Observational studyRespiratory research2017
Extracellular histones are clinically relevant mediators in the pathogenesis of acute respiratory distress syndrome.
Observational study in Respiratory research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
48 citing papers in PubMed, 1 synthesis or guideline pooled it, 77 citations in OpenAlex.
- The effect of reparixin on survival in patients at high risk for in-hospital mortality: a meta-analysis of randomized trials.Frontiers in immunology · 2022Pooled it
- Portable histone assay technology (PHAST) for the sample-to-answer detection of circulating histones in whole blood.Sensors and actuators. B, Chemical · 2026Article
- Transcriptomic analysis reveals immune dysregulation and identifies key genes in ICU patients with severe ARDS.Frontiers in immunology · 2026Article
- Regulation of histones in thromboinflammation.Frontiers in immunology · 2026Review
- Acute Respiratory Distress Syndrome: Pathophysiological Insights, Subphenotypes, and Clinical Implications-A Comprehensive Review.Journal of clinical medicine · 2025Review
- Circulating Nucleosomes and Histones in the Development of Lung Injury and Sepsis.Current issues in molecular biology · 2025Review
- COVID-19 patient serum-derived extracellular vesicles deliver miR-20b-5p induces neutrophil extracellular traps.Cell communication and signaling : CCS · 2025Article
- Unfractionated heparin attenuated histone-induced pulmonary endothelial glycocalyx injury through Ang/Tie2 pathway.Journal of inflammation (London, England) · 2025Article
- Extracellular Histones as Exosome Membrane Proteins Regulated by Cell Stress.Journal of extracellular vesicles · 2025Article
- Regulated cell death and DAMPs as biomarkers and therapeutic targets in normothermic perfusion of transplant organs. Part 2: implementation strategies.Frontiers in transplantation · 2025Review
- Extracellular histones promote TWIK2-dependent potassium efflux and associated NLRP3 activation in alveolar macrophages during sepsis-induced lung injury.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Article
- M6229 Protects against Extracellular-Histone-Induced Liver Injury, Kidney Dysfunction, and Mortality in a Rat Model of Acute Hyperinflammation.International journal of molecular sciences · 2024Article
- Cell death of alveolar lymphocytes and monocytes is negatively correlated with driving pressure and mechanical power in patients with acute respiratory distress syndrome.European journal of medical research · 2024Article
- Emerging therapeutic strategies targeting extracellular histones for critical and inflammatory diseases: an updated narrative review.Frontiers in immunology · 2024Review
- Extracellular Acetylated Histone 3.3 Induces Inflammation and Lung Tissue Damage.Biomolecules · 2023Article
- The Polyanionic Drug Suramin Neutralizes Histones and Prevents Endotheliopathy.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- Extracellular histone proteins activate P2XR7 channel current.The Journal of general physiology · 2023Article
- Inhalation of an RNA aptamer that selectively binds extracellular histones protects from acute lung injury.Molecular therapy. Nucleic acids · 2023Article
- Targeting circulating high mobility group box-1 and histones by extracorporeal blood purification as an immunomodulation strategy against critical illnesses.Critical care (London, England) · 2023Review
- STC3141 improves acute lung injury through neutralizing circulating histone in rat with experimentally-induced acute respiratory distress syndrome.Frontiers in pharmacology · 2023Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundExtracellular histones were recently identified as an inflammatory mediator involved in the pathogenesis of various organ injuries. This study aimed to examine extracellular histone levels and their clinical implications in acute respiratory distress syndrome (ARDS) patients and to explore histone-mediated effects through ex-vivo investigations.
methodsExtracellular histones, cytokine profiles and clinical data from 96 ARDS patients and 30 healthy volunteers were obtained. Human bronchial epithelial cells (BEAS-2B), human pulmonary artery endothelial cells (HPAEC), and human monocytic U937 cells were exposed to bronchoalveolar lavage fluid (BALF) collected from ARDS patients, and cellular damage and cytokine production were assessed. Furthermore, the effect of histone-targeted interventions by heparin or anti-histone antibody was evaluated.
resultsPlasma and BALF extracellular histone levels were much higher in ARDS patients than in healthy controls. There was a significant association between extracellular histones and ARDS severity and mortality. In addition, extracellular histones correlated with an evident systemic inflammation detected in ARDS patients. Ex-vivo analysis further showed that ARDS patient's BALF remarkably induced epithelial and endothelial cell damage and stimulated cytokine production in the supernatant of U937 cells. The adverse effects on these cells could be abrogated by heparin or anti-histone antibody.
conclusionsExtracellular histones in ARDS patients are excessively increased and may contribute to disease aggravation by inducing cellular damage and promoting systemic inflammation. Targeting extracellular histones may provide a promising approach for treating ARDS.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.