N 6-methyladenosine modification contributes to respiratory syncytial virus infection.

Background: Respiratory syncytial virus (RSV) is the second leading cause of death due to lower respiratory tract infections. Effective prevention and treatment measures are lacking, posing a huge socioeconomic burden to the world. N 6-methyladenosine (m6A) is the most common internal modification in messenger RNA and noncoding RNA. Numerous recent studies have shown that the dysregulation of m6A modification is associated with diseases caused by pathogenic viruses. Methods: The changes in m6A modification were evaluated using m6A RNA methylation assay. The differences in gene expression levels of various m6A-modifying enzymes were observed using Quantitative Real-time PCR (qRT-PCR) during RSV infection. The autophagosomes were observed using transmission electron microscopy, and the expression of autophagy-associated protein Microtubule Associated Protein 1 Light Chain 3 Beta Ⅱ/Ⅰ (LC3B Ⅱ/Ⅰ) and Beclin1 in Human Normal Lung Epithelial Cells (BEAS-2B) cells using Western blot during RSV infection. The significantly differentially expressed genes were screened guided by bioinformatics. Their relationship with m6A-modifying enzymes was analyzed through protein-protein interaction network and expression correlation analysis. Results: The m6A abundance decreased and demethylase Fat Mass and Obesity- Associated Protein (FTO) significantly increased during RSV infection after 24 h. We also found that the DNA Damage-Inducible Transcript 3 Protein (DDIT3) level significantly increased during RSV infection after 24 h and observed autophagosomes in BEAS-2B cells. In addition, RSV infection could cause the upregulation of LC3B Ⅱ/Ⅰ and Beclin1. The expression correlation analysis showed that DDIT3 levels were positively correlated with the FTO level, and Methyltransferase Like 3 (METTL3), RNA Binding Motif Protein 15B (RBM15B), YTH Domain-Containing Family Protein 1 (YTHDF1), and levels were negatively correlated with the DDIT3 level. Conclusions: We uncovered a significant role for m6A modification during RSV infection. Also, a correlation was found between m6A and autophagy, providing new ideas for therapeutic advancements in RSV treatment.

Docosahexaenoic acid and phosphatidylserine improves the antioxidant activities in vitro and in vivo and cognitive functions of the developing brain.

Fish oil during early postnatal period may modulate the impact of oxidative stress in the developing brain and thus improve memory and cognitive behaviour. This study investigated the impacts of docosahexaenoic acid (DHA, C22:6, n-3) and/or phosphatidylserine (PS) on antioxidant activities in vitro, and the beneficial effects of feeding with DHA and/or PS on antioxidant activities in brain and liver tissues and on the cognitive functions of the developing brain. Results indicated that DHA and/or PS significantly enhanced antioxidant activities and increased cell viabilities in vitro. Feeding with DHA and/or PS supplementation not only significantly improved escape latency of animals, but it also improved the oxidative parameters in the brain, enhanced glutathione peroxidase activity as well as reduced nitric mono-oxide levels in the liver. DHA and PS may serve to protect cells from oxidative stress and further improve learning and memory ability in vivo.

Docosahexaenoic acid and phosphatidylserine supplementations improve antioxidant activities and cognitive functions of the developing brain on pentylenetetrazol-induced seizure model.

Epilepsy provoked by pentylenetetrazol (PTZ) is caused by an abnormal excitatory postsynaptic potential, which results in increased production of reactive oxygen species, and finally reducing cognitive functions. The objective of this study was to investigate the effects of dietary supplementation with DHA and PS, administered either alone or in combination, on oxidative stress and behavioral and cognitive spatial memory in neonatal rats with PTZ-induced epileptic seizure. In this study, rat pups received repetitive doses of PTZ for induction of epileptic seizure and docosahexaenoic acid (DHA, C22:6, n-3) and phosphatidylserine (PS) were orally administrated alone or together to the PTZ-induced epileptic animals daily for 36 d. The spatial memory, nitric mono-oxide (NO) production, and enzymatic activities of superoxide dismutase (SOD) and catalase in brain and liver tissues were determined. PTZ administration significantly reduced the cell numbers in the hippocampus, shortened the escape latency in the safe target region, decreased activities of SOD and catalase, but increased NO content in both brain and liver tissues, while DHA and PS significantly extended the escape latency, reversed the oxidative parameters observed in the brain, and enhanced SOD activity in the liver. Dietary supplementation with DHA and PS may protect brain tissue from the oxidative stress caused by epileptic seizures and could serve to improve learning and memory ability in vivo.