Experimental Dermatology最新文献

{"title":"The Impacts of Seasonal Factors on Psoriasis","authors":"Jundan Yang,&nbsp;Guohao Li,&nbsp;Lixin Yue,&nbsp;Erle Dang,&nbsp;Pei Qiao","doi":"10.1111/exd.70078","DOIUrl":"https://doi.org/10.1111/exd.70078","url":null,"abstract":"<p>Psoriasis is a chronic inflammatory skin condition driven by immune system dysfunction, genetic predisposition and environmental factors. Patients with psoriasis experience a well-known clinical phenomenon of ‘winter severity and summer relief’, in which seasonal environmental factors play critical roles in the onset and progression of psoriasis. These factors include temperature, humidity, infection, light exposure and psychological stress. Seasonal changes in temperature and humidity can compromise skin barrier function and exacerbate inflammatory responses, thereby worsening psoriasis symptoms. Notably, during the winter, decreased light exposure leads to reduced vitamin D (VD) levels, reaching their lowest levels from late winter to early spring. This decline in VD levels is associated with increased disease activity, greater disease severity and more frequent flare-ups in patients with psoriasis. During the winter, influenza and <i>Streptococcus pneumoniae</i> infections are more prevalent, which can further exacerbate psoriasis symptoms. Moreover, the environmental conditions in winter can trigger or intensify feelings of depression, which may adversely affect psoriasis through the brain–skin axis. In this comprehensive review, we thoroughly examined the influence of seasonal environmental factors on the incidence, recurrence and severity of psoriasis. By clarifying these complex relationships, we aimed to support the future development of more personalised and effective treatment and management strategies for patients with psoriasis.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 3","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70078","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143645689","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":"Altered Sensory and Stress Responses in Atopic Dermatitis: Effects of Acute Stress on Lesional and Non-Lesional Skin","authors":"Macarena Tejos-Bravo,&nbsp;Dixon Cid,&nbsp;Fernanda Espinoza,&nbsp;Felipe Rojas-Thomas,&nbsp;Gustavo Torres,&nbsp;María-Laura Cossio,&nbsp;Arturo Borzutzky,&nbsp;Margarita Calvo","doi":"10.1111/exd.70083","DOIUrl":"https://doi.org/10.1111/exd.70083","url":null,"abstract":"<div>\u0000 \u0000 <p>Itch and pain are both mediated by small sensory fibres. Atopic dermatitis (AD) patients usually report stress-induced flares, but the impact of stress on sensory fibres in lesional and non-lesional skin remains inconclusive. This observational study assessed the effect of acute stress on sensory profiles in subjects with AD (<i>n</i> = 18) and healthy controls (HC, <i>n</i> = 21). Participants completed clinical and psychological questionnaires, and quantitative sensory testing was performed on lesional and non-lesional skin in AD and healthy skin in HC. Assessments were done before and after the Montreal Imaging Stress Task, an acute stress protocol. Stress responses were evaluated by anxiety ratings, heart rate (HR) and salivary cortisol (CORT). Cortisol binding globulin (CBG) was quantified as an indirect measure for circulating CORT. AD participants reported higher anxiety, depression and stress perception than HC. HR was similar between groups, but AD participants showed a blunted CORT response post-stress and lower CBG levels, suggesting altered stress regulation. Acute stress reduced cold sensitivity in HC and non-lesional AD skin but had no effect on lesions. These findings indicate that the effects of stress on small fibres depend on the condition of the skin and emphasise the sensory alterations experienced by AD patients.