Experimental Dermatology最新文献

Incontinence-associated dermatitis (IAD) is one of the most serious complications in older people with incontinence. Controlling urine property in absorbent pads could be effective for preventing IAD caused by bacterial urine. However, no animal model has been established to evaluate their effectiveness. This study aimed to induce IAD-like skin changes using absorbent pads containing bacterial urine and to confirm their pathophysiology in rats. Hairless Wistar Yagi rats were divided into the bacteria-containing urine (BU) and the bacteria-free urine (U) groups. A 10-h-attachment of absorbent pads containing artificial urine with/without bacteria to the skin pretreated with sodium lauryl sulfate was performed repeatedly for 5 days. Macroscopic findings and skin barrier function were examined every day, and histological changes, inflammatory responses and bacterial quantification in tissue samples were examined on Day 5. The BU group exhibited significant skin redness from Day 3, significant elevation of transepidermal water loss from Day 1, and histological changes, including significantly thickened epidermis, abnormal keratinocyte differentiation and erythrocyte leakage. Inflammation, confirmed by higher myeloperoxidase-positive cells, elevated tumour necrosis factor-α expression, and vascular endothelial damage, indicated by CD31 and pentraxin 3-positive cells, were observed in the BU group. The bacterial quantification showed no significant difference between the groups. IAD-like skin changes including histological changes and inflammation were suggested to be caused by urine properties altered by bacteria. This study proposed a new animal model for evaluating the effectiveness of absorbent pads in controlling the urine properties of bacterial urine on preventing IAD.

Dab2 is an endocytic adaptor protein involved in various physiological processes and signaling pathways. Dab2 is deregulated in various cancers; however, its role in skin squamous cell carcinoma ( SCC) has not been elucidated yet. In the present study, we used the DMBA/TPA induced murine skin carcinogenesis model to examine the role of Dab2 in skin tumour progression. We generated tamoxifen inducible Dab2 conditional knockout system for our study. Loss of Dab2 led to delayed papilloma initiation and reduced papilloma burden. Delayed papilloma initiation was due to reduce proliferative potential of the papillomas due to Dab2 loss. Furthermore, while the WT papillomas progressed to SCC, the papillomas formed in Dab2 cKO mice failed to undergo malignant conversion to SCC. Dab2 cKO tumours showed reduced expression of K8, a marker for aggressive tumour. Moreover, Dab2 ckO tumours failed to undergo EMT as shown by reduced expression of Vimentin and Twist1. Dab2 cKO tumours also showed reduced expression of Sox2, a stem cell marker. Furthermore, qPCR analysis showed upregulation of Dab2 expression in the human skin cancer cell lines as compared to normal human skin keratinocytes. In patients, TCGA data analysis of skin cancer melanoma (SKCM) showed a trend where high levels of Dab2 correlated with poor overall survival. The present study shows that Dab2 promotes tumour progression in skin SCC.

Neurofibromatosis Type 1 (NF1) is the most common neurocutaneous disorder in the United States. Due to a nonfunctional mutation in the NF1 gene, the disorder may initially present with café-au-lait spots and later numerous neurofibromas across the body. Epilepsy is a rare comorbidity of NF1, with an incidence of just 4%-7%. While abnormal electroencephalograms have been seen in up to 25% of NF1 patients, very few studies have investigated the association between epilepsy and the NF1 patient profile. This study was aimed at evaluating the associations between epilepsy and demographics, comorbidities and healthcare outcomes in NF1 patients. The 2017 National Inpatient Sample (NIS) database was retrospectively queried for patients with NF1 using ICD-10 PCS codes. Chi-square tests were used in univariable analysis to compare patients within this cohort with and without epilepsy. Regression analysis was used in multivariable analysis to identify comorbidities that were predictors of epilepsy and the effect of comorbidities on outcomes. 4635 patients with NF1 were identified, of which 655 (14.1%) had epilepsy and 3980 (85.9%) did not. The NF1 patient population with epilepsy was largely comprised of White males of lower household income in larger urban/teaching hospitals and who used Medicare or Medicaid. Multivariable logistic regression revealed that malignant brain neoplasms, paralytic ileus, scoliosis, pregnancy complications, paralysis, other neurological disorders, metastatic cancer, coagulopathy, drug abuse and hypertension were predictors of developing epilepsy in NF1 patients. Additionally, epilepsy in NF1 patients was associated with a shorter length of stay, lower total charges and fewer total procedures.

