The widespread expression of circular RNAs (circRNAs) is regarded as a feature of gene expression in highly diverged eukaryotes. Recent studies have shown that circRNAs can act as a miRNA sponge to repress miRNA function, participate in splicing of target genes, translate genes into protein and interact with RNA binding proteins (RBPs). RBPs are a broad class of proteins involved in gene transcription and translation, and interaction with RBPs is considered an important part of circRNA function, which can serve as an essential element underlying the functions of circRNAs, including genesis, translation, transcriptional regulation of target genes, and extracellular transport. In this mini‐review, we attempt to explore in detail the relationship between circRNAs and RBPs, and the interactions between the two factors. The goal of this review is to investigate the emerging studies of RBPs and circRNAs to better understand how their interaction alters cellular function.

Designing translational antioxidative agents that could scavenge free radicals produced during reperfusion in brain ischemia stroke and alleviate neurologic damage is the main objective for ischemic stroke treatment. Herein, we explored and simply synthesized a biomimic and translational Mn3O4 nanoenzyme (HSA-Mn3O4) to constrain ischemic stroke reperfusion-induced nervous system injury. This nanosystem exhibits reduced levels of inflammation and prolonged circulation time and potent ROS scavenging activities. As expected, HSA-Mn3O4 effectively inhibits oxygen and glucose deprivation-mediated cell apoptosis and endoplasmic reticulum stress and demonstrates neuroprotective capacity against ischemic stroke and reperfusion injury of brain tissue. Furthermore, HSA-Mn3O4 effectively releases Mn ions and promotes the increase of superoxide dismutase 2 activity. Therefore, HSA-Mn3O4 inhibits brain tissue damage by restraining cell apoptosis and endoplasmic reticulum stress in vivo. Taken together, this study not only sheds light on design of biomimic and translational nanomedicine but also reveals the neuroprotective action mechanisms against ischemic stroke and reperfusion injury.

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Background: Acute ischemic stroke (AIS) is a leading cause of disability and mortality worldwide. Prediction of penumbra existence after AIS is crucial for making decision on reperfusion therapy. Yet a fast, inexpensive, simple, and noninvasive predictive biomarker for the poststroke penumbra with clinical translational potential is still lacking. We aim to investigate whether the CircOGDH (circular RNA derived from oxoglutarate dehydrogenase) is a potential biomarker for penumbra in patients with AIS and its role in ischemic neuronal damage. Methods: CircOGDH was screened from penumbra of middle cerebral artery occlusion mice and was assessed in plasma of patients with AIS by quantitative polymerase chain reaction. Magnetic resonance imaging was used to examine the penumbra volumes. CircOGDH interacted with miR-5112 in primary cortical neurons was detected by fluorescence in situ hybridization, RNA immunoprecipitation, and luciferase reporter assay. ADV-mediated CircOGDH knockdown ameliorated neuronal apoptosis induced by COL4A4 (Gallus collagen, type VI, alpha VI) overexpression. Transmission electron microscope, nanoparticle tracking analysis, and Western blot were performed to confirm exosomes. Results: CircOGDH expression was dramatically and selectively upregulated in the penumbra tissue of middle cerebral artery occlusion mice and in the plasma of 45 patients with AIS showing a 54-fold enhancement versus noncerebrovascular disease controls. Partial regression analysis revealed that CircOGDH expression was positively correlated with the size of penumbra in patients with AIS. Sequestering of miR-5112 by CircOGDH enhanced COL4A4 expression to elevate neuron damage. Additionally, knockdown of CircOGDH significantly enhanced neuronal cell viability under ischemic conditions. Furthermore, the expression of CircOGDH in brain tissue was closely related to that in the serum of middle cerebral artery occlusion mice. Finally, we found that CircOGDH was highly expressed in plasma exosomes of patients with AIS compared with those in noncerebrovascular disease individuals. Conclusions: These results demonstrate that CircOGDH is a potential therapeutic target for regulating ischemia neuronal viability, and is enriched in neuron-derived exosomes in the peripheral blood, exhibiting a predictive biomarker of penumbra in patients with AIS.