MiR-20a-5p targets RBM24 and alleviates hypertensive intracerebral hemorrhage.

Hypertensive intracerebral hemorrhage (HICH) poses a significant challenge due to its high incidence, mortality, and diagnostic complexities. The underlying molecular mechanisms of HICH development remain enigmatic. In this study, we identified differentially expressed miRNAs in HICH patients by employing miRNA microarray analysis. We found that miR-20a-5p was one of the miRNAs significantly down-regulated in HICH patients and was significantly associated with clinicopathological features of the patients. Subsequently, Human umbilical vein endothelial cells (HUVECs) were transfected with miR-20a-5p mimics or inhibitors to investigate the role of miR-20a-5p in proliferation, apoptosis, migration, and angiogenesis. Similarly, a mimic of miR-20a-5p or its inhibitor was injected into the HICH animal model and measured HICH markers in brain tissue. We next employed a bioinformatic approach to investigate the potential targets of miR-20a-5p which was further confirmed using gain and loss of function assays in HUVECs and animal models. The results show that overexpression of miR-20a-5p in HUVECs enhanced cell proliferation, migration, and tube formation while suppressing apoptosis, and attenuated HICH development in vivo. miR-20a-5p mediated its effects by directly targeting RBM24 and silencing RBM24 could partially recover the suppressive effects of miR-20a-5p on the development of HICH. Interestingly, miR-20a-5p hindered the development of HICH and its influence relied on the HIF1α/VEGFA pathway.

Application of f-FeNC@GOx cascade enzyme nanomaterials in the healing of infected wounds.

AIMS: Bacterial infection is a significant factor contributing to the deterioration of wounds, and the misuse of antibiotics has exacerbated bacterial resistance. Therefore, there is an urgent need to develop a novel antibacterial strategy to replace conventional therapies. This study aims to construct a self-activated cascade reaction nanozyme, f-FeNC@GOx, which triggers a cascade reaction in the presence of glucose. This cascade reaction generates highly toxic hydroxyl radicals (OH), thereby achieving the goal of eliminating bacteria and promoting wound healing. MATERIAL AND METHODS: In vitro antibacterial experiments, bacterial spread plate method, Live/Dead staining, and crystal violet staining were conducted to analyze the antibacterial ability and mechanism of f-FeNC@GOx. In vivo experiments, a mouse wound model was established, and H&E and Masson staining of wound tissues were performed to assess the antibacterial activity of the f-FeNC@GOx in vivo. KEY FINDINGS: The in vivo and in vitro experiments confirmed that f-FeNC@GOx exhibited significant antibacterial effect against both Staphylococcus aureus and Escherichia coli in the presence of glucose. Furthermore, it showed optimal wound healing performance in the wound models. SIGNIFICANCE: These findings suggested that f-FeNC@GOx was a novel and effective antibacterial nanomaterial, which provided a promising antibacterial strategy using nanoenzyme based cascade reaction.

Transcriptome Analysis and Single-Cell Sequencing Analysis Constructed the Ubiquitination-Related Signature in Glioma and Identified USP4 as a Novel Biomarker.

Background: Glioma, the most frequent malignant tumor of the neurological system, has a poor prognosis and treatment problems. Glioma's tumor microenvironment is also little known. Methods: We downloaded glioma data from the TCGA database. The patients in the TCGA database were split into two groups, one for training and the other for validation. The ubiquitination genes were then evaluated in glioma using COX and Lasso regression to create a ubiquitination-related signature. We assessed the signature's predictive usefulness and role in the immune microenvironment after it was generated. Finally, in vitro experiment were utilized to check the expression and function of the signature's key gene, USP4. Results: This signature can be used to categorize glioma patients. Glioma patients can be separated into high-risk and low-risk groups in both the training and validation cohorts, with the high-risk group having a significantly worse prognosis (P<0.05). Following further investigation of the immune microenvironment, it was discovered that this risk grouping could serve as a guide for glioma immunotherapy. The activity, invasion and migration capacity, and colony formation ability of U87-MG and LN229 cell lines were drastically reduced after the important gene USP4 in signature was knocked down in cell tests. Overexpression of USP4 in the A172 cell line, on the other hand, greatly improved clonogenesis, activity, invasion and migration. Conclusions: Our research established a foundation for understanding the role of ubiquitination genes in gliomas and identified USP4 as a possible glioma biomarker.

Increasing miR-126 Can Prevent Brain Injury after Intracerebral Hemorrhage in Rats by Regulating ZEB1.

Background: Studies have found that microRNA (miR) is abnormally expressed in intracerebral hemorrhage (ICH) and is considered a therapeutic target for ICH. Objective: To investigate the expression and role of miR-126 in the ICH rat model. Methods: The ICH rat model was established, and miR-126 agomir and ZEB1 antagomir were injected into the lateral ventricle of ICH rats. The neurological function and water content of brain tissue were evaluated 48 hours later. Brain tissue around the hematoma of rats was taken to detect the expression of miR-126, ZEB1, glial fibrillary acidic protein (GFAP), and inflammatory cytokines (TNF-α, IL-1ß, and IL-6). The luciferase reporter gene was applied to analyze the relationship between miR-126 and ZEB1. Results: miR-126 was downregulated in the ICH rat model, while ZEB1 was upregulated. miR-126 agomir or ZEB1 antagomir injection could improve neurological function and cerebral edema in ICH rats. In addition, it could also reduce the expression of TNF-α, IL-1ß, IL-6, and GFAP in the brain tissue of ICH rats. Luciferase reporter gene showed that ZEB1 could be targeted and regulated by miR-126. Conclusion: miR-126 is downregulated in ICH rats, and miR-126 can reduce brain injury in ICH rats by inhibiting ZEB1 expression.