Reduce negative life events to Increase satisfaction: A daily diary study on the relationship between negative life events and life satisfaction.

Life satisfaction refers to an individual' s cognitive evaluation of the overall quality of their life considering the various aspects therein. Although the existing research has demonstrated the between-person relationship between negative life events and life satisfaction based on retrospective measures, less is known about this relationship at the within-person level. A daily diary method could examine this within-person relationship and decrease systematic recall biases. Therefore, this study investigated the link between daily negative life events and daily life satisfaction, as well as the mediating role of perceived stress and the moderating role of trait rumination in 146 young adults (Mage = 20.75, SD = 1.35) using a 14-day daily diary design. Multilevel regression analysis showed that daily negative life events had negative predictive effects on daily life satisfaction. In addition, the multilevel 1-1-1 mediation analysis indicated that daily perceived stress mediated the association between daily negative life events and daily life satisfaction. More importantly, the mediating effect of perceived stress was moderated by trait rumination, with the within-person mediating effect being stronger for individuals with higher than those with lower trait rumination tendencies. These findings contribute to the understanding of the underlying pathways in the relationship between daily negative life events and daily life satisfaction and provide a new perspective for improving individuals' life satisfaction.

Xanthatin suppresses proliferation and tumorigenicity of glioma cells through autophagy inhibition via activation of the PI3K-Akt-mTOR pathway.

Glioma is the most common and aggressive primary brain tumor in adults with high morbidity and mortality. Rapid proliferation and diffuse migration are the main obstacles to successful glioma treatment. Xanthatin, a sesquiterpene lactone purified from Xanthium strumarium L., possesses a significant antitumor role in several malignant tumors. In this study, we report that xanthatin suppressed glioma cells proliferation and induced apoptosis in a time- and concentration-dependent manner, and was accompanied by autophagy inhibition displaying a significantly reduced LC3 punctate fluorescence and LC3II/I ratio, decreased level of Beclin 1, while increased accumulation of p62. Notably, treating glioma cells with xanthatin resulted in obvious activation of the PI3K-Akt-mTOR signaling pathway, as indicated by increased mTOR and Akt phosphorylation, decreased ULK1 phosphorylation, which is important in modulating autophagy. Furthermore, xanthatin-mediated pro-apoptosis in glioma cells was significantly reversed by autophagy inducers (rapamycin or Torin1), or PI3K-mTOR inhibitor NVP-BEZ235. Taken together, these findings indicate that anti-proliferation and pro-apoptosis effects of xanthatin in glioma are most likely by inhibiting autophagy via activation of PI3K-Akt-mTOR pathway, suggesting a potential therapeutic strategy against glioma.

Genipin protects against mitochondrial damage of the retinal pigment epithelium under hyperglycemia through the AKT pathway mediated by the miR-4429/JAK2 signaling axis.

Background: To investigate the protective effect and mechanism of genipin (GE) on mitochondrial damage in retinal pigment epithelial (RPE) cells induced by high glucose. Methods: Differential genes of GE in the treatment of diabetic retinopathy (DR) were screened by the Gene Expression Omnibus (GEO) database. Differential genes located in the AKT pathway were obtained. TargetScan, miRDB, and DIANA databases were used to predict the targeted microRNAs (miRNAs) of differential genes. A high-fat diet combined with streptomycin (STZ) intraperitoneal injection were used to establish a diabetic mouse model. Diabetic mice were treated with GE by intragastric administration. The functional and molecular changes of the retina were detected by electroretinogram (ERG) and reverse transcription-polymerase chain reaction (RT-PCR). ARPE-19 cells were cultured under hyperglycemic conditions with AKT and JAK2 inhibitors. MiR-4429 was knocked down/overexpressed to detect changes in cell function, activity, and mitochondrial function. The dual luciferase reporter assay confirmed the targeted binding of miR-4429 with JAK2. Results: Bioinformatics analysis finally yielded JAK2 as the research target gene. miR-4429 was predicted to be the targeted miRNA of JAK2 by online databases. The results of animal experiments showed that the retinal function of mice recovered after GE administration (P<0.05), the expression of AKT and miR-4429 in RPE cells was significantly increased (P<0.05), and the expression of JAK2 was significantly decreased (P<0.05). The results of cell experiments showed that the functions of cells and mitochondria recovered after the addition of GE under hyperglycemia (P<0.05). Cell and mitochondrial functions were decreased after the addition of AKT inhibitor (P<0.05). Overexpression of miR-4429 or inhibition of JAK2 increased cell activity and mitochondrial function (P<0.05). The results of the dual luciferase reporter assay showed that miR-4429 had a targeted binding site with JAK2. Conclusions: GE protects ARPE-19 cell functional activity, inflammatory responses, and mitochondrial damage by promoting the AKT signaling pathway and regulating the expression of the miR-4429/JAK2 signaling axis.

Xanthatin induces glioma cell apoptosis and inhibits tumor growth via activating endoplasmic reticulum stress-dependent CHOP pathway.

Xanthatin is a natural sesquiterpene lactone purified from Xanthium strumarium L., which has shown prominent antitumor activity against a variety of cancer cells. In the current study, we investigated the effect of xanthatin on the growth of glioma cells in vitro and in vivo, and elucidated the underlying mechanisms. In both rat glioma C6 and human glioma U251 cell lines, xanthatin (1-15 µM) dose-dependently inhibited cell viability without apparent effect on the cell cycle. Furthermore, xanthatin treatment dose-dependently induced glioma cell apoptosis. In nude mice bearing C6 glioma tumor xenografts, administration of xanthatin (10, 20, 40 mg·kg-1·d-1, ip, for 2 weeks) dose-dependently inhibited the tumor growth, but did not affect the body weight. More importantly, xanthatin treatment markedly increased the expression levels of the endoplasmic reticulum (ER) stress-related markers in both the glioma cell lines as well as in C6 xenografts, including glucose-regulated protein 78, C/EBP-homologous protein (CHOP), activating factor 4, activating transcription factor 6, spliced X-box binding protein-1, phosphorylated protein kinase R-like endoplasmic reticulum kinase, and phosphorylated eukaryotic initiation factor 2a. Pretreatment of C6 glioma cells with the ER stress inhibitor 4-phenylbutyric acid (4-PBA, 7 mM) or knockdown of CHOP using small interfering RNA significantly attenuated xanthatin-induced cell apoptosis and increase of proapoptotic caspase-3. These results demonstrate that xanthatin induces glioma cell apoptosis and inhibits tumor growth via activating the ER stress-related unfolded protein response pathway involving CHOP induction. Xanthatin may serve as a promising agent in the treatment of human glioma.