Experimental Dermatology[JOURNAL]
Sun
200 papers
Determining a Stability Prognostic Panel for 636 Patients With Melanoma Using a Machine Learning Computational Framework.
Guan H, Jiang Y, Cui Y … +6 more , Zhang S, Chen Y, Li Y, Han F, Yuan Q, Lin J
Exp Dermatol · 2025 Nov · PMID 41229385 · Full text
Current prognostic evaluation in melanoma primarily relies on traditional histopathological and clinical staging evaluation; however, these conventional approaches exhibit limited accuracy and fail to account for individ...
Current prognostic evaluation in melanoma primarily relies on traditional histopathological and clinical staging evaluation; however, these conventional approaches exhibit limited accuracy and fail to account for individual patient heterogeneity. To address these limitations, we developed a machine learning-driven prognostic signature, with the objectives of identifying pivotal biomarkers and establishing a precision medicine framework for prognostic assessment in melanoma management. Bulk RNA-seq data of 636 melanoma patients were obtained from TCGA and GEO databases, followed by univariate Cox regression to identify prognosis-associated genes. Intersecting results across cohorts identified consistently prognostic genes. Heterogeneity of the selected genes was assessed between primary and metastatic melanoma using scRNA-seq data. The consensus prognosis-related signature was developed by systematically integrating 101 machine learning algorithms, with model performance rigorously evaluated through multidimensional metrics. Finally, molecular experiments validated the prognostic relevance of the model's hub genes, and the biological role of CUL2 was investigated in melanoma. 53 protective prognosis-related genes (PRGs) were identified in melanoma. Single-cell analysis revealed elevated PRGs activity in primary melanoma tissues compared to metastatic lesions. A 14-gene consensus prognosis-related signature was developed using LASSO and RSF algorithms. The model achieved a C-index of 0.908 in the TCGA-SKCM cohort and a mean C-index of 0.758 across four independent validation cohorts. Furthermore, the model outperformed 19 existing prognostic models across multiple cohorts. This study developed a 14-gene consensus prognosis-related signature validated for robust prognostic performance across cohorts. CUL2, identified as a pivotal protective biomarker in melanoma, demonstrates potent tumour-suppressive activity through significant inhibition of proliferation and migration potential.
Putting AI Chatbots to the Test: A Comparative Analysis of Large Language Models' Performance in the Context of Basal Cell Carcinoma.
Ortner VK, Lent HC, Karmisholt KE … +9 more , Lei U, Gyldenløve M, Omland SH, Kaur-Knudsen D, Kainu KH, Togsverd-Bo K, Wiegell SR, Bjerva J, Hædersdal M
Exp Dermatol · 2025 Nov · PMID 41217077 · Publisher ↗
Large language models (LLMs) have been explored in various dermato-oncological conditions. In this study, we aimed to compare different LLMs' potential to guide clinicians on the treatment of basal cell carcinoma (BCC)....
Large language models (LLMs) have been explored in various dermato-oncological conditions. In this study, we aimed to compare different LLMs' potential to guide clinicians on the treatment of basal cell carcinoma (BCC). Four authors formulated 24 questions on the topic of clinical management of BCC. The blinded responses of three LLMs (Gemini, Copilot and ChatGPT 4.0) were presented to a panel of nine dermato-oncologists for assessment of (i) factual accuracy, (ii) concision, (iii) comprehensiveness and (iv) overall preference. In addition, the responses were then quantitatively compared based on lexical (i.e., vocabulary) and semantic (i.e., meaning) similarity to three additional LLMs (ChatGPT 3.5, ChatGPT 4o and Claude). ChatGPT 4.0 had the highest accuracy rate (87.5%, i.e., 21/24 responses), followed by Gemini (50%) and Copilot (25%). All models scored lower for concision and comprehensiveness, with ChatGPT 4.0 in the lead (62.5% comprehensive; 54.2% concise), followed by Gemini (33.3%; 12.5%) and Copilot (16.7%; 8.3%). The panel achieved consensus on model preference in 16 questions (ChatGPT 4.0: 54.2%; Gemini: 8.3%; Copilot: 4.2%; no consensus: 33.3%). While the lexical similarity was found to be low (x̄ ~0.07-0.10 across models), the semantic similarity between the LLM responses was moderate (x̄ ~0.60-0.70 across models). LLMs may assist clinicians in settings where expert dermato-oncological guidance is not readily available, with ChatGPT 4.0 currently outperforming both Gemini and Copilot. Since quantitative methods are unable to detect clinically relevant differences between LLMs, surveying dermatologists is necessary to identify useful models in this rapidly developing field.
