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Circulating nucleosomes

Louise Rasmussen, Ib Jarle Christensen, Marielle Herzog, Jake Micallef, Hans Jørgen Nielsen
The aim was to evaluate serum levels of circulating cell-free nucleosomes (ccfn) containing a variety of epigenetic signals including 5-methylcytosine DNA, histone modifications H3K9Me3, H3K9Ac, H3S10PO4, H3K36Me3, H4K20Me3, H4PanAc and pH2AX, nucleosome variant H2AZ and nucleosome adducts with HMGB1 and EZH2 as well as ccfn per se, in addition to develop and evaluate predictor models based on the above mentioned ccfn and including serum levels of carcinoembryonic antigen (CEA), in early detection of colorectal cancer (CRC)...
February 13, 2018: Oncotarget
K H Lee, L Cavanaugh, H Leung, F Yan, Z Ahmadi, B H Chong, F Passam
INTRODUCTION: Neutrophil extracellular traps (NETs) are networks of extracellular fibres produced from neutrophil DNA with a pathogenic role in infection, thrombosis and other conditions. Reliable assays for measuring NETs are desirable as novel treatments targeting NETs are being explored for the treatment of these conditions. We compare a whole blood flow cytometry method with serum assays to measure NETs-associated markers in patients with sepsis and thrombosis. METHODS: Patients with deep venous thrombosis (n = 25), sepsis (n = 21) and healthy controls (n = 23) were included in the study...
March 9, 2018: International Journal of Laboratory Hematology
Barbora Konečná, Lucia Lauková, Barbora Vlková
Cell-free self-DNA or RNA may induce an immune response by activating specific sensing receptors. During pregnancy, placental nucleic acids present in the maternal circulation further activate these receptors due to the presence of unmethylated CpG islands. A higher concentration of cell-free fetal DNA is associated with pregnancy complications and a higher risk for fetal rejection. Cell-free fetal DNA originates from placental trophoblasts. It appears in different forms: free, bound to histones in nucleosomes, in neutrophil extracellular traps and in extracellular vesicles...
February 26, 2018: Scandinavian Journal of Immunology
Miguel Jiménez-Alcázar, Andreas Limacher, Rachita Panda, Marie Méan, Josephine Bitterling, Sven Peine, Thomas Renné, Jürg H Beer, Drahomir Aujesky, Bernhard Lämmle, Tobias A Fuchs
BACKGROUND: Venous thromboembolism (VTE) is a major cause of morbidity and mortality in elderly patients. Extracellular DNA is a pro-inflammatory and pro-thrombotic mediator in vitro and in animal models. Levels of circulating extracellular DNA (ceDNA) are increased in VTE patients, but the association of ceDNA with VTE extent and clinical outcome is poorly understood. OBJECTIVES: We analyzed the association of ceDNA with the extent of VTE, categorized as distal and proximal deep vein thrombosis and pulmonary embolism, and with the clinical outcomes VTE recurrence and mortality...
2018: PloS One
Jordina Munrós, Dolors Tàssies, Joan Carles Reverter, Lidia Martin, Amelia Pérez, Francisco Carmona, María Ángeles Martínez-Zamora
Neutrophil extracellular traps (NETs) have been described to be related to the pathogenesis of inflammatory and autoimmune conditions. Endometriosis is currently considered a chronic inflammatory condition. Therefore, we performed a preliminary case-control study to compare the circulating plasma NET levels in patients with surgically confirmed endometriosis (E group, n = 82) and those of patients without surgical findings of endometriosis (C group, n = 35). Venous blood samples were obtained at the time of surgery...
January 1, 2018: Reproductive Sciences
K E Cervantes-Luevano, N Caronni, M C Castiello, E Fontana, G Piperno, A Naseem, P Uva, M Bosticardo, G E Marcovecchio, L D Notarangelo, M P Cicalese, A Aiuti, A Villa, F Benvenuti
BACKGROUND: Wiskott-Aldrich syndrome (WAS) is a rare primary immunodeficiency caused by mutations in WASp, a key regulator of cytoskeletal dynamics in hematopoietic cells. A high proportion of patients develop autoimmunity due to a breakdown in T and B cell tolerance. Moreover, excessive production of type-I interferon by plasmacytoid DCs contribute to autoimmune signs, however, the factors that triggers excessive innate activation have not been defined. OBJECTIVE: Neutrophils extracellular traps (NETs) emerged as major initiating factors in diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA)...
February 12, 2018: Journal of Allergy and Clinical Immunology
Rahmi Oklu, Rahul A Sheth, Keith H K Wong, Amin H Jahromi, Hassan Albadawi
Background: A single center, prospective tissue-based study was conducted to investigate an association between neutrophil extracellular traps (NETs) and venous thromboembolic disease in patients with malignancy. Methods: Plasma was collected from 65 patients in which 27 were cancer patients and 38 were age-matched non-cancer patients. Plasma NETs, circulating free DNA (cfDNA), DNase-1, endonuclease-G, endonuclease activity and thrombin-antithrombin III (TAT) complex levels was quantified...
