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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Animals, Animals, Newborn, Cardiotonic Agents, Cell Hypoxia, Dose-Response Relationship, Drug, Gene Knockdown Techniques, Hypoxia-Inducible Factor 1, Imidazoles, Ischemic Preconditioning, Myocardial, Myocytes, Cardiac, NF-kappa B, Nitric Oxide Synthase Type II, Oxidative Stress, Oxygen, Rats, Rats, Wistar, Reactive Oxygen Species, Toll-Like Receptor 7, Toll-Like Receptor 8.
user
Does toll-like receptor 7/8 agonist resiquimod induce late preconditioning in neonatal cardiac myocytes? Context: To investigate whether R-848 (resiquimod, toll-like receptor 7/8 agonist) can induce late preconditioning in neonatal cardiac myocytes. The protective effects of R-848 on neonatal myocytes against anoxia-reoxygenation-induced injury were tested, and intracellular reactive oxygen species (ROS) were determined. The protein synthesis inhibitor cyclohexamide (CH) and the ROS scavenger N-acetylcysteine (NAC) were used in this model to test if new protein synthesis and oxidative stress were necessary for their cardioprotective effects. The activation of nuclear factor kappa B (NFκB) and hypoxia inducible factor 1 (HIF1) was investigated by electrophoretic mobility shift assays (EMSA), and inducible nitric oxide synthase (iNOS) was assessed by immunoblotting. After iNOS was down-regulated by small interfering RNA (siRNA) transfection, the cardioprotective effect was reassessed. ROS were triggered soon after R-848 (0.01-1.0 μg/L) administration, however, the cardioprotective effect of which was induced 24 h later. This protection was abolished by CH or NAC pretreatment. NFκB and HIF1 activation and iNOS up-regulation were involved in this protective mechanism. The cardioprotective effect was also attenuated after iNOS was knocked down.
assistant
R-848 provided a cardioprotective effect through a late preconditioning mechanism via a ROS/NFκB-HIF1/iNOS-dependent pathway. Final Decision: yes