Experimental Dermatology最新文献

Skin vascular endothelial cells (VECs) play a crucial role in regulating vascular function, orchestrating local immune responses, and contributing to the progression of immune-mediated inflammatory skin disorders. Despite their importance, the shared and distinct features of VECs across various inflammatory skin conditions remain poorly understood. We analysed single-cell data from 94 skin samples, encompassing healthy individuals and patients with psoriasis, atopic dermatitis, and lupus erythematosus and established a comprehensive VEC atlas spanning multiple inflammatory skin diseases. Our results highlight both common and disease-specific features of VECs, particularly in immune cell activation, angiogenesis, metabolic processes, and intercellular communication. Notably, post-capillary VECs (cluster P) emerged as the most activated subpopulation, exhibiting significant enrichment in pro-inflammatory signalling pathways. Interestingly, cluster P showed distinct pseudotemporal relationships with different VEC clusters across different inflammatory conditions, suggesting disease-specific transcriptional state transitions. Besides, VECs employ both disease-specific ligand–receptor networks to recruit immune cells and remodel stromal niches, alongside conserved mechanisms preserving vascular-immune crosstalk across pathologies. Our study provides a detailed characterisation of VEC pathology in various forms of skin inflammation and offers novel insights into the role of vascular biology in the pathogenesis of skin diseases.

Tranexamic acid (TXA), a well-known anti-fibrinolytic agent, has been proven effective in the treatment of hyperpigmentation, particularly melasma. Oestrogen is known as an important cause of melasma and has been reported to induce pigmentation through the oestrogen receptor or the G protein-coupled oestrogen receptor. Although various mechanisms by which TXA improves skin pigmentation have been reported, its effect on oestrogen (17β-estradiol, E2)-induced pigmentation has not yet been elucidated. In this study, we investigated the effect of TXA on melanogenesis induced by 17β-estradiol. Cell viability was assessed in primary human epidermal melanocytes treated with 17β-estradiol or TXA. The effect of TXA on pigmentation was evaluated by western blot analysis, measuring the protein levels of phosphorylated CREB (p-CREB), MITF, and tyrosinase following treatment with 17β-estradiol. First, 17β-estradiol increases melanin production through the induction of the protein expressions of melanogenesis-associated molecules, including p-CREB, MITF, and tyrosinase. Our findings demonstrate that TXA inhibits 17β-estradiol-induced melanogenesis by downregulating the cAMP–PKA pathway. Given that TXA also reduces α-MSH-induced pigmentation via decreased phospho-PKA levels, our results suggest that TXA likely inhibits E2-induced melanogenesis by modulating the cAMP–PKA–CREB–MITF axis, contributing to its depigmenting effect.

Sensitive skin is characterised by unpleasant skin sensations in response to normally non-provocative stimuli. While its pathophysiology remains incompletely understood, environmental factors and impaired barrier function are key contributors. Because many of these environmental factors also promote extrinsic skin aging, a link between sensitive skin and skin aging phenotypes has been proposed. To examine this hypothesis, we analysed data from 810 participants of the Chinese Taizhou Longitudinal Study (2012–2014). Sensitive skin was classified into subtypes based on questionnaire responses, and skin aging phenotypes were assessed using a subset of items from the SCINEXA (Score of Intrinsic and Extrinsic Skin Aging). Associations between sensitive skin subtypes and specific skin aging phenotypes were examined using multivariate regression models. Environmentally triggered sensitive skin was associated with the presence of pigment spots on the cheeks in participants aged ≥ 50 years, particularly among women. Intrinsically triggered sensitive skin was associated with perioral wrinkles, again most prominently in older women. This is the first large-scale study demonstrating objective associations between sensitive skin subtypes and specific skin aging phenotypes. The findings identify subpopulations potentially more vulnerable to environmental stressors, underscoring the need for targeted prevention strategies.

