Insights into the roles of non-coding RNAs and angiogenesis in glioblastoma: An overview of current research and future perspectives.

Glioblastoma (GBM) is a highly aggressive type of primary brain cancer with a poor prognosis, and despite intensive research, survival rates have not significantly improved. Non-coding RNAs (ncRNAs) are emerging as critical regulators of GBM pathogenesis, including angiogenesis, which is essential for tumor growth and invasion. MicroRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) have been identified as regulators of angiogenesis in GBM. miRNAs such as miR-21, miR-10b, and miR-26a promote angiogenesis by targeting anti-angiogenic factors, while lncRNAs such as H19 and MALAT1 inhibit angiogenesis by regulating pro-angiogenic factors. CircRNAs, such as circSMARCA5 and circBACH2, also regulate angiogenesis through various mechanisms. Similarly, signaling pathways such as the vascular endothelial growth factor (VEGF) pathway play critical roles in angiogenesis and have been targeted for GBM therapy. However, resistance to anti-angiogenic therapies is a significant obstacle in clinical practice. Developing novel therapeutic strategies targeting ncRNAs and angiogenesis is a promising approach for GBM. Potential targets include miRNAs, lncRNAs, circRNAs, and downstream signaling pathways that regulate angiogenesis. This review highlights the critical roles of ncRNAs and angiogenesis in GBM pathogenesis and the potential for new therapeutic strategies targeting these pathways to improve the prognosis and quality of life for GBM patients.

Single Versus Double Burr Hole Craniostomy in Surgical Treatment of Chronic Subdural Hematoma: A Meta-Analysis.

BACKGROUND: Chronic subdural hematoma (cSDH) is one of the most common illnesses seen in neurosurgery departments worldwide. For surgical treatment, some neurosurgeons prefer single burr hole craniostomy (SBHC), whereas others prefer double burr hole craniostomy (DBHC). We performed a meta-analysis to investigate whether DBHC is associated with increased risks of recurrence, complications and mortality compared with SBHC in patients with cSDH. METHODS: Retrospective observational trial or randomized controlled trial (RCT) studies concerning burr hole craniostomy to treat cSDH were systematically identified through a search of electronic databases: PubMed, Web of Science, Embase, and Cochrane. Inclusion and exclusion criteria were defined for the eligible studies. The random fixed-effects model was used when heterogeneity was indicated; otherwise, a fixed-effects model was adopted. RESULTS: This meta-analysis included 12 studies, 3 of which were RCTs. Our findings can be summarized as follows. First, SBHC did not increase the risk of recurrence compared with DBHC in patients with cSDH (odds ratio [OR], 1.28; 95% confidence interval [CI], 0.92-1.78; P =0.07). Second, DBHC was not associated with an increased complication rate compared with SBHC in patients with cSDH (OR, 0.74; 95% CI, 0.20-2.76; P = 0.11). Third, DBHC did not increase mortality compared with SBHC in patients with cSDH (OR, 1.38; 95% CI, 0.55-3.46; P = 0.58). CONCLUSIONS: This meta-analysis demonstrates that there are no significant differences in recurrence rate, complication rate, and morbidity between SBHC and DBHC in the treatment of patients with cSDH.

Calcium-sensing receptor antagonist NPS2390 attenuates neuronal apoptosis though intrinsic pathway following traumatic brain injury in rats.

Traumatic brain injury (TBI) initiates a complex cascade of neurochemical and signaling changes that leads to neuronal apoptosis, which contributes to poor outcomes for patients with TBI. Previous study indicates that calcium-sensing receptor (CaSR) activation contributes to neuron death in focal cerebral ischemia-reperfusion mice, however, its role in neuronal apoptosis after TBI is not well-established. Using a controlled cortical impact model in rats, the present study was designed to determine the effect of CaSR inhibitor NPS2390 upon neuronal apoptosis after TBI. Rats were randomly distributed into three groups undergoing the sham surgery or TBI procedure, and NPS2390 (1.5 mg/kg) was infused subcutaneously at 30 min and 120 min after TBI. All rats were sacrificed at 24 h after TBI. Our data indicated that NPS2390 significantly reduced the brain edema and improved the neurological function after TBI. In addition, NPS2390 decreased caspase-3 levels and the number of apoptotic neurons. Furthermore, NPS2390 up-regulated anti-apoptotic protein Bcl-2 expression and down-regulated pro-apoptotic protein Bax, and reduced subsequent release of cytochrome c into the cytosol. In summary, this study indicated that inhibition of CaSR by NPS2390 attenuates neuronal apoptosis after TBI, in part, through modulating intrinsic apoptotic pathway.

