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Oxidative stress from environmental exposures is thought to play a role in neurodevelopmental disorders; therefore, understanding the underlying molecular regulatory network is essential for mitigating its impacts. In this study, we analysed the competitive endogenous RNA (ceRNA) network mediated by circRNAs, a novel class of regulatory molecules, in an SH-SY5Y cell model of oxidative stress, both prior to and during neural differentiation, using RNA sequencing and in silico analysis. We identified 146 differentially expressed circRNAs, including 93 upregulated and 53 downregulated circRNAs, many of which were significantly co-expressed with mRNAs that potentially interact with miRNAs. We constructed a circRNA–miRNA–mRNA network and identified 15 circRNAs serving as hubs within the regulatory axes, with target genes enriched in stress- and neuron-related pathways, such as signaling by VEGF, axon guidance, signaling by FGFR, and the RAF/MAP kinase cascade. These findings provide insights into the role of the circRNA-mediated ceRNA network in oxidative stress during neuronal differentiation, which may help explain the regulatory mechanisms underlying neurodevelopmental disorders associated with oxidative stress. [ABSTRACT FROM AUTHOR]

Oxidative stress is one of the most important environmental exposures associated with psychiatric disorders, but the underlying molecular mechanisms remain to be elucidated. In a previous study, we observed a substantial alteration of the gene expression landscape in neuron-like cells that were differentiated from SH-SY5Y cells after or during exposure to oxidative stress, with a subset of dysregulated genes being enriched for neurodevelopmental processes. To further explore the regulatory mechanisms that might account for such profound perturbations, we have now applied small RNA-sequencing to investigate changes in the expression of miRNAs. These molecules are known to play crucial roles in brain development and response to stress through their capacity to suppress gene expression and influence complex biological networks. Through these analyses, we observed more than a hundred differentially expressed miRNAs, including 80 previously reported to be dysregulated in psychiatric disorders. The seven most influential miRNAs associated with pre-treatment exposure, including miR-138-5p, miR-96-5p, miR-34c-5p, miR-1287-5p, miR-497-5p, miR-195-5p, and miR-16-5p, supported by at least 10 negatively correlated mRNA connections, formed hubs in the interaction network with 134 genes enriched with neurobiological function, whereas in the co-treatment condition, miRNA-mRNA interaction pairs were enriched in cardiovascular and immunity-related disease ontologies. Interestingly, 12 differentially expressed miRNAs originated from the DLK1-DIO3 location, which encodes a schizophrenia-associated miRNA signature. Collectively, our findings suggest that early exposure to oxidative stress, before and during prenatal neuronal differentiation, might increase the risk of mental illnesses in adulthood by disturbing the expression of miRNAs that regulate neurodevelopmentally significant genes and networks. [ABSTRACT FROM AUTHOR]

Groebke-Blackburn-Bienayme reaction has been utilized for the synthesis of new imidazo[1,2- a]pyrimidine derivatives as novel anticancer agents. The cytotoxic activities of compounds were evaluated against human cancer cell lines including MCF-7, T-47D, and MDA- MB-231, compared with etoposide as the standard drug. Among the tested compounds, hydroxy- and/or methoxy-phenyl derivatives ( 6a-c and 6k) with IC50 values of 6.72-14.36 μ m were more potent than etoposide against all cell lines. The acridine orange/ethidium bromide double staining and DNA fragmentation studies demonstrated that the cytotoxic effect of 3-hydroxy-4-methoxyphenyl derivative 6c is associated with apoptosis in cancer cells. [ABSTRACT FROM AUTHOR]