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The Potential Role of β-Asarone in Calcium Imbalance and Mitochondrial Dysfunction in Melanoma Cells. β-细辛酮在黑色素瘤细胞钙失衡和线粒体功能障碍中的潜在作用。
IF 1.3 Pub Date : 2026-02-01 DOI: 10.5021/ad.25.122
Yuze Liu, Wei Tang, Biao Yu, Qinghua Yang, Wenbing Lai

Background: The treatment landscape for melanoma, a particularly malignant skin cancer, is constrained by notable drug resistance and toxicity. β-Asarone, a natural compound from Acorus tatarinowii, has shown anticancer potential. Disruption of calcium homeostasis and mitochondrial dysfunction are key regulators of tumor cell survival and death.

Objective: This research was conducted to investigate the impact of β-Asarone on B16F10 melanoma cells, focusing on its potential to induce apoptosis by modulating calcium signaling and mitochondrial function.

Methods: Cell proliferation and apoptosis were evaluated using CCK-8, colony formation, EdU, and TUNEL assays. Intracellular calcium levels and mitochondrial membrane potential were measured using Fluo-4 AM, Rhod-2 AM, and JC-1 staining. Reactive oxygen species (ROS) generation and adenosine triphosphate (ATP) levels were assessed by fluorescent probes and ATP assay. Western blotting was utilized to detect apoptosis-related proteins, AMP-activated protein kinase (AMPK) pathway activation, and mitochondrial dynamics (OPA1, DRP1, FIS1).

Results: Treatment with β-Asarone notably inhibited the proliferation of B16F10 cells while simultaneously inducing apoptosis. Fluorescent probe analysis revealed that β-Asarone triggered cytosolic and mitochondrial Ca²⁺ overloaded in both the cytosol and mitochondria, accompanied by decreased mitochondrial membrane potential, elevated ROS levels, and reduced ATP production. Western blot analysis showed increased expression of DRP1 and FIS1, decreased OPA1, and enhanced AMPK phosphorylation, indicating that β-Asarone promotes mitochondrial fission through AMPK activation, likely driven by intracellular calcium imbalance.

Conclusion: This study demonstrates that β-Asarone induces apoptosis in B16F10 melanoma cells by triggering Ca²⁺ overload and mitochondrial dysfunction.

背景:黑色素瘤是一种特别恶性的皮肤癌,其治疗前景受到明显的耐药性和毒性的限制。β-细辛酮是一种天然化合物,具有抗癌潜力。钙稳态的破坏和线粒体功能障碍是肿瘤细胞存活和死亡的关键调节因子。目的:本研究旨在探讨β-细丁酮对B16F10黑色素瘤细胞的影响,重点研究其通过调节钙信号和线粒体功能诱导细胞凋亡的可能性。方法:采用CCK-8、菌落形成、EdU和TUNEL检测细胞增殖和凋亡。采用Fluo-4 AM、Rhod-2 AM和JC-1染色测定细胞内钙水平和线粒体膜电位。采用荧光探针和ATP测定法检测活性氧(ROS)生成和三磷酸腺苷(ATP)水平。Western blotting检测凋亡相关蛋白、amp活化蛋白激酶(AMPK)通路激活和线粒体动力学(OPA1, DRP1, FIS1)。结果:β-细辛酮显著抑制B16F10细胞增殖,同时诱导凋亡。荧光探针分析显示,β-细丁酮触发细胞质和线粒体ca2 +在细胞质和线粒体中均超载,并伴有线粒体膜电位降低、ROS水平升高和ATP生成减少。Western blot分析显示,DRP1和FIS1表达增加,OPA1表达降低,AMPK磷酸化增强,表明β-细丁酮通过激活AMPK促进线粒体分裂,可能是由细胞内钙失衡驱动的。结论:本研究证实β-细丁酮通过触发Ca 2 +过载和线粒体功能障碍诱导B16F10黑色素瘤细胞凋亡。
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引用次数: 0
Unraveling the Pathogenesis of Asian Atopic Dermatitis: Key Characteristics and Insights. 揭示亚洲特应性皮炎的发病机制:关键特征和见解。
IF 1.3 Pub Date : 2025-12-01 DOI: 10.5021/ad.25.008
Sul Hee Lee, Nam Gyoung Ha, Yong Hyun Jang

Atopic dermatitis (AD) is a chronic skin condition influenced by genetic, environmental, and immune factors, with notable ethnic variations in its prevalence and mechanisms. In Asian populations, distinct immunopathogenic features include the significant roles of helper (Th) 17 and Th22 cytokine pathways, differing from other ethnic groups. Key genetic variations related to immune regulation and skin barrier function are more prevalent in Asians. Microbiome studies reveal the role of Staphylococcus aureus in AD skin and emerging microbial species linked to microbiome dysbiosis and the gut-skin axis. Environmental factors like pollution and fine dust further exacerbate symptoms in Asia. This study consolidates findings to highlight the genetic, immunological, microbiome, and environmental factors contributing to AD's unique characteristics in Asians. Tailored treatment approaches are essential for improving outcomes and management of AD in diverse populations.

