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Experimental Dermatology

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https://www.readbyqxmd.com/read/28423239/a-novel-jak-inhibitor-jte-052-reduces-skin-inflammation-and-ameliorates-chronic-dermatitis-in-rodent-models-comparison-with-conventional-therapeutic-agents
#1
Atsuo Tanimoto, Yuichi Shinozaki, Yasuo Yamamoto, Yoshiaki Katsuda, Eriko Riya, Kaoru Toyoda, Kochi Kakimoto, Yukari Kimoto, Wataru Amano, Noriko Konishi, Mikio Hayashi
Janus kinases (JAKs) are required for several inflammatory cytokine signaling pathways and are implicated in the pathogenesis of chronic dermatitis, including atopic dermatitis and psoriasis. JAK inhibitors are therefore promising therapeutic candidates for chronic dermatitis. In this study, we evaluated the effects of the novel JAK inhibitor JTE-052 on inflammatory responses associated with chronic dermatitis, and compared its profile with those of conventional therapeutic agents in rodent models of chronic dermatitis...
April 19, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28423238/higher-plasma-leptin-is-associated-with-higher-risk-of-androgenetic-alopecia-in-men
#2
Chao-Chun Yang, Pei-Lun Chung, Li-Yu Lin, Michael W Hughes, Yau-Sheng Tsai
No abstract text is available yet for this article.
April 19, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28423208/combined-activity-of-temozolomide-and-the-mtor-inhibitor-temsirolimus-in-metastatic-melanoma-involves-dkk1
#3
Heike Niessner, Corinna Kosnopfel, Tobias Sinnberg, Daniela Beck, Kathrin Krieg, Ines Wanke, Konstantinos Lasithiotakis, Michael Bonin, Claus Garbe, Friedegund Meier
The BRAFV600E inhibitor vemurafenib achieves remarkable clinical responses in patients with BRAF-mutant melanoma, but its effects are limited by the onset of drug resistance. In the case of resistance, chemotherapy can still be applied as second line therapy. However, it yields low response rates and strategies are urgently needed to potentiate its effects. In a previous study, we showed that the inhibition of the PI3K-AKT-mTOR pathway significantly increases sensitivity of melanoma cells to chemotherapeutic drugs (1)...
April 19, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28423200/cd80cd86-deficiency-disrupts-regulatory-cd4-foxp3-t-cell-homeostasis-and-induces-autoimmune-like-alopecia
#4
Ji-Hyun Bae, Woo-Sung Hwang, Yoo-Jin Jang, Yoon-Hoo Lee, Da-Eun Jang, Jung-Sik Kim, Su-Cheong Yeom
Alopecia areata (AA) is an autoimmune disease that results in spot baldness in humans. Adequate animal models for AA are currently lacking. The objective of this study was to elucidate the mechanism of autoimmune-like alopecia (ALA) in C57BL/6.CD80CD86-deficient (B6.CD80CD86(-/-) ) mice. Incidence and severity of alopecia were analyzed in 58 B6.CD80CD86(-/-) mice by using histological examination, flow cytometry, multiplex enzyme-linked immunosorbent assay, quantitative RT-PCR, and CD25 inhibition test. Both male and female B6...
April 19, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28418623/an-efficient-method-for-gene-knock-down-by-rna-interference-in-human-skin-mast-cells
#5
Tarek Hazzan, Sven Guhl, Metin Artuc, Kristin Franke, Margitta Worm, Torsten Zuberbier, Magda Babina
Mast cells (MCs) from human skin have been notoriously resistant to gene manipulation, and a method to knock-down gene expression in in situ differentiated MCs is highly desired. The Dharmacon Accell(®) transfection system proved successful on several "difficult-to-transfect" cells. In the present work, we therefore tested this method on skin-derived MCs using different siRNA entities. The siRNA was readily taken up, followed by pronounced, specific reduction of gene and protein expression. Hence, we present the first efficient technique for the manipulation of gene expression in primary skin MCs ex vivo, which combines high transfection rates with retained cell viability...
