Nrf2 activation by neferine mitigates microglial neuroinflammation after subarachnoid hemorrhage through inhibiting TAK1-NF-κB signaling.

Oxidative stress and neuroinflammation are two major causes leading to early brain injury after subarachnoid hemorrhage (SAH). Nuclear factor E2-related factor 2 (Nrf2) is a critical transcription factor that contributes to antioxidant responses. Additionally, Nrf2 could inhibit transforming growth factor beta-activated kinase 1 (TAK1), which plays a vital role in microglial activation-mediated neuroinflammation. Neferine (NE) exhibits considerable protective effects in diverse disease models. However, the detailed effect and mechanism of NE on SAH remain unknown. Our data showed that NE treatment significantly reduced behavior and cognitive impairment, and brain edema in the early period after SAH. In addition, NE mitigated SAH-induced oxidative damage, neuroinflammation, and neural death. Moreover, NE inhibited M1 microglial polarization and enhanced M2 phenotype microglia both in vivo and in vitro. Further investigations revealed that NE enhanced the Nrf2-antioxidant response element (ARE) signaling pathway and suppressed TAK1-NF-κB signaling. In contrast, depletion of Nrf2 by ML385 suppressed Nrf2-ARE signaling, induced TAK1-NF-κB activation, and further promoted M1 microglial polarization. Additionally, ML385 abated the neuroprotective effects of NE against SAH. Notably, LPS also aggravated TAK1-NF-κB activation and reversed the beneficial effects of NE after SAH. In summary, NE provides protection after SAH by inhibiting oxidative stress and modulating microglial polarization through Nrf2 activation and TAK1-NF-κB suppression.

Inhibition of NADPH oxidase 2 improves cognitive abilities by modulating aquaporin-4 after traumatic brain injury in mice.

Traumatic brain injury (TBI) is caused by acquired damage that includes cerebral edema after a mechanical injury and may cause cognitive impairment. We explored the role of nicotinamide adenine dinucleotide phosphate oxidase 2 (NADPH oxidase 2; NOX2) and aquaporin-4 (AQP4) in the process of edema and cognitive abilities after TBI in NOX2-/- and AQP4-/- mice by using the Morris water maze test (MWM), step-down test (STD), novel object recognition test (NOR) and western blotting. Knockout of NOX2 in mice decreased the AQP4 and reduce edema in the hippocampus and cortex after TBI in mice. Moreover, inhibiting AQP4 by 2-(nicotinamide)-1,3,4-thiadiazole (TGN-020) or genetic deletion of AQP4 could attenuate neurological deficits without changing reactive oxygen species (ROS) levels after TBI in mice. Taken together, we suspected that inhibiting NOX2 could improve cognitive abilities by modulating ROS levels, then affecting AQP4 levels and brain edema after in TBI mice. Our study demonstrated that NOX2 play a key role in decreasing edema in brain and improving cognitive abilities by modulating AQP4 after TBI.

The Importance of M1-and M2-Polarized Macrophages in Glioma and as Potential Treatment Targets.

Glioma is the most common and malignant tumor of the central nervous system. Glioblastoma (GBM) is the most aggressive glioma, with a poor prognosis and no effective treatment because of its high invasiveness, metabolic rate, and heterogeneity. The tumor microenvironment (TME) contains many tumor-associated macrophages (TAMs), which play a critical role in tumor proliferation, invasion, metastasis, and angiogenesis and indirectly promote an immunosuppressive microenvironment. TAM is divided into tumor-suppressive M1-like (classic activation of macrophages) and tumor-supportive M2-like (alternatively activated macrophages) polarized cells. TAMs exhibit an M1-like phenotype in the initial stages of tumor progression, and along with the promotion of lysing tumors and the functions of T cells and NK cells, tumor growth is suppressed, and they rapidly transform into M2-like polarized macrophages, which promote tumor progression. In this review, we discuss the mechanism by which M1- and M2-polarized macrophages promote or inhibit the growth of glioblastoma and indicate the future directions for treatment.

Blockage of PHLPP1 protects against myocardial ischemia/reperfusion injury in diabetic mice via activation of STAT3 signaling.

