JID innovations : skin science from molecules to population health最新文献

{"title":"Portable System for In-Clinic Differentiation of Skin Cancers from Benign Skin Lesions and Inflammatory Dermatoses","authors":"Michel Nieuwoudt ,&nbsp;Paul Jarrett ,&nbsp;Hannah Matthews ,&nbsp;Michelle Locke ,&nbsp;Marco Bonesi ,&nbsp;Brydon Burnett ,&nbsp;Hannah Holtkamp ,&nbsp;Claude Aguergaray ,&nbsp;Ira Mautner ,&nbsp;Thom Minnee ,&nbsp;M. Cather Simpson","doi":"10.1016/j.xjidi.2023.100238","DOIUrl":"10.1016/j.xjidi.2023.100238","url":null,"abstract":"<div><p>The exquisite sensitivity of Raman spectroscopy for detecting biomolecular changes in skin cancer has previously been explored; however, this mostly required analysis of excised tissue samples using bulky, immobile laboratory instrumentation. In this study, the technique was translated for clinical use with a portable Raman system and customized fiber optic probe and applied to differentiation of skin cancers from benign lesions and inflammatory dermatoses. The aim was to provide an easy-to-use, easy-to-manage assessment tool for clinicians to use in their daily patient examination routine to perform rapid Raman measurements of skin lesions in vivo. Using this system, &gt;867 spectra were measured in vivo from 330 patients with a wide variety of different benign skin lesions (n = 603), inflammatory dermatoses (n = 140), and skin cancers (n = 124). Ethnicities represented were 70% European; 16% Asian; 6% Māori; 5% Pacific people; and 4% Middle East, Latin American, and African. Accurate differentiation of skin cancers from benign lesions and inflammatory dermatoses was achieved using partial least squares discriminant analysis, with area under curve for the receiver operator curves for external validation sets ranging from 0.916 to 0.958. This study shows evidence for robust clinical translation of Raman spectroscopy for rapid, accurate diagnosis of skin cancer.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 1","pages":"Article 100238"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026723000644/pdfft?md5=27035fe51a51ec08108ee2d135bb69b9&pid=1-s2.0-S2667026723000644-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134994567","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":"Evidence-Based Communication to Increase Melanoma Knowledge and Skin Checks","authors":"Ariel Nadratowski ,&nbsp;Brittany Shoots-Reinhard ,&nbsp;Autumn Shafer ,&nbsp;Jerusha Detweiler-Bedell ,&nbsp;Brian Detweiler-Bedell ,&nbsp;Sancy Leachman ,&nbsp;Ellen Peters","doi":"10.1016/j.xjidi.2023.100253","DOIUrl":"10.1016/j.xjidi.2023.100253","url":null,"abstract":"<div><p>Rates of melanoma—the deadliest form of skin cancer—have increased. Early detection can save lives, and patients have a critical role to play in checking their skin. We aim to identify health communication messages that best educate the public and increase intentions toward skin checks. After viewing messages intended to increase melanoma knowledge, participants correctly identified a greater proportion (74.6 vs 70.4%) of moles (mean number = 17.9, 95% confidence interval [CI] = 17.5–18.3 vs 16.9, 95% CI = 16.6–17.3; <em>P</em> &lt; .001, partial eta-squared = 0.03) and had knowledge of more melanoma warning signs (mean number = 5.8, 95% CI = 5.7–5.8 vs 5.6, 95% CI = 5.5–5.7, <em>P</em> = .01, partial eta-squared = 0.02). After viewing messages intended to increase self-confidence in checking their skin accurately, they were also more likely to report greater intentions to do a skin check on a scale of 1–5 (mean number = 3.8, 95% CI = 3.7–3.9 vs 3.6, 95% CI = 3.4–3.7, <em>P</em> = .005, partial eta-squared = 0.02). Online melanoma messages aimed at increasing both melanoma knowledge and skin-check confidence may be most effective in improving the accuracy of skin self-examinations and intentions to do them.