miRNA-448 Regulates the Development of Glioblastoma (GBM) by Regulating Rho-Associated Protein Kinase 1.

Background: Glioblastoma (GBM) is an aggressive adult brain tumor that poses a huge threat to people's health. Previous studies have shown that microRNAs (miRNAs) are important regulators in the progression of GBM. However, the role of miR-448 in GBM remains largely unknown. Therefore, the regulatory mechanism of miR-448 in the development of GBM is elucidated in this study. Methods: The protein and mRNA expressions of miR-448 and ROCK1 were measured by Western blot analysis and RT-qPCR. Cell proliferation, migration, and invasion were detected by CCK-8 assay and Transwell assay. The relationship between miR-448 and ROCK1 was probed by luciferase reporter assay. Results: miR-448 expression was downregulated in GBM tissues and cells. And poor clinical outcomes of GBM patients were related to miR-448 downregulation. Functionally, overexpression of miR-448 restrained cell viability, migration, and invasion in GBM. Additionally, miR-448 reduced ROCK1 expression by binding to its 3'-UTR. Moreover, knockdown of ROCK1 inhibited the progression of GBM. Furthermore, overexpression of ROCK1 abolished the antitumor effect of miR-448 in GBM. Conclusion: miR-448 restrained cell viability, invasion, and migration in GBM by inhibiting ROCK1 expression.

Schisandrin B inhibits the proliferation and invasion of glioma cells by regulating the HOTAIR-micoRNA-125a-mTOR pathway.

Glioma is one of the most common malignant central nervous system tumors in humans. Schisandrin B (Sch B) has been confirmed to cause the proliferation and invasion of glioma cells. In the present study, the potential mechanism underlying the antitumor effect of Sch B on glioma cells was investigated. The glioma cell lines, U251 and U87, were exposed to Sch B, and the cell viability, apoptosis, migration, and invasion were determined using the MTT assay, flow cytometry, and transwell assay, respectively. Then, the effects of HOTAIR and miR-125a on tumor biology and the mammalian target of rapamycin (mTOR) protein expression in cell lines exposed to Sch B were investigated. The results showed that Sch B decreased HOTAIR expression and increased miR-125a-5p expression. HOTAIR overexpression decreased miR-125a expression and increased mTOR expression in cells with the treatment of Sch B. The miR-125a inhibitor reversed the effects of HOTAIR downregulation on cell proliferation and migration. On co-incubation with rapamycin, a specific mTOR inhibitor, the cell viability, migration, and invasion were decreased and cell apoptosis was increased in two cell lines exposed to Sch B after the treatment of pcDNA-HOTAIR. In conclusion, Sch B played an inhibitory role in the proliferation and invasion of glioma cells by regulating the HOTAIR-micoRNA-125a-mTOR pathway.

Microarray data analysis to identify crucial genes regulated by CEBPB in human SNB19 glioma cells.

BACKGROUND: Glioma is one of the most common primary malignancies in the brain or spine. The transcription factor (TF) CCAAT/enhancer binding protein beta (CEBPB) is important for maintaining the tumor initiating capacity and invasion ability. To investigate the regulation mechanism of CEBPB in glioma, microarray data GSE47352 was analyzed. METHODS: GSE47352 was downloaded from Gene Expression Omnibus, including three samples of SNB19 human glioma cells transduced with non-target control small hairpin RNA (shRNA) lentiviral vectors for 72 h (normal glioma cells) and three samples of SNB19 human glioma cells transduced with CEBPB shRNA lentiviral vectors for 72 h (CEBPB-silenced glioma cells). The differentially expressed genes (DEGs) were screened using limma package and then annotated. Afterwards, the Database for Annotation, Visualization, and Integrated Discovery (DAVID) software was applied to perform enrichment analysis for the DEGs. Furthermore, the protein-protein interaction (PPI) network and transcriptional regulatory network were constructed using Cytoscape software. RESULTS: Total 529 DEGs were identified in the normal glioma cells compared with the CEBPB-silenced glioma cells, including 336 up-regulated and 193 down-regulated genes. The significantly enriched pathways included chemokine signaling pathway (which involved CCL2), focal adhesion (which involved THBS1 and THBS2), TGF-beta signaling pathway (which involved THBS1, THBS2, SMAD5, and SMAD6) and chronic myeloid leukemia (which involved TGFBR2 and CCND1). In the PPI network, CCND1 (degree = 29) and CCL2 (degree = 12) were hub nodes. Additionally, CEBPB and TCF12 might function in glioma through targeting others (CEBPB → TCF12, CEBPB → TGFBR2, and TCF12 → TGFBR2). CONCLUSIONS: CEBPB might act in glioma by regulating CCL2, CCND1, THBS1, THBS2, SMAD5, SMAD6, TGFBR2, and TCF12.

Spontaneous epidural hematoma complicated by systemic lupus erythematosus: one case report.

