Seoyeon Kyung, Su Jin Lim, Kyung Eun Lee, Youn-Hwa Nho, Bo Eun Lee, Noviana Wulansari, Jongman Yoo, Soon Re Kim, Byung Cheol Park, Dong Keon Yon, Seunghyun Kang
{"title":"Exploring the efficacy evaluation model for androgenic alopecia using hair organoids: Transcending conventional hair research.","authors":"Seoyeon Kyung, Su Jin Lim, Kyung Eun Lee, Youn-Hwa Nho, Bo Eun Lee, Noviana Wulansari, Jongman Yoo, Soon Re Kim, Byung Cheol Park, Dong Keon Yon, Seunghyun Kang","doi":"10.1016/j.jdermsci.2026.04.001","DOIUrl":"https://doi.org/10.1016/j.jdermsci.2026.04.001","url":null,"abstract":"<p><strong>Background: </strong>The development of effective evaluation tools for anti-hair loss therapies is critical due to limitations in existing experimental systems. Hairy 3D skin models and hairy skin explants are not yet commercially viable, necessitating alternative approaches for assessing androgenic alopecia (AGA).</p><p><strong>Objective: </strong>This study aimed to develop a hair-bearing organoid model derived from embryonic stem (ES) cells to evaluate the efficacy of compounds against AGA.</p><p><strong>Methods: </strong>Organoids were cultured from ES cells for approximately 100 days until hair follicle formation began. AGA conditions were induced by treating organoids with dihydrotestosterone (DHT). The recovery effects were assessed using minoxidil (MXD) and soybean embryo extract (SOYACT), a cosmetic ingredient certified for mitigating hair loss. The efficacy of SOYACT was validated through MTT assays, RT-PCR, and ex vivo organ culture. Hair numbers were quantified, and biomarkers related to hair growth, including SOX2, PCNA were analyzed via immunohistochemistry.</p><p><strong>Results: </strong>DHT treatment at 1 µM significantly reduced pigmented hair numbers and decreased expression of hair growth-associated biomarkers. Conversely, co-treatment with 200 μg/mL SOYACT or MXD mitigated these effects, restoring hair follicle numbers and biomarker expression levels. These findings demonstrated the successful induction of AGA conditions in hair-bearing organoids and their response to anti-hair loss ingredients.</p><p><strong>Conclusion: </strong>This study highlights the utility of hair-bearing organoids as a novel experimental model for evaluating AGA therapies. The organoid model addresses limitations in traditional in vitro systems, providing a robust platform for efficacy testing of therapeutic and cosmetic interventions targeting androgenic alopecia.</p>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147825064","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}
Giada Badiale , Christian Felice Cervellera , Giulia Tonnini , Agnese Pellati , Maria Grazia Romanelli , Andrea Corsi , Angela Valentino , Alberto Righi , Marco Gambarotti , Antoine Touzé , Mahtab Samimi , Aurélie Drouin , Mauro Tognon , Chiara Mazziotta , Fernanda Martini , John Charles Rotondo
{"title":"Hsa-microRNA-34a-5p inhibits virus-negative Merkel cell carcinoma cell proliferation and migration by regulating cell cycle- and EMT-related pathways and suppresses tumor spheroid formation","authors":"Giada Badiale , Christian Felice Cervellera , Giulia Tonnini , Agnese Pellati , Maria Grazia Romanelli , Andrea Corsi , Angela Valentino , Alberto Righi , Marco Gambarotti , Antoine Touzé , Mahtab Samimi , Aurélie Drouin , Mauro Tognon , Chiara Mazziotta , Fernanda Martini , John Charles Rotondo","doi":"10.1016/j.jdermsci.2026.02.002","DOIUrl":"10.1016/j.jdermsci.2026.02.002","url":null,"abstract":"<div><h3>Background</h3><div>The molecular mechanisms of Merkel cell polyomavirus (MCPyV)-negative MCC (VN-MCC) initiation remain poorly understood. Although hsa-miR-34a-5p dysregulation has been reported in MCC, its role in VN-MCC is unknown.</div></div><div><h3>Objective</h3><div>We aimed to investigate the functional role of hsa-miR-34a-5p on the malignant phenotype of VN-MCC and elucidate the potential underlying mechanisms.</div></div><div><h3>Methods</h3><div>Hsa-miR-34a-5p expression was investigated in MCC cell lines (n = 5) and tissues (n = 34), and in fibroblast/epithelial cell lines (n = 2). Functional experiments evaluated the effect of hsa-miR-34a-5p on VN-MCC MCC13 phenotype. Gene expression profiling, enrichment analyses and protein–protein interaction network of hsa-miR-34a-5p target genes (n = 84) were conducted in these cells to identify relevant targets/pathways. The impact of hsa-miR-34a-5p on VN-MCC spheroid volume/growth was investigated.