Glioblastoma (GBM) is the most common type of malignant tumor of the central nervous system. The prognosis of patients with GBM is very poor, with a survival time of ~15 months. GBM is highly heterogeneous and highly aggressive. Surgical removal of intracranial tumors does provide a good advantage for patients as there is a high rate of recurrence. The understanding of this type of cancer needs to be strengthened, and the aim of the present study was to identify gene signatures present in GBM and uncover their potential mechanisms. The gene expression profiles of GSE15824 and GSE51062 were downloaded from the Gene Expression Omnibus database. Normalization of the data from primary GBM samples and normal samples in the two databases was conducted using R software. Then, joint analysis of the data was performed. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed, and the protein-protein interaction (PPI) network of the differentially expressed genes (DEGs) was constructed using Cytoscape software. Identification of prognostic biomarkers was conducted using UALCAN. In total, 9,341 DEGs were identified in the GBM samples, including 9,175 upregulated genes and 166 downregulated genes. The top 1,000 upregulated DEGs and all of the downregulated DEGs were selected for GO, KEGG and prognostic biomarker analyses. The GO results showed that the upregulated DEGs were significantly enriched in biological processes (BP), including immune response, cell division and cell proliferation, and the downregulated DEGs were also significantly enriched in BP, including cell growth, intracellular signal transduction and signal transduction by protein phosphorylation. KEGG pathway analysis showed that the upregulated DEGs were enriched in circadian entrainment, cytokine-cytokine receptor interaction and maturity onset diabetes of the young, while the downregulated DEGs were enriched in the TGF-β signaling pathway, MAPK signaling pathway and pathways in cancer. All of the downregulated genes and the top 1,000 upregulated genes were selected to establish the PPI network, and the sub-networks revealed that these genes were involved in significant pathways, including olfactory transduction, neuroactive ligand-receptor interaction and viral carcinogenesis. In total, seven genes were identified as good prognostic biomarkers. In conclusion, the identified DEGs and hub genes contribute to the understanding of the molecular mechanisms underlying the development of GBM and they may be used as diagnostic and prognostic biomarkers and molecular targets for the treatment of patients with GBM in the future.

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SUMMARYPurpose: To determine whether muscimol delivered epidurally or into the subarachnoid space can prevent and/or terminate acetylcholine (Ach)-induced focal neocortical seizures at concentrations not affecting behavior and background electroencephalography (EEG) activity. Methods: Rats (n = 12) and squirrel monkeys (n = 3) were chronically implanted with an epidural or subarachnoid drug delivery device, respectively, over the right frontal/parietal cortex, with adjacent EEG electrodes. Recordings were performed in behaving rats and chaired monkeys. Via the implants, either a control solution (artificial cerebrospinal fluid, ACSF) or muscimol (0.25-12.5 mm) was delivered locally as a ''pretreatment,'' followed by the similar delivery of a seizure-inducing concentration of Ach. In five additional rats, the quantities of food-pellets consumed during epidural ACSF and muscimol (2.5 mm) exposures were measured. In a last group of four rats, muscimol (0.8-2.5 mm) was delivered epidurally during the ongoing, Achinduced EEG seizure. Results: In contrast to ACSF pretreatments, epidural muscimol pretreatment in rats completely prevented the seizures at and above 2.5 mm. In the monkeys, subarachnoid muscimol pretreatments at 2.5 mm completely prevented the focal-seizure-inducing effect of Ach, whereas similar deliveries of ACSF did not affect the seizures. Furthermore, 2.5 mm epidural muscimol left the eating behavior of rats intact and caused only slight changes in the EEG power spectra. Finally, muscimol delivery during Ach-induced EEG seizures terminated the seizure activity within 1-3 min. Conclusions: The results of this study suggest that muscimol is a viable candidate for the transmeningeal pharmacotherapy of intractable focal epilepsy.

Tissue plasminogen activator, a serine protease encoded by the PLAT gene is present in the trabecular meshwork (TM) and other ocular tissues and has been reported to be downregulated by treatment with steroids in vitro. Steroids are known to cause changes in outflow facility of aqueous humor in many species. In the present study, we tested whether overexpression of PLAT can prevent and/or reverse the outflow facility of mouse eyes treated with steroids. Animals received bilateral injection with 20 µl of triamcinolone acetonide (TA) (40mg/ml) suspension subconjunctivally to induce outflow facility changes. Some animals received unilateral intracameral injection with 2 µl of adenoviral suspension [3-4x1012 virus genomes per milliliter (vg/ml)] carrying sheep PLAT cDNA (AdPLAT) either concurrently with TA injection or one week after TA injection, whereas others received bilateral intracameral injection with 2µl of adenoviral suspension (9x1012 vg/ml) carrying no transgene (AdNull) concurrently with TA injection. Animals were sacrificed one week after AdPLAT or AdNull treatment. Endogenous mRNA expression levels of mouse PAI-1 and MMP-2, -9 and -13 were also measured using qRT-PCR. Outflow facility one week after AdPLAT administration was increased by 60% and 63% respectively for animals that had not or had been pretreated with steroids. Overexpression of PLAT significantly upregulated expression of PAI-1, MMP-2, -9 and -13 compared to the levels found in TA only treated eyes. These findings suggest that overexpression of PLAT in TM of mouse eyes can both prevent and reverse the decrease in outflow facility caused by steroid treatment and is associated with upregulation of MMPs.

Steroid treatment significantly decreases outflow facility in C57BL/6 mice despite having small effect on IOP. This animal model can be useful for studying the pathogenesis of steroid-induced glaucoma.

In 2008, a group of clinicians, scientists, engineers, and industry representatives met to discuss advances in the application of engineering technologies to the diagnosis and treatment of patients with epilepsy. The presentations also provided a guide for further technological development, specifically in the evaluation of patients for epilepsy surgery, seizure onset detection and seizure prediction, intracranial treatment systems, and extracranial treatment systems. This article summarizes the discussions and demonstrates that cross-disciplinary interactions can catalyze collaborations between physicians and engineers to address and solve many of the pressing unmet needs in epilepsy.

Both pro-inflammatory cytokines and anti-inflammatory cytokines generated by chondrocytes play essential roles in the process of Rheumatoid arthritis and osteoarthritis (OA). Bornyl acetate is the main volatile constituent in numerous conifer oils and some Chinese traditional herbs, which has displayed an anti-inflammatory effect before. In this study, we found that bornyl acetate elevates the expression of IL-11 at both the mRNA and protein levels. Interestingly, our results indicated that IL-1b-mediated up-regulation of IL-6, IL-8, MMP-1, and MMP-13 was significantly compromised by IL-11 co-treatment on mRNA levels and protein levels. The antagonistic effects of bornyl acetate on IL-1b induced targets MMP-1 and MMP-13 were diminished by IL-11 knockdown. Mechanistically, our results indicated that bornyl acetate significantly elevates the expression of AP-1 component c-fos, which may influence gross AP-1 activity and initial the transcription of IL-11. Indeed, expression of IL-11 was reversed upon c-fos knockdown. Our results suggest the therapeutic potentials of bornyl acetate in patients with OA. V C 2014 IUBMB Life, 66(12): [854][855][856][857][858][859] 2014