Diabetes can exacerbate myocardial ischemia/reperfusion (IR) injury. However, the sensitivity to IR injury and the underlying mechanisms in diabetic hearts remain unclear. Inhibition of PH domain leucine-rich repeating protein phosphatase (PHLPP1) could reduce myocardial IR injury, our previous study demonstrated that the expression of PHLPP1 was upregulated in diabetic myocardial IR model. Thus, this study aimed to investigate the mechanism of PHLPP1 in diabetic myocardial IR injury. Nondiabetic and diabetic C57BL/6 mice underwent 45 min of coronary artery occlusion followed by 2 h of reperfusion. Male C57BL/6 mice were injected with streptozotocin for five consecutive days to establish a diabetes model. H9c2 cells were exposed to normal or high glucose and subjected to 4 h of hypoxia followed by 4 h of reoxygenation. Diabetes or hyperglycemia increased postischemic infarct size, cellular injury, release of creatine kinase-MB, apoptosis, and oxidative stress, while exacerbating mitochondrial dysfunction. This was accompanied by enhanced expression of PHLPP1 and decreased levels of p-STAT3 and p-Akt. These effects were counteracted by PHLPP1 knockdown. Moreover, PHLPP1 knockdown resulted in an increase in mitochondrial translocation of p-STAT3 Ser727 and nuclear translocation of p-STAT3 Tyr705 and p-STAT3 Ser727. However, the effect of PHLPP1 knockdown in reducing posthypoxic cellular damage was nullified by either Stattic or LY294002. Additionally, a co-immunoprecipitation assay indicated a direct interaction between PHLPP1 and p-STAT3 Ser727, but not p-STAT3 Tyr705. The abnormal expression of PHLPP1 plays a significant role in exacerbating myocardial IR injury in diabetic mice. Knockdown of PHLPP1 to activate the STAT3 signaling pathway may represent a novel strategy for alleviating myocardial IR injury in diabetes.

Folic acid conjugated palygorskite/Au hybrid microgels: Temperature, pH and light triple-responsive and its application in drug delivery.

Herein, folic acid conjugated poly (NIPAM-co-functional palygorskite-Au-co-acrylic acid) (FA-PNFA) hybrid microgels were fabricated by emulsion polymerization. The introduction of acrylic acid can increase the low critical solution temperature (LCST) of FA-PNFA from 36 °C at pH 5.5-42 °C at pH 7.4. Doxorubicin hydrochloride (DOX) was chosen as the load drug, the results show that the DOX release behavior is driven by temperature, pH and light. Cumulative drug release rate can reach 74 % at 37 °C and pH 5.5 while only 20 % at 37 °C and pH 7.4, which effectively avoided the early leakage of the drug. In addition, by exposing FA-PNFA hybrid microgels to laser irradiation, the cumulative release rate was increased by 5 % compared to the release rate under dark conditions. Functional palygorskite-Au as physical crosslinkers not only improves the drug loading content of microgels but also promotes the release of DOX through light drive. Methyl thiazolyl tetrazolium bromide (MTT) assay demonstrated that the FA-PNFA are nontoxic up to 200 µg mL-1 towards 4T1 breast cancer cell. Meanwhile, DOX-loaded FA-PNFA show more significant cytotoxicity than the free DOX. Confocal laser scanning microscope (CLSM) revealed that the DOX-loaded FA-PNFA could be efficiently taken by 4T1 breast cancer cells. FA-PNFA hybrid microgels not only improve the LCST of PNIPAM, but also endow the microgels with photostimulation responsiveness, which can release drugs in response to the triple stimulation response of temperature, pH and light, thus effectively reducing the activity of cancer cells, making them more promising for wider medical applications.

Mucosa­associated lymphoid tissue in the central nervous system presenting as meningioma: A case report.

