Journal of dermatological science最新文献

{"title":"Welcome Message","authors":"","doi":"10.1016/S0923-1811(25)00204-X","DOIUrl":"10.1016/S0923-1811(25)00204-X","url":null,"abstract":"","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"120 2","pages":"Page I"},"PeriodicalIF":4.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145493232","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":"Regulation of melanogenesis via ubiquitin-proteasome system and autophagy by 3,3,5-trimethylcyclohexyl succinate dimethylamide and tranexamic acid","authors":"Jing Wang ,&nbsp;Fanglan Zha ,&nbsp;Simin Lin ,&nbsp;Yun Wei ,&nbsp;Lingling Xuan ,&nbsp;Zhangying Ye ,&nbsp;Hu Huang","doi":"10.1016/j.jdermsci.2025.09.004","DOIUrl":"10.1016/j.jdermsci.2025.09.004","url":null,"abstract":"<div><h3>Background</h3><div>Excessive melanogenesis in skin melanocytes results in hyperpigmentation disorders.</div></div><div><h3>Objective</h3><div>This study investigates the combined effects and mechanisms of 3,3,5-trimethylcyclohexanol succinate dimethylamide (335, a succinic acid derivative) and tranexamic acid (TXA) on melanogenesis.</div></div><div><h3>Methods</h3><div>Skin penetration of 335 was assessed via Raman spectroscopy. Interactions between 335 and TXA were predicted by molecular docking. The anti-melanogenic effect was evaluated by measuring melanin content in human keratinocytes (HaCaT) and mouse melanoma cells (B16). Transcriptome sequencing was performed to identify key pathways by which 335 regulates melanogenesis. Melanosomes were isolated from human melanoma cells (MNT-1) and co-cultured with keratinocytes to validate the specific mechanisms. A 3D melanin skin model was established to evaluate the anti-pigmentation effect of 335 and TXA by analyzing apparent chroma, lightness (L*), and melanin content and distribution.</div></div><div><h3>Results</h3><div>The skin penetration of 335 was enhanced by the addition of TXA, and the two compounds exhibited hydrogen bonding and hydrophobic interactions. The combination of 335 and TXA (1:10) significantly reduced the melanin content in B16 cells compared to individual treatments. Transcriptomics revealed 335 modulates the ubiquitin-proteasome system (UPS) and autophagy. Experimental validation confirmed that 335 and TXA combination inhibited melanin production by promoting ubiquitination degradation of tyrosinase and autophagic degradation of melanosomes. In the 3D skin model, the combination enhanced skin brightness (apparent chroma and L* value) and reduced melanin deposition.</div></div><div><h3>Conclusion</h3><div>The combination of 335 and TXA inhibits melanogenesis by UPS-mediated tyrosinase degradation and autophagy-driven melanosome degradation, offering a promising strategy for hyperpigmentation treatment.</div></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"120 2","pages":"Pages 61-70"},"PeriodicalIF":4.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145228639","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":"Molecular profile of interleukin-17RA blockade by brodalumab in Japanese patients with psoriasis: Results from the ESPRIT study","authors":"James G. Krueger ,&nbsp;Akimichi Morita ,&nbsp;Mona Uchida-Yamada ,&nbsp;Chiharu Tateishi ,&nbsp;Eisaku Ogawa ,&nbsp;Koji Masuda ,&nbsp;Yukie Yamaguchi ,&nbsp;Hong Beom Hur ,&nbsp;Sandra Garcet ,&nbsp;Naomi Shishido-Takahashi ,&nbsp;Yasumasa Kanai","doi":"10.1016/j.jdermsci.2025.09.005","DOIUrl":"10.1016/j.jdermsci.2025.09.005","url":null,"abstract":"<div><h3>Background</h3><div>Brodalumab, an anti-interleukin-17 receptor A antibody, is effective in psoriasis via action on the IL-17 pathway.</div></div><div><h3>Objective</h3><div>This analysis of an exploratory intervention study (ESPRIT) in Japanese patients with moderate to severe plaque psoriasis examined the brodalumab efficacy by clinical changes, and modulation of skin inflammation via changes in skin gene expression and blood sample protein expression.</div></div><div><h3>Methods</h3><div>Primary clinical endpoints were changes in PASI score and PASI score 0 achievement rate at Week 12. For molecular endpoints, biopsies of lesional, non-lesional and healthy volunteer skin were examined by RNA sequencing and RT-PCR. Blood sample serum was analyzed by Olink high-throughput proteomics.