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10.1124/mol.116.103267 http://scihub22266oqcxt.onion/10.1124/mol.116.103267 C4885501!4885501!26989084     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=26989084&cmd=llinks): Failed to open stream: HTTP request failed! 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Repurposing Treprostinil for Enhancing Hematopoietic Progenitor Cell Transplantation |pdf=|usr=}}{{26989084}} gab.com Text Repurposing Treprostinil for Enhancing Hematopoietic Progenitor Cell Transplantation JO: Mol Pharmacol http://www.kidney.de/pget.php?&tw=1&pmid=26989084 #FOAvip Activation of Gs-coupled receptors enhances engraftment of hematopoietic stem and progenitor cells (HSPCs). We tested the hypothesis that treprostinil, a prostacyclin analog approved for the treatment of pulmonary hypertension, can be repurposed to improve hematopoietic stem cell transplantation. Murine and human HSPCs were isolated from bone marrow and umbilical cord blood, respectively. Prostanoid receptor agonists and the combination thereof with forskolin were tested for their capacity to stimulate [3H]cAMP accumulation in HSPCs. Three independent approaches were employed to verify the ability of agonist-activated HSPCs to reconstitute the bone marrow in lethally irradiated recipient mice. The underlying mechanism was explored in cellular migration assays and by blocking C-X-C motif chemokine receptor 4 (CXCR4). Among several prostanoid agonists tested in combination with forskolin, treprostinil was most efficacious in raising intracellular cAMP levels in murine and human HPSCs. Injection of murine and human HSPCs, which had been pretreated with treprostinil and forskolin, enhanced survival of lethally irradiated recipient mice. Survival was further improved if recipient mice were subcutaneously administered treprostinil (0.15 mg kg?1 8 h?1) for 10 days. This regimen also reduced the number of HSPCs required to rescue lethally irradiated mice. Enhanced survival of recipient mice was causally related to treprostinil-enhanced CXCR4-dependent migration of HSPCs. Treprostinil stimulates the engraftment of human and murine hematopoietic stem cells without impairing their capacity for self-renewal. The investigated dose range corresponds to the dose approved for human use. Hence, these findings may be readily translated into a clinical application. Twit Text FOAVip Repurposing Treprostinil for Enhancing Hematopoietic Progenitor Cell Transplantation ????Mol Pharmacol http://www.kidney.de/pget.php?&tw=1&pmid=26989084 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=26989084 #FOAvip English Wikipedia <ref>{{Cite pmid|26989084}}</ref> Repurposing Treprostinil for Enhancing Hematopoietic Progenitor Cell Transplantation #MMPMID26989084 Kazemi Z; Bergmayr C; Prchal-Murphy M; Javaheri T; Themanns M; Pham HTT; Strohmaier W; Sexl V; Freissmuth M; Zebedin-Brandl E Mol Pharmacol 2016[Jun]; 89 (6): 630-44 PMID26989084show ga Activation of Gs-coupled receptors enhances engraftment of hematopoietic stem and progenitor cells (HSPCs). We tested the hypothesis that treprostinil, a prostacyclin analog approved for the treatment of pulmonary hypertension, can be repurposed to improve hematopoietic stem cell transplantation. Murine and human HSPCs were isolated from bone marrow and umbilical cord blood, respectively. Prostanoid receptor agonists and the combination thereof with forskolin were tested for their capacity to stimulate [3H]cAMP accumulation in HSPCs. Three independent approaches were employed to verify the ability of agonist-activated HSPCs to reconstitute the bone marrow in lethally irradiated recipient mice. The underlying mechanism was explored in cellular migration assays and by blocking C-X-C motif chemokine receptor 4 (CXCR4). Among several prostanoid agonists tested in combination with forskolin, treprostinil was most efficacious in raising intracellular cAMP levels in murine and human HPSCs. Injection of murine and human HSPCs, which had been pretreated with treprostinil and forskolin, enhanced survival of lethally irradiated recipient mice. Survival was further improved if recipient mice were subcutaneously administered treprostinil (0.15 mg kg?1 8 h?1) for 10 days. This regimen also reduced the number of HSPCs required to rescue lethally irradiated mice. Enhanced survival of recipient mice was causally related to treprostinil-enhanced CXCR4-dependent migration of HSPCs. Treprostinil stimulates the engraftment of human and murine hematopoietic stem cells without impairing their capacity for self-renewal. The investigated dose range corresponds to the dose approved for human use. Hence, these findings may be readily translated into a clinical application. äRepurposing Treprostinil for Enhancing Hematopoietic Progenitor Cell T(epmc).pdf DeepDyve Pubget Overpricing