OBJECTIVE To observe the effect of natrin from Naja naja atra(Chinese cobra)on intracellular free calcium overload,and to discuss the protective effect and the possible mechanism of natrin on myocardium calcium(Ca2+)and potassium(K+)ion channels in the primary cardiomyocytes of SD neonatal rats. METHODS The primary cardiomyocytes of SD neonatal rats were used,which were respectively pretreated with natrin 5,25 and 125 mg · L-1 for 24 h before injury was induced by H2O2 0.3 mmol · L- 1. The dynamic variation of intracellular calcium was monitored by laser confocal microscopy using Fluo-3 as Ca2+fluorescence probe. Additionally,the cardio myocytes of neonatal rats were pretreated for 24 h using different concentrations of natrin 5,25,125 mg · L-1 and verapamil 5 nmol · L-1,followed by exposure to H2O2 0.3 mmol · L-1 for 15 min. Then,the mRNA expressions of calcium channels subunits Cav1.2,Calm,RyR2 and potassium channel Kir6.2 were analyzed by FQ-PCR method. RESULTS Laser confocal microscopy revealed that H2O2 obviously caused calcium overload in cardiomyocytes, giving rise to 49.37% fluorescence increase in intracellular calcium compared with the control group(P<0.01). However,natrin 5,25 and 125 mg·L-1 resulted in 27.52%, 12.71% and 5.15% fluorescence increase in intracellular calcium,respectively,compared with the control group(P<0.01). Moreover, the PCR results showed that the mRNA expressions of Cav1.2, Calm and RyR2 in the myocardial cells treated with H2O2 were increased 2.78,2.26,and 5.34 times as compared with the control group,while Kir6.2 displayed a 1.79-fold expression level(P<0.01). By contrast, the combination of natrin and verapamil significantly decreased the mRNA expression of Cav1.2,Calm and RyR2,compared to the H2O2-treated group(P<0.01). Meanwhile,the expression of Kir6.2 was considerably higher than that of the H2O2-treated group(P<0.05). CONCLUSION Natrin can reduce the intracellular calcium overload of cardiomyocytes induced by H2O2 and shows a protective effect against oxidative damage for cardiomyocytes. The possible mechanism is that natrin can decrease the mRNA expression of Cav1.2,Calm,RyR2 and increase the expression of Kir6.2 of the H2O2-induced cardiomyocytes.

We summarize the most important advances in RNA delivery and nanomedicine. We describe lipid nanoparticle-based RNA therapeutics and the impacts on the development of novel drugs. The fundamental properties of the key RNA members are described. We introduced recent advances in the nanoparticles to deliver RNA to defined targets, with a focus on lipid nanoparticles (LNPs). We review recent advances in biomedical therapy based on RNA drug delivery and state-of-the-art RNA application platforms, including the treatment of different types of cancer. This review presents an overview of current LNPs based RNA therapies in cancer treatment and provides deep insight into the development of future nanomedicines sophisticatedly combining the unparalleled functions of RNA therapeutics and nanotechnology.

Central nervous system (CNS) injuries, including stroke, traumatic brain injury, and spinal cord injury, are essential causes of death and long-term disability and are difficult to cure, mainly due to the limited neuron regeneration and the glial scar formation. Herein, we apply extracellular vesicles (EVs) secreted by M2 microglia to improve the differentiation of neural stem cells (NSCs) at the injured site, and simultaneously modify them with the injured vascular targeting peptide (DA7R) and the stem cell recruiting factor (SDF-1) on their surface via copper-free click chemistry to recruit NSCs, inducing their neuronal differentiation, and serving as the nanocarriers at the injured site (Dual-EV). Results prove that the Dual-EV could target human umbilical vascular endothelial cells (HUVECs), recruit NSCs, and promote the neuronal differentiation of NSCs in vitro. Furthermore, 10 miRNAs are found to be upregulated in Dual-M2-EVs compared to Dual-M0-EVs via bioinformatic analysis, and further NSC differentiation experiment by flow cytometry reveals that among these miRNAs, miR30b-3p, miR-222-3p, miR-129-5p, and miR-155-5p may exert effect of inducing NSC to differentiate into neurons. In vivo experiments show that Dual-EV nanocarriers achieve improved accumulation in the ischemic area of stroke model mice, potentiate NSCs recruitment, and increase neurogenesis. This work provides new insights for the treatment of neuronal regeneration after CNS injuries as well as endogenous stem cells, and the click chemistry EV/peptide/chemokine and related nanocarriers for improving human health.