The neuroprotective effect of electro-acupuncture on cognitive recovery for patients with mild traumatic brain injury: A randomized controlled clinical trial.

BACKGROUND: Traumatic brain injury (TBI) is a major health and socioeconomic problem that affects all societies. Consciousness disorder is a common complication after TBI while there is still no effective treatment currently. The aim of this study was to investigate the protective effect of electro-acupuncture (EA) on cognitive recovery for patients with mild TBI. METHODS: A total of 83 patients with initial Glasgow coma scale score higher than 12 points were assigned into this study. Then patients were randomly divided into 2 groups: EA group and control group (group C). Patients in group EA received EA treatment at Neiguan and Shuigou for 2 weeks. At 0 minute before EA treatment (T1), 0 minute after EA treatment (T2), and 8 weeks after EA treatment (T3), level of neuron-specific enolase (NSE), glial fibrillary acidic protein (GFAP), hypoxia inducible factor-1α (HIF-1α), and malondialdehyde were tested by enzyme-linked immunosorbent assay. The score of Montreal Cognitive Function Assessment (MoCA) and mini-mental state examination (MMSE) as well as cerebral oxygen saturation (rSO2) were detected at the same time. RESULTS: Compared with the baseline at T1, the level of NSE, GFAP, HIF-1α, MDA, and rSO2 decreased, and the score of MoCA and MMSE increased in the 2 groups were significantly increased at T2-3 (P < .05). Compared with group C, the level of NSE, GFAP, HIF-1α, MDA, and rSO2 decreased, and the score of MoCA and MMSE increased were significantly increased at T2-3 in group EA; the difference were statistically significant (P < .05). CONCLUSIONS: EA treatment could improve the cognitive recovery for patients with mild TBI and the potential mechanism may be related to improving cerebral hypoxia and alleviating brain injury.

[Corrigendum] Quercetin protects rat cortical neurons against traumatic brain injury.

Subsequently to the publication of the above paper, an interested reader drew to the authors' attention that a pair of the data panels in Fig. 4A (on p. 7862), showing the 'Sham' and 'TBI' experiments, were overlapping, such that the data were apparently derived from the same original source. After having examined their original data, the authors have realized that they uploaded the incorrect image for the 'Sham' experiment in this figure. The revised version of Fig. 4 showing the correct data for all the experiments portrayed in Fig. 4A, is shown opposite. Note that the replacement of the erroneous data does not affect either the results or the conclusions reported in this paper, and all the authors agree to the publication of this corrigendum. The authors are grateful to the Editor of Molecular Medicine Reports for granting them this opportunity to publish a Corrigendum, and apologize to the readership for any inconvenience caused.[Molecular Medicine Reports 17: 7859-7865, 2018; DOI: 10.3892/mmr.2018.8801].

LINC01087 inhibits glioma cell proliferation and migration, and increases cell apoptosis via miR-384/Bcl-2 axis.

BACKGROUND: Long non-coding RNA (LncRNA) is associated with disease progression. It is reported that LINC01087 is highly expressed in cancer and participates in tumorigenesis. However, whether it regulates the development of glioma has not been studied. So, the goal of this research is to determine the role of LINC01087 in gliomas and to provide potential targets for clinical treatment. METHODS: The gene expression was detected by quantitative reverse transcriptase polymerase chain reaction (QRT-PCR) and Western blotting (WB). Cell proliferation was analyzed by CCK8 and colony formation test, and apoptosis was detected by flow cytometry. Luciferase report experiment and RNA Binding Protein Immunoprecipitation confirmed the interaction between LINC01087, miR-384 and Bcl-2. The effect of regulating LINC01087 on the growth of glioma was confirmed in vitro. RESULTS: The LINC01087 expression was up-regulated in clinical glioma samples (n = 35). Furthermore, LINC01087 silencing can obviously suppress the proliferation of glioma cells and induce apoptosis. Mechanically, we found that LINC01087 was the molecular sponge of miR-384. LINC01087 could inhibit the miR-384 expression and boost the Bcl-2 expression through sponge expression of miR-384. The repair of Bcl-2 effectively saved the proliferation and apoptosis of glioma cells lacking LINC01087. CONCLUSION: LINC01087 is highly expressed in glioma and can participate in the growth of glioma through miR-384/Bcl-2 axis. So, it is a potential therapeutic target.

ALKBH5 Promotes the Proliferation of Glioma Cells via Enhancing the mRNA Stability of G6PD.