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 2","pages":"Article 100253"},"PeriodicalIF":0.0,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026723000796/pdfft?md5=118f40cd536db7b24ec4a6b4ddd14f1e&pid=1-s2.0-S2667026723000796-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139192774","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":"Identification of Fibroinflammatory and Fibrotic Transcriptomic Subsets of Human Cutaneous Sclerotic Chronic Graft-Versus-Host Disease","authors":"Rachel K. Rosenstein ,&nbsp;Jeremy J. Rose ,&nbsp;Stephen R. Brooks ,&nbsp;Wanxia L. Tsai ,&nbsp;Massimo Gadina ,&nbsp;Steven Z. Pavletic ,&nbsp;Keisuke Nagao ,&nbsp;Edward W. Cowen","doi":"10.1016/j.xjidi.2023.100246","DOIUrl":"https://doi.org/10.1016/j.xjidi.2023.100246","url":null,"abstract":"<div><p>Cutaneous sclerotic chronic graft-versus-host disease (cGVHD) is a common and highly morbid complication of allogeneic hematopoietic stem cell transplantation. Our goals were to identify signals active in the skin of patients with sclerotic cGVHD in an effort to better understand how to treat this manifestation and to explore the heterogeneity of the disease. We identified genes that are significantly upregulated in the skin of patients with sclerotic cGVHD (n = 17) compared with those in the skin of patients who underwent allogeneic hematopoietic stem cell transplantation without cutaneous cGVHD (n = 9) by bulk RNA sequencing. Sclerotic cGVHD was most associated with T helper 1, phagocytic, and fibrotic pathways. In addition, different transcriptomic groups of affected patients were discovered: those with fibrotic and inflammatory/T helper 1 gene expression (the fibroinflammatory group) and those with predominantly fibrotic/TGFβ-associated expression (the fibrotic group). Further study will help elucidate whether these gene expression findings can be used to tailor treatment decisions. Multiple proteins encoded by highly induced genes in the skin (<em>SFRP4</em>, <em>SERPINE2</em>, <em>COMP</em>) were also highly induced in the plasma of patients with sclerotic cGVHD (n = 16) compared with those in plasma of control patients who underwent allogeneic hematopoietic stem cell transplantation without sclerotic cGVHD (n = 17), suggesting these TGFβ and Wnt pathway mediators as candidate blood biomarkers of the disease.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 2","pages":"Article 100246"},"PeriodicalIF":0.0,"publicationDate":"2023-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026723000723/pdfft?md5=3de50b8cb7956c47138b20eda621217a&pid=1-s2.0-S2667026723000723-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139714033","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":"The Influence of Blue Light Exposure on Reconstructed 3-Dimensional Skin Model: Molecular Changes and Gene Expression Profile","authors":"Juliana Carvalhães Lago ,&nbsp;Melissa Dibbernn Ganzerla ,&nbsp;Ana Luisa Abrahão Dias ,&nbsp;Joice Panzarin Savietto","doi":"10.1016/j.xjidi.2023.100252","DOIUrl":"https://doi.org/10.1016/j.xjidi.2023.100252","url":null,"abstract":"<div><p>Recent studies have provided information about digital eye strain and the potential damage that blue light from digital devices can cause to the eyes. In this study, we analyzed the influence of blue light exposure on reconstructed 3-dimensional skin model using RNA sequencing to identify the expression of transcripts and abnormal events. Three-dimensional skin was exposed to visible light spectrum and isolated blue wavelength for 1, 2, and 4 hours to represent acute exposure and 1 hour over 4 sequential days to represent repeated exposure, respectively, in this in vitro model. We compared gene expression levels with those of unexposed control. Samples submitted to repeated exposure showed reduced <em>AK2</em> and <em>DDX47</em>, whereas they showed increased <em>PABPC3</em> gene expression, revealing a significantly negative impact. RT-PCR validation assay with exposed 3-dimensional skin compared with unexposed control regarding 1 and 4 days of incubation showed increased IL-6 signaling mechanism activation and signal transducer and activator of transcription 3 gene <em>STAT3</em> gene expression, whereas it showed decreased peroxisome proliferator–activated receptor signaling mechanism activation, suggesting an influence on inflammatory pathways. We also demonstrate upregulated gene expression of <em>KIT</em>, <em>MAPK2</em>, and <em>PI3KC</em> in samples from exposed condition, corroborating previous findings related to pigmentation signaling stimuli. These results reveal, to our knowledge, previously unreported data that enable studies on molecular response correlation of in vitro digital blue light exposure and human skin studies.