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Experimental Dermatology

Leopold Eckhart, Patrick L J M Zeeuwen
The primary function of the skin is to serve as a barrier against the environment.[1] The epidermis of the skin prevents or minimizes the ingress of microbes[2-5], fungi[6], viruses[7], toxins[8], allergens[9,10], and irritants[11,12], it absorbs ultraviolet radiation[13,14] and reduces damage by mechanical forces.[15] Furthermore, the skin suppresses the loss of water[16], ions, and metabolites.[17,18] The lifestyle and occupation of humans determine the types of environmental factors acting on the skin, and the genetic and epigenetic constitution of the individual determines the quality of the barrier and the sensitivity to a breach of the barrier...
July 10, 2018: Experimental Dermatology
Chi Liu, Xue Yang, Ping Zhu, Masayuki Fujino, Hidenori Ito, Kiwamu Takahashi, Motowo Nakajima, Tohru Tanaka, Jiucun Wang, Jian Zhuang, Hejian Zou, Xiao-Kang Li
Scleroderma or systemic sclerosis (SSc) is a clinically heterogeneous rheumatological autoimmune disease affecting the skin, internal organs and blood vessels. There is at present no effective treatment for this condition. Our study investigated the effects of 5-aminolevulinic acid (5-ALA) which isa precursor of heme synthesis, on graft-versus-host disease (GvHD)-induced SSc murine model. Lymphocytes were intravenously injected from donor mice (B10.D2) into recipient BALB/c mice (recombination activating gene 2 (Rag-2)-null mice) deficient in mature T and B cells to induce sclerodermatous GvHD (scl-GvHD)...
July 6, 2018: Experimental Dermatology
Pierre Balmer, Auxanne K Fellay, Beysa S Sayar, William J Hariton, Dominique J Wiener, Arnaud Galichet, Eliane J Müller, Petra J Roosje
FAM83G/Fam83g genetic variants have been described in dogs, mice and recently also in humans. They are associated with palmoplantar keratoderma and altered hair or coat phenotype, reported as wooly phenotype in mice. FAM83G/Fam83g is an unexplored effector of temporally and spatially coordinated Wnt and BMP signaling which are key pathways in pre- and postnatal hair follicle morphogenesis and differentiation. The aim of this study was to unravel phenotypic consequences of FAM83G/Fam83g variants on hair coat formation in dogs and mice...
July 2, 2018: Experimental Dermatology
Qin Meng, Chong Shen
Continuous contraction of 3D skin equivalents in construction and use restricts their applications in clinical and pharmaceutical practices. So far, no effective method has been developed to inhibit such contraction. Hence, low cytotoxic crosslinkers, 1-ethyl-3-3-dimethylaminopropylcarbodiimide hydrochloride (EDC) and genipin, are investigated to reduce the contraction in this paper. As found, both genipin and EDC at 0.2 and 0.4 mM are non-toxic to collagen entrapped fibroblasts and up-regulate the extracellular matrix expression of fibroblasts in crosslinked collagen...
June 29, 2018: Experimental Dermatology
Émilie Faway, Catherine Lambert de Rouvroit, Yves Poumay
Fungal infections of the skin, known as dermatophytoses, are initiated at the epidermal barrier and lead to dysfunctions of the stratum corneum and cornified skin appendages. Dermatophytosis affects a significant part of the human population and, despite the availability of effective treatments, its prevalence is still increasing. Numerous dermatophytes species are able to induce lesions in both animals and humans, with different clinical pictures and host inflammatory responses. The understanding of the infectious process and of tissue responses has been impeded by discrepancies between observations in vivo or in research models...
June 29, 2018: Experimental Dermatology
Yuan Shao, Zhaoping Qin, James Alexander Wilks, Rebecca Mutesi Balimunkwe, Gary J Fisher, John J Voorhees, Taihao Quan
Fragmentation of collagen fibrils and aberrant elastic material (solar elastosis) in the dermal extracellular matrix (ECM) are among the most prominent features of photodamaged human skin. These alterations impair the structural integrity and create a dermal microenvironment prone to skin disorders. The objective of this study was to determine the physical properties (surface roughness, stiffness, and hardness) of the dermal ECM in photodamaged and subject matched sun-protected human skin. Skin samples were sectioned and analyzed by histology, atomic force microscopy (AFM) and nanoindentation...
June 29, 2018: Experimental Dermatology
Xia Hong, Shan Jiang, Nancy Marmolejo, Ramya Vangipuram, Elmira Ramos-Rojas, Yulin Yuan, Zuan-Tao Lin, Yaxi Li, Jingyi Qiu, Yikun Xing, Christopher Haley, Stephen K Tyring, Tianfu Wu
To discover novel biomarkers of psoriasis, a target-specific antibody array screening of serum samples from psoriasis patients was initially performed. The results revealed that Vascular endothelial growth factor receptor 3 (VEGFR-3) was significantly elevated in the sera of psoriasis patients, compared to healthy controls. Next, ELISA validation studies in a larger cohort of psoriasis patients (N=73) were conducted which confirmed that serum VEGFR-3 was indeed significantly increased in patients with psoriasis compared to healthy controls (P < 0...
