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Charles Nicaise, Laura Weischelbaum, Liliane Schandene, Valérie Gangji, Florence Dehavay, Joanna Bouchat, Benoît Balau, Thomas Vogl, Muhammad S Soyfoo
OBJECTIVES: To determine the role of S100A8/A9 in the pathogenesis of primary Sjögren's syndrome (pSS). METHODS: The serum levels of S100A8/A9 were determined in pSS patients and healthy controls by ELISA. The expression of S100A8/A9 in salivary glands was assessed by immunohistochemistry. The phenotype of S100A8+ and S100A9+ cells was identified using double immunofluorescence. The effects of S100A8/A9 on cytokine production by peripheral blood mononuclear cells (PBMCs) from pSS patients were determined in vitro by flow cytometry...
October 7, 2016: Clinical and Experimental Rheumatology
Lucia Geis-Asteggiante, Suzanne Ostrand-Rosenberg, Catherine Fenselau, Nathan J Edwards
Spectral counting is a straightforward label-free quantitation strategy used in bottom-up proteomics workflows. The application of spectral counting in label-free top-down proteomics workflows can be similarly straightforward, but has not been applied as widely as quantitation by chromatographic peak areas or peak intensities. In this study, we evaluate spectral counting for quantitative comparisons in label-free top-down proteomics workflows by comparison with chromatographic peak areas and intensities. We tested these quantitation approaches by spiking standard proteins into a complex protein background and comparing relative quantitation by spectral counts with normalized chromatographic peak areas and peak intensities from deconvoluted extracted ion chromatograms of the spiked proteins...
October 17, 2016: Analytical Chemistry
Ashley A Basiorka, Kathy L McGraw, Erika A Eksioglu, Xianghong Chen, Joseph Johnson, Ling Zhang, Qing Zhang, Brittany A Irvine, Thomas Cluzeau, David A Sallman, Eric Padron, Rami Komrokji, Lubomir Sokol, Rebecca C Coll, Avril A B Robertson, Matthew A Cooper, John L Cleveland, Luke A O'Neill, Sheng Wei, Alan F List
Despite genetic heterogeneity, myelodysplastic syndromes (MDS) share features of cytological dysplasia and ineffective hematopoiesis. We report that a hallmark of MDS is activation of the NLRP3 inflammasome, which drives clonal expansion and pyroptotic cell death. Independent of genotype, MDS hematopoietic stem/progenitor cells (HSPC) overexpress inflammasome proteins and manifest activated NLRP3 complexes that direct activation of caspase-1, generation of IL-1β and IL-18 and pyroptotic cell death. Mechanistically, pyroptosis is triggered by the alarmin S100A9 that is found in excess in MDS HSPC and bone marrow plasma...
October 13, 2016: Blood
Roni Allaoui, Caroline Bergenfelz, Sofie Mohlin, Catharina Hagerling, Kiarash Salari, Zena Werb, Robin L Anderson, Stephen P Ethier, Karin Jirström, Sven Påhlman, Daniel Bexell, Balázs Tahin, Martin E Johansson, Christer Larsson, Karin Leandersson
Triple-negative (TN) breast cancers (ER(-)PR(-)HER2(-)) are highly metastatic and associated with poor prognosis. Within this subtype, invasive, stroma-rich tumours with infiltration of inflammatory cells are even more aggressive. The effect of myeloid cells on reactive stroma formation in TN breast cancer is largely unknown. Here, we show that primary human monocytes have a survival advantage, proliferate in vivo and develop into immunosuppressive myeloid cells expressing the myeloid-derived suppressor cell marker S100A9 only in a TN breast cancer environment...
October 11, 2016: Nature Communications
Furkan U Ertem, Wenqian Zhang, Kyle Chang, Wan Mohaiza Dashwood, Praveen Rajendran, Deqiang Sun, Ala Abudayyeh, Eduardo Vilar, Maen Abdelrahim, Roderick H Dashwood
Intervention strategies in familial adenomatous polyposis (FAP) patients and other high-risk colorectal cancer (CRC) populations have highlighted a critical need for endoscopy combined with safe and effective preventive agents. We performed transcriptome profiling of colorectal adenomas from FAP patients and the polyposis in rat colon (Pirc) preclinical model, and prioritized molecular targets for prevention studies in vivo. At clinically relevant doses in the Pirc model, the drug Clotam (tolfenamic acid, TA) was highly effective at suppressing tumorigenesis both in the colon and in the small intestine, when administered alone or in combination with Sulindac...