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 2","pages":"Article 100252"},"PeriodicalIF":0.0,"publicationDate":"2023-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026723000784/pdfft?md5=08dc530c0237759cfbbc90392adda77b&pid=1-s2.0-S2667026723000784-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139674542","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":"ATI-1777, a Topical Jak1/3 Inhibitor, May Benefit Atopic Dermatitis without Systemic Drug Exposure: Results from Preclinical Development and Phase 2a Randomized Control Study ATI-1777-AD-201","authors":"Paul Changelian ,&nbsp;Canxin Xu ,&nbsp;Steve Mnich ,&nbsp;Heidi Hope ,&nbsp;Kourtney Kostecki ,&nbsp;Jeff Hirsch ,&nbsp;Chin-Yi Loh ,&nbsp;David Anderson ,&nbsp;James Blinn ,&nbsp;Susan Hockerman ,&nbsp;Evan Dick ,&nbsp;Walter Smith ,&nbsp;Joseph Monahan ,&nbsp;Tooraj Raoof ,&nbsp;Seth Forman ,&nbsp;David Burt ,&nbsp;Brad Barnes ,&nbsp;David Gordon ,&nbsp;Neal Walker ,&nbsp;John Sudzina ,&nbsp;Jon Jacobsen","doi":"10.1016/j.xjidi.2023.100251","DOIUrl":"10.1016/j.xjidi.2023.100251","url":null,"abstract":"<div><h3>Introduction</h3><p>Atopic dermatitis, a chronic, pruritic skin disease, affects 10–30% of children and up to 14% of adults in developed countries. ATI-1777, a potent and selective Jak1/3 inhibitor, was designed with multiple sites of metabolism to deliver local efficacy in the skin and limit systemic exposure. In preclinical studies, ATI-1777 selectively inhibited Jak1/3 with limited systemic exposure and without any adverse effects.</p></div><div><h3>Primary objective</h3><p>The primary goal of this study was to assess the preliminary clinical efficacy of ATI-1777 topical solution in adults with moderate or severe atopic dermatitis.</p></div><div><h3>Design</h3><p>ATI-1777-AD-201, a phase 2a, first-in-human, randomized, double-blind, vehicle-controlled, parallel-group study, evaluated the efficacy, safety, tolerability, and pharmacokinetics of ATI-1777 topical solution in 48 participants with atopic dermatitis over 4 weeks.</p></div><div><h3>Primary endpoint</h3><p>The primary endpoint was a reduction of a modified Eczema Area and Severity Index score from baseline.</p></div><div><h3>Results</h3><p>Reduction was significantly greater in the ATI-1777–treated group on day 28 than in vehicle-treated group (percentage reduction from baseline = 74.45% [standard error = 6.455] and 41.43% [standard error = 6.189], respectively [<em>P</em> &lt; .001]). Average plasma concentrations of ATI-1777 were &lt;5% of the half-maximal inhibitory concentration of ATI-1777 for inhibiting Jak1/3. No deaths or serious adverse events were reported.</p></div><div><h3>Conclusion</h3><p>Topical ATI-1777 does not lead to pharmacologically relevant systemic drug exposure and may reduce clinical signs of atopic dermatitis.</p></div><div><h3>Trial Registration</h3><p>The study was registered at <span>ClinicalTrials.gov</span><svg><path></path></svg> with the number NCT04598269.