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Keratinocyte activation

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https://www.readbyqxmd.com/read/28340212/accelerated-senescence-in-skin-in-a-murine-model-of-radiation-induced-multi-organ-injury
#1
Elizabeth A McCart, Rajesh L Thangapazham, Eric D Lombardini, Steven R Mog, Ronald Allan M Panganiban, Kelley M Dickson, Rihab A Mansur, Vitaly Nagy, Sung-Yop Kim, Reed Selwyn, Michael R Landauer, Thomas N Darling, Regina M Day
Accidental high-dose radiation exposures can lead to multi-organ injuries, including radiation dermatitis. The types of cellular damage leading to radiation dermatitis are not completely understood. To identify the cellular mechanisms that underlie radiation-induced skin injury in vivo, we evaluated the time-course of cellular effects of radiation (14, 16 or 17 Gy X-rays; 0.5 Gy/min) in the skin of C57BL/6 mice. Irradiation of 14 Gy induced mild inflammation, observed histologically, but no visible hair loss or erythema...
March 18, 2017: Journal of Radiation Research
https://www.readbyqxmd.com/read/28332183/retinoic-acid-receptor-related-orphan-receptor-ror%C3%AE-regulates-differentiation-and-survival-of-keratinocytes-during-hypoxia
#2
Hongyu Li, Longjian Zhou, Jun Dai
Low O2 pressures present in the microenvironment of epidermis control keratinocyte differentiation and epidermal barrier function through hypoxia inducible factors (HIFs) dependent gene expression. This study focuses on investigating relations of the retinoic acid receptor-related orphan receptor alpha (RORα) to HIF-1α in keratinocytes under hypoxic conditions. The expression level of RORα is significantly elevated under hypoxia in both human and murine keratinocytes. Gene silencing of RORA attenuates hypoxia-stimulated expression of genes related to late differentiation and epidermal barrier function, and leads to an enhanced apoptotic response...
March 23, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28330776/topical-application-of-glycolic-acid-suppresses-the-uvb-induced-il-6-il-8-mcp-1-and-cox-2-inflammation-by-modulating-nf-%C3%AE%C2%BAb-signaling-pathway-in-keratinocytes-and-mice-skin
#3
Sheau-Chung Tang, Pei-Yun Liao, Sung-Jen Hung, Jheng-Siang Ge, Shiou-Mei Chen, Ji-Ching Lai, Yu-Ping Hsiao, Jen-Hung Yang
BACKGROUND: Glycolic acid (GA), commonly present in fruits, has been used to treat dermatological diseases. Extensive exposure to solar ultraviolet B (UVB) irradiation plays a crucial role in the induction of skin inflammation. The development of photo prevention from natural materials represents an effective strategy for skin keratinocytes. OBJECTIVE: The aim of this study was to investigate the molecular mechanisms underlying the glycolic acid (GA)-induced reduction of UVB-mediated inflammatory responses...
March 11, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28330735/vancomycin-loaded-nanobubbles-a-new-platform-for-controlled-antibiotic-delivery-against-methicillin-resistant-staphylococcus-aureus-infections
#4
Monica Argenziano, Giuliana Banche, Anna Luganini, Nicole Finesso, Valeria Allizond, Giulia Rossana Gulino, Amina Khadjavi, Rita Spagnolo, Vivian Tullio, Giuliana Giribaldi, Caterina Guiot, Anna Maria Cuffini, Mauro Prato, Roberta Cavalli
Vancomycin (Vm) currently represents the gold standard against methicillin-resistant Staphylococcus aureus (MRSA) infections. However, it is associated with low oral bioavailability, formulation stability issues, and severe side effects upon systemic administration. These drawbacks could be overcome by Vm topical administration if properly encapsulated in a nanocarrier. Intriguingly, nanobubbles (NBs) are responsive to physical external stimuli such as ultrasound (US), promoting drug delivery. In this work, perfluoropentane (PFP)-cored NBs were loaded with Vm by coupling to the outer dextran sulfate shell...