Mucosa-associated lymphoid tissue (MALT) lymphoma involving meningeal tissue is rare condition, easily mistaken for meningiomas upon imaging. In this report, a case of primary left temporal lobe MALT lymphoma that was initially misdiagnosed as temporal meningioma is presented, with subsequent investigation into the mechanism and treatments. Clinically, MALT lymphomas can be easily confused with meningiomas based solely on imaging and clinical manifestations. MALT lymphomas are indolent, localized lesions that can be cured through surgical resection and radiotherapy. Currently, radiotherapy is the most commonly used treatment; however, the patient in the present report did not receive any chemotherapy or radiotherapy after surgery, and recent related examinations revealed a recurrence of lymphomas that had metastasized throughout the body. As a result, future patients may benefit from chemotherapy or radiotherapy, and clinicians should be more meticulous regarding patient follow-up.

The Prognosis of Pineal Parenchymal Tumors: Development and Validation of a Nomogram Based on Surveillance, Epidemiology and End Results.

BACKGROUND: Pineal parenchymal tumors are exceedingly rare, and optimal disease management has yet to be defined. In this study, we aimed to identify prognostic factors and establish a predictive model for the prognosis of patients with pineal parenchymal tumors. METHODS: All patients with pineal parenchymal tumors in the Surveillance, Epidemiology and End Results database between 1975 and 2019 were reviewed. Data were summarized, and survival was modeled with Cox regression analyses. In addition, a nomogram predicting 5- and 10-year survival probability for pineal parenchymal tumors was developed and validated. RESULTS: We found 691 pineal parenchymal and 1961 pineal region neoplasms during 1975 and 2019 resulting in an incidence of 35%. In total, 441 patients were excluded due to incomplete data. The final cohort was subdivided into groups based on tumor histology: pineocytomas, pineoblastomas, and pineal parenchymal tumors of intermediate differentiation. Multivariate Cox analysis identified age and beam radiation as prognostic factors in pineoblastomas. Age, histology, tumor size, extent of resection, radiation, and chemotherapy were selected to build a clinical nomogram. The C-index for the nomogram was 0.795 (95% confidence interval 0.738-0.852). The calibration curves of the 5- and 10-year survival rates showed good agreement between the nomogram predictions and actual observations. CONCLUSIONS: This nomogram is a convenient and precise tool for clinicians to evaluate prognosis of pineal parenchymal tumors.

Hyperglycemia-Induced Overexpression of PH Domain Leucine-Rich Repeat Protein Phosphatase 1 (PHLPP1) Compromises the Cardioprotective Effect of Ischemic Postconditioning Via Modulation of the Akt/Mst1 Pathway Signaling.

PURPOSE: Ischemic postconditioning (IPostC) alleviates myocardial ischemia/reperfusion (IR) injury, but the protective effect is lost during diabetes. PH domain leucine-rich repeat protein phosphatase 1 (PHLPP1) is able to inactivate Akt. Our previous study found that PHLPP1 expression was upregulated in diabetic hearts. We presumed that the attenuation of myocardial injury by IPostC might be hindered by PHLPP1 overexpression in diabetic animals. METHODS AND RESULTS: Nondiabetic and diabetic mice were subjected to 45 min of ischemia followed by 2 h of reperfusion with or without IPostC. H9c2 cells were exposed to normal or high glucose and were subjected to 4 h of hypoxia followed by 4 h of reoxygenation with or without hypoxic postconditioning (HPostC). IPostC attenuated postischemic infarction, apoptosis, creatine kinase-MB, and oxidative stress, which were accompanied by increased p-Akt and decreased PHLPP1 expression and p-Mst1 in nondiabetic but not in diabetic mice. PHLPP1 knockdown or an Mst1 inhibitor reduced hypoxia/reoxygenation (HR)-induced cardiomyocyte damage in H9c2 cells exposed to normal glucose, but the effect was abolished by a PI3K/Akt inhibitor. HPostC attenuated HR-induced cardiomyocyte injury and oxidative stress accompanied by increased p-Akt as well as decreased PHLPP1 expression and p-Mst1 in H9c2 cells exposed to normal glucose but not high glucose. In addition, HPostC in combination with PHLPP1 knockdown or PHLPP1 knockdown alone reduced cell death and oxidative stress in H9c2 cells exposed to high glucose, which was hindered by PI3K/Akt inhibitor. CONCLUSION: IPostC prevented myocardial IR injury partly through PHLPP1/Akt/Mst1 signaling, and abnormalities in this pathway may be responsible for the loss of IPostC cardioprotection in diabetes.

