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. Twenty-three patients had mild, 27 moderately severe, and 24 severe AP as defined by the revised Atlanta criteria. 14/24 severe AP patients had no sign of organ dysfunction on admission (modified marshall score <2). Blood samples were obtained on admission and the plasma levels of nucleosomes were measured using enzyme-linked immunosorbent assay.
Results: The on-admission levels of nucleosomes were significantly higher in severe AP than in mild or moderately severe AP (p < 0.001 for all), higher in non-survivors (n = 8) than in survivors (p = 0.019), and correlated with the on-admission levels of C-reactive protein (p < 0.001) and creatinine (p < 0.001). Among the AP patients who presented without organ dysfunction, the on-admission nucleosome level was an independent predictor of severe AP (p = 0.038, gender-adjusted forward-stepping logistic regression).
Conclusions: Circulating nucleosome levels may be helpful in identifying, on admission to hospital, the AP patients who present without clinical signs of organ dysfunction, and, yet, are bound to develop organ dysfunction during hospitalization.
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http://dx.doi.org/10.1186/s40560-016-0135-6 | DOI Listing |
J Mater Chem B
January 2025
College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu 610065, China.
Circulating histones have been identified as essential mediators that lead to hyperinflammation, platelet aggregation, coagulation cascade activation, endothelial cell injury, multiple organ dysfunction, and death in severe patients with sepsis, multiple trauma, COVID-19, acute liver failure, and pancreatitis. Clinical evidence suggests that plasma levels of circulating histones are positively associated with disease severity and survival in patients with such critical diseases. However, safe and efficient therapeutic strategies targeting circulating histones are lacking in current clinical practice.
View Article and Find Full Text PDFCell Rep Med
January 2025
Department of Immunology and Regenerative Biology, Weizmann Institute of Science, Rehovot, Israel. Electronic address:
The analysis of cell-free tumor DNA (ctDNA) and proteins in the blood of patients with cancer potentiates a new generation of non-invasive diagnostic approaches. However, confident detection of tumor-originating markers is challenging, especially in the context of brain tumors, where these analytes in plasma are extremely scarce. Here, we apply a sensitive single-molecule technology to profile multiple histone modifications on individual nucleosomes from the plasma of patients with diffuse midline glioma (DMG).
View Article and Find Full Text PDFVet J
January 2025
Gulbali Institute, School of Agricultural, Environmental and Veterinary Sciences, Faculty of Science and Health, Charles Sturt University, Locked Bag 588, Booroma St, Wagga Wagga, NSW 2678, Australia.
Sepsis is a main cause of death in neonatal foals. While the syndrome is not completely understood, sepsis is a dysregulated inflammatory response of the host to infection. It can be difficult to diagnose because of varying and non-specific clinical signs and imperfect diagnostic tests.
View Article and Find Full Text PDFComput Struct Biotechnol J
December 2024
Berlin Institute of Health (BIH) at Charité - Universitätsmedizin Berlin, Berlin 10178, Germany.
Motivation: The analysis of circulating cell-free DNA (cfDNA) holds immense promise as a non-invasive diagnostic tool across various human conditions. However, extracting biological insights from cfDNA fragments entails navigating complex and diverse bioinformatics methods, encompassing not only DNA sequence variation, but also epigenetic characteristics like nucleosome footprints, fragment length, and methylation patterns.
Results: We introduce Liquid Biopsy Feature extract (LBFextract), a comprehensive package designed to streamline feature extraction from cfDNA sequencing data, with the aim of enhancing the reproducibility and comparability of liquid biopsy studies.
FASEB J
December 2024
Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia and Charlie Norwood VA Medical Center, Augusta, Georgia, USA.
Extracellular histones are released in two major forms: free histones and nucleosomes (DNA-bound histones). However, little distinction has been made between these two forms of circulating extracellular histones. Our study detected increased circulating nucleosomes in acute lung injury patients.
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