March 19, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28329680/major-roles-for-pyrimidine-dimers-nucleotide-excision-repair-and-atr-in-the-alternative-splicing-response-to-uv-irradiation
#5
Manuel J Muñoz, Nicolás Nieto Moreno, Luciana E Giono, Adrián E Cambindo Botto, Gwendal Dujardin, Giulia Bastianello, Stefania Lavore, Antonio Torres-Méndez, Carlos F M Menck, Benjamin J Blencowe, Manuel Irimia, Marco Foiani, Alberto R Kornblihtt
We have previously found that UV irradiation promotes RNA polymerase II (RNAPII) hyperphosphorylation and subsequent changes in alternative splicing (AS). We show now that UV-induced DNA damage is not only necessary but sufficient to trigger the AS response and that photolyase-mediated removal of the most abundant class of pyrimidine dimers (PDs) abrogates the global response to UV. We demonstrate that, in keratinocytes, RNAPII is the target, but not a sensor, of the signaling cascade initiated by PDs. The UV effect is enhanced by inhibition of gap-filling DNA synthesis, the last step in the nucleotide excision repair pathway (NER), and reduced by the absence of XPE, the main NER sensor of PDs...
March 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28327271/novel-anti-staphylococcal-and-anti-biofilm-properties-of-two-anti-malarial-compounds-mmv665953-1-3-chloro-4-fluorophenyl-3-3-4-dichlorophenyl-urea-and-mmv665807-5-chloro-2-hydroxy-n-3-trifluoromethyl-phenyl-benzamide
#6
Marta Zapotoczna, Nabila Boksmati, Sinead Donohue, Baizurina Bahtiar, Ahmad Boland, Hamzah Al Somali, Alysia Cox, Hilary Humphreys, James P O'Gara, Marian Brennan, Eoghan O'Neill
PURPOSE: The treatment of device-related infections is challenging and current anti-microbial compounds have poor anti-biofilm activity. We aimed to identify and characterize novel compounds effective in the eradication of Staphylococcus aureus biofilms. METHODOLOGY: Two novel compounds, MMV665953 {1-(3-chloro-4-fluorophenyl)-3-(3,4-dichlorophenyl)urea} and MMV665807{5-chloro-2-hydroxy-N-[3-(trifluoromethyl)phenyl]benzamide}, effective in killing S. aureus biofilms, were identified by screening of the open access 'malaria box' chemical library...
March 23, 2017: Journal of Medical Microbiology
https://www.readbyqxmd.com/read/28326307/p75-neurotrophin-receptor-in-the-skin-beyond-its-neurotrophic-function
#7
REVIEW
Carlo Pincelli
p75 neurotrophin receptor (p75(NTR)), also known as CD271, is the low-affinity receptor that, together with the tyrosine kinase receptor tropomyosin-receptor kinase (Trk), mediate neurotrophin (NT) functions. Beside their classic role in skin innervation, NT and their receptors constitute a complex cutaneous network associated with a number of autocrine and paracrine activities. In this context, the role of p75(NTR) is becoming more and more important. This review will focus on the intriguing functions of p75(NTR) in healthy and diseased skin...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/28322977/assessment-of-penetration-potential-of-ph-responsive-double-walled-biodegradable-nanogels-coated-with-eucalyptus-oil-for-the-controlled-delivery-of-5-fluorouracil-in-vitro-and-ex-vivo-studies
#8
Prashant Sahu, Sushil K Kashaw, Sanyog Jain, Samaresh Sau, Arun K Iyer
Penetration enhancers coated biodegradable polymeric nanogels loaded with cytotoxic drugs applied via the topical route, can be a promising strategy for improving the chemotherapeutic efficiency of skin cancers. The major objective of proposed research was to investigate the in vitro and ex vivo chemotherapeutic potential of double walled PLGA-chitosan biodegradable nanogel entrapped with 5-fluororuacil (5-FU) coated with eucalyptus oil, topically applied onto the skin. 5-FU was first entrapped in PLGA core by solvent evaporation technique followed by coating with cationic chitosan for ionic interaction with anionic skin cancer cell membrane...