October 5, 2016: International Journal of Cancer. Journal International du Cancer
Hiroki Tanigawa, Keishi Miyata, Zhe Tian, Jun Aoi, Tsuyoshi Kadomatsu, Satoshi Fukushima, Aki Ogata, Naoki Takeda, Jiabin Zhao, Shunshun Zhu, Kazutoyo Terada, Motoyoshi Endo, Jun Morinaga, Taichi Sugizaki, Michio Sato, Masaki Suimye Morioka, Ichiro Manabe, Youichi Mashimo, Akira Hata, Yoshitaka Taketomi, Kei Yamamoto, Makoto Murakami, Kimi Araki, Masatoshi Jinnin, Hironobu Ihn, Yuichi Oike
Psoriasis is a chronic inflammatory skin disease marked by aberrant tissue repair. Mutant mice modeling psoriasis skin characteristics have provided useful information relevant to molecular mechanisms and could serve to evaluate therapeutic strategies. Here, we found that epidermal ANGPTL6 expression was markedly induced during tissue repair in mice. Analysis of mice overexpressing ANGPTL6 in keratinocytes (K14-Angptl6 Tg mice) revealed that epidermal ANGPTL6 activity promotes aberrant epidermal barrier function due to hyperproliferation of prematurely differentiated keratinocytes...
October 4, 2016: Scientific Reports
Karen Put, Jessica Vandenhaute, Anneleen Avau, Annemarie Van Nieuwenhuijze, Ellen Brisse, Tim Dierckx, Omer Rutgeerts, Josselyn Garcia-Perez, Jaan Toelen, Mark Waer, Georges Leclercq, An Goris, Johan Van Weyenbergh, Adrian Liston, Lien de Somer, Carine Wouters, Patrick Matthys
OBJECTIVE: Systemic juvenile idiopathic arthritis (sJIA) is an immune-inflammatory disease characterized by arthritis and systemic features. The role of natural killer (NK) cells in sJIA pathogenesis remains unclear. Therefore, we performed a comprehensive analysis of NK cell phenotype and functionality in sJIA patients. METHODS: NK cell-specific transcriptional alterations were investigated by RNA-sequencing of highly purified NK cells from six active sJIA patients and six healthy controls...
October 1, 2016: Arthritis & Rheumatology
Kevin J Ashton, Melissa E Reichelt, S Jamal Mustafa, Bunyen Teng, Catherine Ledent, Lea M D Delbridge, Polly A Hofmann, R Ray Morrison, John P Headrick
Influences of adenosine 2A receptor (A2AR) activity on the cardiac transcriptome and genesis of endotoxemic myocarditis are unclear. We applied transcriptomic profiling (39 K Affymetrix arrays) to identify A2AR-sensitive molecules, revealed by receptor knockout (KO), in healthy and endotoxemic hearts. Baseline cardiac function was unaltered and only 37 A2AR-sensitive genes modified by A2AR KO (≥1.2-fold change, <5 % FDR); the five most induced are Mtr, Ppbp, Chac1, Ctsk and Cnpy2 and the five most repressed are Hp, Yipf4, Acta1, Cidec and Map3k2...
September 30, 2016: Purinergic Signalling
Shunsuke Sekiya, Makoto Murata, Satoshi Arai, Hiroshi Murayama, Atushi Kawasaki, Noriyuki Ashida, Kohki Okada, Masaki Ikemoto
Calprotectin, a heterodimer of S100A8 and S100A9, has been reported to be a useful biomarker in inflammatory bowel disease (IBD); however, the relationship between the fecal level of S100A9 and the extent of inflammation in IBD remains unclear. Our aim was to develop a new enzyme-linked immunosorbent assay (ELISA) for rat S100A9, and to investigate whether changes in fecal S100A9 levels reflect the inflammatory conditions in the intestinal tracts of rats with dextran sulfate sodium (DSS)-induced colitis. Anti-rat S100A9 monoclonal antibodies were raised in mice and used for the development of a novel ELISA for rat S100A9...
