M alignant gliomas are the most common type of primary malignant brain tumor, and more than half of all gliomas are glioblastomas (Grade IV astrocytoma), one of the most aggressive and lethal types of brain tumor. Glioblastoma cells easily infiltrate into the normal cerebral cortex, ultimately resulting in the death of the patient. Well-defined risk factors for glioblastoma include radiation exposure and certain genetic syndromes. 21Several molecular and genomic datasets have recently been generated that have allowed identification of at least 4 subtypes of glioblastoma: classical, mesenchymal, proneural, and neural.14 Previous studies in glioblastoma geabbreviatioNs FBS = fetal bovine serum; HCC = hepatocellular carcinoma; HUVEC = human umbilical vein endothelial cell; lncRNA = long noncoding RNA; ncRNA = noncoding RNA; RT-qPCR = real-time quantitative reverse transcription polymerase chain reaction; SD = standard deviation. 3 Department of Respiratory Medicine, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing; and 4 Department of Oncology, The Second Affiliated Hospital of Suzhou University, Suzhou, China obJective Increased levels of H19 long noncoding RNA (lncRNA) have been observed in many cancers, suggesting that overexpression of H19 may be important in the development of carcinogenesis. However, the role of H19 in human glioblastoma is still unclear. The object of this study was to examine the level of H19 in glioblastoma samples and investigate the role of H19 in glioblastoma carcinogenesis. methods Glioblastoma and nontumor brain tissue specimens were obtained from tissue obtained during tumor resection in 30 patients with glioblastoma. The level of H19 lncRNA was detected by real-time quantitative reverse transcription polymerase chain reaction. The role of H19 in invasion, angiogenesis, and stemness of glioblastoma cells was then investigated using commercially produced cell lines (U87 and U373). The effects of H19 overexpression on glioblastoma cell invasion and angiogenesis were detected by in vitro Matrigel invasion and endothelial tube formation assay. The effects of H19 on glioblastoma cell stemness and tumorigenicity were investigated by neurosphere formation and an in vivo murine xenograft model. results The authors found that H19 is significantly overexpressed in glioblastoma tissues, and the level of expression was associated with patient survival. In the subsequent investigations, the authors found that overexpression of H19 promotes glioblastoma cell invasion and angiogenesis in vitro. Interestingly, H19 was also significantly overexpressed in CD133 + glioblastoma cells, and overexpression of H19 was associated with increased neurosphere formation of glioblastoma cells. Finally, stable overexpression of H19 was associated with increased tumor growth in the murine xenograft model. coNclusioNs The results of this study suggest that increased expression of H19 lncRNA promotes invasion, angiogenesis, stemness, and tumorigenicity of glioblastoma cells. Taken together, the...

OBJECTIVE Increased levels of H19 long noncoding RNA (lncRNA) have been observed in many cancers, suggesting that overexpression of H19 may be important in the development of carcinogenesis. However, the role of H19 in human glioblastoma is still unclear. The object of this study was to examine the level of H19 in glioblastoma samples and investigate the role of H19 in glioblastoma carcinogenesis. METHODS Glioblastoma and nontumor brain tissue specimens were obtained from tissue obtained during tumor resection in 30 patients with glioblastoma. The level of H19 lncRNA was detected by real-time quantitative reverse transcription polymerase chain reaction. The role of H19 in invasion, angiogenesis, and stemness of glioblastoma cells was then investigated using commercially produced cell lines (U87 and U373). The effects of H19 overexpression on glioblastoma cell invasion and angiogenesis were detected by in vitro Matrigel invasion and endothelial tube formation assay. The effects of H19 on glioblastoma cell stemness and tumorigenicity were investigated by neurosphere formation and an in vivo murine xenograft model. RESULTS The authors found that H19 is significantly overexpressed in glioblastoma tissues, and the level of expression was associated with patient survival. In the subsequent investigations, the authors found that overexpression of H19 promotes glioblastoma cell invasion and angiogenesis in vitro. Interestingly, H19 was also significantly overexpressed in CD133 glioblastoma cells, and overexpression of H19 was associated with increased neurosphere formation of glioblastoma cells. Finally, stable overexpression of H19 was associated with increased tumor growth in the murine xenograft model. CONCLUSIONS The results of this study suggest that increased expression of H19 lncRNA promotes invasion, angiogenesis, stemness, and tumorigenicity of glioblastoma cells. Taken together, these findings indicate that H19 plays an important role in tumorigenicity and stemness of glioblastoma and thus could be a therapeutic target for treatment of glioblastoma in the future.

