{"title":"Ketoconazole alleviates UVB-induced photoaging by suppressing ROS generation and mitochondrial dysfunction in dermal fibroblasts and ex vivo porcine skin models.","authors":"Hye Yeon Kim, Seungmi Lee, Kyung-Min Lim","doi":"10.1016/j.jdermsci.2025.07.001","DOIUrl":"https://doi.org/10.1016/j.jdermsci.2025.07.001","url":null,"abstract":"<p><strong>Background: </strong>Ultraviolet (UV) radiation is a major contributor to skin damage and photoaging, primarily through the generation of reactive oxygen species (ROS), which disrupt cellular functions and degrade extracellular matrix. Demand for effective agents to counteract these effects is increasing.</p><p><strong>Objective: </strong>This study investigated the protective effects of ketoconazole (KCZ), a well-known antifungal agent, against UVB-induced photoaging using human dermal fibroblasts (Hs68) and an ex vivo porcine skin model.</p><p><strong>Methods: </strong>Hs68 cells and ex vivo porcine skin were exposed to UVB radiation and subsequently treated with KCZ. We assessed cell viability, collagen production, MMP-1 expression, ROS levels, mitochondrial function, and the activation of the MAPK-AP-1 signaling pathway.</p><p><strong>Results: </strong>KCZ alleviated UVB-induced reductions in cell viability, suppressed MMP-1 expression, and prevented collagen degradation in Hs68 cells. In the ex vivo porcine skin model, KCZ reduced UVB-induced skin damage and collagen breakdown. Additionally, KCZ significantly inhibited UVB-induced ROS generation and rescued mitochondrial dysfunction, as evidenced by recovery of mitochondrial membrane potential and respiratory capacity. KCZ also blocked activation of the UV-stimulated MAPK-AP-1 signaling pathway.</p><p><strong>Conclusion: </strong>KCZ exhibits significant anti-photoaging effects by reducing UV-induced oxidative stress, preserving mitochondrial function, and preventing degradation of the extracellular matrix. These findings suggest that KCZ may be a potential anti-photoaging agent.</p>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144621614","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}
Daishi Li, Sitao Liu, Yi Ge, Hui Li, Xinchen Ke, Dongsheng Cao, Guangtong Deng, Lixia Lu, Juan Su
{"title":"Eupatilin attenuates vemurafenib resistance through inhibition of ABCB1 in melanoma.","authors":"Daishi Li, Sitao Liu, Yi Ge, Hui Li, Xinchen Ke, Dongsheng Cao, Guangtong Deng, Lixia Lu, Juan Su","doi":"10.1016/j.jdermsci.2025.06.003","DOIUrl":"https://doi.org/10.1016/j.jdermsci.2025.06.003","url":null,"abstract":"<p><strong>Background: </strong>The clinical efficacy of vemurafenib in melanoma patients has been hindered by the development of acquired resistance.</p><p><strong>Objectives: </strong>To comprehend the molecular signaling pathways underlying this resistance and identify potential strategies to overcome it.</p><p><strong>Methods: </strong>We first constructed the vemurafenib-resistant melanoma cell lines A375R and identified ABCB1 as a potential driver through RNA sequence. ABCB1 knockdown on vemurafenib sensitivity was assessed by CCK-8 and colony formation. FDA-approved eupatilin was identified as a novel ABCB1 inhibitor by employing the quantitative structure-activity relationship model and ADMETlab 2.0. The combined effect of eupatilin and vemurafenib was detected in in vitro and in vivo.</p><p><strong>Results: </strong>The expression of ABCB1 was upregulated in A375R. The genetic inhibition of ABCB1 could restore sensitivity to vemurafenib in resistant cells. Eupatilin was a previously unexplored compound that can selectively target ABCB1 and exhibit favorable safety profiles. Notably, we identified eupatilin as a therapeutic intervention to counteract acquired resistance to vemurafenib in cell and animal experiments, resulting in the inhibition of tumor growth. Furthermore, we found upregulation of ABCB1 in resistant cells due to the activation of the PI3K-AKT-mTOR pathway.</p><p><strong>Conclusion: </strong>These findings provided valuable insights into a novel molecular mechanism underlying vemurafenib resistance and highlighted potential ABCB1 as a viable target, in conjunction with its novel inhibitor eupatilin, to enhance effectiveness of vemurafenib.</p>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144593248","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}
Daoning Zhang, Sini Gao, Chunxia Zhao, Xiaomin Cai, Ruiqin Mai, Guohong Zhang, Hang Li
