Eleri Mai Jones , Priya Garcha , Monique Aumailley , Edel Anne O’Toole , Emanuel Rognoni , Matthew Caley
{"title":"Weekly Intraperitoneal Injection of Tamoxifen in an Inducible In Vivo Model of Junctional Epidermolysis Bullosa Generates Early and Advanced Disease Phenotypes","authors":"Eleri Mai Jones , Priya Garcha , Monique Aumailley , Edel Anne O’Toole , Emanuel Rognoni , Matthew Caley","doi":"10.1016/j.xjidi.2024.100331","DOIUrl":"10.1016/j.xjidi.2024.100331","url":null,"abstract":"<div><div>Junctional epidermolysis bullosa caused by loss-of-function variants in genes encoding the skin basement membrane proteins laminin 332, type XVII collagen, or integrin α6β4 affects patients from birth with severe blistering, eventually leading to scarring and early lethality. In this study, we have optimized a previously published junctional epidermolysis bullosa–knockout mouse model with weekly tamoxifen intraperitoneal injections, resulting in a more controllable and severe model. Owing to the titratable dosing, this model now recapitulates both early and advanced stages of the human disease, strengthening its use in therapeutic studies. The gradual loss of laminin-α3 in the skin of the mouse through weekly injections lead to generalized blistering and fibrotic dermal changes in multiple skin sites by week 12 after tamoxifen. Our findings demonstrate the usefulness of optimizing tamoxifen induction in Cre-loxP mouse models of extracellular matrix proteins, an approach that could be applicable to other emerging inducible transgenic disease models to improve their ability to mimic the human disease phenotype.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"5 2","pages":"Article 100331"},"PeriodicalIF":0.0,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11730547/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142985352","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}
Olive C. Osuoji , Taryn DeGrazia , Robin Rolader , Emily F. Cole , Katy Lawson , Henry Hilley , Yanyan Xing , Liang Han , Sarah Chisolm , Henry Claussen , Xiaobo Yan , Yuxian Sun , Yuan Liu , Suephy C. Chen , Ron J. Feldman
{"title":"Exploring Pruritus in Bullous Pemphigoid: Analysis of QOL Metrics and Potential Biological Mechanisms","authors":"Olive C. Osuoji , Taryn DeGrazia , Robin Rolader , Emily F. Cole , Katy Lawson , Henry Hilley , Yanyan Xing , Liang Han , Sarah Chisolm , Henry Claussen , Xiaobo Yan , Yuxian Sun , Yuan Liu , Suephy C. Chen , Ron J. Feldman","doi":"10.1016/j.xjidi.2024.100329","DOIUrl":"10.1016/j.xjidi.2024.100329","url":null,"abstract":"<div><div>Bullous pemphigoid is a devastating autoimmune blistering disease with need for improved therapeutics. Limited data are available on the overall burden of pruritus and alterations over time; however, treatment of itch-specific pathways may provide novel therapeutics. In this paper, we analyzed the QOL impact particularly related to itch and determined corresponding changes in intraepidermal nerve fiber density and gene expression. A total of 43 patients with bullous pemphigoid were followed prospectively on standard-of-care treatment and showed average Bullous Pemphigoid Disease Area Index total activity score decrease from 19.1 ± 19.2 to 8.2 ± 11.3 and improvement in QOL measures Autoimmune Bullous Disease Quality of Life, Treatment of Autoimmune Bullous Disease Quality of Life, and ItchyQoL. At baseline, intraepidermal nerve fiber density in patients with bullous pemphigoid and atopic dermatitis were significantly lower than in healthy controls (7.3 ± 1.5 and 3.2 ± 2.0 vs 9.7 ± 5.4 fibers/mm, <em>P</em> = .031) and increased from baseline to follow-up visit (11.7 ± 0.4 and 5.8 ± 2.7), although only atopic dermatitis reached statistical significance (<em>P</em> = .018). <em>S100A8</em>, <em>S100A9</em>, <em>CCL17</em>, and <em>CCL18</em> genes were highly upregulated in the skin of patients with bullous pemphigoid compared with those in healthy controls. Our data provide evidence for improvements in itch-related QOL over time on standard-of-care therapies with unique alterations in inflammatory mediators related to early immune cell activation and recruitment.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"5 2","pages":"Article 100329"},"PeriodicalIF":0.0,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143150344","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}