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 2","pages":"Article 100251"},"PeriodicalIF":0.0,"publicationDate":"2023-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026723000772/pdfft?md5=78250cf1d25122b4519a0a1e75ccb92f&pid=1-s2.0-S2667026723000772-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139299399","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":"Therapeutic TNF Inhibitors Exhibit Differential Levels of Efficacy in Accelerating Cutaneous Wound Healing","authors":"Yonghao Cao ,&nbsp;Bohdan P. Harvey ,&nbsp;Liang Jin ,&nbsp;Susan Westmoreland ,&nbsp;Jing Wang ,&nbsp;Munish Puri ,&nbsp;Yingli Yang ,&nbsp;Holly M. Robb ,&nbsp;Sultan Tanriverdi ,&nbsp;Chenqi Hu ,&nbsp;Xue Wang ,&nbsp;Xiaofeng Xin ,&nbsp;Yingchun Liu ,&nbsp;Michael P. Macoritto ,&nbsp;Kathleen M. Smith ,&nbsp;Yu Tian ,&nbsp;Kevin White ,&nbsp;Timothy R.D.J. Radstake ,&nbsp;Zehra Kaymakcalan","doi":"10.1016/j.xjidi.2023.100250","DOIUrl":"https://doi.org/10.1016/j.xjidi.2023.100250","url":null,"abstract":"<div><p>Adalimumab but neither etanercept nor certolizumab-pegol has been reported to induce a wound-healing profile in vitro by regulating macrophage differentiation and matrix metalloproteinase expression, which may underlie the differences in efficacy between various TNF-α inhibitors in impaired wound healing in patients with hidradenitis suppurativa, a chronic inflammatory skin disease. To examine and compare the efficacy of various TNF inhibitors in cutaneous wound healing in vivo, a human TNF knock-in Lepr^db/db mouse model was established to model the impaired cutaneous wound healing as seen in hidradenitis suppurativa. The vehicle group exhibited severe impairments in cutaneous wound healing. In contrast, adalimumab significantly accelerated healing, confirmed by both histologic assessment and a unique healing transcriptional profile. Moreover, adalimumab and infliximab showed similar levels of efficacy, but golimumab was less effective, along with etanercept and certolizumab-pegol. In line with histologic assessments, proteomics analyses from healing wounds exposed to various TNF inhibitors revealed distinct and differential wound-healing signatures that may underlie the differential efficacy of these inhibitors in accelerating cutaneous wound healing. Taken together, these data revealed that TNF inhibitors exhibited differential levels of efficacy in accelerating cutaneous wound healing in the impaired wound-healing model in vivo.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 1","pages":"Article 100250"},"PeriodicalIF":0.0,"publicationDate":"2023-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026723000760/pdfft?md5=f4ab8caac6cdc9955299fd7f7706a2ea&pid=1-s2.0-S2667026723000760-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139038398","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":"Identification of Collagen-Suppressive Agents in Keloidal Fibroblasts Using a High-Content, Phenotype-Based Drug Screen","authors":"Anpuchchelvi Rajadurai ,&nbsp;Hensin Tsao","doi":"10.1016/j.xjidi.2023.100248","DOIUrl":"10.1016/j.xjidi.2023.100248","url":null,"abstract":"<div><p>Keloids are characterized by excessive extracellular collagen and exaggerated scarring. Large-volume lesions can be functionally debilitating, therapeutically intractable, and psychologically devastating. A key barrier to translational momentum for novel antikeloid agents is the lack of a faithful high-content screen. We devised, to our knowledge, a previously unreported phenotype-based assay that measures secreted collagen by keloidal fibroblasts in tissue hypoxic conditions (1% oxygen). Four keloidal fibroblasts and 1 normal dermal fibroblast line were exposed to 199 kinase inhibitors. Of 199 kinase inhibitors, 41 (21%) and 71 (36%) increased and decreased the <span><math><mrow><mover><mtext>CI</mtext><mo>¯</mo></mover></mrow></math></span> _norm (mean collagen inhibition normalized to viability) by more than 10%, respectively. The most collagen suppressive agents were CGP60474 (<span><math><mrow><mover><mtext>CI</mtext><mo>¯</mo></mover></mrow></math></span> _norm = 0.36), KIN001-244 (<span><math><mrow><mover><mtext>CI</mtext><mo>¯</mo></mover></mrow></math></span> _norm = 0.55), and RAF265 (<span><math><mrow><mover><mtext>CI</mtext><mo>¯</mo></mover></mrow></math></span> _norm = 0.58). The top candidate, CGP60474, consistently abolished collagens I and VII production, exhibited minimal global toxicity, and induced a fivefold increase in phosphorylated extracellular signal–regulated kinase. This proof-of-concept high-content screen can identify drugs that appear to target critical keloidal pathophysiology—collagen secretion.