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

{"title":"Testing the Reliability of Optical Coherence Tomography to Measure Epidermal Thickness and Distinguish Volar and Nonvolar Skin","authors":"Molly E. Baumann ,&nbsp;Nina Rossa Haddad ,&nbsp;Alyssa Salazar ,&nbsp;W. Lee Childers ,&nbsp;Shawn Farrokhi ,&nbsp;Neil B. Goldstein ,&nbsp;Brad D. Hendershot ,&nbsp;Lisa Reider ,&nbsp;Richard E. Thompson ,&nbsp;Michael S. Valerio ,&nbsp;Christopher L. Dearth ,&nbsp;Luis A. Garza ,&nbsp;Major Extremity Trauma Research Consortium (METRC)","doi":"10.1016/j.xjidi.2024.100276","DOIUrl":"10.1016/j.xjidi.2024.100276","url":null,"abstract":"<div><p>In persons with limb loss, prosthetic devices cause skin breakdown, largely because residual limb skin (nonvolar) is not intended to bear weight such as palmoplantar (volar) skin. Before evaluation of treatment efficacy to improve skin resiliency, efforts are needed to establish normative data and assess outcome metric reliability. The purpose of this study was to use optical coherence tomography to (i) characterize volar and nonvolar skin epidermal thickness and (ii) examine the reliability of optical coherence tomography. Four orientations of optical coherence tomography images were collected on 33 volunteers (6 with limb loss) at 2 time points, and the epidermis was traced to quantify thickness by 3 evaluators. Epidermal thickness was greater (<em>P</em> &lt; .01) for volar skin (palm) (265.1 ± 50.9 μm, n = 33) than for both nonvolar locations: posterior thigh (89.8 ± 18.1 μm, n = 27) or residual limb (93.4 ± 27.4 μm, n = 6). The inter-rater intraclass correlation coefficient was high for volar skin (0.887–0.956) but low for nonvolar skin (thigh: 0.292–0.391, residual limb: 0.211–0.580). Correlation improved when comparing only 2 evaluators who used the same display technique (palm: 0.827–0.940, thigh: 0.633–0.877, residual limb: 0.213–0.952). Despite poor inter-rater agreement for nonvolar skin, perhaps due to challenges in identifying the dermal–epidermal junction, this study helps to support the utility of optical coherence tomography to distinguish volar from nonvolar skin.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 4","pages":"Article 100276"},"PeriodicalIF":0.0,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026724000237/pdfft?md5=ca164c01d75d7275d0fa882b22a3633a&pid=1-s2.0-S2667026724000237-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140272024","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":"Proceedings of the Gunnar Lomholt Symposium during the IPC 2023 Think Tank at Faroe Islands, Friday, September 8, 2023","authors":"Francis Yi Xing Lai ,&nbsp;Hervé Bachelez ,&nbsp;Johann Gudjonsson ,&nbsp;Lone Skov ,&nbsp;Claus Zachariae ,&nbsp;Peter C.M. van de Kerkhof ,&nbsp;Jonathan N.W.N. Barker","doi":"10.1016/j.xjidi.2024.100267","DOIUrl":"10.1016/j.xjidi.2024.100267","url":null,"abstract":"","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 2","pages":"Article 100267"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026724000134/pdfft?md5=64fd1f496d1d8561591613579f2475a0&pid=1-s2.0-S2667026724000134-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139883479","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":"Downregulation of Caveolae-Associated Proteins in Psoriasis: A Case Series Study","authors":"Deborah A. Lin ,&nbsp;Beatriz Abdo Abujamra ,&nbsp;Stephanie Revah ,&nbsp;Leigh Nattkemper ,&nbsp;Brian Morrison ,&nbsp;Paolo Romanelli ,&nbsp;Ivan Jozic","doi":"10.1016/j.xjidi.2024.100265","DOIUrl":"10.1016/j.xjidi.2024.100265","url":null,"abstract":"<div><p>We have previously identified that a structural membrane protein Caveolin-1 (Cav1) is involved in the regulation of aberrant keratinocyte proliferation and differentiation. The aim of this study was to elucidate the role of Cav1, Caveolin-2 (Cav2), and Cavin-1 in the pathogenesis of psoriasis vulgaris and between psoriasis subtypes. We utilized human biopsies from validated cases of psoriasis vulgaris (n = 21) at the University of Miami Hospital and compared the expression of Cav1, Cav2, and Cavin-1 by immunohistochemistry staining with that in normal healthy age-/sex-/location-matched skin (n = 15) and chronic spongiotic dermatitis skin samples (as control inflammatory skin