</div></div><div><h3>Results</h3><div>Hsa-miR-34a-5p was significantly downregulated in VN-MCC cells and tissues compared to MCPyV-positive counterparts, as well as to fibroblast/epithelial cells. Mechanistically, ectopic hsa-miR-34a-5p expression in MCC13 cells significantly inhibited proliferation, colony formation, and migration abilities, while promoted apoptosis. Hsa-miR-34a-5p silencing in epithelial HaCaT cells increased colony formation and partially enhanced migration. Ectopic hsa-miR-34a-5p expression in MCC13 cells negatively regulated key target genes and pathways involved in both G1/S transition of the cell cycle (<em>CDK4</em>, <em>CDK6</em>, <em>CCNE2</em>) and epithelial-to-mesenchymal transition (<em>MET</em>, <em>NOTCH1</em>, <em>JAG1</em>, along with Snail protein), leading to anti-proliferative and anti-migratory effects. Ectopic hsa-miR-34a-5p expression strongly inhibited MCC13 spheroid formation, whereas miRNA inhibition yielded the opposite effect in HaCaT spheroids from intermediate through later time points.</div></div><div><h3>Conclusion</h3><div>We provide the first functional evidence of the pleiotropic tumor suppressor role of hsa-miR-34a-5p in VN-MCC.</div></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"122 1","pages":"Pages 9-18"},"PeriodicalIF":4.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147446600","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":"Characterization of a unique pathogenic variant in the SERPING1 gene of a patient with hereditary angioedema type I","authors":"Takafumi Hisamoto, Kenta Sentoku, Yutaka Shimomura","doi":"10.1016/j.jdermsci.2026.03.005","DOIUrl":"10.1016/j.jdermsci.2026.03.005","url":null,"abstract":"<div><h3>Background</h3><div>Hereditary angioedema (HAE) is a rare genetic disease characterized by sudden onset of edema involving various organs. Among the three subtypes of the disease, HAE types I and II are caused by heterozygous variants in <em>SERPING1</em> gene encoding C1 inhibitor (C1INH). The pathogenicity of each variant, however, has not fully been revealed.</div></div><div><h3>Objective</h3><div>To assess the mechanism how a <em>SERPING1</em> gene-variant identified in a patient with HAE type I caused the disease.</div></div><div><h3>Methods</h3><div>Genetic analysis was conducted for a Japanese patient with HAE type I. The consequences resulting from the <em>SERPING1</em> gene-variant were analyzed at mRNA levels. Overexpression studies in cultured cells were performed to analyze behavior of the mutant C1INH proteins. Effect of a small interfering RNA specific to the mutant <em>SERPING1</em>-mRNA on expression of wild-type C1INH was also tested.</div></div><div><h3>Results</h3><div>We identified a recurrent heterozygous variant c.820 A>G (p.Ile274Val) in the patient’s <em>SERPING1</em> gene. While we did not find any abnormalities in C1INH with the p.Ile274Val-variant, we found that the variant c.820 A>G caused an aberrant splicing event leading to a frameshift and a premature termination codon. This truncated protein clearly showed a dominant-negative effect against the wild-type C1INH. Finally, we showed that knock-down of the mutant <em>SERPING1</em>-mRNA recovered expression of the wild-type C1INH.</div></div><div><h3>Conclusion</h3><div>A unique pathogenic mechanism for the <em>SERPING1</em> gene-variant c.820 A>G has been disclosed. Furthermore, our findings have raised the possibility that RNA interference could be a new therapeutic tool for the disease.</div></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"122 1","pages":"Pages 1-8"},"PeriodicalIF":4.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147482888","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":"Protective effects of the selective JAK2/3 inhibitor AG490 against ulcer formation following cutaneous ischemia-reperfusion injury.","authors":"Shintaro Saito, Akihiko Uchiyama, Takeshi Araki, Yuta Inoue, Mayu Ohtaka, Keiji Kosaka, Takayuki Shuto, Azusa Ida, Yoko Yokoyama, Sachiko Ogino, Ryoko Torii, Yuki Watanuki, Akiko Sekiguchi, Sei-Ichiro Motegi","doi":"10.1016/j.jdermsci.2026.03.004","DOIUrl":"https://doi.org/10.1016/j.jdermsci.2026.03.004","url":null,"abstract":"<p><strong>Background: </strong>Pressure ulcers are refractory skin ulcers that frequently develop at pressure sites in elderly individuals and those with reduced physical activity, and effective preventive strategies are urgently needed. These ulcers are primarily caused by cutaneous ischemia-reperfusion (I/R) injury, in which inflammation and oxidative stress play important roles. JAK inhibitors are widely used for inflammatory disorders and are also known to possess antioxidant effects. However, their therapeutic potential in cutaneous I/R injury remains unclear.