June 29, 2018: Experimental Dermatology
Aude Beyens, Ester Moreno-Artero, Christine Bodemer, Helen Cox, Alper Gezdirici, Elif Yilmaz Gulec, Najoua Kahloul, Philippe Khau Van Kien, Gonul Ogur, Annie Harroche, Marc Vasse, Aïcha Salhi, Sofie Symoens, Smail Hadj-Rabia, Bert Callewaert
In ATP6V0A2-related cutis laxa, the skin phenotype varies from a wrinkly skin to prominent cutis laxa, and typically associates with skeletal and neurological manifestations. The phenotype remains incompletely characterized, especially in adult patients. Glycosylation defects and reduced acidification of secretory vesicles contribute to the pathogenesis, but the consequences at the clinical level remain to be determined. Moreover, the morphology of the elastic fibers has not been studied in ATP6V0A2-related cutis laxa, nor its relation with potential clinical risks...
June 28, 2018: Experimental Dermatology
Takashi Taniguchi, Takuya Miyagawa, Satoshi Toyama, Takashi Yamashita, Kouki Nakamura, Ryosuke Saigusa, Yohei Ichimura, Takehiro Takahashi, Tetsuo Toyama, Ayumi Yoshizaki, Shinichi Sato, Yoshihide Asano
CXCL13, a chemokine for B cells, follicular T cells, T helper 17 cells, and regulatory T cells, is reported to contribute to the development of systemic sclerosis (SSc), reflecting aberrant activation of immune system. To better understand the role of CXCL13 in SSc, we investigated the influence of Fli1 deficiency, a potential predisposing factor of this disease, on CXCL13 expression and assessed clinical correlation of serum CXCL13 levels by multivariate regression analysis. Haploinsufficient loss of Fli1 remarkably induced CXCL13 expression in murine peritoneal macrophages, while gene silencing of FLI1 did not affect the expression of CXCL13 in human dermal fibroblasts and human dermal microvascular endothelial cells...
June 26, 2018: Experimental Dermatology
Trine Bertelsen, Lars Iversen, Claus Johansen
Antagonists of IL-17A and its receptor have proven to be highly effective in the treatment of psoriasis. However, many of the underlying molecular mechanisms involved in the pathogenesis of psoriasis are still to be determined. IκBζ (encoded by the NFKBIZ gene) plays a key role in the development of psoriasis by mediating IL-17A- and IL-17F-driven effects. Both IL-17A and IL-17F expression are increased in lesionel psoriatic skin. IL-17A/A and IL-17F/F homodimers as well as the IL-17A/F heterodimer signal through the same receptors...
June 25, 2018: Experimental Dermatology
Krysta Biniek, Ali Tfayli, Raoul Vyumvuhore, Alessia Quatela, Marie-Florence Galliano, Alexandre Delalleau, Arlette Baillet-Guffroy, Reinhold H Dauskardt, Helene Duplan
An important aspect of the biomechanical behavior of the stratum corneum (SC) is the drying stresses that develop with water loss. These stresses act as a driving force for damage in the form of chapping and cracking. Betasitosterol is a plant sterol with a structure similar to cholesterol, a key component in the intercellular lipids of the outermost layer of human skin, the SC. Cholesterol plays an important role in stabilizing the SC lipid structure, and altered levels of cholesterol have been linked with SC barrier abnormalities...
June 22, 2018: Experimental Dermatology
Yu Tsurekawa, Misaki Morita, Mary Ann Suico, Masataka Moriuchi, Yoshio Nakano, Mariam Piruzyan, Masafumi Takada, Sanako Fukami, Tsuyoshi Shuto, Hirofumi Kai
Psoriasis is a chronic skin disease caused by immune disorder. The chronic skin inflammation involves inflammatory molecules that are released from T lymphocytes and keratinocytes. Therefore, developing an anti-inflammatory therapy that is suitable for long-term treatment is needed. Electrical stimulation induces biological responses by modulating intracellular signaling pathways. Our previous studies showed that the optimized combination treatment of mild electrical stimulation (MES, 0.1-millisecond; ms, 55-pulses per second; pps) and heat shock (HS, 42°C) modulates inflammatory symptoms of metabolic disorders and chronic kidney disease in mice models and clinical trials...
June 21, 2018: Experimental Dermatology
Kelly M Glynn, Penny Anderson, David J Fast, James Koedam, John F Rebhun, Rodney A Velliquette
Glycation and advanced glycation endproducts (AGE) damage skin which is compounded by AGE-induced oxidative stress and inflammation. Lip and facial skin could be susceptible to glycation damage as they are chronically stressed. As Gromwell (Lithospermum erythrorhizon) root (GR) has an extensive traditional medicine history that includes providing multiple skin benefits, our objective was to determine if GR extract and its base naphthoquinone, shikonin, might protect skin by inhibiting glycation, increasing oxidative defenses, suppressing inflammatory responses, and offering ultraviolet (UV) absorptive potential in lip and facial cosmetic matrices...
