Preliminary Analysis of Aging-Related Genes in Intracerebral Hemorrhage by Integration of Bulk and Single-Cell RNA Sequencing Technology.

Background: Aging is recognized as the key risk for intracerebral hemorrhage (ICH). The detailed mechanisms of aging in ICH warrant exploration. This study aimed to identify potential aging-related genes associated with ICH. Methods: ICH-specific aging-related genes were determined by the intersection of differentially expressed genes (DEGs) between perihematomal tissues and corresponding contralateral parts of four patients with ICH (GSE24265) and 349 aging-related genes obtained from the Aging Atlas database. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA) analyses were performed to identify the potential biological functions and pathways in which these ICH-specific aging-related genes may be involved. Then, PPI network was established to identify the hub genes of ICH-specific aging-related genes. Meanwhile, miRNA-mRNA and transcription factor (TF)-mRNA regulatory networks were constructed to further explore the ICH-specific aging-related genes regulation. The relationship between these hub genes and immune infiltration was also further explored. Additional single-cell RNA-seq analysis (scRNA-seq, GSE167593) was used to locate the hub genes in different cell types. Besides, expression levels of the hub genes were validated using clinical samples from our institute and another GEO dataset (GSE206971). Results: This study identified 24 ICH-specific aging-related genes, including 22 up-regulated and 2 down-regulated genes. The results of GO and KEGG suggested that the ICH-specific aging-related genes mainly enriched in immunity and inflammation-related pathways, suggesting that aging may affect the ich pathogenesis by regulating inflammatory and immune-related pathways. Conclusion: Our study revealed 24 ICH-specific aging-related genes and their functions highly pertinent to ICH pathogenesis, providing new insights into the impact of aging on ICH.

LncRNA FOXD3-AS1 Contributes to Glioblastoma Progression Via Sponging miR-3918 to Upregulate CCND1.

AIM: To elucidate the pro-tumorigenic role of IncRNA FOXD3-AS1 in glioblastoma. MATERIAL AND METHODS: The expression of miR-3918, FOXD3-AS1, and CCND1 was measured in glioblastoma cells and tissues using reverse transcriptase quantitative PCR (RT-qPCR). The effect of FOXD3-AS1 silencing on the proliferation of glioblastoma cells was assessed in vitro using CCK-8 and colony formation assays and in vivo using xenograft mouse models. Additionally, the expression levels of the apoptosis-related proteins, Bcl-2 and Bax, were assessed using western blotting. Bioinformatic analysis and luciferase reporter assays assisted by RNA immunoprecipitation (RIP) and RNA pull-down experiments were conducted to validate the interactions among FOXD3-AS1, CCND1, and miR-3918. RESULTS: FOXD3-AS1 and CCND1 were highly expressed in glioblastoma tissues and cells, whereas miR-3918 was poorly expressed. The expressions of FOXD3-AS1 and CCND1 were inversely associated with miR-3918 levels in glioblastoma tissues. FOXD3-AS1 silencing weakened the proliferative capacity and accelerated apoptosis of glioblastoma cells in vitro and hampered tumor growth in vivo. Mechanical investigations showed that FOXD3-AS1 knockdown increased miR-3918 expression and inhibited glioblastoma cell growth. Meanwhile, the miR-3918 inhibitor restored CCND1 expression and induced the opposite outcome. CONCLUSION: FOXD3-AS1 facilitates the CCND1-driven progression of glioblastoma by serving as a competing endogenous RNA (ceRNA) for miR-3918. This suggests that FOXD3-AS1 may be a potential therapeutic target for the management of glioblastoma development.

Neuronavigation-assisted neuroendoscopy versus conventional craniotomy for hypertensive cerebellar hemorrhage: A comparative analysis of efficacy and outcomes.

