No abstract

Purpose Diabetic cardiomyopathy (DCM), a common complication of diabetes mellitus and is characterized by myocardial hypertrophy and myocardial fibrosis. Pyrroloquinoline quinone (PQQ), a natural nutrient, exerts strong protection against various myocardial diseases. Pyroptosis, a type of inflammation-related programmed cell death, is vital to the development of DCM. However, the protective effects of PQQ against DCM and the associated mechanisms are not clear. This study aimed to investigate whether PQQ protected against DCM and to determine the underlying molecular mechanism. Methods Diabetes was induced in mice by intraperitoneal injection of streptozotocin, after which the mice were administered PQQ orally (10, 20, or 40 mg/kg body weight/day) for 12 weeks. AC16 human myocardial cells were divided into the following groups and treated accordingly: control (5.5 mmol/L glucose), high glucose (35 mmol/L glucose), and HG + PQQ groups (1 and 10 nmol/L PQQ). Cells were treated for 24 h. Results PQQ reduced myocardial hypertrophy and the area of myocardial fibrosis, which was accompanied by an increase in antioxidant function and a decrease in inflammatory cytokine levels. Moreover, myocardial hypertrophy—(ANP and BNP), myocardial fibrosis—(collagen I and TGF-β1), and pyroptosis-related protein levels decreased in the PQQ treatment groups. Furthermore, PQQ abolished mitochondrial dysfunction and the activation of NF-κB/IκB, and decreased NLRP3 inflammation-mediated pyroptosis in AC16 cells under high-glucose conditions. Conclusion PQQ improved DCM in diabetic mice by inhibiting NF-κB/NLRP3 inflammasome-mediated cell pyroptosis. Long-term dietary supplementation with PQQ may be greatly beneficial for the treatment of DCM. Graphical abstract Diagram of the underlying mechanism of the effects of PQQ on DCM. PQQ inhibits ROS generation and NF-κB activation, which stimulates activation of the NLRP3 inflammasome and regulates the expression of caspase-1, IL-1β, and IL-18. The up-regulated inflammatory cytokines trigger myocardial hypertrophy and cardiac fibrosis and promote the pathological process of DCM.

No abstract

The cytotoxicity and genotoxicity of AgNPs seems to occur mainly via particles uptake and the subsequent liberation of ions inside the cells. And furthermore, the GADD45α promoter-driven luciferase reporter cells, especially the HepG2-luciferase cells, could provide a new and valuable tool for predicting nanomaterials genotoxicity in humans.

The 3S, 3'S-aSTaxanthin (3S, 3'S-aST) isomer has strong antioxidant activity; however, its protective roles and potential mechanisms against oxidative stress damage in cardiomyocytes have not been investigated. na + /K + -aTPase (nKa)/Src signal activation has an important role in increasing reactive oxygen species (roS) production. The aim of the present study was to investigate the protective effects and mechanism of 3S, 3'S-aST on hydrogen peroxide (H 2 o 2 )-induced oxidative stress injury in H9c2 myocardial cells. The protective effects of 3S, 3'S-aST on H 2 o 2 -induced H9c2 cell injury was observed by measuring lactate dehydrogenase and creatine kinase myocardial band content, cell viability and nuclear morphology. The antioxidant effect was investigated by analyzing roS accumulation and malondialdehyde, glutathione (GSH) peroxidase, GSH and glutathione reductase activity levels. The protein expression levels of Bax, Bcl-2, caspase-3 and cleaved caspase-3 were analyzed using western blotting to determine cardiomyocyte apoptosis. Western blot analysis of the phosphorylation levels of Src and erk1/2 were also performed to elucidate the molecular mechanism involved. The results showed that 3S, 3'S-aST reduced the release of ldH and promoted cell viability, and attenuated roS accumulation and cell apoptosis induced by H 2 o 2 . Furthermore, 3S, 3'S-aST also restored apoptosis-related Bax and Bcl-2 protein expression levels in H 2 o 2 -treated H9c2 cells. The phosphorylation levels of Src and Erk1/2 were significantly higher in the H 2 o 2 treatment group, whereas 3S, 3'S-AST pretreatment significantly decreased the levels of phosphorylated (p)-Src and p-erK1/2. The results provided evidence that 3S, 3'S-aST exhibited a cardioprotective effect against oxidative stress injury by attenuating NKA/Src/Erk1/2-modulated ROS amplification.