Experimental Dermatology最新文献

{"title":"JAK1/2 Inhibitors Alleviate the Damage of Intercellular Adhesion by Reducing Endoplasmic Reticulum Stress-Induced Apoptosis in Pemphigus Vulgaris","authors":"Xi Chen,&nbsp;Mei-Nian Xu,&nbsp;Zheng-Quan Wu,&nbsp;Rong Huang,&nbsp;Hong-Yan Lu,&nbsp;Xiaoming Peng,&nbsp;Kang Zeng,&nbsp;Chang-Xing Li","doi":"10.1111/exd.70121","DOIUrl":"https://doi.org/10.1111/exd.70121","url":null,"abstract":"<div>\u0000 \u0000 <p>Pemphigus vulgaris (PV), a severe autoimmune disease with high morbidity and mortality, necessitates innovative therapies to improve outcomes while minimising the adverse effects of conventional immunosuppressants. Immunohistochemical analysis revealed elevated phosphorylated Janus kinase (p-JAK)1 and p-JAK2 expression in PV lesions, complemented by transcriptome data showing JAK/STAT pathway dysregulation. Using a PV acantholysis model, we demonstrated that Ruxolitinib, a JAK1/2 inhibitor, significantly reduced keratinocyte apoptosis, enhanced cell adhesion, and alleviated endoplasmic reticulum (ER) stress. Additionally, Ruxolitinib mitigated tunicamycin-induced ER stress and apoptosis in HaCaT cells. These findings establish a crucial role for JAK1/2 in PV pathogenesis, demonstrating that their inhibition alleviates ER stress, reduces apoptosis, and improves cell adhesion. Our results provide a theoretical foundation for the clinical application of JAK inhibitors in PV treatment.</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 5","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144091892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nemolizumab Improves Pruritus in Patients With Intrinsic Atopic Dermatitis Lacking Atopic Predisposition: A Single-Centre Pilot Retrospective Cohort Study","authors":"Emi Sato,&nbsp;Hisatomi Arima,&nbsp;Keita Tsutsui,&nbsp;Hiroki Shimizu,&nbsp;Kotaro Ito,&nbsp;Mayuko Iwata,&nbsp;Shinichi Imafuku","doi":"10.1111/exd.70120","DOIUrl":"https://doi.org/10.1111/exd.70120","url":null,"abstract":"<div>\u0000 \u0000 <p>Interleukin (IL)-31 is a key therapeutic target for severe pruritus in atopic dermatitis (AD). Nemolizumab, an IL-31 receptor A antibody, has been available in Japan since 2022 for treating AD-related pruritus. This retrospective study aimed to identify the characteristics of patients with AD for whom nemolizumab is appropriate and most effective, focusing on its efficacy in alleviating pruritus. We reviewed the clinical data of patients with AD who received 60 mg of nemolizumab between 2022 and 2024 at Fukuoka University Hospital. Patients who achieved a ≥ 4-point improvement on the Peak Pruritus Numerical Rating Scale (PP-NRS4) within 16 weeks were classified as responders. Background characteristics, including atopic predisposition and total serum immunoglobulin E (IgE) levels, were compared between responders and non-responders. Multivariate analysis was performed to identify treatment response predictors. Sixteen (64%) of the 25 patients treated with nemolizumab achieved PP-NRS4 within 16 weeks. Of the 25 patients, 14 had extrinsic AD with an atopic predisposition, although only 5 (36%) achieved PP-NRS4. All 11 patients with intrinsic AD achieved PP-NRS4 (<i>p</i> = 0.001). The median total serum IgE level was significantly lower in responders (74.5 IU/mL) than in non-responders (691.5 IU/mL, <i>p</i> = 0.0034). Multivariate analysis revealed that higher baseline IgE levels were associated with poorer PP-NRS4 outcomes (standardised <i>β</i> = −0.63033, <i>p</i> = 0.0154). Serum total IgE levels, indicative of an atopic predisposition, are critical predictors of nemolizumab efficacy in alleviating pruritus. These findings underscore the importance of patient selection based on IgE levels for optimising nemolizumab therapy in AD.