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https://www.readbyqxmd.com/read/28445989/tmprss2-erg-gene-fusion-variants-induce-tgf-%C3%AE-signaling-and-epithelial-to-mesenchymal-transition-in-human-prostate-cancer-cells
#1
Leonie Ratz, Mark Laible, Lukasz A Kacprzyk, Stephanie M Wittig-Blaich, Yanis Tolstov, Stefan Duensing, Peter Altevogt, Sabine M Klauck, Holger Sültmann
TMPRSS2:ERG (T/E) gene fusions are present in approximately 50% of all prostate cancer (PCa) cases. The expression of fusion mRNAs from distinct T/E variants is associated with clinicopathological parameters, while the underlying molecular processes remain unclear. We characterized the molecular mechanisms and functional implications caused by doxycycline (Dox)-inducible overexpression of the frequent T/E III and VI fusion variants in LNCaP cells. Induction of T/E expression resulted in increased cellular migratory and invasive potential, and reduced proliferation and accumulation in G1 phase...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445980/the-pp4r1-sub-unit-of-protein-phosphatase-pp4-is-essential-for-inhibition-of-nf-%C3%AE%C2%BAb-by-merkel-polyomavirus-small-tumour-antigen
#2
Hussein Abdul-Sada, Marietta Müller, Rajni Mehta, Rachel Toth, J Simon C Arthur, Adrian Whitehouse, Andrew Macdonald
Merkel cell carcinoma (MCC) is a highly aggressive skin cancer with a high metastatic potential. The majority of MCC cases are caused by the Merkel cell polyomavirus (MCPyV), through expression of the virus-encoded tumour antigens. Whilst mechanisms attributing tumour antigen expression to transformation are being uncovered, little is known of the mechanisms by which MCPyV persists in the host. We previously identified the MCPyV small T antigen (tAg) as a novel inhibitor of nuclear factor kappa B (NF-kB) signalling and a modulator of the host anti-viral response...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445929/the-kinesin-motor-protein-kif7-is-required-for-t-cell-development-and-normal-mhc-expression-on-thymic-epithelial-cells-tec-in-the-thymus
#3
Ching-In Lau, Alessandro Barbarulo, Anisha Solanki, José Ignacio Saldaña, Tessa Crompton
Kif7 is a ciliary kinesin motor protein that regulates mammalian Hedgehog pathway activation through influencing structure of the primary cilium. Here we show that Kif7 is required for normal T-cell development, despite the fact that T-cells lack primary cilia. Analysis of Kif7-deficient thymus showed that Kif7-deficiency increases the early CD44+CD25+CD4-CD8- thymocyte progenitor population but reduces differentiation to CD4+CD8+ double positive (DP) cell. At the transition from DP to mature T-cell, Kif7-deficiency selectively delayed maturation to the CD8 lineage...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445867/the-mir-106a-363xpcl1-mirna-cluster-induces-murine-t-cell-lymphoma-despite-transcriptional-activation-of-the-p27kip1-cell-cycle-inhibitor
#4
Daniel A Kuppers, Thomas M Schmitt, Harry C Hwang, Lavanya Samraj, Bruce E Clurman, Matthew L Fero
The miR-106a~363 cluster encodes 6 miRNAs on the X-chromosome which are abundant in blood cells and overexpressed in a variety of malignancies. The constituent miRNA of miR-106a~363 have functional activities in vitro that are predicted to be both oncogenic and tumor suppressive, yet little is known about their physiological functions in vivo. Mature miR-106a~363 (Mirc2) miRNAs are processed from an intragenic, non-protein encoding gene referred to as Xpcl1 (or Kis2), situated at an X-chromosomal locus frequently targeted by retroviruses in murine lymphomas...
April 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445856/procyanidin-a-kind-of-biological-flavonoid-induces-protective-anti-tumor-immunity-and-protects-mice-from-lethal-b16f10-challenge
#5
Lina Zhang, Shuang Wang, Zeyuan Liu, Li Zhang, Shanzheng Wang, Bin Wang
Recently, increasing evidences show that procyanidin (PC) modulate immune responses in human. To evaluate adjuvant effects of PC on vaccine immune modulation and anti-tumor activity, we formulated PC with B16F10 tumor antigen as tumor vaccine to immune C57BL/6 mice and used intramuscular injection before challenge with tumor B16F10 cells. Our results revealed that PC enhanced T cell-mediated immune responses both in vitro and in vivo. Moreover, the B16F10 tumor vaccine induced some degree of anti-tumor effects as evaluated by the inhibition of tumor growth and the prolongation of survival...
