Notes

[Research progress upon recognition of 2-acetyl-1-pyrroline, the actual characteristic fragrance element of great smelling rice].
Transcription factor (TF)-mediated regulation of genes is often disrupted during carcinogenesis. The DNA methylation state of TF-binding sites may dictate transcriptional activity of corresponding genes. Stilbenoid polyphenols, such as pterostilbene (PTS), have been shown to exert anticancer action by remodeling DNA methylation and gene expression. However, the mechanisms behind these effects still remain unclear. Here, the dynamics between oncogenic TF OCT1 binding and de novo DNA methyltransferase DNMT3B binding in PTS-treated MCF10CA1a invasive breast cancer cells has been explored. Using chromatin immunoprecipitation (ChIP) followed by next generation sequencing, we determined 47 gene regulatory regions with decreased OCT1 binding and enriched DNMT3B binding in response to PTS. Most of those genes were found to have oncogenic functions. We selected three candidates, PRKCA, TNNT2, and DANT2, for further mechanistic investigation taking into account PRKCA functional and regulatory connection with numerous cancer-driving processes and pathways, and some of the highest increase in DNMT3B occupancy within TNNT2 and DANT2 enhancers. PTS led to DNMT3B recruitment within PRKCA, TNNT2, and DANT2 at loci that also displayed reduced OCT1 binding. selleck inhibitor Substantial decrease in OCT1 with increased DNMT3B binding was accompanied by PRKCA promoter and TNNT2 and DANT2 enhancer hypermethylation, and gene silencing. Interestingly, DNA hypermethylation of the genes was not detected in response to PTS in DNMT3B-CRISPR knockout MCF10CA1a breast cancer cells. It indicates DNMT3B-dependent methylation of PRKCA, TNNT2, and DANT2 upon PTS. Our findings provide a better understanding of mechanistic players and their gene targets that possibly contribute to the anticancer action of stilbenoid polyphenols.Omega (n)-3 polyunsaturated fatty acids (PUFA) are known to regulate lipid metabolism and inflammation; however, the regulation of maternal lipid metabolism and cytokines profile by n-3 PUFA during different gestation stages, and its impact on fetal sustainability is not known. We investigated the effects of maternal diet varying in n-3 PUFA prior to, and during gestation, on maternal metabolic profile, placental inflammatory cytokines, and fetal outcomes. Female C57BL/6 mice were fed either a high, low or very low (9, 3 or 1% w/w n-3 PUFA) diet, containing n-6n-3 PUFA of 51, 201 and 401, respectively for two weeks before mating, and throughout pregnancy. Animals were sacrificed prior to mating (NP), and during pregnancy at gestation days 6.5, 12.5 and 18.5. Maternal metabolic profile, placental cytokines and fetal outcomes were determined. Our results show for the first time that a maternal diet high in n-3 PUFA prevented dyslipidemia in NP mice, and maintained the expected lipid profile during pregnancy. However, females fed the very low n-3 PUFA diet became hyperlipidemic prior to pregnancy, and carried this profile into pregnancy. Maternal diet high in n-3 PUFA maintained maternal plasma progesterone and placental pro-inflammatory cytokines profile, and sustained fetal numbers throughout pregnancy, while females fed the low and very-low n-3 PUFA diet had fewer fetuses. Our findings demonstrate the importance of maternal diet before, and during pregnancy, to maintain maternal metabolic profile and fetus sustainability. These findings are important when designing dietary strategies to optimize maternal metabolism during pregnancy for successful pregnancy outcome.The current study aimed to find neural evidence that trait anxiety interferes with one's shifting function processing efficiency. Twenty-five high trait-anxiety (HTA) and twenty-five low trait-anxiety (LTA) participants were instructed to complete a cue-based Stroop task-switching assessment of shifting function. No group difference in behavioral performance was shown, though event-related potential (ERP) results in the cue-locked period showed that only the LTA group had a general switch benefit in contingent negative variation (CNV) amplitude, indicating the LTA group exerted less task preparation effort. In the subsequent target-locked period, compared to the LTA group, the local switch cost of target-P3 was higher in the HTA group in incompatible trials, suggesting inefficient attentional resource allocation in the HTA group in incompatible trials. These ERP findings indicated that the HTA group ultimately achieved comparable behavioral performance with the LTA group at the expense of using more compensatory strategies at the neural level.Methylmercury (MeHg) is a environmental contaminant, which can induce neurotoxic effects. So far, the exact molecular mechanisms of autophagy and its effect on apoptosis in MeHg-induced neurotoxicity have not been elucidated. Here, rats were exposed to MeHg (4, 8, or 12 μmol/kg) for 4 weeks to evaluate the dose-effect relationship between MeHg and apoptosis, or autophagy in cerebral cortex. On this basis, rapamycin (Rapa) or 3-methyladenine (3-MA) was administrated to further explore the regulatory mechanisms of autophagy on MeHg-induced neuronal apoptosis. The pathological changes, autophagy or apoptosis levels, expression of autophagic or apoptotic-associated factors such as mTOR, S6K1, 4EBP1, Vps34, Beclin1, p62, LC3, Bcl-2/Bax, caspase, or MAPKs were investigated. Results showed that MeHg dose-dependently induced pathological changes in cerebral cortex, and the levels of autophagy and apoptosis were increased. Furthermore, Rapa pretreatment antagonized MeHg-induced apoptosis, whereas 3-MA further aggravated apoptosis, which were supported by findings that Rapa activated mTOR-mediated autophagy while 3-MA inhibited Vps34-related autophagy, further affect neuronal apoptosis through regulation of apoptotic factors mentioned above. In conclusion, the findings indicated that MeHg dose-dependently induced autophagy or apoptosis, and mTOR or Vps34 may play important roles in mediating autophagy, which further regulated apoptosis through MAPKs or mitochondrial apoptosis pathways.Aluminum (Al), as a common environmental pollutant, causes osteoblast (OB) dysfunction and then leads to Al-related bone diseases (ARBD). One of the mechanisms of ARBD is oxidative stress, which leads to an increase in the production of reactive oxygen species (ROS). ROS can induce mitochondrial damage, thereby inducing mitophagy and apoptosis. But whether mitophagy and apoptosis mediated by ROS, and the role of ROS in AlCl3-induced MC3T3-E1 cell dysfunction is still unclear. In this study, MC3T3-E1 cells used 0 mM Al (control group), 2 mM Al (Al group), 5 mM N-acetyl cysteine (NAC) (NAC group), 2 mM Al and 5 mM NAC (Al + NAC group) for 24 h. We found AlCl3-induced MC3T3-E1 cell dysfunction accompanied by oxidative stress, apoptosis, and mitophagy. While NAC, a ROS scavenger treatment, restored cell function and alleviated the mitophagy and apoptosis. These results suggested that mitophagy and apoptosis mediated by ROS participate in AlCl3-induced MC3T3-E1 cell dysfunction.
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