/10.1111/exd.15177","url":null,"abstract":"<p>Efficacy and safety of ritlecitinib (an oral JAK3/TEC family kinase inhibitor) were evaluated in patients with nonsegmental vitiligo (NSV) across Fitzpatrick skin types (FSTs). Patients with FST I-III (‘light skin’; <i>n</i> = 247) and FST IV-VI (‘dark skin’; <i>n</i> = 117) received once-daily ritlecitinib 50 mg (with/without 4-week loading dose), low-dose ritlecitinib or placebo for 24 weeks. At baseline, patients with light skin displayed higher CLM-1 and NCR1 serum levels than patients with dark skin (<i>p</i> &lt; 0.05). At 24 weeks, ritlecitinib 50 mg improved the extent of depigmentation measured by percent change from baseline in facial-vitiligo area scoring index (placebo-adjusted mean difference [90% CI]) in patients with light (−15.2 [−24.7, −5.8]; <i>p</i> = 0.004) and dark (−37.4 [−50.3, −24.4]; <i>p</i> &lt; 0.0001) skin, with continuous re-pigmentation through week 48. Treatment-emergent adverse events were similar across FSTs. At weeks 4 and 24, ritlecitinib 50 mg reduced CXCL11 serum levels (<i>p</i> &lt; 0.001) in patients with light skin, whereas patients with dark skin had increased levels at week 4 (<i>p</i> = 0.05) and no significant change at week 24. Ritlecitinib 50 mg decreased IL-9 and IL-22 expression levels in dark skin compared with light skin (qPCR; <i>p</i> &lt; 0.05). These differences in immune dysregulations may explain why NSV patients with dark skin respond to therapy earlier than patients with light skin.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"33 9","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142273202","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":"Biodistribution of iron oxide tattoo pigment: An experimental murine study","authors":"Kasper Køhler Alsing,&nbsp;Helle Hjorth Johannesen,&nbsp;Rasmus Hvass Hansen,&nbsp;Nina Løth Mårtensson,&nbsp;Daniel Pergament Persson,&nbsp;Klaus Qvortrup,&nbsp;Hans Christian Wulf,&nbsp;Catharina Margrethe Lerche","doi":"10.1111/exd.15183","DOIUrl":"https://doi.org/10.1111/exd.15183","url":null,"abstract":"<p>Tattoo pigment is expected to migrate beyond the skin to regional lymph nodes and the liver. Modern tattoo ink commonly contains metals that may pose a clinical problem during MRI examinations. This study aimed to investigate the biodistribution of iron oxide pigment to internal organs in mice. Moreover, when exposed to a static magnetic field, we studied whether any reactions followed in the tattooed skin. Twenty-seven hairless C3.Cg-Hrhr/TifBomTac mice were included; 20 were tattooed with iron oxide ink in a rectangular 3 cm² pattern; seven were controls. Ten of the tattooed mice were exposed to a 3 T MRI scanner's static magnetic field. Following euthanasia, evaluations of dissected organs involved MRI T2*-mapping, light microscopy (LM) and metal analysis. T2*-mapping measures the relaxation times of hydrogen nuclei in water and fat, which may be affected by neighbouring ferrimagnetic particles, thus enabling the detection of iron oxide particles in organs. Elemental analysis detected a significant level of metals in the tattooed skin compared to controls, but no skin reactions occurred when exposed to a 3 T static magnetic field. No disparity was observed in the liver samples with metal analysis. T2* mapping found no significant difference between the two groups. Only minute clusters of pigment particles were observed in the liver by LM. Our results demonstrate a minimal systemic distribution of the iron oxide pigments to the liver, whereas the kidney and brain were unaffected. The static magnetic field did not trigger skin reactions in magnetic tattoos but may induce image artefacts during MRI.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"33 9","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142273191","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}