Combination of Antiplatelet Therapy in Psoriatic Diseases With Cardiovascular Comorbidities: A Thromboinflammatory Perspective in the Era of Biologic Therapies.
Chen L, Shen Z
Exp Dermatol · 2025 Nov · PMID 41217076 · Publisher ↗
Cardiovascular disease (CVD) remains the leading cause of death worldwide and represents the most significant comorbidity associated with psoriatic disease. Despite significant advancements in biologic therapies for psor...
Cardiovascular disease (CVD) remains the leading cause of death worldwide and represents the most significant comorbidity associated with psoriatic disease. Despite significant advancements in biologic therapies for psoriasis skin lesions, the lack of specific recommendations in current clinical guidelines for managing psoriasis with cardiovascular comorbidities has left the burden of these comorbidities continuing to significantly impair patients' quality of life and impose a substantial economic strain on society. Platelets, as unique cells with dual roles in haemostasis and inflammation, are critically involved in both psoriatic disease and its cardiovascular comorbidities. Recent evidence suggests that combining antiplatelet agents with biologic therapy may be a promising strategy for treating psoriatic patients with coexisting cardiovascular diseases. This article covers the involvement of platelets in inflammatory responses, their role in linking cardiovascular comorbidities to psoriasis, the theoretical rationale for combining antiplatelet and biologic therapies, evaluates the current positioning of this therapeutic strategy and provides perspectives on future developments in this field. Current clinical guidelines and ongoing GCP trials lack relevant data on this approach; advancing this strategy could yield valuable evidence for future recommendations.
Exosome-Based Therapy: A Comparative Study of Adipose- and Umbilical Cord-Derived Mesenchymal Stem Cells-Derived Exosomes in Psoriatic Mouse Model.
Siriphanit R, Thanasarnaksorn W, Boonpethkaew S … +7 more , Ponnikorn S, Charoensuksira S, Deenonpoe R, Sirithanabadeekul P, Suwanchinda A, Hongeng S, Meephansan J
Exp Dermatol · 2025 Nov · PMID 41217063 · Publisher ↗
Exosomes are nanosized extracellular vesicles that mediate intercellular communication by transferring bioactive molecules. Mesenchymal stem cells (MSCs) from different tissue sources secrete exosomes with potentially di...
Exosomes are nanosized extracellular vesicles that mediate intercellular communication by transferring bioactive molecules. Mesenchymal stem cells (MSCs) from different tissue sources secrete exosomes with potentially distinct therapeutic properties. In this study, we compared the anti-inflammatory efficacy of exosomes derived from human adipose-derived MSCs (hADMSCs-EXOs) and human umbilical cord-derived MSCs (hUCMSCs-EXOs), together with desoximetasone (DSM), in an imiquimod-induced psoriasis mouse model. Psoriasiform lesions were induced, and treatment outcomes were assessed through clinical, histological, and immunological assessments. Both hADMSCs-EXOs and hUCMSCs-EXOs significantly attenuated psoriasiform lesions, as clinically evidenced by reduced cumulative Psoriasis Severity Index (PSI) scores by day 6 of treatment. Notably, hUCMSCs-EXOs and DSM significantly reduced epidermal and dermal thickness to no significant difference compared to the control group. Immune cell infiltration, including CD3, CD4, CD8 T cells, CD68 macrophages, CD117 mast cells, and neutrophils, was also markedly reduced in the hUCMSCs-EXOs and DSM groups. Importantly, unlike DSM, hUCMSCs-EXOs did not induce skin thinning or systemic adverse effects. Growth factor (GF) profiling revealed that hADMSCs-EXOs were enriched in FGFs, PDGFs, and VEGF, whereas hUCMSCs-EXOs contained higher levels of HGF, a key modulator of immunoregulation and tissue repair. Collectively, these findings suggest that MSC-derived exosomes exert therapeutic effects through both anti-inflammatory and regenerative mechanisms, with hUCMSCs-EXOs demonstrating superior anti-inflammatory efficacy over hADMSCs-EXOs and a lower likelihood of inducing local or systemic adverse effects compared with DSM. Given the influence of MSC tissue origin on exosome content and function, our results support the potential of hUCMSCs-EXOs as a promising steroid-sparing therapeutic approach for psoriasis.
The Role of Mast Cells in Skin Aging: Mechanisms and Therapeutic Advances.
Zhou L, Cao Z, Shen S … +5 more , Zhao Y, Yin X, Zeng Q, Wang X, Wang P
Exp Dermatol · 2025 Nov · PMID 41159513 · Publisher ↗
Mast cells (MCs) are innate immune cells primarily located in the papillary layer of the dermis that play a crucial role in the skin immune response by secreting mediators and recruiting effector cells. Increasing labora...
