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https://www.readbyqxmd.com/read/28646234/electroporation-as-a-vaccine-delivery-system-and-a-natural-adjuvant-to-intradermal-administration-of-plasmid-dna-in-macaques
#1
Biliana Todorova, Lucille Adam, Slobodan Culina, Raphaël Boisgard, Frédéric Martinon, Antonio Cosma, Mart Ustav, Thierry Kortulewski, Roger Le Grand, Catherine Chapon
In vivo electroporation (EP) is used to enhance the uptake of nucleic acids and its association with DNA vaccination greatly stimulates immune responses to vaccine antigens delivered through the skin. However, the effect of EP on cutaneous cell behavior, the dynamics of immune cell recruitment and local inflammatory factors, have not been fully described. Here, we show that intradermal DNA vaccination combined with EP extends antigen expression to the epidermis and the subcutaneous skin muscle in non-human primates...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28645160/chronic-pseudomonas-aeruginosa-biofilm-infection-impairs-murine-s100a8-a9-and-neutrophil-effector-cytokines-implications-for-delayed-wound-closure
#2
Hannah Trøstrup, Christian Johann Lerche, Lars Jackie Christophersen, Kim Thomsen, Peter Østrup Jensen, Hans Petter Hougen, Niels Høiby, Claus Moser
The impact of Pseudomonas aeruginosa biofilm infections in chronic wounds and clinical implication for healing is receiving increased attention. However, the pathophysiology of host/pathogen interplay is not fully understood. By further revealing the mechanisms, necessary new treatment strategies may be identified. Since the background for chronic wounds is diverse, representative animal models are important. We assessed host response and spontaneous wound closure in the relatively resistant C3H/HeN and the susceptible BALB/c mouse strain...
June 22, 2017: Pathogens and Disease
https://www.readbyqxmd.com/read/28644888/fragmentation-of-the-mitochondrial-network-in-skin-in-vivo
#3
Daniel Mellem, Martin Sattler, Sonja Pagel-Wolff, Sören Jaspers, Horst Wenck, Michael Alexander Rübhausen, Frank Fischer
Mitochondria form dynamic networks which adapt to the environmental requirements of the cell. We investigated the aging process of these networks in human skin cells in vivo by multiphoton microscopy. A study on the age-dependency of the mitochondrial network in young and old volunteers revealed that keratinocytes in old skin establish a significantly more fragmented network with smaller and more compact mitochondrial clusters than keratinocytes in young skin. Furthermore, we investigated the mitochondrial network during differentiation processes of keratinocytes within the epidermis of volunteers...
2017: PloS One
https://www.readbyqxmd.com/read/28643415/cultivation-of-human-dermal-fibroblasts-and-epidermal-keratinocytes-on-keratin-coated-silica-bead-substrates
#4
Bee Yi Tan, Luong T H Nguyen, Hyo-Sop Kim, Jae-Ho Kim, Kee Woei Ng
Human hair keratin is promising as a bioactive material platform for various biomedical applications. To explore its versatility further, human hair keratin was coated onto monolayers of silica beads to produce film-like substrates. This combination was hypothesized to provide a synergistic effect in improving the biochemical properties of the resultant composite. Atomic Force Microscopy analysis showed uniform coatings of keratin on the silica beads with a slight increase in the resulting surface roughness...
June 23, 2017: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/28643235/design-and-evaluation-of-rgd-modified-gemini-surfactant-based-lipoplexes-for-targeted-gene-therapy-in-melanoma-model
#5
Waleed Mohammed-Saeid, Jackson Chitanda, Mays Al-Dulaymi, Ronald Verrall, Ildiko Badea
PURPOSE: We have developed and evaluated novel peptide-targeted gemini surfactant-based lipoplexes designed for melanoma gene therapy. METHODS: Integrin receptor targeting peptide, cyclic-arginylglycylaspartic acid (cRGD), was either chemically coupled to a gemini surfactant backbone or physically co-formulated with lipoplexes. Several formulations and transfection techniques were developed. Transfection efficiency and cellular toxicity of the lipoplexes were evaluated in an in vitro human melanoma model...