The Mediating Effects of Resilience on Perceived Social Support and Fear of Cancer Recurrence in Glioma Patients.

Objective: To investigate the mediating effect of resilience on perceived social support and fear of cancer recurrence (FCR) in glioma patients. Methods: A total of 128 glioma patients were enrolled for the survey by Connor-Davidson resilience scale (CD-RISC), perceived social support scale (PSSS) and Chinese version of fear of progression questionnaire-short form (FoP-Q-SF). Structural equation model was used to analyze the effects of resilience. Results: The score of FCR in glioma patients was 29.52±8.30. A total of 47 patients had FCR (total score ≥34), with an incidence of 36.7%. There was a correlation between FCR, resilience and social support (P<0.01). The resilience between perceived social support and FCR in glioma patients had good fitting with the structural equation model. Resilience played a mediating role between perceived social support and FCR, with a mediating effect of 48.4%. Conclusion: The level of resilience can be improved by improving the perceived social support in patients with glioma to reduce the FCR of patients.

[Retracted] MicroRNA­186 targets IGF­1R and exerts tumor-suppressing functions in glioma.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the cell migration assay data shown in Fig. 2C were strikingly similar to data that had appeared in different form in another article by different authors. Owing to the fact that the contentious data in the above article had already been published elsewhere prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they agreed with the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 16: 7821­7828, 2017; DOI: 10.3892/mmr.2017.7586].

DBX2 Promotes Glioblastoma Cell Proliferation by Regulating REST Expression.

BACKGROUND: Glioblastoma (GBM) is the most common but lethal brain cancer with poor prognosis. The developing brain homeobox 2 (DBX2) has been reported to play important roles in tumor growth. However, the mechanisms of DBX2 in GBM are still unknown. OBJECTIVES: This study aims to investigate the function and mechanisms of DBX2 in GBM. METHODS: The expressions of DBX2 and REST in GBM were measured by analyzing data from databases, and the results were checked by qPCR and/or western blot of GBM cell lines. Cell proliferation was determined by CCK8 assay, immunohistochemistry and colony formation assay. ChIP-qPCR was used to determine the binding sites of DBX2 on REST. RESULTS: In this study, we found that the expression of DBX2 was upregulated in the GBM cell lines. The cell proliferation was damaged after blocking DBX2 expression in U87 and U251 GBM cell lines. The expression level of DBX2 had a positive relationship with that of REST. Our ChIPqPCR results showed that DBX2 is directly bound to the promoter region of REST. Additionally, the increased GBM cell proliferation caused by DBX2 overexpression can be rescued by REST loss of function. CONCLUSION: DBX2 could promote cell proliferation of GBM by binding to the promoter region of REST gene and increasing REST expression.

Microvascular decompression for hemifacial spasm involving the vertebral artery.

OBJECTIVE: Microvascular decompression (MVD) has become an accepted treatment modality for the vertebral artery (VA)-involved hemifacial spasm (HFS). The aim of this retrospective study was to evaluate clinical and surgical outcomes of HFS patients undergoing MVD and surgical and cranial nerve complications and investigate reasonable transposition procedures for two different anatomic variations of VA. METHODS: Between January and December 2018, 109 patients underwent first MVD for HFS involving VA at Nanjing Drum Tower Hospital. Based on whether the VA could be moved ventrally at the lower cranial nerves (LCNs) level, patients were assigned to Group A (movable VA, n = 72) or B (unmovable VA, n = 37), and clinical and surgical outcomes and complications on the day of post-surgery and during follow-up were assessed. All patients were followed up ranging from 17 to 24 months with a mean follow-up period of 21 months. RESULTS: After a mean follow-up of 21 months, the total cure rate significantly decreased in all patients compared to that achieved on the day of surgery, and Group A patients exhibited a higher cure rate versus Group B (93.1% vs. 75.7%, P = 0.015). Group B patients with unmovable VA revealed both higher incidence of surgical complications (45.9% vs. 15.3%, P = 0.001) and frequency of bilateral VA compression (27% vs. 8.3%, P = 0.009) versus Group A. No significant difference was observed in long-term cranial nerve complications. CONCLUSIONS: VA-involved HFS can benefit from MVD strategies after preoperative assessment of VA compression. HFS patients with movable VA may receive better long-term efficacy and fewer complications. A Teflon bridge wedged between the distal VA and medulla gives rise to adequate space for decompression surgery.