</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 3","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143632904","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":"Comparative Analysis of the Skin Microbiota of Rosacea, Steroid-Induced Rosacea and Perioral Dermatitis","authors":"Akiko Mochizuki,&nbsp;Toshifumi Osaka,&nbsp;Yasuko Fukuya,&nbsp;Naoko Yanagisawa,&nbsp;Naoko Ishiguro","doi":"10.1111/exd.70084","DOIUrl":"https://doi.org/10.1111/exd.70084","url":null,"abstract":"<div>\u0000 \u0000 <p>Rosacea, steroid-induced rosacea, also known as corticosteroid-induced rosacea-like dermatitis, and perioral dermatitis cause erythema, red papules, and pustules on the face. Tetracycline therapy is often effective for these skin diseases, suggesting that skin bacteria may be involved in these pathogeneses. To explore the etiologic significance of skin bacteria, we examined the microbiota of rosacea, steroid-induced rosacea, and perioral dermatitis, as well as healthy participants (<i>n</i> = 50), using swab specimens that were obtained by rubbing the skin surface and vellus hair specimens that were collected from the perioral lesions. Skin microbiota was determined with short-amplicon sequence analysis for 16S rRNA gene (V1–V2 regions). Comparative analysis of the microbiota showed that the bacterial composition in perioral dermatitis cases was clearly different from that of rosacea cases and healthy participants but similar to that of some cases of steroid-induced rosacea. The uncultured <i>Neisseriales</i> bacterium was prevalent in the skin microbiota of some cases of steroid-induced rosacea and perioral dermatitis cases. After antibiotic therapy to steroid-induced rosacea and perioral dermatitis cases, the uncultured <i>Neisseriales</i> bacterium disappeared with improvement of the skin rash. These results indicate that the skin bacteria involving unculturable bacterium in the skin microbiota had a significant impact on steroid-induced rosacea and perioral dermatitis pathogeneses, and that microbiota-targeted treatment may be effective for steroid-induced rosacea and perioral dermatitis.</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 3","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143632903","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":"Altered Arginine Metabolism Affects Proliferation and Radiosensitivity of Keloids","authors":"Wei Li,&nbsp;Xiaoqian Li,&nbsp;Yange Zhang,&nbsp;Baochen Zhu,&nbsp;Xuewen Xu,&nbsp;Haitao Xiao,&nbsp;Shuyu Zhang","doi":"10.1111/exd.70077","DOIUrl":"https://doi.org/10.1111/exd.70077","url":null,"abstract":"<div>\u0000 \u0000 <p>Keloid is characterised by the reprogramming of cellular metabolism, wherein keloid cells adapt their metabolic pathways to meet the demands for energy and biosynthetic precursors. Investigating the intricate relationship between cellular metabolism and the biological behaviour of keloid holds the potential to yield novel therapeutic strategies for keloid. To elucidate the molecular alterations and potential underlying regulatory mechanisms in keloids, we created comprehensive metabolic profiling at the pathway level by analysing metabolomic, transcriptomic and single-cell RNA-sequencing data from keloids and adjacent skin. Viability assay and clonogenic assay were performed to validate the function of the metabolic pathway(s) in primary keloid fibroblast cells. Integrated analysis revealed an upregulation of arginine and proline metabolism in keloids. According to single-cell RNA-seq data, elevated expression of genes related to arginine and proline metabolism, such as <i>P4HA3, P4HA2, P4HA1, PYCR1, OAT</i> and <i>ASS1</i>, was predominately highly expressed in fibroblast-2. Fibroblast-2 displayed more obvious phenotypes of mesenchymal fibroblast. Critical genes from integrated analysis including <i>P4HA3, P4HA2, P4HA1, PYCR1</i> and <i>AZIN2</i>, and metabolites including fumaric acid and 2-oxo-5-amino-pentanoic acid showed prognostic relevance with disease-free survival of keloid. Additionally, an In vitro study showed that arginine deprivation therapy (ADT) inhibited and radiosensitised the proliferation of keloid-derived fibroblasts. In conclusion, our thorough multiomics study deepens our understanding of the link between arginine and proline metabolism and keloid proliferation and radiosensitivity. Elevated activity of arginine and proline metabolism in mesenchymal fibroblasts may be a potential therapeutic pathway for keloid.