SMIM20: a new biological signal associated with the prognosis of glioblastoma.

Background: Glioblastoma multiforme (GBM) is the most prevalent fatal central nervous system tumor. Notably, the survival rates after surgical intervention and active radiotherapy are not optimistic. Therefore, identifying new GBM-related biomarkers is a top priority in current research. Methods: Transcriptome and clinical information of patients with GBM were obtained from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. According to the SMIM20 expression levels, the samples were divided into high- and low-expression groups and used for differential expression gene (DEG) analysis. Functional enrichment analyses, including Gene Ontology (GO), gene set enrichment analysis, and immune cell infiltration, were performed on SMIM20-related DEGs. Subsequently, univariate and multivariate Cox regression analyses were performed to screen the risk factors associated with the poor prognosis of SMIM20, and the clinical significance of SMIM20 in GBM was explored by constructing a prognostic nomogram. Results: In total, 156 DEGs were screened, of which 131 were upregulated and 25 were downregulated. Kaplan-Meier analysis revealed that the total survival time of the SMIM20 high expression group was significantly lower than that of the SMIM20 low-expression group. Finally, the nomogram map had good predictive value for evaluating GBM prognosis of patients. Conclusions: High expression of SMIM20 is associated with poor outcomes in GBM. The DEGs and pathways identified in this study reveal potential molecular mechanisms underlying the occurrence and progression of GBM. Our study identifies potential new biomarkers and therapeutic targets for the treatment of GBM.

Delayed rupture of traumatic anterior cerebral artery A4 segment aneurysm: A case report.

RATIONALE: Delayed rupture of traumatic intracranial aneurysms is relatively rare, and traumatic anterior A4 segment aneurysms may be associated with trauma to the cerebral falx. The mortality rate in patients with delayed traumatic rupture of intracranial aneurysms is>50%. Therefore, early diagnosis and treatment are critical. Herein, we present a case of a patient who did not have an intracranial aneurysm on computed tomographic angiography (CTA) after admission. Subsequently, the patient consciousness deteriorated, and CTA revealed aneurysm and bleeding. PATIENT CONCERNS: A 55-year-old man fell from a 3-meter-high truck and was unconscious. During the following few hours, the gradually regained consciousness. No intracranial aneurysms were found on CTA of the patient head immediately after admission. DIAGNOSES: The final diagnosis was delayed rupture of traumatic intracranial aneurysms. INTERVENTIONS: The patient underwent endovascular and symptomatic treatments. OUTCOMES: The patient gradually recovered and was referred to the rehabilitation department for further treatment. LESSONS: Considering the catastrophic consequences of the disease, we should review CTA or digital subtraction angiography many times after admission, and take appropriate surgical procedures in time.

Feasibility and Safety of Flow Diversion in the Treatment of Intracranial Aneurysms via Transradial Approach: A Single-Arm Meta-Analysis.

Background: While studies have confirmed that flow diversion (FD) can treat intracranial aneurysms via transradial approach (TRA), it remains unclear whether their treatment ultimately impacts safety and feasibility. We aim to conduct a systematic review and meta-analysis assessing the safety and feasibility after FD treatment of intracranial aneurysms via TRA. Methods: PubMed, EMBASE, and Web of Science were systematically reviewed. The primary outcomes were the success rate and the access-related complications of deploying FD via TRA. Meta-analysis was performed using a random or fixed effect model based on heterogeneity. And the publication bias was evaluated using a funnel plot. This study was registered with PROSPERO, number CRD42021244448. Results: Data from 8 studies met inclusion criteria (250 non-duplicated patients). The success rate was 93% (95% confidence interval [CI] 0.86-0.98; I 2 = 61.05%; p = 0.01). The access-related complications rate was 1% (95% CI 0-0.03; I 2 = 0.00%; p < 0.01). The mainly access-related complications included radial artery spasm (85.7%) and radial artery occlusion (14.3%). The TRA convert to transfemoral approach (TFA) was 7% (95% CI 0.02-0.14; I 2 = 61.05%; p = 0.01). Conclusions: Although TFA is still the main access for FD in the treatment of intracranial aneurysms, the TRA also has a higher success rate and lower access-related complications rate. With the improvement of future experience and equipment, the TRA may become the main access for FD which has more advantages. Future studies should design prospective, multicenter randomized controlled studies for long-term follow-up.

Preclinical anti-angiogenic and anti-cancer activities of BAY1143269 in glioblastoma via targeting oncogenic protein expression.