Skin aging is driven by a complex set of cellular pathways. Among these, epigenetic mechanisms have garnered particular attention, because of their sensitivity to environmental and lifestyle factors. DNA methylation represents the longest known and best understood epigenetic mechanism. We explain how DNA methylation might function as an interface between the environment and the genome of human skin. Exposures to different environmental factors and lifestyles are known to modulate age-related methylation patterns, as illustrated by their effect on DNA methylation clocks. Human skin provides a particularly well-suited tissue for understanding age-related methylation changes and it has been shown recently that modulation of DNA methylation can induce skin rejuvenation. We explain how the use of mildly demethylating agents can be safeguarded to ensure the specific removal of age-related DNA methylation changes. We also identify important areas of future research, leading to a deeper understanding of the mechanisms that drive epigenetic aging and to the development of further refined intervention strategies.

Vitamin D activates the vitamin D receptor (VDR), which dimerizes preferentially with the retinoid X receptor-α (RXRα). This heterodimer connects with genetic elements responsive to vitamin D, inhibiting or stimulating gene activity. We performed Nanostring® analysis of VDR/RXRα to compare the mRNA expression of this heterodimer and their correlated transcriptomes in non-melanoma skin cancer (basal cell carcinomas (BCC) and squamous cell carcinomas (SCC)) and melanocytic lesions (intradermal nevi (IN), and melanomas (MM)) with control skin. To evaluate VDR, RXRα and other 22 correlated genes in BCC, SCC, IN and MM, paraffin samples had their transcriptomes analysed using Nanostring®, a platform that allows multiple mRNA analyses. There were 46 samples, including 11 BCC, 10 SCC, 10 IN, 12 MM and 3 pools of control skins. Most mRNAs differed between the lesion groups and the control group. BCC and SCC NCOR2 were upregulated; in MM and IN, RXRγ was higher than in the control group. TP53, FOXO3 and MED1 showed a significant difference when we compared the BCC group to the SCC group. Melanoma and intradermal nevi differed only in AhR. VDR and RXRα were lower than the control in all groups. The panel shows a clear difference between the non-melanocytic cancers and, on the other hand, a slight difference between the melanocytic lesions. The study of vitamin D's influence through its receptor and RXRα is an exciting issue for understanding the importance of this pathway, and the present study can impact the prevention and treatment strategies, mainly in non-melanocytic tumours.

Atopic dermatitis (AD) is the most prevalent chronic inflammatory skin disorder, characterised by intense pruritus and recurrent eczematous lesions. Recently, the US FDA has approved Janus kinase (JAK) inhibitors for oral treatment in AD patients. However, oral immunomodulatory agents have demonstrated adverse effects. In previous studies, we demonstrated the efficacy of topical taurodeoxycholate (TDCA), a G protein-coupled receptor 19 (GPCR19) agonist, on AD. In this study, we further evaluated the efficacy of orally administered TDCA on MC903- and dinitrochlorobenzene (DNCB)-induced AD mouse models. Oral administration of TDCA significantly ameliorated AD symptoms and reduced both epidermal and dermal thickness. Additionally, oral TDCA treatment inhibited the infiltration of myeloid and lymphoid cells into AD lesions. TDCA also suppressed the expression of thymic stromal lymphopoietin (TSLP), interleukin (IL)-4, IL-13, IL-33, IL-1β, tumour necrosis factor-alpha (TNF-α) and chemokine (C-C motif) ligand 17 in the skin and blood. Given the previously demonstrated safety profiles of TDCA, oral TDCA may offer a beneficial and safer alternative for AD patients.