JID innovations : skin science from molecules to population health最新文献_第7页

Surgical Debulking Modifies Notch Signaling and May Improve Vismodegib Effectiveness for Locally Advanced Basal Cell Carcinoma 手术切除可改变 Notch 信号转导，并可提高 vismodegib 对局部晚期基底细胞癌的疗效

JID innovations : skin science from molecules to population health Pub Date : 2024-06-06 DOI: 10.1016/j.xjidi.2024.100288

{"title":"Surgical Debulking Modifies Notch Signaling and May Improve Vismodegib Effectiveness for Locally Advanced Basal Cell Carcinoma","authors":"","doi":"10.1016/j.xjidi.2024.100288","DOIUrl":"10.1016/j.xjidi.2024.100288","url":null,"abstract":"<div><p>Smoothened inhibitors, such as vismodegib, exhibit remarkable success in treating patients with locally advanced basal cell carcinoma (LaBCC). Yet, vismodegib efficacy is hindered by notable side effects, which often lead to treatment discontinuation and subsequent relapse in patients with LaBCC. Prolonged remission was previously reported in patients with LaBCCs who underwent surgical debulking before starting vismodegib. In this study, we enrolled 4 patients with LaBCC who underwent debulking followed by vismodegib therapy to assess their clinical outcomes and analyze the cutaneous molecular changes occurring as a result of surgical intervention. After LaBCC debulking, patients underwent a punch biopsy of residual basal cell carcinoma tissue 1 week later. RT-qPCR analysis of 24 Notch and Wnt signaling–associated genes revealed elevated <em>PTCH1</em>, <em>HEY2</em>, <em>LGR6</em>, <em>FZD2</em>, <em>LEF1</em>, <em>ALCAM</em>, and <em>RUNX1</em> expressions in follow-up biopsies compared with those in patient-matched debulked tissue. Immunoblot and immunostaining further confirmed elevated Notch signaling in follow-up biopsy tissue compared with that in patient-matched debulked tumor tissue. Patients 1, 3, and 4 displayed a clinical response to debulking followed by vismodegib, whereas patient 2 was lost to follow-up after debulking. These findings suggest that surgical manipulation of LaBCCs is correlated with molecular alterations in signaling pathways associated with cellular reprogramming.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 5","pages":"Article 100288"},"PeriodicalIF":0.0,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026724000353/pdfft?md5=8e38d3493d42fc9fadec23a5fb353a36&pid=1-s2.0-S2667026724000353-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141405897","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

Metastatic Cutaneous Squamous Cell Carcinoma in Immunosuppressed Patient: A Systematic Review 免疫抑制患者的转移性皮肤鳞状细胞癌：系统综述

JID innovations : skin science from molecules to population health Pub Date : 2024-06-05 DOI: 10.1016/j.xjidi.2024.100294

{"title":"Metastatic Cutaneous Squamous Cell Carcinoma in Immunosuppressed Patient: A Systematic Review","authors":"","doi":"10.1016/j.xjidi.2024.100294","DOIUrl":"10.1016/j.xjidi.2024.100294","url":null,"abstract":"<div><p>Patients who are immunosuppressed, such as solid organ transplant recipients (SOTRs), are at a higher risk of developing cutaneous squamous cell carcinoma (cSCC). This population is at a higher risk of metastasis and worse disease-specific survival. The objective of this review is to better characterize the immunosuppressed population with metastatic cSCC. A literature search was conducted to identify reports of lymphatic metastases in immunosuppressed patients with cSCC. Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were followed during creation of a cohort with desired inclusion and exclusion criteria. One hundred and thirty-five articles met the inclusion/exclusion criteria, yielding 1020 total cases. We discovered that the most common forms of immunosuppression within the cohort were solid organ transplantation and hematologic malignancy. White males and cSCC tumors involving the head and neck comprised most cases. Using Brigham and Women’s Hospital and Eighth edition of American Joint Committee on Cancer tumor staging criteria, we observed a trend toward higher stage tumors in SOTR than in patients with hematologic malignancy. This review confirms that known clinical risk factors for metastatic cSCC appear to be similar among the immunosuppressed population and the cSCC population at large. Interestingly, our data suggest that current staging systems may not accurately reflect metastatic risk among patients with hematologic malignancy.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 5","pages":"Article 100294"},"PeriodicalIF":0.0,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026724000419/pdfft?md5=69c95570f1b3b57d39721c9bab2639e4&pid=1-s2.0-S2667026724000419-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141397624","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

The Role of the Neurotrophin Network in Skin Squamous Cell Cancer and the Novel Use of the Zebrafish System 神经营养素网络在皮肤鳞状细胞癌中的作用以及斑马鱼系统的新应用

