No abstract

Cadmium (Cd) is a potent neurotoxic metal present in the environment and food. In this study, CdCl2 (2 or 4 μM) induced cytotoxicity and neurotoxicity in PC12 cells, causing decreases in cell viability and NEP protein expression and increase in p‐tau protein expression. For the first time, CdCl2‐initiated injury was found to result from the induction of not only apoptosis but also ferroptosis, as evidenced by the increased iron content, ROS production, and mitochondrial membrane potential along with changes in the expressions of iron death‐related genes (FTH1, GPX4, ASCL4, PTGS2, and NOX1) and levels of caspase9, Bax, and Bcl‐2 proteins. The molecular mechanisms leading to apoptosis and ferroptosis at least included the participation of the miR‐34a‐5p/Sirt1 axis, in which miR‐34a‐5p promoted CdCl2‐induced neurotoxicity through targeting Sirt1. Knocking out miR‐34a‐5p attenuated CdCl2‐induced damage of PC12 cells, cytotoxicity and neurotoxicity. This research provides the underlying molecular mechanisms of CdCl2‐induced damage and asserts the role of miRNAs as critical regulators.

No abstract

No abstract

No abstract

No abstract

High‐fat diets (HFDs) can trigger lipid accumulation, insulin resistance, and inflammatory responses in the body, causing glucose and lipid metabolism dysfunction. This study aimed to explore the role of nuciferine on HFD‐induced disorders of glucose and lipid metabolism in obesity mice models, and further to identify the possible underlying mechanisms. In our experiments, nuciferine effectively ameliorated HFD‐induced insulin resistance by IRS/PI3K/AKT pathway, and alleviated HFD‐induced lipid accumulation via AMPK‐mediated regulation of FAS and ATGL expression. Nuciferine also suppressed HFD‐induced intestinal pathological damage, as evidenced by the improvement of intestinal barrier integrity and the increasing in expressions of tight junction proteins of claudin, ZO‐1, and occludin. In addition, 16S rRNA gene sequencing of the fecal microbiota suggested that nuciferine changed the diversity and the composition of gut microbiota in HFD‐fed mice. Nuciferine decreased the ratio of Firmicutes/Bacteroidetes, the relative abundance of LPS‐producing genus Desulfovibrio and the bacteria which involved in lipid metabolism. In summary, nuciferine ameliorated the disorders of glucose and lipid metabolism in obese mice via balancing the gut–liver axis.

No abstract