September 28, 2016: Journal of Immunological Methods
Jan Máca, Filip Burša, Pavel Ševčík, Peter Sklienka, Michal Burda, Michal Holub
PURPOSE: Tissue injury causing immune response is an integral part of surgical procedure. Evaluation of the degree of surgical trauma could help to improve postoperative management and determine the clinical outcomes. MATERIALS AND METHODS: We analyzed serum levels of alarmins, including S100A5, S100A6, S100A8, S100A9, S100A11, and S100A12; high-mobility group box 1; and heat-shock protein 70, after elective major abdominal surgery (n = 82). Blood samples were collected for three consecutive days after surgery...
September 30, 2016: Journal of Investigative Surgery: the Official Journal of the Academy of Surgical Research
Demetrios Moris, Eleftherios Spartalis, Anastasios Angelou, Georgios-Antonios Margonis, Alexandros Papalambros, Athanasios Petrou, Antonios Athanasiou, Dimitrios Schizas, Dimitrios Dimitroulis, Evangelos Felekouras
PURPOSE: Associations between inflammation and carcinogenesis have been reported for many years, as originally postulated by Virchow in his studies, but the results from prospective cohort studies remain controversial. We evaluated the role of calprotectin as a biomarker for colorectal cancer (CRC). METHODS: The MEDLINE/PubMed database was thoroughly searched using the keywords: "inflammation", "colorectal cancer, "calprotectin", "carcinogenesis" and/or "biomarkers"...
July 2016: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
Maria Sole Chimenti, Paola Triggianese, Elisabetta Botti, Alessandra Narcisi, Paola Conigliaro, Alessandro Giunta, Miriam Teoli, Roberto Perricone, Antonio Costanzo
OBJECTIVE: To evaluate levels of the calcium-binding proteins S100A8 and S100A9 in the skin of patients with psoriatic arthritis. METHODS: Skin punch biopsies were obtained from patients with psoriatic arthritis and healthy control subjects. S100A8/A9 were semiquantified via immunohistochemistry and semiquantitative polymerase chain reaction. RESULTS: The study included biopsies from nine patients with psoriatic arthritis and nine control subjects...
September 2016: Journal of International Medical Research
Débora Orcia, Ana Eliza Zeraik, José L S Lopes, Joci N A Macedo, Clarissa Romano Dos Santos, Katia C Oliveira, Leticia Anderson, B A Wallace, Sergio Verjovski-Almeida, Ana Paula Ulian Araujo, Ricardo DeMarco
BACKGROUND: The Micro-Exon Gene-14 (MEG-14) displays a remarkable structure that allows the generation of antigenic variation in Schistosomes. Previous studies showed that the soluble portion of the MEG-14 protein displays features of an intrinsically disordered protein and is expressed exclusively in the parasite esophageal gland. These features indicated a potential for interaction with host proteins present in the plasma and cells from ingested blood. METHODS: A yeast two-hybrid experiment using as bait the soluble domain of Schistosoma mansoni MEG-14 (sMEG-14) against a human leukocyte cDNA library was performed...
September 15, 2016: Biochimica et Biophysica Acta
Martin Sill, Christoph Schröder, Ying Shen, Aseel Marzoq, Radovan Komel, Jörg D Hoheisel, Henrik Nienhüser, Thomas Schmidt, Damjana Kastelic
In this study, protein profiling was performed on gastric cancer tissue samples in order to identify proteins that could be utilized for an effective diagnosis of this highly heterogeneous disease and as targets for therapeutic approaches. To this end, 16 pairs of postoperative gastric adenocarcinomas and adjacent non-cancerous control tissues were analyzed on microarrays that contain 813 antibodies targeting 724 proteins. Only 17 proteins were found to be differentially regulated, with much fewer molecules than the numbers usually identified in studies comparing tumor to healthy control tissues...
July 8, 2016: Microarrays
Dominique de Seny, Gaël Cobraiville, Pierre Leprince, Marianne Fillet, Charlotte Collin, Myrielle Mathieu, Jean-Philippe Hauzeur, Valérie Gangji, Michel G Malaise
BACKGROUND: Nonunion is a failure of healing following a bone fracture. Its physiopathology remains partially unclear and the discovery of new mediators could promote the understanding of bone healing. METHODS: Thirty-three atrophic nonunion (NU) patients that failed to demonstrate any radiographic improvement for 6 consecutive months were recruited for providing serum samples. Thirty-five healthy volunteers (HV) served as the control group. Proteomics studies were performed using SELDI-TOF-MS and 2D-DIGE approaches, associated or not with Proteominer® preprocessing, to highlight biomarkers specific to atrophic nonunion pathology...
