JID innovations : skin science from molecules to population health最新文献_第4页

Lack of Hypoxia Inducible Factor-1α Influences on Macrophages Ability to Deal with Leishmania braziliensis In Vitro and Affects Pathology In Vivo 缺乏缺氧诱导因子-1α对巨噬细胞体外处理巴西利什曼原虫能力的影响及体内病理

JID innovations : skin science from molecules to population health Pub Date : 2025-01-08 DOI: 10.1016/j.xjidi.2025.100347

Rodrigo C.O. Sanches , Leonardo G. Vaz , Fabio V. Marinho , Erika S. Guimarães , Edgar M. Carvalho , Lucas P. Carvalho , Sergio C. Oliveira

{"title":"Lack of Hypoxia Inducible Factor-1α Influences on Macrophages Ability to Deal with Leishmania braziliensis In Vitro and Affects Pathology In Vivo","authors":"Rodrigo C.O. Sanches , Leonardo G. Vaz , Fabio V. Marinho , Erika S. Guimarães , Edgar M. Carvalho , Lucas P. Carvalho , Sergio C. Oliveira","doi":"10.1016/j.xjidi.2025.100347","DOIUrl":"10.1016/j.xjidi.2025.100347","url":null,"abstract":"<div><div>Cutaneous leishmaniasis, caused by <em>Leishmania braziliensis</em>, still represents a serious health problem in Brazil, especially in the northeast region. Currently, to our knowledge, no report describes the role of hypoxia inducible factor-1α (HIF-1α) during <em>L braziliensis</em> infection. In this study, we demonstrated that the parasite induces HIF-1α expression and stabilization in bone marrow–derived macrophages only when added with exogenous IFN-γ plus lipopolysaccharide. Coherently, we did not find an enrichment in the glycolytic pathway upon bone marrow–derived macrophage infection. Evaluating the impact of HIF-1α absence during macrophage infection in vitro, we observed HIF-1α–knockout cells present at high levels of IL-10, reduced production of nitric oxide, and decreased expression of VEGF-A. As a result, parasite viability improves within HIF-1α–knockout cells. However, in vivo, the absence of myeloid cells expressing HIF-1α had no influence on nitric oxide at tissue levels and in parasite burden. Conversely, lack of HIF-1α significantly affects <em>L braziliensis</em>–induced pathology. Ear lesions induced in myeloid HIF-1α–knockout mice were thicker, presenting higher frequency of macrophages, neutrophils, CD4<sup>+</sup>, and CD8<sup>+</sup> T cells as well as higher levels of IL-12, IL-1β, and IFN-γ, compared with those in wild-type mice. Moreover, draining lymph nodes from myeloid HIF-1α–knockout mice also harbored increased populations of T cells. Our data demonstrate that HIF-1α plays an important role during <em>L braziliensis</em> infection influencing skin pathology in vivo.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"5 3","pages":"Article 100347"},"PeriodicalIF":0.0,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143199481","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

Transcriptionally Active Human Papillomavirus in Male Genital Lichen Sclerosus, Penile Intraepithelial Neoplasia, and Penile Squamous Cell Carcinoma 转录活性人乳头瘤病毒在男性生殖器地衣硬化、阴茎上皮内瘤变和阴茎鳞状细胞癌中的作用。

JID innovations : skin science from molecules to population health Pub Date : 2025-01-01 DOI: 10.1016/j.xjidi.2024.100320

Georgios Kravvas , Boyu Xie , Aiman Haider , Michael Millar , Hussain M Alnajjar , Alex Freeman , Asif Muneer , Christopher B Bunker , Aamir Ahmed

