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Circulating nucleosomes

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https://www.readbyqxmd.com/read/28075351/circulating-nucleosomes-and-nucleosome-modifications-as-biomarkers-in-cancer
#1
REVIEW
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
https://www.readbyqxmd.com/read/28039554/serum-level-of-dnase1l3-in-patients-with-dermatomyositis-polymyositis-systemic-lupus-erythematosus-and-rheumatoid-arthritis-and-its-association-with-disease-activity
#2
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...
December 30, 2016: Clinical and Experimental Medicine
https://www.readbyqxmd.com/read/27974641/proper-cytoskeletal-architecture-beneath-the-plasma-membrane-of-red-blood-cells-requires-ttll4
#3
Faryal Ijaz, Yasue Hatanaka, Takahiro Hatanaka, Koji Tsutsumi, Takayuki Iwaki, Kazuo Umemura, Koji Ikegami, Mitsutoshi Setou
Mammalian red blood cells (RBCs) circulate through blood vessels, including capillaries, for tens of days under high mechanical stress. RBCs tolerate this mechanical stress while maintaining their shape because of their elastic membrane skeleton. This membrane skeleton consists of spectrin-actin lattices arranged as quasi-hexagonal units beneath the plasma membrane. In this study, we found that the organization of the RBC cytoskeleton requires tubulin tyrosine ligase-like 4 (Ttll4). RBCs from Ttll4-knockout mice showed larger average diameters in smear tests...
December 14, 2016: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/27958278/neutrophil-extracellular-trap-formation-and-circulating-nucleosomes-in-patients-with-chronic-myeloproliferative-neoplasms
#4
Cecilia P Marin Oyarzún, Agostina Carestia, Paola R Lev, Ana C Glembotsky, Miguel A Castro Ríos, Beatriz Moiraghi, Felisa C Molinas, Rosana F Marta, Mirta Schattner, Paula G Heller
The mechanisms underlying increased thrombotic risk in chronic myeloproliferative neoplasms (MPN) are incompletely understood. We assessed whether neutrophil extracellular traps (NETs), which promote thrombosis, contribute to the procoagulant state in essential thrombocythemia, polycythemia vera and myelofibrosis (MF) patients. Although MPN neutrophils showed increased basal reactive oxygen species (ROS), enhanced NETosis by unstimulated neutrophils was an infrequent finding, whereas PMA-triggered NETosis was impaired, particularly in MF, due to decreased PMA-triggered ROS production...
December 13, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27929534/extracellular-histones-cell-free-dna-or-nucleosomes-differences-in-immunostimulation
#5
REVIEW
Gerben Marsman, Sacha Zeerleder, Brenda M Luken
In inflammation, extensive cell death may occur, which results in the release of chromatin components into the extracellular environment. Individually, the purified chromatin components double stranded (ds)DNA and histones have been demonstrated, both in vitro and in vivo, to display various immunostimulatory effects, for example, histones induce cytotoxicity and proinflammatory signaling through toll-like receptor (TLR)2 and 4, while DNA induces signaling through TLR9 and intracellular nucleic acid sensing mechanisms...
December 8, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27926661/the-effect-of-intraoperative-and-6-h-postoperative-intravenous-administration-of-low-dose-prostacyclin-on-the-endothelium-hemostasis-and-hemodynamics-in-patients-undergoing-a-pancreaticoduodenoctemy-a-randomized-controlled-pilot-study
#6
Pär I Johansson, Christian R Mortensen, Tatiana Nielsen, Carsten Tollund, Jakob Stensballe, Carsten P Hansen, Hans J Frederiksen, Sisse R Ostrowski
BACKGROUND: Capillary leakage, secondary to endothelial breakdown, is common in patients undergoing major surgical procedures with extensive tissue injury and this is associated with increased morbidity and mortality. Prostacyclin has been ascribed cytoprotective properties together with its vasodilatory and antiplatelet effects. The present pilot study investigated the safety and endothelial protective effects of low-dose prostacyclin infusion. PATIENTS AND METHODS: A randomized placebo-controlled pilot study evaluating the effect of prostacyclin (iloprost) infusion (1...
