Identification of a Novel Gene Signature Based on Kinesin Family Members to Predict Prognosis in Glioma.

Background and Objectives: Extensive research indicates that the kinesin superfamily (KIFs) regulates tumor progression. Nonetheless, the potential prognostic and therapeutic role of KIFs in glioma has been limited. Materials and Methods: Four independent cohorts from The Cancer Genome Atlas (TCGA) database and the Chinese Glioma Genome Atlas (CGGA) database were generated into a large combination cohort for identification of the prognostic signature. Following that, systematic analyses of multi-omics data were performed to determine the differences between the two groups. In addition, IDH1 was selected for the differential expression analysis. Results: The signature consists of five KIFs (KIF4A, KIF26A, KIF1A, KIF13A, and KIF13B) that were successfully identified. Receiver operating characteristic (ROC) curves indicated the signature had a suitable performance in prognosis prediction with the promising predictive area under the ROC curve (AUC) values. We then explored the genomic features differences, including immune features and tumor mutation status between high- and low-risk groups, from which we found that patients in the high-risk group had a higher level of immune checkpoint modules, and IDH1 was identified mutated more frequently in the low-risk group. Results of gene set enrichment analysis (GSEA) analysis showed that the E2F target, mitotic spindle, EMT, G2M checkpoint, and TNFa signaling were significantly activated in high-risk patients, partially explaining the differential prognosis between the two groups. Moreover, we also verified the five signature genes in the Human Protein Atlas (HPA) database. Conclusion: According to this study, we were able to classify glioma patients based on KIFs in a novel way. More importantly, the discovered KIFs-based signature and related characteristics may serve as a candidate for stratification indicators in the future for gliomas.

Gene Expression Profiling of Glioblastoma to Recognize Potential Biomarker Candidates.

Glioblastoma is an aggressive malignant tumor of the brain and spinal cord. Due to the blood-brain barrier, the accessibility of its treatments still remains significantly challenging. Unfortunately, the recurrence rates of glioblastoma upon surgery are very high too. Hence, understanding the molecular drivers of disease progression is valuable. In this study, we aimed to investigate the molecular drivers responsible for glioblastoma progression and identify valid biomarkers. Three microarray expression profiles GSE90604, GSE50601, and GSE134470 containing healthy and glioblastoma-affected samples revealed overlapping differentially expressed genes (DEGs). The interrelational pathway enrichment analysis elucidated the halt of cell cycle checkpoints and activation of signaling pathways and led to the identification of 6 predominant hub genes. Validation of hub genes in comparison with The Cancer Genome Atlas datasets identified the potential biomarkers of glioblastoma. The study evaluated two significantly upregulated genes, SPARC (secreted protein acidic and rich in cysteine) and VIM (vimentin) for glioblastoma. The genes CACNA1E (calcium voltage-gated channel subunit alpha1 e), SH3GL2 (SH3 domain-containing GRB2-like 2, endophilin A1), and DDN (dendrin) were identified as under-expressed genes as compared to the normal and pan-cancer tissues along with prominent putative prognostic biomarker potentials. The genes DDN and SH3GL2 were found to be upregulated in the proneural subtype, while CACNA1E in the mesenchymal subtype of glioblastoma exhibits good prognostic potential. The mutational analysis also revealed the benign, possibly, and probably damaging substitution mutations. The correlation between the DEG and survival in glioblastoma was evaluated using the Kaplan-Meier plots, and VIM had a greater life expectancy of 60.25 months. Overall, this study identified key candidate genes that might serve as predictive biomarkers for glioblastoma.

Revealing the source of Jupiter's x-ray auroral flares.

Jupiter's rapidly rotating, strong magnetic field provides a natural laboratory that is key to understanding the dynamics of high-energy plasmas. Spectacular auroral x-ray flares are diagnostic of the most energetic processes governing magnetospheres but seemingly unique to Jupiter. Since their discovery 40 years ago, the processes that produce Jupiter's x-ray flares have remained unknown. Here, we report simultaneous in situ satellite and space-based telescope observations that reveal the processes that produce Jupiter's x-ray flares, showing surprising similarities to terrestrial ion aurora. Planetary-scale electromagnetic waves are observed to modulate electromagnetic ion cyclotron waves, periodically causing heavy ions to precipitate and produce Jupiter's x-ray pulses. Our findings show that ion aurorae share common mechanisms across planetary systems, despite temporal, spatial, and energetic scales varying by orders of magnitude.

Edaravone Plays Protective Effects on LPS-Induced Microglia by Switching M1/M2 Phenotypes and Regulating NLRP3 Inflammasome Activation.