April 23, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28445726/sirtuin-1-activation-controls-tumor-growth-by-impeding-th17-differentiation-via-stat3-deacetylation
#6
Emeric Limagne, Marion Thibaudin, Romain Euvrard, Hélène Berger, Pauline Chalons, Frédérique Végan, Etienne Humblin, Romain Boidot, Cédric Rébé, Valentin Derangère, Sylvain Ladoire, Lionel Apetoh, Dominique Delmas, François Ghiringhelli
Sirtuin-1 deacetylates proteins and has emerged as a critical regulator of different cellular processes, particularly inflammation. Basal SIRT1 activity was previously found to limit Th9 and enhance Th17 differentiation in mice, but the effect of pharmacological SIRT1 activation on T cell differentiation and antitumor responses remains unclear. Here, we find that SIRT1 pharmacological agonists selectively impede mouse and human Th17 cell differentiation. SIRT1 activation induces STAT3 deacetylation, thus reducing its ability to translocate into the nucleus, bind to Rorc promoter, and induce its transcription...
April 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28445509/functional-genetic-variants-within-the-sirt2-gene-promoter-in-acute-myocardial-infarction
#7
Wentao Yang, Feng Gao, Pei Zhang, Shuchao Pang, Yinghua Cui, Lixin Liu, Guanghe Wei, Bo Yan
Coronary artery disease (CAD), including acute myocardial infarction (AMI) is the complication of atherosclerosis. Recently, genome-wide association studies have identified a large number of CAD-related genetic variants. However, only 10% of CAD cases could be explained. Low frequent and rare genetic variants have been recently proposed to be main causes for CAD. SIRT2 is a member of sirtuin family, NAD(+)-dependent class III deacetylases. SIRT2 is involved in genomic stability, metabolism, inflammation, oxidative stress and autophagy, as well as in platelet function...
2017: PloS One
https://www.readbyqxmd.com/read/28445497/prostaglandin-e2-produced-following-infection-with-theiler-s-virus-promotes-the-pathogenesis-of-demyelinating-disease
#8
Seung Jae Kim, Young-Hee Jin, Byung S Kim
Infection of various cells with Theiler's murine encephalomyelitis virus (TMEV) activates the TLR- and melanoma differentiation-associated gene 5 (MDA5)-dependent pathways, resulting in the production of IL-1β via the activation of caspase-1 upon assembly of the node-like receptor protein 3 (NLRP3) inflammasome. The role of IL-1β in the pathogenesis of TMEV-induced demyelinating disease was previously investigated. However, the signaling effects of prostaglandin E2 (PGE2) downstream of the NLRP3 inflammasome on the immune responses to viral determinants and the pathogenesis of demyelinating disease are unknown...
2017: PloS One
https://www.readbyqxmd.com/read/28445479/in-vitro-and-in-vivo-antivirus-activity-of-an-anti-programmed-death-ligand-1-pd-l1-rat-bovine-chimeric-antibody-against-bovine-leukemia-virus-infection
#9
Asami Nishimori, Satoru Konnai, Tomohiro Okagawa, Naoya Maekawa, Ryoyo Ikebuchi, Shinya Goto, Yamato Sajiki, Yasuhiko Suzuki, Junko Kohara, Satoshi Ogasawara, Yukinari Kato, Shiro Murata, Kazuhiko Ohashi
Programmed death-1 (PD-1), an immunoinhibitory receptor on T cells, is known to be involved in immune evasion through its binding to PD-ligand 1 (PD-L1) in many chronic diseases. We previously found that PD-L1 expression was upregulated in cattle infected with bovine leukemia virus (BLV) and that an antibody that blocked the PD-1/PD-L1 interaction reactivated T-cell function in vitro. Therefore, this study assessed its antivirus activities in vivo. First, we inoculated the anti-bovine PD-L1 rat monoclonal antibody 4G12 into a BLV-infected cow...
2017: PloS One
https://www.readbyqxmd.com/read/28445246/single-delivery-of-high-diversity-fecal-microbiota-preparation-by-colonoscopy-is-safe-and-effective-in-increasing-microbial-diversity-in-active-ulcerative-colitis
#10
Vinita Jacob, Carl Crawford, Shirley Cohen-Mekelburg, Monica Viladomiu, Gregory G Putzel, Yecheskel Schneider, Fatiha Chabouni, Sarah OʼNeil, Brian Bosworth, Viola Woo, Nadim J Ajami, Joseph F Petrosino, Ylaine Gerardin, Zain Kassam, Mark Smith, Iliyan D Iliev, Gregory F Sonnenberg, David Artis, Ellen Scherl, Randy S Longman
BACKGROUND: Recent trials suggest fecal microbiota transplantation (FMT) with repeated enemas and high-diversity FMT donors is a promising treatment to induce remission in ulcerative colitis. METHODS: We designed a prospective, open-label pilot study to assess the safety, clinical efficacy, and microbial engraftment of single FMT delivery by colonoscopy for active ulcerative colitis using a 2-donor fecal microbiota preparation (FMP). Safety and clinical endpoints of response, remission, and mucosal healing at week 4 were assessed...
