Increased expression of long noncoding RNA LINC00961 suppresses glioma metastasis and correlates with favorable prognosis.

OBJECTIVE: Long non-coding RNA LINC00961 (LINC00961) has been reported to play an important role in tumor development and metastasis of lung cancer. However, the expression and role of LINC00961 in glioma remains unclear. The present study aimed to investigate the expression of LINC00961 in patients with glioma and to investigate its effect on glioma cells. PATIENTS AND METHODS: Quantitative Real-Time PCR (qRT-PCR) was performed to detect the expression of LINC00961 in glioma tissues and cell lines. Then, the association between LINC00961 expression and clinical pathological parameters and prognosis of glioma patients were further evaluated. Gain of function studies were performed to determine the effects of LINC00961 on proliferation and metastasis of glioma cells. Western blotting assay was used to explore the regulation mechanism. RESULTS: We found that LINC00961 was significantly downregulated in glioma tissues and cell lines compared with that of adjacent normal brain tissues and normal human astrocytes. Low expression of LINC00961 was significantly correlated with WHO grade and KPS score. Clinical analysis indicated that patients with low LINC00961 expression had a shorter overall survival than those with high expression. Univariate and multivariable Cox regression analyses further identified that down-regulated LINC00961 might act as an independent prognostic factor for glioma patients. Functionally, overexpression of LINC00961 significantly suppressed glioma cells proliferation, migration, and invasion. Mechanistically, we found that overexpression of LINC00961 inhibited glioma cell EMT. CONCLUSIONS: LINC00961 might be considered as a novel molecule involved in glioma development, which provides an independent prognostic indicator and a potential therapeutic target for glioma patients.

Icariin decreases both APP and Aß levels and increases neurogenesis in the brain of Tg2576 mice.

Icariin is derived most commonly from the traditional Chinese herb Epimedium brevicornum Maxim. Our previous studies have shown that icariin protects neurons from neurotoxic and ischemic conditions. This study aims to investigate the effect of icariin on the expression of amyloid precursor protein (APP) and the level of amyloid-ß peptide (Aß), as well as neurogenesis in the brain of Tg2576 mice, an animal model of Alzheimer's disease (AD). Tg2576 mice and wild-type littermates (WT) were randomized into the following three groups: Tg2576, Tg2576+icariin, and WT groups. All 9-month-old mice were treated with icariin (60mg/kg/d) or distilled water for 3months. Following this, the spatial working memory of Tg2576+icariin mice, as examined in the Y-maze task, was found to improve. Furthermore, reduced levels of insoluble Aß1-40 (69%) and Aß1-42 (50%) after icariin treatment were determined in the brain by enzyme-linked immunosorbent assay (ELISA). Western blot analysis indicated the downregulation of APP expression after icariin treatment, and double staining showed an increased number of 5-bromo-2-deoxyuridine (BrdU)/Neuron-specific nuclear protein (NeuN) double-positive cells in the dentate gyrus region of the hippocampus in Tg2576+icariin mice compared with the Tg2576 mice. The current study demonstrated that icariin improved memory function, decreased the levels of Aß and APP in the brain, and enhanced neurogenesis in the hippocampus of Tg2576 mice. Collectively, these results suggest the potential therapeutic value of icariin in AD.

Pathway enrichment analysis of human osteosarcoma U-2 OS bone cells expose to dexamethasone.

OBJECTIVE: Osteosarcoma is the second highest cause of cancer-related death in children, mainly due to development of often fatal metastasis, usually in the lungs. Glucocorticoids play an important role in the treatment of a number of inflammatory diseases and immune diseases. The objective of this study was to explore the molecular mechanism of osteosarcoma in response to dexamethasone (DEX, a kind of synthetic glucocorticoid), with a view to obtain information on the pathways activated by DEX. MATERIALS AND METHODS: By using the GSE6711 Affymetrix microarray data accessible from Gene Expression Omnibus database, we first identified the differentially expressed genes (DEGs) among different time course treatment with dexamethasone of each isoform, and the DEGs among cells expressing different GR isoforms, followed by the pathway enrichment analysis of the DEGs. RESULTS: The results indicated that DEX could inhibit osteosarcoma cell proliferation and promote osteosarcoma cell apoptosis through induction of lots of related genes expression at the transcription level. CONCLUSIONS: Our data provide a comprehensive bioinformatics analysis of pathways which may be involved in the response to glucocorticoids.

Protective effect and mechanism of Ginkgo biloba leaf extracts for Parkinson disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.

AIM: To observe the effects of extracts of Ginkgo biloba leaves (EGb) on the Parkinson disease (PD) models induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its ion 1-methyl-4-phenylpyridinium (MPP+). METHODS: MPTP was microinjected into substantia nigra of rats to induce a behavior change of rotation. EGb (ip, 50 or 100 mg.kg(1 . d-1) was pretreated consecutively for 19 d before MPTP administered and 1 d after MPTP administered. The contents of malondialdehyde (MDA), superoxide dismutase (SOD), and dopamine (DA) in substantia nigra of model rats were determined. Apoptosis of PC12 cells was induced by MPP+, and the protective effect of EGb (25, 50, and 100 mg/L) was also observed. The cells of apoptosis were observed under a microscope and counted under a fluoroscope after stained with AO/EB. RESULTS: EGb (100 mg . kg-1 . d-1) decreased the duration and frequency of the rotation of rats (P < 0.05, n = 10 ) while EGb (50 or 100 mg/L)inhibited the decreases of DA and SOD and the increase of MDA induced by MPTP, (P < 0.05 or P < 0.01, n = 10). MPP+ (10 micromol/L) induced the apoptosis of PC12 cells, and EGb (50 or 100 mg/L) prevented cells from apoptosis at 6 h, 12 h, and 24 h (P < 0.05 or P < 0.01, n = 3). CONCLUSION: EGb possesses protective effect on the PD models in vivo and in vitro. The anti-oxidation and anti-apoptosis may be one of the mechanisms underlying the neuroprotective effect of EGb.