Glioblastoma angiogenesis is critical for tumor growth, making it an appealing target for treatment development. BAY1143269 is a novel inhibitor of mitogen-activated protein kinase interacting serine/threonine-protein kinase 1 (MKN1) and has potent anti-cancer activity. We identified BAY1143269 as an angiogenesis inhibitor, by in vitro and in vivo glioblastoma angiogenesis models. BAY1143269 inhibited the capillary network formation of glioblastoma microvascular endothelial cells (GMECs), particularly the early stage of tubular structure formation. It also inhibited migration and proliferation, and induced apoptosis of GMECs isolated from glioblastoma patients. We found that BAY1143269 acted on GMECs by suppressing the eukaryotic translation initiation factor 4E (eIF4E) and eIF4E-mediated expression of oncogenic proteins, including those involved in cell cycle, epithelial-mesenchymal transition (EMT), and pro-survival. In addition, BAY1143269 suppressed eIF4E phosphorylation, inhibited proliferation, and induced apoptosis of glioblastoma cells. Interestingly, it reduced vascular endothelial growth factor (VEGF) level in tumor cells and culturing medium, demonstrating the inhibitory effect of BAY1143269 on tumor proangiogenic microenvironment. We finally challenged BAY1143269 on the glioblastoma xenograft mice model and observed a significant tumor growth reduction without toxicity in mice receiving oral BAY1143269. Immunoblotting analysis demonstrated significantly less phosphorylated-eIF4E (p-eIF4E), cluster of differentiation 31 (CD31) (microvascular endothelial cell marker), and VEGF in tumors from drug-treated mice. In summary, the inhibition of glioblastoma angiogenesis with BAY1143269 may provide an alternative approach for anti-glioblastoma therapy.

Ischemic stroke associated with COVID-19: a systematic review and meta-analysis.

BACKGROUND: Coronavirus disease 2019 (COVID-19), a contagious infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread across the world. Apart from respiratory complications, an increasing number of patients with ischemic stroke have been reporting. OBJECTIVE: This systematic review and meta-analysis aims to explore the characteristics of ischemic stroke after SARS-CoV-2 infection, and provides valuable reference materials for subsequent clinical treatment. MATERIALS AND METHODS: PubMed, Web of Science, and Ovid-Embase databases were searched up to 24th March 2021. We utilized the search strategy of medical subject headings combined with entry terms to search all related literatures. All studies identified with the electronic and manual searches were listed by citation, title, authors, and abstract. Only studies involving patients with COVID-19-related stroke were eligible. The references of included studies were also manually screened. RESULTS: The meta-analysis was conducted following the PRISMA and MOOSE reporting guidelines. Bias risk was assessed using the Newcastle-Ottawa Scale (NOS). Ten articles, including 26,691 participants and 280 patients with ischemic stroke and COVID-19, were selected. The pooled prevalence of ischemic stroke in COVID-19 was 2% (95% CI 1-2%; p < 0.01). The pooled proportions of hypertension, hyperlipidemia and diabetes in COVID-19-related ischemic stroke was 66% (95% CI 51-81%; p < 0.01), 48% (95% CI 19-76%; p < 0.01) and 40% (95% CI 29-51%; p < 0.01), respectively. Notably, the pooled proportions of female was 36% (95% CI 21-50%; p < 0.01) in patients with COVID-19 and stroke. In addition, in TOAST classification, cryptogenic stroke subtype was associated with a high trend, and its pooled proportion was 35% (95% CI 12-59%; p < 0.01). CONCLUSION: Ischemic stroke caused by COVID-19 has its own unique clinical features. Although common high-risk factors can also be observed, its importance may have changed. The major inflammatory storm of COVID-19 is more likely to occur in male patients. The increase in the proportion of cryptogenic stroke has also made stroke related to COVID-19 complicated.

Flow diverters for the posterior inferior cerebellar artery aneurysms: A systematic review and a single-arm meta-analysis.