{"title":"Transcriptionally Active Human Papillomavirus in Male Genital Lichen Sclerosus, Penile Intraepithelial Neoplasia, and Penile Squamous Cell Carcinoma","authors":"Georgios Kravvas , Boyu Xie , Aiman Haider , Michael Millar , Hussain M Alnajjar , Alex Freeman , Asif Muneer , Christopher B Bunker , Aamir Ahmed","doi":"10.1016/j.xjidi.2024.100320","DOIUrl":"10.1016/j.xjidi.2024.100320","url":null,"abstract":"<div><div>Penile intraepithelial neoplasia (PeIN) and penile squamous cell carcinoma (PeSCC) are both thought to be associated with male genital lichen sclerosus and human papillomavirus (HPV) infection through dichotomous pathways: (i) undifferentiated PeIN and warty/basaloid PeSCC are thought to be HPV related, whereas (ii) differentiated PeIN and usual PeSCC are considered HPV independent. Tissue arrays were constructed from male genital lichen sclerosus, undifferentiated and differentiated PeIN, usual-type PeSCC, and unaffected tissues. Staining for p16 and for high-risk and low-risk HPV subtypes through RNAscope was performed. The expression of HPV RNA and p16 were quantified, and appropriate statistical comparisons were undertaken. High-risk HPV was prevalent in undifferentiated PeIN (77%) and less so in PeSCC (46%) and was exiguous or absent in all other tissues. LR HPV was only observed in 2 tissue cores. Strong p16 staining exhibited 96.15% sensitivity and 100% specificity for high-risk HPV. Transcriptionally active HPV is unlikely to be implicated in male genital lichen sclerosus and differentiated PeIN, although it is clearly important in undifferentiated PeIN. The high prevalence of high-risk HPV in usual PeSCC challenges the existing paradigm. Strong p16 positivity was a reliable surrogate marker for the detection of transcriptionally active high-risk HPV.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"5 1","pages":"Article 100320"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11696787/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142933841","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

Langerhans Cells Directly Interact with Resident T Cells in the Human Epidermis 朗格汉斯细胞与人体表皮中的驻留 T 细胞直接相互作用

JID innovations : skin science from molecules to population health Pub Date : 2025-01-01 DOI: 10.1016/j.xjidi.2024.100324

Tomonori Oka , Tatsuya Hasegawa , Truelian Lee , Valeria S. Oliver-Garcia , Mahsa Mortaja , Marjan Azin , Satoshi Horiba , Sabrina S. Smith , Sara Khattab , Kathryn E. Trerice , Steven T. Chen , Yevgeniy R. Semenov , Shadmehr Demehri

{"title":"Langerhans Cells Directly Interact with Resident T Cells in the Human Epidermis","authors":"Tomonori Oka , Tatsuya Hasegawa , Truelian Lee , Valeria S. Oliver-Garcia , Mahsa Mortaja , Marjan Azin , Satoshi Horiba , Sabrina S. Smith , Sara Khattab , Kathryn E. Trerice , Steven T. Chen , Yevgeniy R. Semenov , Shadmehr Demehri","doi":"10.1016/j.xjidi.2024.100324","DOIUrl":"10.1016/j.xjidi.2024.100324","url":null,"abstract":"<div><div>Adult human skin contains nearly twice as many T cells as the peripheral blood, which include tissue-resident memory T cells. However, the precise mechanisms maintaining tissue-resident memory T cells in the healthy skin remain unclear. Using normal human skin samples, we find that Langerhans cells (LCs) contact T cells in the epidermis of the elderly. LCs with high HLA-II, CD86, and PD-L2 expression directly contacted PD-1<sup>+</sup> tissue-resident memory T cells and CTLA-4<sup>+</sup> regulatory T cells in the epidermis, indicating an axis of peripheral tolerance in a steady state. Environmental insults, UVB radiation, and hapten downregulated HLA-II and CD86 on LCs in the epidermis, suggesting that disruption of LC–T cell tolerogenic axis contributes to skin inflammation. Interestingly, immune checkpoint blockade therapy was associated with decreased epidermal LC–T cell contact in the normal skin of patients with cancer affected by cutaneous immune-related adverse events. Collectively, our findings indicate that LCs may contribute to T cell tolerance in the epidermis.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"5 1","pages":"Article 100324"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11720605/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142973688","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