April 18, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28418613/complement-independent-blistering-mechanisms-in-bullous-pemphigoid
#6
Hiroaki Iwata, Hideyuki Ujiie
Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease that clinically demonstrates tense blisters with widespread erythema, histologically demonstrates subepidermal blistering and immunologically demonstrates the presence of circulating autoantibodies against hemidesmosomal molecules. Complement activation has long been regarded as necessary for the generation of the BP. However, certain evidence has recently come to support non-complemental blistering mechanisms. The story of BP blistering mechanisms is a complicated one...
April 18, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28418611/ectopic-expression-of-the-transcription-factor-mafb-in-basal-keratinocytes-induces-hyper-proliferation-and-perturbs-epidermal-homeostasis
#7
Masashi Miyai, Yukino Tsunekage, Michiko Saito, Kenji Kohno, Kenzo Takahashi, Kohsuke Kataoka
Mammalian epidermis is composed of four morphologically and functionally distinct layers of keratinocytes. The innermost basal layer consists of proliferating self-renewing keratinocytes, which also undergo asymmetric cell division to differentiate into post-mitotic suprabasal cells throughout life. Control of the balance between growth and differentiation of basal cells is important for epidermal homeostasis to prevent skin disorders including malignancies; however, the underlying mechanism remains to be elucidated...
April 18, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28418608/methods-for-the-isolation-and-3d-culture-of-dermal-papilla-cells-from-human-hair-follicles
#8
H Topouzi, N J Logan, G Williams, C A Higgins
The dermal papilla is a cluster of mesenchymal cells located at the base of the hair follicle which have a number of important roles in the regulation of hair growth. As a consequence, in vitro models of these cells are widely used to study the molecular mechanisms which underlie hair follicle induction, growth and maintenance. While dermal papilla from rodent hair follicles can be digested prior to cell isolation, the unique extracellular matrix composition found in human dermal papilla renders enzymes such as trypsin and collagenase insufficient for digestion of the dermal papilla into a single cell suspension...
April 18, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28418604/loss-of-ink4a-arf-gene-enhances-ultraviolet-radiation-induced-cutaneous-tumor-development
#9
Israr Ahmad, Purushotham Guroji, Amanda H DeBrot, Padma P Manapragada, Santosh K Katiyar, Craig A Elmets, Nabiha Yusuf
The CDKN2A locus encodes for tumor suppressor genes p16(INK)(4a) and p14(Arf) which are frequently inactivated in human skin tumors. The purpose of this study was to determine the relationship between loss of INK4a/Arf activity and inflammation in the development of ultraviolet (UV) radiation-induced skin tumors. Panels of INK4a/Arf(-/-) mice and wild type (WT) mice were treated with a single dose of UVB (200 mJ/cm(2) ). For long-term studies, these mice were irradiated with UVB (200 mJ/cm(2) ) three times weekly for 30 weeks...
April 18, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28418602/expression-of-low-density-lipoprotein-related-receptors-5-and-6-lrp5-6-in-psoriasis-skin
#10
Albert Duvetorp, Renate Slind Olsen, Helena Nyström, Marita Skarstedt, Olaf Dienus, Ulrich Mrowietz, Jan Söderman, Oliver Seifert
Low-density lipoprotein-related receptors 5 and 6 (LRP5/6) are transmembrane receptors with key functions in canonical Wnt signaling. Wnt ligands are thought to play an important role in innate immunity and psoriasis and recent studies assigned LRP5/6 anti-inflammatory properties. The objective of this study was to investigate the expression of LRP5 and LRP6 in lesional and non-lesional skin in peripheral blood and in mononuclear cells of patients with chronic plaque type psoriasis compared with control individuals...
