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https://www.readbyqxmd.com/read/29212897/genetic-variants-contributing-to-circulating-matrix-metalloproteinase-8-levels-and-their-association-with-cardiovascular-diseases-a-genome-wide-analysis
#1
Aino Salminen, Efthymia Vlachopoulou, Aki S Havulinna, Taina Tervahartiala, Wolfgang Sattler, Marja-Liisa Lokki, Markku S Nieminen, Markus Perola, Veikko Salomaa, Juha Sinisalo, Seppo Meri, Timo Sorsa, Pirkko J Pussinen
BACKGROUND: Matrix metalloproteinase 8 (MMP-8) is a proinflammatory enzyme expressed mainly by neutrophils. Elevated serum and plasma concentrations of MMP-8 are associated with the risk for and outcome of cardiovascular diseases (CVDs). The origin of circulating MMP-8 is not completely clear. METHODS AND RESULTS: We performed a genome-wide association study of serum MMP-8 levels in 2 populations comprising altogether 6049 individuals. Moreover, we studied whether MMP-8-associated variants are linked to increased risk of CVDs and overall mortality in >20 000 subjects...
December 2017: Circulation. Cardiovascular Genetics
https://www.readbyqxmd.com/read/29211955/biochemical-and-spectroscopic-observation-of-mn-ii-sequestration-from-bacterial-mn-ii-transport-machinery-by-calprotectin
#2
Rose C Hadley, Derek M Gagnon, Megan Brunjes Brophy, Yu Gu, Toshiki G Nakashige, R David Britt, Elizabeth M Nolan
Human calprotectin (CP, S100A8/S100A9 oligomer) is a metal-sequestering host-defense protein that prevents bacterial acquisition of Mn(II). In this work, we investigate Mn(II) competition between CP and two solute-binding proteins that Staphylococcus aureus and Streptococcus pneumoniae, Gram-positive bacterial pathogens of significant clinical concern, use to obtain Mn(II) when infecting a host. Biochemical and electron paramagnetic resonance (EPR) spectroscopic analyses demonstrate that CP outcompetes staphylococcal MntC and streptococcal PsaA for Mn(II)...
December 6, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29204146/intracellular-s100a9-promotes-myeloid-derived-suppressor-cells-during-late-sepsis
#3
Jun Dai, Ajinkya Kumbhare, Dima Youssef, Charles E McCall, Mohamed El Gazzar
Myeloid precursor cell reprogramming into a myeloid-derived suppressor cell (MDSC) contributes to high mortality rates in mouse and human sepsis. S100A9 mRNA and intracellular protein levels increase during early sepsis and remain elevated in Gr1+CD11b+ MDSCs after pro-inflammatory sepsis transitions to the later chronic anti-inflammatory and immunosuppressive phenotype. The purpose of this study was to determine whether intracellular S100A9 protein might sustain Gr1+CD11b+ MDSC repressor cell reprogramming during sepsis...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29198531/laparoscopic-sleeve-gastrectomy-improves-nonalcoholic-fatty-liver-disease-related-liver-damage-in-adolescents-by-reshaping-cellular-interactions-and-hepatic-adipocytokine-production
#4
Valerio Nobili, Guido Carpino, Francesco De Peppo, Romina Caccamo, Antonella Mosca, Ilaria Romito, Diletta Overi, Antonio Franchitto, Paolo Onori, Anna Alisi, Eugenio Gaudio
OBJECTIVES: To investigate whether the modulation of local cellular cross-talks and the modification of hepatic adipocytokine expression could mechanistically explain the improvement of liver histopathology after laparoscopic sleeve gastrectomy (LSG) in adolescents with nonalcoholic fatty liver disease (NAFLD). STUDY DESIGN: Twenty obese (body mass index of ≥35 kg/m2) adolescents who underwent LSG and with biopsy-proven NAFLD were included. At baseline (T0) and 1 year after treatment, patients underwent clinical evaluation, blood tests, and liver biopsy...