June 15, 2018: Experimental Dermatology
D Crisan, K Scharffetter-Kochanek, M Crisan, S Schatz, H Hainzl, L Olenic, A Filip, L A Schneider, A Sindrilaru
New biomaterials based on nanoparticles (NPs) carrying polyphenols-rich extracts (Cornus mas) recently showed promising anti-inflammatory activity in psoriasis. We aimed to understand how topically delivered silver and gold nanoparticles complexed with Cornus mas (Ag-NPs-CM, Au-NPs-CM) modulate inflammation in psoriasis at cellular and molecular level. The impact on psoriatic inflammation was assessed in vitro on pro-inflammatory macrophages, by clinical score, high-frequency ultrasonography and immunohistology of psoriasis plaques treated with Ag-NPs-CM, Au-NPs-CM or control...
June 15, 2018: Experimental Dermatology
Ivone Jakasa, Jacob P Thyssen, Sanja Kezic
Skin diseases represent one of the most common work-related diseases and may have a detrimental effect on social, personal and occupational aspects of life. Contact dermatitis, which comprises predominately irritant contact dermatitis (ICD) and allergic contact dermatitis (ACD) accounts for vast majority of occupational skin diseases, especially in occupations associated with frequent skin contact with irritants and contact allergens. Although ICD and ACD have similar clinical manifestation, their pathophysiology and the role of the skin barrier is different...
June 12, 2018: Experimental Dermatology
Takashi Hashimoto, Jordan D Rosen, Kristen M Sanders, Gil Yosipovitch
Basophils are blood granulocytes and normally constitute less than 1% of blood peripheral leukocytes. Basophils share some morphological and functional similarities with mast cells, and basophils were once regarded as redundant and negligible circulating mast cells. However, recent studies reveal the indispensable roles of basophils in various diseases, including allergic and pruritic diseases. Basophils may be involved in itch through the mediation of a Th2 immune response, interaction with other cells in the skin, and secretion of a wide variety of itch-related mediators, e...
June 12, 2018: Experimental Dermatology
Eunah Suhng, Bo Hee Kim, You Won Choi, Hae Young Choi, Hyunjin Cho, Ji Yeon Byun
BACKGROUND: Rosacea is one of the most common dermatoses of adults. Although the detailed pathophysiology remains unknown, it is thought that rosacea is caused by a consistently aberrant, innate immune response, and that LL-37 plays an important role. However, involvement of the inflammatory cytokine IL-33 has not yet been studied. OBJECTIVES: We explored the role played by IL-33 in the pathophysiology of rosacea. METHODS: First, we immunohistochemically evaluated the expression of IL-33 and its receptor (ST2) in rosacea skin...
June 6, 2018: Experimental Dermatology
Leopold Eckhart, Erwin Tschachler
The function of the skin as a barrier to the environment is mainly achieved by the outermost layers of the epidermis. In the granular layer, epidermal keratinoytes undergo the last steps of their terminal differentiation program resulting in cornification. The coordinated conversion of living keratinocytes into corneocytes, the building blocks of the cornified layer, represents a unique form of programmed cell death. Recent studies have identified numerous genes that are specifically expressed in terminally differentiated keratinocytes and, surprisingly, this genetic program does not only include mediators of cornification but also suppressors of pyroptosis, another mode of programmed cell death...
June 4, 2018: Experimental Dermatology
Rudolf Stadler, René Stranzenbach
Primary cutaneous T-cell lymphoma (CTCL) comprises the second most common group of extra-nodal non-Hodgkin lymphoma. They represent incurable primary extra-nodal lymphomas of major T-cells, uniformly present in the skin with 1-2% risk of systemic dissemination in mycosis fungoides (MF) which represents the most common subtype of CTCL. In general, long-term antigen stimulation is thought, through key cytokine signalling pathways, to induce an inflammatory response with T-cell proliferation, leading to a clonal malignant T-cell with continuous expansion...
June 4, 2018: Experimental Dermatology
Alexander Boehner, Alexander A Navarini, Kilian Eyerich
Generalized pustular psoriasis (GPP) psoriasis is a rare, multisystemic skin disease characterized by recurrent episodes of pustulation. GPP can be life-threatening and is often difficult to treat. In the era of precision medicine in dermatology, GPP stands exemplary for both challenges and chances - while new treatments offer great hope, there is urgent need for better definition and stratification of this severe and heterogeneous disease. Our objective was to systematically review the literature for evidence of efficacy of targeted immunotherapy and their mode of action in the context of clinical phenotype, classification and pathogenesis of adult GPP...
May 31, 2018: Experimental Dermatology
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