April 18, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28418601/to-arginine-residues-in-the-cooh-terminal-of-human-%C3%AE-defensin-3-constitute-an-essential-motif-for-antimicrobial-activity-and-il-6-production
#11
Yoko Sakagami-Yasui, Yoshinori Shirafuji, Osamu Yamasaki, Shin Morizane, Toshihisa Hamada, Hiroshi Umemura, Keiji Iwatsuki
Human β-defensin-3 (HBD-3) possesses antimicrobial activities and the potential to induce proinflammatory cytokines. HBD-3 contains a unique motif of two arginine residues (Arg. R) in the COOH-terminal region. To understand the bioactive properties of the Arg residues of HBD-3, we examined antimicrobial activities against S. aureus and P. aeruginosa using synthetic HBD-2, HBD-3, and two variant peptides of HBD-3: the Arg-truncated variant designated desR HBD-3, and NRR HBD-3, in which both Arg residues were shifted to the N-terminal region...
April 18, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28418596/hair-follicle-dermal-stem-cells-and-skin-derived-precursor-cells-exciting-tools-for-endogenous-and-exogenous-therapies
#12
Natacha A Agabalyan, Nicole L Rosin, Waleed Rahmani, Jeff Biernaskie
Understanding the cellular interactions and molecular signals underlying hair follicle (HF) regeneration may have significant implications for restorative therapies for skin disease that diminish hair growth, whilst also serving to provide fundamental insight into the mechanisms underlying adult tissue regeneration. One of the major, yet underappreciated, players in this process is the underlying HF mesenchyme. Here, we provide an overview of a mesenchymal progenitor pool referred to as hair follicle dermal stem cells (hfDSCs), discuss their potential functions within the skin, their relationship to Skin-derived precursors (SKPs) and consider unanswered questions about the function of these specialized fibroblasts...
April 18, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28418591/a-hypomorphic-egfr-allele-does-not-ameliorate-the-palmoplantar-keratoderma-caused-by-slurp1-deficiency
#13
Christopher M Allan, Deanna Tran, Yiping Tu, Patrick J Heizer, Lorraine C Young, Loren G Fong, Anne P Beigneux, Stephen G Young
Mutations in SLURP1, a secreted protein of keratinocytes, cause a palmoplantar keratoderma (PPK) known as mal de Meleda. Slurp1 deficiency in mice faithfully recapitulates the human disease, with increased keratinocyte proliferation and thickening of the epidermis on the volar surface of the paws. There has long been speculation that SLURP1 serves as a ligand for a receptor that regulates keratinocyte growth and differentiation. We were intrigued that mutations leading to increased signaling through the epidermal growth factor receptor (EGFR) cause PPK...
April 18, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28418589/a-distinct-cutaneous-microbiota-pofile-in-autoimmune-bullous-disease-patients
#14
Mor Miodovnik, Axel Künstner, Ewan A Langan, Detlef Zillikens, Regine Gläser, Eli Sprecher, John F Baines, Enno Schmidt, Saleh M Ibrahim
Bullous Pemphigoid (BP) is the most common autoimmune blistering disease in Europe. As both the incidence of the disease and the relative proportion of the elderly population continue to rise, it represents a significant medical burden. Whereas some progress has been achieved in defining genetic risk factors for autoimmune blistering diseases, no environmental agent has been conclusively identified. Emerging evidence suggests that host immunity may influence the skin microbiota while the latter modulates cutaneous immunity...
April 18, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28418588/intracellular-ros-levels-determine-the-apoptotic-potential-of-keratinocyte-by-quantum-dot-via-blockade-of-akt-phosphorylation
#15
Eun Young Lee, Hyun Cheol Bae, Hana Lee, Yeon Sue Jang, Yoon-Hee Park, Jin Hee Kim, Woo-In Ryu, Byeong Hyeok Choi, Ji Hyun Kim, Sang Hoon Jeong, Sang Wook Son
Quantum dots (QDs) have shown great potential for biomedical use in a broad range including diagnostic agents. However, the regulatory mechanism of dermal toxicity is poorly understood. In this study, we investigated how QDs-induced apoptosis is regulated in human keratinocytes. We also examined the effect of carboxylic acid coated QDs (QD 565 and QD 655) on reactive oxygen species (ROS) production and apoptosis-related cellular signaling. The viability of keratinocyte was inhibited by two types of QDs in a concentration-dependent manner...
