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Journal of Investigative Dermatology

Megan H Noe, Arash Mostaghemi, Misha Rosenbach, Kanade Shinkai, Robert G Micheletti
No abstract text is available yet for this article.
March 17, 2018: Journal of Investigative Dermatology
Michael Loesche, Kamyar Farahi, Kimberly Capone, Steven Fakharzadeh, Andrew Blauvelt, Kristina Callis Duffin, Samuel E DePrimo, Ernesto J Muñoz-Elías, Carrie Brodmerkel, Bidisha Dasgupta, Marc Chevrier, Kevin Smith, Joseph Horwinski, Amanda Tyldsley, Elizabeth A Grice
BACKGROUND: Plaque psoriasis, a chronic inflammatory disease primarily affecting the skin, is thought to have a multifactorial etiology, including innate immune system dysregulation, environmental triggers, and genetic susceptibility. PURPOSE: We sought to further understand the role of skin microbiota in psoriasis pathogenesis, as well as their response to therapy. We systematically analyzed dynamic microbiota colonizing psoriasis lesions and adjacent nonlesional skin in 114 patients prior to and during ustekinumab treatment in a Phase 3b clinical trial...
March 17, 2018: Journal of Investigative Dermatology
Xinhua Yu, Reza Akbarzadeh, Mario Pieper, Thomas Scholzen, Stefanie Gehrig, Carsten Schultz, Detlef Zillikens, Peter König, Frank Petersen
Although uncontrolled proteolytic activity mediated by activated neutrophils is a major reason for tissue damage, therapeutic approaches using protease inhibitors are inefficient. Here, we investigated the role of the immune complex-induced neutrophil adhesion and protease release in tissue damage. We show both in vitro and in vivo that immune complex-mediated neutrophil adhesion to the target tissue depends on β2 integrins. Without affecting elastase or ROS release, blocking of adhesion drastically inhibited tissue damage in an experimental model of autoantibody-mediated skin blistering disease...
March 17, 2018: Journal of Investigative Dermatology
Xiaoyan Shen, Bo Wang, Kejia Li, Lili Wang, Xiaoqing Zhao, Feng Xue, Ruofei Shi, Jie Zheng
Cutaneous T cell lymphoma (CTCL) can have clinical and histological features resembling benign inflammatory dermatosis (BID) and can be difficult to diagnose. Very limited biomarkers are available for CTCL prognosis. We aimed to identify microRNA (miR) signatures to facilitate diagnostic and prognostic evaluations of CTCL. A cross-platform miR microarray identified 10 miRs that were differentially expressed between CTCL and BID patients. Subsequent RT-PCR validation was used to generate a 5-miR based diagnosing classifier, which showed high diagnostic accuracy in CTCL (AUC=0...
March 17, 2018: Journal of Investigative Dermatology
Jason Hellmann, Brian E Sansbury, Blenda Wong, Xiaofeng Li, Mansher Singh, Kristo Nuutila, Nan Chiang, Elof Eriksson, Charles N Serhan, Matthew Spite
Cutaneous injury causes underlying tissue damage that must be quickly repaired to minimize exposure to pathogens and to restore barrier function. While the role of growth factors in tissue repair is established, the role of lipid mediators in skin repair has not been extensively investigated. Using a mass spectrometry-based lipid mediator metabolomics approach, we identified D-series resolvins and related pro-resolving lipid mediators during skin injury in mice and pigs. Differentiation of human epidermal keratinocytes increased expression of 15-lipoxygenase and stereospecific production of 17S-hydroxydocosahexaenoic acid, the common upstream biosynthetic marker and precursor of D-series resolvins...
March 17, 2018: Journal of Investigative Dermatology
Yuwen Zhang, Jiaqing Hao, Jun Zeng, Qiang Li, Enyu Rao, Yanwen Sun, Lianliang Liu, Anita Mandal, V Douglas Landers, Rebecca J Morris, Margot P Cleary, Jill Suttles, Bing Li
Skin lipids (e.g. fatty acids) are essential for normal skin functions. Epidermal fatty acid-binding protein (E-FABP) is the predominant FABP expressed in skin epidermis. However, the role of E-FABP in skin homeostasis and pathology remains largely unknown. Herein, we utilized the 7,12-dimethylbenz(a)anthracene (DMBA) and 12-O-tetradecanolyphorbol-13-acetate (TPA)-induced skin tumorigenesis model to assess the role of E-FABP in chemical-induced skin tumorigenesis. Compared to their wild type (WT) littermates, mice deficient in E-FABP, but not adipose FABP (A-FABP), developed more skin tumors with higher incidence...
March 17, 2018: Journal of Investigative Dermatology
Merel A Hamer, Luba M Pardo, Leonie C Jacobs, Joris Deelen, André G Uitterlinden, Eline Slagboom, Diana van Heemst, Hae-Won Uh, Marian Beekman, Manfred Kayser, Fan Liu, David A Gunn, Tamar Nijsten
No abstract text is available yet for this article.