{"title":"Creating an Extremely Long-lasting Neuroischemic Wound Model","authors":"Sufan Chien , Harshini Sarojini , Arezoo Rajaee , Mohammad Bayat , Samson Chien , Girish Kotwal","doi":"10.1016/j.xjidi.2024.100328","DOIUrl":"10.1016/j.xjidi.2024.100328","url":null,"abstract":"<div><div>In wound study and dressing development, a lack of a suitable animal model that can recapitulate the complex pathophysiology of human chronic wounds has been a major hurdle. Chronic wounds are defined as wounds that heal with a significant delay, usually over a period >2–3 months, but no current animal wound model has such a longischemia. After a longexploration, our group has developed an animal wound model with ischemia and nerve damage lasting for at least 6 months. This model can be easily combined with other conditions such as diabetes and aging for wound mechanistic study and critical testing of dressings. This report presents the method that has significant utility in evaluating therapies that could become the future standard for screening all new wound dressings.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"5 2","pages":"Article 100328"},"PeriodicalIF":0.0,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11728989/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142985845","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}
Thomas Z. Rohan , Jenna L. Mandel , Henry Y. Yang , Lauren Banner , Daniel Joffe , Rachel Zachian , Jaanvi Mehta , Safiyyah Bhatti , Tingting Zhan , Neda Nikbakht
{"title":"Identifying Subsets of Cancer Patients with an Increased Risk of Developing Cutaneous Melanoma: A Surveillance, Epidemiology, and End Results–Based Analysis","authors":"Thomas Z. Rohan , Jenna L. Mandel , Henry Y. Yang , Lauren Banner , Daniel Joffe , Rachel Zachian , Jaanvi Mehta , Safiyyah Bhatti , Tingting Zhan , Neda Nikbakht","doi":"10.1016/j.xjidi.2024.100323","DOIUrl":"10.1016/j.xjidi.2024.100323","url":null,"abstract":"<div><div>Cancer survivors have an increased risk of developing second primary malignancies. We aimed to identify whether certain cancers lead to an increased risk of developing melanoma among cancer survivors. We evaluated the risk of developing cutaneous melanoma after the 20 most common cancers in the United States through the Surveillance, Epidemiology, and End Results database. We identified 9 primary cancers linked to increased risk of developing a subsequent cutaneous melanoma: cutaneous melanoma (standardized incidence ratio [SIR] = 9.65), leukemia (SIR = 1.76), non-Hodgkin lymphoma (SIR = 1.33), thyroid cancer (SIR = 1.32), brain and nervous system cancer (SIR = 1.31), myeloma (SIR = 1.23), breast cancer (SIR = 1.13), oral cavity/pharynx cancer (SIR= 1.12), and prostate cancer (SIR = 1.03). The risk of developing melanoma was highest 1–5 years after diagnosis of most primary cancers. Notably, individuals aged under 50 years with a prior melanoma had a 14-fold increased risk. Our findings highlight specific at-risk groups—such as those aged under 50 years with recent melanoma, individuals in their 60s diagnosed with leukemia, and those aged over 80 years with recent thyroid cancer—who may benefit from heightened clinical vigilance and tailored melanoma screening strategies.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"5 1","pages":"Article 100323"},"PeriodicalIF":0.0,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142759535","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}
{"title":"Corrigendum to ‘Proteomic Profiling of CCCA Reveals Role of Humoral Immune Response Pathway and Metabolic Dysregulation’ JID Innovations, Volume 4, Issue 3, May 2024, 100263","authors":"","doi":"10.1016/j.xjidi.2024.100312","DOIUrl":"10.1016/j.xjidi.2024.100312","url":null,"abstract":"","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 6","pages":"Article 100312"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142660973","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}
Jason C. Klein , Ruchika Mahapatra , Gary C. Hon , Richard C. Wang
