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Experimental Dermatology

Mary Elizabeth Mathyer, Ashley M Quiggle, X F Colin C Wong, Simon L I J Denil, Monique G Kumar, Heather M Ciliberto, Susan J Bayliss, John E Common, Cristina de Guzman Strong
Filaggrin (FLG) loss of function (LOF) variants are a major risk factor for the common inflammatory skin disease, atopic dermatitis (AD), and are often population-specific. African American (AA) children are disproportionately affected with AD, often later developing asthma and/or allergic rhinitis and comprise an atopy health disparity group for which the role of FLG LOF is not well known. Discovery of FLG LOF using exome sequencing is challenging given the known difficulties for accurate short-read alignment to FLG's high homology repeat variation...
May 23, 2018: Experimental Dermatology
Nikolaos Pantelireis, Claire A Higgins
Hair plays a large part in communication and society with its role changing through time and across cultures. Most people don't leave the house before combing their hair or shaving their beard and for many hair loss or irregular hair growth can have a significant impact on their psychological health. Somewhat unsurprisingly, according to GMR Data today's global hair care industry is worth an estimated $87 Billion in 2018, with hair loss estimated at $2.8 Billion. Considering that no current hair loss related products can completely reverse hair loss, it is reasonable to believe this market could expand significantly with the discovery of a comprehensive therapy...
May 22, 2018: Experimental Dermatology
Erin A Brettmann, Cristina de Guzman Strong
The skin is the first line of defense against the environment, with the epidermis as the outermost tissue providing much of the barrier function. Given its direct exposure to and encounters with the environment, the epidermis must evolve to provide an optimal barrier for the survival of an organism. Recent advances in genomics have identified a number of genes for the human skin barrier that have undergone evolutionary changes since humans diverged from chimpanzees. Here we highlight a selection of key and innovative genetic findings for skin barrier evolution in our divergence from our primate ancestors and among modern human populations...
May 22, 2018: Experimental Dermatology
Sophie Seite, Laurent Misery
Sensitive skin is defined by the occurrence of unpleasant sensations, accompanied or not by erythema, in response to stimuli which normally should not provoke such sensations and that cannot be linked to skin disease. Even if its pathophysiology is not completely known, hyper-reactivity of the cutaneous nervous system associated with an abnormal skin barrier has been hypothesized as a primary culprit including more recently a role of the cutaneous microbiota. The objective of this short review is to discuss the relationship between the skin microbiota, skin sensitivity and the skin barrier function...
May 21, 2018: Experimental Dermatology
Jinling Ning, Ying Shen, Ting Wang, Mengru Wang, Wei Liu, Yonghu Sun, Furen Zhang, Lingling Chen, Yiqiang Wang
Preliminary datamining performed with Gene Expression Omnibus datasets implied that psoriasis may involve the matrix remodeling associated 7 (MXRA7), a gene with little function information yet. To test that hypothesis, studies were performed in human samples and murine models. Immunohistochemistry in normal human skin showed that MXRA7 proteins were present across the full epidermal layer, with highest expression level detected in the basal layer. In psoriatic samples, MXRA7 proteins were absent in the basal stem cells layer while suprabasal keratinocytes stained at a higher level than in normal tissues...
May 21, 2018: Experimental Dermatology
Laura Cau, Marie-Claire Méchin, Michel Simon
Deimination or citrullination is a posttranslational modification catalysed by a family of calcium-dependent enzymes called peptidylarginine deiminases (PADs). It corresponds to the transformation of arginine residues within a peptide sequence into citrulline residues. Deimination induces a decreased net charge of targeted proteins; therefore it alters their folding and changes intra and intermolecular ionic interactions. Deimination is involved in several physiological processes (inflammation, gene regulation, etc...
May 13, 2018: Experimental Dermatology
Ryo Utsunomiya, Xiuju Dai, Masamoto Murakami, Hidenori Okazaki, Teruko Tsuda, Hideki Mori, Ken Shiraishi, Mikiko Tohyama, Koji Sayama
Epidermal keratinocytes initiate skin inflammation by activating immune cells. The skin barrier is disrupted in atopic dermatitis (AD) and epidermal keratinocytes can be exposed to environmental stimuli, such as house dust mite (HDM) allergens. We showed previously that HDM allergens activate the NLRP3 inflammasome of keratinocytes, thereby releasing pro-inflammatory cytokines. Heparinoid is an effective moisturizer for atopic dry skin. However, a recent report showed that heparinoid treatment can improve inflammation of lichen planus...
