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Subarachnoid hemorrhage (SAH) is a hemorrhagic stroke with high short-term mortality that can lead to cognitive and neurological impairment. Accurate and appropriate treatment strategies are urgently needed. Nimodipine (NDP) can not only improve blood circulation in SAH patients but also repair ischemic neuronal damage. microRNAs (miRNAs) are abundantly expressed in the brain and are involved in brain injury. Therefore, this study investigated the possible regulatory mechanisms of nimodipine on miRNAs in the process of cognitive dysfunction and neurological injury after SAH. The SAH rat model was established, miR-31-5p and hypoxia-inducible factor 1 subunit alpha inhibitor (HIF1AN) expressions were detected 48 h after modeling, and neurobehavioral function, neuronal apoptosis, activation of microglia, and inflammation were evaluated. Finally, the targeting relationship between miR-31-5p and HIF1AN was verified. The study findings explained that NDP treatment could effectively improve cognitive dysfunction, brain injury, neuronal injury, and neuroinflammation in SAH rats. SAH rats expressed down-regulated miR-31-5p and up-regulated HIF1AN. Overexpressing miR-31-5p or knocking down HIF1AN ameliorated cognitive dysfunction and brain damage in SHA rats. Mechanistically, nimodipine can promote miR-31-5p expression, and HIF1AN took part in the development of SAH as a downstream target gene of miR-31-5p. In conclusion, NDP ameliorates cognitive dysfunction and neurological damage in SHA rats by miR-31-5p/HIF1AN axis. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Colorectal adenomas are an important precancerous lesion of colorectal adenoma with a high incidence. This study aims to explore new prognostic targets for colorectal adenomas through bioinformatics techniques. MATERIALS AND METHODS: In this study, data from 29 colonic adenomas and 38 normal colonic mucosa in GSE37364 were analyzed to screen for differentially expressed genes (DEGs). Then, batch survival analysis, construction of risk model, mutation analysis, Cox regression analysis and expression analysis were performed on DEGs to determine the hub genes of this study. Finally, immune correlation analysis and cell experiments were carried out on the hub gene to explore its potential mechanism. RESULTS: In our study, a total of 431 up-regulated and 809 down-regulated differentially expressed genes (DEGs) were identified. Among these, Unc-5 Netrin Receptor D (UNC5D) emerged as a pivotal gene associated with colorectal adenoma. Notably, UNC5D expression levels were found to be significantly higher in normal tissues compared to colorectal adenoma tissues. Furthermore, our analysis demonstrated that UNC5D showed promising diagnostic potential for patients with colon adenocarcinoma. In vitro experiments revealed that the overexpression of UNC5D had a profound impact on the behavior of colorectal tumor cells. Specifically, it led to a substantial reduction in the proliferation, motility, and invasion of these tumor cells. Additionally, UNC5D was shown to exert control over STAT1/STAT3 phosphorylation, which in turn regulated the expression of PD-L1 in response to interferon (IFN) stimulation. These findings highlight the significant role of UNC5D in modulating immune responses and the development of colorectal adenoma. UNC5D emerges as a potential diagnostic biomarker and an attractive immunotherapeutic target in the context of colorectal malignancies. These results call for further exploration of UNC5D-based strategies for the diagnosis and treatment of colorectal adenoma and adenocarcinoma. CONCLUSIONS: In addition to having the potential to be used as a diagnostic biomarker and an immunotherapeutic target in colorectal malignancies, UNC5D is necessary for the growth of colorectal adenomas. Additionally, UNC5D controlled STAT1/STAT3 phosphorylation to suppress the growth of colorectal cancers by regulating IFN-induced PD-L1 expression. [ABSTRACT FROM AUTHOR]