</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 5","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143950151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Memory T-Cell Phenotype in Cutaneous T-Cell Lymphoma Is Modified by Germline Gene Gametocyte Specific Factor 1","authors":"Amelia Martínez Villarreal,&nbsp;Jennifer Gantchev,&nbsp;Pingxing Xie,&nbsp;Philippe Lefrançois,&nbsp;Brandon Ramchatesingh,&nbsp;Ivan V. Litvinov","doi":"10.1111/exd.70123","DOIUrl":"https://doi.org/10.1111/exd.70123","url":null,"abstract":"<p>Cutaneous T-cell lymphoma (CTCL) is a heterogeneous group of lymphoproliferative disorders characterised by skin infiltration by malignant memory T cells. While most patients will present with an indolent disease, others will follow a highly aggressive clinical course. Currently, defining disease prognosis remains challenging. Ectopic expression of gametocyte-specific factor 1 (GTSF1) has emerged as a potential prognostic biomarker. However, its contribution to CTCL carcinogenesis remains unknown. Here, we report that GTSF1 contributes to carcinogenesis by partially modifying the memory/effector phenotype of the malignant T cells. GTSF1 knockdown in CTCL cells led to T-cell activation and production of IFNγ and TNFα. Advanced stages of the disease are associated with decreased production of these cytokines. Notably, we show that patients classified with high expression of GTSF1 are associated with a worse disease prognosis. Taken together, our findings indicate that GTSF1 expression in CTCL cells allows them to acquire memory T-cell phenotype. Malignant memory T cells have a decreased production of immune-responsive cytokines, leading to a diminished immune response and disease progression. GTSF1 is an important candidate as a prognostic biomarker. Furthermore, understanding the specific function of GTSF1 might help develop novel targeted treatment options for CTCL patients.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 5","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70123","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143949773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extension of Secukinumab and Ixekizumab Dose for Moderate-To-Severe Psoriasis in Low Disease Activity Intervals","authors":"Caiyu Wang,&nbsp;Yanhua Liu,&nbsp;Yang Yang,&nbsp;Jiao Ning,&nbsp;Xiaoyi Xing,&nbsp;Ping Jian,&nbsp;Ziyuan Wang,&nbsp;Guangquan Xu,&nbsp;Zhongrui Xu,&nbsp;Jian Zhou,&nbsp;Xiaoming Liu,&nbsp;Chen Yu,&nbsp;Gang Wang","doi":"10.1111/exd.70122","DOIUrl":"https://doi.org/10.1111/exd.70122","url":null,"abstract":"<div>\u0000 \u0000 <p>Biological agents targeting IL-17A, such as secukinumab and ixekizumab, are highly effective in treating psoriasis, often achieving low disease activity or remission. However, frequent injections, side effects and high costs pose significant challenges. Extending dosing intervals for patients with stable disease and partial response may address these issues while maintaining efficacy, yet standardised dose reduction guidelines remain absent. This study aimed to evaluate the efficacy and safety of reduced dosing regimens of secukinumab and ixekizumab during the maintenance phase of psoriasis treatment. From 2020 to 2023, patients completing induction and maintenance phases with prescribed regimens, achieving a PASI (Psoriasis Area and Severity Index) score below 1 and PASI90 or PASI100 response, underwent clinician evaluations for extended dosing intervals. Secukinumab dosing was adjusted from 300 mg (or 150 mg) Q4W to Q8W, and ixekizumab from 80 mg Q4W to Q8W. Patients were monitored over 36 weeks, with data collected throughout the observation period to assess feasibility and safety. A total of 64 patients with moderate-to-severe plaque psoriasis were enrolled. Following extended dosing intervals, 75.4% maintained a PASI90 response at 12 weeks, with 67.7% sustaining it at 36 weeks. Similarly, 69.8% achieved PASI100 at 12 weeks, and 61.2% maintained this response at 36 weeks. These findings demonstrate that dose reduction strategies for secukinumab and ixekizumab in moderate-to-severe psoriasis can reduce treatment burden while maintaining high therapeutic efficacy, offering valuable insights to guide clinical guidelines and address current knowledge gaps.