Background: Inflammation is a potential crucial factor in the pathogenesis of subarachnoid hemorrhage (SAH). Circulating microRNAs (miRNAs) are involved in the regulation of diverse aspects of neuronal dysfunction. The therapeutic potential of miRNAs has been demonstrated in several CNS disorders and is thought to involve modulation of neuroinflammation. Here, we found that peripherally injected modified exosomes (Exos) delivered miRNAs to the brains of mice with SAH and that the potential mechanism was regulated by regulation of neuroinflammation. Methods: Next-generation sequencing (NGS) and qRT-PCR were used to define the global miRNA profile of plasma exosomes in aSAH patients and healthy controls. We peripherally injected RVG/Exos/miR-193b-3p to achieve delivery of miR-193b-3p to the brain of mice with SAH. The effects of miR-193b-3p on SAH were assayed using a neurological score, brain water content, blood-brain barrier (BBB) injury, and Fluoro-Jade C (FJC) staining. Western blotting analysis, enzyme-linked immunosorbent assay (ELISA), and qRT-PCR were used to measure various proteins and mRNA levels. Results: NGS and qRT-PCR revealed that four circulating exosomal miRNAs were differentially expressed. RVG/Exos exhibited improved targeting to the brains of SAH mice. MiR-193b-3p suppressed the expression and activity of HDAC3, upregulating the acetylation of NF-κB p65. Finally, miR-193b-3p treatment mitigated the neurological behavioral impairment, brain edema, BBB injury, and neurodegeneration induced by SAH, and reduced inflammatory cytokine expression in the brains of mice after SAH. Conclusions: Exos/miR-193b-3p treatment attenuated the inflammatory response by acetylation of the NF-κB p65 via suppressed expression and activity of HDAC3. These effects alleviated neurobehavioral impairments and neuroinflammation following SAH.

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Objective: To investigate the hemodynamic features before and after embolization of paraclinoidal aneurysms using hemodynamic numerical simulation and the influence of embolization on recurrence after embolization. Methods: From January 2016 to December 2017, we enrolled a total of 113 paraclinoidal aneurysms treated with embolization. They were divided into recurrent group and stable group depending on follow-up results. An aneurysm model was generated based on 3D-DSA before and after embolization. The hemodynamic characteristics were analyzed between two groups using Computational fluid dynamic (CFD). Results: In the recurrent group, the peak systolic WSS, OSI and velocity around the aneurysm neck areas prior to embolization were 20.47 ± 3.04 Pa, 0.06 ± 0.02 and 0.07 ± 0.03 m/s, respectively. These values were 23.50 ± 4.11 Pa, 0.06 ± 0.01 and 0.11 ± 0.02 m/s, respectively in the stable group ( P > 0.05). The WSS, OSI, velocity around the same areas in the recurrent group after embolization were 35.59 ± 8.75 Pa, 0.07 ± 0.02 and 0.12 ± 0.03 m/s, respectively ( P < 0.01). In the stable group, the WSS, OSI and velocity were 13.08 ± 2.89 Pa, 0.04 ± 0.01 and 0.07 ± 0.02 m/s, respectively ( P < 0.01). After embolization, the WSS, OSI and velocity around the aneurysm neck areas in the recurrent group were significantly higher than those in the stable group. Conclusions: High peak systolic WSS, OSI and velocity around aneurysm neck areas after embolization of paraclinoidal aneurysms may be important factors leading to recurrence.

