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Late inflammatory monocytes define circulatory immune dysregulation observed in skin microbiome-stratified atopic dermatitis 晚期炎性单核细胞确定了皮肤微生物分层特应性皮炎中观察到的循环免疫失调
IF 4.6 Pub Date : 2023-12-01 DOI: 10.1016/j.jdermsci.2023.10.006
Celine Chua , Raman Sethi , Jocelyn Ong , Jing hui Low , Yik W. Yew , Alicia Tay , Shanshan W. Howland , Florent Ginhoux , Jinmiao Chen , John E.A. Common , Anand K. Andiappan
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引用次数: 0
A20 ameliorates advanced glycation end products-induced melanogenesis by inhibiting NLRP3 inflammasome activation in human dermal fibroblasts A20通过抑制人真皮成纤维细胞中NLRP3炎症小体的激活,改善晚期糖基化终产物诱导的黑色素生成。
IF 4.6 Pub Date : 2023-11-01 DOI: 10.1016/j.jdermsci.2023.09.002
Mengyao Wang , Xianyin Huang , Mengting Ouyang , Jingjing Lan, Jingqian Huang, Hongpeng Li, Wei Lai, Yifeng Gao, Qingfang Xu

Background

Advanced glycation end products (AGEs) promote melanogenesis through activating NLRP3 inflammasome in fibroblasts. Although A20 has been highlighted to inhibit NLRP3 inflammasome activation, its roles and mechanisms remain elusive in photoaging-associated pigmentation.

Objectives

To determine the significance of fibroblast A20 in AGEs-induced NLRP3 inflammasome activation and pigmentation.

Methods

The correlation between A20 and AGEs or melanin was studied in sun-exposed skin and lesions of melasma and solar lentigo. We then investigated A20 level in AGEs-treated fibroblast and the effect of fibroblast A20 overexpression or knockdown on AGEs-BSA-induced NLRP3 inflammasome activation and pigmentation, respectively. Finally, the severity of NLRP3 inflammasome activation and pigmentation was evaluated after mice were injected intradermally with A20-overexpression adeno-associated virus and AGEs-BSA.

Results

Dermal A20 expression was decreased and exhibited negative correlation with either dermal AGEs deposition or epidermal melanin level in sun-exposed skin and pigmentary lesions. Moreover, both AGEs-BSA and AGEs-collagen robustly decreased A20 expression via binding to RAGE in fibroblasts. Further, A20 overexpression or depletion significantly decreased or augmented AGEs-BSA-induced activation of NF-κB pathway and NLRP3 inflammasome and IL-18 production and secretion in fibroblasts, respectively. Importantly, fibroblast A20 potently repressed AGEs-BSA-stimulated melanin content,tyrosinase activity,and expression of microphthalmia-associated transcription factor and tyrosinase in melanocytes. Particularly, fibroblast A20 significantly abrogated AGEs-BSA-promoted melanogenesis in ex vivo skin and mouse models. Additionally, fibroblast A20 inhibited AGEs-BSA-activated MAPKs in melanocytes and the epidermis of ex vivo skin.

Conclusions

Fibroblast A20 suppresses AGEs-stimulate melanogenesis in photoaging-associated hyperpigmentation disorders by inhibiting NLRP3 inflammasome activation.

