👤 Isaac Subirana

In this study, we investigated gene expression related to cholesterol efflux receptors in individuals at high cardiovascular risk undergoing Mediterranean dietary interventions. Through transcriptomic analysis, we examined samples from two randomized controlled trials: PREDIMED and PREDIMED-Plus, with 151 and 89 elderly adults, respectively. Blood cells were isolated at baseline and after a 12-month intervention. In the PREDIMED trial, participants followed different Mediterranean diets: one supplemented with extra-virgin olive oil (traditional Mediterranean diet enriched with extra-virgin olive oil [MedDiet-EVOO]), another with nuts (MedDiet enriched with nuts MedDiet-Nuts [MedDiet-Nuts]), and a low-fat control diet. The PREDIMED-Plus trial compared an energy-reduced Mediterranean diet (Er-MedDiet) with physical activity to an ad libitum Mediterranean diet. Over time, mild but significant upregulation of genes like ATP binding cassette subfamily A member 1 (ABCA1), retinoid X receptor alpha (RXRA), retinoid X receptor beta (RXRB), and Nuclear Receptor Subfamily 1 Group H Member 3 (NR1H3) was observed in response to MedDiet-EVOO, MedDiet-Nuts, and Er-MedDiet. Notably, RXRA expression was higher in both MedDiet-EVOO and MedDiet-Nuts compared to the control diet. Differences in gene expression, particularly RXRA, ATP binding cassette subfamily G member 1 (ABCG1), NR1H3, and Peroxisome Proliferator Activated Receptor Delta (PPARD), were evident between MedDiet-Nuts and the control diet. In the PREDIMED-Plus trial, no significant differences in gene expression were found between dietary groups. Principal component analysis (PCA) and linear discriminant analysis (LDA) showed overlapping gene expression profiles across different Mediterranean diet interventions. In conclusion, our study highlights the cardiovascular health benefits of long-term adherence to a Mediterranean diet, both normocaloric and hypocaloric, primarily reflected by mild upregulation of cholesterol efflux-related genes-specifically involving RXRA, RXRB, ABCA1, ABCG1, Nuclear Receptor Subfamily 1 Group H Member 2(NR1H2), and PPARD-among elderly adults at high cardiovascular risk. This suggests a potential mechanism by which these diets may exert cardiovascular protective effects. Show less

Upon environmental changes, proliferating cells delay cell cycle to prevent further damage accumulation. Yeast Cip1 is a Cdk1 and Cln2-associated protein. However, the function and regulation of Cip1 are still poorly understood. Here we report that Cip1 expression is co-regulated by the cell-cycle-mediated factor Mcm1 and the stress-mediated factors Msn2/4. Overexpression of Cip1 arrests cell cycle through inhibition of Cdk1-G1 cyclin complexes at G1 stage and the stress-activated protein kinase-dependent Cip1 T65, T69, and T73 phosphorylation may strengthen the Cip1and Cdk1-G1 cyclin interaction. Cip1 accumulation mainly targets Cdk1-Cln3 complex to prevent Whi5 phosphorylation and inhibit early G1 progression. Under osmotic stress, Cip1 expression triggers transient G1 delay which plays a functionally redundant role with another hyperosmolar activated CKI, Sic1. These findings indicate that Cip1 functions similarly to mammalian p21 as a stress-induced CDK inhibitor to decelerate cell cycle through G1 cyclins to cope with environmental stresses.A G1 cell cycle regulatory kinase Cip1 has been identified in budding yeast but how this is regulated is unclear. Here the authors identify cell cycle (Mcm1) and stress-mediated (Msn 2/4) transcription factors as regulating Cip1, causing stress induced CDK inhibition and delay in cell cycle progression. Show less