Balloon compression, neuroendoscopy and electrophysiological monitoring-assisted retrosigmoid approach for resection of cholesteatoma in the cerebellopontine angle-Meckel's cave: a technical description.

We report a case of cholesteatoma that caused left facial pain with facial numbness. The tumour was located in the left cerebellopontine angle (CPA) and Meckel's cave. A balloon was first placed into Meckel's cave, and then, under electrophysiological monitoring, the tumour within the CPA cistern was resected via the retrosigmoid approach. The balloon was inflated in Meckel's cave to push the tumour out of Meckel's cave, and then, the tumour was completely removed under endoscopy. The symptoms, including pain and numbness, subsided after surgery.

Gliosarcoma: The Distinct Genomic Alterations Identified by Comprehensive Analysis of Copy Number Variations.

Gliosarcoma (GSM), a histologic variant of glioblastoma (GBM), carries a poor prognosis with less than one year of median survival. Though GSM is similar with GBM in most clinical and pathological symptoms, GBM has unique molecular and histological features. However, as the rarity of GSM samples, the genetic information of this tumor is still lacking. Here, we take a comprehensive analysis of DNA copy number variations (CNV) in GBM and GSM. Whole genome sequencing was performed on 21 cases of GBM and 15 cases of GSM. CNVKIT is used for CNV calling. Our data showed that chromosomes 7, 8, 9, and 10 were the regions where CNV frequently happened in both GBM and GSM. There was a distinct CNV signal in chromosome 2 especially in GSM. The pathway enrichment of genes with CNV was suggested that the GBM and GSM shared the similar mechanism of tumor development. However, the CNV of some screened genes displayed a disparate form between GBM and GSM, such as AMP, BEND2, HDAC6, FOXP3, ZBTB33, TFE3, and VEGFD. It meant that GSM was a distinct subgroup possessing typical biomarkers. The pathways and copy number alterations detected in this study may represent key drivers in gliosarcoma oncogenesis and may provide a starting point toward targeted oncologic analysis with therapeutic potential.

SOCS1/JAK2/STAT3 axis regulates early brain injury induced by subarachnoid hemorrhage via inflammatory responses.

The SOCS1/JAK2/STAT3 axis is strongly associated with tumor growth and progression, and participates in cytokine secretion in many diseases. However, the effects of the SOCS1/JAK2/STAT3 axis in experimental subarachnoid hemorrhage remain to be studied. A subarachnoid hemorrhage model was established in rats by infusing autologous blood into the optic chiasm pool. Some rats were first treated with JAK2/STAT3 small interfering RNA (Si-JAK2/Si-STAT3) or overexpression plasmids of JAK2/STAT3. In the brains of subarachnoid hemorrhage model rats, the expression levels of both JAK2 and STAT3 were upregulated and the expression of SOCS1 was downregulated, reaching a peak at 48 hours after injury. Simultaneously, the interactions between JAK2 and SOCS1 were reduced. In contrast, the interactions between JAK2 and STAT3 were markedly enhanced. Si-JAK2 and Si-STAT3 treatment alleviated cortical neuronal cell apoptosis and necrosis, destruction of the blood-brain barrier, brain edema, and cognitive functional impairment after subarachnoid hemorrhage. This was accompanied by decreased phosphorylation of JAK2 and STAT3 protein, decreased total levels of JAK2 and STAT3 protein, and increased SOCS1 protein expression. However, overexpression of JAK2 and STAT3 exerted opposite effects, aggravating subarachnoid hemorrhage-induced early brain injury. Si-JAK2 and Si-STAT3 inhibited M1-type microglial conversion and the release of pro-inflammatory factors (inducible nitric oxide synthase, interleukin-1ß, and tumor necrosis factor-α) and increased the release of anti-inflammatory factors (arginase-1, interleukin-10, and interleukin-4). Furthermore, primary neurons stimulated with oxyhemoglobin were used to simulate subarachnoid hemorrhage in vitro, and the JAK2 inhibitor AG490 was used as an intervention. The in vitro results also suggested that neuronal protection is mediated by the inhibition of JAK2 and STAT3 expression. Together, our findings indicate that the SOCS1/JAK2/STAT3 axis contributes to early brain injury after subarachnoid hemorrhage both in vitro and in vivo by inducing inflammatory responses. This study was approved by the Animal Ethics Committee of Anhui Medical University and the First Affiliated Hospital of University of Science and Technology of China (approval No. LLSC-20180202) on March 1, 2018.