March 17, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28322333/squamous-epitheliotropism-of-enterovirus-a71-in-human-epidermis-and-oral-mucosa
#9
Win Kyaw Phyu, Kien Chai Ong, Chee Kwan Kong, Abdul Khalil Alizan, Tindivanam Muthurangam Ramanujam, Kum Thong Wong
Hand-foot-and-mouth disease is a self-limiting paediatric infectious disease commonly caused by Enterovirus A71 (Genus: Enterovirus, Family: Picornaviridae). Typical lesions in and around the hands, feet, oral cavity and other places may rarely be complicated by acute flaccid paralysis and acute encephalomyelitis. Although virus is readily cultured from skin vesicles and oral secretions, the cellular target/s of Enterovirus A71 in human skin and oral mucosa are unknown. In Enterovirus A71-infected human skin and oral mucosa organotypic cultures derived from the prepuce and lip biopsies, focal viral antigens and viral RNA were localized to cytoplasm of epidermal and mucosal squamous cells as early as 2 days post-infection...
March 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28322331/targeted-disruption-of-tc-ptp-in-the-proliferative-compartment-augments-stat3-and-akt-signaling-and-skin-tumor-development
#10
Hyunseung Lee, Mihwa Kim, Minwoo Baek, Liza D Morales, Ik-Soon Jang, Thomas J Slaga, John DiGiovanni, Dae Joon Kim
Tyrosine phosphorylation is a vital mechanism that contributes to skin carcinogenesis. It is regulated by the counter-activities of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). Here, we report the critical role of T-cell protein tyrosine phosphatase (TC-PTP), encoded by Ptpn2, in chemically-induced skin carcinogenesis via the negative regulation of STAT3 and AKT signaling. Using epidermal specific TC-PTP knockout (K14Cre.Ptpn2(fl/fl)) mice, we demonstrate loss of TC-PTP led to a desensitization to tumor initiator 7,12-dimethylbenz[a]anthracene (DMBA)-induced apoptosis both in vivo epidermis and in vitro keratinocytes...
March 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28322200/complement-component-c3-and-complement-factor-b-promote-growth-of-cutaneous-squamous-cell-carcinoma
#11
Pilvi Riihilä, Liisa Nissinen, Mehdi Farshchian, Markku Kallajoki, Atte Kivisaari, Seppo Meri, Reidar Grénman, Sirkku Peltonen, Juha Peltonen, Taina Pihlajaniemi, Ritva Heljasvaara, Veli-Matti Kähäri
Cutaneous squamous cell carcinoma (cSCC) is one of the most common metastatic skin cancers with increasing incidence. We examined the roles of complement component C3 and complement factor B (CFB) in the growth of cSCC. Analysis of cSCC cell lines (n = 8) and normal human epidermal keratinocytes (n = 11) with real-time quantitative PCR and Western blotting revealed up-regulation of C3 and CFB expression in cSCC cells. Immunohistochemical staining revealed stronger tumor cell-specific labeling for C3 and CFB in invasive cSCCs (n = 71) and recessive dystrophic epidermolysis bullosa-associated cSCCs (n = 11) than in cSCC in situ (n = 69), actinic keratoses (n = 63), and normal skin (n = 5)...