背景:晚期糖基化终产物(AGEs)通过激活成纤维细胞中的NLRP3炎症小体促进黑色素生成。尽管A20已被强调可抑制NLRP3炎症小体激活,但其在光老化相关色素沉着中的作用和机制仍然难以捉摸。目的:确定成纤维细胞A20在AGEs诱导的NLRP3炎症小体活化和色素沉着中的意义。方法:对日光照射皮肤及黄褐斑、雀斑病变中A20与AGEs或黑色素的相关性进行研究。然后,我们分别研究了AGEs处理的成纤维细胞中A20水平以及成纤维细胞A20过表达或敲低对AGEs-BSA诱导的NLRP3炎症小体激活和色素沉着的影响。最后,在小鼠皮内注射A20过表达腺相关病毒和AGEs-BSA后,评估NLRP3炎症小体激活和色素沉着的严重程度。结果:皮肤A20表达降低,并与暴露在阳光下的皮肤和色素病变中的真皮AGEs沉积或表皮黑色素水平呈负相关。此外,AGEs BSA和AGEs胶原都通过与成纤维细胞中的RAGE结合而显著降低A20的表达。此外,A20过表达或缺失分别显著降低或增强了成纤维细胞中AGEs-BSA诱导的NF-κB通路和NLRP3炎症小体的激活以及IL-18的产生和分泌。重要的是,成纤维细胞A20有效抑制AGEs-BSA刺激的黑色素含量、酪氨酸酶活性以及黑色素细胞中小眼相关转录因子和酪氨酸酶的表达。特别地,在离体皮肤和小鼠模型中,成纤维细胞A20显著消除AGEs-BSA促进黑色素生成。此外,成纤维细胞A20抑制黑素细胞和离体皮肤表皮中的AGEs-BSA激活的MAPKs。结论:成纤维细胞A20通过抑制NLRP3炎症小体激活,抑制AGEs刺激光老化相关色素沉着障碍中的黑色素生成。
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引用次数: 0
Molecular insights of human skin epidermal and dermal aging 人类皮肤表皮和真皮老化的分子洞察力
IF 4.6 Pub Date : 2023-11-01 DOI: 10.1016/j.jdermsci.2023.08.006
Taihao Quan

Human skin is the most widespread and abundant type of tissue in the human body. With the passage of time, most of our organs, including a substantial part of the skin, tend to undergo a gradual thinning or decrease in size. As we age, there is a gradual and progressive reduction in the thickness of both the epidermis and dermis layers of our skin. This is primarily attributed to the decline of epidermal stem cells and the loss of dermal collagen, which is the most abundant protein in the human body. Age-related alterations of the epidermis and dermis impair skin structure/function and create a tissue microenvironment that promotes age-related skin diseases, such as impaired skin barrier, delayed wound healing, and skin cancer development. This review will examine the current body of literature pertaining to our knowledge of skin epidermal and dermal aging.

皮肤是人体中分布最广、数量最多的组织类型。随着时间的推移,我们的大部分器官,包括相当一部分皮肤,都会逐渐变薄或缩小。随着年龄的增长,皮肤表皮层和真皮层的厚度会逐渐减少。这主要归因于表皮干细胞的减少和真皮胶原蛋白的流失,而胶原蛋白是人体中最丰富的蛋白质。表皮层和真皮层与年龄有关的变化会损害皮肤结构/功能,并形成一种组织微环境,促进与年龄有关的皮肤疾病,如皮肤屏障受损、伤口愈合延迟和皮肤癌的发生。本综述将研究目前有关皮肤表皮和真皮老化知识的文献。
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引用次数: 3
Transient receptor potential vanilloid 4 promotes cutaneous wound healing by regulating keratinocytes and fibroblasts migration and collagen production in fibroblasts in a mouse model 在小鼠模型中,瞬时受体电位香草素4通过调节角质形成细胞和成纤维细胞的迁移以及成纤维细胞中胶原的产生来促进皮肤伤口愈合。
IF 4.6 Pub Date : 2023-11-01 DOI: 10.1016/j.jdermsci.2023.10.002
Bayarmaa Taivanbat , Sahori Yamazaki , Bolor Nasanbat , Akihiko Uchiyama , Syahla Nisaa Amalia , Munkhjargal Nasan-Ochir , Yuta Inoue , Mai Ishikawa , Keiji Kosaka , Akiko Sekiguchi , Sachiko Ogino , Yoko Yokoyama , Ryoko Torii , Mari Hosoi , Koji Shibasaki , Sei-ichiro Motegi

Background

Transient receptor potential vanilloid 4 (TRPV4), a cation ion channel, is expressed in different cells, and it regulates the development of different diseases. We recently found a high TRPV4 expression in the wounded skin area. However, the role of TRPV4 in cutaneous wound healing is unknown.

Objective

To investigate the role of TRPV4 in cutaneous wound healing in a mouse model.

Methods

Skin wound healing experiment and histopathological studies were performed between WT and TRPV4 KO mice. The effect of TRPV4 antagonist and agonist on cell migration, proliferation, and differentiation were examined in vitro.