Osimertinib successfully combats EGFR-negative glioblastoma cells by inhibiting the MAPK pathway.

Glioblastoma (GBM) patients have extremely poor prognoses, and currently no effective treatment available including surgery, radiation, and chemotherapy. MAPK-interacting kinases (MNK1/2) as the downstream of the MAPK-signaling pathway regulate protein synthesis in normal and tumor cells. Research has shown that targeting MNKs may be an effective strategy to treat GBM. In this study we investigated the antitumor activity of osimertinib, an FDA-approved epidermal growth factor receptor (EGFR) inhibitor, against patient-derived primary GBM cells. Using high-throughput screening approach, we screened the entire panel of FDA-approved drugs against primary cancer cells derived from glioblastoma patients, found that osimertinib (3 µM) suppressed the proliferation of a subset (10/22) of EGFR-negative GBM cells (>50% growth inhibition). We detected the gene expression difference between osimertinib-sensitive and -resistant cells, found that osimertinib-sensitive GBM cells displayed activated MAPK-signaling pathway. We further showed that osimertinib potently inhibited the MNK kinase activities with IC50 values of 324 nM and 48.6 nM, respectively, against MNK1 and MNK2 kinases; osimertinib (0.3-3 µM) dose-dependently suppressed the phosphorylation of eukaryotic translation initiation factor 4E (eIF4E). In GBM patient-derived xenografts mice, oral administration of osimertinib (40 mg· kg-1 ·d-1, for 18 days) significantly suppressed the tumor growth (TGI = 74.5%) and inhibited eIF4E phosphorylation in tumor cells. Given the fact that osimertinib could cross the blood-brain barrier and its toxicity was well tolerated in patients, our results suggest that osimertinib could be a new and effective drug candidate for the EGFR-negative GBM patients.

Efficacy of and risk factors for percutaneous balloon compression for trigeminal neuralgia in elderly patients.

OBJECTIVE: To investigate the efficacy and safety of percutaneous balloon compression (PBC) for the treatment of trigeminal neuralgia in elderly patients. Methods: We retrospectively analysed data of 105 elderly patients with primary trigeminal neuralgia who were over 70 years and underwent percutaneous balloon compression using anatomic positioning and imaging guidance from January 2019 to November 2019. Results: The immediate cure rate of pain in this group of patients was 97.1% (Barrow Neurological Institute (BNI) pain scores: class I and II; numbness score: class II). Postoperative keratitis was reported in 1 patient, masticatory muscle weakness and muscle atrophy in 1 patient, herpes labialis in 8 patients and lacunar infarction in 2 patients. Facial numbness and decreased sensation occurred in patients with significant pain relief. No serious complications were reported. There was no statistically significant difference in efficacy between the short compression and long compression time groups. Conclusion: PBC is a safe and effective approach to treat trigeminal neuralgia.

HAUSP promoted the growth of glioma cells in vitro and in vivo via stabilizing NANOG.

OBJECTIVE: To investigate the role and mechanisms of HAUSP (Herpesvirus Associated Ubiquitin Specific Protease) and NANOG in pathogenesis of malignant human gliomas progression. METHODS: Lentivirus-mediated HAUSP over-expression and RNAiHAUSP mediated HAUSP down-regulation were established in the glioma cells (U87 and U251 cell lines). Firstly, Real-time qPCR, western-blot (WB) and immunofluorescence staining were performed to detect mRNA levels, protein expressions and deposition of HAUSP and NANOG in the glioma cells, respectively. Then cell proliferation, invasion, apoptosis and xenograft tumor growth in nude mice were assessed by using cell counting kit-8 (CCK-8) assay, transwell assay, flow cytometry (FCM) and Hematoxylin-Eosin (HE) staining. RESULTS: We first demonstrated HAUSP was significantly increased in lentivirus- mediated HAUSP over-expression cells compared to the Control group. HAUSP over-expression could upregulate genes involved in proliferation and invasion such as NANOG. However, the mRNA of NANOG had no significant changes. Similarly, in RNAiHAUSP mediated HAUSP down-regulation group, HAUSP were significantly decreased compared to the Control group. Simultaneously, NANOG protein were decreased significantly, which decreased the proliferation and invasion, increased the apoptosis rate of glioma cells. Finally, low expression of HAUSP could suppress xenograft tumors growth in nude mice in different periods. CONCLUSION: This study revealed that HAUSP-NANOG pathway is a key target to inhibit glioma cells proliferation, and NANOG play important role in the formation and evolution of glioma cells. The regulation of HAUSP could change the biological activity of glioma cells through regulate NANOG expression.