</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 3","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143632902","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":"Multimodal Second-Harmonic-Generation, Two-Photon Excitation Fluorescence, and Brillouin Microscopy for Visualising Dermal Mechanical Properties in Ex Vivo Human Skin","authors":"Eiji Hase,&nbsp;Naoya Okubo,&nbsp;Yuki Ogura,&nbsp;Takeo Minamikawa,&nbsp;Takeshi Yasui","doi":"10.1111/exd.70081","DOIUrl":"https://doi.org/10.1111/exd.70081","url":null,"abstract":"&lt;p&gt;Multiphoton microscopy, particularly second-harmonic-generation (SHG) and two-photon excitation fluorescence (TPEF) microscopy, has been a powerful tool for observing the structural and compositional remodelling of the dermal extracellular matrix (ECM) as it selectively visualises collagen and elastic fibres [&lt;span&gt;1&lt;/span&gt;]. Therefore, combining data from multiphoton microscopy with mechanical tests offers valuable insights into how ECM remodelling resulting from disease or ageing affects the mechanical properties of the dermis. Although various mechanical tests such as rheology [&lt;span&gt;2&lt;/span&gt;], atomic force microscopy-based microindentation [&lt;span&gt;3&lt;/span&gt;], and ultrasound [&lt;span&gt;4&lt;/span&gt;] are commonly used to assess mechanical properties, their spatial resolution or field of view often do not align with that of multiphoton microscopy, limiting the integration of findings related to ECM remodelling and mechanics.&lt;/p&gt;&lt;p&gt;In this study, we used Brillouin microscopy [&lt;span&gt;5&lt;/span&gt;], which provides information about the viscoelastic properties of biological tissues with sub-micrometre, three-dimensional spatial resolution in a label-free, non-contact manner, and combined it with multiphoton microscopy as an alternative to traditional mechanical tests.&lt;/p&gt;&lt;p&gt;We integrated multiphoton microscopy and Brillouin microscopy into a single microscope, allowing switching between them (Figure S1). A femtosecond optical parametric oscillator (central wavelength = 800 nm, pulse duration ≈ 110 fs, repetition rate = 80 MHz) and the laser scanning system were used to capture SHG and TPEF images, visualising the distribution of collagen and elastic fibres, respectively. For Brillouin microscopy, a single-mode diode-pumped solid-state laser (wavelength = 532 nm) was used, and the Brillouin spectra were measured by a tandem VIPA spectrometer and an EMCCD camera (exposure time = 100 ms). A normal abdominal skin sample from a healthy Caucasian female, provided by Obio LLC (CA, USA), was embedded in optimal cutting temperature (OCT) compound, flash-frozen, and stored at −80°C. An 8 μm-thick section was then analysed using multimodal microscopy. To mimic physiological conditions, the sample was kept moist by applying phosphate-buffered saline (PBS) solution.&lt;/p&gt;&lt;p&gt;Figure 1a shows a bright-field image of the sample, with the red square indicating the dermal area measured by multimodal microscopy. The multiphoton imaging results, shown in Figure 1b,c, visualised that both collagen and elastin exist on fibres, with collagen being more densely distributed compared to the sparser distribution of elastin. The optical frequency shift of Brillouin scattering, namely Brillouin shift, is proportional to the longitudinal modulus, which is defined as the ratio of uniaxial stress to strain under a longitudinally confined condition [&lt;span&gt;5&lt;/span&gt;]. Therefore, the Brillouin image shown in Figure 1d reflects the distribution of the local mechanical property linked to elasticity. F","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 3","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70081","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143602673","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":"New Characteristics of Eccrine Sweat Glands in Acquired Idiopathic Generalised Anhidrosis as Determined via Three-Dimensional Fluorescence Imaging of Cleared Skin Tissue","authors":"Satoshi Yoshida,&nbsp;Ryosuke Kawakami,&nbsp;Yosuke Niko,&nbsp;Yasuhiro Fujisawa,&nbsp;Masamoto Murakami","doi":"10.1111/exd.70038","DOIUrl":"https://doi.org/10.1111/exd.70038","url":null,"abstract":"&lt;p&gt;Acquired