</p><p><strong>Objective: </strong>This study aimed to investigate the role of JAK/STAT signaling and the efficacy of the selective JAK2/3 inhibitor AG490 in preventing ulcer formation in a murine cutaneous I/R model.</p><p><strong>Methods: </strong>In vivo, mice underwent four cycles of 3 h ischemia followed by 1 h reperfusion using magnetic skin compression. AG490 or vehicle was administered intraperitoneally before ischemia. In vitro, 10T1/2 cells were subjected to an oxygen-glucose deprivation/reoxygenation (OGD/R) model.</p><p><strong>Results: </strong>Cutaneous I/R induced phosphorylation of JAK2 and STAT3, which was suppressed by AG490. On day 3, ulcer areas were significantly smaller in AG490-treated mice. AG490 also reduced inflammatory cell infiltration, apoptosis, and hypoxia, while enhancing Nrf2 activity in Keap1-dependent oxidative stress detector-luciferase (OKD-LUC) mice. In vitro, AG490 suppressed OGD/R-induced JAK/STAT activation, attenuated ROS production, prevented cell death, and enhanced the expression of HO-1.</p><p><strong>Conclusion: </strong>We demonstrated the protective effect of AG490 against I/R-induced skin damage through the attenuation of inflammation and oxidative stress, highlighting JAK inhibition as a promising approach for pressure ulcer prevention.</p>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147848043","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":"Comprehensive analysis of tonsillar gene expression and the tonsillar microbiota in patients with palmoplantar pustulosis and pustulotic arthro-osteitis","authors":"Satomi Kobayashi , Hideki Nakagawa , Masato Komai","doi":"10.1016/j.jdermsci.2026.01.006","DOIUrl":"10.1016/j.jdermsci.2026.01.006","url":null,"abstract":"<div><h3>Background</h3><div>Tonsillectomy improves symptoms in patients with palmoplantar pustulosis (PPP) and suppresses disease progression in patients with pustulotic arthro-osteitis (PAO), highlighting the important role of tonsils in the pathogenesis of PPP/PAO.</div></div><div><h3>Objective</h3><div>To identify inflammatory pathways involved in the tonsil tissue of patients with PPP/PAO, and to clarify the characteristics of tonsillar microbiota.</div></div><div><h3>Methods</h3><div>We assessed gene expression in tonsil tissue obtained from PPP/PAO or recurrent tonsillitis (RT)/sleep apnea syndrome (SAS) patients using microarray and quantitative reverse transcription polymerase chain reaction analysis. We also performed a comprehensive analysis of the tonsillar microbiota using next-generation sequencing. Potential associations between tonsillar gene expression and bacterial composition or disease activities were evaluated.</div></div><div><h3>Results</h3><div>Twenty-five tonsils from PPP/PAO patients and 15 tonsils from RT/SAS patients were included. The gene expression of inflammatory cytokines and molecules involved in the Th17, Th2, and Treg pathways was significantly higher in PPP/PAO tonsils than in RT/SAS tonsils. A significant positive correlation between <em>Streptococcus</em> spp. and the expression of Th17 and Th2 pathway genes was revealed both in PPP/PAO and RT/SAS, however, different correlation patterns were observed between these groups for the other genera. PAO disease activity showed a negative correlation with the expression of <em>CCR4</em>, <em>FOXP3</em>, and <em>CXCR3</em> genes.</div></div><div><h3>Conclusion</h3><div>PPP/PAO tonsils exhibit enhanced Th17, Th2, and Treg responses relative to RT/SAS, indicating a complex inflammatory condition. <em>Streptococcus</em> genus may be associated with inflammation, and interaction between microbiota and T cell immunity would be suggested in PPP/PAO tonsils. PAO disease activity inversely correlated with Treg response.</div></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"121 3","pages":"Pages 12-21"},"PeriodicalIF":4.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147367660","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}