May 13, 2018: Experimental Dermatology
Serena Di Francesco, Monica Savio, Nora Bloise, Giovanni Borroni, Lucia Anna Stivala, Riccardo G Borroni
Red grape (Vitis vinifera L.) flavonoids including flavan-3-ols (e.g., catechin and epicatechin), flavonols (e.g., quercetin) and anthocyanins (e.g., malvidin) exert anti-inflammatory and antioxidant activities. In the skin they also have a photoprotective action, and their effects have been extensively investigated in keratinocytes, melanocytes and fibroblasts. Despite their known effects also on blood vasculature, little is known on their activities on human dermal blood endothelial cells (HDBECs), which are critically involved in skin homeostasis as well as in the pathogenesis of neoplastic and inflammatory skin diseases...
May 9, 2018: Experimental Dermatology
Nicolas Lebonvallet, Betty Laverdet, Laurent Misery, Alexis Desmoulière, Dorothée Girard
During the resolution phase of normal skin wound healing, there is a considerable loss of various cell types, including myofibroblasts by apoptosis. Inappropriate delay of apoptosis, and thus increased survival of myofibroblasts, may be a factor leading to pathologies and excessive scarring. Considerable data now clearly suggests that innervation plays a major role in wound healing, including the modulation of fibroblast cellular activity. An abnormal level of neuromediators is implicated not only in the development of chronic wounds but also in excessive scar formation...
May 9, 2018: Experimental Dermatology
Pernille Lindsø Andersen, Jonas Olsen, Kersti Brosbøl Engelund Friis, Lotte Themstrup, Kasper Grandahl, Ole Steen Mortensen, Gregor Borut Ernst Jemec
BACKGROUND: Dynamic optical coherence tomography (D-OCT) is a non-invasive imaging technique, suitable for the study of structural and dynamic features of cutaneous microvasculature. Studies with D-OCT have primarily focused on non-melanoma skin cancer (NMSC) and a reference description of healthy skin is lacking. OBJECTIVE: To describe the prevalence of standard microvascular features in normal skin. METHOD: A total of 280 participants without skin disease were D-OCT scanned on four body locations; three sun-exposed areas and one unexposed: forehead, back of the neck, back of the hand and medial side of the upper arm...
May 7, 2018: Experimental Dermatology
Guimei Yin, Zhijing Wang, Zhaoxia Wang, Xirui Wang
The ischemia-reperfusion (I/R) induced skin lesion has been identified as primary cause of pressure ulcers. To date, attempts to prevent pressure ulcers have not produced a significant improvement. Quercetin, one of the most widely distributed flavonoids in fruits and vegetables, exhibits its antioxidant and anti-inflammatory properties against many diseases, including ischemic heart disease, atherosclerosis, and renal injury. In vitro wound scratch assay was first used to assess the function of quercetin in wounding cell model...
May 7, 2018: Experimental Dermatology
Bianca Simon, Dennis C Harrer, Beatrice Schuler-Thurner, Niels Schaft, Gerold Schuler, Jan Dörrie, Ugur Uslu
Chimeric antigen receptor (CAR)-T cells have been used successfully for cancer immunotherapy. While substantial tumor regression was observed in leukemia and lymphoma, CAR-therapy of solid tumors needs further improvement. A major obstacle to the efficiency of engineered T cells is posed by triggering of inhibitory receptors, e.g. programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), leading to an impaired anti-tumor activity. To boost CAR-T-cell function, we co-electroporated T cells with both, mRNA encoding a CAR specific for chondroitin sulfate proteoglycan 4 (CSPG4) and small-interfering RNAs (siRNAs) to downregulate PD-1 (siPD-1) and CTLA-4 (siCTLA-4)...
April 28, 2018: Experimental Dermatology
Akemi Ishida-Yamamoto, Satomi Igawa, Mari Kishibe
The barrier function of skin is indispensable for terrestrial animals. This function is mainly carried out by the epidermis, more specifically by its granular and cornified layers. The major structural components associated with this function are the intercellular lipid layer, desmosomes, corneodesmosomes, tight junctions, cornified cell envelope, and keratin filaments. In this review, we discuss the current knowledge of their ultrastructure, their molecular basis, and their relevance to skin disease. This article is protected by copyright...