June 22, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28642279/role-of-myd88-signaling-in-the-imiquimod-induced-mouse-model-of-psoriasis-focus-on-innate-myeloid-cells
#6
Sara Costa, Olivia Marini, Dalila Bevilacqua, Anthony L DeFranco, Baidong Hou, Silvia Lonardi, William Vermi, Pamela Rodegher, Anna Panato, Franco Tagliaro, Clifford A Lowell, Marco A Cassatella, Giampiero Girolomoni, Patrizia Scapini
Psoriasis is a chronic skin disease associated with deregulated activation of immune cells and keratinocytes. In this study, we used the imiquimod (IMQ)-induced mouse model of psoriasis to dissect better the contribution of hematopoietic and skin-resident stromal cells to psoriasis development. The comparison of disease development in mice carrying the hematopoietic cell-specific deletion of MyD88 (Myd88(fl/fl)Vav-cre(+) mice) with mice carrying the total MyD88 deficiency (Myd88(-/-) mice), we show that the progression of skin and systemic inflammation, as well as of epidermal thickening, was completely dependent on MyD88 expression in hematopoietic cells...
June 22, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28642156/tgf%C3%AE-smad-microrna-486-3p-signaling-axis-mediates-keratin-17-expression-and-keratinocyte-hyperproliferation-in-psoriasis
#7
Man Jiang, Zhongbin Sun, Erle Dang, Bing Li, Hui Fang, Junqin Li, Lin Gao, Kaiming Zhang, Gang Wang
Keratin 17 (K17) is strongly expressed in psoriatic lesions but not healthy skin, and plays a crucial role in disease pathogenesis. The mechanism of aberrant K17 expression in psoriasis has not been fully elucidated. MicroRNAs (miRNAs) are short, single-stranded, noncoding RNAs that play important roles in regulating gene expression. Psoriasis exhibits a specific miRNA expression profile distinct from that of healthy skin. In this study, we showed that miR-486-3p was markedly reduced in psoriatic epidermis and negatively correlated with the psoriasis area and severity index (PASI) score...
June 19, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28640877/identification-of-c-ebp%C3%AE-as-a-novel-target-of-the-hpv8-e6-protein-regulating-mir-203-in-human-keratinocytes
#8
Anna M Marthaler, Marta Podgorska, Pascal Feld, Alina Fingerle, Katrin Knerr-Rupp, Friedrich Grässer, Hans Smola, Klaus Roemer, Elke Ebert, Yoo-Jin Kim, Rainer M Bohle, Cornelia S L Müller, Jörg Reichrath, Thomas Vogt, Magdalena Malejczyk, Sławomir Majewski, Sigrun Smola
Patients suffering from Epidermodysplasia verruciformis (EV), a rare inherited skin disease, display a particular susceptibility to persistent infection with cutaneous genus beta-human papillomavirus (beta-HPV), such as HPV type 8. They have a high risk to develop non-melanoma skin cancer at sun-exposed sites. In various models evidence is emerging that cutaneous HPV E6 proteins disturb epidermal homeostasis and support carcinogenesis, however, the underlying mechanisms are not fully understood as yet. In this study we demonstrate that microRNA-203 (miR-203), a key regulator of epidermal proliferation and differentiation, is strongly down-regulated in HPV8-positive EV-lesions...
June 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28640219/topical-application-of-trisodium-ascorbyl-6-palmitate-2-phosphate-actively-supplies-ascorbate-to-skin-cells-in-an-ascorbate-transporter-independent-manner
#9
Shuichi Shibuya, Ikuyo Sakaguchi, Shintaro Ito, Eiko Kato, Kenji Watanabe, Naotaka Izuo, Takahiko Shimizu
Ascorbic acid (AA) possesses multiple beneficial functions, such as regulating collagen biosynthesis and redox balance in the skin. AA derivatives have been developed to overcome this compound's high fragility and to assist with AA supplementation to the skin. However, how AA derivatives are transferred into cells and converted to AA in the skin remains unclear. In the present study, we showed that AA treatment failed to increase the cellular AA level in the presence of AA transporter inhibitors, indicating an AA transporter-dependent action...
June 22, 2017: Nutrients
https://www.readbyqxmd.com/read/28639932/staphylococcus-epidermidis-lipoteichoic-acid-exocellular-release-and-ltas-gene-expression-in-clinical-and-commensal-isolates
#10
Elizabeth García-Gómez, Jesús F T Miranda-Ozuna, Francisco Díaz-Cedillo, Ernesto A Vázquez-Sánchez, Sandra Rodríguez-Martínez, Janet Jan-Roblero, Mario E Cancino-Diaz, Juan Carlos Cancino-Diaz
PURPOSE: Staphylococcus epidermidis ATCC12228 lipoteichoic acid (LTA) inhibits TNFα production from keratinocytes that are activated with poly I:C. However, this effect has not been proven in clinical or commensal isolates. METHODOLOGY: The <10 kDa fractions of S. epidermidis isolates from ocular infections (n=56), healthy skin (n=35) and healthy conjunctiva (n=32) were obtained. TNFα production was determined by elisa in HaCaT keratinocytes stimulated with poly I:C and with the <10 kDa fractions...