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 2","pages":"Article 100248"},"PeriodicalIF":0.0,"publicationDate":"2023-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026723000747/pdfft?md5=69233229cb67e080c243959f33927281&pid=1-s2.0-S2667026723000747-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139298649","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":"En Route to Targeted Ribosome Editing to Replenish Skin Anchor Protein LAMB3 in Junctional Epidermolysis Bullosa","authors":"Bjoern Wimmer ,&nbsp;Andreas Friedrich ,&nbsp;Katharina Poeltner ,&nbsp;Genevieve Edobor ,&nbsp;Claudia Mosshammer ,&nbsp;Gazmend Temaj ,&nbsp;Adriana Rathner ,&nbsp;Thomas Karl ,&nbsp;Jan Krauss ,&nbsp;Joerg von Hagen ,&nbsp;Christopher Gerner ,&nbsp;Michael Breitenbach ,&nbsp;Helmut Hintner ,&nbsp;Johann W. Bauer ,&nbsp;Hannelore Breitenbach-Koller","doi":"10.1016/j.xjidi.2023.100240","DOIUrl":"10.1016/j.xjidi.2023.100240","url":null,"abstract":"<div><p>Severe junctional epidermolysis bullosa is a rare genetic, postpartum lethal skin disease, predominantly caused by nonsense/premature termination codon (PTC) sequence variants in <em>LAMB3</em> gene. <em>LAMB3</em> encodes LAMB3, the β subunit of epidermal–dermal skin anchor laminin 332. Most translational reads of a PTC mRNA deliver truncated, nonfunctional proteins, whereas an endogenous PTC readthrough mechanism produces full-length protein at minimal and insufficient levels. Conventional translational readthrough-inducing drugs amplify endogenous PTC readthrough; however, translational readthrough-inducing drugs are either proteotoxic or nonselective. Ribosome editing is a more selective and less toxic strategy. This technique identified ribosomal protein L35/uL29 (ie, RpL35) and RpL35-ligands repurposable drugs artesunate and atazanavir as molecular tools to increase production levels of full-length LAMB3. To evaluate ligand activity in living cells, we monitored artesunate and atazanavir treatment by dual luciferase reporter assays. Production levels of full-length LAMB3 increased up to 200% upon artesunate treatment, up to 150% upon atazanavir treatment, and up to 170% upon combinatorial treatment of RpL35 ligands at reduced drug dosage, with an unrelated PTC reporter being nonresponsive. Proof of bioactivity of RpL35 ligands in selective increase of full-length LAMB3 provides the basis for an alternative, targeted therapeutic route to replenish LAMB3 in severe junctional epidermolysis bullosa.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 1","pages":"Article 100240"},"PeriodicalIF":0.0,"publicationDate":"2023-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026723000668/pdfft?md5=fdfc75a682b9369e4d5f25ea8475ea44&pid=1-s2.0-S2667026723000668-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135615075","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":"Circulating Oxidized mtDNA is Associated Broadly with Cardiovascular Disease in a Longitudinal Cohort Study of Psoriasis","authors":"Sundus S. Lateef ,&nbsp;Grace A. Ward ,&nbsp;Haiou Li ,&nbsp;Carla Pantoja ,&nbsp;Elizabeth Florida ,&nbsp;Christin G. Hong ,&nbsp;Justin Rodante ,&nbsp;Andrew Keel ,&nbsp;Marcus Y. Chen ,&nbsp;Alexander V. Sorokin ,&nbsp;Martin P. Playford ,&nbsp;Nehal N. Mehta","doi":"10.1016/j.xjidi.2023.100243","DOIUrl":"10.1016/j.xjidi.2023.100243","url":null,"abstract":"<div><p>Psoriasis (PSO) is a chronic and systemic inflammatory autoimmune disease associated with atherosclerosis and myocardial infarction. Given that atherosclerosis is both inflammation and immune driven, we sought to expand on known immune and inflammatory biomarkers in a PSO cohort. In this study, we focus on oxidized mtDNA (ox-mtDNA), a product of cells undergoing pyroptosis, including keratinocytes, which was quantified in patients with PSO and individuals without PSO by ELISA. Patients with PSO had significantly higher ox-mtDNA levels than healthy subjects (mean ± SD = 9246 ± 2518 pg/ml for patients with PSO vs 7382 ± 2506 