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10.1155/2015/510679

http://scihub22266oqcxt.onion/10.1155/2015/510679
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C4550771!4550771!26351407
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suck abstract from ncbi


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pmid26351407      Mediators+Inflamm 2015 ; 2015 (ä): ä
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  • Synthesis and Validation of a Hydroxypyrone-Based, Potent, and Specific Matrix Metalloproteinase-12 Inhibitor with Anti-Inflammatory Activity In Vitro and In Vivo #MMPMID26351407
  • Aerts J; Vandenbroucke RE; Dera R; Balusu S; Van Wonterghem E; Moons L; Libert C; Dehaen W; Arckens L
  • Mediators Inflamm 2015[]; 2015 (ä): ä PMID26351407show ga
  • A hydroxypyrone-based matrix metalloproteinase (MMP) inhibitor was synthesized and assayed for its inhibitory capacity towards a panel of ten different MMPs. The compound exhibited selective inhibition towards MMP-12. The effects of inhibition of MMP-12 on endotoxemia and inflammation-induced blood-cerebrospinal fluid barrier (BCSFB) disruption were assessed both in vitro and in vivo. Similar to MMP-12 deficient mice, inhibitor-treated mice displayed significantly lower lipopolysaccharide- (LPS-) induced lethality compared to vehicle treated controls. Following LPS injection Mmp-12 mRNA expression was massively upregulated in choroid plexus tissue and a concomitant increase in BCSFB permeability was observed, which was restricted in inhibitor-treated mice. Moreover, an LPS-induced decrease in tight junction permeability of primary choroid plexus epithelial cells was attenuated by inhibitor application in vitro. Taken together, this hydroxypyrone-based inhibitor is selective towards MMP-12 and displays anti-inflammatory activity in vitro and in vivo.
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