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Oculocutaneous albinism type 1B associated with allelic combination of a risk haplotype 1B型皮肤白化病与风险单倍型等位基因组合相关。
IF 4.6 Pub Date : 2025-06-01 DOI: 10.1016/j.jdermsci.2025.04.007
Nikoletta Nagy , Aliasgari Abdolreza , Margit Pál , Barbara Anna Bokor , Amarilla Barcsay-Veres , Noémi Ágnes Varga , Márta Medvecz , Viktória Szabó , Márta Széll
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引用次数: 0
SERPINA12 variants harboured in Nagashima-type palmoplantar keratoderma: Potential inflammatory characteristics 长岛型掌足底角化病中携带的SERPINA12变异:潜在的炎症特征
IF 4.6 Pub Date : 2025-06-01 DOI: 10.1016/j.jdermsci.2025.04.009
Cheng Zhang , Yumeng Wang , Qiaoyu Cao , Hongsong Ge , Xinjie Lin , Xinyi Wang , Anqi Zhao , Wei He , Qin Zeng , Haisheng Huang , Qin Yan , Ming Li
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引用次数: 0
Landscapes of gut microbiome and metabolic signatures in vitiligo patients with co-morbid emotional distress 伴有共病情绪困扰的白癜风患者肠道微生物群和代谢特征的景观。
IF 4.6 Pub Date : 2025-06-01 DOI: 10.1016/j.jdermsci.2025.04.011
Mei Luan , Binyue Mao , Yixin Zhao , Jianan Chen , Pengju Yang , Weizhe Li , Hao Lei , Yi Yang , Wenwan Chang , Kuanhou Mou , Pan Li

Background

Vitiligo is a depigmentation disorder frequently associated with emotional distress; however, the precise mechanisms underlying this co-morbidity remain unclear.

Objective

This study aims to investigate whether gut dysbiosis and gut metabolites contributes to emotional distress in patients with vitiligo.

Methods

Depression and anxiety were assessed using the Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7, respectively. Totally enrolled 28 vitiligo patients were diagnosed with depression or anxiety (VWD), 44 without such conditions (VTD), and 37 healthy controls (HC). Stool samples were analyzed using 16S rRNA gene sequencing and liquid chromatography triple quadrupole tandem mass spectrometry.

Results

The intestinal flora of VWD group changed significantly with reduced α-diversity. The β-diversity varied among groups. Megasphaera and Anaerostipes increased in the VWD group, whereas Bilophila etc. decreased. Linear Discriminant Analysis Effect Size revealed Lachnoclostridium as a representative flora in the VWD and Faecalibacterium as a representative flora in the VTD. Metabolites such as L-glutamic acid and indole were lower in the VWD group than in the HC, while oleamide, cuminaldehyde, and taurine were higher in the VWD with VTD group. Lachnoclostridium negatively correlated with indole and L-glutamic acid. This study identified notable variations in pathways involved in the biosynthesis of phenylalanine, tyrosine, and tryptophan bile secretion, GABAergic synapses, and taurine and hypotaurine metabolism between the VWD and HC groups.