Intermediate nerve neuralgia can be diagnosed and cured by microvascular decompression.

Here, we present a case of a 55-year-old woman with a 10-year history of hemifacial spasm accompanied by 1-month ipsilateral paroxysmal otalgia. Magnetic resonance imaging revealed the presence of vessels around the facial nerve root. Surgical exploration via suboccipital retromastoid craniotomy showed converging compression of the facial nerve root and intermediate nerve from both sides by an anterior inferior cerebellar artery loop. The patient's hemifacial spasm and ipsilateral otalgia were completely relieved after microvascular decompression of the facial nerve root and intermediate nerve. Intraoperative findings and the postoperative result of this case confirmed that vascular compression of the intermediate nerve was the exclusive cause of paroxysmal otalgia. The presence of ipsilateral hemifacial spasm, combined with preoperative neuroimaging studies, contributed to the diagnosis of intermediate nerve neuralgia. Microvascular decompression should be considered for the management of patients with intermediate nerve neuralgia.

Glioblastoma mimicking a cerebral contusion: A case report.

A 61-year-old male presented with a rare case of glioblastoma mimicking a cerebral contusion subsequent to collapsing. The patient had been medicated for hypertension for seven years and diabetes for eight years prior to hospitalization. Brain computed tomography (CT) revealed a cerebral contusion and intracerebral hemorrhage (ICH) in the left temporal region. The patient was initially administered intravenous drugs to reduce the intracranial pressure following the diagnosis of a cerebral contusion. Serial CT revealed ICH resorption. However, the patient was again admitted due to a headache and vomiting two months later. Magnetic resonance imaging (MRI) demonstrated an enhanced ring-shaped mass around the cyst cavity within the left temporal region, with surrounding edema. The patient underwent cyst puncture drainage in the temporal region. No tumor cells were identified in the cyst fluid and the culture was also negative. The patient was admitted for a headache and vomiting for the third time one month after being discharged. A cyst, tumor and meningoencephalitis were suspected following an MRI scan. The patient was treated with a left temporal craniotomy for a mass resection and biopsy. The histological diagnosis of the biopsy specimen was that of a glioblastoma. Two months later, MRI revealed a recurrence of the glioblastoma. In the present case, a brain tumor should have initially been suspected as the cause of the ICH, despite the history of craniocerebral trauma and hypertension. Early awareness of this potential cause of ICH may facilitate a more prompt diagnosis and treatment.

The potential role of Ku80 in primary central nervous system lymphoma as a prognostic factor.

The aim of our study was to detect the expression of Ku80 in primary central nervous system lymphoma and to evaluate the relationship between Ku80 expression level and clinical outcomes. Thirty-eight patients with primary central nervous system lymphoma (PCNSL) were included in this retrospective study. The expression of Ku80 in tumor samples was determined by immunohistochemistry. One thousand neoplastic cells per specimen were counted. The expression levels were compared with the clinical data and statistically analyzed. The results of this study show that the expression of Ku80 can be found in the majority of PCNSLs. The mean expression level of Ku80 in 38 PCNSL is 64.1 ±24.5. A significant difference in Ku80 expression could be found between the age < 65 years group and age ≥ 65 years group (P = 0.006). Kaplan-Meier analysis revealed that patients who showed a high Ku80 expression had a significantly shorter median survival time (MST) than patients who had low Ku80 expression (P = 0.036). Patients' age, tumor location, and treatment protocol were significantly related to prognosis in PCNSL (P < 0.05). The expression of Ku80 was observed in the majority of PCNSLs. Ku80 was a predictive factor for survival in this study. In addition to Ku80, other clinical variables including age, tumor location and therapeutic protocol are correlated significantly with overall survival.

miR-92b controls glioma proliferation and invasion through regulating Wnt/beta-catenin signaling via Nemo-like kinase.