特应性皮炎(AD)是一种受遗传、环境和免疫因素影响的慢性皮肤病,其患病率和发病机制存在显著的民族差异。在亚洲人群中,不同于其他种族的独特的免疫致病特征包括辅助性(Th) 17和Th22细胞因子途径的重要作用。与免疫调节和皮肤屏障功能相关的关键遗传变异在亚洲人中更为普遍。微生物组研究揭示了金黄色葡萄球菌在AD皮肤中的作用,以及与微生物组失调和肠道-皮肤轴相关的新兴微生物物种。污染和微细粉尘等环境因素进一步加剧了亚洲的症状。本研究整合了研究结果,强调了遗传、免疫学、微生物组和环境因素对亚洲人AD独特特征的影响。量身定制的治疗方法对于改善不同人群阿尔茨海默病的预后和管理至关重要。
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引用次数: 0
Updates in Treatment for Androgenetic Alopecia. 雄激素性脱发治疗的最新进展。
IF 1.3 Pub Date : 2025-12-01 DOI: 10.5021/ad.25.042
Jung-Won Shin, Chang-Hun Huh

Androgenetic alopecia (AGA) is a common nonscarring hair loss condition that affects both men and women, often resulting in psychological distress and reduced quality of life. AGA pathogenesis involves genetic predisposition and androgen influence, primarily dihydrotestosterone (DHT), which leads to hair follicle miniaturization and progressive hair thinning. AGA remains challenging to manage due to its chronic progression and the combined influence of genetic and environmental factors. Topical minoxidil and oral finasteride are the most widely used treatments for AGA, addressing follicular miniaturization. However, their reliance on long-term use and potential for side effects or inconvenience has prompted increasing interest in alternative therapies. The mainstream of current AGA treatment can be categorized into androgen-targeting and non-androgen-targeting approaches. Finasteride and dutasteride, both 5-α-reductase inhibitors that reduce DHT levels in hair follicles, are key androgen-targeting treatments, with newer formulations like topical and injectable options emerging alongside traditional oral forms. Topical minoxidil remains central to non-androgen-targeted AGA treatments, though growing evidence supports the efficacy and safety of its low-dose oral form. Additionally, therapies like low-level light therapy, platelet-rich plasma, and exosome treatments are being explored. Recently, therapies targeting the androgen receptor, including small interfering RNA-based approaches, have been developed and are currently in clinical trial stages, offering innovative potential for AGA treatment. This review explores current and emerging treatments for AGA, addressing both androgen-targeted and non-androgen-targeted approaches with an emphasis on their mechanisms, efficacy, and safety. It ultimately aims to provide a comprehensive update on the latest advancements in AGA management.

雄激素性脱发(AGA)是一种常见的无瘢痕性脱发,男性和女性都会受到影响,通常会导致心理困扰和生活质量下降。AGA的发病机制涉及遗传易感性和雄激素的影响,主要是双氢睾酮(DHT),导致毛囊小型化和进行性头发稀疏。由于其慢性进展以及遗传和环境因素的综合影响,AGA仍然具有挑战性。外用米诺地尔和口服非那雄胺是AGA最广泛使用的治疗方法,解决毛囊小型化问题。然而,它们对长期使用的依赖和潜在的副作用或不便促使人们对替代疗法的兴趣日益增加。目前治疗AGA的主流方法可分为雄激素靶向和非雄激素靶向两种。非那雄胺和度他雄胺都是5-α-还原酶抑制剂,可以降低毛囊中的DHT水平,是关键的雄激素靶向治疗药物,除了传统的口服药物外,还出现了外用和注射等新剂型。尽管越来越多的证据支持其低剂量口服形式的有效性和安全性,但外用米诺地尔仍然是非雄激素靶向性AGA治疗的核心。此外,低强度光疗、富血小板血浆和外泌体治疗等疗法正在探索中。最近,针对雄激素受体的治疗方法,包括基于小干扰rna的方法,已经开发出来,目前处于临床试验阶段,为AGA治疗提供了创新潜力。这篇综述探讨了目前和新兴的AGA治疗方法,包括雄激素靶向和非雄激素靶向方法,重点是它们的机制、疗效和安全性。它的最终目的是提供关于AGA管理最新进展的全面更新。
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引用次数: 0
The Efficacy and Safety of 785-nm Picosecond Titanium:Sapphire Laser on Melasma in Asians. 785纳米皮秒钛蓝宝石激光治疗亚洲黄褐斑的疗效和安全性。
IF 1.3 Pub Date : 2025-12-01 DOI: 10.5021/ad.24.133
Mi Soo Choi, Dongho Kim, Kyujin Yeom, Myung Hwa Kim, Byungcheol Park
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引用次数: 0
Perceptions and Experiences of Scalp Micropigmentation Among Dermatology Outpatients With Hair Loss: A Survey-Based Study. 皮肤科门诊脱发患者对头皮微色素沉着的认知与体验:一项基于调查的研究。
IF 1.3 Pub Date : 2025-12-01 DOI: 10.5021/ad.25.104
Myeong Jae Kim, Hei Sung Kim

Background: Scalp micropigmentation (SMP) is a non-surgical procedure used to camouflage hair loss or scalp scars. Although SMP is legally permitted only when performed by licensed medical professionals in South Korea, it is frequently administered in non-medical settings, raising safety and regulatory concerns.