condition) and quantified using QuPath. Distinct subtypes of psoriasis included guttate, inverse, nail, plaque, palmoplantar, and pustular. All biopsy samples exhibited a trend toward downregulation of Cav1, with nail, plaque, and palmoplantar psoriasis exhibiting the most pronounced effects. Only nail and pustular psoriasis samples exhibited significant downregulation of Cav2 and Cavin-1, suggesting Cav1 to be the main caveolar contributor to the pathogenesis of psoriasis. Together, these data support caveolae as pathophysiological targets in nail and pustular psoriasis, whereas Cav1 seems to be a general biomarker of multiple subtypes of psoriasis.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 2","pages":"Article 100265"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026724000110/pdfft?md5=9f2e78ab69fefc00700771ebaf34c34b&pid=1-s2.0-S2667026724000110-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139879302","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":"Assessing Longitudinal Treatment Efficacies and Alterations in Molecular Markers Associated with Glutamatergic Signaling and Immune Checkpoint Inhibitors in a Spontaneous Melanoma Mouse Model","authors":"Kevinn Eddy ,&nbsp;Kajal Gupta ,&nbsp;Mohamad Naser Eddin ,&nbsp;Christina Marinaro ,&nbsp;Sanjana Putta ,&nbsp;John Michael Sauer Jr ,&nbsp;Anna Chaly ,&nbsp;Katie B. Freeman ,&nbsp;Jeffrey C. Pelletier ,&nbsp;Anna Fateeva ,&nbsp;Philip Furmanski ,&nbsp;Ann W. Silk ,&nbsp;Allen B. Reitz ,&nbsp;Andrew Zloza ,&nbsp;Suzie Chen","doi":"10.1016/j.xjidi.2024.100262","DOIUrl":"10.1016/j.xjidi.2024.100262","url":null,"abstract":"<div><p>Previous work done by our laboratory described the use of an immunocompetent spontaneous melanoma-prone mouse model, TGS (TG-3/SKH-1), to evaluate treatment outcomes using inhibitors of glutamatergic signaling and immune checkpoint for 18 weeks. We showed a significant therapeutic efficacy with a notable sex-biased response in male mice. In this follow-up 18-week study, the dose of the glutamatergic signaling inhibitor was increased (from 1.7 mg/kg to 25 mg/kg), which resulted in improved responses in female mice but not male mice. The greatest reduction in tumor progression was observed in male mice treated with single-agent troriluzole and anti–PD-1. Furthermore, a randomly selected group of mice was removed from treatment after 18 weeks and maintained for up to an additional 48 weeks demonstrating the utility of the TGS mouse model to perform a ≥1-year preclinical therapeutic study in a physiologically relevant tumor–host environment. Digital spatial imaging analyses were performed in tumors and tumor microenvironments across treatment modalities using antibody panels for immune cell types and immune cell activation. The results suggest that immune cell populations and cytotoxic activities of T cells play critical roles in treatment responses in these mice. Examination of a group of molecular protein markers based on the proposed mechanisms of action of inhibitors of glutamatergic signaling and immune checkpoint showed that alterations in expression levels of xCT, γ-H2AX, EAAT2, PD-L1, and PD-1 are likely associated with the loss of treatment responses. These results suggest the importance of tracking changes in molecular markers associated with the mechanism of action of therapeutics over the course of a longitudinal preclinical therapeutic study in spatial and temporal manners.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 2","pages":"Article 100262"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026724000080/pdfft?md5=31a2703b3576a894a7599aeea3188176&pid=1-s2.0-S2667026724000080-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139539600","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":"Structural Basis for p19 Targeting by Anti–IL-23 Biologics: Correlations with Short- and Long-Term Efficacy in Psoriasis","authors":"Stefano G. Daniele ,&nbsp;Sherif A. Eldirany ,&nbsp;Giovanni Damiani ,&nbsp;Minh Ho ,&nbsp;Christopher G. Bunick","doi":"10.1016/j.xjidi.2024.100261","DOIUrl":"10.1016/j.xjidi.2024.100261","url":null,"abstract":"<div><p>IL-23 is central to psoriasis pathogenesis. Biologics targeting IL-23 are important therapies against psoriasis. IL-23 inhibitors risankizumab, tildrakizumab, and