Nomogram for Predicting Postoperative Delirium After Deep Brain Stimulation Surgery for Parkinson's Disease.

OBJECTIVE: The purpose of the present study was to construct a nomogram for postoperative delirium (POD) after deep brain stimulation (DBS) surgery in patients with Parkinson's disease (PD). METHODS: The present study retrospectively enrolled 165 patients with PD who had undergone DBS surgery. The patients were assessed using the Confusion Assessment Method for the Intensive Care Unit and were divided into 2 groups: the delirium group and nondelirium group. The nomogram for POD after DBS surgery was constructed from the results of univariate analysis and multivariate logistic analysis of the influencing factors for POD after DBS surgery. RESULTS: Univariate analysis revealed that the preoperative length of stay and the presence of preoperative brain atrophy, preoperative pulmonary inflammation, and postoperative cerebral edema were statistically significant. The results from the nonmotor symptoms scale for PD, mini-mental state examination, PD sleep scale, and unified PD rating scale III were also statistically significant (P < 0.05). Multivariate logistic regression analysis showed that the unified PD rating scale III (odds ratio [OR], 2.284; 95% confidence interval [CI], 1.614-3.232), nonmotor symptoms scale for PD (OR, 8.191; 95% CI, 5.629-11.917), PD sleep scale (OR, 0.058; 95% CI, 0.05-0.067), preoperative length of stay (OR, 1.230; 95% CI, 1.053-1.437), and preoperative brain atrophy (OR, 3.912; 95% CI, 3.5-4.255) were independent factors that influenced the occurrence of POD after DBS surgery. A nomogram model was constructed using these indicators. The model predicted an area under the receiver operating characteristic curve after DBS surgery of 0.870 (95% CI, 0.808-0.918), sensitivity of 74.19%, and specificity of 91.54%. CONCLUSIONS: The present study has presented a reliable and useful nomogram that can accurately predict the occurrence of POD after DBS surgery in patients with PD. This tool is easy to use and could assist physicians during the therapeutic decision-making process.

Neuroprotection mediated by the Wnt/Frizzled signaling pathway in early brain injury induced by subarachnoid hemorrhage.

The Wnt/Frizzled signaling pathway participates in many inflammation-linked diseases. However, the inflammatory response mediated by the Wnt/Frizzled signaling pathway in experimental subarachnoid hemorrhage has not been thoroughly investigated. Consequently, in this study, we examined the potential role of the Wnt/Frizzled signaling pathway in early brain injury in rat models of subarachnoid hemorrhage. Simultaneously, possible neuroprotective mechanisms were also investigated. Experimental subarachnoid hemorrhage rat models were induced by injecting autologous blood into the prechiasmatic cistern. Experiment 1 was designed to examine expression of the Wnt/Frizzled signaling pathway in early brain injury induced by subarachnoid hemorrhage. In total, 42 adult rats were divided into sham (injection of equivalent volume of saline), 6-, 12-, 24-, 48-, 72-hour, and 1-week subarachnoid hemorrhage groups. Experiment 2 was designed to examine neuroprotective mechanisms of the Wnt/Frizzled signaling pathway in early brain injury induced by subarachnoid hemorrhage. Rats were treated with recombinant human Wnt1 (rhwnt1), small interfering Wnt1 (siwnt1) RNA, and monoclonal antibody of Frizzled1 (anti-Frizzled1) at 48 hours after subarachnoid hemorrhage. Expression levels of Wnt1, Frizzled1, ß-catenin, peroxisome proliferator-activated receptor-γ, CD36, and active nuclear factor-κB were examined by western blot assay and immunofluorescence staining. Microglia type conversion and inflammatory cytokine levels in brain tissue were examined by immunofluorescence staining and enzyme-linked immunosorbent assay. Our results show that compared with the sham group, expression levels of Wnt1, Frizzled1, and ß-catenin were low and reduced to a minimum at 48 hours, gradually returning to baseline at 1 week after subarachnoid hemorrhage. rhwnt1 treatment markedly increased Wnt1 expression and alleviated subarachnoid hemorrhage-induced early brain injury (within 72 hours), including cortical cell apoptosis, brain edema, and neurobehavioral deficits, accompanied by increasing protein levels of ß-catenin, CD36, and peroxisome proliferator-activated receptor-γ and decreasing protein levels of nuclear factor-κB. Of note, rhwnt1 promoted M2-type microglia conversion and inhibited release of inflammatory cytokines (interleukin-1ß, interleukin-6, and tumor necrosis factor-α). In contrast, siwnt1 RNA and anti-Frizzled1 treatment both resulted in an opposite effect. In conclusion, the Wnt/Frizzled1 signaling pathway may participate in subarachnoid hemorrhage-induced early brain injury via inhibiting the inflammatory response, including regulating microglia type conversion and decreasing inflammatory cytokine release. The study was approved by the Animal Ethics Committee of Anhui Medical University and First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China (approval No. LLSC-20180202) in May 2017.

