Long-Noncoding RNA TUG1 Promotes Parkinson's Disease via Modulating MiR-152-3p/PTEN Pathway.

Long-noncoding RNA taurine upregulated gene 1 (TUG1) participates in nervous system diseases, but its function in Parkinson's disease (PD) remains unclear. This study explored the function and mechanism of TUG1 in PD. A PD model was constructed using SH-SY5Y cells induced by 1-methyl-4-phenylpyridinium (MPP+) in vitro and mice treated by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in vivo. The expressions of TUG1, miR-152-3p, phosphatase and tensin homologue (PTEN), tyrosine hydroxylase (TH), and Bcl-2, and cleaved caspase-3 expressions were determined by quantitative reverse transcription-PCR and Western blotting. The viability, apoptosis, reactive oxygen species, and release of inflammatory factors from SH-SY5Y cells and substantia nigra tissues were detected by commercial kits. The interaction between TUG1 and miR-152-3p was analyzed by dual-luciferase reporter assay. Hematoxylin/eosin and immunohistochemical staining was performed for assessing the pathological damage and proportion of TH-positive cells. In PD cell model and mice model, TUG1 expression was upregulated and that of miR-152-3p was downregulated. Further research showed that TUG1 sponged and regulated miR-152-3p expression. Silencing of TUG1 not only protected SH-SY5Y cells against cell apoptosis, oxidative stress, and neuroinflammation in vitro, pathological damage and neuroinflammation in vivo, but also suppressed the expressions of PTEN and cleaved caspase-3, and increased the expressions of TH and Bcl-2 in MPP+-treated SH-SY5Y cells. However, the protective role of siTUG1 in SH-SY5Y cells was significantly inhibited by the miR-152-3p inhibitor. Thus, knocking down TUG1 might have a protective effect on PD through the miR-152-3p/PTEN pathway.

MicroRNA-212-3p regulates early neurogenesis through the AKT/mTOR pathway by targeting MeCP2.

Compelling evidence has implicated role of microRNAs (miRNAs) in neurogenesis. Methyl-CpG Binding Protein 2 (MeCP2) was a key contributor to neurological disease. This study investigated whether miR-212-3p affects early neurogenesis associated with MeCP2. Microarray-based gene expression profiling of neurogenesis was employed to identify differentially expressed genes. Next, miR-212-3p expression in neural progenitor cells (NPCs) was detected using in situ hybridization and immunofluorescence. Effect of miR-212-3p and MeCP2 on cell viability, ß-tubulin III expression and the AKT/mammalian target of rapamycin (mTOR) pathway activity was examined with gain- and loss-of-function experiments. In vivo experiments were also performed to verify effects of miR-212-3p on nerve tube development. MiR-212-3p expression was decreased while MeCP2 expression was increased during differentiation of NPCs. MiR-212-3p targets MeCP2 and down-regulates its expression, which resulted in repressed cell differentiation, proliferation as well as blocked AKT/mTOR pathway activation, subsequently early neurogenesis was prevented. Furthermore, overexpression of miR-212-3p inhibited nerve tube development in vivo. Taken together, miR-212-3p could restrain early neurogenesis through the blockade of AKT/mTOR pathway activation by targeting MeCP2, suggesting a promising therapeutic target for neurogenic disorders.

Bioinformatics analysis of gene expression profiling for identification of potential key genes among ischemic stroke.

This study aimed to identify the key differentially expressed genes (DEGs) following ischemic stroke (IS).The GSE22255 microarray dataset, which contains samples from peripheral blood mononuclear cells of 20 IS patients and 20 sex- and age-matched controls, was downloaded from the Gene Expression Omnibus. After data pre-processing, DEGs were identified using the Linear Models for Microarray Data package in R. The Search Tool for the Retrieval of Interacting Genes database was used to predict the interactions among the products of DEGs, and then Cytoscape software was used to visualize the protein-protein interaction (PPI) network. DEGs in the PPI network were then analyzed using the Database for Annotation, Visualization, and Integrated Discovery online software to predict their underlying functions through functional and pathway enrichment analyses.A total of 144 DEGs were identified in IS samples compared with control samples, including 75 upregulated and 69 downregulated genes. Genes with higher degrees in the PPI network included FOS (degree = 26), TP53 (degree = 22), JUN (degree = 20), EGR1 (degree = 18), JUNB (degree = 16), and ATF3 (degree = 15), and these genes may function in IS by interacting with each other (e.g., EGR1-JUN, EGR1-TP53, ATF3-FOS, and JUNB-FOS). Functional enrichment analysis indicated that the downregulated TP53 gene was enriched in immune response and protein targeting categories.ATF3 and EGR1 may have an important protective effect on IS, whereas FOS, JUN, and JUNB may be associated with the development of IS. In addition, TP53 may function as an indicator of poor prognosis for IS through its association with the immune response and protein targeting.

MicroRNA-7 inhibits neuronal apoptosis in a cellular Parkinson's disease model by targeting Bax and Sirt2.