Atopic dermatitis (AD) is a chronic inflammatory skin disease with high heritability, yet its genetic basis, especially in non-European populations, is not fully elucidated. To identify genetic variants associated with AD and to evaluate polygenic risk scores (PRS) for predicting AD risk, severity, and serum IgE levels in a Taiwanese Han population. We conducted a genome-wide association study (GWAS) using data from the China Medical University Hospital Biobank (1031 AD cases, 2106 controls). Two PRS models were developed: PRS_AD (AD risk) and PRS_IgE (IgE levels). The cohort was split into discovery and replication sets (8:2 ratio). Logistic regression, adjusted for age, sex, and population stratification, was used. The GWAS identified a novel AD-associated locus: rs905307 in RANBP2 (OR = 0.66, p = 2.75 × 10⁻⁸). PRS_IgE was significantly associated with increased AD risk (OR = 2.230, 95% CI = 1.815–2.741, p < 0.001) and correlated with serum IgE levels (r = 0.168, p < 0.001). Patients requiring systemic treatment for severe AD had significantly higher PRS_IgE scores (p = 0.017). This study identified a novel genetic locus associated with AD and highlights a shared genetic basis between IgE levels and AD. PRS_IgE demonstrates potential for predicting AD risk and severity, suggesting opportunities for early intervention and personalized management in the Taiwanese Han population. Further research is needed to confirm these findings and explore clinical applications.

Dry skin (xerosis) often involves skin barrier disruption, especially after laser treatment. Moisturisers are crucial for managing dry skin, yet optimal formulations for skin barrier recovery are limited. This study aims to evaluate the effectiveness of a novel moisturiser containing an AIMP1-derived peptide (AdP) in alleviating xerosis after laser treatment and to investigate its effect on skin barrier disruption in vitro. In our randomised controlled clinical trial, we measured transepidermal water loss (TEWL) and Investigative Global Assessment (IGA) scores in participants using AdP-containing moisturisers (ADMP group) versus other moisturisers (CTRL group). The ADMP group demonstrated significant TEWL reduction and improved IGA scores without complications. In vitro study showed that TNF-α levels increased in laser-irradiated skin compared to non-irradiated skin. TNF-α treatment on HaCaT cells disrupted tight junction function, which was rescued by AdP treatment. Additionally, TNF-α affected tight junction proteins ZO-1 and occludin even at very low doses. TNF-α treatment upregulated the downstream signalling proteins TRAF2 and NF-kB, and this effect was mitigated by AdP treatment. Our findings suggest that AdP-containing moisturisers enhance skin barrier function and effectively manage xerosis after laser treatment. These results highlight AdP's potential as a therapeutic cosmeceutical ingredient for treating irradiated and post-procedural dry skin.

Trial Registration: ClinicalTrials.gov identifier: NCT05982509

Discoid lupus erythematosus (DLE) is the most common variant of cutaneous lupus. Histopathology remains the gold standard for diagnosis, but it carries a risk of scarring in a disease already prone to cicatricial outcomes. Additionally, diagnostic delays may occur due to variable processing times, particularly in challenging cases. Line-field confocal optical coherence tomography (LC-OCT) is a novel non-invasive imaging technique offering high-resolution, histology-like features. This study evaluates its diagnostic accuracy in DLE by assessing concordance with histopathology. A cross-sectional study enrolled histologically confirmed DLE from three tertiary referral hospitals. Eleven histological criteria were assessed using LC-OCT and subsequently compared to histopathology. Concordance was evaluated using Cohen's Kappa coefficient (K), with McNemar's test applied to detect significant differences (α = 0.05). Twenty-eight patients with DLE participated in the study. LC-OCT demonstrated strong agreement with histopathology in key diagnostic features of DLE. Near-perfect concordance (K = 1, 100% agreement) was observed for interface dermatitis, dermal vessel dilation, epidermal atrophy, and incontinentia pigmenti. Substantial agreement was found for epidermal disarray (K = 0.85), spongiosis (K = 0.70), necrotic keratinocytes (K = 0.70), and infundibular dilation (K = 0.79). Overall, LC-OCT achieved a Cohen's Kappa of 0.74 with 87.66% concordance, and no statistically significant differences were observed between the two methods (McNemar p = 0.627). LC-OCT is a rapid, effective, and non-invasive diagnostic tool for DLE, demonstrating strong concordance with histopathology and potential for early diagnosis and clinical implementation.