{"title":"Enhancement of skin barrier function and augmentation of epidermal cell-cell interactions by galactomyces ferment filtrate","authors":"","doi":"10.1016/j.jdermsci.2024.03.011","DOIUrl":"10.1016/j.jdermsci.2024.03.011","url":null,"abstract":"","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0923181124000574/pdfft?md5=8d0fd39403ab5f87104e964e890f7e1d&pid=1-s2.0-S0923181124000574-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141629557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Integration of line-field confocal optical coherence tomography and in situ microenvironmental mapping to investigate the living microenvironment of reconstructed human skin and melanoma models","authors":"","doi":"10.1016/j.jdermsci.2024.07.001","DOIUrl":"10.1016/j.jdermsci.2024.07.001","url":null,"abstract":"<div><h3>Background</h3><p>In tissue engineering, real-time monitoring of tumors and of the dynamics of the microenvironment within <em>in vitro</em> models has traditionally been hindered by the need to harvest the cultures to obtain material to analyze. Line-field confocal optical coherence tomography (LC-OCT) has proven to be useful in evaluating <em>in vivo</em> skin conditions, including melanoma, by capturing dynamic, three-dimensional (3D) information without the need for invasive procedures, such as biopsies. Additionally, the M-Duo Technology® developed by IMcoMET presents a unique opportunity for continuous <em>in situ</em> biomarker sampling, providing insights into local cellular behavior and interactions.</p></div><div><h3>Objective</h3><p>This study aimed to validate the non-destructive mapping capabilities of two advanced methodologies (LC-OCT by DAMAE Medical and M-Duo Technology® by IMcoMET) to investigate the living microenvironment of <em>in vitro</em> reconstructed human skin (RhS) and melanoma-RhS (Mel-RhS).</p></div><div><h3>Methods</h3><p>LC-OCT and M-Duo Technology® were compared to conventional analysis of the RhS and Mel-RhS microenvironments.</p></div><div><h3>Results</h3><p>LC-OCT successfully visualized the distinct layers of the epidermis and tumor structures within the Mel-RhS, identifying keratinocytes, melanocytes, tumor nests, and fibroblasts. The M-Duo Technology® revealed differences in <em>in situ</em> cytokine (IL-6) and chemokine (CCL2, CXCL10, and IL-8) secretion between Mel-RhS and the control RhS. Notably, such differences were not detected through conventional investigation of secreted proteins in culture supernatants.</p></div><div><h3>Conclusion</h3><p>The combination of LC-OCT's high-resolution imaging and M-Duo Technology®’s <em>in situ</em> microenvironmental mapping has the potential to provide a synergistic platform for non-invasive, real-time analysis, allowing for prolonged observation of processes within Mel-RhS models without the need for culture disruption.</p></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0923181124001476/pdfft?md5=4a78bb95ef799ad9258a7621626a85d2&pid=1-s2.0-S0923181124001476-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141692014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Topical application of a BCL-2 inhibitor ameliorates imiquimod-induced psoriasiform dermatitis by eliminating senescent cells","authors":"","doi":"10.1016/j.jdermsci.2024.06.002","DOIUrl":"10.1016/j.jdermsci.2024.06.002","url":null,"abstract":"<div><h3>Background</h3><p>Psoriasis is an inflammatory skin disease with unclear pathogenesis and unmet therapeutic needs.</p></div><div><h3>Objective</h3><p>To investigate the role of senescent CD4<sup>+</sup><span> T cells in psoriatic lesion formation and explore the application of senolytics in treating psoriasis.</span></p></div><div><h3>Methods</h3><p>We explored the expression levels of p16<sup>INK4a</sup><span> and p21, classical markers of cellular senescence, in CD4</span><sup>+</sup> T cells from human psoriatic lesions and imiquimod (IMQ)-induced psoriatic lesions. We prepared a senolytic gel using B-cell lymphoma 2 (BCL-2) inhibitor ABT-737 and evaluated its therapeutic efficacy in treating psoriasis.</p></div><div><h3>Results</h3><p>Using multispectrum immunohistochemistry (mIHC) staining, we detected increased expression levels of p16<sup>INK4a</sup> and p21 in CD4<sup>+</sup><span> T cells from psoriatic lesions. After topical application of ABT-737 gel, significant alleviation of IMQ-induced psoriatic lesions was observed, with milder pathological alterations. Mechanistically, ABT-737 gel significantly decreased the percentage of senescent cells, expression of T cell receptor<span> (TCR) α and β chains, and expression of </span></span><span><em>Tet methylcytosine </em><em>dioxygenase</em><em> 2</em></span> (<em>Tet2</em>) in IMQ-induced psoriatic lesions, as determined by mIHC, high-throughput sequencing of the TCR repertoire, and RT-qPCR, respectively. Furthermore, the severity of psoriatic lesions in CD4<sup>cre</sup>Tet2<sup>f/f</sup> mice was milder than that in Tet2<sup>f/f</sup> mice in the IMQ-induced psoriasis model.