ArticleProceedings of the National Academy of Sciences of the United States of America2023
Using heparan sulfate octadecasaccharide (18-mer) as a multi-target agent to protect against sepsis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 22 citations in OpenAlex.
- Fucoidans: a new frontier in brown seaweed research and biotechnology.Cell surface (Amsterdam, Netherlands) · 2026Review
- Anticoagulants beyond coagulation: repurposing heparin to mitigate immunothrombosis and inflammatory cascades in sepsis.Frontiers in pharmacology · 2026Review
- Multiomics reveal plasma constituents associated with thrombosis among trauma patients who do not respond to enoxaparin.Blood vessels, thrombosis & hemostasis · 2025Article
- High-density lipoprotein: a biomarker and therapeutic target in sepsis.Critical care (London, England) · 2025Review
- HMGB1 B-Box Domain Associates Promote Protein-Polyelectrolyte Interactions.The journal of physical chemistry. B · 2025Article
- Applications of Surface Plasmon Resonance in Heparan Sulfate Interactome Research.Biomedicines · 2025Review
- UtilizingAmerican journal of physiology. Cell physiology · 2025Review
- The Preventive and Therapeutic Effects of Acute and Severe Inflammatory Disorders with Heparin and Heparinoid.Biomolecules · 2024Review
- A Novel Drug Candidate for Sepsis Targeting Heparanase by Inhibiting Cytokine Storm.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Biosynthetic production of anticoagulant heparin polysaccharides through metabolic and sulfotransferases engineering strategies.Nature communications · 2024Article
- Article
- The Effects of Heparan Sulfate Infusion on Endothelial and Organ Injury in a Rat Pneumosepsis Model.Journal of clinical medicine · 2023Article
- Treatment Advances in Sepsis and Septic Shock: Modulating Pro- and Anti-Inflammatory Mechanisms.Journal of clinical medicine · 2023Review
- 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
- Targeting heparan sulfate-protein interactions with oligosaccharides and monoclonal antibodies.Frontiers in molecular biosciences · 2023Review
- Heparan sulfates and heparan sulfate binding proteins in sepsis.Frontiers in molecular biosciences · 2023Review
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
Sepsis is a lethal syndrome manifested by an unregulated, overwhelming inflammation from the host in response to infection. Here, we exploit the use of a synthetic heparan sulfate octadecasaccharide (18-mer) to protect against sepsis. The 18-mer not only inhibits the pro-inflammatory activity of extracellular histone H3 and high mobility group box 1 (HMGB1), but also elicits the anti-inflammatory effect from apolipoprotein A-I (ApoA-I). We demonstrate that the 18-mer protects against sepsis-related injury and improves survival in cecal ligation and puncture mice and reduces inflammation in an endotoxemia mouse model. The 18-mer neutralizes the cytotoxic histone-3 (H3) through direct interaction with the protein. Furthermore, the 18-mer enlists the actions of ApoA-I to dissociate the complex of HMGB1 and lipopolysaccharide, a toxic complex contributing to cell death and tissue damage in sepsis. Our study provides strong evidence that the 18-mer mitigates inflammatory damage in sepsis by targeting numerous mediators, setting it apart from other potential therapies with a single target.
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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.