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Using heparan sulfate octadecasaccharide (18-mer) as a multi-target agent to protect against sepsis. | LitMetric

AI Article Synopsis

  • - Sepsis is a serious condition caused by an uncontrolled inflammatory reaction to infection, which can lead to severe injury or death.
  • - A synthetic molecule called a heparan sulfate octadecasaccharide (18-mer) shows promise in protecting against sepsis by inhibiting harmful proteins and promoting anti-inflammatory effects.
  • - Research indicates that the 18-mer improves survival and reduces inflammation in mice models of sepsis by neutralizing toxic histones and disrupting harmful complexes, making it a potentially more effective therapy compared to existing treatments that target only one factor.

Article 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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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9942825PMC
http://dx.doi.org/10.1073/pnas.2209528120DOI Listing

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