ITPRIP promotes glioma progression by linking MYL9 to DAPK1 inhibition.

Epigenetic gene silencing of the tumor suppressor death-associated protein kinase 1 (DAPK1) is implicated in the progression of malignant gliomas. However, the mechanism underlying the repression of DAPK1 in gliomas remains elusive. In this study, we identified the existence of DAPK1-inositol 1,4,5-trisphosphate receptor (IP3R)-interacting protein (ITPRIP) -myosin regulatory light polypeptide 9 (MYL9) complex in malignant glioma cells. Lentivirus co-infection and coimmunoprecipitation showed that ITPRIP bound with the death domain (DD) of DAPK1 in vitro. Further, dissociating ITPRIP-DAPK1 interaction inhibited glioma tumor growth in vitro but not in vivo. Moreover, knockdown of ITPRIP or DAPK1 impaired the ternary complex formation, whereas MYL9 knockdown did not affect ITPRIP-DAPK1 association. We further found that ITPRIP recruited MYL9 to the kinase domain (KD) of DAPK1, and in turn impeded the phosphorylation of MYL9. Accordingly, interference of ITPRIP enhanced the suppressive effects of DAPK1-KD on glioma progression both in vitro and in vivo. Our results demonstrate that ITPRIP plays a crucial role in the inhibition of DAPK1 and enhancement of tumorigenic properties of malignant glioma cells.

PTIP Inhibits Cell Invasion in Esophageal Squamous Cell Carcinoma via Modulation of EphA2 Expression.

Esophageal squamous cell carcinoma (ESCC) is a highly aggressive malignancy and treatment failure is largely due to metastasis and invasion. Aberrant tumor cell adhesion is often associated with tumor progression and metastasis. However, the exact details of cell adhesion in ESCC progression have yet to be determined. In our study, the clinical relevance of Pax2 transactivation domain-interacting protein (PTIP/PAXIP1) was analyzed by immunohistochemistry of ESCC tissues. We found that low expression of PTIP was associated with lymph node metastasis in ESCC, and loss-of-function approaches showed that depletion of PTIP promoted ESCC cell migration and invasion both in vitro and in vivo. Analysis integrating RNA-seq and ChIP-seq data revealed that PTIP directly regulated ephrin type-A receptor 2 (EphA2) expression in ESCC cells. Moreover, PTIP inhibited EphA2 expression by competing with Fosl2, which attenuated the invasion ability of ESCC cells. These results collectively suggest that PTIP regulates ESCC invasion through modulation of EphA2 expression and hence presents a potential therapeutic target for its treatment.

Nanovector Assembled from Natural Egg Yolk Lipids for Tumor-Targeted Delivery of Therapeutics.

Nanomedicine uses nanotechnology-based strategies for precision tumor therapy, including passive and ligand-mediated active tumor targeting by nanocarriers. However, the possible biotoxicity of chemosynthetic nanovectors limits their clinical applications. A novel natural egg yolk lipid nanovector (EYLN) was developed for effective loading and delivery of therapeutic agents. Lipids were extracted from egg yolks and reassembled into nanosized particles. EYLNs' stability, cellular uptake, toxicity, and delivery capacity for therapeutic agents were evaluated in vitro. The systemic toxicity and biodistribution of EYLNs were analyzed in normal mice, and the therapeutic effects of doxorubicin (Dox)-loaded EYLNs were evaluated in mouse breast cancer and hepatoma models. EYLNs had a particle size of ∼40 nm and a surface ζ-potential of -45 mV and were effectively internalized by tumor cells, without showing toxicity and side effects in vitro and in vivo. Importantly, their excellent permeability and retention effect significantly enhanced the distribution of EYLNs at tumor sites, and EYLN-Dox effectively inhibited the tumor growth in both mouse models. Targeted modification with folic acid further promoted vector-mediated drug distribution in tumors. This study demonstrates that lipids with specific proportions in the egg yolk can be used to construct natural drug vectors, providing a new strategy for nano-oncology research.

