Suppression of PDCD4 mediated by the long non-coding RNA HOTAIR inhibits the proliferation and invasion of glioma cells.

Programmed cell death protein 4 (PDCD4) has recently been demonstrated to be implicated in translation and transcription, and the regulation of cell growth. However, the mechanisms underlying PDCD4 function in glioma cells remain to be elucidated. The current study investigated the function and regulation of PDCD4 and the results demonstrated that the expression of PDCD4 was significantly reduced in glioma cells compared with normal cells. When PDCD4 was overexpressed in glioma cells, the proliferation rate and invasive capability of the cells greatly decreased, suggesting that PDCD4 functions as a tumor suppressor in this cell type. In addition, the histone modification status of the PDCD4 gene was analyzed, and chromatin immunoprecipitation assay identified a high density of histone 3 lysine 27 trimethylation on the promoter of PDCD4, which was associated with the long non-coding RNA, homeobox transcript antisense RNA (HOTAIR). The expression of HOTAIR was significantly increased in glioma cells compared with normal cells, and it exerted its function in a polycomb repressive complex 2-dependent manner. These results may provide novel approaches to therapeutically target PDCD4 and HOTAIR in patients with gliomas.

A combined bilateral approach to anterior communicating artery aneurysm.

AIM: To discuss the features, feasibility, and safety of a combined bilateral approach in the endovascular treatment of intracranial anterior communicating artery (ACoA) aneurysm. MATERIAL AND METHODS: We performed a retrospective analysis of the clinical data of patients with ACoA aneurysm treated with a combined bilateral approach. RESULTS: We successfully embolized aneurysms in nine patients with intracranial ACoA aneurysm using a combined bilateral approach. All treated patients had an open ACoA connecting with the bilateral anterior cerebral arteries. CONCLUSION: Because the ACoA connects the intracranial arteries in both hemispheres, patients with ACoA aneurysm can be endovascularly treated with a combined bilateral approach. Notably, surgeon experience and dexterity play important roles in the success of this procedure.

Regulator of telomere elongation helicase 1 (RTEL1) rs6010620 polymorphism contribute to increased risk of glioma.

Regulator of telomere elongation helicase 1 (RTEL1) is critical for genome stability and tumor avoidance. Many studies have reported the associations of RTEL1 rs6010620 with glioma risk, but individually published results were inconclusive. This meta-analysis was performed to quantitatively summarize the evidence for such a relationship. The PubMed, Embase, and Web of Science were systematically searched to identify relevant studies. The odds ratio (OR) and 95 % confidence interval (95 % CI) were computed to estimate the strength of the association using a fixed or random effects model. Ten studies were eligible for meta-analysis including data on glioma with 6,490 cases and 9,288 controls. Overall, there was a significant association between RTEL1 rs6010620 polymorphism and glioma risk in all four genetic models (GG vs. AA: OR=1.87, 95 % CI=1.60-2.18, P heterogeneity=0.552; GA vs. AA: OR=1.30, 95 % CI=1.16-1.46, P heterogeneity=0.495; dominant model-GG+GA vs. AA: OR=1.46, 95 % CI=1.31-1.63, P heterogeneity=0.528; recessive model-GG vs. GA+AA: OR=1.36, 95 % CI=1.27-1.46, P heterogeneity=0.093). Subgroup analyses by ethnicity showed that RTEL1 rs6010620 polymorphism resulted in a higher risk of glioma among both Asians and Caucasians. In the stratified analysis by ethnicity and source of controls, significantly increased risk was observed for Asians and Europeans in all genetic models, population-based studies in all genetic models, and hospital-based studies in three genetic models (heterozygote comparison, homozygote comparison, and dominant model). Our meta-analysis suggested that RTEL1 rs6010620 polymorphism is likely to be associated with increased glioma risk, which lends further biological plausibility to these findings.

Stent placement to treat ruptured vertebral dissecting aneurysms.

Conventional endovascular treatment may have limitations for vertebral dissecting aneurysm involving the origin of the posterior inferior cerebellar artery (PICA). We report our experiences of treating vertebral dissecting aneurysm with PICA origin involvement by placing a stent from the distal vertebral artery (VA) to the PICA to save the patency of the PICA. Stenting from the distal VA to the PICA was attempted to treat ruptured VA dissecting aneurysm involving the PICA origin with sufficient contralateral VA in eight patients. The procedure was successfully performed in seven patients with one failure because of PICA origin stenosis, which was treated with two overlapping stents. In the seven patients, PICAs had good patency on postoperative angiography and transient lateral brainstem ischemia represents a procedure-related complication. Follow-up angiographies were performed in seven patients and showed recanalization of the distal VA in three patients without evidence of aneurysmal filling. There was no evidence of aneurysm rupture during the follow-up period, and eight patients had favorable outcomes (mRS, 0 - 1). Placing a stent from the distal VA to the PICA with VA occlusion may present an alternative to conventional endovascular treatment for vertebral dissecting aneurysm with PICA origin involvement with sufficient contralateral VA.

Resistin protection against endogenous Aß neuronal cytotoxicity from mitochondrial pathway.

Neurotoxicity of amyloid ß (Aß) plays an important role in Alzheimer's disease (AD) pathogenesis. In this study, we researched the potential protective effects of resistin against Aß neurotoxicity in mouse Neuro2a (N2a) cells transfected with the Swedish amyloid precursor protein (Sw-APP) mutant and Presenilin exon 9 deletion mutant (N2a/D9), which overproduced Aß with abnormal intracellular Aß accumulation. The results show increased levels of ROS, NO, protein carbonyls, and 4HNE in N2a/D9 cells, which were attenuated by resistin treatment in a dose dependent manner. We also found that resistin could improve mitochondrial function in N2a/D9 cells through increasing the level of ATP and mitochondrial membrane potential. MTT and LDH assay indicated that N2a/D9 cells show increased vulnerability to H2O2-induced insult, which could be ameliorated by resistin. Mechanically, we found that resistin prevented apoptosis signals through reducing the ratio of Bax/Bcl2, the level of cleaved caspase-3, and attenuating cytochrome C release. Finally, the results demonstrated that resistin did not change the production of Aß1-40 and Aß1-42 in N2a/D9 cells, which suggests that the protective effects of resistin are independent of APP metabolism. This raises the possibility of novel AD therapies using resistin.