JID innovations : skin science from molecules to population health Pub Date : 2024-06-05 DOI: 10.1016/j.xjidi.2024.100295

Marika Quadri , Elisabetta Palazzo

{"title":"The Role of the Neurotrophin Network in Skin Squamous Cell Cancer and the Novel Use of the Zebrafish System","authors":"Marika Quadri , Elisabetta Palazzo","doi":"10.1016/j.xjidi.2024.100295","DOIUrl":"10.1016/j.xjidi.2024.100295","url":null,"abstract":"<div><p>Cutaneous squamous cell carcinoma (cSCC) is the second most prevalent form of skin cancer. An increasing number of cSCCs are associated with dysregulation of key molecules that control skin homeostasis. These observations have increased interest in the role of neurotrophins and their receptors in the pathogenesis of cSCC. They have been demonstrated to have a considerable impact on the aggressiveness potential of skin cancer by both in vitro and in vivo models. In this context, mouse models are classically used to dissect proliferation versus differentiation balance, but they have some limitations in terms of time, space, and costs. Recently, zebrafish models have been implemented as a new tool to obtain information regarding the invasive capacity and metastasis of neoplastic cells. By xenotransplantation technique, cSCC cells from a patient’s biopsy or cell line can be successfully characterized, with or without the presence of genetic manipulation or treatments. In addition, the evaluation of the immune microenvironment contributes to potentially identifying connections and homologies with humans. In this review, we retrace the role of the neurotrophin network in healthy and pathological skin, particularly in cSCC. We review how zebrafish models can be important tools for studying cSCC development, growth, and potential treatments.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 5","pages":"Article 100295"},"PeriodicalIF":0.0,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026724000420/pdfft?md5=d8e7142288443c85db28eaed341b2084&pid=1-s2.0-S2667026724000420-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141403396","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

Guselkumab Reduces Disease- and Mechanism-Related Biomarkers More Than Adalimumab in Patients with Psoriasis: A VOYAGE 1 Substudy 与阿达木单抗相比，古舍库单抗更能降低银屑病患者的疾病和机制相关生物标记物：VOYAGE 1 子研究

JID innovations : skin science from molecules to population health Pub Date : 2024-06-05 DOI: 10.1016/j.xjidi.2024.100287

{"title":"Guselkumab Reduces Disease- and Mechanism-Related Biomarkers More Than Adalimumab in Patients with Psoriasis: A VOYAGE 1 Substudy","authors":"","doi":"10.1016/j.xjidi.2024.100287","DOIUrl":"10.1016/j.xjidi.2024.100287","url":null,"abstract":"<div><h3>Background</h3><p>Psoriasis is an immune-mediated inflammatory disease characterized by activation of IL-23–driven IL-17–producing T cell and other IL-23 receptor–positive IL-17–producing cell responses. Selective blockade of IL-23p19 with guselkumab was superior to blockade of TNF-α with adalimumab (ADA) in treating moderate-to-severe psoriasis. Objective: Pharmacodynamic responses of guselkumab versus ADA were compared in patients with psoriasis in VOYAGE 1.</p></div><div><h3>Design</h3><p>Inflammatory cytokine serum levels were assessed (n = 118), and lesional and nonlesional skin biopsies were collected (n = 38) in patient subsets at baseline and 4, 24, and 48 weeks after treatment to evaluate pharmacodynamic responses of guselkumab versus those of ADA.</p></div><div><h3>Results</h3><p>Guselkumab provided rapid reductions in serum IL-17A, IL-17F, and IL-22 levels by week 4 versus at baseline, which were maintained through weeks 24 and 48 (<em>P</em> < .001). The magnitude of reduction of IL-17A and IL-22 at week 48 and IL-17F at weeks 4, 24, and 48 were greater with guselkumab than with ADA (all <em>P</em> < .05). In the skin, guselkumab reduced the expression of IL-23/IL-17 pathway–associated and psoriasis-associated genes.</p></div><div><h3>Conclusion</h3><p>These data provide extensive characterization of pharmacodynamic anti-inflammatory responses to IL-23p19 and TNF-α inhibition in human blood and tissue over time with FDA-approved doses of guselkumab and ADA. <strong>Trial registration:</strong> <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span><span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> (NCT02207231).</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 5","pages":"Article 100287"},"PeriodicalIF":0.0,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026724000341/pdfft?md5=e41b338ba36749e6935747be01c4f97d&pid=1-s2.0-S2667026724000341-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141414560","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