</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 5","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143949774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characteristics of the MicroRNA-Processing Enzymes in Melanocytic Skin Lesions: Dicer and DGCR8 Are Potential Biomarkers for Primary Cutaneous Melanomas","authors":"Fabiola Schafer,&nbsp;Enrique Bellolio,&nbsp;Tatiana Sepúlveda,&nbsp;Mirta Espinoza,&nbsp;Juan-José Orellana,&nbsp;Isabel Bellolio,&nbsp;Miguel Angel Villaseca,&nbsp;Rodrigo Miranda","doi":"10.1111/exd.70110","DOIUrl":"https://doi.org/10.1111/exd.70110","url":null,"abstract":"<div>\u0000 \u0000 <p>Primary cutaneous melanoma (PCM) is an aggressive skin cancer. Its physiopathology is a challenge with heterogeneous pathways involved. As such, microRNA-processing enzymes have been shown to be deregulated in cancer. The aim of this study was to characterise the expression profile of Dicer, Drosha, DGCR8 and PACT enzymes in melanocytic skin lesions. A total of 126 formalin-fixed paraffin-embedded samples, including 42 benign nevi, 42 dysplastic nevi and 42 PCM, were studied using tissue microarray and immunohistochemistry, which was graded based on the percentage of immunoreactive tumour cells (%IRC). Increased Dicer immunoexpression was found in PCM compared to benign nevi (<i>p</i> = 0.044) and increased DGCR8 immunoexpression was found in PCM compared to dysplastic and benign nevi (<i>p</i> = 0.000). For Drosha and PACT, only dysplastic nevi showed an increased expression (<i>p</i> = 0.011). A ROC curve cut-off of 80% IRC was used. For Dicer, the specificity for non-malignant cutaneous lesions (NMCL) was 98.8%, and sensitivity for PCM was 31.0%. The negative predictive value (NPV) was 98.6% and positive predictive value (PPV) was 34.7%. For DGCR8, the specificity for NMCL was 100%, and sensitivity for PCM was 31.0%. The NPV was 98.6% and PPV was 100%. All cases with positive Dicer and DGCR8 immunoexpression were melanomas. Dicer was increased in nodular histologic subtype (<i>p</i> = 0.011) and DGCR8 was higher in males (<i>p</i> = 0.005). Both Dicer and DGCR8 were increased in ulcerated PCM (<i>p</i> &lt; 0.05). Dicer and DGCR8 play an important role in melanoma development with a potential use as diagnostic tools to differentiate PCM from other melanocytic skin lesions.</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 5","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143925782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Blocking of IL-4/IL-13 Signalling With Dupilumab Results in Restoration of Serum and Cutaneous Abnormalities in Netherton Syndrome","authors":"Stefan Blunder,&nbsp;Natascha Hermann-Kleiter,&nbsp;Rita Mahmuti,&nbsp;Martin Hermann,&nbsp;Daniela Ortner,&nbsp;Daniela Reider,&nbsp;Verena Moosbrugger-Martinz,&nbsp;Barbara Del Frari,&nbsp;Patrizia Stoitzner,&nbsp;Sandrine Dubrac,&nbsp;Matthias Schmuth,&nbsp;Robert Gruber","doi":"10.1111/exd.70113","DOIUrl":"https://doi.org/10.1111/exd.70113","url":null,"abstract":"<div>\u0000 \u0000 <p>Netherton syndrome (NS) is a rare ichthyosis caused by <i>SPINK5-</i>null mutations, resulting in erythroderma, ichthyosis linearis circumflexa, and atopic diathesis. Elevated serum IgE levels and activation of the KLK5-PAR2-TSLP axis suggest involvement of Th2-skewed immunity in NS. In this pilot study, we investigated the effects of IL-4/IL-13 blocking with dupilumab on NS features. At baseline, Th2-chemokines CCL11, CCL17, CCL18, CCL26, and serum IgE were more elevated in atopic dermatitis (AD) than in NS vs. controls (ctrls). AD exhibited elevated serum levels of CCL27, LDH, and eosinophils, while NS showed higher levels of IL-9 and IL-18. Epidermal aberrations, including acanthosis and SC-detachment, were present in NS versus ctrls. The number of CD3+ T cells increased, while CD1a + Langerhans cell numbers decreased in NS skin. Amounts of KLK5 were reduced, and the distribution of KLK7 was abnormal in NS epidermis as compared to ctrls. Reduced amounts of FLG, CDSN, and DSG1 highlight impaired keratinocyte late differentiation in NS. Amounts of epidermal TSLP were diminished. Upon dupilumab treatment, clinical improvement in NS began as early as week 8 and continued up to 30 months, with no serious side effects reported. Serum levels of IgE, CCL17, CCL26, IFN-γ and IL-18 decreased upon IL-4/IL-13 blockade, and alterations of cutaneous immune cells improved in NS. Furthermore, the epidermal protease inhibitor WFDC12 expression increased after dupilumab treatment, concurring with improved and partially normalised epidermal structure, including increased FLG, CDSN, and DSG1. These data highlight Th2-skewed immunity in NS and emphasise the amelioration of NS features through dupilumab treatment.