guselkumab bind the IL-23 p19 subunit, whereas ustekinumab binds p40; however, the structural composition of the IL-23–binding epitopes and how these molecular properties relate to clinical efficacy are not known. Utilizing epitope data derived from hydrogen-deuterium exchange or crystallographic experiments, we mapped inhibitor epitope locations, hydrophobicity, and surface charge onto the IL-23 surface. Molecular properties of each inhibitor epitope, including solvent-accessible surface area, were correlated to binding affinity, kinetic values, and clinical efficacy scores for plaque psoriasis through linear regression analysis. Each IL-23 inhibitor binds an epitope with a unique size, composition, and location except for a 10-residue overlap region outside of the IL-23 receptor epitope. We observed strong correlations between epitope surface area and K_D and k_off but not k_on. Epitope surface area, K_D, and k_off were further associated with short-term (10–16 weeks) and long-term (44–60 weeks) clinical efficacy according to PASI-90 responses, with risankizumab demonstrating highest efficacy among IL-23 biologics. In contrast, k_on, epitope hydrophobicity, polarity, and charge content did not correlate with efficacy. These data exemplify how molecular principles of medications within a therapeutic class can explain their differential clinical responses.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 2","pages":"Article 100261"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026724000079/pdfft?md5=7ef11109ecf7af14c9c15048e351d873&pid=1-s2.0-S2667026724000079-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139537731","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":"Meeting Report: Highlights of 12th World Congress of Itch","authors":"Sarah G. Brooks ,&nbsp;Rami H. Mahmoud ,&nbsp;Gil Yosipovitch","doi":"10.1016/j.xjidi.2023.100254","DOIUrl":"https://doi.org/10.1016/j.xjidi.2023.100254","url":null,"abstract":"","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 2","pages":"Article 100254"},"PeriodicalIF":0.0,"publicationDate":"2024-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026723000814/pdfft?md5=8ad303cb08d64d8043a713efdc5c5011&pid=1-s2.0-S2667026723000814-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139975775","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":"Generative Artificial Intelligence, Large Language Models, and JID Innovations","authors":"Russell P. Hall III (Editor, JID Innovations)","doi":"10.1016/j.xjidi.2024.100256","DOIUrl":"10.1016/j.xjidi.2024.100256","url":null,"abstract":"","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 2","pages":"Article 100256"},"PeriodicalIF":0.0,"publicationDate":"2024-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026724000018/pdfft?md5=3c2b4dd626f753193551095c43074471&pid=1-s2.0-S2667026724000018-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139539827","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":"A Bispecific, Tetravalent Antibody Targeting Inflammatory and Pruritogenic Pathways in Atopic Dermatitis","authors":"Julia Tietz ,&nbsp;Tea Gunde ,&nbsp;Stefan Warmuth ,&nbsp;Christopher Weinert ,&nbsp;Matthias Brock ,&nbsp;Alexandre Simonin ,&nbsp;Christian Hess ,&nbsp;Maria Johansson ,&nbsp;Fabio Spiga ,&nbsp;Simone Muntwiler ,&nbsp;Belinda Wickihalder ,&nbsp;Dana Mahler ,&nbsp;Dania Diem ,&nbsp;Julia Zeberer ,&nbsp;Robin Heiz ,&nbsp;Naomi Flückiger ,&nbsp;Noriko Shiraishi ,&nbsp;Yoshihide Miyake ,&nbsp;Nobuaki Takahashi ,&nbsp;Markus Fehrholz ,&nbsp;Daniel Snell","doi":"10.1016/j.xjidi.2024.100258","DOIUrl":"10.1016/j.xjidi.2024.100258","url":null,"abstract":"<div><p>Inhibition of IL-4/IL-13 signaling has dramatically improved the treatment of atopic dermatitis (AD). However, in many patients, clinical responses are slow to develop and remain modest. Indeed, some symptoms of AD are dependent on IL-31, which is only partially reduced by IL-4/IL-13 inhibition. Thus, there is an unmet need for AD treatments that concomitantly block IL-4/IL-13 and IL-31 pathways. We engineered NM26-2198, a bispecific tetravalent antibody designed to accomplish this task. In reporter cell lines, NM26-2198 concomitantly inhibited IL-4/IL-13 and IL-31 signaling with a potency comparable with that of the combination