December 2017: Cardiovascular Diagnosis and Therapy
Gerben Marsman, Helen von Richthofen, Ingrid Bulder, Florea Lupu, Jan Hazelzet, Brenda M Luken, Sacha Zeerleder
Circulating histones have been implicated as major mediators of inflammatory disease because of their strong cytotoxic effects. Histones form the protein core of nucleosomes; however, it is unclear whether histones and nucleosomes are equally cytotoxic. Several plasma proteins that neutralize histones are present in plasma. Importantly, factor VII-activating protease (FSAP) is activated upon contact with histones and subsequently proteolyzes histones. We aimed to determine the effect of FSAP on the cytotoxicity of both histones and nucleosomes...
December 12, 2017: Blood Advances
Simona Grasso, Ariane Neumann, Irene M Lang, Michael Etscheid, Maren von Köckritz-Blickwede, Sandip M Kanse
The circulating zymogen form of Factor VII activating protease (FSAP) can be activated by histones and nucleosomes in vivo. These cell-death-associated nuclear factors are also actively extruded into the extracellular space by neutrophils through a process called neutrophil extracellular trap (NET) formation (NETosis). NETs are thought to be involved in host defense, inflammation as well as thrombosis. We have investigated the bidirectional interactions of FSAP and NETs. Phorbol ester-mediated NET formation was marginally stimulated by FSAP...
January 2018: Thrombosis Research
Peter Szatmary, Tingting Liu, Simon T Abrams, Svetlana Voronina, Li Wen, Michael Chvanov, Wei Huang, Guozheng Wang, David N Criddle, Alexey V Tepikin, Cheng-Hock Toh, Robert Sutton
BACKGROUND: Clinical and experimental acute pancreatitis feature histone release within the pancreas from innate immune cells and acinar cell necrosis. In this study, we aimed to detail the source of circulating histones and assess their role in the pathogenesis of acute pancreatitis. METHODS: Circulating nucleosomes were measured in patient plasma, taken within 24 and 48 h of onset of acute pancreatitis and correlated with clinical outcomes. Using caerulein hyperstimulation, circulating histones were measured in portal, systemic venous and systemic arterial circulation in mice, and the effects of systemic administration of histones in this model were assessed...
November 2017: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
Martin Beranek, Zdenek Fiala, Jan Kremlacek, Ctirad Andrys, Jan Krejsek, Kvetoslava Hamakova, Marcela Chmelarova, Vladimir Palicka, Lenka Borska
Psoriasis is a multifactorial chronic inflammatory disease. We aimed to examine blood levels of nucleosomes derived from apoptotic cells, nucleosomal cell-free DNA (cfDNA) and immune-inflammatory biomarkers tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), and interleukin 6 (IL-6) in psoriatic subjects. The study included 28 patients with exacerbated psoriasis vulgaris and 22 controls. The clinical and laboratory investigations included the determination of PASI score, BMI, cfDNA (by real-time PCR), nucleosomes, TNF-α, CRP, and IL-6...
October 13, 2017: Archives of Dermatological Research
Lars Eichhorn, Christian Nietzel, Stefan Schröder, Ullrich Siekmann, Andreas Koch, Stefan Weber
BACKGROUND: Oxidative stress caused by elevated partial pressure of oxygen during diving is a major contributor of inflammation and apoptosis. The underlying molecular mechanisms are poorly understood. The aim of the study was to describe apoptotic gene regulation induced by a single air dive. METHODS: 19 healthy volunteers were exposed to a 30-minute dive at 2.8 atmospheres (ATA) absolute in a pressure chamber in ambient air. Blood samples were obtained before, directly after and 24 hours after exposure...
November 2016: Undersea & Hyperbaric Medicine: Journal of the Undersea and Hyperbaric Medical Society, Inc
Eleanor Silk, Hailin Zhao, Hao Weng, Daqing Ma
Histones are intra-nuclear cationic proteins that are present in all eukaryotic cells and are highly conserved across species. Within the nucleus, they provide structural stability to chromatin and regulate gene expression. Histone may be released into the extracellular space in three forms: freely, as a DNA-bound nucleosome or as part of neutrophil extracellular traps, and all three can be detected in serum after significant cellular death such as sepsis, trauma, ischaemia/reperfusion injury and autoimmune disease...