Dermatologic Considerations for Spaceflight and Space Exploration 太空飞行和太空探索中的皮肤科注意事项

JID innovations : skin science from molecules to population health Pub Date : 2024-05-31 DOI: 10.1016/j.xjidi.2024.100293

Megan Zhao , Haig Aintablian , Robert L. Satcher , Roxana Daneshjou , Misha Rosenbach

引用次数: 0

Factors Associated with Adoption of Immune Checkpoint Inhibitor Treatment for Advanced Melanoma: A SEER-Medicare Cohort Study 采用免疫检查点抑制剂治疗晚期黑色素瘤的相关因素： SEER-医保队列研究

JID innovations : skin science from molecules to population health Pub Date : 2024-05-21 DOI: 10.1016/j.xjidi.2024.100289

Cassandra Mohr , Kaiping Liao , Candice L. Hinkston , Mackenzie R. Wehner , Meng Li

{"title":"Factors Associated with Adoption of Immune Checkpoint Inhibitor Treatment for Advanced Melanoma: A SEER-Medicare Cohort Study","authors":"Cassandra Mohr , Kaiping Liao , Candice L. Hinkston , Mackenzie R. Wehner , Meng Li","doi":"10.1016/j.xjidi.2024.100289","DOIUrl":"10.1016/j.xjidi.2024.100289","url":null,"abstract":"<div><p>We aimed to explore the differences in immune checkpoint inhibitor (ICI) immunotherapy utilization for advanced melanoma by examining patient and neighborhood characteristics. We performed a retrospective cohort study using a deidentified, random sample of SEER-Medicare beneficiaries aged ≥65 years with stage III or stage IV melanoma (2011–2017). Our primary outcome was initiation of ICI immunotherapy (ipilimumab, pembrolizumab, nivolumab, or atezolizumab) after stage III or stage IV melanoma diagnosis. We analyzed ICI usage with multivariable logistic regression. After analyzing the entire 2011–2017 cohort, we conducted a secondary analysis in which we separately analyzed the 2011–2014 and 2015–2017 cohorts to assess possible differences over time. We included 3531 beneficiaries, with mean follow-up of 2.1 (SD = 2.0) years. Higher likelihood of ICI usage was associated with male sex (OR = 1.21, 95% confidence interval = 1.04–1.42) and higher density of medical oncologists (OR = 1.02, 95% confidence interval = 1.01–1.04). Lower likelihood of ICI usage was associated with older age group and Charlson comorbidity score (score ≥2; OR = 0.72, 95% confidence interval = 0.60–0.86). These associations were diminished in more recent years (no association with sex, medical oncologist density, Charlson comorbidity score, and association with only the oldest age group in years 2015–2017). We found significant sex- and age-related differences in initiation among SEER-Medicare beneficiaries with stage III or stage IV melanoma, which appear to be improving over time.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 4","pages":"Article 100289"},"PeriodicalIF":0.0,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026724000365/pdfft?md5=9afd44e58671efdf3c0ed9288dd00f3c&pid=1-s2.0-S2667026724000365-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141134453","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

MicroRNA Signatures Associated with Basal Cell Carcinoma Subtypes 与基底细胞癌亚型相关的微RNA特征

JID innovations : skin science from molecules to population health Pub Date : 2024-05-03 DOI: 10.1016/j.xjidi.2024.100286

Suzanne Fastner , Hafeez Rahman , Jose Gutierrez , Nathan Shen , Scott R. Florell , Abigail Florell , Chris J. Stubben , Kenneth M. Boucher , Dekker C. Deacon , Robert L. Judson-Torres , Douglas Grossman

