ArticleNature communications2020
Neutralizing the pathological effects of extracellular histones with small polyanions.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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
53 citing papers in PubMed, 76 citations in OpenAlex.
- Review
- Review
- Review
- From Adaptive Resilience to Catastrophic Systems Collapse: Endothelial Entropy, Ferroptotic Propagation, and the Maternal Point of No Return in Emergency Peripartum Hysterectomy.International journal of molecular sciences · 2026Review
- Current and future strategies aiming at reducing catecholamine exposure in septic shock.Critical care (London, England) · 2026Review
- Emerging biomodels to understand the pathophysiology of sepsis and evaluate new therapeutic strategies targeting extracellular histones.Materials today. Bio · 2026Review
- Barrier breakdown: lung-brain crosstalk in systemic inflammation.Journal of neuroinflammation · 2026Review
- The Role of Histone Modifications in Acute Lung Injury: Molecular Mechanisms and Potential of Traditional Chinese Medicine Treatment.Journal of inflammation research · 2026Review
- Damage-associated molecular patterns in hepatic ischemia-reperfusion injury: spatiotemporal signatures, biomarker potential, and clinical translation.Frontiers in immunology · 2026Review
- Regulation of histones in thromboinflammation.Frontiers in immunology · 2026Review
- Impact of Neutrophils on the Tissue Microenvironment During Intestinal Inflammation.Journal of inflammation research · 2026Review
- Circulating histones as clinical biomarkers in critically ill conditions.FEBS letters · 2025Review
- Cardioprotective effects of the extracellular chaperone clusterin in acute myocardial infarction.European journal of clinical investigation · 2025Article
- Beyond hemostasis, the immunomodulatory nature of platelets.Research and practice in thrombosis and haemostasis · 2025Review
- ENDOTHELIAL-SPECIFIC KNOCKOUT OF THE SCRAMBLASE TMEM16F IMPAIRS IN VIVO CLOT FORMATION.Shock (Augusta, Ga.) · 2025Article
- Neutrophil extracellular traps in tumor metabolism and microenvironment.Biomarker research · 2025Review
- Fantastic proteins and where to find them - histones, in the nucleus and beyond.Journal of cell science · 2024Review
- A dose-adjusted, open-label, pilot study of the safety, tolerability, and pharmacokinetics of STC3141 in critically ill patients with sepsis.Pharmacology research & perspectives · 2024Article
- Neutrophil Extracellular Traps in ST-Segment Elevation Myocardial Infarction: Reduced by Tocilizumab and Associated With Infarct Size.JACC. Advances · 2024Article
- The Preventive and Therapeutic Effects of Acute and Severe Inflammatory Disorders with Heparin and Heparinoid.Biomolecules · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Extracellular histones in neutrophil extracellular traps (NETs) or in chromatin from injured tissues are highly pathological, particularly when liberated by DNases. We report the development of small polyanions (SPAs) (~0.9-1.4 kDa) that interact electrostatically with histones, neutralizing their pathological effects. In vitro, SPAs inhibited the cytotoxic, platelet-activating and erythrocyte-damaging effects of histones, mechanistic studies revealing that SPAs block disruption of lipid-bilayers by histones. In vivo, SPAs significantly inhibited sepsis, deep-vein thrombosis, and cardiac and tissue-flap models of ischemia-reperfusion injury (IRI), but appeared to differ in their capacity to neutralize NET-bound versus free histones. Analysis of sera from sepsis and cardiac IRI patients supported these differential findings. Further investigations revealed this effect was likely due to the ability of certain SPAs to displace histones from NETs, thus destabilising the structure. Finally, based on our work, a non-toxic SPA that inhibits both NET-bound and free histone mediated pathologies was identified for clinical development.
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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.