Bufalin-induced cardiotoxicity: new findings into mechanisms / 中国天然药物

Bufalin is one of the main pharmacological and toxicological components of Venenum Bufonis and many traditional Chinese medicine preparations. The cardiotoxicity clearly limits its application to patients living in countries. Hence, an investigation of its toxicological mechanism is helpful for new drug development and treatment of the related clinical adverse reactions. We investigate the cardiotoxicity of bufalin using human induced pluripotent stem cells-derived cardiomyocytes (hiPSC-CMs) (0.003-0.1 μmol·L), human induced pluripotent stem cells-derived cardiomyocytes (hiPSC-CMs) (0.03-0.3 μmol·L) and eight human cardiac ion channel currents (0.01-100 μmol·L) combined with an impedance-based bioanalytical and patch clamp method. Biphasic effect of bufalin on the contractility in hiPSC-CMs, which has been shown to strengthen myocardial contractility, accelerate conduction, and increase beating rate at the earlier stage of administration, whereas weakened myocardial contractility, abolished conduction, and ceased beating rate at the later stage of administration. Bufalin decreased the action potential duration (Action potential duration at 30%, 50% and 90% repolarization), cardiac action potential amplitude, and maximal depolarization rate and depolarized the resting membrane potential of hiPSC-CMs. Spontaneous beating rates of hiPSC-CMs were markedly increased at 0.03 μmol·L, while were weakened at 0.3 μmol·L after application. Bufalin blocks I in a concentration-dependent manner with half maximal inhibitory concentration of 74.5 μmol·L. Bufalin respectively increased the late sodium current and Na-Ca exchange current with a concentration for 50% of maximal effect of 2.48 and 66.06 μmol·L in hiPSC-CMs. Whereas, bufalin showed no significant effects on other cardiac ion channel currents. The enhancement of the late sodium current is one of the main mechanism for cardiotoxicity of bufalin.

Piwi-interacting RNA(piRNA):a Novel Class of Noncoding Small RNA / 中国生物工程杂志

piRNA(Piwi-interacting RNA) is a novel class of small single strand RNA that were recently isolated from testes of the mammals, associate with PIWI proteins, and are organized into distinct genomic clusters. These RNAs are typically 30 nt long, strikingly different from microRNAs in their length, expression pattern, and genomic organization. piRNA has a role in RNA silencing via the formation of an RNA-induced silencing complex (RISC) with Piwi proteins, these piRNA complexes (piRCs) have been linked to transcriptional gene silencing of retrotransposons and other genetic elements in germ line cells, particularly those in spermatogenesis.Recent researches and progresses of piRNAs are reviewed.