April 28, 2018: Experimental Dermatology
Bruna Romana-Souza, Welker Silva-Xavier, Andréa Monte-Alto-Costa
Stress-induced oxidative damage and the inflammatory response lead to degradation of collagen and elastic fibers and wrinkle formation. Topical retinol (or vitamin A) can be a strategy to attenuate the effects of stress in skin since it promotes collagen and elastic fiber production and reduces protease synthesis. This study investigated the effect of topical retinol in stressed human skin using in vivo and ex vivo models. Human skin explants were treated with high levels of epinephrine (as observed in stressed patients) and topically with retinol for 13 days...
April 28, 2018: Experimental Dermatology
Roopal V Kundu, Julia M Mhlaba, Stephanie M Rangel, I Caroline Le Poole
Vitiligo is characterized by progressive loss of skin pigmentation. The search for etiologic factors has led to the biochemical, the neurologic and the autoimmune theory. The convergence theory was then proposed several years ago to incorporate existing theories of vitiligo development into a single overview of vitiligo etiology. The viewpoint that vitiligo is not caused only by predisposing mutations, or only by melanocytes responding to chemical/radiation exposure, or only by hyperreactive T cells, but rather results from a combination of etiologic factors that impact melanocyte viability, has certainly stood the test of time...
April 28, 2018: Experimental Dermatology
Elizabeth N Ergen, Nabiha Yusuf
Immune cells and cytokines play an important role in the pathogenesis of psoriasis. Interleukin 12 (IL-12) and IL-23 promote cellular responses mediated by T cells, which contribute to an inflammatory loop responsible for the induction and maintenance of psoriatic plaques. Antibodies that inhibit IL-12/23 or IL-23 are key treatment options for patients with psoriasis. IL-12 and IL-23 also play a key role in immune responses to infections and tumors. A growing body of information from clinical trials, cohort studies, postmarketing reports, genetic studies, and animal models provides insights into the potential biological relationships between IL-12/23 inhibition and malignancies...
April 28, 2018: Experimental Dermatology
Yu Inoue, Seiji Hasegawa, Katsuma Miyachi, Takaaki Yamada, Satoru Nakata, Sari Ipponjima, Terumasa Hibi, Tomomi Nemoto, Masahiko Tanaka, Ryo Suzuki, Naohide Hirashima
The epidermis, the outermost layer of the skin, retains moisture and functions as a physical barrier against the external environment. Epidermal cells are continuously replaced by turnover, and thus to understand in detail the dynamic cellular events in the epidermis, techniques to observe live tissues in 3D are required. Here, we established a live 3D imaging technique for epidermis models. We first obtained immortalized human epidermal cell lines which have a normal differentiation capacity and fluorescence-labeled cytoplasm or nuclei...
April 26, 2018: Experimental Dermatology
Alessandra Marconi, Marika Quadri, Annalisa Saltari, Carlo Pincelli
Melanoma is one of the most studied neoplasia, although laboratory techniques used for investigating this tumor are not fully reliable. Animal models may not predict the human response due to differences in skin physiology and immunity. In addition, international guidelines recommend to develop processes that contribute to the reduction, refinement and replacement of animals for experiments (3Rs). Adherent cell culture has been widely used for the study of melanoma to obtain important information regarding melanoma biology...
April 26, 2018: Experimental Dermatology
Kehan Meng, Wencheng Xu, Taro Miura, Shunsuke Suzuki, Masako Chiyotanda, Sachiko Tanaka, Kentaro Sugiyama, Hisashi Kawashima, Toshihiko Hirano
We estimated the pharmacological efficacy of vitamin K1 (VK1 ) and VK2 on the mitogen-activated peripheral-blood mononuclear cells (PBMCs) of pediatric atopic dermatitis (AD) patients. VK2 suppressed the in vitro proliferation of T cell-mitogen-activated PBMCs of AD patients. In contrast, VK1 had little effect on the PBMC proliferation. The IL-2 production from the activated PBMCs of AD patients significantly increased (P<0.05), while the production significantly decreased by 100 μM VK2 (P<0.01). In addition, 100 μM VK2 reduced the percentage of CD4+ and CD4+CD25+cells in PBMCs...
April 26, 2018: Experimental Dermatology
Michael P Philpott
Terence Kealey first pioneered the isolation and organ maintenance of human eccrine and sebaceous glands in the early to mid-1980. This led to subsequent methods describing the isolation and culture of human hair follicles, the human pilosebaceous unit as well as the sebaceous duct. The importance of these models in the study of the biology of human skin glands and appendages has been demonstrated in numerous publications and their importance as models for animal replacement, refinement and reduction (3R's) increasingly important...
April 25, 2018: Experimental Dermatology
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