OBJECTIVE: Hypertensive cerebellar hemorrhage is a severe condition in neurosurgery, associated with high disability and mortality rates. The present study compares the efficacy and outcomes of neuronavigation-assisted neuroendoscopy versus conventional microscope (craniotomy) in treating patients with hypertensive cerebellar hemorrhage. METHODS: A retrospective study was conducted by analyzing medical records of patients with hypertensive cerebellar hemorrhage treated at Wuhan No.1 Hospital between February 2015 and February 2019. The study included 65 patients who underwent either neuronavigation-assisted neuroendoscopy (n = 35) or conventional microscopy treatment (n = 30). All patients underwent standard neurological and clinical examinations, as well as routine laboratory tests upon admission. The diagnosis of hypertensive cerebellar hemorrhage was based on computed tomography (CT) findings. Basic parameters, clinical status on admission, imaging results, management, and outcome measures were evaluated and compared between the two groups. RESULTS: Neuronavigation-assisted neuroendoscopy showed advantages over craniotomy in terms of surgical procedure time and intraoperative blood loss ((81.91 ± 17.77) min vs (195.20 ± 31.97) min, (63.66 ± 12.42) ml vs (335.00 ± 104.26) ml, P < 0.01). The hematoma evacuation rate was higher in neuroendoscopy group ((94.37 ± 5.174)% compared to the craniotomy group ((90.80 ± 5.404)%, P < 0.01). Additionally, the time of ventricular drainage was shorter in the neuroendoscopy group ((4.83 ± 1.671) days) than in the craniotomy group ((7.70 ± 1.878) days, P < 0.01). Neuroendoscopy group also resulted in fewer surgical complications and a shorter hospital stay (P < 0.05). There was no significant difference in the risk of rebleeding and mortality between the neuroendoscopy and craniotomy group (P > 0.05). CONCLUSION: Neuronavigation-assisted neuroendoscopy is a rapid, safe, and effective minimally invasive technique for the treatment of hypertensive cerebellar hemorrhage. It offers potential benefits in reducing surgical complications and hospital stay compared to conventional craniotomy.

Analysis of the effects of stent-induced deformation on the hemodynamics of MCA aneurysms.

The use of a stent to coil an aneurysm can alter the position of the main blood vessel and affect blood flow within the sac. This study thoroughly examines the impact of stent-induced changes on the risk of MCA aneurysm rupture. The research aims to assess the effects of coiling and vessel deformation on blood flow dynamics by comparing the OSI, WSS, and blood structure of two distinct MCA aneurysms to identify high-risk areas for hemorrhage. Computational fluid dynamics is used to model blood flow. The results indicate that aneurysm deformation does not always decrease the risk of rupture, and coiling is more effective in occluding blood flow than aneurysm deformation.

Identification, and Experimental and Bioinformatics Validation of an Immune-Related Prognosis Gene Signature for Low-Grade Glioma Based on mRNAsi.

BACKGROUND: Low-grade gliomas (LGGs), which are the second most common intracranial tumor, are diagnosed in seven out of one million people, tending to develop in younger people. Tumor stem cells and immune cells are important in the development of tumorigenesis. However, research on prognostic factors linked to the immune microenvironment and stem cells in LGG patients is limited. We critically need accurate related tools for assessing the risk of LGG patients. METHODS: In this study, we aimed to identify immune-related genes (IRGs) in LGG based on the mRNAsi score. We employed differentially expressed gene (DEG) methods and weighted correlation network analysis (WGCNA). The risk signature was then further established using a lasso Cox regression analysis and a multivariate Cox analysis. Next, we used immunohistochemical sections (HPA) and a survival analysis to identify the hub genes. A nomogram was built to assess the prognosis of patients based on their clinical information and risk scores and was validated using a DCA curve, among other methods. RESULTS: Four hub genes were obtained: C3AR1 (HR = 0.98, p < 0.001), MSR1 (HR = 1.02, p < 0.001), SLC11A1 (HR = 1.01, p < 0.01), and IL-10 (HR = 1.01, p < 0.001). For LGG patients, we created an immune-related prognostic signature (IPS) based on mRNAsi for estimating risk scores; different risk groups showed significantly different survival rates (p = 3.3 × 10-16). Then, via an evaluation of the IRG-related signature, we created a nomogram for predicting LGG survival probability. CONCLUSION: The outcome suggests that, when predicting the prognosis of LGG patients, our nomogram was more effective than the IPS. In this study, four immune-related predictive biomarkers for LGG were identified and proven to be IRGs. Therefore, the development of efficient immunotherapy techniques can be facilitated by the creation of the IPS.