{"title":"Identification of Associations with Dermatologic Diseases through a Focused GWAS of the UK Biobank","authors":"Jason C. Klein , Ruchika Mahapatra , Gary C. Hon , Richard C. Wang","doi":"10.1016/j.xjidi.2024.100322","DOIUrl":"10.1016/j.xjidi.2024.100322","url":null,"abstract":"<div><div>The UK Biobank includes genotype information for about 500,000 patients for over 7000 phenotypes. However, owing to multiple testing correction for approximately 200 billion tests, many clinically and statistically significant associations remain unappreciated. We perform a focused analysis of the UK Biobank for 13 dermatologic conditions, including malignant melanoma, melanoma in situ, squamous cell carcinoma, basal cell carcinoma, actinic keratosis, seborrheic keratosis, psoriasis, lichen planus, systemic lupus erythematosus, hyperhidrosis, pilonidal cyst, sebaceous cyst, and lipoma. We identify 447 sentinel variants, which are enriched for protein-coding variants and an elevated combined annotation-dependent depletion (CADD) score compared with background variants. Through gene ontology enrichment analysis, we identify known pathways involved in melanoma, actinic keratoses, and squamous cell carcinoma and uncover additional pathways. We also uncover 5 protein-coding variants, which, to our knowledge, have not been previously reported, including <em>LRP3</em> for lipomas, <em>PLCD1</em> for sebaceous cysts, <em>EIF3CL</em> for lichen planus, <em>TTK</em> for pilonidal cysts, and <em>MAPK15</em> for systemic lupus erythematosus.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"5 1","pages":"Article 100322"},"PeriodicalIF":0.0,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142658395","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}
Aygun Israyilova , Tsvetomira Zhivkova Peykova , Ben Kittleson , Paul Caleb Sprowl , Taha Osman Mohammed , Cassandra L. Quave
{"title":"From Plant to Patient: A Historical Perspective and Review of Selected Medicinal Plants in Dermatology","authors":"Aygun Israyilova , Tsvetomira Zhivkova Peykova , Ben Kittleson , Paul Caleb Sprowl , Taha Osman Mohammed , Cassandra L. Quave","doi":"10.1016/j.xjidi.2024.100321","DOIUrl":"10.1016/j.xjidi.2024.100321","url":null,"abstract":"<div><div>Skin conditions are a common health concern faced by patients of all ages. For thousands of years, plants have been used to treat various skin conditions, including acne, vitiligo, and psoriasis, to name a few. Today, with increasing patient preference for natural therapies, modern medicine is now more than ever incorporating age-old knowledge of herbal remedies useful in treating skin conditions into modern-day treatments. This review covers various plant-derived therapeutics (polyphenon E [sincatechins], psoralen, salicylic acid, anthralin, podophyllotoxin, and Filsuvez [birch triterpenes, oleogel-S10]) that have demonstrated scientific evidence of clinical efficacy for dermatologic disorders. The discovery, composition, history of use, and current uses in dermatology are summarized for each botanical ingredient.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"5 1","pages":"Article 100321"},"PeriodicalIF":0.0,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142704288","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}
Alessandra S.P. Cereghetti , Patrick Turko , Phil Cheng , Stephan Benke , Ala’a Al Hrout , Andreas Dzung , Reinhard Dummer , Michael O. Hottiger , Richard Chahwan , Lorenza P. Ferretti , Mitchell P. Levesque
{"title":"DNA Methyltransferase Inhibition Upregulates the Costimulatory Molecule ICAM-1 and the Immunogenic Phenotype of Melanoma Cells","authors":"Alessandra S.P. Cereghetti , Patrick Turko , Phil Cheng , Stephan Benke , Ala’a Al Hrout , Andreas Dzung , Reinhard Dummer , Michael O. Hottiger , Richard Chahwan , Lorenza P. Ferretti , Mitchell P. Levesque","doi":"10.1016/j.xjidi.2024.100319","DOIUrl":"10.1016/j.xjidi.2024.100319","url":null,"abstract":"<div><div>In cutaneous melanoma, epigenetic dysregulation is implicated in drug resistance and tumor immune escape. However, the epigenetic mechanisms that influence immune escape remain poorly understood. To elucidate how epigenetic dysregulation alters the expression