Experimental Dermatology最新文献

Microplastics (MPs) have emerged as a major concern among contemporary pollutants, but there is still limited knowledge regarding their impact on skin function. To address this issue, we conducted a transcriptome analysis on skin tissue that had been exposed to polystyrene (PS), which is one of the most prevalent type of MPs that can be absorbed through the skin. The results of our study, obtained through functional enrichment analysis and the experiment of treating HaCaT with PS, revealed that PS may have an effect on skin barrier function, specifically the permeability barrier through inhibiting keratinocyte differentiation. Additionally, PS also induced dysfunction in the extracellular matrix (ECM). Mechanistically, we observed that PS induced fibroblasts senescence and increased the secretion of senescence-related characteristics. Furthermore, the expression of core genes related to the ECM, such as COL1A1, COL1A2 and SPP1, was found to be down-regulated in PS-treated fibroblasts. Moreover, an in vitro experiment provided evidence of the involvement of PPARγ in PS-induced fibroblast senescence. In conclusion, our study has identified PS as a causal factor for skin barrier dysfunction. Additionally, PS induces fibroblast senescence, leading to ECM dysfunction and contributing to skin aging. These findings further strengthen the understanding and management of the effects of MPs on skin health.

Systemic sclerosis (SSc) is characterised by immune dysregulation, vasculopathy and fibrosis, driven by genetic and environmental factors. S100 proteins, which constitute a unique class of calcium-binding proteins, have been shown to be critically implicated in various inflammatory and fibrotic conditions. In this study, we investigated the possible involvement of S100A11 in SSc by examining its cutaneous expression and systemic serum levels, correlating them with key clinical parameters. First, we performed immunohistochemical (IHC) staining to examine S100A11 localisation in skin specimens from SSc patients and controls, and found that S100A11 was robustly expressed in SSc dermal fibroblasts. Analysis on the publicly available single-cell RNA-sequencing (scRNA-seq) data of SSc skin samples further confirmed that S100A11 was highly expressed in SSc dermal fibroblasts along with several key genes associated with cellular senescence. Finally, we evaluated serum levels of S100A11 in SSc patients and HCs using enzyme-linked immunosorbent assay (ELISA), and found that serum S100A11 levels were significantly elevated in diffuse cutaneous SSc (dcSSc) patients compared to controls. S100A11 serum levels in SSc patients were significantly correlated with modified Rodnan total skin thickness score and key parameters of SSc-related interstitial lung disease. Our data collectively suggested a potential pathophysiological role of S100A11 in the cutaneous and lung fibrosis associated with SSc, warranting further investigation into its functional roles in this disease.

Atopic dermatitis (AD) is a common inflammatory skin disorder characterised by hypersensitivity to allergens, eczematous lesions and pruritus. The aim of this study was to comprehensively characterise a murine model of dermatitis and assess the similarity with the human disease, as well as to profile clinically relevant AD therapies. Four repeated topical administrations of oxazolone in the auricular skin of sensitised mice induced morphological features compatible with AD, including redness and swelling, as well as histological changes typical of spongiotic (eczematous) dermatitis and increased plasmatic IgE. Additionally, key driver Type 2 cytokines involved in the pathophysiology of the disease, IL-4, IL-13 and IL − 31, were upregulated in the skin, along with cytokines related to Type 1, 17 and 22 responses, which have been reported to be relevant in the chronic stages of the disease. RNA-seq studies in OXA model mice samples validate expression changes obtained by q-PCR and suggest a greater significant similarity with the transcriptomic signature of human AD with respect to psoriasis studies. Oral (cyclosporine, prednisolone and baricitinib) and topical treatments (betamethasone, tacrolimus and crisaborole) were effective inhibiting the induced pathology, as well as modulating the cytokine gene signature of AD. In conclusion, our 4 oxazolone challenges model recapitulates many of the key features of the disease and is responsive to AD standard of care therapies in humans.

Skin cancer remains one of the most common and deadly forms of cancer, necessitating accurate and early diagnosis to improve patient outcomes. In order to improve classification performance on unbalanced datasets, this study proposes a distinctive approach for classifying skin cancer that utilises both machine learning (ML) and deep learning (DL) methods. We extract features from three different DL models (DenseNet201, Xception, Mobilenet) and concatenate them to create an extensive feature set. Afterwards, several ML algorithms are given these features to be classified. We utilise ensemble techniques to aggregate the predictions from several classifiers, significantly improving the classification's resilience and accuracy. To address the problem of data imbalance, we employ class weight updates and data augmentation strategies to ensure that the model is thoroughly trained across all classes. Our method shows significant improvements over recent existing approaches in terms of classification accuracy and generalisation. The proposed model successfully received 98.7%, 94.4% accuracy, 99%, 95%, precision, 99%, 96% recall, 99%, and 96% f1-score for the HAM10000 and ISIC datasets, respectively. This study offers dermatologists and other medical practitioners' valuable insights into the classification of skin cancer.

Regulatory T cells (Tregs) are specialised T lymphocytes that sit at the nexus of immune regulation and tissue repair. While it is appreciated that a substantial number of Tregs are present in healthy human skin, less is known about their microanatomic spatial localisation. Knowledge about the specialised niches that Tregs occupy may aid in rational drug development to treat dermatologic diseases. Thus, we performed multiplexed immunohistochemistry for CD4 and FOXP3 (the lineage-defining transcription factor of Tregs) on healthy skin sections obtained from eight different cutaneous sites, and quantified Tregs and Tcon in distinct regions. We found that Tregs (CD4⁺ FOXP3⁺) comprised roughly 20% of CD4⁺ T cells in skin and that Tregs and T-conventional cells (Tcon; CD4⁺ Foxp3⁻) are enriched in follicularly dense skin and show preferential accumulation in perivascular and perifollicular niches in the upper dermis. Additionally, male skin shows a significant increase in the numbers of Tregs and Tcon, while female skin shows a higher Tcon:Treg ratio. We also find that the frequency of skin Tregs declines over time. Overall, we conclude that the upper dermal perivascular region is a niche that supports the accumulation of CD4⁺ T cells in steady-state human skin.