June 22, 2017: Journal of Medical Microbiology
https://www.readbyqxmd.com/read/28638277/titanium-dioxide-nanoparticles-as-radiosensitisers-an-in-vitro-and-phantom-based-study
#11
Esho Qasho Youkhana, Bryce Feltis, Anton Blencowe, Moshi Geso
Objective: Radiosensitisation caused by titanium dioxide nanoparticles (TiO2-NPs) is investigated using phantoms (PRESAGE(®) dosimeters) and in vitro using two types of cell lines, cultured human keratinocyte (HaCaT) and prostate cancer (DU145) cells. Methods: Anatase TiO2-NPs were synthesised, characterised and functionalised to allow dispersion in culture-medium for in vitro studies and halocarbons (PRESAGE(®) chemical compositions). PRESAGE(®) dosimeters were scanned with spectrophotometer to determine the radiation dose enhancement...
2017: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/28638272/bioactivities-of-ethanol-extract-from-the-antarctic-freshwater-microalga-chloromonas-sp
#12
Sung-Suk Suh, Eun Jin Yang, Sung Gu Lee, Ui Joung Youn, Se Jong Han, Il-Chan Kim, Sanghee Kim
Cancer is the principal cause of human death and occurs through highly complex processes that involve the multiple coordinated mechanisms of tumorigenesis. A number of studies have indicated that the microalgae extracts showed anticancer activity in a variety of human cancer cells and can provide a new insight in the development of novel anti-cancer therapy. Here, in order to investigate molecular mechanisms of anticancer activity in the Antarctic freshwater microalga, Chloromonas sp., we prepared ethanol extract of Chloromonas sp...
2017: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/28637950/adam17-regulates-tnf-%C3%AE-expression-upon-lipopolysaccharide-stimulation-in-oral-keratinocytes
#13
Aya Hirayama, Shuji Awano, Yuji Seta, Toshihiro Ansai
A disintegrin and metalloprotease 17 (ADAM17) is a tumor necrosis factor (TNF)-converting enzyme and was first identified as the enzyme that cleaves the prodomain of TNF-α, a proinflammatory cytokine that plays a central role in immune regulation and a variety of inflammatory responses in destructive periodontal disease. The aim of the present study was to verify the presence of ADAM17 in the gingival epithelium and elucidate its involvement in the release of TNF-αin oral keratinocytes. Immunohistochemical analyses of ADAM17 were performed in gingival tissues obtained from patients and in human oral keratinocytes (HOKs)...
2017: Biomedical Research
https://www.readbyqxmd.com/read/28637905/p120-catenin-downregulation-and-pik3ca-mutations-cooperate-to-induce-invasion-through-mmp1-in-hnscc
#14
Michal Kidacki, Heather L Lehman, Michelle V Green, Joshua I Warrick, Douglas B Stairs
Despite recent improvements in treatment for Head and Neck Squamous Cell Carcinoma (HNSCC), half of all patients with a regional or advanced disease will die within five years from diagnosis. Therefore, identification of mechanisms driving the aggressive behavior of HNSCC is of utmost importance. Since p120-catenin (CTNND1/P120CTN) downregulation and PIK3CA mutations are commonly found in HNSCC, the objective of this study was to identify their impact on fundamental processes of metastasis, specifically, migration and invasion...
June 21, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28636748/e-cadherin-mediates-uvr-and-calcium-induced-melanin-transfer-in-human-skin-cells
#15
Suman K Singh, Richard Baker, Stephen K Sikkink, Carine Nizard, Sylvianne Schnebert, Robin Kurfurst, Desmond J Tobin
Skin pigmentation is directed by epidermal-melanin units, characterized by long-lived and dendritic epidermal melanocytes (MC) that interact with viable keratinocytes (KC) to contribute melanin to the epidermis. Previously we reported that MC:KC contact is required for melanosome transfer, that this can be enhanced by filopodial and by UVR/UVA irradiation, which can up-regulate melanosome transfer via Myosin X-mediated control of MC filopodia. Both MC and KC express Ca(2+) -dependent E-cadherins. These homophilic adhesion contacts induce transient increases in intra-KC Ca(2+) , while ultraviolet radiation (UVR) raises intra-MC Ca(2+) via calcium selective ORAI1 ion channels; both are associated with regulating melanogenesis...