idiopathic generalised anhidrosis (AIGA) is an acquired condition characterised by a noticeable decrease in sweating without an obvious cause [&lt;span&gt;1&lt;/span&gt;]. The diagnostic guidelines for AIGA in Japan state that examination of a skin biopsy by optical microscopy and electron microscopy may demonstrate lymphocytic infiltration around the sweat glands and swelling of the secretory cells of the sweat glands; however, microscopy does not reveal marked morphological defects of sweat glands [&lt;span&gt;1&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;We treated a 47-year-old man with AIGA who presented with a 6-year history of reduced sweating involving the trunk and limbs. AIGA was diagnosed using the established criteria [&lt;span&gt;1&lt;/span&gt;]. Blood tests, computed tomography, sialometry and Schirmer's test were performed. Differential diagnosis excluded neuropathy, exocrine gland dysfunction, and Sjögren's syndrome. A starch–iodine test confirmed anhidrosis affecting more than 95% of the trunk and limbs (Figure S1). Despite undergoing three courses of methylprednisolone pulse therapy during the past year, the patient's anhidrosis exhibited no improvement. We took 2-mm-diameter punch biopsy from an anhidrotic region of the lumbar back skin. Haematoxylin and eosin (H&amp;E) staining revealed a lack of eccrine secretory glands. To investigate a potential decrease in sweat gland number due to atrophic changes, we took a 6-mm-diameter punch biopsy. The results were consistent with the initial examination, showing no eccrine secretory glands (Figure 1A). By contrast, tissue samples from patients without AIGA showed multiple glands within the same 6 mm range. Therefore, these results seem to imply that patients with AIGA may lose eccrine sweat gland structures.&lt;/p&gt;&lt;p&gt;However, conventional H&amp;E staining provides only two-dimensional images and has limitations in evaluating the total number and density of ducts and eccrine secretory glands because of their complex three-dimensional architecture. Therefore, we used a new three-dimensional fluorescence deep-imaging technique to compare the skin of patients with and without AIGA [&lt;span&gt;2&lt;/span&gt;]. Briefly, we used HistoBright (Funakoshi, Tokyo, Japan), which is an improved solvatochromic fluorescent dye based on LipiORDER (Data S1) [&lt;span&gt;3&lt;/span&gt;]. Sections of skin tissue were fixed with 4% paraformaldehyde in phosphate-buffered saline and stored frozen. Next, samples were stained with Hoechst and optically cleared using the LUCID method to enhance transparency and fluorescent dye penetration [&lt;span&gt;4&lt;/span&gt;]. Finally, three-dimensional fluorescence imaging was performed using two-photon microscopy (TPM; AXE R MP; Nikon, Tokyo, Japan). The Ehime University Graduate School of Medicine Ethics Committee approved the study protocol, and the study was performed in accordance with the Declaration of Helsinki.&lt;/p&gt;&lt;p&gt;Before evaluating the patient's skin, we imaged a 2-mm punch-biopsy lumbar back skin specimen from a patient without AIGA (Figu","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 3","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70038","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143602674","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":"Clinical Experience of Risankizumab in Patients With a History of Erythrodermic Psoriasis","authors":"Che-Chia Hsu,&nbsp;Chang-Yu Hsieh,&nbsp;Tsen-Fang Tsai","doi":"10.1111/exd.70080","DOIUrl":"https://doi.org/10.1111/exd.70080","url":null,"abstract":"<div>\u0000 \u0000 <p>Erythrodermic psoriasis (EP) is a severe and challenging variant of psoriasis that often shows poor drug survival. While risankizumab, an IL-23 inhibitor, has demonstrated efficacy in patients with moderate-to-severe plaque psoriasis, its effectiveness in patients with a history of EP is less explored. This study aimed to evaluate treatment response to risankizumab and identify potential predictors influencing the treatment response. In this single-center, longitudinal retrospective study, we included 56 patients treated with risankizumab between August 1, 2016, and June 1, 