Conclusion

Specific fecal microbes and metabolites may contribute to the pathogenesis of VWD. These findings provide a novel perspective for addressing emotional distress in patients with vitiligo by targeting the gut-brain-skin axis.
背景:白癜风是一种色素脱失性疾病,通常与情绪困扰有关;然而,这种合并症的确切机制尚不清楚。目的:本研究旨在探讨肠道生态失调和肠道代谢物是否与白癜风患者的情绪困扰有关。方法:分别使用患者健康问卷-9和广泛性焦虑障碍-7对抑郁和焦虑进行评估。共有28例白癜风患者被诊断为抑郁或焦虑(VWD), 44例无抑郁或焦虑(VTD), 37例健康对照(HC)。粪便样品采用16S rRNA基因测序和液相色谱三重四极杆串联质谱分析。结果:VWD组肠道菌群变化明显,α-多样性降低。β-多样性在不同群体间存在差异。VWD组巨噬菌和厌氧菌数量增加,嗜菌等数量减少。线性判别分析效应大小显示Lachnoclostridium是VWD的代表菌群,Faecalibacterium是VTD的代表菌群。VWD组的代谢产物如l -谷氨酸和吲哚低于HC组,而VWD合并VTD组的油酰胺、茴香醛和牛磺酸高于HC组。Lachnoclostridium与吲哚和l -谷氨酸呈负相关。本研究发现,在VWD组和HC组之间,涉及苯丙氨酸、酪氨酸和色氨酸的生物合成、gaba能突触以及牛磺酸和次牛磺酸代谢的途径存在显著差异。结论:特定的粪便微生物和代谢物可能参与了VWD的发病机制。这些发现为针对肠道-脑-皮肤轴治疗白癜风患者的情绪困扰提供了一个新的视角。
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引用次数: 0
The role of PPARs family members in acne ppar家族成员在痤疮中的作用。
IF 4.6 Pub Date : 2025-05-23 DOI: 10.1016/j.jdermsci.2025.04.003
Shaoyang Zhang , Yating Yang , Li Yang, Fangyu Meng, Yizhe Mu, Yuhang Yuan, Yuan Zhang
Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that play a crucial role in the genetic regulation of lipid metabolism and energy homeostasis. There is increasing evidence to suggest that PPARs may have a significant impact on the development and progression of acne, including its role in regulating lipid production, inhibiting keratinocyte proliferation, and reducing acne-related inflammation. As such, PPARs present themselves as promising therapeutic targets for both the prevention and treatment of acne. This article provides an overview of the role of PPARs in the pathological processes underlying acne, with particular emphasis on inflammation and lipid regulation.
过氧化物酶体增殖体激活受体(PPARs)是配体激活的转录因子,在脂质代谢和能量稳态的遗传调控中起着至关重要的作用。越来越多的证据表明,ppar可能对痤疮的发生和发展有重要影响,包括其调节脂质产生、抑制角化细胞增殖和减少痤疮相关炎症的作用。因此,ppar作为预防和治疗痤疮的有希望的治疗靶点。本文概述了ppar在痤疮病理过程中的作用,特别强调炎症和脂质调节。
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引用次数: 0
PRRX1 is a key regulator in the phenotypic transition between human normal dermal and keloid fibroblasts PRRX1是人类正常真皮和瘢痕疙瘩成纤维细胞表型转换的关键调节因子。
IF 4.6 Pub Date : 2025-05-16 DOI: 10.1016/j.jdermsci.2025.05.002
Shuqian Dou , Fengyu Zhang , Yongjing He , Pan Du , Yue Deng , Mingkun Shao , Guoxun Yang , Kongjia Wu , Yueqin Zeng , Cheng Peng , Wenjun Liu

Background

Scarring after skin trauma is a major clinical challenge, as it affects patients’ appearance and function.

Objective

Given that human foetal skin possesses scarless wound healing ability, we aimed to understand the differences among human foetal skin, postnatal skin, and keloid tissue to find out the key factors affecting wound healing outcome.

Methods

We used spatial transcriptomics (ST), histological imaging, and other methods to investigate the cellular and molecular characteristics underlying scarless healing by comparing these skin types.

Results

We identified histological and cellular differences among these samples, including the extracellular matrix, hair follicles, stem cells, and immune cells. Significant heterogeneity was found in fibroblasts across all samples. Among these fibroblast subpopulations, the proportion of paired related homeobox 1 (PRRX1)-positive fibroblast increased from foetus to postnatal skin (PS) and further in keloids. We validated PRRX1’s roles in regulating the phenotypic transition between normal and keloid fibroblasts. A three-dimensional human keloid model was used to further confirm its roles at the tissue level.