Mast cells (MCs) are innate immune cells primarily located in the papillary layer of the dermis that play a crucial role in the skin immune response by secreting mediators and recruiting effector cells. Increasing laboratory and clinical evidence indicates that MCs are not only passive participants but also key regulators of skin aging. MCs act as sensors and amplifiers of aging-related signals, integrating various stimuli, including the nature of the triggering factor, microenvironmental cues such as senescence-associated secretory phenotype (SASP) factors, and specific activation pathways. Upon activation, MCs release diverse mediators that engage signalling pathways including Fc epsilon RI (FcεRI), c-KIT, Toll-like receptors (TLRs) and Mas-related G-protein-coupled receptor X2 (MRGPRX2) thereby eliciting broad target cell responses. MCs engage in pathological crosstalk with fibroblasts, keratinocytes, melanocytes and immune cells, establishing self-perpetuating feedback loops that amplify aging-related processes. Collectively, these findings highlight the dual and context-dependent roles of MCs as not only protectors but also accelerators of skin aging, positioning them as promising therapeutic targets. The use of novel MC stabilisers such as ketotifen or luteolin, as well as phototherapy and other treatments, shows potential in mitigating skin aging and may offer valuable insights into novel therapeutic targets. Nonetheless, additional studies are required to dissect the underlying mechanisms and optimise targeted therapies to facilitate the development of precision medicine strategies.
EXPRESSION OF CONCERN: Dermal Papilla Cell-Secreted Biglycan Regulates Hair Follicle Phase Transit and Regeneration by Activating Wnt/β-Catenin.
Exp Dermatol · 2025 Oct · PMID 41131858 · Publisher ↗
N. Zhu, J. Yan, W. Gu, Q. Yang, E. Lin, S. Lu, B. Cai, B. Xia, X. Liu, C. Lin, "Dermal Papilla Cell-Secreted Biglycan Regulates Hair Follicle Phase Transit and Regeneration by Activating Wnt/β-Catenin," Experimental Derm...
N. Zhu, J. Yan, W. Gu, Q. Yang, E. Lin, S. Lu, B. Cai, B. Xia, X. Liu, C. Lin, "Dermal Papilla Cell-Secreted Biglycan Regulates Hair Follicle Phase Transit and Regeneration by Activating Wnt/β-Catenin," Experimental Dermatology 33, no. 1 (2024): e14969, https://doi.org/10.1111/exd.14969. This Expression of Concern is for the above article, published online on 15 November 2023 in Wiley Online Library (wileyonlinelibrary.com), and has been issued by agreement between the journal Editor-in-Chief, Akimichi Morita, and John Wiley & Sons Ltd. The Expression of Concern has been agreed upon following the identification of duplicated GAPDH bands in Figures 1C and 2C. Additional concerns were raised about the authenticity of bands in Figures 2C and 3C, which lacked characteristics typically associated with original experimental data. Although the authors cooperated and submitted data, the materials provided did not meet the standards for raw data and were insufficient to validate the figures. The editors have decided to issue an Expression of Concern to inform readers of these concerns.
Serum Nectin-4 as a Potential Prognostic Biomarker for Extramammary Paget Disease.
Morita H, Miyagawa T, Oka K … +7 more , Iwasawa O, Saito H, Mori T, Kawashima H, Omatsu J, Yamada D, Sato S
Exp Dermatol · 2025 Oct · PMID 41123286 · Publisher ↗
Nectin cell adhesion molecule 4 (Nectin-4) is overexpressed in the tissue of extramammary Paget disease (EMPD), and its potential role as a circulating biomarker remains poorly explored. We therefore investigated serum l...
Nectin cell adhesion molecule 4 (Nectin-4) is overexpressed in the tissue of extramammary Paget disease (EMPD), and its potential role as a circulating biomarker remains poorly explored. We therefore investigated serum levels of Nectin-4 in EMPD patients and healthy controls by ELISA assay and analysed its clinical relevance. Serum Nectin-4 levels were significantly higher in patients than in controls (p = 0.0015), especially in advanced stages (IIIB-IV; p = 0.028). Serum Nectin-4 levels tended to decrease following effective treatment and increase upon disease progression. Serum Nectin-4 correlated strongly with CEA (r = 0.705) but not with CYFRA. Patients with high serum Nectin-4 levels (cut-off of 394.2 pg/mL) exhibited shorter overall survival (p = 0.012). Further research is needed to elucidate the role of Nectin-4 in EMPD; however, these findings suggest that serum Nectin-4 may serve as a single marker for prognosis and treatment monitoring in EMPD.
