Food therapy of scutellarein ameliorates pirarubicin­induced cardiotoxicity in rats by inhibiting apoptosis and ferroptosis through regulation of NOX2­induced oxidative stress.

Pirarubicin (THP) is one of the most commonly used antineoplastic drugs in clinical practice. However, its clinical application is limited due to its toxic and heart­related side effects. It has been reported that oxidative stress, inflammation and apoptosis are closely associated with cardiotoxicity caused by pirarubicin (CTP). Additionally, it has also been reported that scutellarein (Sc) exerts anti­inflammatory, antioxidant, cardio­cerebral vascular protective and anti­apoptotic properties. Therefore, the present study aimed to investigate the effect of food therapy with Sc on CTP and its underlying molecular mechanism using echocardiography, immunofluorescence, western blot, ROS staining, and TUNEL staining. The in vivo results demonstrated that THP was associated with cardiotoxicity. Additionally, abnormal changes in the expression of indicators associated with oxidative stress, ferroptosis and apoptosis were observed, which were restored by Sc. Therefore, it was hypothesized that CTP could be associated with oxidative stress, ferroptosis and apoptosis. Furthermore, the in vitro experiments showed that Sc and the NADPH oxidase 2 (NOX2) inhibitor, GSK2795039 (GSK), upregulated glutathione peroxidase 4 (GPX4) and inhibited THP­induced oxidative stress, apoptosis and ferroptosis. However, cell treatment with the ferroptosis inhibitor, ferrostatin­1, or inducer, erastin, could not significantly reduce or promote, respectively, the expression of NOX2. However, GSK significantly affected ferroptosis and GPX4 expression. Overall, the results of the present study indicated that food therapy with Sc ameliorated CTP via inhibition of apoptosis and ferroptosis through regulation of NOX2­induced oxidative stress, thus suggesting that Sc may be a potential therapeutic drug against CTP.

A dual-quenched ECL immunosensor for ultrasensitive detection of retinol binding protein 4 based on luminol@AuPt/ZIF-67 and MnO2@CNTs.

BACKGROUND: Retinol binding protein 4 (RBP4) has been regarded as an important serological biomarker for type 2 diabetes mellitus (T2DM). Hence, the construction of a highly sensitive detection method for RBP4 is the key to early prevention and multidisciplinary intervention of T2DM. In this work, a dual-quenched electrochemiluminescence (ECL) immunosensor has been fabricated for ultrasensitive detection of RBP4 by combining zeolitic imidazolate framework-67/AuPt-supported luminol (luminol@AuPt/ZIF-67) with MnO2 nanosheets-grown on carbon nanotubes (MnO2@CNTs). RESULTS: AuPt/ZIF-67 hybrids with high-efficiency peroxidase-like activity could provide multipoint binding sites for luminol and antibodies and significantly boost the amplified initial signal of the ECL immunosensor. Upon glutathione/H2O2 coreactants system, MnO2@CNTs composites could quench the initial signal by inhibiting mimic peroxidase activity of luminol@AuPt/ZIF-67. Moreover, the absorption spectrum of the MnO2@CNTs composites completely overlaps with the emission spectrum of luminol, which can further reduce initial signal by ECL resonance energy transfer (ECL-RET). CONCLUSIONS: Benefiting from the above-mentioned properties, the designed immunoassay sensitivity exhibited excellent sensitivity and relative stability for RBP4 detection range from 0.0001 to 100 ng mL-1 with a low detection limit of 43 fg mL-1. Therefore, our ECL immunosensor provides an alternative assaying strategy for early diagnosis of T2DM.