Objective: This study aimed to evaluate the awareness, perceptions, legal knowledge, treatment experiences, and provider preferences related to SMP among dermatology outpatients with alopecia in South Korea.

Methods: A structured 13-item questionnaire was administered to 131 adult dermatology outpatients with hair loss at Incheon St. Mary's Hospital. The survey assessed participants' awareness of SMP, sources of information, willingness to undergo the procedure, legal knowledge, and previous experiences.

Results: Among the respondents, 90.8% had heard of SMP, most commonly through the Internet or family and friends. A majority (65.6%) were aware that SMP is legally restricted to licensed medical professionals. However, all five participants (3.8%) who had undergone SMP received the procedure in non-medical settings. Notably, 82.5% of participants without prior SMP experience preferred medically supervised settings, and all individuals with prior SMP experience indicated they would choose a hospital for future procedures.

Conclusion: This study reveals a disconnect between legal awareness and actual treatment behavior regarding SMP. While most patients understand that SMP is a medical procedure requiring physician oversight, many still receive treatment in non-medical environments. The findings highlight the need to expand access to physician-led SMP services, enhance public education, and reinforce regulatory enforcement to ensure patient safety and align practices with clinical standards.

背景:头皮微色素沉着(SMP)是一种用于掩饰脱发或头皮疤痕的非手术治疗方法。虽然在韩国,SMP只有在有执照的医疗专业人员实施时才被法律允许,但它经常在非医疗环境中实施,引起了安全和监管方面的关切。目的:本研究旨在评估韩国皮肤科脱发门诊患者对SMP的认知、认知、法律知识、治疗经验和提供者偏好。方法:对仁川圣玛丽医院皮肤科门诊131例成人脱发患者进行问卷调查。调查评估了参与者对SMP的认识、信息来源、接受程序的意愿、法律知识和以前的经验。结果:90.8%的受访者听说过SMP,最常见的是通过网络或家人和朋友。大多数人(65.6%)知道,在法律上,SMP仅限于持牌医疗专业人员。然而,所有接受过SMP的5名参与者(3.8%)都是在非医疗环境中接受的手术。值得注意的是,82.5%没有SMP经验的参与者更喜欢医学监督的环境,所有有SMP经验的人都表示他们会选择医院进行未来的手术。结论:本研究揭示了SMP的法律意识与实际治疗行为之间的脱节。虽然大多数患者明白SMP是一种需要医生监督的医疗程序,但许多患者仍然在非医疗环境中接受治疗。研究结果强调,有必要扩大获得医生主导的SMP服务的机会,加强公众教育,加强监管执法,以确保患者安全,并使实践与临床标准保持一致。
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引用次数: 0
Dynamic Evaluation of Glabellar Area Muscles Movement and Skin Displacement Using 3D Skin Displacement Vector Analysis. 应用三维皮肤位移矢量分析动态评价额骨区肌肉运动和皮肤位移。
IF 1.3 Pub Date : 2025-12-01 DOI: 10.5021/ad.24.018
Hyoung-Jin Moon, Jeong-Mok Cho, Sang-Eun Lee

Background: Three-dimensional (3D) skin displacement vector analysis method provides a deeper understanding of dynamic muscle anatomy. Understanding the dynamic muscle anatomy in the glabellar area during frowning can facilitate safer and effective botulinum toxin injections for treating glabellar wrinkles.

Objective: We aimed to investigate the skin displacement patterns of the glabellar area and adjacent skin during contraction of the glabellar muscles using 3D skin vector displacement analysis.

Methods: Twenty-nine healthy individuals (26 female, 3 male; median age 40.5 years) participated in the study. Photographs of the face were taken at rest and during maximal contraction of the glabellar muscles. Each expression image was aligned to its respective static image to compute the differences in the skin position.

Results: Two skin displacement patterns were identified during frowning: lateral pattern (89.66%), in which main skin vector displacement located on the eyebrow area and central pattern (10.34%), in which skin vector displacement mostly located between eyebrows. 62.07% showed asymmetric skin displacement. Analysis of the glabellar patterns showed that the 'U', '11', 'X', and 'π' patterns were observed in 38%, 38%, 14%, and 10% of cases, respectively, with corresponding skin vector displacement angles of 48°, 32°, 74°, and 24°. Additionally, 20.69% of subjects exhibited upward skin movement in the medial frontalis area during frowning. In 48% of subjects, the lateral and inferior portions of the orbicularis oculi muscle contracted, along with the upper medial portion.