Targeting XIAP and EGFR as an Approach for Treating Melanoma.
Steinkamp J, Mersch N, Kashkar H … +1 more , Zigrino P
Exp Dermatol · 2025 Aug · PMID 41084848 · Publisher ↗
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Nerve Fibres in Psoriatic Skin and Their Relation to Vasculature and Clinical Parameters.
Doppegieter M, van der Beek N, Aalders MCG … +3 more , Bakker ENTP, Neumann M, van Leeuwen TG
Exp Dermatol · 2025 Sep · PMID 40993915 · Full text
Emerging evidence supports the neurogenic origin of psoriasis, yet the morphology and distribution of nerve fibres in psoriatic skin remain poorly characterised due to methodological inconsistencies and limited 3D data....
Emerging evidence supports the neurogenic origin of psoriasis, yet the morphology and distribution of nerve fibres in psoriatic skin remain poorly characterised due to methodological inconsistencies and limited 3D data. The aim of this study was to provide a comprehensive 3D quantification of nerve fibre morphology in psoriatic skin and assess its spatial relation to vasculature and clinical parameters. High-resolution confocal microscopy was used to analyse 69 (70 μm thick) skin sections from 23 psoriasis patients, capturing full-thickness epidermis and dermis. Nerve fibres were segmented by location (epidermal, papillary and reticular) and quantified volumetrically alongside vascular networks. The results show that nerve fibres occupied ~0.1% of total skin volume and predominantly localised near vasculature in the dermis, with epidermal nerves branching from perivascular plexuses. Epidermal nerve fibre volume negatively correlated with erythema, age and epidermal thickness (p < 0.05). No significant correlation was observed between dermal nerve fibre volumes and vascular density or clinical severity scores. This study presents a detailed 3D neurovascular map of psoriatic skin, revealing a distinct topography of nerve-vessel relationships. The findings highlight that epidermal nerve fibres (not total nerve density) show the strongest association with clinical markers. These results provide a critical baseline for evaluating nerve-targeted therapies and modelling neurovascular responses in laser-based psoriasis treatments.
The Role of ROS-Mediated Mitochondrial Dysfunction in the Development of Malignant Melanoma.
Li L, Zeng Z, Ma T … +3 more , Hu B, Guo M, Wang Q
Exp Dermatol · 2025 Sep · PMID 40990316 · Full text
Reactive oxygen species (ROS) are critical to cellular metabolism, signal transduction and apoptosis. Recent studies have revealed the dual role of ROS in malignant melanoma pathogenesis and progression, where they can b...
Reactive oxygen species (ROS) are critical to cellular metabolism, signal transduction and apoptosis. Recent studies have revealed the dual role of ROS in malignant melanoma pathogenesis and progression, where they can both promote tumour proliferation and metastasis or inhibit tumour growth by inducing apoptosis. Mitochondria, often referred to as the energy factories of cells, are closely involved in ROS generation, and their dysfunction significantly affects cellular homeostasis. This review explores the mechanisms by which ROS-mediated mitochondrial dysfunction contributes to malignant melanoma, focusing on its effects within the tumour microenvironment and its potential as a therapeutic target. Understanding these interactions is essential for developing novel strategies to combat malignant melanoma.
Orismilast, a Potent and Selective PDE4B/D Inhibitor, Reduces Protein Levels of Key Disease Driving Cytokines in the Skin of Patients With Plaque Psoriasis.
Warren RB, Weiss A, Felding J … +3 more , Sommer MOA, Garcet S, Krueger JG
Exp Dermatol · 2025 Sep · PMID 40970551 · Full text
Minimally invasive sampling of the skin using tape strips for conducting biomarker research is a growing research area in medical dermatology. The goal of this study was to utilise tape strip sampling to investigate chan...
