Dynamic Changes of Fetal-Derived Hypermethylated RASSF1A and Septin 9 Sequences in Maternal Plasma.

DNA methylation has a tissue-specific feature, and placenta has distinct methylation patterns from peripheral blood cells. Although fetal/placental-derived cell free DNA (cfDNA) in the maternal blood has been reported in recent decades, systematic exploration of dynamic changes of the placental epigenetic signatures across gestation is lacking. The primary goal of this study was to characterize prenatal and postnatal methylation levels of placental-sourced RASSF1A and Septin 9 sequences in maternal plasma. Here, we used a quantitative methylation-sensitive PCR (qMS-PCR) assay to check the methylation status of RASSF1A and Septin 9 in placental tissues of pregnant women and plasma samples from non-pregnant individuals. Then, we examined the methylation levels of the two targets in maternal plasma from expectant women at different gestational ages and postdelivery. Hypermethylated RASSF1A and Septin 9 were identified in placental samples but undetectable in peripheral blood of healthy non-pregnant women. Further, hypermethylated RASSF1A sequence was found in all three trimesters of pregnancy except for early gestation (8 weeks). Moreover, methylation scores of the two targets increased as pregnancy progressed. In addition, hypermethylated RASSF1A sequence was detectable in maternal plasma from 12 h (one case) to 24 h postdelivery (three cases) in 18 pregnant women. Our data on the variation of fetal-sourced methylated RASSF1A levels in maternal plasma in relation to gestational age provide a useful basis for improving the reliability of the methylation assay for non-invasive prenatal diagnosis (NIPD) in clinical practice.

Scorpion Venom Heat-Resistant Peptide is Neuroprotective against Cerebral Ischemia-Reperfusion Injury in Association with the NMDA-MAPK Pathway.

Scorpion venom heat-resistant peptide (SVHRP) is a component purified from Buthus martensii Karsch scorpion venom. Our previous studies have shown that SVHRP is neuroprotective in models of Alzheimer's disease and Parkinson's disease. The present study aimed to explore the potential neuroprotective effects of SVHRP on cerebral ischemia/reperfusion (I/R) injury, using a mouse model of middle cerebral artery occlusion/reperfusion (MCAO/R) and a cellular model of oxygen-glucose deprivation/reoxygenation (OGD/R). Our results showed that SVHRP treatment decreased the neurological deficit scores, edema formation, infarct volume and neuronal loss in the MCAO/R mice, and protected primary neurons against OGD/R insult. SVHRP pretreatment suppressed the alterations in protein levels of N-methyl-D-aspartate receptors (NMDARs) and phosphorylated p38 MAPK as well as some proinflammatory factors in both the animal and cellular models. These results suggest that SVHRP has neuroprotective effects against cerebral I/R injury, which might be associated with inhibition of the NMDA-MAPK-mediated excitotoxicity.