{"title":"Integrative genomic and transcriptomic profiling reveals dysregulation of FOXA1-AGR2 axis in penoscrotal extramammary Paget's disease.","authors":"Daoning Zhang, Sini Gao, Chunxia Zhao, Xiaomin Cai, Ruiqin Mai, Guohong Zhang, Hang Li","doi":"10.1016/j.jdermsci.2025.06.002","DOIUrl":"https://doi.org/10.1016/j.jdermsci.2025.06.002","url":null,"abstract":"<p><strong>Background: </strong>Extramammary Paget's disease (EMPD) is a rare cutaneous mucinous adenocarcinoma primarily affect the penoscrotal skin, characterized by the presence of Paget cells scattered within the epidermis. The molecular features of Paget cells remain poorly understood.</p><p><strong>Objectives: </strong>To describe the genomic and transcriptomic landscape of penoscrotal EMPD, identify the driver mutation or core transcription factor through integrative analysis, identify biological markers and provide new insights for the pathogenesis of penoscrotal EMPD.</p><p><strong>Methods: </strong>Whole exome sequencing was performed on penoscrotal EMPD tissues from 37 patients, of whom 28 patients also underwent RNA sequencing, and the findings was validated in an additional 72 patients, encompassing 120 multi-region tumor tissues to identify core transcription factors. The dysregulation was further confirmed by immunohistochemistry.</p><p><strong>Results: </strong>Genomic landscape did not reveal FOXA1 or SPDEF mutations penoscrotal EMPD. Transcriptomic profiling identified the upregulation of lineage-specific transcription factors FOXA1 and SPDEF, along with their targeted genes AGR2 and MUC5AC. Upregulation of FOXA1, SPDEF and AGR2 without gene fusion were consistently replicated in the validation cohort. Further analysis of multiple tissue regions confirmed FOXA1 and SPDEF as driver transcription factors in penoscrotal EMPD. We identify key transcription factors regulating co-expressed modules FOXA1-SPDEF-AGR2, suggesting goblet cells features of penoscrotal EMPD. The immunohistochemistry confirmed the co-expression of FOXA1-AGR2 pattern in Paget cells.</p><p><strong>Conclusions: </strong>Our study provides novel insights into the molecular characteristics of Paget cells, and also highlights the critical role of FOXA1 in Paget cell development in EMPD.</p>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144700776","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":"Healthy skin, Healthy brain.","authors":"Kyeong-No Yoon, Jin Ho Chung","doi":"10.1016/j.jdermsci.2025.06.001","DOIUrl":"https://doi.org/10.1016/j.jdermsci.2025.06.001","url":null,"abstract":"<p><p>Skin aging extends beyond aesthetic concerns and is increasingly recognized as a key contributor to brain aging through neuroendocrine, inflammatory, and neurochemical mechanisms. Traditionally considered as a peripheral barrier, the skin is now recognized as a neuroendocrine organ capable of communicating with the central nervous system (CNS) via hormone secretion, cytokine signaling, and neurotransmitter modulation. Recent literature has begun to formalize the concept of the skin-brain axis as a bidirectional communication system, particularly within the contexts of psychodermatology and neuroimmunology. This review highlights how extrinsic factors such as ultraviolet (UV) radiation and intrinsic aging disrupt skin homeostasis and trigger systemic effects on brain functions. Chronic UV exposure activates the cutaneous hypothalamic-pituitary-adrenal (HPA) axis and increases systemic cortisol levels, impairing hippocampal neurogenesis and cognitive function. UV-induced alterations in neurotransmitters including glutamate, dopamine, and β-endorphins affect learning, memory, and emotion regulation. Importantly, both photoaging and natural skin aging are associated with reduced synthesis of brain-derived neurotrophic factor (BDNF) in the skin, potentially diminishing systemic BDNF availability, and contributing to cognitive decline. Recent studies explored the protective effects of sunscreen and moisturizers in mitigating cutaneous inflammation and reducing neurodegenerative risk. Additionally, topical or dietary interventions, such as plant-derived polyphenols, may restore skin BDNF levels and enhance skin-brain resilience. Collectively, these findings support a paradigm shift: preserving skin health is not only a dermatological goal, but also a promising strategy for mitigating brain aging and promoting cognitive resilience.</p>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144669177","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}
Jin Tang, Peng Chen, Chuchu Huang, Wanjing Wang, Ben Wang, Wei Shi, Yan Tang, Zhili Deng, Yiya Zhang, Ji Li, Dan Jian
{"title":"17β-Estradiol promotes LL37-induced rosacea-like skin inflammation via G protein-coupled estrogen receptor 30.","authors":"Jin Tang, Peng Chen, Chuchu Huang, Wanjing Wang, Ben Wang, Wei Shi, Yan Tang, Zhili Deng, Yiya Zhang, Ji Li, Dan Jian","doi":"10.1016/j.jdermsci.2025.05.005","DOIUrl":"https://doi.org/10.1016/j.jdermsci.2025.05.005","url":null,"abstract":"<p><strong>Background: </strong>Rosacea is a common chronic inflammatory skin condition that predominantly affects females, though its underlying mechanisms remain unclear.</p><p><strong>Objective: </strong>To explore the role of 17β-estradiol (E2) and the G-coupled estrogen receptor 30 (GPR30) in the pathogenesis of rosacea.</p><p><strong>Methods: </strong>We conducted a cross-sectional analysis of UK Biobank data to investigate the association between exogenous hormone use and rosacea risk in females. Additionally, ovariectomized (OVX) LL37-induced rosacea mouse models were utilized to evaluate the effects of ovarian E2 loss and exogenous E2 supplementation. GPR30 expression was measured in rosacea skin lesions, LL37-treated mice, and HaCaT keratinocytes. The impact of GPR30 deletion on rosacea inflammation was assessed using GPR30 knockout mice. Finally, the efficacy of GPR30 inhibition or silencing in reducing inflammation was examined in LL37 or LL37 plus E2 treated mice and HaCaT cells.