Effects of lentivirus-mediated CYP17A1 gene silencing on the biological activity of glioma.

Gliomas are the most common malignant primary brain tumors with poor prognosis. We attempted to explore the role of CYP17A1 in glioma progression. We demonstrated that the expression of CYP17A1 was significantly higher in the glioma tissues than the normal brain tissues, especially in malignant glioma. Moreover, the expression of CYP17A1 gene was positively correlative with glioma pathological grades. In vitro, CYP17A1 gene silence inhibited the proliferation and invasion of glioma cells and promoted the apoptosis in glioma cells. Also, the subcutaneously transplanted tumour in BALB/C-nu showed that CYP17A1 gene silence inhibited glioma growth. These results reveal that CYP17A1 plays a major role in the progress of glioma.

Altered attention networks and DMN in refractory epilepsy: A resting-state functional and causal connectivity study.

PURPOSE: Epilepsy is considered a disorder of neural networks. Patients diagnosed with refractory epilepsy frequently experience attention impairments. Seizure activity in epilepsy may disturb brain networks and damage the brain function of attention. The aims of this study were to assess functional and causal connectivities of the attention networks and default mode network using resting-state functional magnetic resonance imaging (fMRI). METHOD: Resting-state fMRI data were gathered from 19 patients with refractory epilepsy (mixed localization and aetiologies) and 21 healthy people. The fMRI data were analyzed by group independent component analysis (ICA) fMRI toolbox to extract dorsal attention network (DAN), ventral attention network (VAN), and default mode network (DMN). The components of the selected networks were compared between patients and healthy controls to explore the change in functional connectivity (FC). Granger causality analysis was performed by taking the aforementioned significant brain areas as regions of interest (ROIs) to calculate autoregression coefficients of each pair of ROIs. Comparisons were done to find the significantly different causal connectivity when FC was changed between patients and healthy controls. RESULTS: In DAN, the FC values of the bilateral frontal eye field (FEF) and left intraparietal sulcus (IPS) were decreased. In VAN, the FC values of the double-side ventral prefrontal cortex (vPFC) and the temporoparietal junction (TPJ) were reduced. As for DMN, the FC values of the bilateral medial prefrontal cortices (mPFC) were decreased whereas those for the bilateral precuneus (PCUN) were increased. Granger causal connectivity values were correlated: causal influence was decreased significantly from the left IPS (in DAN) to the double side of the vPFC but remained the same for the right FEF (in DAN) to the right TPJ. The value was decreased from the left PCUN (in DMN) to the right TPJ and FEF, and the causal flow from the right PCUN to the right TPJ and bilateral vPFC was also significantly inhibited (p < 0.05). CONCLUSION: Frequent seizures in patients with refractory epilepsy may damage the cortex and disturb DAN, VAN, and DMN, leading to functional and causal connectivity alteration. In addition, epileptic activity may disrupt network interactions and further influence information communication.

G-protein-coupled receptor kinase-5 promotes glioblastoma progression by targeting the nuclear factor kappa B pathway.

G-protein-coupled receptor kinase-5 (GRK5) plays essential roles in multiple celluar events. However, its role in the development and progression of glioma is poorly understood. In this research, we found that GRK5 is significantly upregulated in human gliomas. For the first time, a close relationship was noted between GRK5 expression and blood vessel development in human glioma. Specifically co-expression of GRK5 and the tumor stem cell marker CD133 was observed in the cytoplasm of high grade glioma cells. The depletion of GRK5 suppressed the proliferation, migration and invasion in glioma cells, and promoted apoptosis. We next discovered that GRK5 knockdown inhibits the nuclear factor kappa B (NF-κB) pathway, thus resulting in downregulation of key downstream secretory products CCL2, IL-6 and IL-8 in glioma cell conditioned medium (CM). In addition, treatment of cells with the NF-κB stimulator PMA reversed this effect and increased the GRK5 level. Our results demonstrate an oncogenic role for GRK5 and reveal an activation of the GRK5-NF-κB pathway during the malignant progression of glioma.