2016: Journal of Translational Medicine
Priscila F de Aquino, Paulo Costa Carvalho, Fábio C S Nogueira, Clovis Orlando da Fonseca, Júlio Cesar Thomé de Souza Silva, Maria da Gloria da Costa Carvalho, Gilberto B Domont, Nilson I T Zanchin, Juliana de Saldanha da Gama Fischer
Tumors consist of cells in different stages of transformation with molecular and cellular heterogeneity. By far, heterogeneity is the hallmark of glioblastoma multiforme (GBM), the most malignant and aggressive type of glioma. Most proteomic studies aim in comparing tumors from different patients, but here we dive into exploring the intratumoral proteome diversity of a single GBM. For this, we profiled tumor fragments from the profound region of the same patient's GBM but obtained from two surgeries a year's time apart...
2016: Frontiers in Oncology
Eric Peter Thelin, David Just, Arvid Frostell, Anna Häggmark-Månberg, Mårten Risling, Mikael Svensson, Peter Nilsson, Bo-Michael Bellander
INTRODUCTION: The serum proteome following traumatic brain injury (TBI) could provide information for outcome prediction and injury monitoring. The aim with this affinity proteomic study was to identify serum proteins over time and between normoxic and hypoxic conditions in focal TBI. MATERIAL AND METHODS: Sprague Dawley rats (n=73) received a 3mm deep controlled cortical impact ("severe injury"). Following injury, the rats inhaled either a normoxic (22% O2) or hypoxic (11% O2) air mixture for 30minutes before resuscitation...
August 31, 2016: Behavioural Brain Research
Hazuki Tanaka, Ayaka Ohtsu, Shogo Shiratsuki, Ryoka Kawahara-Miki, Hisataka Iwata, Takehito Kuwayama, Koumei Shirasuna
The mammalian oviduct is an essential site for sperm storage, the transport of gametes, fertilization, and embryo development-functions that are aided by cytokines secreted from oviduct epithelial cells (OECs). Aging leads to cellular and organ dysfunction, with infertility associated with advanced maternal age. Few studies have investigated age-dependent changes in the oviduct as a possible cause of infertility, so we compared OECs from young (30-50 months) versus aged (more than 120 months) cattle. Next-generation sequencing was first used to identify age-related differences in gene expression...
September 2016: Molecular Reproduction and Development
Kyoung A Jhang, Eun Ok Lee, Kim Hee-Sun, Keun A Chang, Yoo-Hun Suh, Young Hae Chong
The S100A9 protein is an important proinflammatory factor of innate immunity that has been proposed to participate in inflammation associated with the pathogenesis of Alzheimer's disease. Here, we provide insights into the potential roles of extracellular S100A9 in the interaction with the immune response in human THP-1 monocytic cells that have been challenged with amyloid b1-42 (Aβ1-42) monomers instead of oligomers. Extracellular S100A9 alone produced a stimulatory effect on tumor necrosis factor-a and interleukin-1b, expression as well as released monocyte chemoattractant protein-1 into culture supernatants, which was accompanied by an increased level of matrix metalloproteinas-9 activity...
August 15, 2016: CNS & Neurological Disorders Drug Targets
Meike J Saul, Stefan Stein, Manuel Grez, Per-Johan Jakobsson, Dieter Steinhilber, Beatrix Suess
UPF1 is a key player in nonsense mediated mRNA decay (NMD) but also involved in posttranscriptional gene regulation. In this study we found that UPF1 regulates the expression of genes with functions in inflammation and myeloid cell differentiation via hnRNP E2. The majority of the UPF1-regulated genes identified in monocytic cells contain a binding site for hnRNP E2 within 5' UTR located introns with hnRNP E2 acting here as splicing regulator. We found that miRNA-328 which is significantly induced during monocytic cell differentiation acts independently from its gene silencing function as RNA decoy for hnRNP E2...
2016: Scientific Reports
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