March 16, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28316371/znf395-is-an-activator-of-a-subset-of-ifn-stimulated-genes
#12
Linda Schroeder, Christine Herwartz, Darko Jordanovski, Gertrud Steger
Activation of the interferon (IFN) pathway in response to infection with pathogens results in the induction of IFN-stimulated genes (ISGs) including proinflammatory cytokines, which mount the proper antiviral immune response. However, aberrant expression of these genes is pathogenic to the host. In addition to IFN-induced transcription factors non-IFN-regulated factors contribute to the transcriptional control of ISGs. Here, we show by genome wide expression analysis, siRNA-mediated suppression and Doxycycline-induced overexpression that the cellular transcription factor ZNF395 activates a subset of ISGs including the chemokines CXCL10 and CXCL11 in keratinocytes...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28314912/differences-in-the-melanosome-distribution-within-the-epidermal-melanin-units-and-its-association-with-the-impairing-background-of-leukoderma-in-vitiligo-and-halo-nevi-a-retrospective-study
#13
Xi-Xi Xiong, Gao-Zhong Ding, Wen-E Zhao, Xue Li, Yu-Ting Ling, Li Sun, Qing-Li Gong, Yan Lu
Skin color is determined by the number of melanin granules produced by melanocytes that are transferred to keratinocytes. Melanin synthesis and the distribution of melanosomes to keratinocytes within the epidermal melanin unit (EMU) within the skin of vitiligo patients have been poorly studied. The ultrastructure and distribution of melanosomes in melanocytes and surrounding keratinocytes in perilesional vitiligo and normal skin were investigated using transmission electron microscopy (TEM). Furthermore, we performed a quantitative analysis of melanosome distribution within the EMUs with scatter plot...
March 17, 2017: Archives of Dermatological Research
https://www.readbyqxmd.com/read/28314260/induction-of-apoptosis-in-human-oral-keratinocyte-by-doxorubicin
#14
Hiroshi Sakagami, Noriyuki Okudaira, Yoshiko Masuda, Osamu Amano, Satoshi Yokose, Yumiko Kanda, Madoka Suguro, Takenori Natori, Hiroshi Oizumi, Takaaki Oizumi
BACKGROUND/AIM: We have previously reported that doxorubicin (DXR) showed much higher cytotoxicity against human oral squamous cell carcinoma cell lines compared to normal human mesenchymal normal oral cells (gingival fibroblast, periodontal ligament fibroblast, pulp cell), yielding high tumor-specificity. However, we unexpectedly found that doxorubicin showed potent cytotoxicity against human normal oral keratinocytes and primary gingival epithelial cells. In the present study, we investigated the reproducibility, underlining mechanisms and generality of this unexpected finding...
March 2017: Anticancer Research
https://www.readbyqxmd.com/read/28314151/cadmium-lead-and-arsenic-contamination-in-paddy-soils-of-a-mining-area-and-their-exposure-effects-on-human-hepg2-and-keratinocyte-cell-lines
#15
Shengguo Xue, Lizheng Shi, Chuan Wu, Hui Wu, Yanyan Qin, Weisong Pan, William Hartley, Mengqian Cui
A mining district in south China shows significant metal(loid) contamination in paddy fields. In the soils, average Pb, Cd and As concentrations were 460.1, 11.7 and 35.1mgkg(-1) respectively, which were higher than the environmental quality standard for agricultural soils in China (GB15618-1995) and UK Clea Soil Guideline Value. The average contents of Pb, Cd and As in rice were 5.24, 1.1 and 0.7mgkg(-1) respectively, which were about 25, 4.5 or 2.5 times greater than the limit values of the maximum safe contaminant concentration standard in food of China (GB 2762-2012), and about 25, 10 or 1 times greater than the limit values of FAO/WHO standard...
March 14, 2017: Environmental Research
https://www.readbyqxmd.com/read/28306742/hpv16-and-18-genome-amplification-show-different-e4-dependence-with-16e4-enhancing-e1-nuclear-accumulation-and-replicative-efficiency-via-its-cell-cycle-arrest-and-kinase-activation-functions
#16
Nagayasu Egawa, Qian Wang, Heather M Griffin, Isao Murakami, Deborah Jackson, Radma Mahmood, John Doorbar
To clarify E1^E4's role during high-risk HPV infection, the E4 proteins of HPV16 and 18 were compared side by side using an isogenic keratinocyte differentiation model. While no effect on cell proliferation or viral genome copy number was observed during the early phase of either virus life cycle, time-course experiments showed that viral genome amplification and L1 expression were differently affected upon differentiation, with HPV16 showing a much clearer E4 dependency. Although E4 loss never completely abolished genome amplification, its more obvious contribution in HPV16 focused our efforts on 16E4...