MicroRNA-485-5p inhibits glioblastoma progression by suppressing E2F transcription factor 1 under cisplatin treatment.

Cisplatin (CDDP) has been widely used for glioblastoma treatment. miR-485-5p and E2F transcription factor 1 (E2F1) dysfunction has been reported in glioblastoma. Nonetheless, whether CDDP affects glioblastoma progression via the miR-485-5p-E2F1 axis requires investigation. The expression of miR-485-5p and E2F1 was investigated by quantitative real-time polymerase chain reaction or western blotting in glioblastoma tissues and cell lines. The interaction between miR-485-5p and E2F1 was confirmed using a luciferase assay. The malignancy of glioblastoma was detected using Cell Counting Kit-8, bromodeoxyuridine (BrdU), cell adhesion, flow cytometry, and transwell assays. We identified miR-485-5p downregulation and E2F1 upregulation in glioblastoma, and miR-485-5p inhibited cell growth and elevated cell apoptosis in glioblastoma cells after CDDP treatment. Moreover, miR-485-5p targeting E2F1 repressed cell growth and improved cell apoptosis in glioblastoma cells after CDDP treatment. Our study revealed that CDDP retarded glioblastoma cell development via the miR-485-5p-E2F1 axis, which may be a new direction for glioblastoma therapy.

Homer1a protects against neuronal injury via PI3K/AKT/mTOR signaling pathway.

Purpose: Homer1a is a member of the post-synaptic density protein family that plays an important role in neuronal synaptic activity and is extensively involved in neurological disorders. The aim of this study is to investigate the role of Homer1a in modulating neuronal survival using an in vitro traumatic neuronal injury model.Materials and methods: Neurons were extracted from rats and identifited. Then, the cells were treated with Homerla overexpression or interference vectors. Western blot was performed to evaluate the expression of Homerla, apoptosis-related proteins(caspase3, caspase8, caspase9, Fasl, Bax, and p53), autophagy-related proteins (LC3ll and Beclin1), and the activiation of PI3K/AKT/mTOM pathway. In addition, the cell viability and apoptosis rate were measured. Results: After transfection with overexpression or interference vectors, the mRNA and protein expression of Homer1a increased or decreased significantly, respectively. Upregulation of Homer1a significantly alleviated apoptosis and enhanced cell viability and autophagy after traumatic neuronal injury. Homer1a overexpression also significantly decreased the expression of the pro-apoptosis proteins caspase 3, caspase 8, caspase 9, Fasl, Bax, and p53 in neurons. Furthermore, neuron autophagy was increased after traumatic neuronal injury as demonstrated by the greater accumulation of autophagosomes and higher expression of LC3II and Beclin1 induced by Homer1a overexpression. In addition, Homer1a overexpression inhibited the activation of PI3K/AKT/mTOR signaling. Conclusion: These findings indicated that Homer1a potentially protects neurons from traumatic injury by regulating apoptosis and autophagy via the caspase and PI3K/AKT/mTOR signaling pathways and may be an effective intervention target in traumatic brain injury.

Endoscopic Surgery versus External Ventricular Drainage Surgery for Severe Intraventricular Hemorrhage.

The efficacy and applied value of endoscopic hematoma evacuation vs. external ventricular drainage (EVD) in the treatment of severe ventricular hemorrhage (IVH) were explored and compared. From Jan. 2015 to Dec. 2016, the clinical data of 42 cases of IVH were retrospectively analyzed, including 18 patients undergoing endoscopic hematoma evacuation (group A), and 24 patients receiving EVD (group B). The hematoma clearance rate was calculated by 3D Slicer software, and complications and outcomes were compared between the two groups. There were no significant differences in age, sex and Graeb score between groups A and B (P>0.05). The hematoma clearance rate was 70.81%±27.64% in group A and 48.72%±36.58% in group B with a statistically significant difference (P<0.05). The operative time in groups A and B was 72.45±25.26 min and 28.54±15.27 min, respectively (P<0.05). The Glasgow Coma Scale (GCS) score increased from 9.28±2.72 at baseline to 11.83±2.91 at 1 week postoperatively in group A, and from 8.25±2.62 at baseline to 10.79±4.12 at 1 week postoperatively in group B (P<0.05). The length of hospital stay was 12.67±5.97 days in group A and 17.33±8.91 days in group B with a statistically significant difference (P<0.05). The GOS scores at 6 months after surgery were 3.83±1.12 in group A, and 2.75±1.23 in group B (P<0.05). These results suggested that endoscopic hematoma evacuation has an advantage of a higher hematoma clearance rate, fewer complications and better outcomes in the treatment of severe IVH, indicating it is a safe, effective and promising approach for severe IVH.