Results

TRPV4 expression was enhanced in wounded area in the skin. TRPV4 KO mice had impaired cutaneous wound healing compared with the WT mice. Further, they had significantly suppressed re-epithelialization and formation of granulation tissue, amount of collagen deposition, and number of α-SMA-positive myofibroblasts in skin wounds. qPCR revealed that the KO mice had decreased mRNA expression of COL1A1 and ACTA2 in skin wounds. In vitro, treatment with selective TRPV4 antagonist suppressed migrating capacity, scratch stimulation enhanced the expression of phospho-ERK in keratinocytes, and TGF-β stimulation enhanced the mRNA expression of COL1A1 and ACTA2 in fibroblasts. Selective TRPV4 agonist suppressed cell migration in keratinocytes, and did not enhance proliferation and migration, but promoted differentiation in fibroblasts.

Conclusion

TRPV4 mediates keratinocytes and fibroblasts migration and increases collagen deposition in the wound area, thereby promoting cutaneous wound healing.

背景:瞬时受体电位香草素4(TRPV4)是一种阳离子通道,在不同的细胞中表达,它调节不同疾病的发展。我们最近发现TRPV4在受伤的皮肤区域有高表达。然而,TRPV4在皮肤伤口愈合中的作用尚不清楚。目的:探讨TRPV4在小鼠皮肤创伤愈合中的作用。方法:在WT和TRPV4 KO小鼠之间进行皮肤创伤愈合实验和组织病理学研究。体外检测TRPV4拮抗剂和激动剂对细胞迁移、增殖和分化的影响。结果:TRPV4在皮肤损伤区表达增强。与WT小鼠相比,TRPV4 KO小鼠的皮肤伤口愈合受损。此外,它们显著抑制了皮肤伤口中上皮再上皮化和肉芽组织的形成、胶原沉积量和α-SMA阳性肌成纤维细胞的数量。qPCR显示KO小鼠在皮肤伤口中COL1A1和ACTA2的mRNA表达降低。在体外,用选择性TRPV4拮抗剂处理抑制了迁移能力,划痕刺激增强了角质形成细胞中磷酸ERK的表达,TGF-β刺激增强了成纤维细胞中COL1A1和ACTA2的mRNA表达。选择性TRPV4激动剂抑制角质形成细胞的细胞迁移,不增强增殖和迁移,但促进成纤维细胞的分化。结论:TRPV4介导角质形成细胞和成纤维细胞迁移,增加伤口胶原沉积,从而促进皮肤伤口愈合。
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引用次数: 0
Presence of microfibril associated glycoprotein 4 and type V collagen and the possible absence of fibrillin-1 in bead-like structures in elastofibroma 弹性纤维瘤中微纤维相关糖蛋白4和V型胶原的存在以及珠状结构中可能不存在原纤维蛋白-1。
IF 4.6 Pub Date : 2023-11-01 DOI: 10.1016/j.jdermsci.2023.09.005
Haruto Nishida , Takako Sasaki , Yuki Taga , Yusuke Murasawa , Siro Simizu , Shigeto Matsushita , Zenzo Isogai , Shunji Hattori , Tsutomu Daa , Nobuo Nagamine , Akihiro Sekine , Sakuhei Fujiwara
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引用次数: 0
Painting and dissecting Epidermolysis Bullosa Simplex-associated keratin aggregates 绘制和解剖大疱性表皮松解症相关角蛋白聚集体。
IF 4.6 Pub Date : 2023-11-01 DOI: 10.1016/j.jdermsci.2023.08.007
Katrin Rietscher , Melanie Homberg , Ilya Kovalenko , Jonathan Z. Sexton , Robert H. Rice , Cristina Has , M. Bishr Omary , Thomas M. Magin
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引用次数: 0
In vitro evaluation of Neosetophomone B inducing apoptosis in cutaneous T cell lymphoma by targeting the FOXM1 signaling pathway 靶向FOXM1信号通路诱导皮肤T细胞淋巴瘤细胞凋亡的体外评价。
IF 4.6 Pub Date : 2023-11-01 DOI: 10.1016/j.jdermsci.2023.10.001
Shilpa Kuttikrishnan , Tariq Masoodi , Fareed Ahmad , Gulab Sher , Kirti S. Prabhu , Jericha M. Mateo , Joerg Buddenkotte , Tamam El-Elimat , Nicholas H. Oberlies , Cedric J. Pearce , Ajaz A. Bhat , Feras Q. Alali , Martin Steinhoff , Shahab Uddin

Background

Cutaneous T cell lymphoma (CTCL) is a T cell-derived non-Hodgkin lymphoma primarily affecting the skin, with treatment posing a significant challenge and low survival rates.