Parkinson's disease (PD) is the second most common age-related neurodegenerative disease. MicroRNA-7 (miR-7) displays neuroprotective properties against PD. However, the biological roles of miR-7 and its underlying molecular mechanisms in PD remain unclear. We demonstrated herein that 1-methyl-4-phenylpyridinium ion (MPP(+)) confers toxic effects on dopaminergic neuron in a dose-dependent manner in a cellular PD model, although this phenomenon is attenuated by miR-7 treatment. Introduction of miR-7 inhibits MPP(+)-induced neuronal apoptosis as reflected by the reduced terminal transferase-mediated dUTP nick end labeling-positive rate, mitochondrial permeability potential, caspase 3 activity, and nucleosomal enrichment factor. Bax and sirtuin 2 (Sirt2) are the direct targets of miR-7. Moreover, the effects of miR-7 were counteracted by Bax and Sirt2 overexpression, respectively. The altered molecular expressions downstream of Bax and Sirt2 are also involved in miR-7 regulation of the MPP(+)-triggered neuronal apoptosis. These findings have implications on the potential application of miR-7 in PD treatment.

Clinical features and magnetic resonance image analysis of 15 cases of demyelinating leukoencephalopathy induced by levamisole.

The aim of this study was to explore the diagnostic value of magnetic resonance imaging (MRI) for levamisole-induced demyelinating leukoencephalopathy. The clinical features and MRI findings of 15 patients with levamisole-induced demyelinating leukoencephalopathy were retrospectively analyzed. The abnormality rate of the patients was demonstrated to be 100% by MRI, and scattered multiple cerebral foci were observed in all of the patients. The majority of the foci were located at the centrum ovale, peri-lateral cerebral ventricles and basal ganglia, while the remainder were located in the brain stem and cerebellum, as well as in the white matter regions of the temporal, frontal, apical and occipital lobes. In addition, mottling and ring-shaped enhancements were observed. The study demonstrated that MRI effectively displays demyelinating leukoencephalopathy, and that the combination of MRI with the medical history of the patient is of significance for the early diagnosis, differentiation and treatment of demyelinating leukoencephalopathy.

Total laparoscopic hysterectomy versus total abdominal hysterectomy for endometrial cancer: a meta-analysis.

The standard surgery for early-stage endometrial cancer is total abdominal hysterectomy (TAH), while total laparoscopic hysterectomy (TLH) is less invasive and assumed to be associated with lower morbidity. This meta- analysis was performed to investigate the effects of TLH versus TAH in women with early-stage endometrial cancer. We searched the PubMed, EMBASE, CBM and Cochrane Review databases for randomized trials assessing the effects of TLH versus TAH in women with early-stage endometrial cancer. The relative risks (RR) with 95% confidence intervals (CIs) from each study were pooled using meta-analysis. In our study, 9 randomized trials with a total of 1,263 patients were included. Meta-analyses showed that TLH was associated with lower risks of major complications (RR = 0.53, 95%CI 0.29-0.98, P = 0.042), total complications (RR = 0.59, 95%CI 0.42-0.82, P = 0.002) and postoperative complications (RR = 0.57, 95%CI 0.40-0.83, P = 0.003). However, there were no obvious differences in risks of intra-operative complications (RR = 0.98, 95%CI 0.62-1.55, P = 0.919) and mortality (RR = 0.96, 95%CI 0.66-1.40, P = 0.835). In conclusion, our results provide new evidence of a benefit for TLH over TAH in terms of major complications, total complications and postoperative complications in endometrial cancer patients.

Executive dysfunction in patients with cerebral hypoperfusion after cerebral angiostenosis/occlusion.

Impairment of executive functions (EFs) was investigated in patients with cerebral hypoperfusion after cerebral angiostenosis/occlusion. Several EFs were measured in patients with cerebral angiostenosis/occlusion and healthy subjects. The vascular conditions, regional cerebral blood flow (rCBF), regional cerebral blood volume (rCBV), mean transit time (MTT), time to peak (TTP), and delay time were assessed. The scores of the vascular stenosis/occlusion group were significantly lower than those of the control group. rCBV and rCBF were negatively correlated with the error response times in the Stroop test, and the persistent error responses in the Wisconsin Card Sorting Test (WCST) were positively correlated with the Montreal Cognitive Assessment (MoCA) scores. TTP was positively correlated with the reaction and error reaction times, and the persistent error response in WCST was negatively correlated with the times of sorting in WCST and MoCA scores. MTT was positively correlated with the persistent error response in WCST. In the Stroop test, delay time was positively correlated with response time, and negatively correlated with error response times, and the persistent error response in WCST and MoCA scores. Patients with cerebral hypoperfusion after cerebral angiostenosis/occlusion had executive dysfunctions in working memory, sustained attention, response inhibition, cognitive flexibility, thought organization, planning, and implementation. Moreover, their executive dysfunctions were related with the decline in rCBF and rCBV. The prolonged TTP, MTT, and delay time suggested a slow blood flow and the poor compensation of collateral circulation, resulting in impairment of the EFs.