Minimally invasive sampling of the skin using tape strips for conducting biomarker research is a growing research area in medical dermatology. The goal of this study was to utilise tape strip sampling to investigate changes in protein skin levels of psoriasis patients after oral treatment with orismilast (a PDE4B/D inhibitor). The proteins were measured in extracts of tape-strip samples taken from the skin of patients with moderate-severe psoriasis participating in a 16-week Ph2b study (IASOS). The proteins were measured using the Olink technology or an ELISA assay. Our results show that protein levels of multiple proteins (32/71) were upregulated at baseline in the lesional skin compared to non-lesional skin, including three key biomarkers of the psoriasis disease pathology (IL-17A, CCL20 and TNFα). The protein levels of these three biomarkers were significantly reduced at Week 16, reaching a percent reduction of 52% and 51% for IL-17A, 66% and 60% for TNFα, and 41% and 54% for CCL20 for the two doses analysed (20 and 30 mg bid, respectively). In addition, we observed that the clinical response of a 75% reduction in PASI (PASI75) was associated with a 98% reduction in IL-17A protein levels in lesional skin, irrespective of the orismilast dose. In summary, a significant reduction of key proteins related to the T17 axis and T1 axis was observed in the skin of psoriasis patients after treatment with oral orismilast, supporting the observed clinical effect. Finally, this constitutes the first report where protein levels from the skin of psoriasis patients are quantified using tape strips as a minimally invasive skin sampling technology in combination with the Olink technology. Trial Registration: ClinicalTrials.gov identifier: NCT05190419.
IL-13 From Murine Epidermal γδ T Cells Promotes Wound Healing by Inducing Arginase-1-Positive Hypodermal Macrophages in the Early Inflammatory Phase.
Ibusuki A, Kawai K, Ito A … +2 more , Egawa G, Kanekura T
Exp Dermatol · 2025 Sep · PMID 40963327 · Publisher ↗
Murine epidermal γδ T cells, known as dendritic epidermal T cells (DETCs), play critical roles in cutaneous wound healing by secreting chemokines, cytokines and growth factors. Although DETCs predominantly produce IL-13...
Murine epidermal γδ T cells, known as dendritic epidermal T cells (DETCs), play critical roles in cutaneous wound healing by secreting chemokines, cytokines and growth factors. Although DETCs predominantly produce IL-13 early after activation, the specific role of DETC-derived IL-13 in wound repair remains unknown. Here, we show that periwound DETCs are the primary source of IL-13 at early wound sites (4 h after full-thickness skin wounding). The delayed wound closure in DETC-deficient Tcrd mice was restored by the local application of IL-13 immediately after wounding. Previous studies have demonstrated that macrophages infiltrating the wound granulation tissue undergo a phenotypic shift from iNOS-positive, proinflammatory type to arginase-1-positive, anti-inflammatory type during the late inflammatory phase (3-5 days post injury). At 24 h post wounding, however, most macrophages infiltrating the periwound hypodermis expressed arginase-1. In Tcrd mice, both the number of macrophages in the periwound hypodermis and their arginase-1 expression were significantly reduced. Local IL-13 administration restored arginase-1 expression in the hypodermal macrophages without altering their overall number in Tcrd mice. These results indicate that IL-13 rapidly produced by DETCs upon skin injury plays a critical role in wound healing by inducing arginase-1-positive macrophages in the periwound hypodermis during the early inflammatory phase.
Rice Bran Extract Alleviates Inflammation and Promotes Wound Healing in Radiation Dermatitis.
Kuan CH, Hideki T, Wu CH … +4 more , Kung PJ, Wang WH, Lin SJ, Perng CK
Exp Dermatol · 2025 Sep · PMID 40922545 · Publisher ↗
Radiation dermatitis is a common side effect of radiotherapy, affecting up to 95% of cancer patients receiving radiation therapy and often leading to skin damage, inflammation, and ulceration. The pathogenesis of radiati...
Radiation dermatitis is a common side effect of radiotherapy, affecting up to 95% of cancer patients receiving radiation therapy and often leading to skin damage, inflammation, and ulceration. The pathogenesis of radiation dermatitis involves complex mechanisms, such as the production of reactive oxygen species (ROS) and sustained inflammatory responses. Current treatments, including topical steroids, moisturisers, and non-steroidal anti-inflammatory drugs (NSAIDs), often provide limited efficacy, primarily addressing symptoms rather than the underlying pathophysiological processes. In this study, we evaluated the therapeutic potential of rice bran extract (RBE) in mitigating radiation-induced skin injury. High-performance liquid chromatography (HPLC) analysis revealed that RBE is rich in bioactive compounds, including pyrogallol, gallic acid, and ferulic acid, known for their antioxidant and anti-inflammatory properties. In vitro assays demonstrated that RBE exhibited fair biocompatibility, reduced IL-6 production, enhanced 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, stimulated procollagen synthesis, and promoted fibroblast migration. In a murine dorsal skin irradiation model, topical RBE application alleviated dermatitis severity, reduced skin ulceration, minimised histological signs of inflammation and fibrosis, and promoted epithelial regeneration. Bulk RNA sequencing revealed that RBE modulated key pathways related to inflammation resolution, epidermal repair, and metabolic adaptation, with Pparg identified as a central upstream regulator. Overall, RBE demonstrates antioxidant, anti-inflammatory, and pro-regenerative activities that support its potential for preventing and treating radiation dermatitis.
