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Breast cancer is the second leading primary cause for cancer-related mortality among women and metastasis to the brain is a disastrous event for patients with increasing incidence. A previous study confirmed the critical function of RRM2 in breast cancer cell growth. Unfortunately, the role and fundamental molecular mechanism of RRM2 in breast cancer metastasis remains elusive. In the current study, higher RRM2 expression was validated in breast cancer tissues, especially in the brain metastasis group. Simultaneously, the expression of RRM2 was increased in breast cancer cells relative to the normal breast epithelial cell line MCF-10A, concomitant with higher levels of RRM2 in the highly metastatic MDA-MB-231 cell line relative to the weakly metastatic MCF-7 cell line. Knockdown of RRM2 by small interfering-RRM2 transfection notably suppressed the malignant metastatic behavior of breast cancer cells, including invasion and migration. Simultaneously, RRM2 downregulation also restrained the transcription and release of vascular endothelial growth factor (VEGF) in breast cancer cells. Moreover, inhibition of RRM2 dampened the activation of phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) signaling by decreasing phosphorylated-AKT and downstream matrix metalloproteinases-2 expression.Intriguingly, reactivation of the PI3K/AKT pathway with its agonist insulin-like growth factor-1 reversed the adverse effects of RRM2 suppression on cancer cell invasion, migration and VEGF expression. Together, these findings suggest that RRM2 may act as a pro-metastatic factor to facilitate breast cancer metastasis by evoking cell invasion, migration and VEGF expression through the PI3K/AKT signaling pathway. This study may provide an attractive target for metastatic intervention in breast cancer.Key words: breast cancer, brain metastasis, RRM2, cell invasion and migration, vascular endothelial growth factor, phosphatidyl inositol 3 kinase/protein kinase B

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MiR-30c has been acknowledged as a tumor suppressor in various human cancers, such as ovarian cancer, gastric cancer and prostate cancer. However, the role of miR-30c in glioblastoma (GBM) needs to be investigated. In our study, we found that the expression of miR-30c was significantly downregulated in GBM tissues and cell lines. We found that overexpression of miR-30c inhibited cellular proliferation of GBM cells and. More GBM cells were arrested in G0 phase after miR-30c overexpression. Moreover, we showed that miR-30c overexpression suppressed the migration and invasion of GBM cells. In mechanism, we found that SOX9 was a direct target of miR-30c in GBM cells. Overexpression of miR-30c inhibited the mRNA and protein levels of SOX9 in GBM cells. Moreover, there was a negative correlation between the expression of miR-30c and SOX9 in GBM tissues. Finally, we showed that restoration of SOX9 in GBM cells reversed the proliferation, migration and invasion of GBM cells transfected with miR-30c mimics. Collectively, our results demonstrated that miR-30c suppressed the proliferation, migration and invasion of GBM cells via targeting SOX9.

Our study aimed to investigate the effect of intravenous thrombolysis with alteplase and edaravone on cerebral hemodynamics and T lymphocyte level in patients harboring acute cerebral infarction. There involved a total of 118 patients with acute cerebral infarction from November 2017 to May 2019 in our hospital were randomly divided into 2 groups: the observation group (59 patients were treated with intravenous thrombolysis with alteplase combined with edaravone) and the control group (59 patients were treated with intravenous thrombolysis of alteplase). The clinical effect, neurological function, cerebral hemodynamic index, T lymphocyte level, oxygen free radical scavenging level and oxidative stress index of the 2 groups were observed and compared. Before the treatment, there were no significant differences in neurological function, cerebral hemodynamic indexes, T-lymphocyte level, oxygen free radical scavenging level and oxidative stress indexes between the 2 groups ( P > .05). After the treatment, the neurological function, cerebral hemodynamic indexes, T-lymphocyte level, oxygen free radical scavenging level and oxidative stress indexes of the 2 groups were significantly improved. In addition, the observation group exerted greater beneficial effect in terms of the clinical effect, neurologic function, cerebral hemodynamic index, T lymphocyte level, oxygen free radical scavenging level and oxidative stress index than those of the control group ( P < .05). The intravenous thrombolysis with alteplase and edaravone is effective in the treatment of acute cerebral infarction, which also provides better results in terms of improving the clinical efficacy and prognosis of patients and might be an alternative option for clinical practice.