Aminoguanidine reverses cognitive deficits and activation of cAMP/CREB/BDNF pathway in mouse hippocampus after traumatic brain injury (TBI).

PRIMARY OBJECTIVE: We aim to study the effects of chronic aminoguanidine (AG) administration on learning and memory impairment after TBI and explore the potential mechanism involved in this process. RESEARCH DESIGN: Male C57BL/6J mice were divided into 6 groups: Control, TBI + Veh, TBI+ AG (50, 100, 200 and 400 mg/kg, i.p.). METHODS AND PROCEDURES: Then, we measured cyclicadenosine 3', 5'-monophosphate (cAMP) content, phosphorylated form of cAMP-response element binding protein (p-CREB) level, iNOS, brain-derived neurotrophic factor (BDNF) and postsynaptic density-93/95 (PSD-93/95) expression in hippocampus. The learning and memory abilities were assessed using Morris water maze and step-down test. MAIN OUTCOMES AND RESULTS: The results demonstrate that TBI induced down-regulation of BDNF, loss of PSD-93/95, learning and memory deficits with down-regulation of cAMP content and p-CREB/CREB ratio. Administration of AG (200 and 400 mg/kg) reversed TBI induced down-regulation of BDNF and PSD-93/95, up-regulated the cAMP content and p-CREB/CREB ratio, which resulted in improvement of learning and memory ability. CONCLUSIONS: We suspect that AG (200 and 400 mg/kg) might reverse TBI-induced selective loss of postsynaptic proteins and learning and memory deficits with the activation of cAMP/CREB/BDNF signalling pathway.

Circular RNA Complement Factor H (CFH) Promotes Glioma Progression by Sponging miR-149 and Regulating AKT1.

BACKGROUND Circular RNAs (circRNAs) are widely expressed in mammals and can regulate the development and progression of human tumors. has_circ_0015758 (circ-CFH) is an exon circRNA transcript from the GRCh37/hg19 fragment of chromosome 1 and is homologous to the protein-coding gene complement factor H (CFH). Currently, the function of circ-CFH in glioma remains unclear. MATERIAL AND METHODS In our study, circ-CFH, miR-149, and Akt1 mRNA expression levels were analyzed by qRT-PCR assays. To investigate the function of circ-CFH in cell proliferation, circ-CFH knockdown models were established by using circ-CFH siRNAs. Cell proliferation abilities were measured by CCK-8 and colony formation assays and in vivo experiments. In addition, the interaction between circ-CFH and miR-149 was assessed by luciferase reporter assays. RESULTS Circ-CFH expression was significantly upregulated in glioma tissue and was correlated with tumor grade. Circ-CFH expression levels were also markedly higher in U251 and U373 glioma cell lines. Circ-CFH knockdown inhibited cell proliferation and colony formation abilities. Luciferase assays indicated that circ-CFH functions as a miR-149 sponge and inhibits its function in U251 and U373 cells. Subsequently, AKT1 was identified as a direct target of the circ-CFH/miR-149 axis. CONCLUSIONS Circ-CFH promotes glioma progression by sponging miR-149 and regulating the AKT1 signaling pathway. The circ-CFH/miR-149/AKT1 regulation axis may be a potential target for glioma therapy.

Mir-758-5p Suppresses Glioblastoma Proliferation, Migration and Invasion by Targeting ZBTB20.

