Apoptosis,a key mechanism of programmed cell death,is triggered by caspase-3 protein and lowering its levels with gene therapy may rescue cell death after central nervous system damage.We developed a novel,non-viral g...Apoptosis,a key mechanism of programmed cell death,is triggered by caspase-3 protein and lowering its levels with gene therapy may rescue cell death after central nervous system damage.We developed a novel,non-viral gene therapy to block caspase-3 gene expression using small interfering RNA(siRNA)delivered by polybutylcyanoacrylate nanoparticles(CaspNPs).In vitro CaspNPs significantly blocked caspase-3 protein expression in C6 cells,and when injected intraocularly in vivo,CaspNPs lowered retinal capsase-3 immunofluorescence by 57.9%in rats with optic nerve crush.Longitudinal,repeated retinal ganglion cell counts using confocal neuroimaging showed that post-traumatic cell loss after intraocular CaspNPs injection was only 36.1%versus 63.4%in lesioned controls.Because non-viral gene therapy with siRNA-nanoparticles can selectively silence caspace-3 gene expression and block apoptosis in post-mitotic neurons,siRNA delivery with nanoparticles may be promising for neuroprotection or restoration of central visual system damage and other neurological disorders.The animal study procedures were approved by the German National Act on the use of experimental animals(Ethic Committee Referat Verbraucherschutz,Veterinärangelegenheiten;Landesverwaltungsamt Sachsen-Anhalt,Halle,Germany,#IMP/G/01-1150/12 and#IMP/G/01-1469/17).展开更多
The optimal duration of dual antiplatelet therapy(DAPT)of aspirin and a P2Y12 receptor blocker after stenting is still being debated.The current recommendations for DAPT duration are signifi cantly focused on reducing...The optimal duration of dual antiplatelet therapy(DAPT)of aspirin and a P2Y12 receptor blocker after stenting is still being debated.The current recommendations for DAPT duration are signifi cantly focused on reducing stent thrombosis;a less frequent event with later than earlier generation drug eluting stents(DES).A persistent occurrence of late and very late stent thrombosis with first generation DES supported extended use of DAPT beyond one year.However,recent studies have demonstrated that extended duration DAPT is associated with increased bleeding;an independent predictor for poor outcomes,including long-term mortality.Second-generation DES are associated with less late and very late stent thrombosis.Some recent studies have supported a shorter duration of DAPT for second generation DES.However,these studies were inadequately powered to assess signifi cant differences in stent thrombosis.Furthermore,extended duration DAPT has been associated with a reduced risk of thrombotic events in non-culprit vessels in addition to stent thrombosis in patients with acute coronary syndromes(ACS).The higher risk of bleeding associated with extended DAPT therapy provides a strong rationale for personalized DAPT based on patient risk factors(e.g.ACS vs.non-ACS),type of stents,and cost-benefit analyses.展开更多
基金MT was funded by the Leistungsorientierte Mittelvergabe(LOM)scholarship offered by the medical faculty of Magdeburg and the Deutscher Akademischer Austauschdienst(DAAD).
文摘Apoptosis,a key mechanism of programmed cell death,is triggered by caspase-3 protein and lowering its levels with gene therapy may rescue cell death after central nervous system damage.We developed a novel,non-viral gene therapy to block caspase-3 gene expression using small interfering RNA(siRNA)delivered by polybutylcyanoacrylate nanoparticles(CaspNPs).In vitro CaspNPs significantly blocked caspase-3 protein expression in C6 cells,and when injected intraocularly in vivo,CaspNPs lowered retinal capsase-3 immunofluorescence by 57.9%in rats with optic nerve crush.Longitudinal,repeated retinal ganglion cell counts using confocal neuroimaging showed that post-traumatic cell loss after intraocular CaspNPs injection was only 36.1%versus 63.4%in lesioned controls.Because non-viral gene therapy with siRNA-nanoparticles can selectively silence caspace-3 gene expression and block apoptosis in post-mitotic neurons,siRNA delivery with nanoparticles may be promising for neuroprotection or restoration of central visual system damage and other neurological disorders.The animal study procedures were approved by the German National Act on the use of experimental animals(Ethic Committee Referat Verbraucherschutz,Veterinärangelegenheiten;Landesverwaltungsamt Sachsen-Anhalt,Halle,Germany,#IMP/G/01-1150/12 and#IMP/G/01-1469/17).
文摘The optimal duration of dual antiplatelet therapy(DAPT)of aspirin and a P2Y12 receptor blocker after stenting is still being debated.The current recommendations for DAPT duration are signifi cantly focused on reducing stent thrombosis;a less frequent event with later than earlier generation drug eluting stents(DES).A persistent occurrence of late and very late stent thrombosis with first generation DES supported extended use of DAPT beyond one year.However,recent studies have demonstrated that extended duration DAPT is associated with increased bleeding;an independent predictor for poor outcomes,including long-term mortality.Second-generation DES are associated with less late and very late stent thrombosis.Some recent studies have supported a shorter duration of DAPT for second generation DES.However,these studies were inadequately powered to assess signifi cant differences in stent thrombosis.Furthermore,extended duration DAPT has been associated with a reduced risk of thrombotic events in non-culprit vessels in addition to stent thrombosis in patients with acute coronary syndromes(ACS).The higher risk of bleeding associated with extended DAPT therapy provides a strong rationale for personalized DAPT based on patient risk factors(e.g.ACS vs.non-ACS),type of stents,and cost-benefit analyses.