November 30, 2017: Journal of Pediatrics
https://www.readbyqxmd.com/read/29197551/allelic-variants-of-the-aryl-hydrocarbon-receptor-differentially-influence-uvb-mediated-skin-inflammatory-responses-in-skh1-mice
#5
Kayla J Smith, Iain A Murray, Jacob A Boyer, Gary H Perdew
The mouse strain SKH1 is widely used in skin research due to its hairless phenotype and intact immune system. Due to the complex nature of aryl hydrocarbon receptor (AHR) function in the skin, the development of additional in vivo models is necessary to study its role in cutaneous homeostasis and pathology. Variants of the Ah allele, exist among different mouse strains. The Ahb-1 and Ahd alleles express high and low affinity ligand binding forms of the AHR, respectively. The outbred SKH1 mice express the Ahb-2 and/or Ahd alleles...
November 29, 2017: Toxicology
https://www.readbyqxmd.com/read/29190116/alarmins-in-frozen-shoulder-a-molecular-association-between-inflammation-and-pain
#6
Jonathon Z B Cher, Moeed Akbar, Susan Kitson, Lindsay A N Crowe, Emma Garcia-Melchor, Stephen C Hannah, Michael McLean, Umberto G Fazzi, Shauna C Kerr, George A C Murrell, Neal L Millar
BACKGROUND: The pathophysiological mechanisms behind proliferation of fibroblasts and deposition of dense collagen matrix in idiopathic frozen shoulder remain unclear. Alarmins (also known as danger signals) are endogenous molecules that are released into the extracellular milieu after infection or tissue injury and that signal cell and tissue damage. PURPOSE: To investigate whether the presence of alarmins is higher in patients with idiopathic frozen shoulder than in control subjects...
November 1, 2017: American Journal of Sports Medicine
https://www.readbyqxmd.com/read/29185197/a-non-peptidic-s100a9-specific-ligand-for-optical-imaging-of-phagocyte-activity-in-vivo
#7
Tom Völler, Andreas Faust, Johannes Roth, Michael Schäfers, Thomas Vogl, Sven Hermann
PURPOSE: Non-invasive assessment of inflammatory activity in the course of various diseases is a largely unmet clinical challenge. An early feature of inflammation is local secretion of the alarmin S100A8/A9 by activated phagocytes. We here evaluate a novel S100A9-targeted small molecule tracer Cy5.5-CES271 for in vivo optical imaging of inflammatory activity in exemplary disease models. PROCEDURES: Dynamics of Cy5.5-CES271 was characterized in a model of irritant contact dermatitis by sequential fluorescence reflectance imaging (FRI) up to 24 h postinjection (p...
November 28, 2017: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/29178941/s100a8-a9-and-srage-kinetic-after-polytrauma-an-explorative-observational-study
#8
Philippe Joly, John C Marshall, Philippe A Tessier, Chantal Massé, Nathalie Page, Anne Julie Frenette, François Khazoom, Soazig Le Guillan, Yves Berthiaume, Emmanuel Charbonney
BACKGROUND: Following tissue injury after trauma, the activation of innate immune pathways results in systemic inflammation, organ failure and an increased risk of infections. The objective of this study was to characterize the kinetics of the S100A8/S100A9 complex, a new-recognized alarmin, as well as its soluble receptor sRAGE, over time after trauma as potential early biomarkers of the risk of organ damage. METHODS: We collected comprehensive data from consenting patients admitted to an ICU following severe trauma...