</p></div><div><h3>Conclusion</h3><p>We revealed the roles of senescent CD4<sup>+</sup> T cells in developing psoriasis and highlighted the therapeutic potential of topical ABT-737 gel in treating psoriasis through the elimination of senescent cells, modulation of the TCR αβ repertoire, and regulation of the TET2-Th17 cell pathway.</p></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141499960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"miR-25–5p in exosomes derived from UVB-induced fibroblasts regulates melanogenesis via TSC2-dominated cellular organelle dysfunction","authors":"","doi":"10.1016/j.jdermsci.2024.06.001","DOIUrl":"10.1016/j.jdermsci.2024.06.001","url":null,"abstract":"<div><h3>Background</h3><p><span>Few reports have confirmed whether exosomes derived from fibroblasts can regulate the process of </span>melanogenesis<span>. We wondered whether exosomes<span> derived from fibroblasts could have a potent regulatory effect on melanogenesis and explored the underlying mechanisms.</span></span></p></div><div><h3>Objective</h3><p>This study aimed to find the role of fibroblasts in melanocytes and revealed the related mechanisms.</p></div><div><h3>Methods</h3><p>RT-qPCR, Western blot analysis<span><span><span><span> were conducted to measure the RNA and </span>protein expression level of various related genes. </span>miRNA<span><span> sequencing, mass spectrum analysis and subsequent bioinformatics analysis were employed to find the underlying targets. Zebrafish were employed to measure the </span>melanin synthesis related process in vivo. Furthermore, </span></span>electron microscopy<span>, ROS measurement and dual-luciferase reporter assay were adopted to investigate the relationship between these processes.</span></span></p></div><div><h3>Results</h3><p><span><span><span>We found that exosomes derived from human primary dermal fibroblasts were internalized by human primary </span>melanocytes<span> and MNT1 cells and that the melanin<span> content and the expression of melanin synthesis-related proteins TYR and </span></span></span>MITF<span><span> was inhibited by exosomes derived from UVB-induced human primary dermal fibroblasts. The miRNA expression profile in secreted exosomes changed significantly, with miR-25–5p identified as capable of regulating </span>TSC2<span> expression via the CDS region. The miR-25–5p-TSC2 axis could affect the melanin content through subsequent cellular organelle dysfunction, such as mitochondrial dysfunction, </span></span></span>endoplasmic reticulum stress<span> and dysregulation of lysosomal cysteine proteases.</span></p></div><div><h3>Conclusion</h3><p>We unveiled a novel regulatory role of fibroblasts in melanocytes<span>, facilitated by the secretion of exosomes. miR-25–5p within exosomes plays a pivotal role in regulating melanogenesis via TSC2-induced cellular organelle dysfunction.</span></p></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141408728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Necrosulfonamide promotes hair growth and ameliorates DHT-induced hair growth inhibition","authors":"","doi":"10.1016/j.jdermsci.2024.04.004","DOIUrl":"10.1016/j.jdermsci.2024.04.004","url":null,"abstract":"<div><h3>Background</h3><p><span>Alopecia<span> affects patients' appearance and psychology. Mixed-lineage kinase domain-like pseudokinase (MLKL)-mediated </span></span>necroptosis<span> plays a role in various skin diseases, but its effect on hair growth is unclear.</span></p></div><div><h3>Objective</h3><p>To investigate the effects of MLKL on hair growth and its regulatory mechanisms and to determine the potential clinical value of Necrosulfonamide (NSA, a MLKL-targeting inhibitor) in promoting hair growth and counteracting dihydrotestosterone (DHT) inhibition of hair growth.</p></div><div><h3>Methods</h3><p><span>The expression level of MLKL was detected in the scalp of </span>androgenetic alopecia (AGA) patients and the skin tissues of mice. Knock down MLKL expression or use NSA to observe hair growth in vivo and in vitro.</p></div><div><h3>Results</h3><p><span>In AGA patients, MLKL expression is elevated in the alopecia areas. In mice, MLKL is significantly expressed in the outer root sheath (ORS) cells of </span>hair follicles<span><span>, peaking during the catagen phase. Knockdown expression of MLKL in mice skin promoted hair growth. NSA enhanced hair growth and prevented hair follicle regression via the Wnt signaling. Reduced MLKL boosts ORS </span>cell proliferation without directly impacting DPCs' growth. Interestingly, NSA boosts DPCs' proliferation and induction when co-cultured with ORS cells. Besides, NSA alleviated the inhibition of DHT on hair growth in vivo and vitro.</span></p></div><div><h3>Conclusion</h3><p>NSA inhibited the activation of MLKL in ORS cells, promoted the activation of Wnt signal in DPC cells, and improved the inhibition of hair growth by DHT, illuminating a new alopecia mechanism and aiding anti-alopecia drug development.