Experimental Dermatology最新文献

Vitiligo is a multifactorial chronic depigmentary disorder characterised by the loss of functional melanocytes. Its pathogenesis involves complex interactions among genetic predisposition, environmental factors, and autoimmune dysregulation. In recent years, extensive research has highlighted the critical role of epigenetic regulation in vitiligo development, including aberrant DNA methylation, dysregulated histone modifications, and non-coding RNA (ncRNA) expression disturbances. These abnormal epigenetic modifications contribute to disease progression by disrupting melanogenesis, promoting oxidative stress–induced melanocyte apoptosis, and driving autoimmune responses. From a translational perspective, specific epigenetic alterations show potential as diagnostic biomarkers, disease severity indicators, and therapeutic response monitors. Furthermore, epigenetic drugs, CRISPR/dCas9-based epigenetic editing, and targeted epigenetic reprogramming of tissue-resident memory T cells demonstrate promising clinical applications. This review systematically summarises the molecular mechanisms underlying epigenetic dysregulation in vitiligo pathogenesis and explores its translational implications, providing a theoretical foundation for advancing disease understanding and developing novel therapeutic strategies.

Inflammatory skin diseases are common and often difficult to differentiate. Ex vivo confocal laser scanning microscopy (EVCM) offers a rapid and promising approach. This study aimed to assess the diagnostic utility of EVCM in differentiating inflammatory dermatoses, particularly eczema, psoriasis and lichen planus, by comparing its performance with gold standard histopathology. Tissue samples of 110 patients presenting with inflammatory skin conditions were subjected to both EVCM and conventional histopathology. EVCM images were analysed by three blinded observers, with varying knowledge in histopathology and EVCM, utilising pattern analysis based on Ackermann's classification and single-cell analysis focusing on neutrophil (neutrophils) and eosinophil (eosinophils) granulocytes. Sensitivity and specificity were calculated using contingency tables. We used Cohen's Kappa coefficient and Firth's logistic regression models to evaluate the correlations between disease-associated histopathological features observed via EVCM and histopathology, as well as their impact on accurate histopathological diagnoses. Our findings demonstrate that EVCM provides rapid and insightful visualisation of characteristic features associated with inflammatory dermatological diseases. Diagnostic accuracy varied based on observer experience. The specialist proficient in both EVCM and histopathology achieved the highest accuracy rates for correctly diagnosing lichen planus (97.27%), psoriasis (95.45%) and eczema (92.73%). In conclusion EVCM emerges as a promising adjunct to histopathology, offering a swift and meaningful visualisation of inflammatory disease features. The integration of EVCM could significantly contribute to expediting diagnostic workflows and facilitating prompt, targeted therapeutic interventions. Further research and validation are warranted to establish EVCM's role in routine clinical practice.

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.

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.

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: 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.