Visible Light-Induced Pigmentation: Improved In Vivo Methodology for Measuring Efficacy of 30 Products in 9 Randomised Controlled Trials and Correlation With In Vitro Assessment.
Renoux P, Jouni H, Laloux C … +6 more , Touti R, Vieu DL, Lamarche F, Santos SM, Bernerd F, Marionnet C
Exp Dermatol · 2025 Sep · PMID 40922539 · Full text
As hyperpigmentation can worsen with exposure to ultraviolet (UV) and visible light (VL), sunscreens with well-balanced UVB/UVA protection and VL-blocking pigments are recommended. Assessing efficiency against VL-induced...
As hyperpigmentation can worsen with exposure to ultraviolet (UV) and visible light (VL), sunscreens with well-balanced UVB/UVA protection and VL-blocking pigments are recommended. Assessing efficiency against VL-induced pigmentation is then mandatory. Recently, an in vivo pigmentation assessment allowing a VL protection factor (pVL-PF) determination, and an in vitro predictive method based on transmittance measures were introduced. However, the number of volunteers, tested sunscreens, and protection range were limited. Moreover, no statistical assessment was associated. This study aimed at testing the robustness and improving these methodologies by conducting a series of 9 monocentric, double-blind, randomised controlled in vivo studies involving 188 volunteers and 30 products, alongside an in vitro approach, in 2 independent laboratories. Our results first allowed us to improve pVL-PF calculation by better fitting to VL-induced pigmentation dynamics. Based on the 30 established pVL-PF, we evidenced that VL-protection level strongly correlated with the amount of pigments in products. Second, a statistical Bayesian approach, accounting for kinetic and inter-individual response variability over time, was proposed. This enabled us to determine that 24 out of 30 products significantly reduced VL-induced pigmentation. Finally, we showed that in vitro transmittance reduction was highly predictive of in vivo results. In conclusion, through several independent studies involving a large number of products and volunteers, a refined pVL-PF calculation associated with statistical indicators was proposed together with a predictive in vitro assessment. These methodologies to assess the efficacy of tinted products against VL-induced pigmentation are complementary and could also be of interest for other pathologies induced or aggravated by VL. Trial Registration: NCT06827392, NCT06796192, NCT06803901, NCT06796140, NCT06796153, NCT06796010, NCT06796088, NCT06796205, NCT06796179.
The Association Between Non-High-Density Lipoprotein Cholesterol to High-Density Lipoprotein Cholesterol Ratio With Psoriasis: A Cross-Sectional Survey and Genetic Approach.
Dai H, Li Z, Hu J … +5 more , Chen W, Wang Q, Liu K, He Y, Li L
Exp Dermatol · 2025 Sep · PMID 40913017 · Publisher ↗
This study utilised NHANES data from 2003 to 2006 and 2009 to 2014 to explore the association between the non-high-density lipoprotein to high-density lipoprotein cholesterol ratio (NHHR) and psoriasis. A total of 15 437...
This study utilised NHANES data from 2003 to 2006 and 2009 to 2014 to explore the association between the non-high-density lipoprotein to high-density lipoprotein cholesterol ratio (NHHR) and psoriasis. A total of 15 437 U.S. adults were analysed using multivariable logistic regression models that adjusted for cardiovascular disease, medication use, glucocorticoid therapy, and other covariates. Subgroup analyses by age, sex, and income were conducted. In addition, severity-stratified analyses were performed using data from the 2003 to 2006 and 2011 to 2014 cycles, where psoriasis severity information was available. Additional regression models comparing NHHR with traditional lipid markers (HDL-C, TC, non-HDL-C) were performed. Subsequently, Mendelian randomisation (MR) using GWAS summary statistics across European, East Asian, African, and Middle Eastern populations was conducted, with meta-analysis applied to improve precision. The results showed that NHHR was significantly associated with psoriasis (OR = 1.08, 95% CI: 1.00-1.17, p = 0.039), and those in the highest NHHR quartile had a 48% higher likelihood of developing psoriasis compared to those in the lowest quartile (OR = 1.48, 95% CI: 1.09-2.00).
The Role of Cutaneous B-Cells in Hidradenitis Suppurativa: From Preclinical Evidence to Novel Targeted Therapies.
Romagnuolo M, Calabrese L, D'Onghia M … +4 more , Cioppa V, Rubegni P, Marzano AV, Moltrasio C
Exp Dermatol · 2025 Sep · PMID 40898716 · Full text
Hidradenitis Suppurativa (HS) is a chronic autoinflammatory skin disease of the terminal hair follicle, whose pathogenesis is complex and multifactorial. Alongside a predisposing genetic background, environmental/epigene...