December 6, 2016: European Journal of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/27843374/potential-serum-and-urine-biomarkers-in-patients-with-lupus-nephritis-and-the-unsolved-problems
#7
REVIEW
Song-Chou Hsieh, Chang-Youh Tsai, Chia-Li Yu
Lupus nephritis (LN) is one of the most frequent and serious complications in the patients with systemic lupus erythematosus. Autoimmune-mediated inflammation in both renal glomerular and tubulointerstitial tissues is the major pathological finding of LN. In clinical practice, the elevated anti-dsDNA antibody titer concomitant with reduced complement C3 and C4 levels has become the predictive and disease-activity surrogate biomarkers in LN. However, more and more evidences suggest that autoantibodies other than anti-dsDNA antibodies, such as anti-nucleosome, anti-C1q, anti-C3b, anti-cardiolipin, anti-endothelial cell, anti-ribonuclear proteins, and anti-glomerular matrix (anti-actinin) antibodies, may also involve in LN...
2016: Open Access Rheumatology: Research and Reviews
https://www.readbyqxmd.com/read/27571261/inferring-expressed-genes-by-whole-genome-sequencing-of-plasma-dna
#8
Peter Ulz, Gerhard G Thallinger, Martina Auer, Ricarda Graf, Karl Kashofer, Stephan W Jahn, Luca Abete, Gunda Pristauz, Edgar Petru, Jochen B Geigl, Ellen Heitzer, Michael R Speicher
The analysis of cell-free DNA (cfDNA) in plasma represents a rapidly advancing field in medicine. cfDNA consists predominantly of nucleosome-protected DNA shed into the bloodstream by cells undergoing apoptosis. We performed whole-genome sequencing of plasma DNA and identified two discrete regions at transcription start sites (TSSs) where nucleosome occupancy results in different read depth coverage patterns for expressed and silent genes. By employing machine learning for gene classification, we found that the plasma DNA read depth patterns from healthy donors reflected the expression signature of hematopoietic cells...
October 2016: Nature Genetics
https://www.readbyqxmd.com/read/27488091/evidence-of-netosis-in-septic-shock-induced-disseminated-intravascular-coagulation
#9
Xavier Delabranche, Laure Stiel, François Severac, Anne-Cécile Galoisy, Laurent Mauvieux, Fatiha Zobairi, Thierry Lavigne, Florence Toti, Eduardo Anglès-Cano, Ferhat Meziani, Julie Boisramé-Helms
INTRODUCTION: Neutrophils extracellular traps (NETs) have recently emerged as a new potential link between inflammation, immunity and thrombosis and could play a key role in septic shock-induced disseminated intravascular coagulation (DIC) pathogenesis. The objective of our study was to investigate a potential link between NETosis and septic-shock induced DIC. METHODS: Twenty patients with septic shock (10 without and 10 with DIC according to JAAM 2006 score) were prospectively included in our study...
August 2, 2016: Shock
https://www.readbyqxmd.com/read/27484224/endothelial-dysfunction-in-resuscitated-cardiac-arrest-endo-rca-safety-and-efficacy-of-low-dose-prostacyclin-administration-and-blood-pressure-target-in-addition-to-standard-therapy-as-compared-to-standard-therapy-alone-in-post-cardiac-arrest-syndrome-patients
#10
Anna Sina P Meyer, Sisse R Ostrowski, Jesper Kjaergaard, Pär I Johansson, Christian Hassager
BACKGROUND: Morbidity and mortality following initial survival of cardiac arrest remain high despite great efforts to improve resuscitation techniques and post-resuscitation care, in part due to the ischemia-reperfusion injury secondary to the restoration of the blood circulation. Patients resuscitated from cardiac arrest display evidence of endothelial injury and coagulopathy (hypocoagulability, hyperfibrinolysis), which in associated with poor outcome. Recent randomized controlled trials have revealed that treatment with infusion of prostacyclin reduces endothelial damage after major surgery and AMI...