BACKGROUND/AIMS: To determine the cellular functions and clinical significance of micro-758-5p (miR-758-5p) in glioblastoma (GBM) by targeting zinc finger and BTB domain-containing protein 20 (ZBTB20). METHODS: Fifty-five paired GBM tissues and adjacent normal tissues, GBM cell lines (U118, LN-299, H4, A172, U87-MG, and U251), and normal human astrocyte cell line (HEB) were used. miR-758-5p mimics, ZBTB20 siRNA, and pcDNA3.1-ZBTB20 were transiently transduced into cancer cells independently or together. qRT-PCR was conducted to analyze the expression of miR-758-5p and ZBTB20. Luciferase reporter assays were performed to determine the effect of miR-758-5p on ZBTB20. Western blot was applied to measure the expression of ZBTB20, PCNA, and cleaved caspase3. Cell Counting Kit-8 (CCK8), colony formation, FACS, and Transwell assays were carried out to detect cellular proliferation, apoptosis, migration, and invasion. Xenograft experiments were implemented to evaluate tumor growth and metastasis in vivo. RESULTS: miR-758-5p was significantly downregulated in GBM tissues and cell lines compared with that in adjacent normal tissues and HEB cells. miR-758-5p overexpression inhibited the proliferation, migration, and invasion of GBM cells and induced apoptosis by regulating the ZBTB20 expression. Pearson correlation analysis also confirmed that miR-758-5p was inversely correlated with ZBTB20 in GBM tissues. miR-758-5p suppressed tumor growth and metastasis in vivo. The restored ZBTB20 expression partially rescued the miR-758-5p-induced inhibition of GBM cell proliferation, migration, and invasion. Kaplan-Meier curve analysis revealed that a high miR-758-5p expression indicated an enhanced prognosis of patients with GBM. CONCLUSION: miR-758-5p suppressed GBM progression by targeting ZBTB20. The miR-758-5p/ZBTB20 axis might be a promising therapeutic target for GBM treatment.

Decreased BRMS1L expression is correlated with glioma grade and predicts poor survival in glioblastoma via an invasive phenotype.

AIMS: To evaluate the prognostic and clinicopathological features of glioma with BRMS1L expression. METHODS: Total 120 glioma samples were obtained as discovery cohort. CGGA, GSE and TCGA datasets were obtained as validation sets. Furthermore, Kaplan-Meier survival and multivariate Cox analysis were used to evaluate the survival distributions. Moreover, the functional role of BRMS1L was also analyzed by transwell assay. RESULTS: In the discovery cohort, decreased BRMS1L expression was significantly associated with high-grade glioma as well as the higher mortality in survival analysis (log-rank test, p< 0.01). And the three validation cohorts showed the similar results. Furthermore, BRMS1L act as an independent prognostic factor in glioblastoma patients. Additionally, functional assay showed that ectopic of BRMS1L suppressed glioma cells' invasion. CONCLUSION: BRMS1L plays as an anti-oncogene in GBM and indicates a new potential therapeutic target.

Cerebral vasomotor reactivity predicts the development of acute stroke in patients with internal carotid artery stenosis.

OBJECTIVE: To investigate the relationship between cerebral vasomotor reactivity (VMR) and acute stroke in patients with internal carotid artery stenosis. METHODS: 54 patients with internal carotid artery stenosis were enrolled. VMR was calculated by transcranial Doppler monitoring of the velocity of blood flow. 3-Dimensional dynamic contrast enhanced magnetic resonance angiography was used to detect stenosis, and diffusion weighted imaging was used to detect infarction. RESULTS: VMR value was significantly lower in patients with carotid artery stenosis than in control group (T=3.112, P=0.002), and significantly lower in patients with aortic atherosclerotic stroke than in non-infarct group (T=10.930, P=0.000). However, VMR value was significantly higher in patients with new-onset small-artery occlusion stroke than in non-infarction group (T=-2.538, P=0.013). Scatter plots showed that aortic atherosclerotic stroke occurred mainly in patients with severe internal carotid artery stenosis, and VMR value in cerebral artery significantly decreased. CONCLUSION: Decreased VMR value is an important prognostic factor for the occurrence of aortic atherosclerotic stroke, and can be used as a reference for preoperative hemodynamic evaluation in patients with internal carotid artery stenosis.