Meeting Report on “10th Anniversary Symposium on Inflammatory Skin Disease” “炎症性皮肤病十周年研讨会”会议报告

JID innovations : skin science from molecules to population health Pub Date : 2024-12-24 DOI: 10.1016/j.xjidi.2024.100344

Shirin Emtenani , John F. Baines , Katja Bieber , Evelyn Gaffal , Stephanie Goletz , Gema Hernández , Misa Hirose , Markus Hoffmann , Pascal Joly , Henriette Kirchner , Jörg Köhl , Sripriya Murthy , Sabrina Patzelt , Frank Petersen , Manuela Pigors , Gabriela Riemekasten , Leon F. Schmidt-Jiménez , Tanya Sezin , Malte Spielmann , Diamant Thaçi , Enno Schmidt

引用次数: 0

Efficient Dual Cas9 Nickase Correction of a Prevalent Pathogenic LAMB3 Variant for Junctional Epidermolysis Bullosa 结性大疱性表皮松解症常见致病性LAMB3变异的有效双Cas9缺失酶校正

JID innovations : skin science from molecules to population health Pub Date : 2024-12-24 DOI: 10.1016/j.xjidi.2024.100343

Alex du Rand , John Hunt , Daniel Verdon , Ben Buttle , P. Rod Dunbar , Diana Purvis , Vaughan Feisst , Hilary Sheppard

{"title":"Efficient Dual Cas9 Nickase Correction of a Prevalent Pathogenic LAMB3 Variant for Junctional Epidermolysis Bullosa","authors":"Alex du Rand , John Hunt , Daniel Verdon , Ben Buttle , P. Rod Dunbar , Diana Purvis , Vaughan Feisst , Hilary Sheppard","doi":"10.1016/j.xjidi.2024.100343","DOIUrl":"10.1016/j.xjidi.2024.100343","url":null,"abstract":"<div><div>Gene editing facilitated by homology-directed repair represents a promising strategy for precisely correcting pathogenic variants underlying monogenic disorders, including the life-threatening skin blistering condition junctional epidermolysis bullosa (JEB). Frequent reports of unintended off-target genotoxicity associated with conventional Cas9 nuclease editing have increasingly led to the adoption of dual-Cas9 nickases (dual-Cas9n) owing to their improved safety profile. However, rates of precise repair obtained with such strategies remain low. In this study, we establish a dual-Cas9n approach targeting <em>LAMB3</em>, using electroporation to deliver Cas9-nickase ribonucleoproteins and modified single-stranded oligodeoxynucleotide repair templates into primary JEB keratinocytes. Targeting a hotspot pathogenic variant (c.1903C>T, p.R635∗), we report perfect correction efficiencies of up to 54% based on standard next-generation sequencing. Using a high-fidelity Cas9 nuclease, we also report perfect repair of up to 74% when using a small-molecule modulator of DNA repair. Dual-Cas9n–corrected JEB keratinocytes demonstrated restored laminin-332 expression and secretion <em>in vitro</em>, leading to improved cellular adhesion and accurate laminin-332 localization in engineered skin equivalents. This protocol represents a significant improvement in precision gene repair using Cas9 nickases for epidermolysis bullosa, with the potential to be applied to a large cohort of patients harboring this prevalent pathogenic variant.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"5 3","pages":"Article 100343"},"PeriodicalIF":0.0,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143101038","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

Meeting Report on “The International Congress on Autoimmune Pre-disease (2024)” “自身免疫性疾病前期国际大会（2024）”会议报告

JID innovations : skin science from molecules to population health Pub Date : 2024-12-18 DOI: 10.1016/j.xjidi.2024.100342

Justus Ohmes , Afsaneh Mehrpouyan , Julia Wimmer-Groß , Abdul Razzaque Ahmed , Kyle T. Amber , Swayanka Biswas , Angela Christiano , Shirin Emtenani , Stephanie Goletz , Jennifer Elisabeth Hundt , Laura Kirchhoff , Khalaf Kridin , Julie Lasselin , Matthias Laudes , Wing Yu Lee , Ralf J. Ludwig , Sripriya Murthy , Sadegh Mousavi , Tamas Nemeth , Mareike Neumann , Sarah Stenger