pg/ml for those without; <em>P</em> = .006). Importantly, ox-mtDNA was positively associated with IL-17a (β = 0.25; <em>P</em> = .03) and low-density granulocytes (β = 0.37; <em>P</em> = .005) but negatively associated with high-density lipoprotein-cholesterol (β = −0.29; <em>P</em> = .006). After adjusting for traditional cardiovascular risk factors, we found that ox-mtDNA was associated with noncalcified coronary burden, which was measured by coronary computed tomography angiography (β = 0.19; <em>P</em> = .003). Biologic-naïve patients with PSO receiving anti–IL-17a therapy had a 14% decrease in ox-mtDNA (mean ± SD: 10540 ± 614 pg/ml at baseline to 9016 ± 477 pg/ml at 1 year; <em>P</em> = .016) and a 10% reduction in noncalcified coronary artery burden (mean ± SD: 1.06 ± 0.45 at baseline, reducing to 0.95 ± 0.35 at 1 year; <em>P</em> = .0037). In summary, levels of ox-mtDNA in PSO are associated with measures of coronary plaque formation, indicating that this biomarker may be an autoimmune-driven early atherosclerotic feature.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 1","pages":"Article 100243"},"PeriodicalIF":0.0,"publicationDate":"2023-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026723000693/pdfft?md5=a3ffc8a314f631e47e11add3d33b50dd&pid=1-s2.0-S2667026723000693-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135410791","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":"Strategic Approach to Heterogeneity Analysis of Cutaneous Adnexal Carcinomas Using Computational Pathology and Genomics","authors":"Yuuki Nishimura ,&nbsp;Eijitsu Ryo ,&nbsp;Satoshi Inoue ,&nbsp;Masahito Kawazu ,&nbsp;Toshihide Ueno ,&nbsp;Kenjiro Namikawa ,&nbsp;Akira Takahashi ,&nbsp;Dai Ogata ,&nbsp;Akihiko Yoshida ,&nbsp;Naoya Yamazaki ,&nbsp;Hiroyuki Mano ,&nbsp;Yasushi Yatabe ,&nbsp;Taisuke Mori","doi":"10.1016/j.xjidi.2023.100229","DOIUrl":"https://doi.org/10.1016/j.xjidi.2023.100229","url":null,"abstract":"<div><p>Cutaneous adnexal tumors are neoplasms that arise from skin appendages. Their morphologic diversity and phenotypic variability with rare progression to malignancy make them difficult to diagnose and classify, and there is currently no established treatment strategy. To overcome these difficulties, this study investigated the transcription factor SOX9 expression, morphology, and genetics of skin adnexal tumors for understanding their biology, especially their histogenesis. We showed that cutaneous adnexal tumors and their nontumor counterparts of skin and appendages exhibit expression patterns similar to that of SOX9. Its expression intensity and pattern, as well as histopathologic evaluation of tumors, were analyzed using digital images of 69 normal skin adnexal 9-type organs and 185 skin adnexal 29-type tumors as references. It was possible to distinguish basal cell carcinoma from squamous cell carcinoma, sebaceous carcinoma, and pilomatrixoma with significant differences, along with porocarcinoma from squamous cell carcinoma. Furthermore, unsupervised machine learning “computational pathology” was used to derive a multiregion whole-exome sequencing fusion method termed “genocomputed pathology.” The genocomputed pathology of three representable adnexal carcinomas (porocarcinoma, hidradenocarcinoma, and spiradenocarcinoma) was evaluated for total nine cases. We showed that there was more heterogeneity than expected within the tumors as well as the coexistence of components lacking driver fusion genes. The presence or absence of potential driver genes, such as <em>PIK3CA</em>, <em>YAP1</em>, and <em>PTEN</em>, in each region was identified, highlighting a therapeutic strategy for cutaneous adnexal carcinoma encompassing heterogeneous tumors.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"3 6","pages":"Article 100229"},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026723000553/pdfft?md5=5bafdd911a89cbf7bbf564649a7f0837&pid=1-s2.0-S2667026723000553-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92042333","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}