Objective: The aim of this study was to evaluate the safety and efficacy of endovascular treatment for ruptured very small (≤3 mm) intracranial aneurysms (VSIAs).Methods: The clinical data and imaging results for 152 patients with VSIAs treated with coil embolization from August 2014 to June 2020 were retrospectively reviewed. The influential factors related to the preoperative complications, aneurysm recurrence, and clinical outcomes for these patients were analyzed.Results: Among 152 patients with ruptured VSIAs, 90 were treated with coil embolization alone, while 62 were treated with stent-assisted coil embolization. Eighteen patients experienced intra and/or postoperative complications (overall incidence = 11.8%). One person died of intraoperative aneurysm re-rupture and postoperative rebleeding (mortality rate = 0.65%). Twenty patients had various degrees of neurological dysfunction (morbidity rate = 13.1%). Statistical analysis showed that there was no independent risk factor associated with perioperative complications. The rate of complete aneurysm occlusion at discharge and follow-up was 76.3 and 86.2%, respectively. A total of 105 patients underwent digital subtraction angiography during follow-up, and 18 of them experienced postoperative recurrence (recurrence rate = 17.1%). Seven patients were retreated (retreatment rate = 6.7%). The use of stents was the only factor that affected the postoperative recurrence of aneurysm. The incidence of favorable clinical outcomes (Glasgow Outcome Scale score ≥ 4) at discharge and follow-up was 86.2 and 97.1%, respectively. Univariate analysis showed that the preoperative Hunt-Hess grade, CT Fisher grade, and perioperative complications were risk factors for poor clinical outcomes. Multiple logistic regression analysis showed that perioperative complication was the most significant risk factor for the clinical prognosis of patients with ruptured VSIAs.Conclusion: Endovascular treatment is a safe and efficient approach for ruptured VSIAs. Stent-assisted coiling reduced the recurrence rate of aneurysm without increasing the incidence of perioperative complications. The Hunt-Hess grade, CT Fisher grade, and perioperative complications were independent factors associated with the clinical outcomes of patients with ruptured VSIAs, and perioperative complication was the most significant risk factor for poor prognosis in patients.

IntroductionS100 calcium-binding protein A8 (S100A8) is also known as macrophage-related protein 8, which is involved in various pathological processes in the central nervous system post-traumatic brain injury (TBI), and plays a critical role in inducing inflammatory cytokines. Accumulating evidences have indicated that toll-like receptor 4 (TLR4) is considered to be involved in inflammatory responses post TBI. The present study was designed to analyze the hypothesis that S100A8 is the key molecule that induces inflammation via TLR4 in TBI.MethodsThe weight-drop TBI model was used and randomly implemented on mice that were categorized into six groups: Sham, NS, S100A8, S100A8+TAK-242, TBI, and TBI+TAK-242 groups. In the S100A8+TAK-242 and TBI+TAK-242 groups, at half an hour prior to the intracerebroventricular administration of S100A8 or TBI, mice were intraperitoneally treated with TAK-242 that acts as a selective antagonist and inhibitor of TLR4. Furthermore, the protein recombinant of S100A8 was injected into the lateral ventricle of the brain of mice in the S100A8 and S100A8+TAK-242 groups. Sterile normal saline was injected into the lateral ventricle in the NS group. To evaluate the association between S100A8 and TLR4, Western blot, immunofluorescence, enzyme-linked immunosorbent assay (ELISA), and Nissl staining were employed. Simultaneously, the neurological score and brain water content were assessed. In the in vitro analysis, BV-2 microglial cells were stimulated with lipopolysaccharide LPS or S100A8 recombinant protein, with or without TAK-242. The expression of the related proteins was subsequently detected by Western blot or enzyme-linked immunosorbent assay.ResultsThe levels of S100A8 protein and pro-inflammatory cytokines were significantly elevated after TBI. There was a reduction in the neurological scores of non-TBI animals with remarkable severe brain edema after the intracerebroventricular administration of S100A8. Furthermore, the TLR4, p-p65, and myeloid differentiation factor 88 (MyD88) levels were elevated after the administration of S100A8 or TBI, which could be restored by TAK-242. Meanwhile, in the in vitro analysis, due to the stimulation of S100A8 or LPS, there was an upregulation of p-p65 and MyD88, which could also be suppressed by TAK-242.ConclusionThe present study demonstrated that the TLR4-MyD88 pathway was activated by S100A8, which is essential for the development of inflammation in the brain after TBI.