The long non-coding RNA CRNDE acts as a ceRNA and promotes glioma malignancy by preventing miR-136-5p-mediated downregulation of Bcl-2 and Wnt2.

The colorectal neoplasia differentially expressed (CRNDE) gene encodes a long non-coding RNA (lncRNA) that is the most unregulated among 129 lncRNAs differentially expressed in gliomas. In this study, we confirmed high CRNDE expression in clinical glioma specimens and observed through experiments in human glioma cell lines a novel molecular mechanism by which CRNDE may contribute to glioma pathogenesis. By inducing or silencing CRNDE expression, we detected a positive correlation between CRNDE levels and the proliferative, migratory, and invasive capacities of glioma cells, which were concomitant with a decreased apoptosis rate. Our experiments also suggest that these effects are mediated by downregulation of miR-136-5p, which correlated with the glioma WHO grade. Based on predicted CRNDE/miR-136-5p/mRNA interactions, both the mRNA and protein expression analyses suggested that miR-136-5p-mediated repression of Bcl-2 and Wnt2 underlies the pro-tumoral actions of CRNDE. We therefore propose that CRNDE functions as a competing endogenous RNA (ceRNA) that binds to and negatively regulates miR-136-5p, thereby protecting Bcl-2 and Wnt2 from miR-136-5p-mediated inhibition in glioma.

How does conserved dopamine neurotrophic factor protect against and rescue neurodegeneration of PC12 cells?

Conserved dopamine neurotrophic factor protects and rescues dopaminergic neurodegeneration induced by 6-hydroxydopamine in vivo, but its potential value in treating Parkinson's disease remains controversial. Here, we used the proteasome inhibitors lactacystin and MG132 to induce neurodegeneration of PC12 cells. Afterwards, conserved dopamine neurotrophic factor was administrated as a therapeutic factor, both pretreatment and posttreatment. Our results showed that (1) conserved dopamine neurotrophic factor enhanced lactacystin/MG132-induced cell viability and morphology, and attenuated alpha-synuclein accumulation in differentiated PC12 cells. (2) Enzyme linked immunosorbent assay showed up-regulated 26S proteasomal activity in MG132-induced PC12 cells after pre- and posttreatment with conserved dopamine neurotrophic factor. Similarly, 26S proteasome activity was upregulated in lactacystin-induced PC12 cells pretreated with conserved dopamine neurotrophic factor. (3) With regard proteolytic enzymes (specifically, glutamyl peptide hydrolase, chymotrypsin, and trypsin), glutamyl peptide hydrolase activity was up-regulated in lactacystin/MG132-administered PC12 cells after pre- and posttreatment with conserved dopamine neurotrophic factor. However, upregulation of chymotrypsin activity was only observed in MG132-administered PC12 cells pretreated with conserved dopamine neurotrophic factor. There was no change in trypsin expression. We conclude that conserved dopamine neurotrophic factor develops its neurotrophic effects by modulating proteasomal activities, and thereby protects and rescues PC12 cells against neurodegeneration.

Effects of CDNF on 6-OHDA-induced apoptosis in PC12 cells via modulation of Bcl-2/Bax and caspase-3 activation.

Progressive dopamine neuron degeneration in the substantia nigra pars compacta is considered the most prominent pathological characteristic of Parkinson's disease (PD). Currently, there is no cure, but only the capability to relieve the symptoms of PD. The conserved dopamine neurotrophic factor (CDNF) protects and rescues dopamine neurons in vivo. However, the molecular function of CDNF in PD remains unclear. In present study, we investigated the role and intrinsic mechanism of CDNF in preventing and reversing rat pheochromocytoma (PC12) cells from apoptosis induced by 6-hydroxydopamine (6-OHDA). We demonstrate that 6-OHDA induces cell death in PC12 cells, but that CDNF attenuates this effect in a dose-dependent manner. Further study shows that upregulation of the Bcl-2/Bax ratio and downregulation of caspase-3 activity are observed in a dose-dependent manner upon pre-treatment or post-treatment with CDNF, suggesting a pathway of regulation of apoptosis by CDNF. These data demonstrate that CDNF prevents the apoptosis of PC12 cells induced by 6-OHDA by modulating Bcl-2/Bax and caspase-3 activation.

