The damage of vascular endothelial cells induced by oxidative stress plays an important role in the pathogenesis of atherosclerosis. Dihydromyricetin (DMY) is considered as a natural antioxidant. However, the mechanism of DMY on endothelial cell injury induced by oxidative stress remains unclear. In this study, we found that DMY could reduce the oxidative damage of HUVECs induced by sodium nitroprusside (SNP), HUVECs pre‐treated with DMY suppressed SNP‐induced apoptosis by reduced ROS overproduction of intracellular, decreased MDA level and elevated the superoxide dismutase activity. Meanwhile, we found that DMY could promote the expression of phosphorylated FoxO3a and Akt, and affect the nuclear localization of FoxO3a, when treated with the PI3K inhibitor LY294002, the effect of DMY was blocked. These data suggest that DMY protects HUVECs from oxidative stress by activating PI3K/Akt/FoxO3a signalling pathway. Therefore, DMY may have great therapeutic potential as a new drug for atherosclerosis.

Uveal melanoma (UM) is a highly invasive intraocular malignancy with high mortality. Presently, there is no FDA‐approved standard for the treatment of metastatic UM. Pristimerin is a natural quinine methide triterpenoid compound with anti‐angiogenic, anti‐cancer and anti‐inflammatory activities. However, Pristimerin potential cytotoxic effect on UM was poorly investigated. In the present study, we found the migration and invasion of UM‐1 cells were inhibited by Pristimerin which also caused a rapid increase of ROS, decreased mitochondrial membrane potential, induced the accumulation of cells in G0/G1 phase, ending with apoptotic cell death. Pristimerin inhibited Akt and FoxO3a phosphorylation and induced nuclear accumulation of FoxO3a in UM‐1 cells, increased the expression of pro‐apoptotic proteins Bim、p27^Kip1, cleaved caspase‐3, PARP and Bax, and decreased the expression of Cyclin D1 and Bcl‐2. LY294002 or Akt‐siRNA inhibited the PI3K/Akt/FoxO3a pathway and promoted the Pristimerin‐induced apoptosis, while Pristimerin effects were partially abolished in FoxO3a knockdown UM‐1 cell cultures. Taken together, present results showed that Pristimerin induced apoptotic cell death through inhibition of PI3K/Akt/FoxO3a pathway in UM‐1 cells. These findings indicate that Pristimerin may be considered as a potential chemotherapeutic agent for patients with UM.

Type 2 diabetes mellitus (T2DM) is a multifactorial disorder that leads to alterations in gene regulation. ncRNAs have the characteristics of tissue specificity, disease specificity, timing specificity, high stability and post transcriptional regulation effect. These preconditions are more conducive to promote ncRNA to become a new biomarker for clinical diagnosis. Our study aims to explore the relationship between circRNA, lncRNA, miRNA and T2DM, and to evaluate their diagnostic value for T2DM. A total of 101 pairs of T2DM and controls were conducted in the study. QRT-PCR was used to study the differential expression of circRNAs, miRNAs and lncRNAs. ROC curve was used to estimate their diagnostic value in T2DM. Compared with healthy controls, the expression levels of hsa_circ_0071106, hsa_circ_0000284, hsa_circ_0071271, hsa-miR-29a-5p, hsa-miR-3690, hsa-miR-607, lncRNA MEG3 and lncRNA TUG1were higher in T2DM (all P < 0.05). The AUCs of hsa_circ_0071106, hsa-miR-607 and lncRNA TUG1 for diagnosis of T2DM were 0.563,0.645 and 0.642, respectively. The combined AUC of hsa-miR-607, lncRNA TUG1 and hsa_circ_0071106 was 0.798 ([0.720~0.875], P < 0.001). Moreover, the sensitivity of combined diagnosis was 75.2% and the specificity was 100.0%. The levels of lncRNA TUG1, hsa-miR-607 and hsa_circ_0071106 in peripheral blood have potential clinical diagnostic value for T2DM.

Microglial HO‐1 regulates iron metabolism in the brain. Intracerebral haemorrhage (ICH) shares features of ferroptosis and necroptosis; hemin is an oxidized product of haemoglobin from lysed red blood cells, leading to secondary injury. However, little is known about the underlying molecular mechanisms attributable to secondary injury by hemin or ICH. In this study, we first show that FoxO3a was highly co‐located with neurons and microglia but not astrocytes area of ICH model mice. Hemin activated FoxO3a/ATG‐mediated autophagy and HO‐1 signalling resulting in ferroptosis in vitro and in a mice model of brain haemorrhage. Accordingly, autophagy inhibitor Baf‐A1 or HO‐1 inhibitor ZnPP protected against hemin‐induced ferroptosis. Hemin promoted ferroptosis of neuronal cells via FoxO3a/ATG‐mediated autophagy and HO‐1 signalling pathway. Knock‐down of FoxO3a inhibited autophagy and prevented hemin‐induced ferroptosis dependent of HO‐1 signalling. We first showed that hemin stimulated microglial FoxO3a/HO‐1 expression and enhanced the microglial polarisation towards the M1 phenotype, while knockdown of microglial FoxO3a inhibited pro‐inflammatory cytokine production in microglia. Furthermore, the microglia activation in the striatum showed significant along with a high expression level of FoxO3a in the ICH mice. We found that conditional knockout of FoxO3a in microglia in mice alleviated neurological deficits and microglia activation as well as ferroptosis‐induced striatum injury in the autologous blood‐induced ICH model. We demonstrate, for the first time, that FoxO3a/ATG‐mediated autophagy and HO‐1 play an important role in microglial activation and ferroptosis‐induced striatum injury of ICH, identifying a new therapeutic avenue for the treatment of ICH.