Hidradenitis Suppurativa (HS) is a chronic autoinflammatory skin disease of the terminal hair follicle, whose pathogenesis is complex and multifactorial. Alongside a predisposing genetic background, environmental/epigenetic factors, alterations in the skin microbiome, and dysregulation of both innate and adaptive immune responses contribute to the persistent inflammatory network. Despite advancing knowledge, the exact molecular and cellular mechanisms underlying HS have yet to be untangled. Moreover, the lack of experimental disease models that closely mimic disease phenotypes or pathophysiological processes has hindered the development of effective therapeutic strategies. Recent advances in immunology highlighted the important role of B cells in HS pathogenesis, not only in the chronic but also in the early stages of the disease, implying great potential for the development of novel therapeutic targets. This study gathers the preclinical and clinical scientific evidence that supports the role of cutaneous B-cells in HS pathogenesis and the therapeutic potential of their targeting.
Targeting Melanin Heterogeneity in Metastatic Melanoma: A Dual-Tumour Mouse Melanoma Model.
Delmas M, Chaussin B, Harismendy N … +12 more , Dougé A, Rouzaire PO, Montemagno C, Durivault J, Moreau E, Miot-Noirault E, Quintana M, Besse S, D'Incan M, Chautard E, Jouberton E, Rouanet J
Exp Dermatol · 2025 Sep · PMID 40898695 · Full text
The combination of melanin-targeted radionuclide therapy (TRT) and immunotherapy offers potential in overcoming melanoma resistance to conventional therapies. Studying the potential abscopal effect induced by TRT is esse...
The combination of melanin-targeted radionuclide therapy (TRT) and immunotherapy offers potential in overcoming melanoma resistance to conventional therapies. Studying the potential abscopal effect induced by TRT is essential to evaluate such combination. We develop here a preclinical murine model comprising a target (pigmented) and non-target (non-pigmented) tumour to study the abscopal effect induced by melanin-TRT in melanoma. Murine melanoma cell lines were tested: two pigmented (B16-F10 and B16-OVA) and one non-pigmented (B16-G4F), inoculated in C57BL/6 mice to assess pigmentation levels and immune infiltration. Heterogeneous tumour growth and repigmentation of the B16-G4F tumour led us to develop a non-pigmented cell line (B16-OVAmTYR-/-) by tyrosinase invalidation using CRISPR/Cas9. A dual-tumour model comprising the B16-OVA tumour and the B16-OVAmTYR tumour was evaluated in terms of tumour growth, pigmentation, and immune infiltrate. The B16-OVA model displayed homogeneous tumour growth, pigmentation and high immune infiltrate (CD8+ T cells p < 0.001; CD4+ T cells p < 0.05, regulatory T cells p < 0.001). The new B16-OVAmTYR-/- cell line ensured a consistent genetic background for comparative studies. The B16-OVAmTYR-/- maintained a non-pigmented phenotype without repigmentation (no melanin expression) and demonstrated similar tumour growth characteristics to its pigmented counterpart (DT = 2.4 ± 0.5 days). Establishing a dual-tumour model using both B16-OVA and B16-OVAmTYR-/- cell lines enabled concurrent study of pigmented and non-pigmented tumours in a single host, closely mirroring clinical scenarios of metastatic melanoma. We have successfully developed a new dual-tumour pigmented and non-pigmented mouse melanoma model mimicking clinical observations to study the abscopal effect in metastatic melanoma.
Targeting Melanoma Cell Adhesion Molecule as a Novel Therapeutic Approach for Acral Melanoma.
Tanaka Y, Ito T, Nishio K … +2 more , Tanegashima K, Nakahara T
Exp Dermatol · 2025 Sep · PMID 40898663 · Full text
Acral melanoma (AM) is a rare subtype of cutaneous melanoma mainly found in acral locations. The treatment of advanced AM remains challenging due to its rarity and the distinct features of this subtype compared with the...