of surface proteins that may be involved in drug targeting and immune escape, we performed a 3-dimensional surfaceome screen in primary melanoma cultures and identified the DNA-methyltransferase inhibitor decitabine as significantly upregulating the costimulatory molecule ICAM-1. By analyzing The Cancer Genome Atlas melanoma dataset, we further propose ICAM-1 upregulation on melanoma cells as a biomarker of a proinflammatory and antitumorigenic signature. Specifically, we showed that DNA-methyltransferase inhibitor administration upregulated the expression of the antigen-presenting machinery, HLA class I/II, as well as the secretion of the proinflammatory chemokines CXCL9 and CXCL10. Our in silico analysis on The Cancer Genome Atlas and ex vivo experiments on human primary melanoma samples revealed that increased ICAM-1 expression positively correlated with increased immunogenicity of human melanoma cells and correlated with increased immune cell infiltration. These findings suggest a therapeutic approach to modulate the immunogenic phenotype of melanoma cells, hence supporting the exploration of DNA-methyltransferase inhibitor as a potential inducer of infiltration in immunologically cold tumors.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"5 2","pages":"Article 100319"},"PeriodicalIF":0.0,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11759630/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143049022","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}
Christina Cho , Nazgol-Sadat Haddadi , Michal Kidacki , Gavitt A. Woodard , Saeed Shakiba , Ümmügülsüm Yıldız-Altay , Jillian M. Richmond , Matthew D. Vesely
{"title":"Spatial Transcriptomics in Inflammatory Skin Diseases Using GeoMx Digital Spatial Profiling: A Practical Guide for Applications in Dermatology","authors":"Christina Cho , Nazgol-Sadat Haddadi , Michal Kidacki , Gavitt A. Woodard , Saeed Shakiba , Ümmügülsüm Yıldız-Altay , Jillian M. Richmond , Matthew D. Vesely","doi":"10.1016/j.xjidi.2024.100317","DOIUrl":"10.1016/j.xjidi.2024.100317","url":null,"abstract":"<div><div>The spatial organization of the skin is critical for its function. In particular, the skin immune microenvironment is arranged spatially and temporally, such that imbalances in the immune milieu are indicative of disease. Spatial transcriptomic platforms are helping to provide additional insights into aberrant inflammation in tissues that are not captured by tissue processing required for single-cell RNA sequencing. In this paper, we discuss a technical and user experience overview of NanoString's GeoMx Digital Spatial Profiler to perform in-depth spatial analysis of the transcriptome in inflammatory skin diseases. Our objective is to provide potential pitfalls and methods to optimize RNA capture that are not readily available in the manufacturer’s guidelines. We use concrete examples from our experiments to demonstrate these strategies in inflammatory skin diseases, including psoriasis, lichen planus, and discoid lupus erythematosus. Overall, we hope to illustrate the potential of digital spatial profiling to dissect skin disease pathogenesis in a spatially resolved manner and provide a framework for other skin biology investigators using digital spatial profiling.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"5 1","pages":"Article 100317"},"PeriodicalIF":0.0,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142593706","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}
Dominique du Crest , Philipp Wustrow , Oliver Worsley , Barbara Geusens , Omar Badri , Monisha Madhumita , Art Papier , Alexander Zink , Merete Hædersdal , Lilit Garibyan
{"title":"Skin & Digital: The 2023 Startups/Innovators","authors":"Dominique du Crest , Philipp Wustrow , Oliver Worsley , Barbara Geusens , Omar Badri , Monisha Madhumita , Art Papier , Alexander Zink , Merete Hædersdal , Lilit Garibyan","doi":"10.1016/j.xjidi.2024.100316","DOIUrl":"10.1016/j.xjidi.2024.100316","url":null,"abstract":"","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"5 1","pages":"Article 100316"},"PeriodicalIF":0.0,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142440949","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}