April 25, 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28445193/a-pilot-randomized-trial-on-safety-and-efficacy-of-a-novel-topical-combined-inhibitor-of-janus-kinase-1-3-and-spleen-tyrosine-kinase-for-gvhd-associated-ocular-surface-disease
#11
Ahmad Kheirkhah, Antonio Di Zazzo, Vannarut Satitpitakul, Merle Fernandez, Daniel Magilavy, Reza Dana
PURPOSE: Janus kinase (JAK) and spleen tyrosine kinase (SYK) play critical functions in T-cell activation and in inflammation. Because of their antiinflammatory effects, JAK and SYK inhibitors have recently been evaluated in several immunopathogenic disorders. This pilot study was designed to assess the safety and efficacy of a topical combined JAK/SYK inhibitor, R348, ophthalmic solution for treatment of ocular surface disease in graft-versus-host disease (GVHD). METHODS: This phase 2, double-masked, randomized, pilot trial included 30 patients with ocular surface disease due to GVHD who were randomized to receive topical 0...
April 25, 2017: Cornea
https://www.readbyqxmd.com/read/28445076/image-based-phenotypic-screening-with-human-primary-t-cells-using-one-dimensional-imaging-cytometry-with-self-tuning-statistical-gating-algorithms
#12
Steve S Wang, Daniel J Ehrlich
The parallel microfluidic cytometer (PMC) is an imaging flow cytometer that operates on statistical analysis of low-pixel-count, one-dimensional (1D) line scans. It is highly efficient in data collection and operates on suspension cells. In this article, we present a supervised automated pipeline for the PMC that minimizes operator intervention by incorporating multivariate logistic regression for data scoring. We test the self-tuning statistical algorithms in a human primary T-cell activation assay in flow using nuclear factor of activated T cells (NFAT) translocation as a readout and readily achieve an average Z' of 0...
April 1, 2017: SLAS Discovery
https://www.readbyqxmd.com/read/28444932/the-association-of-lamb1-polymorphism-and-expression-changes-with-the-risk-of-coal-workers-pneumoconiosis
#13
Xiaoming Ji, Baiqun Wu, Ruhui Han, Jingjin Yang, Esther Ayaaba, Ting Wang, Lei Han, Chunhui Ni
BACKGROUND: Pneumoconiosis is a serious occupational disease worldwide, which is characterized by irreversible and diffuse lung fibrotic lesions. Laminin beta 1(LAMB1) is widely expressed in tissues and it is crucial for both lung morphogenesis and physiological function. In this study, we explored the association between LAMB1 rs4320486 and risk of pneumoconiosis in a Chinese population, as well as its mechanisms. METHODS: In this case-control study, 600 CWP patients and 605 controls were genotyped for the LAMB1 rs4320486 polymorphism using TaqMan methods...
April 26, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/28444928/antiinflammatory-activity-of-cinnamon-cinnamomum-zeylanicum-bark-essential-oil-in-a-human-skin-disease-model
#14
Xuesheng Han, Tory L Parker
The effect of cinnamon (Cinnamomum zeylanicum) bark essential oil (CBEO) on human skin cells has not been elucidated. Therefore, we investigated the activity of a commercially available CBEO in a validated human dermal fibroblast system, a model of chronic inflammation and fibrosis. We first evaluated the impact of CBEO on 17 protein biomarkers that play critical roles in inflammation and tissue remodeling. The impact of CBEO on genome-wide gene expression was also evaluated. CBEO showed strong anti-proliferative effects on skin cells and significantly inhibited the production of several inflammatory biomarkers, including vascular cell adhesion molecule-1, intercellular cell adhesion molecule-1, monocyte chemoattractant protein-1, interferon gamma-induced protein 10, interferon-inducible T-cell alpha chemoattractant, and monokine induced by gamma interferon...
April 26, 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/28444859/roles-of-samhd1-in-antiviral-defense-autoimmunity-and-cancer
#15
REVIEW
Miaomiao Li, Dong Zhang, Mengying Zhu, Yuxian Shen, Wei Wei, Songcheng Ying, Heinrich Korner, Jun Li
The enzyme, sterile α motif and histidine-aspartic acid domain-containing protein 1 (SAMHD1) diminishes infection of human immunodeficiency virus type 1 (HIV-1) by hydrolyzing intracellular deoxynucleotide triphosphates (dNTPs) in myeloid cells and resting CD4+ T cells. This dNTP degradation reduces the dNTP concentration to a level insufficient for viral cDNA synthesis, thereby inhibiting retroviral replication. This antiviral enzymatic activity can be inhibited by viral protein X (Vpx). The HIV-2/SIV Vpx causes degradation of SAMHD1, thus interfering with the SAMHD1-mediated restriction of retroviral replication...