Acral melanoma (AM) is a rare subtype of cutaneous melanoma mainly found in acral locations. The treatment of advanced AM remains challenging due to its rarity and the distinct features of this subtype compared with the other common types of melanomas. There is thus an urgent need to develop effective therapeutic approaches for AM. This study was established to screen and evaluate potential therapeutic targets for AM. DNA microarray analysis comparing normal epidermal melanocytes and AM cell lines (SM2-1 and MMG-1) showed that approximately 500 genes were highly expressed in the AM cell lines compared with the levels in normal melanocytes. Among them, melanoma cell adhesion molecule (MCAM) was selected for further analyses and was found to be significantly highly expressed in AM cell lines compared with the levels in melanocytes and keratinocytes. Knockdown of MCAM significantly inhibited the proliferation of AM cell lines with decreased expression of cyclin D1 and BCL2. The cytotoxicity of MCAM-targeted antibody-drug conjugate was further evaluated and it significantly decreased the viability of AM cell lines. In conclusion, MCAM is highly expressed in AM cell lines and affects their proliferation, likely through modulating the expression of cyclin D1 and BCL2. These findings highlight the potential of MCAM as a therapeutic target of AM.
Exploring Novel Biomarkers for Rosacea Through Cohort Study and Mendelian Randomisation.
Mao R, Wang F, Zhang T … +1 more , Li J
Exp Dermatol · 2025 Sep · PMID 40890957 · Publisher ↗
The current therapeutic landscape for rosacea is notably deficient in targeted medications, underscoring an urgent need for the identification of novel biomarkers. Utilising a longitudinal cohort of 54 306 individuals fr...
The current therapeutic landscape for rosacea is notably deficient in targeted medications, underscoring an urgent need for the identification of novel biomarkers. Utilising a longitudinal cohort of 54 306 individuals from the UK Biobank (UKB), we conducted a comprehensive assessment of the associations between 2923 serum proteins and the risk for rosacea. Our cohort analysis identified 18 proteins significantly associated with rosacea risk. Next, we complemented the two-sample Mendelian randomisation (TSMR) and Mendelian randomisation (SMR) analysis based on pooled data to identify genetic links between protein targets and rosacea. TSMR analysis refined this list to nine proteins demonstrating significant causal relationships with at least one form of rosacea. Further refinement through SMR and differential expression analysis reduced this to five key proteins, including four (ABHD14B, CHMP6, DBNL and MCFD2) that inhibit rosacea onset and one (MSR1) that promotes it. The differential expression of these five biomarkers was validated by multiple omics datasets as well as in vitro experiments. We calculated the protein score based on the expression levels of these proteins, noting that participants with higher scores demonstrated an increased incidence of rosacea. The integrative examination of proteomic and genetic data from a European adult cohort provides robust causal evidence for several proteins as promising new biomarkers for the development of rosacea treatments.
Clinical, Dermoscopic and Reflectance Confocal Microscopy Characteristics Associated With the Presence of Negative Pigment Network Among Spitzoid Neoplasms.
Spadafora M, Farnetani F, Borsari S … +7 more , Kaleci S, Porat D, Ciardo S, Stanganelli I, Longo C, Pellacani G, Scope A
Exp Dermatol · 2025 Aug · PMID 40862321 · Full text
Negative pigment network (NPN) is a dermoscopic structure frequently associated with melanoma. Though commonly observed in Spitz naevi (SN) and Spitzoid melanoma (SM), its reflectance confocal microscopy (RCM) correlates...
Negative pigment network (NPN) is a dermoscopic structure frequently associated with melanoma. Though commonly observed in Spitz naevi (SN) and Spitzoid melanoma (SM), its reflectance confocal microscopy (RCM) correlates have been primarily studied in non-Spitzoid melanocytic neoplasms. This study aimed to identify clinical, dermoscopic, and RCM features associated with dermoscopic NPN in Spitzoid neoplasms and explore its histopathological correlates. We retrospectively analysed clinical, dermoscopic, and RCM images from 128 histopathologically confirmed SN and SM cases diagnosed between 2014 and 2020. Lesions were grouped by presence or absence of dermoscopic NPN, and comparisons were made across clinical, dermoscopic, and RCM features. A subset of 20 cases underwent histopathologic correlation. Of the 128 cases, 96 (74%) were SN and 32 (26%) SM. NPN was present in 58 lesions (45%)-40 SN (42%) and 18 SM (56%). NPN was associated with lesion diameter ≥ 5 mm, presence of shiny white structures, dotted vessels, and inversely associated with diffuse blue-white veil. SMs showed higher frequencies of asymmetry, multicomponent patterns, and extensive NPN. RCM features previously linked to NPN-round or linear surface disruptions, bright suprabasal areas, and broadened interpapillary spaces-were seen in 87% of cases but did not correlate with diagnosis or dermoscopic NPN. Corresponding histologic features included keratin-filled dells, hypergranulosis, and broadened rete ridges or infundibula. RCM correlates of dermoscopic NPN are frequently observed in Spitzoid neoplasms, independent of visible dermoscopic NPN, suggesting perceptibility may depend on contrast within dermoscopic patterns.
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