</p><p><strong>Results: </strong>UK Biobank data revealed significant associations between oral contraceptive use (OR: 1.20; 95 % CI: 1.06, 1.37) and hormone-replacement therapy (OR: 1.31; 95 % CI: 1.18, 1.46) with increased rosacea risk. OVX mice exhibited reduced skin erythema and dermal infiltration, effects reversed by E2 supplementation, which exacerbated rosacea inflammation. GPR30 was overexpressed in rosacea lesions, LL37-treated mice, and HaCaT cells, with TFAP2C potentially mediating this effect. GPR30-deficient mice showed reduced inflammation, while GPR30 inhibition or knockdown significantly improved rosacea-like inflammation in LL37 or LL37 plus E2 treated models.</p><p><strong>Conclusion: </strong>Activation of the E2/GPR30 pathway plays a significant role in rosacea inflammation, and GPR30 inhibition may represent a novel therapeutic strategy for rosacea.</p>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144651667","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":"Councilor’s Meeting/General Assembly of Members at the 49th Annual General Meeting of the Japanese Society for Investigative Dermatology (JSID)","authors":"","doi":"10.1016/j.jdermsci.2025.04.013","DOIUrl":"10.1016/j.jdermsci.2025.04.013","url":null,"abstract":"","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"118 3","pages":"Pages 107-109"},"PeriodicalIF":4.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144221771","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}
Kecen Liu , Huizhong Wang , Jingyang Dang , Jiajia Zhu , Yujie Wen , Zhuojing Chen , Yang Wang , Jingru Sun
{"title":"Overexpression of FOXM1 drives mycosis fungoides progression by regulating the cell cycle","authors":"Kecen Liu , Huizhong Wang , Jingyang Dang , Jiajia Zhu , Yujie Wen , Zhuojing Chen , Yang Wang , Jingru Sun","doi":"10.1016/j.jdermsci.2025.04.010","DOIUrl":"10.1016/j.jdermsci.2025.04.010","url":null,"abstract":"<div><h3>Background</h3><div>Mycosis fungoides (MF), the most prevalent variant of cutaneous T-cell lymphoma (CTCL), is characterized by the clonal proliferation of skin-homing CD4+ T lymphocytes. Forkhead box M1 (FOXM1) plays significant roles in the progression of various solid tumors. Its expression has been reported to diminish following treatment with Neosetophomone B in CTCL cells <em>in vitro</em>. However, the role of FOXM1 in the pathogenesis of MF remains unclear.</div></div><div><h3>Objectives</h3><div>To evaluate the expression pattern and underlying mechanism of FOXM1 in MF.</div></div><div><h3>Methods</h3><div>FOXM1 expression in lesional skin samples was accessed <em>via</em> immunohistochemistry analyses. Inhibition of FOXM1 was performed through lenti-virus shRNA vector mediated gene knockdown and treatment with specific FOXM1 inhibitors (RCM1 and FDI-6). Furthermore, animal experiments were conducted to evaluate the effects of FOXM1 knockdown or treatment with FOXM1 inhibitors on tumor growth <em>in vivo</em>.</div></div><div><h3>Results</h3><div>Overexpression of FOXM1 was observed in MF with a stage-dependent pattern and poor prognosis. Inhibition of FOXM1 <em>via</em> either shRNA or specific inhibitors, significantly impaired MF cell proliferation by inducing cell cycle arrest and apoptosis, while also suppressing tumorigenicity <em>in vitro</em> and <em>in vivo</em>. Transcriptomic analysis revealed that FOXM1 suppression led to the downregulation of genes involved in cell cycle regulation, including CCNB2, CDK1, and E2F1.</div></div><div><h3>Conclusions</h3><div>The overexpression of FOXM1 contributes significantly to the progression of MF primarily by regulating the cell cycle. Furthermore, FOXM1 may serve as a reliable prognostic biomarker and a promising therapeutic target for MF.</div></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"118 3","pages":"Pages 83-91"},"PeriodicalIF":4.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144082933","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}
Nikoletta Nagy , Aliasgari Abdolreza , Margit Pál , Barbara Anna Bokor , Amarilla Barcsay-Veres , Noémi Ágnes Varga , Márta Medvecz , Viktória Szabó , Márta Széll
{"title":"Oculocutaneous albinism type 1B associated with allelic combination of a risk haplotype","authors":"Nikoletta Nagy , Aliasgari Abdolreza , Margit Pál , Barbara Anna Bokor , Amarilla Barcsay-Veres , Noémi Ágnes Varga , Márta Medvecz , Viktória Szabó , Márta Széll","doi":"10.1016/j.jdermsci.2025.04.007","DOIUrl":"10.1016/j.jdermsci.2025.04.007","url":null,"abstract":"","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"118 3","pages":"Pages 101-103"},"PeriodicalIF":4.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144047358","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}