</div></div><div><h3>Results</h3><div>Twenty healthy volunteers and 40 patients were enrolled; 37 underwent molecular profiling. Clinical assessment showed that the median baseline PASI score (19.0) significantly decreased to 0.4 at Week 12 (<em>P</em> &lt; 0.0001), with more rapid decline in higher PASI responders. Molecular assessment demonstrated that differential expressed genes in lesional skin were suppressed equivalently to non-lesional skin, establishing the molecular improvement with brodalumab. The transcriptomes of Japanese and Western patients were similar, and top-upregulated genes included IL-17-inducible and cardiovascular disease-related genes, which were suppressed by brodalumab. Serum protein analysis identified 22 proteins elevated by psoriasis. Several inflammatory and cardiovascular risk proteins correlated with psoriasis severity and BMI, but at lower rates than in Western patients.</div></div><div><h3>Conclusions</h3><div>In summary, the transcriptome and the proteome characteristics of Japanese and Western psoriasis patients were similar. Brodalumab rapidly improved skin and serum molecular levels and reduced cardiovascular disease risk factor expression.</div></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"120 2","pages":"Pages 52-60"},"PeriodicalIF":4.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145282235","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":"Deep intronic variant in TYR causes OCA1A in Japanese families through pseudoexon activation","authors":"Ken Okamura ,&nbsp;Toru Saito ,&nbsp;Sachiko Ohori ,&nbsp;Fumio Takada ,&nbsp;Toshifumi Nomura ,&nbsp;Etsuko Oba ,&nbsp;Yutaka Hozumi ,&nbsp;Tamio Suzuki","doi":"10.1016/j.jdermsci.2025.09.003","DOIUrl":"10.1016/j.jdermsci.2025.09.003","url":null,"abstract":"","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"120 2","pages":"Pages 77-79"},"PeriodicalIF":4.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145214844","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":"Novel ATP2C1 genetic variants in a Dutch cohort of patients with Hailey-Hailey disease","authors":"Marie-Eline P.H. Debeuf ,&nbsp;Valerie L.R.M. Verstraeten ,&nbsp;Peter C. van den Akker ,&nbsp;Ruud G.L. Nellen ,&nbsp;Henny H. Lemmink ,&nbsp;Antoni H. Gostyński ,&nbsp;Peter M. Steijlen ,&nbsp;Marieke C. Bolling ,&nbsp;Michel van Geel","doi":"10.1016/j.jdermsci.2025.07.004","DOIUrl":"10.1016/j.jdermsci.2025.07.004","url":null,"abstract":"","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"120 1","pages":"Pages 43-44"},"PeriodicalIF":4.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144857209","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":"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 ,&nbsp;Seungmi Lee ,&nbsp;Kyung-Min Lim","doi":"10.1016/j.jdermsci.2025.07.001","DOIUrl":"10.1016/j.jdermsci.2025.07.001","url":null,"abstract":"<div><h3>Background</h3><div>Ultraviolet (UV) radiation is a major contributor to skin damage<span> and photoaging, primarily through the generation of reactive oxygen species<span> (ROS), which disrupt cellular functions and degrade extracellular matrix. Demand for effective agents to counteract these effects is increasing.</span></span></div></div><div><h3>Objective</h3><div><span>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 </span><span><em>ex vivo</em></span> porcine skin model.</div></div><div><h3>Methods</h3><div>Hs68 cells and <em>ex vivo</em><span> porcine skin were exposed to UVB radiation and subsequently treated with KCZ. We assessed cell viability<span>, collagen production, MMP-1 expression, ROS levels, mitochondrial function, and the activation of the MAPK-AP-1 signaling pathway.</span></span></div></div><div><h3>Results</h3><div><span><span>KCZ alleviated UVB-induced reductions in cell viability, suppressed MMP-1 expression, and prevented </span>collagen degradation in Hs68 cells. In the </span><em>ex vivo</em><span><span> 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 </span>mitochondrial membrane potential<span> and respiratory capacity. KCZ also blocked activation of the UV-stimulated MAPK-AP-1 signaling pathway.</span></span></div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"120 1","pages":"Pages 11-20"},"PeriodicalIF":4.6,"publicationDate":"2025-10-01","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}

