Clioquinol as an inhibitor of JmjC-histone demethylase exhibits common and unique histone methylome and transcriptome between clioquinol and hypoxia.

Clioquinol (CQ) is a hypoxic mimicker to activate hypoxia-inducible factor-1α (HIF-1α) by inhibiting HIF-1α specific asparaginyl hypoxylase (FIH-1). The structural similarity of the Jumonji C (JmjC) domain between FIH-1 and JmjC domain-containing histone lysine demethylases (JmjC-KDMs) led us to investigate whether CQ could inhibit the catalytic activities of JmjC-KDMs. Herein, we showed that CQ inhibits KDM4A/C, KDM5A/B, and KDM6B and affects H3K4me3, H3K9me3, and H3K27me3 marks, respectively.

Determination of donepezil in human plasma using ultra performance liquid chromatography-tandem mass spectrometry.

An ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the quantification of donepezil in human plasma. Donepezil and donepezil-D4 were extracted from human plasma by liquid-liquid extraction using a mixture of hexane and ethyl acetate (70:30 v/v). The extracted samples were analyzed using a Thermo Hypersil Gold C18 column with 5% acetic acid in 20 mM ammonium acetate buffer (pH 3.