Rhein induces apoptosis and autophagy in human and rat glioma cells and mediates cell differentiation by ERK inhibition.

In this study, we investigated the anticancer potentials of Rhein, an anthraquinone derivative of most commonly used Chinese rhubarb on the rat F98 glioma cells. The experimental studies revealed that Rhein induced cell cycle arrest, caspase mediated apoptosis. It results in the formation of intracellular acidic vesicles in cytoplasm, leading to autophagy. Differentiation of viable cells towards elongation of matured astrocytes was proved by monitoring dramatic changes in morphological characteristics as well as identified from the elevation of glial fibrillary acidic protein (GFAP) expression. Rhein treatment did not alter the phosphorylated MAPKs activation including p-38, JNK and NF-κB, transcription unit whereas rhein significantly inhibited ERK1/2 activation in F98 glioma cells. PD98059, a specific inhibitor for ERK activation imitates rhein effects on morphology and expressions of GFAP but did not help to induce any apoptosis or autophagy. Collective data exhibited that potentials of rhein in anti-cancer property in ERK-independent apoptosis and autophagy in association with downregulated ERK-dependent differentiation process of glioma cell lines.

[Retracted] Retinoic acid­incorporated glycol chitosan nanoparticles inhibit the expression of Ezh2 in U118 and U138 human glioma cells.

We wish to retract our research article entitled "Retinoic acid-incorporated glycol chitosan nanoparticles inhibit Ezh2 expression in U118 and U138 human glioma cells" published in Molecular Medicine Reports 12: 6642-6648, 2015. An interested reader noted some anomalies in the presentation of Fig. 4 in our paper, calling into question the validity of the reported data. In examining our original article, we acknowledge that the data for RA (25 µm) did not show a higher density of cells compared with RA (10 µm), as shown in Fig. 4, and therefore Fig. 4 conveyed inaccurate information for the readers. Owing to the importance of these results, which bear significantly upon the conclusions that one may draw from this work, we have decided to withdraw our paper from Molecular Medicine Reports [the original article was published in Molecular Medicine Reports 12: 6642-6648, 2015; DOI: 10.3892/mmr.2015.4294.

Flow diverter treatment of posterior circulation aneurysms. A meta-analysis.

INTRODUCTION: Treatment of complex anterior circulation aneurysms with flow diverters (FDs) has become common practice in neurovascular centers. However, this treatment method for posterior circulation aneurysms (PCAs) still remains controversial. METHODS: Through searches for reports on the treatment of PCAs with FDs, we conducted a systematic review of the literature on its clinical efficacy and safety using random-effect binomial meta-analysis. RESULTS: We included 14 studies, which reported on a total of 225 PCAs in 220 patients. Procedure-related good outcome rate was 79% (95% confidence interval (CI), 72-84), with significantly lower odds among patients with ruptured aneurysms and basilar artery aneurysms. Procedure-related mortality rate was 15% (95% CI 10-21), with significantly higher rates among patients with giant aneurysms and basilar artery aneurysms. The rate of complete aneurysm occlusion at 6-month digital subtraction angiography (DSA) was 84%. Ischemic stroke rate was 11%. Perforator infarction rate was 7%. Postoperative subarachnoid hemorrhage (SAH) rate was 3%. Intraparenchymal hemorrhage (IPH) rate was 4%. CONCLUSIONS: Flow diverter treatment of PCAs is an effective method, which provides a high rate of complete occlusion at 6-month DSA. However, compared with anterior circulation aneurysms, patients with PCAs are at significantly higher risk of mortality, ischemic stroke and perforator infarction. Our findings indicate that, in most clinical centers, flow diverter treatment of PCAs should be conducted in carefully selected patients with poor natural history and no optimal treatment strategy. For ruptured and giant basilar artery aneurysms, there is still no good treatment option.

Retinoic acid­incorporated glycol chitosan nanoparticles inhibit the expression of Ezh2 in U118 and U138 human glioma cells.

At present, one of the most life threatening types of adult brain tumor is glioblastoma multiforme (GBM). The molecular mechanism underlying the progression of GBM remains to be fully elucidated. The modern method of clinical treatment has only improved the average survival rates of a newly diagnosed patients with GBM by ~15 months. Therefore, the discovery of novel molecules, which are involved in glioma inhibition is required. In the present study, U118 and U138 human glioma cells were transfected with all­trans retinoic acid (RA)-incorporated glycol chitosan (GC) nanoparticles.An MTT assay was used for the analysis of cell proliferation and flow cytometric analysis and ssDNA detection assays were performed for the determination of induction of cell apoptosis. Cell cycle distribution was analyzed by flow cytometry. Exposure of the U118 and U138 human glioma cells to the RA­incorporated GC nanoparticles for 24 h resulted in a concentration­dependent inhibition of cell proliferation. Among the range of experimental RA concentrations, the minimum effective treatment concentration was 10 µM, with a half maximal inhibitory concentration of 25 µM. The results also demonstrated that RA transfection resulted in the inhibition of cell proliferation, inhibition of the expression of Ezh2, and apoptosis through the mitochondrial signaling pathway by a decrease in membrane potential, the release of cytochrome c, and cell cycle arrest in the G0/G1 phase.

Biphasic activation of nuclear factor-kappa B in experimental models of subarachnoid hemorrhage in vivo and in vitro.

It has been proven that nuclear factor-kappa B (NF-κB) is activated as a well-known transcription factor after subarachnoid hemorrhage (SAH). However, the panoramic view of NF-κB activity after SAH remained obscure. Cultured neurons were signed into control group and six hemoglobin- (Hb-) incubated groups. One-hemorrhage rabbit SAH model was produced, and the rabbits were divided randomly into one control group and five SAH groups. NF-κB activity was detected by electrophoretic mobility shift assay (EMSA) and immunohistochemistry. Real-time polymerase chain reaction (PCR) was performed to assess the downstream genes of NF-κB. NeuN immunofluorescence and lactate dehydrogenase (LDH) quantification were used to estimate the neuron injury. Double drastically elevated NF-κB activity peaks were detected in rabbit brains and cultured neurons. The downstream gene expressions showed an accordant phase peaks. NeuN-positive cells decreased significantly in day 3 and day 10 groups. LDH leakage exhibited a significant increase in Hb-incubated groups, but no significant difference was found between the Hb incubated groups. These results suggested that biphasic increasing of NF-κB activity was induced after SAH, and the early NF-κB activity peak indicated the injury role on neurons; however, the late peak might not be involved in the deteriorated effect on neurons.