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10.1038/mt.2014.111

http://scihub22266oqcxt.onion/10.1038/mt.2014.111
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C4428396!4428396!24930602
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suck abstract from ncbi


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pmid24930602      Mol+Ther 2014 ; 22 (10): 1817-28
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  • Serum-stabilized Naked Caspase-3 siRNA Protects Autotransplant Kidneys in a Porcine Model #MMPMID24930602
  • Yang C; Zhao T; Zhao Z; Jia Y; Li L; Zhang Y; Song M; Rong R; Xu M; Nicholson ML; Zhu T; Yang B
  • Mol Ther 2014[Oct]; 22 (10): 1817-28 PMID24930602show ga
  • The naked small interfering RNA (siRNA) of caspase-3, a key player in ischemia reperfusion injury, was effective in cold preserved and hemoreperfused kidneys, but not autotransplanted kidneys in our porcine models. Here, chemically modified serum stabilized caspase-3 siRNAs were further evaluated. The left kidney was retrieved and infused by University of Wisconsin solution with/without 0.3?mg caspase-3 or negative siRNA into the renal artery for 24-hour cold storage (CS). After an intravenous injection of 0.9?mg siRNA and right-uninephrectomy, the left kidney was autotransplanted for 2 weeks. The effectiveness of caspase-3 siRNA was confirmed by caspase-3 knockdown in the post-CS and/or post-transplant kidneys with reduced apoptosis and inflammation, while the functional caspase-3 siRNA in vivo was proved by detected caspase-3 mRNA degradation intermediates. HMGB1 protein was also decreased in the post-transplanted kidneys; correlated positively with renal IL-1? mRNA, but negatively with serum IL-10 or IL-4. The minimal off-target effects of caspase-3 siRNA were seen with favorable systemic responses. More importantly, renal function, associated with active caspase-3, HMGB1, apoptosis, inflammation, and tubulointerstitial damage, was improved by caspase-3 siRNA. Taken together, the 2-week autotransplanted kidneys were protected when caspase-3 siRNA administrated locally and systemically, which provides important evidence for future clinical trials.
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