BACKGROUND: Nemo-like kinase (NLK) is an evolutionarily conserved protein kinase involved in Wnt/beta-catenin signaling, which has been reported to be associated with gliomagenesis. In the present study, we aimed to identify a concrete mechanism of Wnt/beta-catenin pathway regulation by microRNAs (miRNAs) in glioma. METHODS: Quantitative reverse-transcription polymerase chain reaction and in situ hybridization were conducted to detect the expression of miR-92b. The cell proliferation rate and cell cycle kinetics were detected using 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay and flow cytometry, cell invasion and migration were evaluated using Transwell assay and wound healing assay, and cell apoptosis was detected using annexin V staining. Furthermore, the relevant molecules regulating proliferation and invasion were examined using Western blot analysis, immunohistochemistry, and immunofluorescence staining. Luciferase reporter assay was used to identify the direct regulation of NLK by miR-92b and beta-catenin/TCF4 activity. RESULTS: We first showed that the expression of miR-92b was elevated in both glioma samples and glioma cells. Furthermore, down-regulation of miR-92b triggered growth inhibition, induced apoptosis, and suppressed invasion of glioma in vitro and in vivo. Luciferase assay and Western blot analysis revealed that NLK is a direct target of miR-92b. Restoring expression of NLK inhibited glioma proliferation and invasion. Mechanistic investigation revealed that miR-92b deletion suppressed beta-catenin/TCF-4 transcription activity by targeting NLK. Moreover, expression of NLK was inversely correlated with miR-92b in glioma samples and was predictive of patient survival in a retrospective analysis. CONCLUSIONS: Our findings identify a role for miR-92b in glioma proliferation and invasion after activation of Wnt/beta-catenin signaling via NLK.

A predicted miR-27a-mediated network identifies a signature of glioma.

The dysregulation of physiological microRNA (miRNA) activity has been shown to play an important role in gliomagenesis. In a previous study, using microRNA arrays and glioma tissues found that miR-27a was upregulated, which was also identified in the glioma cell lines and samples by quantitative real-time polymerase chain reaction (qRT-PCR). In this study, in order to explore the potential roles of miR-27a in the progression of glioma, we first utilized text-mining of PubMed abstracts with natural language processing (NLP) to identify 1,168 glioma-related molecules. In addition, miR-27a targets predicted by computational methods were integrated with the results from NLP analysis, followed by Gene Ontology (GO), pathway and network analysis. We identified 33 hub genes by overlap calculation and demonstrated that miR-27a may be involved in the progression of glioma through adherens junction, focal adhesion, the neurotrophin signaling pathway, the MAPK signaling pathway, the transforming growth factor-ß (TGF-ß) signaling pathway, cytokine-cytokine receptor interactions, the p53 signaling pathway, the apoptotic signaling pathway, as well as others. Our data may provide researchers with a better understanding of the mechanisms of the miR-27a-target network in glioma initiation and progression.

miR-92a is a critical regulator of the apoptosis pathway in glioblastoma with inverse expression of BCL2L11.

Recent studies have revealed that miR-92a is overexpressed in several types of malignancies and provides a protumorigenic effect. Our findings demonstrate that the high expression of miR-92a in human glioma specimens is significantly correlated with low levels of BCL2L11 (Bim) protein and high-grade glioma. Here, we present the first evidence that miR-92a antisense oligonucleotide (AS-miR-92a) provides a tumor suppressive effect via induction of apoptosis in human glioma cells. In addition, we show that Bim is a direct functional target of miR-92a. Introducing Bim cDNA without 3'UTR abrogates miR-92a-induced cell survival. Further investigations will focus on the therapeutic use of AS-miR­92a-mediated antitumor effects in glioma.