May 25, 2017: Cell Death & Disease
Jean-François Rahier, Anne Druez, Laurence Faugeras, Jean-Paul Martinet, Myriam Géhénot, Eléonore Josseaux, Marielle Herzog, Jake Micallef, Fabienne George, Monique Delos, Thierry De Ronde, Abdenor Badaoui, Lionel D'Hondt
BACKGROUND: Colonoscopy is currently widely accepted as the gold standard for detection of colorectal cancer (CRC) providing detection of up to 95% of pre-cancerous lesions during the procedure. However, certain limitations exist in most countries including cost and access to the procedure. Moreover, colonoscopy is an invasive technique with risk inherent to the endoscopic procedure. For this reason, alternative screening tests, in particular, fecal occult blood-based tests, have been widely adopted for frontline screening...
2017: Clinical Epigenetics
Janine Aucamp, Abel J Bronkhorst, Dimetrie L Peters, Hayley C Van Dyk, Francois H Van der Westhuizen, Piet J Pretorius
Although circulating DNA (cirDNA) analysis shows great promise as a screening tool for a wide range of pathologies, numerous stumbling blocks hinder the rapid translation of research to clinical practice. This is related directly to the inherent complexity of the in vivo setting, wherein the influence of complex systems of interconnected cellular responses and putative DNA sources creates a seemingly arbitrary representation of the quantitative and qualitative properties of the cirDNA in the blood of any individual...
July 2017: Cellular and Molecular Life Sciences: CMLS
Pascal Syren, Roland Andersson, Monika Bauden, Daniel Ansari
Pancreatic ductal adenocarcinoma (PDAC) prognosis remains very poor and has only marginally improved during the last decades. Epigenetic alterations have been the focus of many recent studies and offer valuable options for PDAC detection, prognosis and treatment. DNA methylation, histone modifications and microRNA (miR) level changes can be used as biomarkers. These alterations occur early in carcinogenesis and may be specific for PDAC. Additionally, epigenetic alterations can be analyzed from cell-free DNA, free-circulating nucleosomes or shed tumor cells in blood...
June 2017: Scandinavian Journal of Gastroenterology
Charlotte Thålin, Maud Daleskog, Sophie Paues Göransson, Daphne Schatzberg, Julie Lasselin, Ann-Charlotte Laska, Anders Kallner, Thomas Helleday, Håkan Wallén, Mélanie Demers
There is an emerging interest in the diverse functions of neutrophil extracellular traps (NETs) in a variety of disease settings. However, data on circulating NETs rely largely upon surrogate NET markers such as cell-free DNA, nucleosomes, and NET-associated enzymes. Citrullination of histone H3 by peptidyl arginine deiminase 4 (PAD4) is central for NET formation, and citrullinated histone H3 (H3Cit) is considered a NET-specific biomarker. We therefore aimed to optimize and validate a new enzyme-linked immunosorbent assay (ELISA) to quantify the levels of H3Cit in human plasma...
June 2017: Immunologic Research
Clara Pérez-Barrios, Irene Nieto-Alcolado, María Torrente, Carolina Jiménez-Sánchez, Virginia Calvo, Lourdes Gutierrez-Sanz, Magda Palka, Encarnación Donoso-Navarro, Mariano Provencio, Atocha Romero
BACKGROUND: The implementation of liquid biopsy for biomarker testing and response to treatment monitoring in cancer patients would presumable increase laboratory throughput, requiring the development of automated methods for circulating free DNA (cfDNA) isolation. METHODS: The present study compares the MagNA Pure Compact (MPC) Nucleic Acid Isolation Kit I and Maxwell(®) RSC (MR) ccfDNA Plasma Kit and the later with QIAamp Circulating Nucleid Acid (QCNA) Kit using 57 plasma samples from cancer patients...
December 2016: Translational Lung Cancer Research
Peter McAnena, James A L Brown, Michael J Kerin
Traditionally the stratification of many cancers involves combining tumour and clinicopathological features (e.g., patient age; tumour size, grade, receptor status and location) to inform treatment options and predict recurrence risk and survival. However, current biomarkers often require invasive excision of the tumour for profiling, do not allow monitoring of the response to treatment and stratify patients into broad heterogeneous groups leading to inconsistent treatment responses. Here we explore and describe the benefits of using circulating biomarkers (nucleosomes and/or modifications to nucleosomes) as a non-invasive method for detecting cancer and monitoring response to treatment...
January 8, 2017: Cancers
Qi Zhao, Chunshu Yang, Jianing Wang, Yujia Li, Pingting Yang
DNase1l3 is an endonuclease to degrade the chromatin of apoptotic or necrotic cells. Serum DNase1l3 may fulfill the function of clearance of chromatin released into the circulation by dying cells, which can trigger autoimmune responses. To date, it remains unclear whether serum DNase1l3 level associates with the pathogenesis of autoimmune diseases. Sixty-eight patients with dermatomyositis/polymyositis (DM/PM, n = 30), systemic lupus erythematosus (SLE, n = 20) and rheumatoid arthritis (RA, n = 18), as well as 26 healthy blood donors were enrolled in the present study...
November 2017: Clinical and Experimental Medicine
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