of an anti–IL-4Rα antibody (dupilumab) and an anti–IL-31 antibody (BMS-981164). In human PBMCs, NM26-2198 inhibited IL-4–induced upregulation of CD23, demonstrating functional binding to FcγRII (CD32). NM26-2198 also inhibited the secretion of the AD biomarker thymus and activation-regulated chemokine (TARC) in blood samples from healthy human donors. In male cynomolgus monkeys, NM26-2198 exhibited favorable pharmacokinetics and significantly inhibited IL-31–induced scratching at a dose of 30 mg/kg. In a repeat-dose, good laboratory practice toxicology study in cynomolgus monkeys, no adverse effects of NM26-2198 were observed at a weekly dose of 125 mg/kg. Together, these results justify the clinical investigation of NM26-2198 as a treatment for moderate-to-severe AD.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 2","pages":"Article 100258"},"PeriodicalIF":0.0,"publicationDate":"2024-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026724000043/pdfft?md5=2f04d58000317f1b35b83dcef9c6e90d&pid=1-s2.0-S2667026724000043-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139538703","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":"Responsible but Innovative Use of Artificial Intelligence in Scientific Publishing","authors":"Trevor Champagne ,&nbsp;Neil Shear","doi":"10.1016/j.xjidi.2024.100257","DOIUrl":"10.1016/j.xjidi.2024.100257","url":null,"abstract":"","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 2","pages":"Article 100257"},"PeriodicalIF":0.0,"publicationDate":"2024-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S266702672400002X/pdfft?md5=fdd74f3438343feaf3a4c72d50b3fec7&pid=1-s2.0-S266702672400002X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139540272","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":"Inhibition of UV-Induced Stress Signaling and Inflammatory Responses in SKH-1 Mouse Skin by Topical Small-Molecule PD-L1 Blockade","authors":"Sally E. Dickinson ,&nbsp;Prajakta Vaishampayan ,&nbsp;Jana Jandova ,&nbsp;Yuchen (Ella) Ai ,&nbsp;Viktoria Kirschnerova ,&nbsp;Tianshun Zhang ,&nbsp;Valerie Calvert ,&nbsp;Emanuel Petricoin III ,&nbsp;H-H. Sherry Chow ,&nbsp;Chengcheng Hu ,&nbsp;Denise Roe ,&nbsp;Ann Bode ,&nbsp;Clara Curiel-Lewandrowski ,&nbsp;Georg T. Wondrak","doi":"10.1016/j.xjidi.2023.100255","DOIUrl":"10.1016/j.xjidi.2023.100255","url":null,"abstract":"<div><p>The immune checkpoint ligand PD-L1 has emerged as a molecular target for skin cancer therapy and might also hold promise for preventive intervention targeting solar UV light–induced skin damage. In this study, we have explored the role of PD-L1 in acute keratinocytic photodamage testing the effects of small-molecule pharmacological inhibition. Epidermal PD-L1 upregulation in response to chronic photodamage was established using immunohistochemical and proteomic analyses of a human skin cohort, consistent with earlier observations that PD-L1 is upregulated in cutaneous squamous cell carcinoma. Topical application of the small-molecule PD-L1 inhibitor BMS-202 significantly attenuated UV-induced activator protein-1 transcriptional activity in SKH-1 bioluminescent reporter mouse skin, also confirmed in human HaCaT reporter keratinocytes. RT-qPCR analysis revealed that BMS-202 antagonized UV induction of inflammatory gene expression. Likewise, UV-induced cleavage of procaspase-3, a hallmark of acute skin photodamage, was attenuated by topical BMS-202. NanoString nCounter transcriptomic analysis confirmed downregulation of cutaneous innate immunity- and inflammation-related responses, together with upregulation of immune response pathway gene expression. Further mechanistic analysis confirmed that BMS-202 antagonizes UV-induced PD-L1 expression both at the mRNA and protein levels in SKH-1 epidermis. These data suggest that topical pharmacological PD-L1 antagonism using BMS-202 shows promise for skin protection against photodamage.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 2","pages":"Article 100255"},"PeriodicalIF":0.0,"publicationDate":"2024-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026723000826/pdfft?md5=3d07b8adc86d48e1b946287656546618&pid=1-s2.0-S2667026723000826-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139392996","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}