Conclusion: This data will serve as an important guide for Botulinum Toxin treatment of glabella wrinkles in Korean patients.

背景:三维(3D)皮肤位移矢量分析方法提供了对动态肌肉解剖的更深入理解。了解眉间区皱眉时的动态肌肉解剖学,有助于更安全有效地注射肉毒杆菌毒素治疗眉间皱纹。目的:应用三维皮肤矢量位移分析方法,探讨骨间肌收缩过程中骨间区及邻近皮肤的皮肤位移规律。方法:29例健康个体(女性26例,男性3例,中位年龄40.5岁)参与研究。面部的照片是在休息时和在额骨肌最大收缩时拍摄的。每个表情图像与其各自的静态图像对齐,以计算皮肤位置的差异。结果:在皱眉时发现两种皮肤位移模式:侧移模式(89.66%),主要的皮肤矢量位移位于眉区;中心模式(10.34%),主要的皮肤矢量位移位于眉间。62.07%为不对称皮肤移位。glabellar pattern分析显示,“U”型、“11”型、“X”型和“π”型分别占38%、38%、14%和10%,对应的皮肤矢量位移角分别为48°、32°、74°和24°。此外,20.69%的受试者在皱眉时前额内侧区域出现皮肤向上运动。在48%的受试者中,眼轮匝肌的外侧和下方部分以及上内侧部分收缩。结论:本研究结果对肉毒杆菌毒素治疗韩国眉间皱纹具有重要的指导意义。
{"title":"Dynamic Evaluation of Glabellar Area Muscles Movement and Skin Displacement Using 3D Skin Displacement Vector Analysis.","authors":"Hyoung-Jin Moon, Jeong-Mok Cho, Sang-Eun Lee","doi":"10.5021/ad.24.018","DOIUrl":"10.5021/ad.24.018","url":null,"abstract":"<p><strong>Background: </strong>Three-dimensional (3D) skin displacement vector analysis method provides a deeper understanding of dynamic muscle anatomy. Understanding the dynamic muscle anatomy in the glabellar area during frowning can facilitate safer and effective botulinum toxin injections for treating glabellar wrinkles.</p><p><strong>Objective: </strong>We aimed to investigate the skin displacement patterns of the glabellar area and adjacent skin during contraction of the glabellar muscles using 3D skin vector displacement analysis.</p><p><strong>Methods: </strong>Twenty-nine healthy individuals (26 female, 3 male; median age 40.5 years) participated in the study. Photographs of the face were taken at rest and during maximal contraction of the glabellar muscles. Each expression image was aligned to its respective static image to compute the differences in the skin position.</p><p><strong>Results: </strong>Two skin displacement patterns were identified during frowning: lateral pattern (89.66%), in which main skin vector displacement located on the eyebrow area and central pattern (10.34%), in which skin vector displacement mostly located between eyebrows. 62.07% showed asymmetric skin displacement. Analysis of the glabellar patterns showed that the 'U', '11', 'X', and 'π' patterns were observed in 38%, 38%, 14%, and 10% of cases, respectively, with corresponding skin vector displacement angles of 48°, 32°, 74°, and 24°. Additionally, 20.69% of subjects exhibited upward skin movement in the medial frontalis area during frowning. In 48% of subjects, the lateral and inferior portions of the orbicularis oculi muscle contracted, along with the upper medial portion.</p><p><strong>Conclusion: </strong>This data will serve as an important guide for Botulinum Toxin treatment of glabella wrinkles in Korean patients.</p>","PeriodicalId":94298,"journal":{"name":"Annals of dermatology","volume":"37 6","pages":"344-349"},"PeriodicalIF":1.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12715876/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145663163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Impact of Hydrochlorothiazide on Nonmelanoma Skin Cancer: A Distributed Network Analysis of 11 Real-world Databases. 氢氯噻嗪对非黑色素瘤皮肤癌的影响:11个真实世界数据库的分布式网络分析。
IF 1.3 Pub Date : 2025-12-01 DOI: 10.5021/ad.25.024
Yeon-Jung Park, Man S Kim, Yoonsung Lee, Bark-Lynn Lew, Soon-Hyo Kwon

Background: Hydrochlorothiazide (HCTZ) has carcinogenic effects owing to its photosensitizing properties. Recent studies have reported inconsistent results regarding the association between HCTZ and skin cancer.

Objective: This study aimed to clarify the effects of HCTZ on the risk of developing nonmelanoma skin cancer (NMSC) in Korean patients with hypertension.

Methods: This multicenter, retrospective cohort study was conducted using clinical data from 11 hospitals in Korea, and converted to the Observational Medical Outcomes Partnership-Common Data Model. Large-scale 1:1 propensity score-matching was conducted to balance the target and comparator cohorts. Cox regression analysis was used to examine the hazard ratio (HR) for NMSC in HCTZ users compared to HCTZ never-users.