April 25, 2017: Reviews in Medical Virology
https://www.readbyqxmd.com/read/28444847/complement-dependence-of-murine-costimulatory-blockade-resistant-cellular-cardiac-allograft-rejection
#16
Nicholas Chun, Robert L Fairchild, Yansui Li, Jinhua Liu, Ming Zhang, William M Baldwin, Peter S Heeger
Building upon studies showing that ischemia/reperfusion-(IR)-injury is complement-dependent, we tested links among complement activation, transplant associated ischemia-reperfusion injury, and murine cardiac allograft rejection. We transplanted BALB/c hearts subjected to 8h cold ischemic storage (CIS) into CTLA4Ig-treated WT or c3(-/-) B6 recipients. Whereas allografts subjected to 8h CIS rejected in WT recipients with a median survival time (MST) of 37d, identically treated hearts survived >60d in c3(-/-) mice (p<0...
April 26, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28444759/dysregulated-cd46-shedding-interferes-with-th1-contraction-in-systemic-lupus-erythematosus
#17
Ursula Ellinghaus, Andrea Cortini, Christopher L Pinder, Gaelle Le Friec, Claudia Kemper, Timothy J Vyse
IFN-γ-producing T helper 1 (Th1) cell responses mediate protection against infections but uncontrolled Th1 activity also contributes to a broad range of autoimmune diseases. Autocrine complement activation has recently emerged as key in the induction and contraction of human Th1 immunity: Activation of the complement regulator CD46 and the C3aR expressed by CD4(+) T cells via autocrine generated ligands C3b and C3a, respectively, are critical to IFN-γ production. Further, CD46-mediated signals also induce co-expression of immunosuppressive IL-10 in Th1 cells and transition into a (self)-regulating and contracting phase...
April 26, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28444612/wbp2nl-pawp-mrna-and-protein-expression-in-sperm-cells-are-not-related-to-semen-parameters-fertilization-rate-or-reproductive-outcome
#18
T Freour, M Barragan, A Ferrer-Vaquer, A Rodríguez, Rita Vassena
PURPOSE: WBP2NL/PAWP, a protein found in the post-acrosomal region of mammalian spermatozoa, has been proposed as a sperm-borne oocyte-activating factor (SOAF) contributing to Ca(2+) release within the oocyte and subsequent fertilization and embryo development. However, its relevance as either a diagnostic or a prognostic marker of fertilization failure has been questioned in the recent literature. We analyzed WBP2NL/PAWP gene and protein expression level and localization in patients without previous intracytoplasmic sperm injection (ICSI) cycles in order to assess its association with both sperm characteristics and ability to fertilize...
March 21, 2017: Journal of Assisted Reproduction and Genetics
https://www.readbyqxmd.com/read/28444390/characterisation-of-drug-specific-signalling-between-primary-human-hepatocytes-and-immune-cells
#19
Monday O Ogese, Lee Faulkner, Roz E Jenkins, Neil S French, Ian M Copple, Daniel J Antoine, Mohamed Elmasry, Hasan Malik, Christopher E Goldring, B Kevin Park, Catherine Betts, Dean J Naisbitt
It is now apparent that antigen-specific T-cells are activated in certain patients with drug-induced liver injury (DILI). Since cross-talk between hepatocytes and immune cells is likely to be critical in determining the outcome of drug exposure, the aim of this study was to profile the signals released by drug-treated hepatocytes and to characterise the impact of these molecules on dendritic cells. Human hepatocytes were exposed to three drugs (flucloxacillin, amoxicillin and isoniazid) associated with DILI potentially mediated by the adaptive immune system as drug-specific T-cells have been isolated from DILI patients, and the metabolite nitroso-sulfamethoxazole (SMX-NO)...
April 21, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28444310/arl3-and-rp2-regulate-the-trafficking-of-ciliary-tip-kinesins
#20
Nele Schwarz, Amelia Lane, Katarina Jovanovich, David A Parfitt, Monica Aguila, Clare L Thompson, Lyndon da Cruz, Peter J Coffey, J Paul Chapple, Alison J Hardcastle, Michael E Cheetham
Ciliary trafficking defects are the underlying cause of many ciliopathies, including Retinitis Pigmentosa (RP). Anterograde intraflagellar transport (IFT) is mediated by kinesin motor proteins; however, the function of the homodimeric Kif17 motor in cilia is poorly understood, whereas Kif7 is known to play an important role in stabilising cilia tips. Here we identified the ciliary tip kinesins Kif7 and Kif17 as novel interaction partners of the small GTPase Arl3 and its regulatory GTPase activating protein (GAP) Retinitis Pigmentosa 2 (RP2)...
April 21, 2017: Human Molecular Genetics
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