CircRNA circ_POLA2 overexpression suppresses cell apoptosis by downregulating PTEN in glioblastoma.

The oncogenic role of circ_POLA2 has only been explored in lung cancer, whereas the role of which in glioblastoma (GBM) is unclear. Our research explored the involvement of circ_POLA2 in GBM. Circ_POLA2 and phosphatasetensinhomolog (PTEN) mRNA levels in GBM and paired nontumor tissues collected from 58 GBM patients were analyzed by real-time quantitative PCR (RT-qPCR). Circ_POLA2 and PTEN were overexpressed in GBM cells to study their interaction by RT-qPCR and Western blot. The roles of circ_POLA2 and PTEN in regulating GBM cell apoptosis were explored using cell apoptosis assay. Our data revealed that circ_POLA2 was upregulated and PTEN was downregulated in GBM. PTEN showed an inverse correlation to circ_POLA2 across GBM tissues, In GBM cells, circ_POLA2 overexpression decreased PTEN accumulation, but PTEN overexpression failed to significantly affect circ_POLA2 expression. Moreover, PTEN reduced the inhibitory effects of circ_POLA2 on GBM cell apoptosis. Circ_POLA2 is overexpressed in MCL and might promote GBM cell apoptosis through downregulating PTEN.

RUNX3 inhibits glioma survival and invasion via suppression of the ß-catenin/TCF-4 signaling pathway.

INTRODUCTION: Runt-related transcription factor 3 (RUNX3) exerts a tumor suppressor gene associated with gastric and other cancers, including glioma. However, how its anti-tumor mechanism in functions glioma is unclear. METHODS: We assayed expression of RUNX3 with a tissue microarray (TMA), frozen cancer tissues and malignant glioma cell lines using immunohistochemistry, qRT-PCR and Western bolt analysis. Cell proliferation, invasion, cell cycle distribution and apoptosis were also examined to confirm the effect of RUNX3 medicated malignant phenotype. TOP/FOP experiment was used to detect the ß-catenin/Tcf-4 transcription activity by RUNX3. RESULTS: Enforced RUNX3 expression inhibited proliferation and invasion, induced cell cycle arrest and promoted apoptosis in vitro and in vivo, Bim siRNA partically reversed the effect of RUNX3-induced apoptosis in LN229 and U87 cells, suggesting a dependent role of Bim-caspase pathway. Moreover, Mechanism investigations revealed that restoration of RUNX3 suppressed ß-catenin/Tcf-4 transcription activity. CONCLUSIONS: RUNX3 plays a pivotal role in glioma initiation and progression as a tumor suppressor via attenuation of Wnt signaling, highlighting it as a potential therapeutic target for glioma.

Molecular pathological expression in malignant gliomas resected by fluorescein sodium-guiding under the YELLOW 560 nm surgical microscope filter.

BACKGROUND: This study aimed to analyze the relationship between molecular pathologic expression of GFAP and Ki-67 and fluorescence levels, and to provide molecular pathological basis for the removal of malignant gliomas (MG) by Fluorescein Sodium (FLS) navigation under the YELLOW 560 nm surgical microscope filter. METHODS: A retrospective analysis of clinical data of 18 MG cases confirmed by the postoperative pathology was performed. All cases were resected by FLS guiding under the YELLOW 560 nm filter. Hematoxylin-eosin (HE) staining, molecular pathology markers GFAP, and Ki-67 immunohistochemical staining of the specimens were performed. The relationship between fluorescence staining levels and GFAP positive rate, Ki-67 proliferation index, and WHO grades was studied. RESULTS: There were 69 pathological specimens with fluorescence levels of "bright" fluorescence (n = 32), "low" fluorescence (n = 18), and "no" fluorescence (n = 19). Immunohistochemical staining showed GFAP-positive expression in both tumor cells and normal glial cells. The staining levels of the specimens in the fluorescence regions were higher than that in the non-fluorescence regions. GFAP expression was positive in 61 specimens and negative in 8 specimens. Comparison of Ki-67 proliferation index using chi-square test showed different fluorescence levels had different Ki-67 proliferation indexes (χ2 = 14.678, p = 0.005). With high proliferation index of specimens, fluorescence level was brighter. WHO grade had no correlation with fluorescence levels (χ2 = 3.531, p = 0.171). CONCLUSION: FLS-guided resection of MG is safe and effective. In the boundary area of MG, fluorescence levels and Ki-67 proliferation index showed correlation. FLS-guided resection achieved the function of "reducing tumor cell," thus reducing the proliferation index in the lesion area.

PARP14 correlates with GBM proliferation and poor prognosis by elevating expression of SAMD/SAMD9L.