April 18, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28418585/mir-128-1-is-not-required-for-hair-pigmentation-in-mice
#16
Abigail R Wark, Elizabeth J Terman, Clifford J Tabin
MicroRNAs are endogenous, regulatory RNAs implicated in many biological processes including pigmentation. Software algorithms and in vitro experiments predict that microRNAs can target pigmentation pathway genes, but few have been tested in vivo. MiR-128-1, a microRNA within the strongly selected lactase locus in the human genome, has predicted pigmentation targets. To test the role of miR-128-1 in pigment regulation, we created C57BL/6 agouti miR-128-1 knockout mice and quantified melanin deposition in hair...
April 18, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28418584/transforming-growth-factor-%C3%AE-inhibitor-repsox-down-regulates-collagen-expression-of-scleroderma-dermal-fibroblasts-and-prevents-bleomycin-induced-mice-skin-fibrosis
#17
Maho Ide, Masatoshi Jinnin, Yukiko Tomizawa, Zhongzhi Wang, Ikko Kajihara, Satoshi Fukushima, Yoshinobu Hashizume, Yoshihide Asano, Hironobu Ihn
Inhibition of transforming growth factor (TGF)-β1 signaling may be one of the most reliable approaches to treat skin fibrosis of scleroderma. Although there have been a lot of basic researches of TGF-β blockade reagents, few of them was proved to have inhibitory effects on fibrosis both in vitro and in vivo. In the present study, we randomly chose four commercially available low molecular compounds (Repsox, LY2109761, LY364947, and K02288) from TGF-β1 inhibitor library, and compared their anti-fibrotic effects in vitro and in vivo...
April 18, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28419554/the-major-mir-31-target-genes-stk40-and-lats2-and-their-implications-in-the-regulation-of-keratinocyte-growth-and-hair-differentiation
#18
Liming Luan, Jianyun Shi, Zhengquan Yu, Thomas Andl
Emerging evidence indicates that even subtle changes in the expression of key genes of signaling pathways can have profound effects. MicroRNAs (miRNAs) are masters of subtleness and generally have only mild effects on their target genes. The microRNA miR-31 is one of the major microRNAs in many cutaneous conditions associated with activated keratinocytes such as the hyperproliferative diseases psoriasis, non-melanoma skin cancer, and hair follicle growth. miR-31 is a marker of the hair growth phase, and in our miR-31 transgenic mouse model it impairs the function of keratinocytes, subsequently leading to aberrant proliferation, apoptosis and differentiation that result in altered hair growth, while loss of miR-31 leads to increased hair growth...
April 17, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28370710/probing-skin-physiology-through-the-volatile-footprint-discriminating-volatile-emissions-before-and-after-acute-barrier-disruption
#19
Emer Duffy, Matthew R Jacobs, Brian Kirby, Aoife Morrin
Volatile organic compounds emitted by human skin were sampled before and after acute barrier disruption of the volar forearm to investigate the significance of this approach to skin physiology research. A small wearable housing integrating a solid phase micro-extraction fibre permitting rapid enclosed headspace sampling of human skin volatiles is presented, enabling non-invasive sample collection in 15 minutes, in a comfortable wearable format. Gas chromatography-mass spectrometry was utilised to separate and identify the volatile metabolites...
March 31, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28370639/transcriptional-activation-of-hedgehog-pathway-components-in-aggressive-hemangioma
#20
Danielle S Wendling-Keim, Lynn Wanie, Rainer Grantzow, Roland Kappler
Infantile hemangioma is a vascular neoplasm and is one of the most common tumors diagnosed in young children. Although most hemangiomas are harmless and involute spontaneously, some show severe progression, leading to serious complications, such as high output cardiac failure, ulcerations, compression of the trachea or deprivation amblyopia, depending on their size and localization. However, the pathogenesis and cause of hemangioma are largely unknown to date. The goal of this study was to identify markers that could predict hemangiomas with aggressive growth and severe progression that would benefit from early intervention...
March 31, 2017: Experimental Dermatology
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