In this study, an unusual case of intracranial hemorrhage is presented. It is spontaneous epidural hemorrhage, the complication of Systemic Lupus Erythematosus. In this case, a 29-year-old female presented with vomiting and continuous headache and computed tomography revealed the right frontal parietal and temporal epidural hematoma. The patient had been diagnosed SLE one year ago. Together, these observations indicated that the patient needs a surgery to reduce the intracranial pressure. Following surgery, the symptoms were eradicated but 7 hours later after surgery the review head CT showed that left epidural hemorrhage. According to the surgery index, we decided to give the patient non-operative treatment and the intracranial hemorrhage was under control. We thought this was the surgery complication but it's not. On the eighth day after surgery, the patient had a sudden headache with vomiting again and head CT revealed that left epidural hemorrhage. But this time we just gave non-operative treatment and especially added the dose of glucocorticosteroid. 12 days later, the patient's symptoms were under control and she was discharged from hospital. We also reviewed the literature about spontaneous epidural hemorrhage and bilateral epidural hematomas.

Schisandrin B suppresses glioma cell metastasis mediated by inhibition of mTOR/MMP-9 signal pathway.

BACKGROUND: Malignant glioma is the aggressive tumor in the brain and is characterized by high morbidity, high mortality. The main purpose of the present study was to investigate the therapeutic effects of Schisandrin B on glioma cells and preliminary explore the possible mechanism underlying anti-metastasis of Schisandrin B. METHODS: Two glioma cell lines, U251 and U87, were used in present study. The ability of metastasis of glioma cells was evaluated using transwell migration assay and invasion assay. Expression of Akt, mTOR, MMP-2 and MMP-9 was determined using Western blotting. Antagonist or agonist was used to activated or inactivated signal molecules. RESULTS: Schisandrin B suppressed cell migration and invasion in manner of dose dependent as well as inhibited expression of p-Akt, p-mTOR and MMP-9. Activation of PI3K by 740Y-P treatment leaded to upregulation of p-Akt, mTOR and MMP-9; inactivation of mTOR by Rapamycin treatment inhibited expression MMP-9 while activation of mTOR by l-Leucine treatment enhanced MMP-9 expression in Schisandrin B incubated cells. Anti-migration and invasion action of Schisandrin B was also reversed by mTOR activation. CONCLUSION: Our findings demonstrate that Schisandrin B can suppress migration and invasion of glioma cell via PI3K/Akt-mTOR-MMP-9 signaling pathway.

Endovascular management of vertebrobasilar artery dissecting aneurysms.

AIM: The prognosis of VBA aneurysms seems poor and surgical management of VBA dissecting aneurysms is challenging. We evaluated our endovascular experience in management of ruptured and unruptured VBA dissecting aneurysms. MATERIAL AND METHODS: Eleven consecutive patients with eleven VBA aneurysms (3 ruptured and 8 unruptured) between 2008 and 2010 were retrospectively reviewed. RESULTS: Immediate postprocedural angiograms showed complete occlusion in 5 and subtotal occlusion in 2 aneurysms treated with stentassisted coiling, whereas no occlusion in 4 aneurysms treated with stenting alone. A clinical improvement or stable outcome was achieved in all patients. There was no complication in our patients and no patient died after treatment. Angiographic follow-up (mean 9.7 months, 1 to 23 months) showed complete cure in 8 aneurysms, subtotal occlusion in 2 and no occlusion in 1. CONCLUSION: VBA dissecting aneurysms can be managed by endovascular stent placement with or without coiling. In cases that cannot be treated with neurostents, proximal occlusion could be an option.

Characteristics and endovascular treatment of aneurysms of posterior cerebral artery.

BACKGROUND: Aneurysms of the posterior cerebral artery (PCA) are a distinct rarity and present with some peculiar morphologic features and specific clinical findings. These aneurysms can be managed endovascularly with good results. OBJECTIVE: To evaluate the clinical features and endovascular management of PCA aneurysms. MATERIAL AND METHODS: Between 2000 and 2008, we treated 24 patients (14 male and 10 female; mean age: 36 years) with PCA aneurysms. Clinical presentations, radiologic images, and endovascular management were reviewed. RESULTS: There were 11 saccular aneurysms, including 4 giant or large aneurysms, and 13 dissecting aneurysms, including 11 giant or large aneurysms. Of the 24 patients, 13 presented with hemorrhage and 6 with neurologic deficits. Five patients presented with headaches without any neurologic deficits. Parent vessel occlusion was performed in 12 patients, selective coil embolization was performed in 11 patients, and 1 patient conservatively. Eighteen patients had a good recovery, 5 had a moderate disability (one with 1 visual deficit after the treatment) related to hemorrhage, vasospasm, or infarction before aneurysm trapping, and 1 patient died because of rebleeding. The conservatively treated patient made a good recovery. CONCLUSION: PCA aneurysms have specific clinical characteristics compared with aneurysms located elsewhere. Endovascular technique can achieve good outcomes despite the aneurysmal site and size.