BACKGROUND: The treatment of posterior inferior cerebellar artery aneurysms is controversial. Recently, flow diverters have emerged as an attractive treatment option. Here, we performed a systematic review and meta-analysis of the angiographic and clinical outcomes of flow diverter-treated posterior inferior cerebellar artery aneurysms. METHODS: We searched the PubMed, EMBASE and Web of Science databases for studies published from inception to January 2021. We included studies that described flow diverters procedures for posterior inferior cerebellar artery aneurysms with ≥2 patients. The outcomes were the complete occlusion rate and flow diverter-related complication rate. Meta-analysis was performed using a random or fixed effects model based on heterogeneity. RESULTS: We included six studies involving 46 posterior inferior cerebellar artery aneurysms. There were 14 ruptured aneurysms. All flow diverters were successfully released and the technical success rate was 100%. The complete occlusion rate was 81% (95% confidence interval = 65-93%; I2 = 0.00%; P < 0.01). The flow diverter-related complication rate was 18% (95% confidence interval = 5-36%; I2 = 0.00%; P < 0.01). One patient died of rebleeding. The mortality rate was <1% (95% confidence interval = -1-1%; I2 = 0.00%; P = 0.951). CONCLUSIONS: Treatment of posterior inferior cerebellar artery aneurysms with flow diverters is feasible and carries a high degree of technical success. However, this treatment is underutilized in patients with posterior inferior cerebellar artery aneurysms due to a higher complication rate and lower occlusion rate compared with clipping and traditional endovascular treatment. Further well-designed prospective and randomized studies are required to fully understand the effects of flow diverters especially in posterior inferior cerebellar artery aneurysms patients requiring endovascular treatment.

miR-34c inhibits PDGF-BB-induced HAVSMCs phenotypic transformation and proliferation via PDGFR-ß/SIRT1 pathway.

The purpose of this study was to explore the effect of miR-34c on PDGF-BB-induced HAVSMCs phenotypic transformation and proliferation via PDGFR-ß/SIRT1 pathway, so as to find a new method for early diagnosis and treatment of cardiovascular disease. HA-VSMCs were treated with platelet-derived growth factor-BB (PDGF-BB) at 0 h, 12 h, 24 h, 48 h or 36 h to explore the optimal time for phenotypic transformation of VSMCs. And then, PDGF-BB-induced HA-VSMCs were transfected with miR-34c mimics/mimics NC and pcDNA3.1-PDGFR-ß/pcDNA3.1-NC to observe cell biological behaviour. CCK8 was used to detect cell proliferation activity. Transwell chamber assay was used to detect cell invasion. Early apoptosis was analyzed by flow cytometry. The expression of α-SMA and Smemb was detected by immunofluorescence staining. The expressions of PDGFR-ß, IRF9, Acetyl-NF-κB/p65, Acetyl-p53 and CyclinD1 were analyzed by Western blot analysis. The expression of miR-34a, miR-34b and miR-34c was detected by RT-PCR, and the targeting relationship between miR-34c and PDGFR-ß was detected by luciferase reporting assay. The results indicated the proliferation and migration of PDGF-BB-induced HA-VSMCs significantly increased, and apoptosis significantly decreased. Besides, α-SMA decreased significantly, while Smemb increased significantly. Furthermore, expressions of PDGFR-ß, IRF9, Acetyl-NF-κB/p65, Acetyl-p53 and CyclinD1 increased significantly, and SIRT1 decreased significantly. Experimental results showed that, miR-34c mimics significantly inhibited cell proliferation and migration, and promoted cell apoptosis, and miR-34c inhibitor had the opposite effects. MiR-34c mimics significantly increased α-SMA expression and decreased Smemb expression, while the opposite effects were reflected after transfection with miR-34c inhibitor. Moreover, miR-34c mimics significantly decreased the expressions of PDGFR-ß, IRF9, Acetyl-NF-κB/p65, Acetyl-p53 and CyclinD1, and significantly increased the expression of SIRT1, while miR-34c inhibitor had the opposite effects. Luciferase assay confirmed that PDGFR-ß was a potential target of miR-34c. Subsequently, PDGF-BB-induced HA-VSMCs were co-transfected with miR-34c mimics and pcDNA3.1-PDGFR-ß. The results indicated that PDGFR-ß reversed the biological function of miR-34c mimic. The results revealed the potential application value of miR-34c as a marker molecule of phenotypic transformation, providing a potential target for improving phenotypic transformation.

Monensin inhibits glioblastoma angiogenesis via targeting multiple growth factor receptor signaling.