November 25, 2017: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine
https://www.readbyqxmd.com/read/29160692/s100a9-protein-aggregates-boost-hippocampal-glutamate-modifying-monoaminergic-neurochemistry-a-glutamate-antibody-sensitive-outcome-on-alzheimer-like-memory-decline
#9
Marina A Gruden, Tatiana V Davydova, Vladimir S Kudrin, Chao Wang, Victor B Narkevich, Ludmilla A Morozova-Roche, Robert D E Sewell
Alzheimer's disease (AD) involves dementia conceivably arising from integrated inflammatory processes, amyloidogenesis and neuronal apoptosis. Glutamate can also cause neuronal death via excitotoxicity and this is similarly implicated in some neurological diseases. The aim was to examine treatment with in vitro generated pro-inflammatory protein S100A9 aggregate species alone or with glutamate antibodies (Glu-Abs) on Morris water maze (MWM) spatial learning and memory performance in 12-month old mice. Amino acid and monoamine cerebral neurotransmitter metabolic changes were concurrently monitored...
November 21, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29158436/pathogenic-role-of-the-damage-associated-molecular-patterns-s100a8-and-s100a9-in-coxsackievirus-b3-induced-myocarditis
#10
Irene Müller, Thomas Vogl, Kathleen Pappritz, Kapka Miteva, Konstantinos Savvatis, David Rohde, Patrick Most, Dirk Lassner, Burkert Pieske, Uwe Kühl, Sophie Van Linthout, Carsten Tschöpe
BACKGROUND: The alarmins S100A8 and S100A9 are damage-associated molecular patterns, which play a pivotal role in cardiovascular diseases, inflammation, and viral infections. We aimed to investigate their role in Coxsackievirus B3 (CVB3)-induced myocarditis. METHODS AND RESULTS: S100A8 and S100A9 mRNA expression was 13.0-fold (P=0.012) and 5.1-fold (P=0.038) higher in endomyocardial biopsies from patients with CVB3-positive myocarditis compared with controls, respectively...
November 2017: Circulation. Heart Failure
https://www.readbyqxmd.com/read/29135655/neutrophil-activation-and-enhanced-release-of-granule-products-in-hiv-tb-immune-reconstitution-inflammatory-syndrome
#11
Justine K Nakiwala, Naomi F Walker, Collin R Diedrich, William Worodria, Graeme Meintjes, Robert J Wilkinson, Harriet Mayanja-Kizza, Robert Colebunders, Luc Kestens, Katalin A Wilkinson, David M Lowe
BACKGROUND: Tuberculosis Immune Reconstitution Inflammatory Syndrome (TB-IRIS) remains incompletely understood. Neutrophils are implicated in tuberculosis pathology but detailed investigations in TB-IRIS are lacking. We sought to further explore the biology of TB-IRIS and in particular the role of neutrophils. SETTING: Two observational, prospective cohort studies in HIV/TB co-infected patients starting antiretroviral therapy, one to analyze gene expression and subsequently one to explore neutrophil biology...
November 6, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/29075268/calreticulin-fragment-39-272-promotes-b16-melanoma-malignancy-through-myeloid-derived-suppressor-cells-in-vivo
#12
Xiao-Yan He, Fang-Yuan Gong, Yong Chen, Zhe Zhou, Zheng Gong, Xiao-Ming Gao
Calreticulin (CRT), a multifunctional Ca(2+)-binding glycoprotein mainly located in the endoplasmic reticulum, is a tumor-associated antigen that has been shown to play protective roles in angiogenesis suppression and anti-tumor immunity. We previously reported that soluble CRT (sCRT) was functionally similar to heat shock proteins or damage-associated molecular patterns in terms of ability to activate myeloid cells and elicit strong inflammatory cytokine production. In the present study, B16 melanoma cell lines expressing recombinant CRT fragment 39-272 (sCRT/39-272) in secreted form (B16-CRT), or recombinant enhanced green fluorescence protein (rEGFP) (B16-EGFP), were constructed for investigation on the roles of sCRT in tumor development...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29061560/bitter-melon-prevents-the-development-of-4-nqo-induced-oral-squamous-cell-carcinoma-in-an-immunocompetent-mouse-model-by-modulating-immune-signalling
#13
Ratna B Ray, Subhayan Sur, Robert Steele, Rajeev Aurora, Mark Vavares, Katherine E Schwetye
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide, and tobacco is one of the most common factors for HNSCC of the oral cavity. We have previously observed that bitter melon (Momordica charantia) extract (BME) exerts anti-proliferative activity against several cancers including HNSCC. In this study, we investigated the preventive role of BME in 4-nitroquinoline 1-oxide (4-NQO) carcinogen-induced HNSCC. We observed that BME feeding significantly reduced the incidence of 4-NQO induced oral cancer in a mouse model...