2023, of whom 22 had a history of EP. Treatment response was assessed using the Psoriasis Area and Severity Index (PASI), and the impact of patient characteristics, including prior biologic exposure and HLA-Cw genotypes, on treatment response was analysed using the Mann–Whitney <i>U</i> test. Throughout the 100-week follow-up, patients with a history of EP exhibited a poorer treatment response compared to those without such a history. Among patients with a history of EP, those with prior exposure to guselkumab and those treated with more than five biologics demonstrated a decreased response to risankizumab. Additionally, there was a non-significant trend indicating that HLA-Cw1–negative patients responded better to risankizumab. This case series indicated that risankizumab might be an effective and sustainable treatment option for most patients with a history of EP. However, prior exposure to multiple biologics, particularly those with a similar mode of action targeting IL-23, may reduce its effectiveness. The potential association between HLA-Cw1 genotype and treatment response warrants further investigation.</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 3","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143595403","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":"Skin-Protective Performance of Alternative Stratum Corneum Formed by a Pseudo-Ceramide-Containing Steroid Lamellar Cream","authors":"Masafumi Yokota,&nbsp;Tomohiro Matsumoto,&nbsp;Akane Kawamoto,&nbsp;Kumiko Dojo,&nbsp;Sumika Toyama,&nbsp;Catharina Sagita Moniaga,&nbsp;Junko Ishikawa,&nbsp;Daiki Murase,&nbsp;Noriyasu Ota,&nbsp;Mitsutoshi Tominaga,&nbsp;Kenji Takamori","doi":"10.1111/exd.70041","DOIUrl":"https://doi.org/10.1111/exd.70041","url":null,"abstract":"<p>Ceramides in the stratum corneum (SC) are important for epidermal barrier function. We previously developed a synthetic pseudo-ceramide for medical (SPCM)-containing steroid cream [SPCM (+)]. This cream forms films on the skin surface and exerts anti-inflammatory effects through steroids. However, the preventive effects of this cream on the disruption of the skin barrier remained unclear. Therefore, in this study, we aimed to evaluate the protective role of SPCM (+) cream against atopic dermatitis (AD)-associated protease allergens on the skin in recovery from barrier-broken skin. We used three-dimensional (3D) skin and mouse models of disrupted skin barriers to evaluate the protective effect of SPCM (+) cream against V8 protease produced by <i>Staphylococcus aureus</i>. In NC/Nga mice with itching caused by living mites, SPCM (+) cream was repeatedly applied once a day for 2 weeks, and scratching behaviour was assessed every week using the MicroAct system. In the 3D skin model, the SPCM (+) cream directly blocked SC degradation by V8 protease of <i>S. aureus</i> and suppressed the expression of interleukin-36 gamma. The application of SPCM (+) cream to mite-parasitised mice suppressed scratching, reduced elevated activity of skin proteases, and inhibited upregulation of thymic stromal lymphopoietin. These beneficial effects of SPCM (+) cream were not observed with steroid creams without SPCM. These results suggest that the SPCM (+) cream is effective in relieving inflammation and itching by protecting the skin from proteases and allergens through its lamellar structure. This cream may be a promising treatment option for skin barrier disorders including AD and xerosis.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 3","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70041","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143595122","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":"IKZF1 and Ikaros Overexpression Results in Alopecia Areata-Like Phenotype in Mice","authors":"Yukiyasu Arakawa,&nbsp;Risa Tamagawa-Mineoka,&nbsp;Mayumi Ueta,&nbsp;Mari Nakanishi,&nbsp;Hiromi Nishigaki,&nbsp;Norito Katoh","doi":"10.1111/exd.70074","DOIUrl":"https://doi.org/10.1111/exd.70074","url":null,"abstract":"<div>\u0000 \u0000 <p>Ikaros, which is encoded by the Ikaros family zinc finger 1 (<i>IKZF1</i>) gene, is a zinc finger transcription factor. We have previously generated K5-<i>Ikzf1</i>-EGFP