</p></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141753673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"JSID2024-1","authors":"","doi":"10.1016/S0923-1811(24)00154-3","DOIUrl":"10.1016/S0923-1811(24)00154-3","url":null,"abstract":"","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142048983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Maximizing the potential of biobanks in dermatology research","authors":"","doi":"10.1016/j.jdermsci.2024.03.003","DOIUrl":"10.1016/j.jdermsci.2024.03.003","url":null,"abstract":"","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140268281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Dysregulated tryptophan metabolism and AhR pathway contributed to CXCL10 upregulation in stable non-segmental vitiligo","authors":"","doi":"10.1016/j.jdermsci.2024.06.003","DOIUrl":"10.1016/j.jdermsci.2024.06.003","url":null,"abstract":"<div><h3>Background</h3><p>Tryptophan metabolism dysregulation has been observed in vitiligo. However, drawing a mechanistic linkage between this metabolic disturbance and vitiligo pathogenesis remains challenging.</p></div><div><h3>Objective</h3><p>Aim to reveal the characterization of tryptophan metabolism in vitiligo and investigate the role of tryptophan metabolites in vitiligo pathophysiology.</p></div><div><h3>Methods</h3><p>LC-MS/MS, dual-luciferase reporter assay, ELISA, qRT-PCR, small interfering RNA, western blotting, and immunohistochemistry were employed.</p></div><div><h3>Results</h3><p>Kynurenine pathway activation and KYAT enzyme-associated deviation to kynurenic acid (KYNA) in the plasma of stable non-segmental vitiligo were determined. Using a public microarray dataset, we next validated the activation of kynurenine pathway was related with inflammatory-related genes expression in skin of vitiligo patients. Furthermore, we found that KYNA induced CXCL10 upregulation in keratinocytes <em>via</em> AhR activation. Moreover, the total activity of AhR agonist was increased while the AhR concentration <em>per se</em> was decreased in the plasma of vitiligo patients. Finally, higher KYAT, CXCL10, CYP1A1 and lower AhR expression in vitiligo lesional skin were observed by immunohistochemistry staining.</p></div><div><h3>Conclusion</h3><p>This study depicts the metabolic and genetic characterizations of tryptophan metabolism in vitiligo and proposes that KYNA, a tryptophan-derived AhR ligand, can enhance CXCL10 expression in keratinocytes.</p></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141494685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"LEKTI domain 6 displays anti-inflammatory action in vitro and in a murine atopic dermatitis model","authors":"","doi":"10.1016/j.jdermsci.2024.03.004","DOIUrl":"10.1016/j.jdermsci.2024.03.004","url":null,"abstract":"<div><h3>Background</h3><p>Lympho-epithelial Kazal-type-related inhibitor (LEKTI) is a serine protease inhibitor consisting of multiple domains. A loss of function mutation is described in Netherton patients that show severe symptoms of atopic lesions and itch.</p></div><div><h3>Objectives</h3><p>LEKTI domain 6 (LD6) has shown strong serine protease-inhibitory action in <em>in vitro</em> assays and thus it was tested <em>in vitro</em> and <em>in vivo</em> for potential anti-inflammatory action in models of atopic skin disease.</p></div><div><h3>Methods</h3><p>Human skin equivalents were treated with LD6 and an inflammatory reaction was challenged by kallikrein-related endopeptidase 5 (KLK5). Furthermore, LD6 was tested on dorsal root ganglia cells stimulated with KLK5, SLIGRL and histamine by calcium imaging. The effect of topically administered LD6 (0.4–0.8%) in lipoderm was compared to a topical formulation of betamethasone-diproprionate (0.1%) in a therapeutic setting on atopic dermatitis-like lesions in NC/Nga mice sensitized to house dust mite antigen. Endpoints were clinical scoring of the mice as well as determination of scratching behaviour.</p></div><div><h3>Results</h3><p>KLK5 induced an upregulation of CXCL-8, CCL20 and IL-6 in skin equivalents. This upregulation was reduced by pre-incubation with LD6. KLK5 as well as histamine induced calcium influx in a population of neurons. LD6 significantly reduced the calcium response to both stimuli. When administered onto lesional skin of NC/Nga mice, both LD6 and betamethasone-dipropionate significantly reduced the inflammatory reaction. The effect on itch behaviour was less pronounced.</p></div><div><h3>Conclusion</h3><p>Topical administration of LD6 might be a new therapeutic option for treatment of lesional atopic skin.</p></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0923181124000501/pdfft?md5=f8c0be6d25d62f1e26d970990ec01145&pid=1-s2.0-S0923181124000501-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140156275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}