Effect of cyclooxygenase­2 inhibition on the development of post­traumatic stress disorder in rats.

Post­traumatic stress disorder (PTSD) is characterized by re­experiencing of a traumatic event, avoidance of trauma­associated stimulation, general changes in mood and cognition, and hyper arousal symptoms. Cyclooxygenase is involved in the production of prostaglandins and thromboxanes, and its inducible form cyclooxygenase­2(COX­2), an important mediator of cell injury in inflammation, is primarily expressed in leukocytes and brain cells. The present study investigated the expression of COX­2 in the hippocampi of rats with PTSD and evaluated the effect of COX­2 inhibition on PTSD. Adult male Wistar rats were randomly divided into three groups: Control (n=20), PTSD (n=20) and intervention group (PTSD+COX­2 inhibitor treatment, n=20). The expression of COX­2 was detected by immunohistochemistry, reverse transcription­quantitative polymerase chain reaction and western blotting. Terminal deoxynucleotidyl transferase mediated dUTP nick end labeling staining was used to observe the apoptosis of rat hippocampal neurons. Tumor necrosis factor α (TNF­α), interleukin (IL)­6 and prostaglandin E2 (PGE2) levels were analyzed by ELISA. Nitric oxide (NO) was detected using the Griess test. The behavioral and cognitive function of rats in the PTSD group was significantly decreased compared with the control group, while the behavioral and cognitive function of rats in the intervention group were improved. The COX­2 mRNA and protein expression levels in hippocampi of rats in the PTSD group were higher than in the control and intervention group. The apoptosis of hippocampus in rats with PTSD was significantly increased compared with the control group and following treatment with COX­2 inhibitor, apoptosis was decreased. In addition, compared with the control group and intervention group, the levels of TNF­α, IL­6, PGE2 and NO in hippocampi of rats were increased in the PTSD group. The present study indicated that COX­2 may be involved in the pathogenesis of PTSD, and inhibition of its expression serves a neuroprotective role in hippocampi of PTSD rats.

Down-regulation of BAG3 inhibits proliferation and promotes apoptosis of glioblastoma multiforme through BAG3/HSP70/HIF-1α signaling pathway.

Bcl2-associated athanogene 3 (BAG3) belongs to the BAG family and regulates many biologic behaviors of tumors. When tumor cells are in a hypoxic condition, BAG3 protein expression level increases, as does HIF-1α which is an important transcription factor induced by hypoxia. Glioblastoma is one of the typical solid tumors existing in a hypoxic microenvironment that can activate expression of BAG3 and HIF-1α. This research aimed to reveal the relationship between BAG3 and HIF-1α and their effects in glioblastoma multiforme. We found that down-regulated BAG3 inhibited proliferation and promoted apoptosis of glioblastoma multiforme U87 and U251 cell lines by decreasing HIF-1α expression level. The mechanism of BAG3 regulating HIF-1α is mainly through increasing degradation of HIF-1α by HSP70. When HIF-1α was up-regulated, induced by HIF-1α plasmid transfection on the basis of down-regulation of BAG3, the proliferation inhibition and apoptosis promotion were partially reversed. This novel result showed, for the first time, that down-regulation of BAG3 resulted in a low expression of HIF-1α under both normoxic or hypoxic conditions and finally caused inhibited proliferation and promoted apoptosis in glioblastoma. The mechanism of down-regulated BAG3 decreased HIF-1α protein expression through enhancing formation of HSP70-HIF-1α complex and promoting degradation of HIF-1α by HSP70.