Experimental Dermatology最新文献

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.

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.

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 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.

Psoriasis (PSO) is a chronic, systemic immune-mediated inflammatory disease that has been increasingly recognised as being significantly comorbid with various cardiovascular diseases (CVDs). However, the underlying shared genetic architecture and biological mechanisms connecting these conditions remain largely unclear. This study aimed to systematically evaluate the genetic correlations between PSO and four major CVDs—hypertension, coronary heart disease, coronary atherosclerosis, and heart failure—and to identify shared genetic loci, functional genes, and immune-mediated pathways that may serve as potential targets for comorbidity intervention. We integrated multiple large-scale publicly available genome-wide association study datasets and employed a multidimensional genetic analysis framework. This included linkage disequilibrium score regression (LDSC), high-definition likelihood (HDL), stratified LDSC (S-LDSC), multi-dimensional gene-set enrichment (MAGMA), pleiotropy analysis under the composite null hypothesis (PLACO), and summary-data-based Mendelian randomisation (SMR). These approaches were used to elucidate the shared genetic architecture and to functionally annotate the biological mechanisms underlying PSO–CVD comorbidity. LDSC and HDL analyses revealed significant positive genetic correlations between PSO and all four CVDs (p < 0.05). PLACO identified a total of 653 pleiotropic SNPs, enriched in key genomic loci such as 12q24.12 (e.g., SH2B3, BRAP) and 5q31.1 (e.g., IL3, C5orf56). S-LDSC results demonstrated significant enrichment of these shared signals in disease-relevant tissues including the aorta, coronary arteries, peripheral blood, and spleen. Immune colocalization analysis further highlighted the involvement of T cells, monocytes/macrophages, and NK cells in the genetic comorbidity between PSO and CVDs. Integrative analyses combining MAGMA, SMR, and FUMA identified multiple potential therapeutic targets, such as APOE, IL13, and C5orf56, that may play key roles in the pathogenesis of both diseases. This study provides the first comprehensive genetic dissection of the comorbidity between PSO and CVDs. We propose a “genetics–immunity–tissue” regulatory model underlying the shared pathophysiology. Our findings provide potential evidence that PSO, as a systemic condition, may influence cardiovascular pathophysiology.