Objective

In this study, we investigated the anti-cancer potential of Neosetophomone B (NSP-B), a fungal-derived secondary metabolite, on CTCL cell lines H9 and HH.

Methods

Cell viability was measured using Cell counting Kit-8 (CCK8) assays. Apoptosis was measured by annexin V/PI dual staining. Immunoblotting was performed to examine the expression of proteins. Applied Biosystems' high-resolution Human Transcriptome Array 2.0 was used to examine gene expression.

Results

NSP-B induced apoptosis in CTCL cells by activating mitochondrial signaling pathways and caspases. We observed downregulated expression of BUB1B, Aurora Kinases A and B, cyclin-dependent kinases (CDKs) 4 and 6, and polo-like kinase 1 (PLK1) in NSP-B treated cells, which was further corroborated by Western blot analysis. Notably, higher expression levels of these genes showed reduced overall and progression-free survival in the CTCL patient cohort. FOXM1 and BUB1B expression exhibited a dose-dependent reduction in NSP-B-treated CTCL cells.FOXM1 silencing decreased cell viability and increased apoptosis via BUB1B downregulation. Moreover, NSP-B suppressed FOXM1-regulated genes, such as Aurora Kinases A and B, CDKs 4 and 6, and PLK1. The combined treatment of Bortezomib and NSP-B showed greater efficacy in reducing CTCL cell viability and promoting apoptosis compared to either treatment alone.

Conclusion

Our findings suggest that targeting the FOXM1 pathway may provide a promising therapeutic strategy for CTCL management, with NSP-B offering significant potential as a novel treatment option.

