RESUMO
BACKGROUND: Non-restorative sleep (NRS) is a core symptom of insomnia that has considerable consequences for daily life. However, the association between NRS and psychotic-like experiences (PLEs) remains unclear. The current study was designed to explore the relationship between NRS and PLEs as well as the mediation/moderation role of rumination and resilience among college students in China. METHODS: 3060 college students were recruited from two universities in South China from September 21st to October 26th, 2022. Non-restorative Sleep Scale, 8-item Positive Subscale of the Community Assessment of Psychic Experiences, Ruminative Response Scale, and 10-item Connor-Davidson Resilience Scale were administered. Latent profile analysis and moderated mediation analysis were performed. RESULTS: 11.3 % participants reported frequent PLEs in the past one month. Three profiles of rumination were identified and named as "low rumination" group (27.7 %), "medium rumination" group (55.3 %), and "high rumination" group (16.9 %). NRS directly predicted PLEs, and rumination played a significant mediation role between NRS and PLEs. Resilience significantly moderated the association between NRS and rumination as well as the association between NRS and PLEs. CONCLUSIONS: NRS, rumination and resilience are important predictors to PLEs. Strategies on increasing restorative sleep, decreasing rumination, and enhancing resilience are of great significance in the prevention of PLEs.
RESUMO
BACKGROUND: N6 -methyladenosine (m6A) is of great importance in renal physiology and disease progression, but its function and mechanism in renal fibrosis remain to be comprehensively and extensively explored. Hence, this study will explore the function and potential mechanism of critical regulator-mediated m6A modification during renal fibrosis and thereby explore promising anti-renal fibrosis agents. METHODS: Renal tissues from humans and mice as well as HK-2 cells were used as research subjects. The profiles of m6A modification and regulators in renal fibrosis were analysed at the protein and RNA levels using Western blotting, quantitative real-time polymerase chain reaction and other methods. Methylation RNA immunoprecipitation sequencing and RNA sequencing coupled with methyltransferase-like 3 (METTL3) conditional knockout were used to explore the function of METTL3 and potential targets. Gene silencing and overexpression combined with RNA immunoprecipitation were performed to investigate the underlying mechanism by which METTL3 regulates the Ena/VASP-like (EVL) m6A modification that promotes renal fibrosis. Molecular docking and virtual screening with in vitro and in vivo experiments were applied to screen promising traditional Chinese medicine (TCM) monomers and explore their mechanism of regulating the METTL3/EVL m6A axis and anti-renal fibrosis. RESULTS: METTL3 and m6A modifications were hyperactivated in both the tubular region of fibrotic kidneys and HK-2 cells. Upregulated METTL3 enhanced the m6A modification of EVL mRNA to improve its stability and expression in an insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2)-dependent manner. Highly expressed EVL binding to Smad7 abrogated the Smad7-induced suppression of transforming growth factor-ß (TGF-ß1)/Smad3 signal transduction, which conversely facilitated renal fibrosis progression. Molecular docking and virtual screening based on the structure of METTL3 identified a TCM monomer named isoforsythiaside, which inhibited METTL3 activity together with the METTL3/EVL m6A axis to exert anti-renal fibrosis effects. CONCLUSIONS: Collectively, the overactivated METTL3/EVL m6A axis is a potential target for renal fibrosis therapy, and the pharmacological inhibition of METTL3 activity by isoforsythiaside suggests that it is a promising anti-renal fibrosis agent.