August 2, 2016: Trials
https://www.readbyqxmd.com/read/27459701/a-review-of-radiation-induced-coagulopathy-and-new-findings-to-support-potential-prevention-strategies-and-treatments
#11
Ann R Kennedy, Amit Maity, Jenine K Sanzari
Results from our recent studies have led to the novel hypothesis that radiation-induced coagulopathy (RIC) and associated hemorrhage occurring as part of the acute radiation syndrome (ARS) is a major cause of death resulting from radiation exposure in large mammals, including humans. This article contains information related to RIC, as well as potential strategies for the prevention and treatment of RIC. In addition, new findings are reported here on the occurrence of RIC biomarkers in humans exposed to radiation...
August 2016: Radiation Research
https://www.readbyqxmd.com/read/27450524/-investigation-of-autoimmunity-markers-during-interferon-alpha-therapy-of-chronic-hepatitis-b-and-c-twenty-years-of-experience
#12
Irena Orságová, Luděk RoŽnovský, Lenka Petroušová, Michaela Konečná, Libuše Kabieszová, Jan Martinek, Alena Kloudová, Ladislav Pavliska
OBJECTIVE: To determine the prevalence of autoimmune parameters in patients with chronic hepatitis B and C (HBV, HCV) treated with conventional or pegylated interferon alpha (IFN) and monitor the development of autoimmune diseases in connection with this treatment. PATIENTS AND METHODS: In the years 1992-2014, autoimmune parameters were evaluated in 324 patients (271 with HCV, 53 with HBV) treated with IFN at the Department of Infectious Diseases in Ostrava. Prior to, during and after completion of IFN treatment, antinuclear antibodies (ANA), antimitochondrial antibodies (AMA), smooth muscle antibodies (SMA), anti-liver/kidney microsomal antibodies (anti-LKM-1), anti-double-stranded DNA antibodies (anti-ds-DNA), antibodies against granulocytes (ANCA), anti-deoxyribonucleoprotein antibodies (anti-DNP), anti-nucleosomes antibodies, rheumatoid factor (RF) and circulating immune complexes (CIC) were determined and clinical manifestations of autoimmune diseases were evaluated...
June 2016: Klinická Mikrobiologie a Infekc̆ní Lékar̆ství
https://www.readbyqxmd.com/read/27424188/epigenetic-memory-a-macrophage-perspective
#13
REVIEW
Colin Logie, Hendrik G Stunnenberg
The molecular basis of cellular memory is a fascinating topic that progressed with great strides during the last few decades. In the case of cells of the immune system, cellular memory likely extends beyond cell fate determination mechanisms, since immunity can tailor its responses to a potentially hostile environment that is a priori variable if not unpredictable. One particularly versatile innate immune system cell type is the macrophage. These phagocytes occur in all organs and tissues as resident cells or as differentiation products of recruited circulating blood monocytes...
August 2016: Seminars in Immunology
https://www.readbyqxmd.com/read/27392603/origins-structures-and-functions-of-circulating-dna-in-oncology
#14
A R Thierry, S El Messaoudi, P B Gahan, P Anker, M Stroun
While various clinical applications especially in oncology are now in progress such as diagnosis, prognosis, therapy monitoring, or patient follow-up, the determination of structural characteristics of cell-free circulating DNA (cirDNA) are still being researched. Nevertheless, some specific structures have been identified and cirDNA has been shown to be composed of many "kinds." This structural description goes hand-in-hand with the mechanisms of its origins such as apoptosis, necrosis, active release, phagocytosis, and exocytose...
September 2016: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/27387552/the-architecture-of-neutrophil-extracellular-traps-investigated-by-atomic-force-microscopy
#15
Ricardo H Pires, Stephan B Felix, Mihaela Delcea
Neutrophils are immune cells that engage in a suicidal pathway leading to the release of partially decondensed chromatin, or neutrophil extracellular traps (NETs). NETs behave as a double edged sword; they can bind to pathogens thereby ensnaring them and limiting their spread during infection; however, they may bind to host circulating materials and trigger thrombotic events, and are associated with autoimmune disorders. Despite the fundamental role of NETs as part of an immune system response, there is currently a very poor understanding of how their nanoscale properties are reflected in their macroscopic impact...
