Background Stroke serves as a prevalent cerebrovascular disorder with severe cerebral ischemia/reperfusion (CIR) injury, in which neural stem cells (NSCs) play critical roles in the recovery of cerebral function. Circular RNAs (circRNAs) have been widely found to participate in stroke and NSC modulation. However, the role of circRNA TTC3 (circTTC3) in the regulation of CIR injury and NSCs remains elusive. Here, we aimed to explore the impact of circTTC3 on CIR injury and NSCs. Methods The middle cerebral artery occlusion/repression (MCAO/R) model was established in C57BL/6J mice. The primary astrocytes were isolated from the cerebellum from C57BL/6J mice. The primary NSCs were obtained from rat embryos. The effect of circTTC3 on CIR injury and NSCs was analyzed by TTC staining, qPCR, Western blot, LDH colorimetric kits, MTT assays, Annexin V-FITC Apoptosis Detection Kit, luciferase reporter gene assays, and others in the system. Results Significantly, the expression of circTTC3 was elevated in the MCAO/R mice and oxygen and glucose deprivation (OGD)-treated astrocytes. The depletion of circTTC3 attenuated cerebral infarction, neurological score, and brain water content. The OGD treatment induced apoptosis and the levels of lactate dehydrogenase (LDH) in the astrocytes, in which circTTC3 depletion reduced this phenotype in the system. Moreover, the depletion of circTTC3 promoted the proliferation and upregulated the nestin and β-tubulin III expression in NSCs. Mechanically, circTTC3 was able to sponge miR-372-3p, and miR-372-3p can target Toll-like receptor 4 (TLR4) in NSCs. The miR-372-3p inhibitor or TLR4 overexpression could reverse circTTC3 depletion-mediated astrocyte OGD injury and NSC regulation. Conclusion Thus, we conclude that circTTC3 regulates CIR injury and NSCs by the miR-372-3p/TLR4 axis in cerebral infarction. Our finding presents new insight into the mechanism by which circTTC3 modulates CIR injury and NSC dysfunction. CircTTC3, miR-372-3p, and TLR4 may serve as potential targets for the treatment of CIR injury during stroke.

The function of lncRNA CRNDE and its role in prostate cancer (PC) remains unclear. The aim of this study was to determine the expression level of lncRNA CRNDE in PC tissues and to elucidate its role in PC. The expression levels of lncRNA CRNDE were measured by quantitative reverse transcription polymerase chain reaction. The role of lncRNA CRNDE in PC cells was studied using loss-of-function assays in vitro. Cell proliferation, migration, invasion, and apoptosis were assessed via Cell Counting Kit-8, colony formation, flow cytometry, wound healing, and transwell chamber assays. A luciferase reporter assay was used to characterize the interaction between lncRNA CRNDE and miR-146a-5p. In PC tissues, the expression level of lncRNA CRNDE was upregulated. Moreover, knockdown of lncRNA CRNDE suppressed PC cell proliferation and migration and induced apoptosis in vitro. miR-146a-5p was verified as a direct target of lncRNA CRNDE. Moreover, the inhibition of miR-146a-5p partially counteracted the effects of lncRNA CRNDE on PC cell proliferation, migration, and invasion. In conclusion, lncRNA CRNDE may serve as a cancer promoter in PC by targeting miR-146a-5p. Therefore, lncRNA CRNDE could be a promising target for the clinical treatment of PC.

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Upstream‐stimulating factor 1 (USF1) is a ubiquitously expressed transcription factor implicated in multiple cellular processes, including metabolism and proliferation. This study focused on the function of USF1 in glycolysis and the malignant development of prostate adenocarcinoma (PRAD). Bioinformatics predictions suggested that USF1 is poorly expressed in PRAD. The clinical PRAD samples revealed a low level of USF1, which was correlated with an unfavorable prognosis. Artificial upregulation of USF1 significantly repressed glycolytic activity in PRAD cells and reduced cell growth and metastasis in vitro and in vivo. Potential downstream genes of USF1 were probed by integrated bioinformatics analyses. The chromatin immunoprecipitation and luciferase assays indicated that USF1 bound to the α‐ketoglutarate‐dependent dioxygenase alkB homolog 5 (ALKBH5) promoter for transcription activation. Flightless I (FLII) was identified as the gene showing the highest degree of correlation with ALKBH5. As an m6A demethylase, ALKBH5 enhanced FLII mRNA stability by inducing m6A demethylation in an m6A‐YTH N6‐methyladenosine RNA‐binding protein F2 (YTHDF2)‐dependent manner. Either silencing of ALKBH5 or FLII blocked the role of USF1 in PARD cells and restored glycolysis, cell proliferation, and invasion. This study demonstrates that USF1 activates ALKBH5 to stabilize FLII mRNA in an m6A‐YTHDF2‐dependent manner, thereby repressing glycolysis processes and the progression of PRAD.

Stroke is a significant cardiovascular disease that influences the health of human beings all over the world, especially the elderly population. It is reported that the blood–brain barrier (BBB) can be easily destroyed by stroke, which is one of the main factors responsible for macrophage infiltration and central nervous inflammation. Here, we report the protective effects of Trelagliptin against BBB injury and macrophage infiltration. Our results indicate that the infraction volume, the neurological score, and macrophage infiltration staining with CD68 were increased in middle cerebral artery occlusion (MCAO) mice but significantly reversed by treatment with Trelagliptin. Additionally, Trelagliptin reduced the permeability of the BBB by increasing the expression of the tight junction zonula occludens protein-1 (ZO-1) in the cerebral cortex. In an in vitro hypoxia model of endothelial cells, the increased migration of macrophages, enlarged permeability of endothelial monolayer, downregulation of ZO-1, and elevated expression level of CXCL1 by hypoxic conditions were all reversed by treatment with Trelagliptin in a dose-dependent manner. Our results demonstrate that Trelagliptin might mitigate macrophage infiltration by preventing the breakdown of the blood–brain barrier in the brains of MCAO mice.

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