BACKGROUND: Glioblastoma(GBM) is the most common primary tumor of the central nervous system with an extremely dismal prognosis. Many progresses have been made such as the discovery of new molecular biomarkers and target drugs especially IDH inhibitors. However, GBM prognosis is still poor, which requires more biomarkers and drug targets for more precision classification and treatment. MATERIALS AND METHODS: Potential prognostic biomarkers of GBM were screened by TCGA database, and ectopic up-regulation of PARP14 was identified. Expression and clinical significance of PARP14 were detected in our GBM cohort consisting of 143 patients with gross total surgical resection. Related genes with PARP14 were further screened and identified by in silico analysis and in vitro experiments. The expression and prognostic significance of SAMD9 and SAMD9L were verified with IHC and survival analysis in our cohort. RESULTS: PARP14 was up-regulated in GBM compared with non-tumor adjacent tissues. PARP14 correlated with poor prognosis and can be regarded as an independent prognostic biomarker of GBM. PARP14 expression was positively associated with SAMD9 and SAMD9L in GBM. In GBM cells, PARP14 could increase the expression of SAMD9 and SAMD9L. SAMD9 and SAMD9L were highly expressed in high-PARP14 subset and were both prognostic biomarkers of GBM. Moreover, PARP14 increased GBM proliferation by inducing SAMD9 and SAMD9L expression. CONCLUSIONS: PARP14, SAMD9, and SAMD9L are prognostic biomarkers of GBM predicting poor prognosis. PARP14 promotes GBM cell proliferation by inducing SAMD9 and SAMD9L expression. Our results indicate that PARP14/SAMD9/SAMD9L are prognostic biomarkers and potential drug targets of GBM.

Integrative analysis identifies an immune-relevant epigenetic signature for prognostication of non-G-CIMP glioblastomas.

The clinical and molecular implications of DNA methylation alterations remain unclear among the majority of glioblastomas (GBMs) without glioma-CpGs island methylator phenotype (G-CIMP); integrative multi-level molecular profiling may provide useful information. Independent cohorts of non-G-CIMP GBMs or IDH wild type (wt) lower-grade gliomas (LGGs) from local and public databases with DNA methylation and gene expression microarray data were included for discovery and validation of a multimarker signature, combined using a RISK score model. Bioinformatic and in vitro functional analyses were employed for biological validation. Using a strict multistep selection approach, we identified eight CpGs, each of which was significantly correlated with overall survival (OS) of non-G-CIMP GBMs, independent of age, the O-6-methylguanine-DNA methyltransferase (MGMT) methylation status, treatments and other identified CpGs. An epigenetic RISK signature of the 8 CpGs was developed and validated to robustly and independently prognosticate prognosis in different cohorts of not only non-G-GIMP GBMs, but also IDHwt LGGs. It also showed good discriminating value in stratified cohorts by current clinical and molecular factors. Bioinformatic analysis revealed consistent correlation of the epigenetic signature to distinct immune-relevant transcriptional profiles of GBM bulks. Functional experiments showed that S100A2 appeared to be epigenetically regulated by one identified CpG and was associated with GBM cell proliferation, apoptosis, invasion, migration and immunosuppression. The prognostic 8-CpGs RISK score signature may be of promising value for refining current glioma risk classification, and its potential links to distinct immune phenotypes make it a promising biomarker candidate for predicting response to anti-glioma immunotherapy.

'Cool and quiet' therapy for malignant hyperthermia following severe traumatic brain injury: A preliminary clinical approach.

Malignant hyperthermia increases mortality and disability in patients with brain trauma. A clinical treatment for malignant hyperthermia following severe traumatic brain injury, termed 'cool and quiet' therapy by the authors of the current study, was investigated. Between June 2003 and June 2013, 110 consecutive patients with malignant hyperthermia following severe traumatic brain injury were treated using mild hypothermia (35-36°C) associated with small doses of sedative and muscle relaxant. Physiological parameters and intracranial pressure were monitored, and the patients slowly rewarmed following the maintenance of mild hypothermia for 3-12 days. Consecutive patients who had undergone normothermia therapy were retrospectively analyzed as the control. In the mild hypothermia group, the recovery rate was 54.5%, the mortality rate was 22.7%, and the severe and mild disability rates were 11.8 and 10.9%, respectively. The mortality rate of the patients, particularly that of patients with a Glasgow Coma Scale (GCS) score of between 3 and 5 differed significantly between the hypothermia group and the normothermia group (P<0.05). The mortality of patients with a GCS score of between 6 and 8 was not significantly different between the two groups (P> 0.05). The therapy using mild hypothermia with a combination of sedative and muscle relaxant was beneficial in decreasing the mortality of patients with malignant hyperthermia following severe traumatic brain injury, particularly in patients with a GCS score within the range 3-5 on admission. The therapy was found to be safe, effective and convenient. However, rigorous clinical trials are required to provide evidence of the effectiveness of 'cool and quiet' therapy for hyperthermia.

[Essence of meridians and collaterals: circulatory conduction system of bio-electricity of human].

The running courses of twelve meridians are explained through the electrical properties of cell membrane, and the phenomenon related with meridians such as mechanism of acupuncture analgesia and acupuncture anesthesia, pause of the propagated sensation along channels, nature of propagated sensation and width of propagated sensation is expounded in this article. As a result, it is held that the meridian system, a circulatory conduction system of bio-electricity of human, is an independent system from the known nine large systems.