[RP-HPLC method for determination of protopine in plasma and pharmacokinetics in rats].

AIM: To develop a reversed phase high performance liquid chromatographic method (RP-HPLC) for determination of protopine (Pro) in rat plasma and to investigate the pharmacokinetics of Pro in rats. METHODS: The column was packed with 5 microns C18. The mobile phase (pH 5.6) was a mixture of methanol-water-10% acetic acid (80:20:2). After twice extracted with ether under basic condition, and reextracted with 0.02 mol.L-1 sulfuric acid, protopine in the plasma samples was isolated well. The content of protopine in the plasma sample was measured by UV detector at 285 nm. RESULTS: The lowest limit of detection was 50 ng.mL-1. The intraday and interday precisions were 1.5%-3.0% and 2.1%-6.2%, respectively. The mean recovery was 80.6%-97.6%. A good linear relationship between the peak height and the concentration of protopine in rat plasma was observed. The pharmacokinetics of protopine had been investigated in rats after intravenous administration 10 mg.kg-1. The concentration-time curve of protopine in rat was confirmed to two-compartment open model. The T1/2 alpha, T1/2 beta, Ke, CL, Vd were 0.05 h, 1.85 h, 1.52 h, 6.41 L.h-1 and 17.27 L, respectively. CONCLUSION: This method is suitable for studies on pharmacokinetics of protopine.

[Glutamate-related mechanism of ginsenosides against anoxic-ischemic brain damage].

AIM AND METHODS: To observe the antagonist effect of ginsenosides upon excitatory neurotoxicity of glutamate in rat hippocampal slices, and to observe the inhibitory and facilitated effects of ginsenosides upon glutamate release from cultured mice cortical neurons and upon glutamate uptake by cultured astrocytes, respectively, during simulated ischemia, in order to elucidate whether the protective effect of ginsenosides against anoxic-ischemic brain damage is related to reducing the excitatory neurotoxicity of glutamate. RESULTS: The orthodromic population spikes (OPS) recorded in hippocampal slice decreased in amplitude and disappeared finally during 20-min glutamate (1 mmol/L) exposure, and recovered less 1 h after the end of this exposure. However, OPS recovered well after the use of ginsenosides at different concentrations, especially at 20 microg/ml. In cultured mice cortical neurons and astrocytes, glutamate released from neurons up to several times of control and its uptake by astrocytes decreased markedly during simulated ischemia, ginsenosides (20 microg/ml) could significantly inhibit glutamate release from neurons and facilitate glutamate uptake by astrocytes during the same ischemia exposure. CONCLUSIONS: Reducing the excitatory neurotoxicity of glutamate may be an important mechanism of ginsenosides against anoxic-ischemic brain damage.

Effects of rhynchophylline on motor activity of mice and serotonin and dopamine in rat brain.

Rhynchophylline (Rhy) reduced the spontaneous motor activity and enhanced the sedative and hypnotic effects of sodium pentobarbital in mice. The effects of Rhy on serotonin (5-HT) and dopamine (DA) concentrations in rat brain, and the release of 5-HT and DA from the regional brain slices were studied by a fluorescence detector. Rhy increased the 5-HT content in the hypothalamus and cortex, but reduced the DA concentrations in the cortex, amygdala, and spinal cord. Rhy promoted the release of endogenous DA from 4 brain regions. The release of 5-HT was increased in 2 brain regions and decreased in hypothalamus slice. However, Rhy inhibited the release of both 5-HT and DA evoked by high potassium.

[Effects of rhynchophylline and isorhynchophylline on blood pressure and blood flow of organs in anesthetized dogs].

In anesthetized thoracotomized dogs, rhynchophylline (Rhy 5 mg.kg-1, iv) reduced the mean arterial pressure (MAP), heart rate (HR), and coronary blood flow (CBF) by 1.16 +/- s 0.67 kPa, 19 +/- 12 beats/min, and 0.12 +/- 0.04 ml.min-1.g-1, whereas isorhynchophylline (Isorhy 1 mg.kg-1, iv) reduced the parameters by 3.58 +/- 0.19 kPa, 26 +/- 18 beats/min, and 0.10 +/- 0.04 ml.min-1.g-1, respectively. In unthoracotomized dogs, Rhy (10 mg.kg-1, iv) decreased renal blood flow (RBF) by 0.35 +/- 0.16 ml.min-1.g-1, but did not change the MAP. Isorhy (5 mg.kg-1, iv) reduced the MAP by 3.44 +/- 1.44 kPa, but the RBF remained unaffected. These results indicated that the hypotensive effect of Isorhy in a dosage not affecting RBF was more potent than that of Rhy.