背景:皮肤T细胞淋巴瘤(CTCL)是一种主要影响皮肤的T细胞衍生的非霍奇金淋巴瘤,其治疗具有重大挑战性和低生存率。目的:在本研究中,我们研究了真菌衍生的次级代谢产物新毛霉素B(NSP-B)对CTCL细胞系H9和HH的抗癌潜力。方法:使用细胞计数Kit-8(CCK8)测定细胞活力。膜联蛋白V/PI双染色法检测细胞凋亡。进行免疫印迹以检测蛋白质的表达。应用生物系统公司的高分辨率人类转录组阵列2.0用于检测基因表达。结果:NSP-B通过激活线粒体信号通路和胱天蛋白酶诱导CTCL细胞凋亡。我们观察到,在NSP-B处理的细胞中,BUB1B、Aurora激酶A和B、细胞周期蛋白依赖性激酶(CDKs)4和6以及polo-like激酶1(PLK1)的表达下调,Western印迹分析进一步证实了这一点。值得注意的是,在CTCL患者队列中,这些基因的高表达水平显示出总体生存率和无进展生存率降低。FOXM1和BUB1B的表达在NSP-B处理的CTCL细胞中表现出剂量依赖性降低。FOXM1沉默通过BUB1B下调降低细胞活力并增加细胞凋亡。此外,NSP-B抑制FOXM1调节的基因,如极光激酶A和B、CDKs 4和6以及PLK1。与单独治疗相比,硼替佐米和NSP-B的联合治疗在降低CTCL细胞活力和促进细胞凋亡方面显示出更大的疗效。结论:我们的研究结果表明,靶向FOXM1通路可能为CTCL管理提供一种有前景的治疗策略,NSP-B作为一种新的治疗选择具有重要的潜力。
{"title":"In vitro evaluation of Neosetophomone B inducing apoptosis in cutaneous T cell lymphoma by targeting the FOXM1 signaling pathway","authors":"Shilpa Kuttikrishnan ,&nbsp;Tariq Masoodi ,&nbsp;Fareed Ahmad ,&nbsp;Gulab Sher ,&nbsp;Kirti S. Prabhu ,&nbsp;Jericha M. Mateo ,&nbsp;Joerg Buddenkotte ,&nbsp;Tamam El-Elimat ,&nbsp;Nicholas H. Oberlies ,&nbsp;Cedric J. Pearce ,&nbsp;Ajaz A. Bhat ,&nbsp;Feras Q. Alali ,&nbsp;Martin Steinhoff ,&nbsp;Shahab Uddin","doi":"10.1016/j.jdermsci.2023.10.001","DOIUrl":"10.1016/j.jdermsci.2023.10.001","url":null,"abstract":"<div><h3>Background</h3><p>Cutaneous T cell lymphoma<span> (CTCL) is a T cell-derived non-Hodgkin lymphoma primarily affecting the skin, with treatment posing a significant challenge and low survival rates.</span></p></div><div><h3>Objective</h3><p>In this study, we investigated the anti-cancer potential of Neosetophomone B (NSP-B), a fungal-derived secondary metabolite, on CTCL cell lines H9 and HH.</p></div><div><h3>Methods</h3><p><span><span>Cell viability was measured using Cell counting Kit-8 (CCK8) assays. </span>Apoptosis<span> was measured by annexin V/PI dual staining. Immunoblotting was performed to examine the expression of proteins. Applied Biosystems' high-resolution Human </span></span>Transcriptome Array 2.0 was used to examine gene expression.</p></div><div><h3>Results</h3><p><span><span>NSP-B induced apoptosis in CTCL cells by activating mitochondrial signaling pathways and </span>caspases<span>. We observed downregulated expression of BUB1B, Aurora Kinases A and B, cyclin-dependent kinases (CDKs) 4 and 6, and polo-like kinase 1 (PLK1) in NSP-B treated cells, which was further corroborated by Western blot analysis. Notably, higher expression levels of these genes showed reduced overall and progression-free survival in the CTCL patient cohort. FOXM1 and BUB1B expression exhibited a dose-dependent reduction in NSP-B-treated CTCL cells.FOXM1 silencing decreased cell viability and increased apoptosis via BUB1B downregulation. Moreover, NSP-B suppressed FOXM1-regulated genes, such as Aurora Kinases A and B, CDKs 4 and 6, and PLK1. The combined treatment of </span></span>Bortezomib and NSP-B showed greater efficacy in reducing CTCL cell viability and promoting apoptosis compared to either treatment alone.</p></div><div><h3>Conclusion</h3><p>Our findings suggest that targeting the FOXM1 pathway may provide a promising therapeutic strategy for CTCL management, with NSP-B offering significant potential as a novel treatment option.</p></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49686677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Invention of automated numerical algorithm adopting binarization for the evaluation of scalp hair coverage: An image analysis providing a substitute for phototrichogram and global photography assessment for hair diseases 采用二值化评估头皮毛发覆盖率的自动数值算法的发明:一种图像分析,为毛发疾病的光富集图和全局摄影评估提供了替代品。
IF 4.6 Pub Date : 2023-11-01 DOI: 10.1016/j.jdermsci.2023.09.003
Masaya Takagi , Misaki Kinoshita-Ise , Masahiro Fukuyama , Saori Nishikawa , Mami Miyoshi , Takaki Sugimoto , Masako Yamazaki , Masashi Ogo , Manabu Ohyama

Background

The efficacy of therapeutic modalities for hair disease can be evaluated globally by photo assessment and more precisely by phototrichogram (PTG). However, the latter procedure is laborious, time consuming, subject to inter-observer variation, and requires hair clipping.

Objective

To establish an automated and patient/investigator friendly methodology enabling quantitative hair amount evaluation for daily clinical practice.

Methods

A novel automated numerical algorithm (aNA) adopting digital image binarization (i.e., black and white color conversion) was invented to evaluate hair coverage and measure PTG parameters in scalp images. Step-by-step improvement of aNA was attempted through comparative analyses of the data obtained respectively by the novel approach and conventional PTG/global photography assessment (GPA).

