FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2892310905> ?p ?o ?g. }

• W2892310905 endingPage "S167" @default.
• W2892310905 startingPage "S167" @default.
• W2892310905 abstract "Gastrointestinal perforation and appendicitis are the common cause of leakage of alimentary contents into the peritoneal cavity, leading to sepsis with a mortality rate between 14.7% and 29.9%. Besides its clinical challenge, the treatment of sepsis and its complications impose an enormous economic burden on health care systems worldwide. In sepsis caused by gram-negative bacteria, the bacterial endotoxin, lipopolysaccharide (LPS), activates the immune system through signaling the MD2-toll like receptor 4 complex (TLR4) to initiate the infection process for production of inflammatory cytokines (TNF-α, IL-1β, IL-6) that are responsible for hyperinflammation. Thus, development of antagonists that block these receptors either by inhibition of activation of TLRs or downstream signaling pathways would be beneficial in ameliorating the hyperinflammation if introduced early in the therapy. At AyuVis Research, we have designed a series of dual-acting small molecules (AVR-25, 48) that block TLR4 receptor, which inhibits the production of proinflammatory cytokines; stimulate production of macrophages leading to organ protection; and limit tissue injury. Our lead compound, AVR-25, has efficaciously demonstrated survival, organ protection, downregulation of inflammatory cytokines, and upregulation of M2 biomarkers and cytokines such as arginase-1 and IL-10 in vivo in a cecal ligation and puncture (CLP) sepsis mouse model via intravenous (IV) dosing. Our published and unpublished in silico modeling experiment has demonstrated that our compounds have a unique binding mode where they either bind to the dimerization site or to the middle of the TLR4 protein restricting the dimerization of protein, which is a critical step in downstream signaling. In our CLP model of both young and aged mice, compounds AVR-45 and AVR-48 efficaciously protected them against CLP-induced death and organ dysfunction at a 10-mg/kg (q8h) IV dose. These compounds also possess modest antibacterial activities against both gram-positive and gram-negative bacteria, as well as synergistic/additive activity in combination with standard of care antibiotics such as primaxin (PRM, Imipenem + cilastatin), indicating good potential for adjuvant antimicrobial therapy. We are the first and only key investigator team to observe the effects of AVR-25 and AVR-48 natural oligosaccharide-derived small molecules in preventing sepsis-induced death in the murine CLP-induced peritonitis model. We believe that development of this class of compounds will lead to a paradigm shift and could become a very high-gain project in the treatment management of inflammation and organ dysfunction in intra-abdominal sepsis. These significant research capabilities will open a new facet to combination therapy with antibiotic and standard antihypotensive agents for critically ill patients." @default.
• W2892310905 created "2018-09-27" @default.
• W2892310905 creator A5005028642 @default.
• W2892310905 creator A5047520708 @default.
• W2892310905 creator A5065036747 @default.
• W2892310905 creator A5069385173 @default.
• W2892310905 date "2018-09-21" @default.
• W2892310905 modified "2023-09-25" @default.
• W2892310905 title "Novel Chitohexaose Compounds to Treat Abdominal Peritonitis Leading to Sepsis" @default.
• W2892310905 doi "https://doi.org/10.1093/ajcp/aqy112.385" @default.
• W2892310905 hasPublicationYear "2018" @default.
• W2892310905 type Work @default.
• W2892310905 sameAs 2892310905 @default.
• W2892310905 citedByCount "0" @default.
• W2892310905 crossrefType "journal-article" @default.
• W2892310905 hasAuthorship W2892310905A5005028642 @default.
• W2892310905 hasAuthorship W2892310905A5047520708 @default.
• W2892310905 hasAuthorship W2892310905A5065036747 @default.
• W2892310905 hasAuthorship W2892310905A5069385173 @default.
• W2892310905 hasBestOaLocation W28923109051 @default.
• W2892310905 hasConcept C104317684 @default.
• W2892310905 hasConcept C126322002 @default.
• W2892310905 hasConcept C127561419 @default.
• W2892310905 hasConcept C164027704 @default.
• W2892310905 hasConcept C203014093 @default.
• W2892310905 hasConcept C2776070231 @default.
• W2892310905 hasConcept C2776914184 @default.
• W2892310905 hasConcept C2778384902 @default.
• W2892310905 hasConcept C2778754761 @default.
• W2892310905 hasConcept C2779489039 @default.
• W2892310905 hasConcept C2780199535 @default.
• W2892310905 hasConcept C523546767 @default.
• W2892310905 hasConcept C54355233 @default.
• W2892310905 hasConcept C55493867 @default.
• W2892310905 hasConcept C6977687 @default.
• W2892310905 hasConcept C71924100 @default.
• W2892310905 hasConcept C86803240 @default.
• W2892310905 hasConcept C8891405 @default.
• W2892310905 hasConcept C98274493 @default.
• W2892310905 hasConceptScore W2892310905C104317684 @default.
• W2892310905 hasConceptScore W2892310905C126322002 @default.
• W2892310905 hasConceptScore W2892310905C127561419 @default.
• W2892310905 hasConceptScore W2892310905C164027704 @default.
• W2892310905 hasConceptScore W2892310905C203014093 @default.
• W2892310905 hasConceptScore W2892310905C2776070231 @default.
• W2892310905 hasConceptScore W2892310905C2776914184 @default.
• W2892310905 hasConceptScore W2892310905C2778384902 @default.
• W2892310905 hasConceptScore W2892310905C2778754761 @default.
• W2892310905 hasConceptScore W2892310905C2779489039 @default.
• W2892310905 hasConceptScore W2892310905C2780199535 @default.
• W2892310905 hasConceptScore W2892310905C523546767 @default.
• W2892310905 hasConceptScore W2892310905C54355233 @default.
• W2892310905 hasConceptScore W2892310905C55493867 @default.
• W2892310905 hasConceptScore W2892310905C6977687 @default.
• W2892310905 hasConceptScore W2892310905C71924100 @default.
• W2892310905 hasConceptScore W2892310905C86803240 @default.
• W2892310905 hasConceptScore W2892310905C8891405 @default.
• W2892310905 hasConceptScore W2892310905C98274493 @default.
• W2892310905 hasIssue "suppl_1" @default.
• W2892310905 hasLocation W28923109051 @default.
• W2892310905 hasOpenAccess W2892310905 @default.
• W2892310905 hasPrimaryLocation W28923109051 @default.
• W2892310905 hasRelatedWork W178181029 @default.
• W2892310905 hasRelatedWork W2028557727 @default.
• W2892310905 hasRelatedWork W2073865733 @default.
• W2892310905 hasRelatedWork W2093246706 @default.
• W2892310905 hasRelatedWork W2372867219 @default.
• W2892310905 hasRelatedWork W2438788984 @default.
• W2892310905 hasRelatedWork W2971786659 @default.
• W2892310905 hasRelatedWork W2989917496 @default.
• W2892310905 hasRelatedWork W3102465713 @default.
• W2892310905 hasRelatedWork W4307870797 @default.
• W2892310905 hasVolume "150" @default.
• W2892310905 isParatext "false" @default.
• W2892310905 isRetracted "false" @default.
• W2892310905 magId "2892310905" @default.
• W2892310905 workType "article" @default.