Results: 8,821 patients and same number of controls were pooled from 11 databases. HCTZ use was not associated with a decreased risk of NMSC (HR, 1.01; 95% confidence interval [CI], 0.70-1.47). In the dose-response analysis, no significant correlation was found between NMSC risk and HCTZ dose for <1 year (HR, 1.17; 95% CI, 0.64-2.17) and ≥1 year (HR, 1.02; 95% CI, 0.64-1.61). No significant increase in the risk of NMSC was observed in the subgroup analyses for either age or sex.

Conclusion: HCTZ was not associated with the development of NMSC in a Korean hypertensive population, regardless of the duration of drug exposure.

背景:氢氯噻嗪(HCTZ)具有光敏性,具有致癌性。最近的研究报告了关于HCTZ和皮肤癌之间关系的不一致的结果。目的:本研究旨在阐明HCTZ对韩国高血压患者发生非黑色素瘤皮肤癌(NMSC)风险的影响。方法:本研究采用韩国11家医院的临床数据进行多中心回顾性队列研究,并将其转换为观察性医疗结果伙伴关系-通用数据模型。进行大规模1:1倾向评分匹配,以平衡目标和比较者队列。采用Cox回归分析检验HCTZ使用者与从未使用过HCTZ者NMSC的风险比(HR)。结果:从11个数据库中共纳入8821例患者和相同数量的对照组。使用HCTZ与NMSC风险降低无关(HR, 1.01; 95%可信区间[CI], 0.70-1.47)。在剂量-反应分析中,未发现NMSC风险与HCTZ剂量之间存在显著相关性。结论:在韩国高血压人群中,与药物暴露时间无关,HCTZ与NMSC的发生无关。
{"title":"Impact of Hydrochlorothiazide on Nonmelanoma Skin Cancer: A Distributed Network Analysis of 11 Real-world Databases.","authors":"Yeon-Jung Park, Man S Kim, Yoonsung Lee, Bark-Lynn Lew, Soon-Hyo Kwon","doi":"10.5021/ad.25.024","DOIUrl":"10.5021/ad.25.024","url":null,"abstract":"<p><strong>Background: </strong>Hydrochlorothiazide (HCTZ) has carcinogenic effects owing to its photosensitizing properties. Recent studies have reported inconsistent results regarding the association between HCTZ and skin cancer.</p><p><strong>Objective: </strong>This study aimed to clarify the effects of HCTZ on the risk of developing nonmelanoma skin cancer (NMSC) in Korean patients with hypertension.</p><p><strong>Methods: </strong>This multicenter, retrospective cohort study was conducted using clinical data from 11 hospitals in Korea, and converted to the Observational Medical Outcomes Partnership-Common Data Model. Large-scale 1:1 propensity score-matching was conducted to balance the target and comparator cohorts. Cox regression analysis was used to examine the hazard ratio (HR) for NMSC in HCTZ users compared to HCTZ never-users.</p><p><strong>Results: </strong>8,821 patients and same number of controls were pooled from 11 databases. HCTZ use was not associated with a decreased risk of NMSC (HR, 1.01; 95% confidence interval [CI], 0.70-1.47). In the dose-response analysis, no significant correlation was found between NMSC risk and HCTZ dose for <1 year (HR, 1.17; 95% CI, 0.64-2.17) and ≥1 year (HR, 1.02; 95% CI, 0.64-1.61). No significant increase in the risk of NMSC was observed in the subgroup analyses for either age or sex.</p><p><strong>Conclusion: </strong>HCTZ was not associated with the development of NMSC in a Korean hypertensive population, regardless of the duration of drug exposure.</p>","PeriodicalId":94298,"journal":{"name":"Annals of dermatology","volume":"37 6","pages":"350-356"},"PeriodicalIF":1.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12715869/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145663178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Polyunsaturated Fatty Acids and Skin Cancer: Two-Sample Mendelian Randomization Study. 多不饱和脂肪酸与皮肤癌:两样本孟德尔随机化研究。
IF 1.3 Pub Date : 2025-12-01 DOI: 10.5021/ad.25.095
Gahyun Kim, Bo Ri Kim, Kyungho Paik, Seon-Pil Jin, Hyunsun Park, Woojae Myung, Jin-Ku Lee, Chong Won Choi, Jinho Kim

Background: Observational studies have suggested associations between dietary polyunsaturated fatty acids (PUFAs) and cancer risk; however, causal inference regarding skin cancer remains limited due to potential recall bias, confounding, and reverse causation.

Objective: This study aimed to evaluate the causal association between genetically predicted circulating PUFA levels and the risk of skin cancers, including basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma.

Methods: We conducted a 2-sample Mendelian randomization (MR) study using genome-wide association study summary statistics from the UK Biobank (PUFAs, n=115,006) and the FinnGen consortium (BCC, n=26,272; SCC, n=4,663; melanoma, n=5,753). Genetic instruments were derived for omega-3, docosahexaenoic acid, omega-6, linoleic acid, and the omega-6:3 ratio. Multiple MR methods-including inverse-variance weighted, MR-Egger, weighted median, weighted mode, and MR-PRESSO-were applied to test for consistency and assess pleiotropy and heterogeneity.