October 23, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/29039489/id1-contributes-to-cell-growth-invasion-and-migration-in-salivary-adenoid-cystic-carcinoma
#14
Xiao-Meng Hu, Ting Lin, Xiao-Yu Huang, Rui-Huan Gan, Yong Zhao, Yan Feng, Lin-Can Ding, Bo-Hua Su, Da-Li Zheng, You-Guang Lu
Previous studies have reported that inhibitor of DNA binding 1 (ID1) exerts an oncogenic role in a number of tumors. In the present study, the role of ID1 in the growth, invasion and migration of salivary adenoid cystic carcinoma (SACC) cells was investigated. ID1 expression in clinical SACC samples was compared with that in normal salivary tissues using immunohistochemical staining, and the correlation between ID1 expression and clinical pathological characteristics was then determined. Subsequently, ID1 was overexpressed or silenced to investigate the effects of ID1 expression on SACC cell proliferation, invasion and migration...
December 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28986057/myeloid-related-protein-8-14-in-acute-coronary-syndrome
#15
Masashi Sakuma, Atsushi Tanaka, Norihiko Kotooka, Yutaka Hikichi, Shigeru Toyoda, Shichiro Abe, Isao Taguchi, Koichi Node, Daniel I Simon, Teruo Inoue
BACKGROUND: The alarmin family member myeloid-related protein (MRP)-14 (S100A9), which has been identified by platelet transcriptional profiling as an acute myocardial infarction gene, regulates vascular inflammation and thrombosis. Elevated plasma levels of MRP-8/14 (S100A8/A9) heterodimer predict first and recurrent cardiovascular events. The aim of this study was to elucidate pathophysiological roles of MRP-8/14 in acute coronary syndrome (ACS). METHODS AND RESULTS: In 38 consecutive ACS patients, the MRP-8/14 level in coronary artery blood obtained at thrombus aspiration was higher in 23 patients, in whom aspirated thrombus was confirmed, compared to the 15 patients, in whom it was absent [4...
December 15, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28984903/whole-genome-microarray-expression-analysis-in-blood-leucocytes-identifies-pathways-linked-to-signs-and-symptoms-of-a-patient-with-hypercalprotectinaemia-and-hyperzincaemia
#16
Helena S Isaksson, Sanja A Farkas, Patrick Müller, Dan Gustafsson, Torbjörn K Nilsson
A child, 2 yr with the "hypercalprotectinemia with hyperzincemia" clinical syndrome presented with atypical symptoms and signs, notably persistent fever of around 38°C, thrombocythaemia of >700 x 10(9) /L, and a predominance of persistent intestinal symptoms. In an effort to find a cure by identifying the dysregulated pathways we analyzed whole-genome mRNA expression by the Affymetrix HG U133 PLUS 2.0 array on three occasions 3 to 5 months apart. Major upregulation was demonstrated for the JAK/STAT pathway including in particular CD177, S100A8, S100A9, and S100A12, accounting for the thrombocytosis; a large number of interleukins, their receptors, and activators, accounting for the febrile apathic state; and the HMBG1 gene, possibly accounting for part of the intestinal symptoms...