</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 5","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143925783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Generation of a Novel Inducible and Dermal Papilla-Specific Wif1-CreER Knock-In Mouse Line for Hair Follicle Research","authors":"Rina Su,&nbsp;Guangqian Shen,&nbsp;Xin Xiao,&nbsp;Yinghui Zheng,&nbsp;Fang Liu,&nbsp;Daoming Chen","doi":"10.1111/exd.70109","DOIUrl":"https://doi.org/10.1111/exd.70109","url":null,"abstract":"<div>\u0000 \u0000 <p>Dermal papilla (DP) cells are essential niche cells that regulate hair follicle development, cycling and regeneration. Despite the establishment of several DP cell mouse lines in prior research, these tools are limited by incomplete specificity and spatiotemporal control. The Wnt inhibitory factor 1 (Wif1) has been identified as a DP signature gene. To address the need for precise labelling and manipulation of DP cells, we developed a novel genetic tool—<i>Wif1-CreER</i> knock-in mice. Using CRISPR/Cas9-mediated homologous recombination, the CreERT2 sequences were inserted into the endogenous <i>Wif1</i> locus, under the control of the native promoter. PCR and sequencing analysis confirmed the accurate insertion of the CreERT2 sequence. Crossing <i>Wif1-CreER</i> mice with a reporter line demonstrated efficient and specific Cre recombinase activity in DP cells during anagen, catagen and telogen upon tamoxifen treatment across hair types. Importantly, DP-restricted labelling was confirmed by immunofluorescence and colocalised with Crabp1 and alkaline phosphatase (AP)-staining activity, exhibiting minimal to negligible expression in other tissues. This innovative mouse model overcomes the limitations of current tools and provides a valuable resource for advancing our understanding of hair biology and developing targeted therapies for hair-related disorders, offering unprecedented precision in the manipulation of dermal papilla cells.</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 5","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143914046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The TRPM5 Antagonist Triphenylphosphine Oxide Increases Sebaceous Lipogenesis and Modulates Immune Phenotype of Human Sebocytes in a TRPM5-Independent Manner","authors":"Dorottya Ádám,&nbsp;József Arany,&nbsp;Kinga Fanni Tóth,&nbsp;Orsolya Pető,&nbsp;Tamara Nyitrai,&nbsp;Balázs István Tóth,&nbsp;Szilárd Póliska,&nbsp;Christos C. Zouboulis,&nbsp;Attila Oláh","doi":"10.1111/exd.70115","DOIUrl":"https://doi.org/10.1111/exd.70115","url":null,"abstract":"<p>Transient receptor potential melastatin 5 (TRPM5) ion channel is expressed in human hair follicles, where its spontaneous activity contributes to the maintenance of the growing, anagen phase of the hair cycle. Because adjacent sebaceous glands also exhibited TRPM5 immunopositivity, topically applied TRPM5 modulators administered to influence hair growth may also affect sebaceous glands. Hence, we aimed to assess expression of TRPM5 as well as effects of TRPM5 modulators [activators: 2,5-dimethylpyrazine, 2-heptanone; antagonist: triphenylphosphine oxide (TPPO)] on human SZ95 sebocytes, i.e., on the best available in vitro model to study human sebaceous glands. First, using complementary methods [RNA-Seq, RT-qPCR, western blot, siRNA-mediated gene silencing and fluorescent Na⁺- (SBFI AM) and Ca²⁺-measurements (Fura-2 AM)], we found that TRPM5 is not expressed in human sebocytes in a functionally active form. Importantly, while non-cytotoxic (MTT-assay) concentrations of the activators were ineffective, TPPO promoted sebaceous lipogenesis (Nile Red labelling). This effect was TRPM5-independent and was found to be mediated in an Akt- and epidermal growth factor receptor (EGFR)-dependent manner, most likely via the Akt-induced up-regulation of diacylglycerol O-acyltransferase (DGAT)-2. Moreover, TPPO up-regulated interleukin (IL)-6 in an EGFR- and p38α MAPK-dependent manner (RT-qPCR), whereas it decreased the release of IL-8 (ELISA), and down-regulated additional pro-inflammatory cytokines [chemokine (C-X-C motif) ligand [CXCL]-1, CXCL2, CXCL6, colony-stimulating factor 2, IL-32; RNA-Seq]. Collectively, specific TRPM5 modulators are unlikely to exert direct sebaceous gland-related side effects, while safe TPPO analogues may induce beneficial moderate lipogenic and anti-inflammatory effects in dry skin dermatoses.