Results: A higher genetically predicted linoleic acid to total fatty acid ratio was associated with a significantly lower risk of BCC and SCC. Conversely, higher genetically proxied serum omega-3 levels were associated with increased risks of BCC, SCC, and melanoma. The risk effect on SCC was attenuated upon exclusion of rs174528, a variant in the fatty acid desaturase 1 (FADS1) gene, suggesting a role for endogenous PUFA metabolism in carcinogenesis.

Conclusion: This MR analysis supports a causal role of circulating PUFAs in skin cancer development and highlights the importance of FADS-mediated endogenous PUFA metabolism. These findings provide novel insights into the genetic and metabolic underpinnings of skin cancer susceptibility.

背景:观察性研究表明,膳食多不饱和脂肪酸(PUFAs)与癌症风险之间存在关联;然而,由于潜在的回忆偏倚、混淆和反向因果关系,关于皮肤癌的因果推理仍然有限。目的:本研究旨在评估遗传预测的循环PUFA水平与皮肤癌(包括基底细胞癌(BCC)、鳞状细胞癌(SCC)和黑色素瘤)风险之间的因果关系。方法:我们使用来自UK Biobank (PUFAs, n=115,006)和FinnGen联盟(BCC, n=26,272; SCC, n=4,663;黑色素瘤,n=5,753)的全基因组关联研究汇总统计数据进行了一项2样本孟德尔随机化(MR)研究。基因仪器被用于omega-3,二十二碳六烯酸,omega-6,亚油酸和omega-6:3的比例。多种磁共振方法——包括反方差加权、MR- egger、加权中位数、加权模式和MR- presso——被用于检验一致性和评估多效性和异质性。结果:较高的基因预测亚油酸与总脂肪酸比值与BCC和SCC的风险显著降低相关。相反,较高的基因介导血清omega-3水平与BCC、SCC和黑色素瘤的风险增加有关。在排除rs174528(脂肪酸去饱和酶1 (FADS1)基因的一种变异)后,对SCC的风险效应减弱,这表明内源性PUFA代谢在致癌过程中起作用。结论:这项MR分析支持循环PUFA在皮肤癌发展中的因果作用,并强调了fads介导的内源性PUFA代谢的重要性。这些发现为皮肤癌易感性的遗传和代谢基础提供了新的见解。
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引用次数: 0
A Chronic Psoriasis Model Using Long-Term Imiquimod Application in IL-10-Deficient Mice: Recapitulating Skin Inflammation, Comorbidities, and Gut-Skin Axis Alterations. 长期应用咪喹莫特治疗il -10缺陷小鼠的慢性银屑病模型:再现性皮肤炎症、合并症和肠道-皮肤轴改变
IF 1.3 Pub Date : 2025-12-01 DOI: 10.5021/ad.25.108
Jee Hyun Kim, Soo Ran Lee, Hyun Keun Ahn, Hyun Taek Hong, Ui Hyeon Jo, Jong Pil Im, Joo Sung Kim, Min Jung Kim, Jeonghwan Lee, Jeong Hwan Park, Hyunsun Park, Seong-Joon Koh

Background: Psoriasis is a persistent systemic inflammatory condition mediated by the interleukin (IL)-23/IL-17 signaling pathway. Existing murine models, including imiquimod (IMQ)-applied wild-type (WT) mice, may not reflect chronicity and systemic comorbidities of psoriasis, particularly gut-related manifestations linked to the gut-skin axis.

Objective: To establish a murine model that more accurately reflects chronic psoriasis, its systemic comorbidities, and associated gut environment alterations.

Methods: C57BL/6 IL-10-deficient (IL-10 knockout [KO]) and WT mice received topical IMQ or vehicle for 6 weeks. Subsequently, tissue samples from skin, colon, joints, kidneys, liver, abdominal aortas, lymph nodes, and spleens, as well as fecal and blood samples, were collected for histopathologic, immunologic, gut environment analysis.

Results: IMQ-treated IL-10 KO mice developed prolonged psoriatic inflammatory responses with increased epidermal thickness and higher infiltration of CD45+, myeloperoxidase+, and IL-17+ cells. They also exhibited early-onset, severe colitis with marked weight loss, shortened colon length, and elevated colitis severity scores. While IMQ induced systemic inflammation in multiple organs, IL-10 KO mice did not show more severe joint, liver, or kidney involvement than WT mice. Elevated serum tumor necrosis factor alpha and plasminogen activator inhibitor-1 levels, increased heart/body weight ratio, enhanced gut permeability, and distinct gut microbiota profiles were observed in IL-10 KO mice.

Conclusion: The 6-week IMQ-applied IL-10 KO model may better reflect chronic and severe psoriasis with gut-related comorbidities, offering a valuable platform to investigate the gut-skin axis.