August 7, 2016: Nanoscale
https://www.readbyqxmd.com/read/27297799/single-stranded-dna-library-preparation-uncovers-the-origin-and-diversity-of-ultrashort-cell-free-dna-in-plasma
#16
Philip Burnham, Min Seong Kim, Sean Agbor-Enoh, Helen Luikart, Hannah A Valantine, Kiran K Khush, Iwijn De Vlaminck
Circulating cell-free DNA (cfDNA) is emerging as a powerful monitoring tool in cancer, pregnancy and organ transplantation. Nucleosomal DNA, the predominant form of plasma cfDNA, can be adapted for sequencing via ligation of double-stranded DNA (dsDNA) adapters. dsDNA library preparations, however, are insensitive to ultrashort, degraded cfDNA. Drawing inspiration from advances in paleogenomics, we have applied a single-stranded DNA (ssDNA) library preparation method to sequencing of cfDNA in the plasma of lung transplant recipients (40 samples, six patients)...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27291394/pre-analytical-variables-of-circulating-cell-free-nucleosomes-containing-5-methylcytosine-dna-or-histone-modification-h3k9me3
#17
Louise Rasmussen, Marielle Herzog, Eva Rømer, Jake Micallef, Orhan Bulut, Michael Wilhelmsen, Ib Jarle Christensen, Hans J Nielsen
AIM: To evaluate pre-analytical variables of circulating cell-free nucleosomes containing 5-methylcytosine DNA (5mC) or histone modification H3K9Me3 (H3K9Me3). MATERIALS AND METHODS: Six studies were designed to assess the possible influence of pre-analytical variables. Study 1: influence of stasis and contamination with white-cells and platelets. Study 2: influence of within-day variations. Study 3: influence of day-to-day variation. Study 4: influence of temperature during handling and storage, and of neoplastic disease...
October 2016: Scandinavian Journal of Clinical and Laboratory Investigation
https://www.readbyqxmd.com/read/27230920/induction-of-neutrophil-extracellular-traps-in-shiga-toxin-associated-hemolytic-uremic-syndrome
#18
Maria Victoria Ramos, Maria Pilar Mejias, Florencia Sabbione, Romina Jimena Fernandez-Brando, Adriana Patricia Santiago, Maria Marta Amaral, Ramon Exeni, Analia Silvina Trevani, Marina Sandra Palermo
Hemolytic uremic syndrome (HUS), a vascular disease characterized by hemolytic anemia, thrombocytopenia, and acute renal failure, is caused by enterohemorrhagic Shiga toxin (Stx)-producing bacteria, which mainly affect children. Besides Stx, the inflammatory response mediated by neutrophils (PMN) is essential to HUS evolution. PMN can release neutrophil extracellular traps (NET) composed of DNA, histones, and other proteins. Since NET are involved in infectious and inflammatory diseases, the aim of this work was to investigate the contribution of NET to HUS...
2016: Journal of Innate Immunity
https://www.readbyqxmd.com/read/27130528/circulating-nucleosomes-are-associated-with-mortality-in-pediatric-acute-respiratory-distress-syndrome
#19
Nadir Yehya, Neal J Thomas, Susan S Margulies
Mechanisms underlying pediatric acute respiratory distress syndrome (PARDS) are poorly understood. The recent implication of circulating nucleosomes as pathogenic in sepsis and trauma-associated ARDS in adults led us to investigate the significance of nucleosomes in PARDS. We conducted a prospective, observational study on children with PARDS at the Children's Hospital of Philadelphia between July 2014 and September 2015. Plasma was collected within 48 h of PARDS onset and nucleosomes quantified by enzyme-linked immunosorbent assay...
June 1, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/26893906/circulating-nucleosomes-as-predictive-markers-of-severe-acute-pancreatitis
#20
Anne K Penttilä, Ari Rouhiainen, Leena Kylänpää, Harri Mustonen, Pauli Puolakkainen, Heikki Rauvala, Heikki Repo
BACKGROUND: The components of nucleosomes, which contain DNA and histones, are released into the circulation from damaged cells and can promote inflammation. We studied whether the on-admission levels of circulating nucleosomes predict the development of severe acute pancreatitis (AP), in particular among the patients who present without clinical signs of organ dysfunction. METHODS: This is a prospective study of 74 AP patients admitted to Helsinki University Hospital from 2003 to 2007...
2016: Journal of Intensive Care
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