Resveratrol (RSV) has been reported to induce autophagy and apoptosis in non-small-cell lung cancer A549 cells, and the nerve growth factor receptor (NGFR) regulates autophagy and apoptosis in many other cells. However, the effect of NGFR on autophagy and apoptosis induced by RSV in A549 cells remains unclear. Here, we found that RSV reduced the cell survival rate in time- and concentration-dependent manners, activating autophagy and apoptosis. Lethal autophagy was triggered by RSV higher than 55 μM. The relationship between autophagy and apoptosis depended on the type of autophagy. Specifically, mutual promotion was observed between apoptosis and lethal autophagy. Conversely, cytoprotective autophagy facilitated apoptosis but was unaffected by apoptosis. RSV enhanced NGFR by increasing mRNA expression and prolonging the lifespan of NGFR mRNA and proteins. RSV antagonized the enhanced autophagy and apoptosis caused by NGFR knockdown. As the downstream pathway of NGFR, AMPK-mTOR played a positive role in RSV-induced autophagy and apoptosis. Overall, RSV-induced autophagy and apoptosis in A549 cells are regulated by the NGFR-AMPK-mTOR signaling pathway.

Resveratrol (RSV) has been reported to exhibit cytotoxic activity in multiple types of malignant cells; however, the mechanisms underlying the antitumor effects of RSV in non-small-cell lung cancer (NSCLC) cells remain undetermined. Combining bioinformatics analysis with experimental validation, the present study aimed to examine the effects of RSV on the apoptosis and autophagy of A549 NSCLC cells, and to determine the potential underlying molecular mechanisms. Bioinformatics analysis was used to determine the differentially expressed genes (DEGs) and identify the enriched biological functions and pathways associated with these DEGs following RSV treatment. Cell viability was determined by MTT assay, and flow cytometry and TUNEL assay were used to evaluate cell apoptosis. Monodansylcadaverine staining combined with a transmission electron microscope were used to evaluate the extent of autophagy. The expression levels of apoptosis-, autophagy-, or pathway-associated molecular markers were measured by reverse transcription-quantitative PCR and/or western blot analysis. By bioinformatics analysis, a total of 1,031 DEGs were identified in the RSV-treated A549 cells, which were enriched in apoptosis-, or autophagy-related biological functions and the p53 signaling pathway. In validation experiments, RSV significantly reduced cell viability and initiated apoptosis, with an increase in the number of apoptotic cells; it also upregulated cleaved caspase-3 expression and Bax expression, and downregulated the Bcl-2 expression levels. Additionally, there was an increase in the accumulation of green dot-like structures, indicative of autophagic vesicles, observed under a fluorescence microscope, and an increase in the presence of autophagic vacuoles observed using a transmission electron microscope following RSV treatment. Furthermore, the expression levels of the autophagy-related proteins, LC3-II/LC3-I and Beclin-1, were increased and p62 expression was decreased. 3-methyladenine (3-MA), an inhibitor of autophagy, partially reversed the RSV-induced cytotoxic effects, but did not significantly alter the number of apoptotic cells. RSV elevated the p53 levels and decreased the phosphorylated (p-)Mdm2 and p-Akt levels. Pifithrin-α, an inhibitor of p53, partially reduced RSV-induced apoptosis and autophagy. On the whole, the results of the present study demonstrated that RSV initiates the apoptosis and autophagic death of A549 cells via the activation of the p53 signaling pathway, further highlighting the potential of RSV for the treatment of NSCLC.

Background Diet, as a modifiable factor, plays an important role in cognitive function. However, the association between adherence to the 2015–2020 Dietary Guidelines for Americans (DGA), measured by Healthy Eating Index (HEI)-2015, and cognitive function remains unclear. This study aims to explore whether HEI-2015 is associated with various cognitive domains and whether such association is modified by age, gender, or ethnicity in the US adults aged 60 years or older using data from the National Health and Nutrition Examination Survey (NHANES) 2011–2014. Methods HEI-2015 scores were calculated from 24-h dietary recall interviews. Cognitive function was evaluated by Digit Symbol Substitution Test (DSST, a measure of processing speed), Animal Fluency Test (AFT, a measure of executive function), a subtest from Consortium to Establish a Registry for Alzheimer’s disease (CERAD, a measure of memory), and a composite-z score calculated by summing z scores of individual tests. The associations between HEI-2015 scores and cognitive performance were explored using multiple linear regression models. Results A total of 2450 participants aged 60 years or older were included. Participants with higher HEI-2015 scores were more likely to have higher DSST, AFT as well as composite-z scores (P<0.05). Significant interaction effects were identified between HEI-2015 and ethnicity in specific cognitive domains (Pinteraction<0.05). Among HEI-2015 components, higher intakes of whole fruits and seafood and plant protein were associated with better cognitive performance (P<0.05). Conclusion Higher adherence to DGA is associated with better cognitive performance, especially regarding processing speed and executive function among the US adults aged 60 years or older.

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