March 17, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28303029/tmf-and-glycitin-act-synergistically-on-keratinocytes-and-fibroblasts-to-promote-wound-healing-and-anti-scarring-activity
#17
Ga Young Seo, Yoongho Lim, Dongsoo Koh, Jung Sik Huh, Changlim Hyun, Young Mee Kim, Moonjae Cho
Keratinocyte-fibroblast interactions are critical for skin repair after injury. During the proliferative phase of wound healing, proliferation, migration and differentiation of these cells are the major mechanisms leading to tissue remodeling. We have previously reported that glycitin, a major soy isoflavone, stimulates dermal fibroblast proliferation; and the phytochemical, 4',6,7-trimethoxyisoflavone (TMF), induces migration of HaCaT keratinocyte cells. We therefore investigated whether these compounds display synergistic effects on skin cells during wound healing in vitro and in vivo...
March 17, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28302215/-altered-treg-and-il-1a-expression-in-the-immune-microenvironment-%C3%A2-of-lung-squamous-cell-cancer-after-egfr-blockade
#18
Haiyang He, Luyu Qi, Yiling Hou
BACKGROUND: Targeting the mutations and amplifications in the epidermal growth factor receptor (EGFR) gene has curative effects on cancers of the lung, oral cavity, and gastrointestinal system. However, a systemic immune inflammation is an adverse effect of this therapeutic strategy. In this study, we aimed to identify the possible changes in the tumor microenvironment that contribute to the anti-cancer activity of EGFR inhibition. METHODS: Squamous-cell cancers were induced by the syngeneic transplantation of either EGFR-null or wild-type mouse primary keratinocytes that had been transduced with an oncogenic H-ras retrovirus...
March 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/28301666/adaptation-of-the-keratinosens%C3%A2-skin-sensitisation-test-to-animal-product-free-cell-culture
#19
Nathalie Belot, Bushra Sim, Christopher Longmore Longmore, Lottie Roscoe, Carol Treasure
Skin sensitisation is the process by which a substance leads to an allergic reaction following skin contact. The process has been described as an adverse outcome pathway (AOP), including several key events, from skin penetration and covalent protein binding, to keratinocyte activation, dendritic cell activation and T-lymphocyte proliferation. The in vitro assay KeratinoSens™ measures the activation of keratinocytes. It is fully accepted at a regulatory level (OECD TG 442d) and appropriate for compliance with a range of legislation including the EU Cosmetics Regulation, REACH, and the CLP Regulation...
March 16, 2017: ALTEX
https://www.readbyqxmd.com/read/28301547/epidermal-loss-of-g%C3%AE-q-confers-a-migratory-and-differentiation-defect-in-keratinocytes
#20
Colleen L Doçi, Constantinos M Mikelis, Juan Luis Callejas-Valera, Karina K Hansen, Alfredo A Molinolo, Asuka Inoue, Stefan Offermanns, J Silvio Gutkind
G-protein coupled receptors (GPCRs), which activate heterotrimeric G proteins, are an essential class of transmembrane receptors that are responsible for a myriad of signaling events in normal and pathologic conditions. Two members of the G protein family, Gαq and Gα11, activate one of the main GPCR pathways and function as oncogenes by integrating mitogen-stimulated signaling cascades that are active under malignant conditions. Recently, it has been shown that targeted deletion of Gα11 and Gαq from endothelial cells impairs the Rho-mediated formation of focal adherens junctions, suggesting that Gα11/q signaling may also play a significant role in cytoskeletal-mediated cellular responses in epithelial cells...
2017: PloS One
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