背景:银屑病是一种由白细胞介素(IL)-23/IL-17信号通路介导的持续性全身性炎症。现有的小鼠模型,包括咪喹莫特(IMQ)野生型(WT)小鼠,可能不能反映银屑病的慢性和系统性合并症,特别是与肠道-皮肤轴相关的肠道相关表现。目的:建立一种更准确反映慢性牛皮癣及其全身合并症和相关肠道环境改变的小鼠模型。方法:C57BL/6 IL-10缺失(IL-10敲除[KO])小鼠和WT小鼠给予外用IMQ或载药6周。随后,收集皮肤、结肠、关节、肾脏、肝脏、腹主动脉、淋巴结、脾脏以及粪便和血液样本进行组织病理学、免疫学和肠道环境分析。结果:imq处理的IL-10 KO小鼠出现了延长的银屑病炎症反应,表皮厚度增加,CD45+、髓过氧化物酶+和IL-17+细胞的浸润增加。他们还表现出早发性严重结肠炎,体重明显减轻,结肠长度缩短,结肠炎严重程度评分升高。虽然IMQ诱导了多个器官的全身性炎症,但IL-10 KO小鼠没有表现出比WT小鼠更严重的关节、肝脏或肾脏受累。IL-10 KO小鼠血清肿瘤坏死因子α和纤溶酶原激活物抑制剂-1水平升高,心/体重比增加,肠道通透性增强,肠道微生物群特征明显。结论:6周imq应用IL-10 KO模型可以更好地反映慢性和重度银屑病伴肠相关合并症,为研究肠-皮轴提供了有价值的平台。
{"title":"A Chronic Psoriasis Model Using Long-Term Imiquimod Application in IL-10-Deficient Mice: Recapitulating Skin Inflammation, Comorbidities, and Gut-Skin Axis Alterations.","authors":"Jee Hyun Kim, Soo Ran Lee, Hyun Keun Ahn, Hyun Taek Hong, Ui Hyeon Jo, Jong Pil Im, Joo Sung Kim, Min Jung Kim, Jeonghwan Lee, Jeong Hwan Park, Hyunsun Park, Seong-Joon Koh","doi":"10.5021/ad.25.108","DOIUrl":"10.5021/ad.25.108","url":null,"abstract":"<p><strong>Background: </strong>Psoriasis is a persistent systemic inflammatory condition mediated by the interleukin (IL)-23/IL-17 signaling pathway. Existing murine models, including imiquimod (IMQ)-applied wild-type (WT) mice, may not reflect chronicity and systemic comorbidities of psoriasis, particularly gut-related manifestations linked to the gut-skin axis.</p><p><strong>Objective: </strong>To establish a murine model that more accurately reflects chronic psoriasis, its systemic comorbidities, and associated gut environment alterations.</p><p><strong>Methods: </strong>C57BL/6 IL-10-deficient (IL-10 knockout [KO]) and WT mice received topical IMQ or vehicle for 6 weeks. Subsequently, tissue samples from skin, colon, joints, kidneys, liver, abdominal aortas, lymph nodes, and spleens, as well as fecal and blood samples, were collected for histopathologic, immunologic, gut environment analysis.</p><p><strong>Results: </strong>IMQ-treated IL-10 KO mice developed prolonged psoriatic inflammatory responses with increased epidermal thickness and higher infiltration of CD45+, myeloperoxidase+, and IL-17+ cells. They also exhibited early-onset, severe colitis with marked weight loss, shortened colon length, and elevated colitis severity scores. While IMQ induced systemic inflammation in multiple organs, IL-10 KO mice did not show more severe joint, liver, or kidney involvement than WT mice. Elevated serum tumor necrosis factor alpha and plasminogen activator inhibitor-1 levels, increased heart/body weight ratio, enhanced gut permeability, and distinct gut microbiota profiles were observed in IL-10 KO mice.</p><p><strong>Conclusion: </strong>The 6-week IMQ-applied IL-10 KO model may better reflect chronic and severe psoriasis with gut-related comorbidities, offering a valuable platform to investigate the gut-skin axis.</p>","PeriodicalId":94298,"journal":{"name":"Annals of dermatology","volume":"37 6","pages":"383-396"},"PeriodicalIF":1.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12715878/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145663117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Real-World Prevalence and Associated Factors of Nipple Eczema in Patients With Atopic Dermatitis. 特应性皮炎患者乳头湿疹的真实世界患病率及相关因素。
IF 1.3 Pub Date : 2025-12-01 DOI: 10.5021/ad.24.141
Jung Min Lee, Yu Jin Lee, Yun Jeong Choi, June Hyunkyung Lee, Jae Eun Choi, Byeol Han, Tae Young Han

Background: Nipple eczema (NE) manifests as pruritic or painful erythema, often accompanied by oozing, erosion, and lichenification. NE is observed in 6%-23% of patients with atopic dermatitis (AD); its prevalence is higher among adolescent and young adult women.

Objective: To determine the prevalence and clinical correlates of NE in patients with AD.