March 16, 2018: Journal of Investigative Dermatology
Arianna L Kim, Jung Ho Back, Sandeep C Chaudhary, Yucui Zhu, Mohammad Athar, David R Bickers
Currently available SMO targeted therapies in patients with basal cell nevus syndrome (BCNS) are associated with substantial tumor recurrence and clinical resistance. Strategies bypassing SMO and/or identifying additional downstream components of the Hedgehog (Hh) pathway could provide novel anti-tumor targets with a better therapeutic index. SOX9 is a Hh/GLI-regulated transcription factor known to be overexpressed in BCCs. A sequence motif search for SOX9-responsive elements identified three motifs in the promoter region of mTOR...
March 14, 2018: Journal of Investigative Dermatology
Ágnes Kemény, Xenia Kodji, Szabina Horváth, Rita Komlódi, Éva Szőke, Zoltán Sándor, Anikó Perkecz, Csaba Gyömörei, György Sétáló, Balázs Kelemen, Tamás Bíró, Balázs István Tóth, Susan D Brain, Erika Pintér, Rolland Gyulai
The present study revealed the modulatory role of Transient Receptor Potential Ankyrin 1 (TRPA1) and Vanilloid 1 (TRPV1) cation channels in Aldara-induced (5% imiquimod, IMQ) murine psoriasis model using selective antagonists and genetically altered animals. We have also developed a refined localized model to enable internal controls and reduce systemic effects. Skin pathology was quantified by measuring skin thickness, scaling, blood flow and analyzing dermal cellular infiltrate, while nocifensive behaviours were also observed...
March 14, 2018: Journal of Investigative Dermatology
Jakub Tolar, Johann W Bauer, Daniel H Kaplan, Sancy A Leachman, John A McGrath, Amy S Paller, Kelly A Griffith-Bauer, Clara E Stemwedel, Molly F Kulesz-Martin
No abstract text is available yet for this article.
March 14, 2018: Journal of Investigative Dermatology
Jacob B Hall, Zhaoyuan Cong, Yuka Imamura-Kawasawa, Brian A Kidd, Joel T Dudley, Diane M Thiboutot, Amanda M Nelson
Our understanding of the microbiome and the role of P. acnes in skin homeostasis and acne pathogenesis is evolving. Multiple methods for sampling and identifying the skin's microbiome exist and understanding the differences between the abilities of various methods to characterize the microbial landscape is warranted. This study compared the microbial diversity of samples obtained from the cheeks of twenty volunteers, collected by surface swab, pore strips, and cyanoacrylate glue follicular biopsy, all sequenced with 16S rRNA sequencing (V1-V3) and whole-genome metagenomic sequencing (WGS)...
March 13, 2018: Journal of Investigative Dermatology
Yu-Na Im, Yu-Dong Lee, Jeong-Soo Park, Hae-Kyoung Kim, Suhn-Young Im, Hwa-Ryung Song, Hern-Ku Lee, Myung-Kwan Han
Many itch mediators activate G-protein coupled receptor (GPCR), and trigger itch via activation of GPCR-mediated signaling pathways. GPCRs are desensitized by G protein-coupled receptor kinases (GRKs). The aim of this study is to explore the role of GRKs in itch response and the linkage between GRKs and glutamine (Gln), an amino acid previously demonstrated as an itching reliever. Itch responses were evoked by histamine, chloroquine (CQ), and dinitrochlorobenzene (DNCB)-induced contact dermatitis (CD). Phosphorylation and protein expression were detected by immunofluorescent staining and Western blotting...
March 9, 2018: Journal of Investigative Dermatology
Mayumi Kamaguchi, Hiroaki Iwata, Hideyuki Ujiie, Ken Natsuga, Wataru Nishie, Yoshimasa Kitagawa, Hiroshi Shimizu
The basement membrane zone (BMZ) consists of multiple components, including collagen XVII (COL17), which is the target of bullous pemphigoid (BP). No research has addressed the differences in BMZ components between the skin and the oral mucosa; therefore, we investigated the BMZ proteins, with a focus on COL17. The mRNA and protein expression levels of COL17 were significantly higher in oral keratinocytes (OKCs) than in skin keratinocytes (SKCs). Hemidesmosomal COL17 expression was markedly higher in OKCs than in SKCs, and its level was associated with adhesion strength...
March 9, 2018: Journal of Investigative Dermatology
Christine L Monteleon, Tanvir Agnihotri, Ankit Dahal, Mingen Liu, Vito W Rebecca, Gregory L Beatty, Ravi K Amavaradi, Todd W Ridky
Keratinocytes undergo significant structural remodeling during epidermal differentiation, including a broad transformation of the proteome coupled with a reduction in total cellular biomass. This suggests that intracellular digestion of proteins and organelles is necessary for keratinocyte differentiation. Here, we use both genetic and pharmacologic approaches to demonstrate that autophagy and lysosomal functions are required for keratinocyte differentiation in organotypic human skin. Lysosomal activity was required for mTOR signaling and mitochondrial oxidative metabolism...