Glioblastoma is characterized by the extensive vascularization with poor prognosis. Targeting both tumor cell and angiogenesis may present an effective therapeutic strategy for glioblastoma. Monensin, a polyether ionophore antibiotic, has been recently recognized as promising anticancer drug candidate due to its potent and selective anti-tumor activities. However, little is known on the effects of monensin on tumor angiogenesis. In this work, we investigated the effects and underlying mechanisms of monensin on glioblastoma angiogenesis and growth. We show that monensin at nanomolar concentrations inhibits early stages of capillary network formation of glioblastoma endothelial cell. Monensin inhibited multiple endothelial cellular events, including migration, growth and survival, without affecting adhesion to Matrigel. We further demonstrate that monensin acts on endothelial cells via suppressing VEGFR- and EGFR-mediated signaling pathways. Monensin also inhibits proliferation and induces apoptosis in a panel of glioblastoma cells. However, monensin is more effective in targeting endothelial cells than tumor cells. Using glioblastoma growth xenograft mice model, we show that monensin at tolerable dose effectively inhibits glioblastoma growth. Of note, there is a significant decreased tumor vascularization from monensin-treated mice. Our work clearly demonstrates the anti-angiogenic activity of monensin and its ability in suppressing multiple tyrosine kinase receptor-mediated pathways. Our findings suggest that is a useful addition to the treatment armamentarium for glioblastoma.

The Association Between Serum Macrophage Migration Inhibitory Factor and Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage.

Inflammatory processes have long been implicated in the development of delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH). Macrophage migration inhibitory factor (MIF) has been implicated in inflammation. The aim of this study was to assess whether serum levels of MIF at admission helps to predict which patients with aSAH would subsequently develop DCI. All patients with first-ever aSAH admitted between 2016 and 2017 were considered for inclusion in this prospective study. Primary study outcome was development of DCI at discharge. Serum levels of MIF, C-reactive protein (CRP), and interleukin-6 (IL-6) were tested at admission. The relation of serum levels of MIF at admission with DCI was assessed by the logistic regression models. In this study, 201 patients were included. A correlation between Hunt and Hess score and serum levels of MIF was found (r = 0.340; P < 0.001). Fifty-two of the 201 aSAH (25.9%) were defined as DCI, and the obtained MIF level in those patients was higher than in those patients without DCI [26.4 (IQR, 22.6-32.4) ng/ml vs. 20.4 (16.4-24.6) ng/ml; P < 0.001). As a continuous variable, MIF was associated with the risk of DCI. When serum level of MIF was elevated by each 1 ng/ml, the unadjusted risk of DCI was increased by 18% (OR = 1.18 [1.12-1.25], P < 0.001), while the adjusted risk was increased by 10% (1.10 [1.03-1.19], P = 0.001). With the area under the curve (AUC) of 0.780 (95% CI, 0.710-0.849), the MIF showed a great discriminatory ability for DCI than CRP (0.665, 0.582-0.748; P < 0.001) and IL-6 (0.721, 0.642-0.799; P = 0.001). Interestingly, the combined model (MIF/IL-6/CRP) improved the MIF to predict DCI (AUC of the combined model: 0.811; 95% CI, 0.751-0.871; P = 0.024). Furthermore, inclusion of MIF in the existing risk factors for the prediction of DCI enhanced the index and net reclassification improvement (NRI) (P < 0.001) and integrated discrimination improvement (IDI) (P = 0.005) values, confirming the effective reclassification and discrimination. The data showed that elevated MIF serum level accurately identifies patients at highest risk for developing DCI following aSAH.

Snare technique for endovascular retrieval of coil extending to the atrium after embolization of a dural arteriovenous fistula.

BACKGROUND: No data exist regarding retrieval of displaced or stretched coil extending to the right atrium after endovascular embolization of cerebrovascular diseases. We describe a snare technique for retrieval of a displaced coil extending to the right atrium after embolization of dural arteriovenous fistula (DAVF). METHODS: A 35-year-old female with a DAVF underwent transjugular coil embolization that failed with displaced coil extending to the right atrium at an outside hospital. After admission to our hospital, Onyx embolization of the DAVF was performed through left facial vein-inner canthus vein-superior ophthalmic vein to the cavernous sinus. Post-embolization angiography showed complete occlusion of the DAVF. Then we attempted to snare the tip of the displaced coil that extended to the right atrium through femoral vein-inferior vena cava approach. However, current snare techniques failed to retrieve the extended coil after several attempts. Then one week later, we used a modified dual microcatheter and microwire technique to retrieve the displaced coil. One suite of microcatheter and microwire was used to produce a handmade snare device (HMD). The other suite of microcatheter and microwire was used to assist the HMD to snare the displaced coil. RESULTS: Through transjugular vein approach, we used our modified dual microcatheter and microwire snare technique (handmade snare device system) to retrieve the extended coil. After several attempts, the extended coil in the atrium was successfully retrieved. Post-procedure angiography and cardiac examinations did not show any signs of abnormality. CONCLUSIONS: For displaced coil extending to the right atrium after transvenous embolization, our method of modified dual microcatheter technique with HMD snare device system is an effective method to retrieve the extending coil.