Methods: We conducted a retrospective cross-sectional study from July to December 2023, enrolling patients diagnosed with AD. Participants completed a questionnaire regarding their symptoms of AD and NE, as well as the impact of NE on their daily lives.

Results: Of the 200 patients, 55 (27.5%) reported of having experienced NE. The mean age at NE onset was 22.75±9.77 years. The proportion of females with NE (70.9%) was significantly higher relative to those without NE (38.6%) (p<0.001). Factors significantly associated with the presence of NE in AD patients included female sex (odds ratio [OR], 4.90; 95% confidence interval [CI], 1.99-12.07; p=0.001), increased AD itch numerical rating scale (NRS) score (OR, 1.46; 95% CI, 1.11-1.91; p=0.007), increased AD pain NRS score (OR, 1.20; 95% CI, 1.01-1.44; p=0.041) and higher Investigator Global Assessment score (OR, 5.38; 95% CI, 2.07-13.99; p=0.001). Regarding nipple-specific health-related quality of life (HRQoL), 35.8% of patients reported severe impairment in HRQoL due to NE, and 45.3% experienced severe emotional distress.

Conclusion: Although the area affected by NE is small, dermatologists should be aware of its association with severe AD characteristics, and its significant impact on patient HRQoL.

背景:乳头湿疹(NE)表现为瘙痒性或疼痛性红斑,常伴有渗出、糜烂和苔藓样变。在6%-23%的特应性皮炎(AD)患者中观察到NE;其发病率在青少年和年轻成年妇女中较高。目的:了解AD患者NE的患病率及临床相关因素。方法:我们于2023年7月至12月进行了一项回顾性横断面研究,纳入了诊断为AD的患者。参与者完成了一份关于AD和NE症状的调查问卷,以及NE对他们日常生活的影响。结果:在200例患者中,55例(27.5%)报告经历过NE。NE发病的平均年龄为22.75±9.77岁。患有NE的女性比例(70.9%)明显高于没有NE的女性(38.6%)(pp=0.001), AD瘙痒数值评定量表(NRS)评分升高(OR, 1.46; 95% CI, 1.11-1.91; p=0.007), AD疼痛NRS评分升高(OR, 1.20; 95% CI, 1.01-1.44; p=0.041),研究者总体评估评分升高(OR, 5.38; 95% CI, 2.07-13.99; p=0.001)。关于乳头特异性健康相关生活质量(HRQoL), 35.8%的患者报告因NE导致的HRQoL严重受损,45.3%的患者经历了严重的情绪困扰。结论:虽然NE影响的面积很小,但皮肤科医生应该意识到它与严重AD特征的关联,以及它对患者HRQoL的显著影响。
{"title":"Real-World Prevalence and Associated Factors of Nipple Eczema in Patients With Atopic Dermatitis.","authors":"Jung Min Lee, Yu Jin Lee, Yun Jeong Choi, June Hyunkyung Lee, Jae Eun Choi, Byeol Han, Tae Young Han","doi":"10.5021/ad.24.141","DOIUrl":"10.5021/ad.24.141","url":null,"abstract":"<p><strong>Background: </strong>Nipple eczema (NE) manifests as pruritic or painful erythema, often accompanied by oozing, erosion, and lichenification. NE is observed in 6%-23% of patients with atopic dermatitis (AD); its prevalence is higher among adolescent and young adult women.</p><p><strong>Objective: </strong>To determine the prevalence and clinical correlates of NE in patients with AD.</p><p><strong>Methods: </strong>We conducted a retrospective cross-sectional study from July to December 2023, enrolling patients diagnosed with AD. Participants completed a questionnaire regarding their symptoms of AD and NE, as well as the impact of NE on their daily lives.</p><p><strong>Results: </strong>Of the 200 patients, 55 (27.5%) reported of having experienced NE. The mean age at NE onset was 22.75±9.77 years. The proportion of females with NE (70.9%) was significantly higher relative to those without NE (38.6%) (<i>p</i><0.001). Factors significantly associated with the presence of NE in AD patients included female sex (odds ratio [OR], 4.90; 95% confidence interval [CI], 1.99-12.07; <i>p</i>=0.001), increased AD itch numerical rating scale (NRS) score (OR, 1.46; 95% CI, 1.11-1.91; <i>p</i>=0.007), increased AD pain NRS score (OR, 1.20; 95% CI, 1.01-1.44; <i>p</i>=0.041) and higher Investigator Global Assessment score (OR, 5.38; 95% CI, 2.07-13.99; <i>p</i>=0.001). Regarding nipple-specific health-related quality of life (HRQoL), 35.8% of patients reported severe impairment in HRQoL due to NE, and 45.3% experienced severe emotional distress.</p><p><strong>Conclusion: </strong>Although the area affected by NE is small, dermatologists should be aware of its association with severe AD characteristics, and its significant impact on patient HRQoL.</p>","PeriodicalId":94298,"journal":{"name":"Annals of dermatology","volume":"37 6","pages":"336-343"},"PeriodicalIF":1.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12715881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145663154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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Annals of dermatology
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