October 6, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28983059/pro-inflammatory-proteins-s100a9-and-tnf%C3%AE-suppress-erythropoietin-elaboration-in-myelodysplastic-syndromes
#17
Thomas Cluzeau, Kathy L McGraw, Brittany Irvine, Erico Masala, Lionel Ades, Ashley A Basiorka, Jaroslaw P Maciejewski, Patrick Auberger, Sheng Wei, Pierre Fenaux, Valeria Santini, Alan List
Accumulating evidence implicates innate immune activation in the pathobiology of myelodysplastic syndromes. A key myeloid related inflammatory protein, S100A9, serves as a Toll-like receptor ligand regulating TNFα and IL-1β production. The role of MDS-related inflammatory proteins in endogenous Epo regulation and response to erythroid stimulating agents or lenalidomide has not been investigated. The HepG2 hepatoma cell line was used to investigate in vitro Epo elaboration. Serum collected from 311 MDS patients were investigated (125 prior to erythroid stimulating agents and 186 prior to lenalidomide)...
October 5, 2017: Haematologica
https://www.readbyqxmd.com/read/28969686/s100a8-a9-increases-the-mobilization-of-pro-inflammatory-ly6c-high-monocytes-to-the-synovium-during-experimental-osteoarthritis
#18
Niels A J Cremers, Martijn H J van den Bosch, Stephanie van Dalen, Irene Di Ceglie, Giuliana Ascone, Fons van de Loo, Marije Koenders, Peter van der Kraan, Annet Sloetjes, Thomas Vogl, Johannes Roth, Edwin J W Geven, Arjen B Blom, Peter L E M van Lent
BACKGROUND: Monocytes are dominant cells present within the inflamed synovium during osteoarthritis (OA). In mice, two functionally distinct monocyte subsets are described: pro-inflammatory Ly6C(high) and patrolling Ly6C(low) monocytes. Alarmins S100A8/A9 locally released by the synovium during inflammatory OA for prolonged periods may be dominant proteins involved in stimulating recruitment of Ly6C(high) monocytes from the circulation to the joint. Our objective was to investigate the role of S100A8/A9 in the mobilization of Ly6C(high) and Ly6C(low) monocytic populations to the inflamed joint in collagenase-induced OA (CiOA)...
September 29, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28967919/chromosome-1q21-3-amplification-is-a-trackable-biomarker-and-actionable-target-for-breast-cancer-recurrence
#19
Jian Yuan Goh, Min Feng, Wenyu Wang, Gokce Oguz, Siti Maryam J M Yatim, Puay Leng Lee, Yi Bao, Tse Hui Lim, Panpan Wang, Wai Leong Tam, Annette R Kodahl, Maria B Lyng, Suman Sarma, Selena Y Lin, Alexander Lezhava, Yoon Sim Yap, Alvin S T Lim, Dave S B Hoon, Henrik J Ditzel, Soo Chin Lee, Ern Yu Tan, Qiang Yu
Tumor recurrence remains the main reason for breast cancer-associated mortality, and there are unmet clinical demands for the discovery of new biomarkers and development of treatment solutions to benefit patients with breast cancer at high risk of recurrence. Here we report the identification of chromosomal copy-number amplification at 1q21.3 that is enriched in subpopulations of breast cancer cells bearing characteristics of tumor-initiating cells (TICs) and that strongly associates with breast cancer recurrence...
November 2017: Nature Medicine
https://www.readbyqxmd.com/read/28964306/expression-of-calcium-binding-proteins-s100a8-s100a9-and-s100a12-in-otitis-media
#20
Wenzhou Hong, Pawjai Khampang, Tina L Samuels, Joseph E Kerschner, Ke Yan, Pippa Simpson
OBJECTIVES: Calgranulins (calcium-binding proteins S100A8, S100A9 and S100A12) are predominant cytoplasmic proteins of neutrophils and produced by various cells, playing multiple functions in innate immunity and the inflammatory process. Although up-regulated expression of S100A8 and S100A9 genes were observed in an animal model of otitis media (OM), their expressions have not been studied in human middle ear epithelial cells in response to the OM pathogen or in patients with recurrent or chronic OM (recurrent OM/RecOM or chronic OM with effusion/COME)...
October 2017: International Journal of Pediatric Otorhinolaryngology
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