June 21, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28636114/set-i2pp2a-overexpression-induces-phenotypic-molecular-and-metabolic-alterations-in-an-oral-keratinocyte-cell-line
#16
Lays M Sobral, Ricardo D Coletta, Luciane C Alberici, Carlos Curti, Andréia Machado Leopoldino
The multifunctional SET/I2PP2A protein is known to be overexpressed in head and neck squamous cell carcinoma. However, SET has been reported to have apparently conflicting roles in promoting cancer cell survival under oxidative stress conditions and preventing invasion and metastasis, complicating efforts to understand the contribution of SET to carcinogenesis. In the present study, we overexpressed SET in a spontaneously immortalized oral keratinocyte cell line (NOK-SI SET) and demonstrated that SET up-regulation alone was sufficient to transform cells...
June 21, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28634035/psoriasis-associated-late-cornified-envelope-lce-proteins-have-antibacterial-activity
#17
Hanna Niehues, Lam C Tsoi, Danique A van der Krieken, Patrick A M Jansen, Merel A W Oortveld, Diana Rodijk-Olthuis, Ivonne M J J van Vlijmen, Wiljan J A J Hendriks, Richard W Helder, Joke A Bouwstra, Ellen H van den Bogaard, Philip E Stuart, Rajan P Nair, James T Elder, Patrick L J M Zeeuwen, Joost Schalkwijk
Terminally differentiating epidermal keratinocytes express a large number of structural and antimicrobial proteins that are involved in the physical barrier function of the stratum corneum and provide innate cutaneous host defense. Late cornified envelope (LCE) genes, located in the epidermal differentiation complex on chromosome 1, encode a family of 18 proteins of unknown function, whose expression is largely restricted to epidermis. Deletion of two members, LCE3B and LCE3C (LCE3B/C-del), is a widely replicated psoriasis risk factor that interacts with the major psoriasis-psoriasis risk gene HLA-C*06...
June 17, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28634034/absence-of-%C3%AE-chain-in-keratinocytes-alters-chemokine-secretion-resulting-in-reduced-immune-cell-recruitment
#18
Karolin Nowak, Daniela Linzner, Adrian J Thrasher, Paul F Lambert, Wei Li Di, Siobhan O Burns
Loss of function mutations in the common gamma (γc) chain cytokine receptor subunit give rise to severe combined immunodeficiency (SCID) characterised by lack of T and natural killer cells and infant death from infection. Haematopoietic stem cell transplantation or gene therapy offer cure but despite successful replacement of lymphoid immune lineages a long-term risk of severe cutaneous human papilloma virus (HPV) infections persists, possibly related to persistent γc-deficiency in other cell types. Here we demonstrate that keratinocytes, the only cell type directly infected by HPV, express functional γc and its co-receptors...
June 17, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28633807/differential-induction-of-atf3-and-ho-1-in-myeloid-cells-and-keratinocytes-via-dimethylfumarate-or-cyclosporine-a
#19
Stefanie Müller, Nikola Smatlik, Marc Burian, Kamran Ghoreschi, Martin Röcken, Amir S Yazdi
BACKGROUND: Chronic inflammatory skin diseases are characterized by controlled proliferation of keratinocytes. Here, activating transcription factor 3 (ATF3) might play a fundamental role. In these inflammatory diseases, proliferation is controlled and only rarely leads to cancer development which can be supported by an inflammatory microenvironment. ATF3 is a dual function protein as it suppresses pro-inflammatory IL-6 and IL-8, but also acts as a pro-oncogenic factor by the suppression of p53...
June 12, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28633806/il-17-for-therapy
#20
REVIEW
Florian C Kurschus, Sonja Moos
The cytokine IL-17 is now a target for an array of therapeutic monoclonal antibodies supposed to treat a variety of inflammatory diseases. The forerunner Secukinumab, an IL-17A neutralizing antibody, is meanwhile approved as first-line treatments for moderate-to-severe plaque psoriasis, and as second-line treatment for psoriatic arthritis and ankylosing spondylitis. Ixekizumab and Brodalumab, both also targeting the IL-17 pathway, were also recently approved by the FDA for plaque psoriasis. Using mice overexpressing IL-17A in a tissue of choice, we showed that the ectopic expression of this cytokine in keratinocytes resulted in a spontaneous and very strong form of psoriasis-like dermatitis...
June 15, 2017: Journal of Dermatological Science
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