Neuronavigation-assisted endoscopic unilateral cyst fenestration for treatment of symptomatic septum pellucidum cysts.

BACKGROUND: Traditional surgical treatments for this rare disease include open surgical procedures and ventriculoperitoneal shunting. In 1995, endoscopic fenestration was first applied to treatment of cysts of the septum pellucidum (CSP). However, cyst fenestration generally takes a bilateral approach by making two burr holes leading to two fenestrations in the lateral walls of the cyst. Some disadvantages are related to bilateral fenestration. So far, there is no consensus on the surgical indications, the endoscopic approaches, and techniques for CSPs. Based on our experience with 14 cases of symptomatic CSP treated with neuronavigation-assisted endoscopic unilateral cyst fenestration via a single burr hole, we discuss the operative indications and the utility of endoscope-assisted techniques in combination with neuronavigation. METHODS: 14 patients underwent endoscopic CSP fenestration via a right frontal approach using a rigid endoscope and neuronavigation. Neuronavigation helped locating optimal skin incision, puncture point, optimal operation trajectory, and real-time operation monitoring. Postoperatively, a follow-up study on the 14 patients was performed. RESULTS: The follow-up period ranged from 6 months to 2 years. Postoperatively, the mass effect of the cysts and the self-reported symptoms disappeared immediately. In 7 patients with papilledema, the optic fundus examinations showed that papilledema improved. The computerized tomography (CT) or magnetic resonance imaging (MRI) scans showed significant decrease in the cyst size and no recurrence during the follow-up. In 2 patients with accompanying hydrocephalus, the hydrocephalus disappeared. CONCLUSION: The results after uni- and bilateral CSP fenestration show no significant difference. Avoiding damage of contralateral tissue, the surgical trauma in unilateral fenestration is less than in bilateral fenestration. Furthermore, the unilateral approach shortens the operation time. We believe that unilateral cyst fenestration is a better therapeutic option in symptomatic CSP.

Pin1-Nanog expression in human glioma is correlated with advanced tumor progression.

The stemness gene Nanog has been shown to play an important role in tumor development, including glioma. Nanog is phosphorylated at multiple Ser/Thr-Pro motifs, which promotes the interaction between Nanog and the prolyl isomerase Pin1, leading to Nanog stabilization by suppressing its ubiquitination. The present study investigated the expression and relationship of Pin1 and Nanog in human gliomas. Significantly higher mRNA and protein expression levels of Pin1 and Nanog were demonstrated in 120 glioma specimens of different pathological grades by RT-PCR, immunohistochemistry staining and western blot analysis. The relative levels of Pin1 expression, as well as Nanog expression, were significantly positively correlated with pathological grade. Moreover, a positive correlation of Pin1 and Nanog expression in human gliomas was noted. Co-localization of Pin1 and Nanog was observed in the perinuclear space in the cytoplasm of glioma cells detected by immunofluorescence staining. Significantly positive correlation between Pin1 and Nanog in gliomas indicated that Pin1 and Nanog may be related to tumorigenesis and development of glioma cells.

MiR-134 regulates the proliferation and invasion of glioblastoma cells by reducing Nanog expression.

MiR-134 is a brain-enriched miRNA that plays an essential role in the development of the embryonic stem cell-orientated differentiation to central nervous system by suppression of Nanog and neural development (including neurons, cylindraxile and dendrites) and has been shown to be downregulated in oligodendrogliomas (ODG) and glioblastomas (GBM), suggesting its possible involvement in brain tumor progression. In this study, we defined the expression and function of miR-134, which we found to be downregulated in glioma samples and the glioblastoma cell line U87 by SYBR green real-time quantitative reverse transcription-PCR (real-time PCR). Early reports have characterized Nanog as a direct target of miR-134 by a dual-luciferase reporter assay in 293T cells. In our study, overexpression of miR-134 in U87 glioblastoma cells resulted in significant downregulation of Nanog mRNA levels as well as protein levels. miR-134 overexpression reduced the proliferation, invasiveness and migration capability of U87 cells while promoted apoptosis of these cells in vitro and suppressed the growth of tumor xenografts in vivo. These findings demonstrated that miR-134 deregulation is common in human gliomas. Restoration of its function inhibits cell proliferation, invasion and migration capability and promotes apoptosis, which could be partly due to its inhibitory effect on Nanog protein expression in glioblastoma cells. MiR-134 could play an important role as a tumor suppressor relying on its direct translational attenuation of Nanog.