Conclusions

In summary, our work explores the unique characteristics of foetal skin and identifies an important transcription factor in regulating scarless healing, which provides the translational potential for future clinical treatments aimed at promoting scarless wound healing.
背景:皮肤创伤后瘢痕形成是一个重大的临床挑战,因为它影响患者的外观和功能。目的:鉴于人类胎儿皮肤具有无疤痕的创面愈合能力,我们旨在了解人类胎儿皮肤与出生后皮肤和瘢痕疙瘩组织的差异,找出影响创面愈合结果的关键因素。方法:通过比较这些皮肤类型,我们使用空间转录组学(ST)、组织学成像和其他方法来研究无疤痕愈合背后的细胞和分子特征。结果:我们确定了这些样本之间的组织学和细胞差异,包括细胞外基质、毛囊、干细胞和免疫细胞。在所有样本的成纤维细胞中发现了显著的异质性。在这些成纤维细胞亚群中,配对相关同源盒1 (PRRX1)阳性成纤维细胞的比例从胎儿到出生后皮肤(PS)增加,在瘢痕疙瘩中进一步增加。我们验证了PRRX1在调节正常瘢痕疙瘩成纤维细胞和瘢痕疙瘩成纤维细胞之间的表型转变中的作用。使用三维人体瘢痕疙瘩模型进一步确认其在组织水平上的作用。结论:总之,我们的工作探索了胎儿皮肤的独特特征,并确定了调节无疤痕愈合的重要转录因子,这为未来旨在促进无疤痕伤口愈合的临床治疗提供了转化潜力。
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引用次数: 0
Stratum corneum pH and ceramides: Key regulators and biomarkers of skin barrier function in atopic dermatitis 角质层pH值和神经酰胺:特应性皮炎中皮肤屏障功能的关键调节因子和生物标志物
IF 4.6 Pub Date : 2025-05-01 DOI: 10.1016/j.jdermsci.2025.04.001
Takashi Sakai , Yutaka Hatano
The skin, as the outermost layer of the body, serves as a crucial protective barrier against environmental insults while maintaining homeostasis. Atopic dermatitis (AD), a chronic inflammatory skin disorder characterized by recurrent eczema and type 2 inflammation, affects a significant global population. The pathophysiology of AD is closely linked to skin barrier dysfunction, which contributes to increased permeability, immune dysregulation, and microbial imbalances. Historically, skin barrier research has centered on the stratum corneum (SC) and intercellular lipids within the epidermis, primarily conceptualized through the "brick-and-mortar" model. However, recent advancements have revealed a more intricate interplay among various barrier components. Two key determinants of skin barrier—SC pH and SC ceramides—have gained substantial attention. Elevated SC pH leads to enhanced serine protease activity, impaired lipid metabolism, and microbiome dysbiosis, all of which exacerbate barrier dysfunction and inflammation in AD. Concurrently, alterations in SC ceramide profiles and structures compromise skin barrier function. Emerging evidence underscores the potential of SC pH and ceramides as biomarkers for disease progression and as therapeutic targets for barrier restoration. Advances in lipid analyses and non-invasive pH assessment offer promising prospects for personalized dermatologic interventions. This review explores the complex interactions of SC pH and ceramides in AD pathogenesis, discussing their implications for predicting disease flares, guiding treatment strategies, and identifying novel drug targets. A deeper understanding of these mechanisms could pave the way for next-generation therapeutic approaches in AD and other skin barrier-related disorders.
皮肤,作为身体的最外层,在维持体内平衡的同时,也是抵御环境侵害的重要保护屏障。特应性皮炎(AD)是一种以复发性湿疹和2型炎症为特征的慢性炎症性皮肤病,影响着全球大量人群。AD的病理生理学与皮肤屏障功能障碍密切相关,皮肤屏障功能障碍导致渗透性增加、免疫失调和微生物失衡。从历史上看,皮肤屏障研究主要集中在角质层(SC)和表皮内的细胞间脂质上,主要通过“砖瓦”模型概念化。然而,最近的进展揭示了各种屏障成分之间更复杂的相互作用。皮肤屏障的两个关键决定因素- SC pH和SC神经酰胺-已经获得了大量的关注。SC pH升高导致丝氨酸蛋白酶活性增强,脂质代谢受损,微生物群失调,所有这些都加剧了AD的屏障功能障碍和炎症。同时,SC神经酰胺剖面和结构的改变会损害皮肤屏障功能。新出现的证据强调SC pH和神经酰胺作为疾病进展的生物标志物和屏障恢复的治疗靶点的潜力。脂质分析和非侵入性pH值评估的进展为个性化皮肤病学干预提供了广阔的前景。这篇综述探讨了SC pH和神经酰胺在AD发病机制中的复杂相互作用,讨论了它们在预测疾病爆发、指导治疗策略和确定新的药物靶点方面的意义。对这些机制的深入了解可以为阿尔茨海默病和其他皮肤屏障相关疾病的下一代治疗方法铺平道路。
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引用次数: 0
Immune signatures across different stages of cutaneous squamous cell carcinoma 皮肤鳞状细胞癌不同阶段的免疫特征。
IF 4.6 Pub Date : 2025-05-01 DOI: 10.1016/j.jdermsci.2025.03.002
Laure Favot-Laforge , Elodie Muzotte , Walid Mahfouf , Jerome Rambert , Muriel Cario , François Moisan , Lea Dousset , Hamid-Reza Rezvani
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引用次数: 0
Dupilumab treatment decreases expression of microRNAs related to B cell activation in peripheral blood mononuclear cells of atopic dermatitis patients 杜匹单抗治疗可降低特应性皮炎患者外周血单核细胞中与 B 细胞活化相关的 microRNAs 的表达。
IF 4.6 Pub Date : 2025-05-01 DOI: 10.1016/j.jdermsci.2025.02.004
Kenichiro Matsui , Mariko Ogawa-Momohara , Akira Yokoi , Takuya Takeichi , Kosuke Yoshida , Masami Kitagawa , Tomoki Taki , Chiaki Murase , Yoshinao Muro , Masashi Akiyama
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引用次数: 0
Single-cell and spatial transcriptomic analyses reveal transcriptional cell lineage heterogeneity in extracranial arteriovenous malformation 单细胞和空间转录组学分析揭示了颅外动静脉畸形的转录细胞谱系异质性。
IF 4.6 Pub Date : 2025-05-01 DOI: 10.1016/j.jdermsci.2025.02.005
Yi Sun , Haoyang Xu , Yanze Zhu , Yamin Rao , Xindong Fan , Zhenfeng Wang , Hao Gu , Xiaojie Yue , Xiong Zhao , Lixin Su , Ren Cai