This study aims to investigate the biological role of 6-methyladenine (m6A) methylation in inducing the carcinogenesis of glioma and its proliferation. Relative levels of ALKBH5 and glucose-6-phosphate dehydrogenase (G6PD) in glioma tissues and cell lines were determined by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. Gain-of-function and loss-of-function approaches were used to investigate the role of ALKBH5 in mediating proliferation and energy metabolism of glioma cells. The regulatory effect of ALKBH5 on G6PD was analyzed using m6A-qRT-PCR. Our results showed that ALKBH5 was upregulated in glioma, which stimulated glioma cells to proliferate. Serving as a m6A eraser, ALKBH5 demethylated the target transcript G6PD and enhanced its mRNA stability, thereby promoting G6PD translation and activating the pentose phosphate pathway (PPP). Collectively, ALKBH5 stimulates glioma cells to proliferate through erasing the m6A methylation of G6PD, which can be utilized as a potential therapeutic target for glioma.

Prognostic Value of Abnormal Muscle Response During Microvascular Decompression for Hemifacial Spasm: A Meta-Analysis.

OBJECTIVE: To perform a comprehensive meta-analysis to systematically assess the value of abnormal muscle response (AMR) in predicting the surgical outcome of patients with hemifacial spasm. METHODS: The electronic database PubMed, Embase, Web of Science, and ScienceDirect were searched, and relevant articles were identified up to September 30, 2019. These data were extracted for pooled analysis, heterogeneity testing, sensitivity analysis, publication bias analysis, and Fagan plot analysis. RESULTS: The disappearance of AMR during microvascular decompression was associated with a favorable short-term surgical outcome (pooled relative risk [RR], 1.42; 95% confidence interval [CI], 1.24-1.62; pooled RR adjusted for publication bias, 1.30; 95% CI, 1.08-1.57). The corresponding pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 0.91 (95% CI, 0.88-0.94), 0.34 (95% CI, 0.27-0.42), 1.4 (95% CI, 1.2-1.6), 0.26 (95% CI, 0.17-0.38), and 5 (95% CI, 3-9), respectively. The disappearance of AMR was almost ineffective in predicting the long-term surgical outcome (pooled RR, 1.09; 95% CI, 1.02-1.17; pooled RR adjusted for publication bias, 1.001; 95% CI, 0.92-1.09). The corresponding pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 0.90 (95% CI, 0.85-0.93), 0.28 (95% CI, 0.20-0.37), 1.2 (95% CI, 1.1-1.4), 0.38 (95% CI, 0.22-0.63), and 3 (95% CI, 2-6), respectively. CONCLUSIONS: The disappearance of AMR during microvascular decompression demonstrates limited prognostic value for a favorable short-term outcome, and does not appear effective in predicting the long-term outcome of patients with hemifacial spasm.

Quercetin protects rat cortical neurons against traumatic brain injury.

Previous studies have demonstrated that traumatic brain injury (TBI) may cause neurological deficits and neuronal cell apoptosis. Quercetin, one of the most widely distributed flavonoids, possesses anti­inflammatory, anti­blood coagulation, anti­ischemic and anti­cancer activities, and neuroprotective effects in the context of brain injury. The purpose of the present study was to investigate the neuroprotective effects of quercetin in TBI. A total of 75 rats were randomly arranged into 3 groups as follows: Sham group (Sham); TBI group (TBI); and TBI + quercetin group (Que). Brain edema was evaluated by analysis of brain water content. The neurobehavioral status of the rats was evaluated by Neurological Severity Scoring. Immunohistochemical and western blot analyses were used to measure the expression of certain proteins. The results of the present study demonstrated that post­TBI administration of quercetin may attenuate brain edema, in addition to improving motor function in rats. Additionally, quercetin caused a marked inhibition of extracellular signal­regulated kinase 1/2 phosphorylation and activated Akt serine/threonine protein kinase phosphorylation, which may result in attenuation of neuronal apoptosis. The present study provided novel insights into the mechanism through which quercetin may exert its neuroprotective activity in a rat model of TBI.

MAPK pathway mediates the anti-oxidative effect of chicoric acid against cerebral ischemia-reperfusion injury in vivo.

The aim of the present study was to investigate the protective effect of chicoric acid on oxidative stress and inflammation in rats with cerebral ischemia-reperfusion injury. A cerebral ischemia-reperfusion injury rat model was created via transient middle cerebral artery occlusion (MCAO) and rats were treated with various doses of chicoric acid (0, 1, 10 and 100 mg/kg). Neurological deficits and infarct volume were used to estimate the protective effects of chicoric acid treatment. Levels of reactive oxygen species (ROS), tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, nitric oxide (NO) and prostaglandin E2 (PGE2) were assessed. Western blot analysis was also used to measure the expression of cyclooxygenase (COX)-2, p38-mitogen activated protein kinase (MAPK), c-Jun, phosphorylated protein kinase B (p-AKT) and AKT. Chicoric acid exposure was observed to reduce neurological deficits and infarct volume in rats with cerebral ischemia-reperfusion injury. In addition, ROS production and inflammation were significantly suppressed following treatment with chicoric acid. Chicoric acid was demonstrated to significantly inhibit the upregulation of NO and PGE2 levels in rats following MCAO. Furthermore, chicoric acid significantly suppressed the MCAO-induced promotion of COX-2, p38-MAPK and c-Jun protein expression and enhanced the inhibition of p-AKT/AKT. These results suggest that chicoric acid has a protective effect, preventing oxidative stress and inflammation in rats with cerebral ischemia-reperfusion injury via the p38-MAPK, c-Jun and AKT signaling pathways.