{"title":"Risankizumab differentially modulates circulating T-cell populations in psoriasis according to autoreactivity status","authors":"Rebecca Favaro ,&nbsp;Paola Facheris ,&nbsp;Alessandra Formai ,&nbsp;Luigi Gargiulo ,&nbsp;Luciano Ibba ,&nbsp;Giovanni Fiorillo ,&nbsp;Roberta Valeria Latorre ,&nbsp;Jessica Avagliano ,&nbsp;Alessandra Narcisi ,&nbsp;Giampiero Girolomoni ,&nbsp;Santo Raffaele Mercuri ,&nbsp;Antonio Costanzo","doi":"10.1016/j.jdermsci.2025.08.002","DOIUrl":"10.1016/j.jdermsci.2025.08.002","url":null,"abstract":"<div><h3>Background</h3><div>In a recent paper, our group described that the presence of double autoreactivity to both LL37 and ADAMTSL5 autoantigens in psoriatic patients decreased the clinical responses to risankizumab, but how this influences the changes in the peripheral inflammatory T-cell populations is still unknown.</div></div><div><h3>Objective</h3><div>This study aims to evaluate how risankizumab modulates the circulating inflammatory T-cell populations in psoriatic patients and, specifically, in autoreactive subjects.</div></div><div><h3>Methods</h3><div>The presence of LL37- and ADAMTSL5-reactive circulating T-cells was assessed in a cohort of 142 psoriatic patients, and 87 demonstrated autoreactivity at baseline. Patients were treated with risankizumab for 52 weeks, and specific T-cell populations were analyzed at different timepoints.</div></div><div><h3>Results</h3><div>The frequency of Ki67⁺CD4⁺, Ki67⁺CD8⁺ T-cells, CD8⁺IL-17⁺ and CD8⁺IL-22⁺ T-cells showed a positive correlation with baseline PASI and decreased with treatment. Notably, CD8⁺IL-17⁺ T-cells decreased both in single-LL37 and single-ADAMTSL5-reactive subjects, but not in subjects that showed autoreactivity to both autoantigens. LL37 autoreactivity of CD4⁺ and CD8⁺ T-cells decreased with treatment, but not for CD4⁺ in double-reactive subjects. While Treg frequency negatively correlated with baseline PASI and increased within 16 weeks of treatment, significantly decreasing the IL-17⁺CD4⁺/Treg ratio over time, Treg modulation was not evident in double-reactive subjects.</div><div>Interestingly, the subpopulations of CD8⁺MAIT IL-17⁺ and CD3⁺MAIT IL-22⁺ cells, involved also in psoriatic arthritis, decreased in treated subjects following IL-23 inhibition.</div></div><div><h3>Conclusion</h3><div>Rizankizumab efficiently decreases the circulating inflammatory T-cell populations and modulates Tregs’ plasticity in single-LL37- or single-ADAMTSL5-reactive subjects, but not in double-reactive subjects.</div></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"120 1","pages":"Pages 1-10"},"PeriodicalIF":4.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144983922","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":"Granzyme K contributes to acute itch in psoriasis","authors":"Aoi Hiroyasu ,&nbsp;Beni Amatya ,&nbsp;Daisuke Tsuruta ,&nbsp;David J. Granville ,&nbsp;Sho Hiroyasu","doi":"10.1016/j.jdermsci.2025.08.003","DOIUrl":"10.1016/j.jdermsci.2025.08.003","url":null,"abstract":"","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"120 1","pages":"Pages 39-42"},"PeriodicalIF":4.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145093354","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":"Prevalence of FOXA1 and ERBB2 activating mutations in extramammary Paget’s disease: A retrospective multicenter analysis of 99 cases from Japanese and Taiwanese cohorts","authors":"Michiya Omi ,&nbsp;Takuya Takeichi ,&nbsp;Yusuke Okuno ,&nbsp;Chao-Kai Hsu ,&nbsp;Cheng-Lin Wu ,&nbsp;Yi-Han Chang ,&nbsp;Shoichiro Mori ,&nbsp;Yuta Yamashita ,&nbsp;Akira Miyazaki ,&nbsp;Takaya Taira ,&nbsp;Teruki Yanagi ,&nbsp;Keitaro Fukuda ,&nbsp;Tatsuhiro Noda ,&nbsp;Yuika Suzuki ,&nbsp;Yoshinao Muro ,&nbsp;Masashi Akiyama","doi":"10.1016/j.jdermsci.2025.08.001","DOIUrl":"10.1016/j.jdermsci.2025.08.001","url":null,"abstract":"<div><h3>Background</h3><div>Extramammary Paget’s disease (EMPD) occurs in areas where apocrine glands are abundant. EMPD is associated with the known somatic hotspot mutation g.chr14:38064406 G&gt;A in the promoter region of <em>FOXA1</em> and S310F in <em>ERBB2</em>. Whether EMPD patients in non-Japanese populations have <em>FOXA1</em> driver mutations remains undetermined, and the relationship between the clinical characteristics of EMPD patients and the presence of somatic <em>FOXA1</em> driver mutations has yet to be investigated.