Background

Extracranial arteriovenous malformations (eAVMs) are rare congenital vascular anomalies consisting of abnormal artery-vein bypass with no intervening capillary network, and can lead to disability and death. The critical genetic determination factors and key transcriptional pathways of the eAVMs genesis process are still unclear.

Objective

To generate an overview of the molecular information within eAVMs at the single-cell level.

Methods

We performed single-cell RNA sequencing (scRNA-seq) on nine samples of eAVMs receiving a confirmatory histopathologic evaluation from a board-certified dermatopathologist and two nonlesional tissue sample controls. 10x Visium spatial transcriptomics (ST) was performed on one eAVM to spatially localize heterogeneous cells and profile the gene expression dynamics of the cells in their morphological context. The scRNA-seq and ST data were integrated and analyzed to further query for spatially restricted mapping of intrapopulation heterogeneous cells.

Results

We identified different cell states of endothelial cells (ECs), perivascular cells and immune cells in eAVMs, uncovered the presence of MAFB+ nidus ECs, characterized mesenchymal activation in ECs, and identified transcriptional variation within perivascular cells and the presence of smooth muscle–like pericytes in eAVMs. Dysregulated cell to cell interactions among ECs, perivascular cells and immune cells that are associated with eAVMs, including those involving MDK, VEGF, ANGPT, SEMA3 and GALECTIN-9 were cataloged. Together, our results depicted the heterogeneity underlying cell function and interaction of eAVMs at a single-cell resolution.