{"title":"MicroRNA Signatures Associated with Basal Cell Carcinoma Subtypes","authors":"Suzanne Fastner , Hafeez Rahman , Jose Gutierrez , Nathan Shen , Scott R. Florell , Abigail Florell , Chris J. Stubben , Kenneth M. Boucher , Dekker C. Deacon , Robert L. Judson-Torres , Douglas Grossman","doi":"10.1016/j.xjidi.2024.100286","DOIUrl":"10.1016/j.xjidi.2024.100286","url":null,"abstract":"<div><p>Basal cell carcinoma (BCC) is classified histologically into subtypes that determine treatment decisions. MicroRNAs (miRs) are short noncoding RNAs that may serve as diagnostic biomarkers. We investigated if particular miRs could distinguish BCC subtypes. We sequenced miRs from 55 archival BCC and 9 control skin specimens and then validated these miRs by qRT-PCR assay on a second BCC cohort (18 superficial, 16 nodular, 15 infiltrative) and control skin (n = 12). Expression values for individual miRs were normalized to miR-16-5p, which was the least variant among the control skin and BCC samples. We found that (i) miR-383-5p and miR-145-5p are downregulated in all BCC subtypes compared with control skin, (ii) miR-181c-5p is downregulated in superficial compared with invasive (nodular/infiltrative) BCC, and (iii) miR-22-5p and miR-708-5p are upregulated in infiltrative compared with superficial/nodular BCC and miR-30c-5p is downregulated in infiltrative compared with nodular BCC. Receiver operating characteristic analysis demonstrated excellent capacity of these miRs to discriminate between BCC and control skin (area under the curve, 0.94–0.98), whereas the capacity to discriminate between superficial and invasive subtypes was less robust (area under the curve, 0.7–0.8). Future prospective studies may determine the utility of these miRs as diagnostic biomarkers to guide biopsy and treatment of BCC.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 4","pages":"Article 100286"},"PeriodicalIF":0.0,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S266702672400033X/pdfft?md5=5b73694006f30288640b9ea9f57e5331&pid=1-s2.0-S266702672400033X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141035605","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

NOD/Scid IL2Rγnull Mice Reconstituted with PBMCs from Patients with Atopic Dermatitis or Psoriasis Vulgaris Reflect the Respective Phenotype 用特应性皮炎或寻常型银屑病患者的外周血单核细胞重组的 NOD/Scid IL2Rγ 空鼠反映了各自的表型。

JID innovations : skin science from molecules to population health Pub Date : 2024-05-01 DOI: 10.1016/j.xjidi.2024.100268

Marietta Schindler , Paula Schuster-Winkelmann , Veronika Weß , Sophia Czell , Franziska Rueff , Andreas Wollenberg , Matthias Siebeck , Roswitha Gropp

{"title":"NOD/Scid IL2Rγnull Mice Reconstituted with PBMCs from Patients with Atopic Dermatitis or Psoriasis Vulgaris Reflect the Respective Phenotype","authors":"Marietta Schindler , Paula Schuster-Winkelmann , Veronika Weß , Sophia Czell , Franziska Rueff , Andreas Wollenberg , Matthias Siebeck , Roswitha Gropp","doi":"10.1016/j.xjidi.2024.100268","DOIUrl":"10.1016/j.xjidi.2024.100268","url":null,"abstract":"<div><p>NSG (NOD/Scid IL2Rγ<sup>null</sup>) mice reconstituted with PBMCs donated by patients with ulcerative colitis or Crohn’s disease highly reflect the respective pathological phenotype. To determine whether these findings could be applicable to atopic dermatitis (AD) and psoriasis vulgaris (PV), PBMCs isolated from patients with AD and PV were first subjected to immunological profiling. Subsequently, NSG mice were reconstituted with these PBMCs. Hierarchical clustering and network analysis revealed a distinct profile of patients with AD and PV with activated CD4+ T cells (CD69, CD25) occupying a central position in the AD network and CD4+ CD134+ cells acting as the main hub in the PV network. After dermal application of DMSO, both NSG mice reconstituted with PBMCs from donors with AD (ie, NSG-AD mice) and NSG mice reconstituted with PBMCs from donors with PV (ie, NSG-PV mice) exhibited increased clinical, skin, and histological scores. Immunohistochemical analysis, frequencies of splenic human leukocytes, and cytokine expression levels indicated that CD4+ CD69+ cells, M1 and TSLP receptor–expressing monocytes, switched B cells, and monocyte chemoattractant protein 3 were the driving factors of inflammation in NSG-AD mice. In contrast, inflammation in NSG-PV mice was characterized by an increase in fibroblasts in the epidermis, frequencies of CD1a-expressing monocytes, and IL-17 levels. Therefore, the pathological phenotypes of NSG-AD mice and NSG-PV mice differ and partially reflect the respective human diseases.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 3","pages":"Article 100268"},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026724000146/pdfft?md5=00fd321e7bee9d649d4f7311c571778b&pid=1-s2.0-S2667026724000146-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139875284","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

Identification of Keratinocyte Cytoprotectants against Toxicity by the Multikinase Inhibitor Sorafenib Using Drug Repositioning 利用药物重定位技术鉴定角质形成细胞细胞保护剂，以对抗多激酶抑制剂索拉非尼的毒性

JID innovations : skin science from molecules to population health Pub Date : 2024-05-01 DOI: 10.1016/j.xjidi.2024.100271

Yayoi Kamata , Rui Kato , Mitsutoshi Tominaga , Sumika Toyama , Eriko Komiya , Jun Utsumi , Takahide Kaneko , Yasushi Suga , Kenji Takamori