March 8, 2018: Journal of Investigative Dermatology
David A Rafei-Shamsabadi, Saskia van de Poel, Britta Dorn, Stefanie Kunz, Stefan F Martin, Christoph S N Klose, Sebastian J Arnold, Yakup Tanriver, Karolina Ebert, Andreas Diefenbach, Timotheus Y F Halim, Andrew N J McKenzie, Thilo Jakob
Allergic contact dermatitis and its animal model, contact hypersensitivity (CHS), are T cell-mediated inflammatory skin diseases that require activation of the innate immune system. Here we investigate the role of innate lymphoid cells (ILCs) during the elicitation phase of TNCB-induced CHS using EomesGfp/+ x Rorc(γt)-CreTg x Rosa26RYfp/+ reporter mice. Ear swelling responses, cutaneous ILC numbers and cytokine production were determined at different time points. Functional analyses were performed in a CD90...
March 8, 2018: Journal of Investigative Dermatology
Felix Lauffer, Manja Jargosch, Linda Krause, Natalie Garzorz-Stark, Regina Franz, Sophie Roenneberg, Alexander Böhner, Nikola S Mueller, Fabian J Theis, Carsten B Schmidt-Weber, Tilo Biedermann, Stefanie Eyerich, Kilian Eyerich
Interface dermatitis (ID) is a characteristic histological pattern which occurs in autoimmune and chronic inflammatory skin diseases. It is unknown whether a common mechanism orchestrates this distinct type of skin inflammation. Here we investigated the overlap of two different ID positive skin diseases, lichen planus (LP) and lupus erythematosus (LE). The shared transcriptome signature pointed towards a strong type I immune response and biopsy derived T cells were dominated by IFN-γ and TNF-α positive cells...
March 8, 2018: Journal of Investigative Dermatology
Ling Shih Quek, Nicolas Grasset, Joanita Binte Jasmen, Kim S Robinson, Sophie Bellanger
Cdc20 and Cdh1 activate the Anaphase Promoting Complex/Cyclosome (APC/C), a master cell cycle regulator. Although cell cycle modifications occur during differentiation of stem cells, a role for the APC/C on stem cell fate has not been established in embryonic or adult human tissues. We found that differentiated human primary keratinocytes (HPKs) from the skin express extremely low levels of Cdc20 compared to HPK stem cells (holoclones). In agreement with this, staining of human skin biopsies showed that Cdc20 is expressed in occasional cells from the basal and epibasal layers of the epidermis and is absent from the differentiated layers...
March 8, 2018: Journal of Investigative Dermatology
Nirmala Pandeya, Marina Kvaskoff, Catherine M Olsen, Adèle C Green, Susan Perry, Catherine Baxter, Marcia B Davis, Rohan Mortimore, Lorraine Westacott, Dominic Wood, Joe Triscott, Richard Williamson, David C Whiteman
A proportion of cutaneous melanomas display neval remnants on histologic examination. Converging lines of epidemiologic and molecular evidence suggest that melanomas arising from nevus precursors differ from melanomas arising de novo. In a large, population-based study comprising 636 cutaneous melanomas subjected to dermatopathology review, we explored the molecular, host and environmental factors associated with the presence of neval remnants. We found nevus-associated melanomas were significantly associated with younger age at presentation, non-brown eye color, trunk site, thickness <0...
March 7, 2018: Journal of Investigative Dermatology
Zhongyi Xu, Li Chen, Min Jiang, Qianqian Wang, Chengfeng Zhang, Leihong Flora Xiang
Fibroblast-derived melanogenic paracrine mediators are known to play a role in melanogenesis. To investigate the effect of CCN1 (also called CYR61, cysteine-rich 61) on melanogenesis, normal human epidermal melanocytes (NHEMs) were treated with recombinant CCN1 protein. Our findings reveal that CCN1 activates melanogenesis through promoting melanosome maturation and upregulation of microphthalmia-associated transcription factor (MITF), tyrosinase-related protein 1 (TRP-1) and tyrosinase via integrin α6β1, p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK) signaling pathways...
March 3, 2018: Journal of Investigative Dermatology
Kazuhiko Matsuo, Daisuke Nagakubo, Yuhei Komori, Shun Fujisato, Natsumi Takeda, Mizuki Kitamatsu, Keiji Nishiwaki, Ying-Shu Quan, Fumio Kamiyama, Naoki Oiso, Akira Kawada, Osamu Yoshie, Takashi Nakayama
Atopic dermatitis (AD) is a chronic inflammatory skin disease involving Th2 cells, eosinophils, and mast cells. Although CCR4 is a major chemokine receptor expressed on Th2 cells and regarded as a potential therapeutic target for allergic diseases, its role in AD still remains unclear. Here, by using a hydrogel patch as a transcutaneous delivery device for ovalbumin (an antigen) and Staphylococcus aureus δ-toxin (a mast cell activator), we efficiently induced acute AD-like skin lesions in BALB/c mice, a strain prone to Th2 responses, that were characterized by (1) increased numbers of eosinophils, mast cells, and CCR4-expressing Th2 cells in the skin lesions, (2) elevated levels of total and ovalbumin-specific IgE in the sera, and (3) increased expression of IL-4, IL-17A, IL-22, CCL17, CCL22, and CCR4 in the skin lesions...
March 3, 2018: Journal of Investigative Dermatology
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