IntroductionPreviously published articles have suggested that BDNF rs6265 G>A polymorphism is a potential risk factor for epilepsy. However, the results were not consistent.MethodsWe conducted a meta-analysis to explore the association between BDNF rs6265 G>A polymorphism and epilepsy risk. Four online databases were searched, and related studies were reviewed from their inception up to June 20, 2017. ORs and corresponding 95% CIs were used to calculate the associations of each genetic model. Overall, 10 case–control publications involving 9,512 subjects were included in this meta-analysis.ResultsSignificant associations were found between BDNF rs6265 G>A polymorphism and epilepsy (A vs G: OR=0.88, 95% CI=0.83–0.94, P<0.01, I2=0%; GA vs GG: OR=0.88, 95% CI=0.79–0.97, P=0.01, I2=0%; AA vs GG: OR=0.79, 95% CI=0.70–0.90, P<0.01, I2=0%; GA+AA vs GG: OR=0.85, 95% CI=0.77–0.94, P<0.01, I2=0%; AA vs GG+GA: OR=0.85, 95% CI=0.76–0.95, P=0.01, I2=0%). Subgroup analysis also showed similar results in an Asian population.ConclusionOur meta-analysis indicated that BDNF rs6265 G>A polymorphism might be involved in epilepsy susceptibility, especially in the Asian population.

Purpose The present clinical study was conducted to investigate the effect of oxiracetam combined with ginkgo biloba extract in treating patients with acute intracerebral hemorrhage. Methods Ninety‐eight patients with acute cerebral hemorrhage admitted to our hospital were divided into three groups. The differences of brain edema and cerebral hemorrhage were compared between the three groups after 1 and 2 weeks of treatment, and the recovery of neurological function, serum inflammatory factors, AQP‐4, MMP‐9, cognitive function, activities of daily living, and adverse reactions were compared between the three groups after 2 weeks of treatment. Results There was no significant difference among the three groups before treatment ( p > .05). After treatment, the recovery of neurological function, serum inflammatory factors, AQP‐4, MMP‐9 levels, cognitive function, and activities of daily living were improved. Among them, the neurological function recovery, serum inflammatory factors, AQP‐4, MMP‐9 levels, cognitive function, and activities of daily living in the combined treatment group and the control group elicited greater results than those in the routine group. The results of the combined treatment group showed the most significant difference ( p < .05). The concentration of IL‐6 decreased from 135.98 ± 12.54 to 91.83 ± 7.69 pg/ml, AQP‐4 from 227.55 μg/L ± 21.06 to 114.31 ± 9.22 μg/L, and MMP‐9 from 172.39 ± 9.81 to 94.98 ± 5.01 ng/ml. In addition, the neurological function recovery, the levels of serum inflammatory factors, cognitive function, and activities of daily living in the combined treatment group were better than those in the control group ( p < .05). The mean score of MRS in the combined treatment group decreased from 3.36 ± 0.98 at admission to 1.91 ± 0.38. Conclusion Oxiracetam combined with Ginkgo biloba extract in the treatment of acute cerebral hemorrhage has a significant improvement effect.

Background Germacrone (GM) is a terpenoid compound which is reported to have anti-inflammatory and anti-oxidative effects. However, its role in treating traumatic brain injury (TBI) remains largely unknown. Methods Male C57BL/6 mice were divided into the following groups: control group, TBI group [controlled cortical impact (CCI) model], CCI + 5 mg/kg GM group, CCI + 10 mg/kg GM group and CCI + 20 mg/kg GM group. GM was administered via intraperitoneal injection. The neurological functions (including motor coordination, spatial learning and memory abilities) and brain edema were measured. Nissl staining was used to detect the neuronal apoptosis. Colorimetric assays and enzyme linked immunosorbent assay (ELISA) kits were used to determine the expression levels of oxidative stress markers including myeloperoxidase (MPO), malondialdehyde (MDA) and superoxide dismutase (SOD), as well as the expressions of inflammatory markers, including tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). Additionally, protein levels of Nrf2 and p-p65 were detected by Western blot assay. Results GM significantly ameliorated motor dysfunction, spatial learning and memory deficits of the mice induced by TBI and it also reduced neuronal apoptosis and microglial activation in a dose-dependent manner. Besides, GM treatment reduced neuroinflammation and oxidative stress compared to those in the CCI group in a dose-dependent manner. Furthermore, GM up-regulated the expression of antioxidant protein Nrf2 and inhibited the expression of inflammatory response protein p-p65. Conclusions GM is a promising drug to improve the functional recovery after TBI via repressing neuroinflammation and oxidative stress.