Parkinson's disease is a neurodegenerative disorder in which activated microglia may appear prior to motor symptoms, but the specific therapeutic mechanisms remain unclear. This study investigated the potential effects of Edaravone (EDA) on M1/M2 polarization of microglia in rats with dopaminergic neurons damage induced by lipopolysaccharide (LPS) and its mechanism. Rats were randomly grouped as the following (n = 10): Control, EDA alone (10 mg/kg), LPS-model (LPS 5 µg), LPS + EDA (5 mg/kg) and LPS + EDA (10 mg/kg). After intragastric administration of EDA once a day for seven consecutive days, LPS was injected into SN pars unilaterally. Rotarod test, pole test, and traction test were used to analyze the intervention effect of EDA on neurobehavioral function in rats. Protein expression levels of TH, TNF-α, Arg-1, Iba-1, NLRP3 and caspase-1 were measured by immunofluorescence staining and western blot. In vitro, BV-2 cells were treated with LPS (100 ng/ml) before adding different doses of EDA. Levels of inflammatory cytokines in culture medium were detected by ELISA. Western blot and immunofluorescence were used to evaluate microglial activation and polarization. First, rotarod test, pole test, and traction test all showed that EDA mitigated motor dysfunction of PD rats. Second, pathological analysis suggested that EDA inhibited LPS-induced microglial activation and remitted declines of dopaminergic neurons. In addition, EDA shifted M1 pro-inflammatory phenotype of microglia to M2 anti-inflammatory state, while decreased expression of M1 markers (TNF-α and IL-1ß) and facilitated expression of M2 markers (Arg-1 and IL-10). EDA suppressed inflammatory responses through inhibiting the expression of pro-inflammatory factors (IL-1ß, IL-18 and NO), but the neuroprotective effects were invalid while siRNA NLRP3 existed. In conclusion, these results indicated that EDA could improve neurobehavioral functions and play anti-neuroinflammatory roles in PD rats, possibly by inhibiting NLPR3 inflammasome activation and regulating microglia M1/M2 polarization.

The top cited articles on glioma stem cells in Web of Science.

BACKGROUND: Glioma is the most common intracranial tumor and has a poor patient prognosis. The presence of brain tumor stem cells was gradually being understood and recognized, which might be beneficial for the treatment of glioma. OBJECTIVE: To use bibliometric indexes to track study focuses on glioma stem cell, and to investigate the relationships among geographic origin, impact factors, and highly cited articles indexed in Web of Science. METHODS: A list of citation classics for glioma stem cells was generated by searching the database of Web of Science-Expanded using the terms "glioma stem cell" or "glioma, stem cell" or "brain tumor stem cell". The top 63 cited research articles which were cited more than 100 times were retrieved by reading the abstract or full text if needed. Each eligible article was reviewed for basic information on subject categories, country of origin, journals, authors, and source of journals. Inclusive criteria: (1) articles in the field of glioma stem cells which was cited more than 100 times; (2) fundamental research on humans or animals, clinical trials and case reports; (3) research article; (4) year of publication: 1899-2012; and (5) citation database: Science Citation Index-Expanded. Exclusive criteria: (1) articles needing to be manually searched or accessed only by telephone; (2) unpublished articles; and (3) reviews, conference proceedings, as well as corrected papers. RESULTS: Of 2 040 articles published, the 63 top-cited articles were published between 1992 and 2010. The number of citations ranged from 100 to 1 754, with a mean of 280 citations per article. These citation classics came from nineteen countries, of which 46 articles came from the United States. Duke University and University of California, San Francisco led the list of classics with seven papers each. The 63 top-cited articles were published in 28 journals, predominantly Cancer Research and Cancer Cell, followed by Cell Stem Cell and Nature. CONCLUSION: Our bibliometric analysis provides a historical perspective on the progress of glioma stem cell research. Articles originating from outstanding institutions of the United States and published in high-impact journals are most likely to be cited.

[Studies on IFN-gamma-mediated reversion of CIK killing sensitivity to edited human lung cancer A549 cells].

AIM: To explore IFN-gamma-mediated reversion of CIK killing sensitivity to immunoedited lung cancer A549 cells. METHODS: RT-PCR and MTT methods were used to detect the effect on MICA mRNA expression induced by IFN-gamma in the edited A549 cells and the change of CIK killing sensitivity to A549 cells, respectively. RESULTS: Low expression of cell surface MICA and low killing sensitivity of CIKs were observed in edited A549 cells. IFN-gamma could significantly increase MICA mRNA expression in the edited A549 cells and improve CIK cell cytotoxicity. CONCLUSION: IFN-gamma could reverse CIK killing sensitivity to the edited A549 cells by enhancing the MICA mRNA expression.