Conclusion

We present a comprehensive picture of the cell-resolution atlas that describes the transcriptomic heterogeneity underlying cell function and interaction in eAVMs.
背景:颅外动静脉畸形(eAVMs)是一种罕见的先天性血管异常,包括异常的动静脉旁路,没有介入毛细血管网络,可导致残疾和死亡。eAVMs发生过程的关键遗传决定因子和关键转录途径尚不清楚。目的:在单细胞水平上对eAVMs的分子信息进行综述。方法:我们对9个eems样本进行了单细胞RNA测序(scRNA-seq),这些样本接受了来自委员会认证的皮肤病理学家和两个非病变组织样本对照的确认性组织病理学评估。在一个eAVM上进行10x Visium空间转录组学(ST),以空间定位异质细胞并描绘细胞在其形态背景下的基因表达动态。将scRNA-seq和ST数据进行整合和分析,以进一步查询群体内异质细胞的空间限制性定位。结果:我们鉴定了eAVMs中内皮细胞(ECs)、血管周围细胞和免疫细胞的不同细胞状态,揭示了MAFB+ 病灶内皮细胞的存在,表征了内皮细胞的间充质活化,鉴定了eAVMs中血管周围细胞的转录变异和平滑肌样周细胞的存在。与eAVMs相关的内皮细胞、血管周围细胞和免疫细胞间相互作用失调,包括涉及MDK、VEGF、ANGPT、SEMA3和GALECTIN-9的细胞间相互作用失调。总之,我们的结果在单细胞分辨率上描述了细胞功能和eavm相互作用的异质性。结论:我们提供了一个全面的细胞分辨率图谱,描述了eavm中细胞功能和相互作用的转录组异质性。
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引用次数: 0
P300 regulates Melanophilin expression by modulating TFAP2A binding through histone acetylation P300通过组蛋白乙酰化调节TFAP2A结合调节嗜黑素的表达
IF 4.6 Pub Date : 2025-05-01 DOI: 10.1016/j.jdermsci.2025.04.002
Chan Song Jo, Zhao Hairu, Gyu Cheol Baek, Eun Jeong Lee, Chang Mo You, Jae Sung Hwang

Background

Melanophilin is an effector protein that interacts with Rab27a and Myosin Va and regulates melanosome transport in melanocytes. Type 3 Griscelli syndrome, a mutation in Mlph gene, is characterized by partial pigment dilution, without any associated systemic problems. P300 plays roles in histone acetylation and changes chromatin state. There has been considerable interest in epigenetic regulation of melanocytes. However, epigenetic control of Mlph expression is still poorly understood.

Objectives

We investigated the underlying mechanisms by which P300 controls Mlph expression by histone acetylation.

Methods

siRNA transfection was performed to knock down gene expression. We used numerous methods, including western blotting, quantitative PCR (qPCR), co-immunoprecipitation (co-IP), and chromatin immunoprecipitation (ChIP), to identify the mechanisms of epigenetic regulation via P300.

Results

Perinuclear aggregation of melanosome is induced and Mlph expression is decreased by knockdown of P300. In this process, TFAP2A acts as a transcription factor and regulates Mlph transcription. Knockdown of P300 decreased TFAP2A binding to intron region of Mlph and H3K27ac level and then finally reduced Mlph expression. Our study revealed that P300 facilitates an open chromatin state through acetylation of H3K27 and TFAP2A could regulate Mlph expression by binding to the intron 1 region of Mlph.

Conclusion

Mlph expression is regulated by epigenetic regulation via P300 in melanocytes. These findings provide new insights into the epigenetic mechanism of melanosome transport.
嗜黑素是一种与Rab27a和Myosin Va相互作用并调节黑素细胞中黑素小体运输的效应蛋白。3型Griscelli综合征是一种Mlph基因突变,其特征是色素部分稀释,没有任何相关的全身问题。P300参与组蛋白乙酰化,改变染色质状态。黑素细胞的表观遗传调控已经引起了相当大的兴趣。然而,对Mlph表达的表观遗传控制仍知之甚少。目的研究P300通过组蛋白乙酰化调控Mlph表达的潜在机制。方法转染sirna敲低基因表达。我们使用了多种方法,包括western blotting,定量PCR (qPCR),共免疫沉淀(co-IP)和染色质免疫沉淀(ChIP),以确定P300的表观遗传调控机制。结果敲低P300可诱导黑素小体核聚集,降低Mlph表达。在这个过程中,TFAP2A作为转录因子,调控Mlph的转录。P300的敲低降低了TFAP2A与Mlph内含子区的结合,降低了H3K27ac水平,最终降低了Mlph的表达。我们的研究发现P300通过H3K27的乙酰化促进染色质开放状态,TFAP2A通过结合Mlph的内含子1区调节Mlph的表达。结论黑色素细胞中mlph的表达受P300的表观遗传调控。这些发现为黑素体转运的表观遗传机制提供了新的见解。
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引用次数: 0
期刊
Journal of dermatological science
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