Results

For measuring scalp hair coverage, the initial version of aNA generally agreed with the cumulative hair diameter as assessed using PTG, showing a coefficient of 0.60. However, these outcomes were influenced by the angle of hair near the parting line. By integrating an angle compensation formula, the standard deviation of aNA data decreased from 5.7% to 1.2%. Consequently, the coefficient of determination for hair coverage calculated using the modified aNA and cumulative hair diameter assessed by PTG increased to 0.90. Furthermore, the change in hair coverage as determined by the modified aNA protocol correlated well with changes in the GPA score of images obtained using clinical trials.

Conclusion

The novel aNA method provides a valuable tool for enabling simple and accurate evaluation of hair growth and volume for clinical trials and for treatment of hair disease.

背景:毛发疾病的治疗方法的疗效可以通过照片评估进行全球评估,更准确地说可以通过光富集图(PTG)进行评估。然而,后一种程序费力、耗时、受观察者之间变化的影响,并且需要修剪头发。目的:建立一种自动化、患者/研究者友好的方法,为日常临床实践提供定量毛发量评估。方法:提出一种新的采用数字图像二值化(即黑白颜色转换)的自动数值算法(aNA)来评估头皮图像中的头发覆盖率和测量PTG参数。通过对新方法和传统PTG/全局摄影评估(GPA)分别获得的数据进行比较分析,尝试逐步改善aNA。结果:对于测量头皮毛发覆盖率,aNA的初始版本通常与使用PTG评估的累积毛发直径一致,显示系数为0.60。然而,这些结果受到分模线附近头发角度的影响。通过整合角度补偿公式,aNA数据的标准偏差从5.7%下降到1.2%。因此,使用修正后的aNA和PTG评估的累积头发直径计算的头发覆盖率的确定系数增加到0.90。此外,由改良的aNA方案确定的头发覆盖率的变化与使用临床试验获得的图像的GPA得分的变化良好相关。结论:新的aNA方法为临床试验和头发疾病的治疗提供了一种有价值的工具,可以简单准确地评估头发的生长和体积。
{"title":"Invention of automated numerical algorithm adopting binarization for the evaluation of scalp hair coverage: An image analysis providing a substitute for phototrichogram and global photography assessment for hair diseases","authors":"Masaya Takagi ,&nbsp;Misaki Kinoshita-Ise ,&nbsp;Masahiro Fukuyama ,&nbsp;Saori Nishikawa ,&nbsp;Mami Miyoshi ,&nbsp;Takaki Sugimoto ,&nbsp;Masako Yamazaki ,&nbsp;Masashi Ogo ,&nbsp;Manabu Ohyama","doi":"10.1016/j.jdermsci.2023.09.003","DOIUrl":"10.1016/j.jdermsci.2023.09.003","url":null,"abstract":"<div><h3>Background</h3><p><span>The efficacy of therapeutic modalities for hair disease can be evaluated globally by photo assessment and more precisely by </span><u>p</u>hoto<u>t</u>richo<u>g</u>ram (PTG). However, the latter procedure is laborious, time consuming, subject to inter-observer variation, and requires hair clipping.</p></div><div><h3>Objective</h3><p>To establish an automated and patient/investigator friendly methodology enabling quantitative hair amount evaluation for daily clinical practice.</p></div><div><h3>Methods</h3><p>A novel <u>a</u>utomated <u>n</u>umerical <u>a</u><span>lgorithm (aNA) adopting digital image binarization (i.e., black and white color conversion) was invented to evaluate hair coverage and measure PTG parameters in scalp images. Step-by-step improvement of aNA was attempted through comparative analyses of the data obtained respectively by the novel approach and conventional PTG/</span><u>g</u>lobal <u>p</u>hotography <u>a</u>ssessment (GPA).</p></div><div><h3>Results</h3><p><span>For measuring scalp hair coverage, the initial version of aNA generally agreed with the cumulative hair diameter as assessed using PTG, showing a coefficient of 0.60. However, these outcomes were influenced by the angle of hair near the parting line. By integrating an angle compensation formula, the standard deviation of aNA data decreased from 5.7% to 1.2%. Consequently, the coefficient of determination for hair coverage calculated using the modified aNA and cumulative hair diameter assessed by PTG increased to 0.90. Furthermore, the change in hair coverage as determined by the modified aNA protocol correlated well with changes in the GPA score of images obtained using </span>clinical trials.</p></div><div><h3>Conclusion</h3><p>The novel aNA method provides a valuable tool for enabling simple and accurate evaluation of hair growth and volume for clinical trials and for treatment of hair disease.</p></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41126188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Management of the human hair follicle microbiome by a synthetic odorant 通过合成气味剂管理人类毛囊微生物组。
IF 4.6 Pub Date : 2023-11-01 DOI: 10.1016/j.jdermsci.2023.09.006
Janin Edelkamp , Marta B. Lousada , Daniela Pinto , Jérémy Chéret , Francesco Maria Calabrese , Francisco Jiménez , Hanieh Erdmann , Julia Wessel , Bodo Phillip , Maria De Angelis , Fabio Rinaldi , Marta Bertolini , Ralf Paus