The silencing of LncRNA-H19 decreases chemoresistance of human glioma cells to temozolomide by suppressing epithelial-mesenchymal transition via the Wnt/ß-Catenin pathway.

INTRODUCTION: Temozolomide (TMZ) is commonly used for glioma chemotherapy. However, TMZ resistance limits the therapeutic effect of TMZ in glioma treatment. LncRNA-H19 acts as an oncogenic LncRNA in some types of cancers and has been reported to be up-regulated in glioma. MATERIALS AND METHODS: In our present study, we established TMZ-resistant glioma cells (U-251TMZ and M059JTMZ) to explore the effect of H19 on the chemoresistance of glioma cells. RESULTS: We observed that the expression of H19 was significantly increased in U-251TMZ and M059JTMZ cells. Knockdown of H19 expression using specific shRNA in U-251TMZ and M059JTMZ led to decreased half maximal inhibitory concentration (IC50) values for TMZ and increased cell apoptosis rates, indicating that the silencing of H19 decreased chemoresistance of glioma cells to TMZ. In addition, silencing of H19 suppressed epithelial-mesenchymal transition (EMT) by increasing the expression of epithelial marker E-cadherin and decreasing the expression of mesenchymal marker Vimentin and ZEB1. Moreover, inducing EMT by TGF-ß1 treatment led to increased IC50 values for TMZ and decreased cell apoptosis rates compared with TMZ+H19 shRNA group, suggesting that the induction of EMT counteracted the inhibitory effect of H19 shRNA on chemoresistance of glioma cells to TMZ. Furthermore, the reduced expression of H19 down-regulated the expression of ß-Catenin and its downstream targets c-myc and Survivin in TMZ-treated glioma cells. Activation of Wnt/ß-Catenin pathway by Licl treatment promoted EMT and enhanced chemoresistance to TMZ compared with TMZ+H19 shRNA group. CONCLUSION: Taken together, our data suggest that H19 decreased chemoresistance of glioma cells to TMZ by suppressing EMT via the inhibition of Wnt/ß-Catenin pathway. Our study might represent a novel therapeutic target for TMZ-resistant glioma.

Quercetin attenuates neuronal autophagy and apoptosis in rat traumatic brain injury model via activation of PI3K/Akt signaling pathway.

OBJECTIVE: Neuronal autophagy and apoptosis play an irreplaceable role in brain injury pathogenesis and may represent a hopeful target for treatment. Previous studies have demonstrated that administration of quercetin-attenuated brain damage in a variety of brain injury models including traumatic brain injury (TBI). However, whether PI3K/Akt signaling pathway mediates the neuroprotection of quercetin following TBI is not well clarified. We sought to propose a hypothesis that quercetin could attenuate neuronal autophagy and apoptosis via enhancing PI3K/Akt signaling. METHODS: All rats were randomly arranged into four groups as follows: sham group (n = 25), TBI group (n = 25), TBI + quercetin group (n = 25), TBI + quercetin + LY294002 group (n = 25). Quercetin (Sigma, USA, dissolved in 0.9% saline solution) was administered intraperitoneally at a dose of 50 mg/kg at 30 min, 12 h, and 24 h after TBI. The neurological impairment and spatial cognitive function was assessed by the neurologic severity score and Morris water maze, respectively. Immunohistochemistry staining and western blotting was used to evaluate the expression of LC3, p-Akt, caspase-3, Bcl-2, and Bax. RESULTS: Quercetin treatment significantly attenuated TBI-induced neurological impairment (1-3 days, p < 0.05) and improved cognitive function (5-8 days, p < 0.05). Double immunolabeling demonstrated that quercetin significantly reduced the LC3-positive cells co-labeled with NeuN, whereas significantly enhanced p-Akt-positive cells co-labeled with NeuN. Furthermore, quercetin treatment reduced the expression of LC3、caspase-3 and Bax levels induced following TBI (p < 0.05), and increased the expression of p-Akt and Bcl-2 at 48 h (p < 0.05). CONCLUSION: In conclusion, our observations indicate that post-injury treatment with quercetin could inhibit neuronal autophagy and apoptosis in the hippocampus in a rat model of TBI. The neuroprotective effects of quercetin may be related to modulation of PI3K/Akt signaling pathway.