</div></div><div><h3>Objective</h3><div>To assess the prevalence and clinical significance of the <em>FOXA1</em> and <em>ERBB2</em> hotspot somatic mutations.</div></div><div><h3>Methods</h3><div>Surgical specimens from 99 EMPD patients who underwent surgery from January 2013 to March 2024 were collected from five facilities in Japan and Taiwan. To detect the somatic mutations, amplicon sequencing was performed for <em>FOXA1</em>, and ddPCR was conducted for <em>ERBB2.</em> Immunohistochemical analysis for FOXA1 was performed on 38 samples.</div></div><div><h3>Results</h3><div>The frequencies of the <em>FOXA1</em> (g.chr14:38064406 G&gt;A) mutation and the <em>ERBB2</em> S310F mutation were 8/93 (8.6 %) and 37/93 (40.0 %), respectively, among the non-fresh-frozen specimens. <em>FOXA1</em> somatic hotspot mutation-positive cases were found at all five medical institutions. Regardless of the mutational status of the <em>FOXA1</em> promoter mutation, all examined cases immunohistochemically exhibited strong FOXA1 expression in the Paget cell nuclei. No significant correlation was found between the <em>FOXA1</em> somatic mutation or the <em>ERBB2</em> somatic mutation and any clinical parameter.</div></div><div><h3>Conclusion</h3><div>The <em>FOXA1</em> somatic hotspot mutation was found in both Japanese and Taiwanese EMPD patients. We cannot rule out the possibility that <em>FOXA1</em> might be a potential target for EMPD therapies in Japan and Taiwan.</div></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"120 1","pages":"Pages 32-38"},"PeriodicalIF":4.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144983949","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":"NELL2-Robo3 signaling promotes keratinocyte proliferation and inhibits keratinocyte apoptosis in condyloma acuminatum through autocrine and paracrine mechanisms","authors":"Xiaohang Xie ,&nbsp;Charat Rin ,&nbsp;Yinyi Feng ,&nbsp;Yichuan Li ,&nbsp;Deqiao Qin ,&nbsp;Yuchun Cao ,&nbsp;Xiaochao Zhang ,&nbsp;Yong Zhang","doi":"10.1016/j.jdermsci.2025.09.001","DOIUrl":"10.1016/j.jdermsci.2025.09.001","url":null,"abstract":"<div><h3>Background</h3><div>Condyloma acuminatum (CA) is caused by low-risk HPV infection and characterized by benign epithelial proliferation. NELL2, as a secreted glycoprotein, is strongly linked to dermatosis, but its function in CA remains unknown.</div></div><div><h3>Objective</h3><div>To investigate the expression, function and mechanism of NELL2 in CA.</div></div><div><h3>Methods</h3><div>The expression of NELL2 was detected in CA and normal skin tissues. HaCaT cells stably expressing HPV11-E7 (HPV11-E7-HaCaT) and control group (Vector-HaCaT) were constructed to explore the relationship between HPV infection and NELL2 expression. We downregulated <em>NELL2</em> expression in HPV11-E7-HaCaT cells and added recombinant human NELL2 to medium of Vector-HaCaT and HPV11-E7-HaCaT cells to examine the effects of NELL2 on cell proliferation and apoptosis. The activation of MAPK pathway and the role of Robo3 were evaluated to explore the mechanisms underlying these effects.</div></div><div><h3>Results</h3><div>NELL2 was overexpressed in CA, and increased NELL2 expression was positively associated with high HPV copy number and high Ki67 expression. HPV11-E7 induced the expression of NELL2 in HaCaT cells. In addition, NELL2 promoted proliferation and inhibited apoptosis in HPV11-E7-HaCaT and Vector-HaCaT cells through autocrine and paracrine mechanisms. NELL2 treatment activated the ERK pathway, and ERK inhibition by U0126 confirmed that ERK pathway was essential for the function of NELL2 in CA. Moreover, Robo3 acts as the NELL2 receptor in CA.</div></div><div><h3>Conclusion</h3><div>NELL2 binds Robo3 to promote keratinocyte proliferation and inhibit keratinocyte apoptosis in CA through autocrine and paracrine mechanisms. NELL2-Robo3 signaling may be regarded as a potential target for CA treatment in the future.</div></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"120 1","pages":"Pages 21-31"},"PeriodicalIF":4.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145152463","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}