Background

Human scalp hair follicles (HFs) engage in olfactory receptor (OR)-dependent chemosensation. Activation of olfactory receptor family 2 subfamily AT member 4 (OR2AT4) by the synthetic, sandalwood-like odorant Sandalore® up-regulated HF antimicrobial peptide expression of dermcidin (DCD), which had previously been thought to be produced exclusively by sweat and sebaceous glands.

Objectives

To understand if intrafollicular DCD production can be stimulated by a commonly used cosmetic odorant, thus altering human HF microbiome composition in a clinically beneficial manner.

Methods

DCD expression was compared between fresh-frozen scalp biopsies and microdissected, full-length scalp HFs, organ-cultured in the presence/absence of the OR2AT4 agonist, Sandalore® and/or antibiotics and/or the competitive OR2AT4 antagonist, Phenirat®. Amplicon-based sequencing and microbial growth assays were performed to assess how this treatment affected the HF microbiome.

Results

Synthetic odorant treatment upregulated epithelial DCD expression and exerted antimicrobial activity in human HFs ex vivo. Combined antibiotic and odorant treatment, during an ex vivo dysbiosis event, prevented HF tissue damage and favoured a more physiological microbiome composition. Sandalore®-conditioned medium, containing higher DCD content, favoured Staphylococcus epidermidis and Malassezia restricta over S. aureus and M. globosa, while exhibiting antimicrobial activity against Cutibacterium acnes. These effects were reversed by co-administration of Phenirat®.

Conclusions

We provide the first proof-of-principle that a cosmetic odorant impacts the human HF microbiome by up-regulating antimicrobial peptide production in an olfactory receptor-dependent manner. Specifically, a synthetic sandalwood-like odorant stimulates intrafollicular DCD production, likely via OR2AT4, and thereby controls microbial overgrowth. Thus, deserving further exploration as an adjuvant therapeutic principle in the management of folliculitis and dysbiosis-associated hair diseases.