Gray matter and white matter abnormalities in online game addiction.

Online game addiction (OGA) has attracted greater attention as a serious public mental health issue. However, there are only a few brain magnetic resonance imaging studies on brain structure about OGA. In the current study, we used voxel-based morphometry (VBM) analysis and tract-based spatial statistics (TBSS) to investigate the microstructural changes in OGA and assessed the relationship between these morphology changes and the Young's Internet Addiction Scale (YIAS) scores within the OGA group. Compared with healthy subjects, OGA individuals showed significant gray matter atrophy in the right orbitofrontal cortex, bilateral insula, and right supplementary motor area. According to TBSS analysis, OGA subjects had significantly reduced FA in the right genu of corpus callosum, bilateral frontal lobe white matter, and right external capsule. Gray matter volumes (GMV) of the right orbitofrontal cortex, bilateral insula and FA values of the right external capsule were significantly positively correlated with the YIAS scores in the OGA subjects. Our findings suggested that microstructure abnormalities of gray and white matter were present in OGA subjects. This finding may provide more insights into the understanding of the underlying neural mechanisms of OGA.

[Impulsive decision-making behaviors in heroin addicts: a study of functional magnetic resonance imaging].

OBJECTIVE: To explore the brain regions associated with impulsive decision-making behaviors and interpret the nervous mechanism for addiction and relapse in heroin abusers. METHODS: Using the paradigms of psychological experiment, the subjects in both heroin addiction group (HA group) and normal control group (HC group) performed Iowa gambling task (IGT) and simultaneously underwent functional magnetic resonance imaging (fMRI) scan. All the above data were gathered and then analyzed by SPM5 software to explore both the brain regions and their functional changes correlated with impulsive decision-making. RESULTS: Evidence by IGT behavioral consequences demonstrated that the net scores in HC group increased with numbers of decision-making whereas no increment (fluctuating between-1 and 0) was observed in HA group. Based on the results of fMRI analysis, right orbitofrontal cortex (OFC), dorsolateral prefrontal cortex (DLPFC), left ventromedial prefrontal cortex (MPFC) and anterior cingulate cortex (ACC) were activated in both groups. But the right OFC was more active while the right DLPFC and left MPFC were weaker in HA group versus the HC group. Meanwhile, activation of right lenticular nucleus, right thalamus, right insula, hippocampus and left caudate nucleus were observed in HA group. CONCLUSION: Heroin abusers are incapable of impulsive decision-making in behavioral studies. Such a brain region as prefrontal cortex participates in the decision-making performance and control of impulsiveness. Functionally abnormal brain regions correlated with impulsive decision-making may be one cause of genesis, maintenance and relapse of heroin addiction.

Correlation between glioblastoma stem-like cells and tumor vascularization.

Glioblastoma multiforme (GBM) is the most lethal type of brain tumor. The formation of abnormal, dysfunctional tumor vasculature and glioblastoma stem-like cells (GSCs) are believed to be the major components of the inability to treat these tumors effectively. We analyzed 70 glioblastoma samples by immunohistochemistry and double immunofluorescence staining. The immunohistochemical expression of the putative brain tumor stem cell markers CD133 and Nestin in paraffin sections was analyzed using morphometry. In all GBM samples, CD133 or Nestin was expressed in tumor and endothelial cells. Double immunofluorescence stainings showed that the two different marked GSCs were found accumulated around the CD31+ blood vessels and CD133/CD31 or Nestin/CD31 co-expression was found in the endothelial cells and GSCs. Furthermore, the vascular endothelial growth factor (VEGF) and the endothelial marker CD31 were co-expressed in GSCs. Therefore, GSCs not only showed distinct perivascular distribution but were capable of differentiating into endothelial cells. We demonstrate that GSCs contribute directly to the tumor vasculature by endothelial cell differentiation. GSCs and tumor vascularization are closely related to each other, not only in the regional distribution but also in biological function. These findings describe a new mechanism for tumor vasculo-genesis and may provide new insights for targeted therapy against brain tumors.