transgenic mice (<i>Ikzf1</i> Tg) by introducing the IKZF1 isoform into epithelial cells expressing keratin 5, which develop patchy alopecia. However, there has been no detailed in vivo investigation of the function of <i>IKZF1</i> in alopecia or of Ikaros expression in hair follicles of alopecia patients. Our aim was to investigate whether <i>IKZF1</i> overexpression is involved in the pathogenesis of alopecia areata (AA) using <i>Ikzf1</i> Tg and to examine Ikaros expression in human scalp skin. We grossly and histologically examined the alopecic lesions of <i>Ikzf1</i> Tg and the skin of wild-type (WT) mice and the associated mRNA expression of inflammatory mediators. We also examined Ikaros' expression in human scalp skin. Grossly and histologically, we found that the <i>Ikzf1</i> Tg developed AA-like lesions. Immunohistochemically, the hair follicles of the <i>Ikzf1</i> Tg expressed high levels of the NKG2D ligand H60 and contained infiltrating CD8⁺NKG2D⁺ T cells. Interleukin 15, tumour necrosis factor-α, CXC chemokine ligand (Cxcl)1, Cxcl10, Cxcl11, signal transducer and activator of transcription (STAT)1, STAT3, Janus kinase (JAK)1 and JAK3 mRNA expression were significantly higher in the alopecic lesions of the <i>Ikzf1</i> Tg than in the WT mice. <i>Ikzf1</i> Tg given corticosteroid injections exhibited hair regrowth. Immunohistochemical analysis of scalp hair follicles showed that Ikaros was more highly expressed in AA patients than in non-AA controls. Our study suggests that <i>IKZF1</i> and Ikaros are involved in the pathogenesis of AA.</p>\u0000 </div>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 3","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143595001","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":"A Novel Ammonium Carboxylate Salt of Undecylenic Acid for the Topical Treatment of Gram-Positive and Antibiotic-Resistant Skin Infections","authors":"Alyce Mayfosh,&nbsp;Thomas Rau","doi":"10.1111/exd.70075","DOIUrl":"https://doi.org/10.1111/exd.70075","url":null,"abstract":"<p>Uncomplicated topical skin infections like impetigo, caused by gram-positive bacteria such as <i>Staphylococcus aureus</i> and <i>Streptococcus pyogenes</i>, are a common global health issue, particularly affecting children. With increasing antimicrobial resistance, conventional treatments such as mupirocin are becoming ineffective, highlighting the necessity for new antimicrobial development. Fatty acids have long shown potential as novel antimicrobials, but their development has been limited by solubility and efficacy concerns in topical applications. We previously discovered that combining the amino acid L-arginine with an 11-carbon fatty acid, undecylenic acid, produced a water-soluble ammonium carboxylate salt, arginine undecylenate, referred to as GS-1, that elicits potent antimicrobial activity. Under CLSI test conditions, GS-1 showed effective antibacterial activity against clinical isolates of methicillin-sensitive <i>S. aureus</i> (MSSA), methicillin-resistant <i>S. aureus</i> (MRSA), vancomycin-intermediate <i>S. aureus</i>, and <i>S. pyogenes</i>, with MICs of 0.60–1.26 mg/mL and MBCs of 0.63–5.04 mg/mL, respectively. Fluorescence microscopy revealed GS-1 to elicit antibacterial activity by rapidly permeabilising bacterial membranes and inducing reactive oxygen species formation. Serial exposure of 5 MRSA clinical isolates to sub-lethal doses of GS-1 did not appear to induce resistance. In fact, compared to mupirocin, repeated exposures to GS-1 appeared to sensitise bacteria to GS-1. In an animal model of skin infection, topical GS-1 successfully eradicated MRSA from infected, abraded skin after 6 days of treatment with no signs of toxicity. Finally, repeated topical GS-1 exposure in humans caused no irritation or sensitisation. These results support GS-1 as a potential novel topical antibacterial for the treatment of impetigo and other skin infections.</p>","PeriodicalId":12243,"journal":{"name":"Experimental Dermatology","volume":"34 3","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/exd.70075","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143581672","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}