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10.1016/j.ebiom.2020.103039 http://scihub22266oqcxt.onion/10.1016/j.ebiom.2020.103039 33038762!7648121!33038762     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       EBioMedicine 2020 ; 61 (ä): 103039 Nephropedia Template TP {{tp|p=33038762|t=2020. Pharmacological validation of targets regulating CD14 during macrophage differentiation |pdf=|usr=}}{{33038762}} gab.com Text Pharmacological validation of targets regulating CD14 during macrophage differentiation JO: EBioMedicine http://www.kidney.de/pget.php?&tw=1&pmid=33038762 #FOAvip The signalling receptor for LPS, CD14, is a key marker of, and facilitator for, pro-inflammatory macrophage function. Pro-inflammatory macrophage differentiation remains a process facilitating a broad array of disease pathologies, and has recently emerged as a potential target against cytokine storm in COVID19. Here, we perform a whole-genome CRISPR screen to identify essential nodes regulating CD14 expression in myeloid cells, using the differentiation of THP-1 cells as a starting point. This strategy uncovers many known pathways required for CD14 expression and regulating macrophage differentiation while additionally providing a list of novel targets either promoting or limiting this process. To speed translation of these results, we have then taken the approach of independently validating hits from the screen using well-curated small molecules. In this manner, we identify pharmacologically tractable hits that can either increase CD14 expression on non-differentiated monocytes or prevent CD14 upregulation during macrophage differentiation. An inhibitor for one of these targets, MAP2K3, translates through to studies on primary human monocytes, where it prevents upregulation of CD14 following M-CSF induced differentiation, and pro-inflammatory cytokine production in response to LPS. Therefore, this screening cascade has rapidly identified pharmacologically tractable nodes regulating a critical disease-relevant process. Twit Text FOAVip Pharmacological validation of targets regulating CD14 during macrophage differentiation ????EBioMedicine http://www.kidney.de/pget.php?&tw=1&pmid=33038762 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=33038762 #FOAvip English Wikipedia <ref>{{Cite pmid|33038762}}</ref> Pharmacological validation of targets regulating CD14 during macrophage differentiation #MMPMID33038762 Jimenez-Duran G; Luque-Martin R; Patel M; Koppe E; Bernard S; Sharp C; Buchan N; Rea C; de Winther MPJ; Turan N; Angell D; Wells CA; Cousins R; Mander PK; Masters SL EBioMedicine 2020[Nov]; 61 (ä): 103039 PMID33038762show ga The signalling receptor for LPS, CD14, is a key marker of, and facilitator for, pro-inflammatory macrophage function. Pro-inflammatory macrophage differentiation remains a process facilitating a broad array of disease pathologies, and has recently emerged as a potential target against cytokine storm in COVID19. Here, we perform a whole-genome CRISPR screen to identify essential nodes regulating CD14 expression in myeloid cells, using the differentiation of THP-1 cells as a starting point. This strategy uncovers many known pathways required for CD14 expression and regulating macrophage differentiation while additionally providing a list of novel targets either promoting or limiting this process. To speed translation of these results, we have then taken the approach of independently validating hits from the screen using well-curated small molecules. In this manner, we identify pharmacologically tractable hits that can either increase CD14 expression on non-differentiated monocytes or prevent CD14 upregulation during macrophage differentiation. An inhibitor for one of these targets, MAP2K3, translates through to studies on primary human monocytes, where it prevents upregulation of CD14 following M-CSF induced differentiation, and pro-inflammatory cytokine production in response to LPS. Therefore, this screening cascade has rapidly identified pharmacologically tractable nodes regulating a critical disease-relevant process. |Biomarkers[MESH] |Cell Differentiation/*drug effects[MESH] |Cells, Cultured[MESH] |Cytokines/metabolism[MESH] |Humans[MESH] |Immunophenotyping[MESH] |Leukocytes, Mononuclear/drug effects/immunology/metabolism[MESH] |Lipopolysaccharide Receptors/*metabolism[MESH] |Lipopolysaccharides/adverse effects[MESH] |Macrophages/drug effects/*immunology/*metabolism[MESH]Pharmacological validation of targets regulating CD14 during macrophag(epmc).pdf DeepDyve Pubget Overpricing