背景:人类头皮毛囊(HFs)参与嗅觉受体(OR)依赖性化学补偿。合成的檀香类气味剂Sandalore®对嗅觉受体家族2 AT成员4亚家族(OR2AT4)的激活上调了皮霉素(DCD)的HF抗菌肽表达,此前人们认为皮霉素仅由汗液和皮脂腺产生。目的:了解一种常用的化妆品气味剂是否可以刺激毛囊内DCD的产生,从而以临床有益的方式改变人类HF微生物组的组成。方法:比较新鲜冷冻头皮活检与显微切割的全长头皮HFs、在存在/不存在OR2AT4激动剂Sandalore®和/或抗生素和/或竞争性OR2AT4拮抗剂Phenirat®的情况下培养的器官之间的DCD表达。进行了基于扩增子的测序和微生物生长测定,以评估这种治疗如何影响HF微生物组。结果:合成气味剂处理上调了人HFs离体上皮DCD的表达并发挥了抗菌活性。在离体微生态失调事件中,抗生素和气味剂的联合治疗可以防止HF组织损伤,并有利于更具生理学意义的微生物组组成。Sandalore®条件培养基含有更高的DCD含量,与金黄色葡萄球菌和球形葡萄球菌相比,有利于表皮葡萄球菌和限制性马拉色菌,同时对痤疮杆菌表现出抗菌活性。Phenirat®联合给药可逆转这些影响。结论:我们首次证明了化妆品气味剂通过以嗅觉受体依赖的方式上调抗菌肽的产生来影响人类HF微生物组的原理。具体而言,合成檀香类气味剂可能通过OR2AT4刺激卵泡内DCD的产生,从而控制微生物过度生长。因此,作为毛囊炎和微生态失调相关毛发疾病的辅助治疗原则,值得进一步探索。
{"title":"Management of the human hair follicle microbiome by a synthetic odorant","authors":"Janin Edelkamp ,&nbsp;Marta B. Lousada ,&nbsp;Daniela Pinto ,&nbsp;Jérémy Chéret ,&nbsp;Francesco Maria Calabrese ,&nbsp;Francisco Jiménez ,&nbsp;Hanieh Erdmann ,&nbsp;Julia Wessel ,&nbsp;Bodo Phillip ,&nbsp;Maria De Angelis ,&nbsp;Fabio Rinaldi ,&nbsp;Marta Bertolini ,&nbsp;Ralf Paus","doi":"10.1016/j.jdermsci.2023.09.006","DOIUrl":"10.1016/j.jdermsci.2023.09.006","url":null,"abstract":"<div><h3>Background</h3><p><span>Human scalp </span>hair follicles<span><span> (HFs) engage in olfactory receptor<span> (OR)-dependent chemosensation. Activation of olfactory receptor family 2 subfamily AT member 4 (OR2AT4) by the synthetic, sandalwood-like odorant Sandalore® up-regulated HF antimicrobial peptide expression of </span></span>dermcidin<span> (DCD), which had previously been thought to be produced exclusively by sweat and sebaceous glands.</span></span></p></div><div><h3>Objectives</h3><p>To understand if intrafollicular DCD production can be stimulated by a commonly used cosmetic odorant, thus altering human HF microbiome composition in a clinically beneficial manner.</p></div><div><h3>Methods</h3><p><span>DCD expression was compared between fresh-frozen scalp biopsies and microdissected, full-length scalp HFs, organ-cultured in the presence/absence of the OR2AT4 agonist, Sandalore® and/or antibiotics and/or the competitive OR2AT4 antagonist, Phenirat®. Amplicon-based sequencing and microbial growth assays were performed to assess how this </span>treatment affected the HF microbiome.</p></div><div><h3>Results</h3><p><span>Synthetic odorant treatment upregulated epithelial DCD expression and exerted antimicrobial activity in human HFs </span><span><em>ex vivo</em></span>. Combined antibiotic and odorant treatment, during an <em>ex vivo</em><span> dysbiosis event, prevented HF tissue damage and favoured a more physiological microbiome composition. Sandalore®-conditioned medium, containing higher DCD content, favoured </span><span><em>Staphylococcus epidermidis</em></span> and <span><em>Malassezia</em><em> restricta</em></span> over <span><em>S. aureus</em></span> and <em>M. globosa,</em> while exhibiting antimicrobial activity against <span><em>Cutibacterium acnes</em></span>. These effects were reversed by co-administration of Phenirat®.</p></div><div><h3>Conclusions</h3><p>We provide the first proof-of-principle that a cosmetic odorant impacts the human HF microbiome by up-regulating antimicrobial peptide production in an olfactory receptor-dependent manner. Specifically, a synthetic sandalwood-like odorant stimulates intrafollicular DCD production, likely via OR2AT4, and thereby controls microbial overgrowth. Thus, deserving further exploration as an adjuvant therapeutic principle in the management of folliculitis and dysbiosis-associated hair diseases.</p></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49686678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Corrigendum to “A new susceptibility index to predict the risk of severe herpes zoster-associated pain: A Japanese regional population-based cohort study, the Shizuoka study” [J. Dermatol. Sci. 105 (2022) 170–175] “预测严重带状疱疹相关疼痛风险的新易感性指数:一项基于日本区域人群的队列研究,静冈研究”的更正。北京医学。科学通报,2015(5):391 - 391。
IF 4.6 Pub Date : 2023-11-01 DOI: 10.1016/j.jdermsci.2023.11.001
Hideo Hashizume , Eiji Nakatani , Yoko Sato , Haruka Goto , Hiroaki Yagi , Yoshiki Miyachi
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引用次数: 0
期刊
Journal of dermatological science
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