引用次数: 0

Enhancing Transcutaneous Drug Delivery: Advanced Perspectives on Skin Models 加强经皮给药：皮肤模型的先进观点

JID innovations : skin science from molecules to population health Pub Date : 2024-12-17 DOI: 10.1016/j.xjidi.2024.100340

Ana Ribeiro , Catarina Pereira-Leite , Catarina Rosado , Edlira Aruci , Helen E. Colley , Inge Kortekaas Krohn , Ioana Baldea , Ivana Pantelić , Joachim W. Fluhr , Sandra I. Simões , Snežana Savić , Sofia A. Costa Lima

{"title":"Enhancing Transcutaneous Drug Delivery: Advanced Perspectives on Skin Models","authors":"Ana Ribeiro , Catarina Pereira-Leite , Catarina Rosado , Edlira Aruci , Helen E. Colley , Inge Kortekaas Krohn , Ioana Baldea , Ivana Pantelić , Joachim W. Fluhr , Sandra I. Simões , Snežana Savić , Sofia A. Costa Lima","doi":"10.1016/j.xjidi.2024.100340","DOIUrl":"10.1016/j.xjidi.2024.100340","url":null,"abstract":"<div><div>Skin acts as a dynamic interface with the environment. Pathological alterations in the skin barrier are associated with skin diseases. These conditions are characterized by specific impairments in epidermal barrier functions. Despite its protective nature, the skin can be a relevant route of drug administration, both for topical and transdermal therapy, allowing for improved drug delivery and reducing the incidence of adverse reactions. This manuscript reviews transcutaneous drug delivery as a strategy for treating localized and systemic conditions, highlighting the importance of skin models in the evaluation of drug efficacy and barrier function. It explores advances in in vitro, ex vivo, in vivo, and in silico models for studying cellular uptake, wound healing, oxidative stress, anti-inflammatory, and immune modulation activities. Disease-specific skin models are also discussed.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"5 2","pages":"Article 100340"},"PeriodicalIF":0.0,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143150345","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

Advances in Pemphigus and Pemphigoid: A Report of the International Meeting of the Pemphigus and Pemphigoid Foundation in Thessaloniki, Greece 天疱疮和类天疱疮的进展：在希腊塞萨洛尼基举行的天疱疮和类天疱疮基金会国际会议报告。

JID innovations : skin science from molecules to population health Pub Date : 2024-12-11 DOI: 10.1016/j.xjidi.2024.100339

Meropi Karakioulaki , Patrick Dunn , Dedee F. Murrell , Aimee Payne , Enno Schmidt , Victoria Werth , Marc Yale , Jun Yamagami , Valeria Aoki , Luca Borradori , Frédéric Caux , Donna Culton , Maryam Daneshpazhooh , Dipankar De , Janet Fairley , Christoph Hammers , Michael Hertl , Maike Holtsche , Pascal Joly , Hiroshi Koga , Aikaterini Patsatsi

引用次数: 0

Capture of Patient Itch Scores in Practice Reveals Disparate Itch Impact on the Basis of Age, Gender, and Race: A Cross-Sectional Survey Analysis 在实践中捕获患者瘙痒评分揭示了不同年龄、性别和种族对瘙痒的影响：一项横断面调查分析。

JID innovations : skin science from molecules to population health Pub Date : 2024-12-11 DOI: 10.1016/j.xjidi.2024.100338