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 5","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70115","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143914527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Systematic Review of Mendelian Pyoderma Gangrenosum: Clinical and Genetic Characteristics in 120 Published Patients","authors":"Leyla Norouzi-Barough,&nbsp;Sajjad Biglari,&nbsp;Roya Sherkat,&nbsp;Johann E. Gudjonsson,&nbsp;Hakon Hakonarson,&nbsp;Hassan Vahidnezhad","doi":"10.1111/exd.70112","DOIUrl":"https://doi.org/10.1111/exd.70112","url":null,"abstract":"<p>Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis characterised by sterile, recurrent ulcers with a predominantly multifactorial aetiology. However, in a small subset of patients carrying highly penetrant Mendelian mutations in single genes, PG presents as a part of a genetic syndrome. This study aimed to systematically review Mendelian susceptibilities to PG and summarise the clinical and genetic characteristics of patients. Search criteria encompassed case reports, case series and other original articles focusing on causal sequence variants associated with PG pathogenicity. We screened 1577 articles and selected 79 studies, encompassing 120 PG patients and 19 distinct genes, for quantitative analysis. The most prevalent mode of inheritance was autosomal dominant, and the mean age of onset was 23.39 ± 19.76 years. Seventeen of 19 genes are categorised under the Inborn Errors of Immunity (IEI) compiled by the International Union of Immunological Societies (IUIS). According to this, the most reported genes (37%) belong to ‘Autoinflammatory Disorders.’ All 19 genes were linked to cutaneous ulcers, with <i>PSTPIP1</i> and <i>MEFV</i> being the only genes associated with all three lesion types (cutaneous, anogenital, mucosal). <i>PSTPIP1</i> was the most frequently reported PG-related gene, followed by <i>MEFV, ITGB2, NOD2, NFKB1, RAG1, JAK2,</i> and <i>NCSTN</i>. <i>Pseudomonas aeruginosa</i> was the most frequently identified infectious agent in PG skin lesions. This study identifies at least 19 genes associated with PG susceptibility, emphasising the crucial role of genetic factors in disease pathogenesis. Gaining insight into the genetic basis and molecular mechanisms involved may facilitate the development of more targeted therapeutic strategies for PG.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 5","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70112","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143914529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of Mitochondrial Dysfunction in UV-Induced Photoaging and Skin Cancers","authors":"Xinghua Yuan,&nbsp;Huixin Li,&nbsp;Ji Su Lee,&nbsp;Dong Hun Lee","doi":"10.1111/exd.70114","DOIUrl":"https://doi.org/10.1111/exd.70114","url":null,"abstract":"<p>Ultraviolet radiation (UVR) is the most detrimental external factor that induces acute photodamage, photoaging and skin cancers, with complex underlying molecular mechanisms initiated mainly by increased DNA damage and reactive oxygen species (ROS) generation. Mitochondria are the main organelles in skin cells that produce ROS and energy and regulate various physiological and pathological signalling pathways. Continuous UVR on human skin can induce mitochondrial DNA mutations and excessive ROS production, creating feedback between each other and subsequently causing a reduction in mitochondrial membrane potential (MMP) and respiratory capacity. Deficiencies in mitochondrial function can induce apoptosis, mitophagy and senescence, resulting in UVR-induced skin photodamage and photoaging. Mitochondrial biogenesis and metabolic pathways play critical roles in the progression of skin cancers, particularly melanoma, which is the most malignant and infrequent type of cancer. In this review, we describe the recent advances in determining the intimate relationship between mitochondrial function and UVR-induced skin damage, suggesting potential molecular candidates and novel chemical/natural components to protect the skin from photoaging and skin cancers via mitochondrial targeting mechanisms.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 5","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70114","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143896974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}