{"doi":"10.1073/pnas.2209528120","title":"Using heparan sulfate octadecasaccharide (18-mer) as a multi-target agent to protect against sepsis","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.","journal":"Proceedings of the National Academy of Sciences","year":2023,"id":332162,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":25,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9529,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":288975,"name":"Yongmei Xu","orcid":"0000-0002-3756-581X","position":1,"is_corresponding":false},{"id":288974,"name":"Katelyn Arnold","orcid":"0000-0002-1750-1253","position":2,"is_corresponding":false},{"id":233177,"name":"Fuming Zhang","orcid":"0000-0003-2803-3704","position":3,"is_corresponding":false},{"id":1058236,"name":"Jine Li","orcid":"0000-0002-5542-4973","position":4,"is_corresponding":false},{"id":65828,"name":"Rani S. Sellers","orcid":"0000-0001-8870-4675","position":5,"is_corresponding":false},{"id":579097,"name":"Chaoyin Yin","orcid":null,"position":6,"is_corresponding":false},{"id":288982,"name":"Vijayakanth Pagadala","orcid":"0000-0001-7349-4230","position":7,"is_corresponding":false},{"id":1058237,"name":"Anna Marie Inman","orcid":"0000-0002-8947-7627","position":8,"is_corresponding":false},{"id":286697,"name":"Robert J. Linhardt","orcid":"0000-0003-2219-5833","position":9,"is_corresponding":false},{"id":288985,"name":"Ding Xu","orcid":"0000-0001-9380-2712","position":10,"is_corresponding":false},{"id":287688,"name":"Rafał Pawliński","orcid":"0000-0001-5162-7135","position":11,"is_corresponding":false},{"id":288986,"name":"Jian Liu","orcid":"0000-0001-8552-1400","position":12,"is_corresponding":false},{"id":395055,"name":"Yi-En Liao","orcid":"0000-0002-2114-8181","position":0,"is_corresponding":true}],"reference_count":55,"raw_metadata":null,"created_at":"2026-07-19T01:09:30.139849Z","pmid":"36649428","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}