Yin Li , Robert A. Swerlick

{"title":"Capture of Patient Itch Scores in Practice Reveals Disparate Itch Impact on the Basis of Age, Gender, and Race: A Cross-Sectional Survey Analysis","authors":"Yin Li , Robert A. Swerlick","doi":"10.1016/j.xjidi.2024.100338","DOIUrl":"10.1016/j.xjidi.2024.100338","url":null,"abstract":"<div><h3>Background</h3><div>Skin symptom burden, varying with patient populations, may not be readily observed by clinicians, resulting in incomplete appreciation of total skin disease burden.</div></div><div><h3>Objective</h3><div>The purpose of this study was to define patient itch burdens and associated health-related QOL affecting different patient demographics and to identify potential population health disparities.</div></div><div><h3>Methods</h3><div>This is a cross-sectional, secondary data analysis of data captured using an automated routine electronic previsit survey completed by patients who visited Emory Healthcare Dermatology clinic between March 2021 and October 2022 (6532 patient visits). Descriptive statistics and ordered logit regression analyses were used to examine the prevalence and intensity of itch and the impacts of itch on QOL.</div></div><div><h3>Results</h3><div>Overall itch burden increases as age increases; females and African Americans experienced more itch burden than males and other racial groups. Itch places significant symptom, emotional, and functional burdens on patients’ QOL, impacts that are independent of patients’ demographics.</div></div><div><h3>Limitations</h3><div>The data collected were from a single dermatology practice and may not be reflective of other practices or populations.</div></div><div><h3>Conclusion</h3><div>Dermatology previsit surveys are feasible in examining the significant pruritus burden, especially for older individuals, females, and African Americans with chronic skin conditions.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"5 2","pages":"Article 100338"},"PeriodicalIF":0.0,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11773235/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143061472","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

Development and Evaluation of the Dermatomyositis Outcomes for Muscle and Skin as an Outcome Measure in Dermatomyositis Clinical Trials 皮肌炎临床试验中肌肉和皮肤皮肌炎结果的发展和评价。

JID innovations : skin science from molecules to population health Pub Date : 2024-12-09 DOI: 10.1016/j.xjidi.2024.100337

Rachita Pandya , Joshua Dan , Julianne Kleitsch , Darosa Lim , Barbara White , Victoria P. Werth

{"title":"Development and Evaluation of the Dermatomyositis Outcomes for Muscle and Skin as an Outcome Measure in Dermatomyositis Clinical Trials","authors":"Rachita Pandya , Joshua Dan , Julianne Kleitsch , Darosa Lim , Barbara White , Victoria P. Werth","doi":"10.1016/j.xjidi.2024.100337","DOIUrl":"10.1016/j.xjidi.2024.100337","url":null,"abstract":"<div><div>The Total Improvement Score (TIS), which is used as the primary efficacy measure in dermatomyositis (DM) clinical trials, lacks a skin-specific measure. However, skin is a defining feature of DM. In this study, data were analyzed from the phase 3 trial of lenabasum in DM. Cutaneous Dermatomyositis Disease Area and Severity Index-Activity scores and all components of the TIS were collected at baseline and weeks 16, 28, 40, and 52. From these assessments, a composite outcome was developed, named Dermatomyositis Outcomes for Muscle and Skin, which includes certain components of the TIS and the Cutaneous Dermatomyositis Disease Area and Severity Index-Activity scores. The relative sensitivities of the TIS and Dermatomyositis Outcomes for Muscle and Skin to detect improvement in DM skin and muscle disease activity were analyzed. A total of 174 patients with DM were included, 82% were female, and 75% were White. Mean (SD) age was 51.9 (12.20) years. Treatment effect using the TIS ranged between 17.6 and 21.7 points for muscle and skin responders versus nonresponders across time points. The Dermatomyositis Outcomes for Muscle and Skin score displayed a statistically significantly greater treatment effect of 25.9–40.0 points for responders than for nonresponders, depending on the response assessed and the time point. Dermatomyositis Outcomes for Muscle and Skin is a more sensitive composite measure that reflects improvement from baseline in both skin and muscle disease activity, suggesting usefulness for use in future DM clinical trials.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"5 2","pages":"Article 100337"},"PeriodicalIF":0.0,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11773231/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143061475","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