{"title":"Identification of Keratinocyte Cytoprotectants against Toxicity by the Multikinase Inhibitor Sorafenib Using Drug Repositioning","authors":"Yayoi Kamata , Rui Kato , Mitsutoshi Tominaga , Sumika Toyama , Eriko Komiya , Jun Utsumi , Takahide Kaneko , Yasushi Suga , Kenji Takamori","doi":"10.1016/j.xjidi.2024.100271","DOIUrl":"10.1016/j.xjidi.2024.100271","url":null,"abstract":"<div><p>Hand–foot skin reaction is the most common adverse event of multikinase inhibitors, such as sorafenib. Although hand–foot skin reaction is not life threatening, severe cases impair quality of life because of pain and reduced activities of daily living. However, the pathological mechanisms of hand–foot skin reaction have not yet been elucidated in detail, and there is currently no effective treatment. We aimed to identify keratinocyte cytoprotectants against sorafenib toxicity. The screening of cytoprotectants against sorafenib toxicity was performed using cultured normal human epidermal keratinocytes or a reconstructed human epidermis model and off-patent approved drugs in the Prestwick Chemical library. Among 1273 drugs in the chemical library, 8 dose-dependently increased cell viability by >200% in the presence of sorafenib. In the presence of sorafenib, the number of proliferating cell nuclear antigen–positive cells was significantly higher in clofazimine-, cyclosporin A–, and itraconazole-treated reconstructed human epidermis models than in sorafenib-treated models, and candidate drugs suppressed sorafenib-induced apoptosis in normal human epidermal keratinocytes. In addition, clofazimine, itraconazole, and pyrvinium pamoate significantly recovered the phosphorylation of extracellular signal–regulated kinase 1/2 in the presence of sorafenib. Collectively, hit drugs promoted cell viability and normalized keratinocyte proliferation in the presence of sorafenib. These candidate drugs have potential as treatments for multikinase inhibitor–induced hand–foot skin reaction.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 3","pages":"Article 100271"},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026724000183/pdfft?md5=6ac09b2f5c88dad96300d97f7d0fd131&pid=1-s2.0-S2667026724000183-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140470031","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

In Silico Elucidation of Key Drivers of Staphyloccocus aureus–Staphyloccocus epidermidis–Induced Skin Damage in Atopic Dermatitis Lesions 在特应性皮炎皮损中，金黄色葡萄球菌-表皮茵诱发皮肤损伤的关键驱动因素的硅学阐释

JID innovations : skin science from molecules to population health Pub Date : 2024-05-01 DOI: 10.1016/j.xjidi.2024.100269

Jamie Lee , Ahmad A. Mannan , Takuya Miyano , Alan D. Irvine , Reiko J. Tanaka

{"title":"In Silico Elucidation of Key Drivers of Staphyloccocus aureus–Staphyloccocus epidermidis–Induced Skin Damage in Atopic Dermatitis Lesions","authors":"Jamie Lee , Ahmad A. Mannan , Takuya Miyano , Alan D. Irvine , Reiko J. Tanaka","doi":"10.1016/j.xjidi.2024.100269","DOIUrl":"10.1016/j.xjidi.2024.100269","url":null,"abstract":"<div><p><em>Staphylococcus aureus</em> (SA) colonizes and can damage skin in atopic dermatitis lesions, despite being commonly found with <em>Staphylococcus epidermidis</em> (SE), a commensal that can inhibit SA’s virulence and kill SA. In this study, we developed an <em>in silico</em> model, termed a virtual skin site, describing the dynamic interplay between SA, SE, and the skin barrier in atopic dermatitis lesions to investigate the mechanisms driving skin damage by SA and SE. We generated 10<sup>6</sup> virtual skin sites by varying model parameters to represent different skin physiologies and bacterial properties. <em>In silico</em> analysis revealed that virtual skin sites with no skin damage in the model were characterized by parameters representing stronger SA and SE growth attenuation than those with skin damage. This inspired an <em>in silico</em> treatment strategy combining SA-killing with an enhanced SA–SE growth attenuation, which was found through simulations to recover many more damaged virtual skin sites to a non-damaged state, compared with SA-killing alone. This study demonstrates that <em>in silico</em> modelling can help elucidate the key factors driving skin damage caused by SA–SE colonization in atopic dermatitis lesions and help propose strategies to control it, which we envision will contribute to the design of promising treatments for clinical studies.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 3","pages":"Article 100269"},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S266702672400016X/pdfft?md5=178aabaf5651f027521d8120342ea113&pid=1-s2.0-S266702672400016X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140467524","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