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10.1073/pnas.2018090118 http://scihub22266oqcxt.onion/10.1073/pnas.2018090118 33658363!7958265!33658363     free     free     free Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Proc+Natl+Acad+Sci+U+S+A 2021 ; 118 (10): ä Nephropedia Template TP {{tp|p=33658363|t=2021. Sialoglycan recognition is a common connection linking acidosis, zinc, and HMGB1 in sepsis |pdf=|usr=}}{{33658363}} gab.com Text Sialoglycan recognition is a common connection linking acidosis, zinc, and HMGB1 in sepsis JO: Proc Natl Acad Sci U S A http://www.kidney.de/pget.php?&tw=1&pmid=33658363 #FOAvip Blood pH is tightly maintained between 7.35 and 7.45, and acidosis (pH <7.3) indicates poor prognosis in sepsis, wherein lactic acid from anoxic tissues overwhelms the buffering capacity of blood. Poor sepsis prognosis is also associated with low zinc levels and the release of High mobility group box 1 (HMGB1) from activated and/or necrotic cells. HMGB1 added to whole blood at physiological pH did not bind leukocyte receptors, but lowering pH with lactic acid to mimic sepsis conditions allowed binding, implying the presence of natural inhibitor(s) preventing binding at normal pH. Testing micromolar concentrations of divalent cations showed that zinc supported the robust binding of sialylated glycoproteins with HMGB1. Further characterizing HMGB1 as a sialic acid-binding lectin, we found that optimal binding takes place at normal blood pH and is markedly reduced when pH is adjusted with lactic acid to levels found in sepsis. Glycan array studies confirmed the binding of HMGB1 to sialylated glycan sequences typically found on plasma glycoproteins, with binding again being dependent on zinc and normal blood pH. Thus, HMGB1-mediated hyperactivation of innate immunity in sepsis requires acidosis, and micromolar zinc concentrations are protective. We suggest that the potent inflammatory effects of HMGB1 are kept in check via sequestration by plasma sialoglycoproteins at physiological pH and triggered when pH and zinc levels fall in late stages of sepsis. Current clinical trials independently studying zinc supplementation, HMGB1 inhibition, or pH normalization may be more successful if these approaches are combined and perhaps supplemented by infusions of heavily sialylated molecules. Twit Text FOAVip Sialoglycan recognition is a common connection linking acidosis, zinc, and HMGB1 in sepsis ????Proc Natl Acad Sci U S A http://www.kidney.de/pget.php?&tw=1&pmid=33658363 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=33658363 #FOAvip English Wikipedia <ref>{{Cite pmid|33658363}}</ref> Sialoglycan recognition is a common connection linking acidosis, zinc, and HMGB1 in sepsis #MMPMID33658363 Siddiqui SS; Dhar C; Sundaramurthy V; Sasmal A; Yu H; Bandala-Sanchez E; Li M; Zhang X; Chen X; Harrison LC; Xu D; Varki A Proc Natl Acad Sci U S A 2021[Mar]; 118 (10): ä PMID33658363show ga Blood pH is tightly maintained between 7.35 and 7.45, and acidosis (pH <7.3) indicates poor prognosis in sepsis, wherein lactic acid from anoxic tissues overwhelms the buffering capacity of blood. Poor sepsis prognosis is also associated with low zinc levels and the release of High mobility group box 1 (HMGB1) from activated and/or necrotic cells. HMGB1 added to whole blood at physiological pH did not bind leukocyte receptors, but lowering pH with lactic acid to mimic sepsis conditions allowed binding, implying the presence of natural inhibitor(s) preventing binding at normal pH. Testing micromolar concentrations of divalent cations showed that zinc supported the robust binding of sialylated glycoproteins with HMGB1. Further characterizing HMGB1 as a sialic acid-binding lectin, we found that optimal binding takes place at normal blood pH and is markedly reduced when pH is adjusted with lactic acid to levels found in sepsis. Glycan array studies confirmed the binding of HMGB1 to sialylated glycan sequences typically found on plasma glycoproteins, with binding again being dependent on zinc and normal blood pH. Thus, HMGB1-mediated hyperactivation of innate immunity in sepsis requires acidosis, and micromolar zinc concentrations are protective. We suggest that the potent inflammatory effects of HMGB1 are kept in check via sequestration by plasma sialoglycoproteins at physiological pH and triggered when pH and zinc levels fall in late stages of sepsis. Current clinical trials independently studying zinc supplementation, HMGB1 inhibition, or pH normalization may be more successful if these approaches are combined and perhaps supplemented by infusions of heavily sialylated molecules. |Acidosis/*blood/immunology/metabolism/pathology[MESH] |Carrier Proteins[MESH] |HMGB1 Protein/*blood/pharmacology[MESH] |Humans[MESH] |Hydrogen-Ion Concentration[MESH] |Immunity, Innate[MESH] |Lipopolysaccharides/pharmacology[MESH] |Polysaccharides/chemistry[MESH] |Sepsis/*blood/immunology/pathology[MESH] |Sialic Acids/chemistry[MESH] |Sialoglycoproteins/*blood/chemistry[MESH]Sialoglycan recognition is a common connection linking acidosis, zinc,(epmc).pdf DeepDyve Pubget Overpricing