Crosstalk between peripheral and the brain-resident immune components in epilepsy.

Epilepsy is one of the most common neurology diseases. It is characterized by recurrent, spontaneous seizures and accompanied by various comorbidities which can significantly affect a person's life. Accumulating evidence indicates an essential pathophysiological role for neuroinflammation in epilepsy, which involves activation of microglia and astrocytes, recruitment of peripheral leukocytes into the central nervous system, and release of some inflammatory mediators, including pro-inflammatory factors and anti-inflammatory cytokines. There is complex crosstalk between the central nervous system and peripheral immune responses associated with the progression of epilepsy. This review provides an update of current knowledge about the contribution of this crosstalk associated with epilepsy. Additionally, how gut microbiota is involved in epilepsy and its possible influence on crosstalk is also discussed. Such recent advances in understanding suggest innovative methods for targeting the molecules correlated with the crosstalk and may provide a better prognosis for patients diagnosed with epilepsy.

[Effects of Different Shading Treatment and Planting Patterns on Several Main Characters and Yield of Elephantopus scaber].

OBJECTIVE: To study the growth and yield of Elephantopus scaber under different light conditions. METHODS: Several main characters and yield performances were studied under six shading treatment as well as two planting patterns. RESULTS: The plant height, leaf number, root length and root-shoot ratio were increased under moderate shading. With the increase of shading ratio, the process of Elephantopus scaber vegetative growth to reproductive growth were shortened, seed yield, dry biomass and root yield decreased as well. Among different shading treatments, dry seed-yield showed 8. 46 ~31. 10 kg/667 m2 dry biomass showed 327. 28 ~ 800. 95 kg/ 667 m2 and dry root yield showed 30. 65 ~ 70. 72 kg/667 m2. CONCLUSION: Elephantopus scaber is a light-demanding but shade-tolerant plant. The patterns of hole seeding were suggested in planting, and not more than 60% shade density may be good under plantations.

Association between 5-HTTLPR polymorphism and Parkinson's disease: a meta analysis.

To investigate the genetic association of 5-HTTLPR polymorphism and Parkinson's disease (PD) or depression in PD by using meta analysis. Published association studies on genotype or allele frequencies of the 5-HTTLPR in patients with or without PD or in PD patients with or without depression in all ethnic groups were included. A biallelic meta-analysis, including biallelic frequency model, biallelic dominant model (BDM) and biallelic recessive model, was performed using the Cochrane Review Manager (RevMan, version 5.2) to calculate the pooled odds ratio and its corresponding 95 % CI with a random-effect model. Six studies met the criteria for the meta-analysis of association of 5-HTTLPR and three studies were included for the association of 5-HTTLPR and depression in PD. The meta-analysis results did not show significant association between 5-HTTLPR and PD or depression in PD, except for a moderate negative association between 5-HTTLPR and PD in Asian subgroup (2 studies) using the BDM approach. Our meta-analysis result does not support a direct primary effect of 5-HTTLPR on PD or depression in PD. Further association studies with larger sample sizes preferably taking into consideration factors such as additional allelic variants in the 5-HTTLPR, ethnic variation of the 5-HTTLPR distribution and gene-gene interaction are necessary to reach a more definite conclusion.

Gene expression profiling analysis of the putamen for the investigation of compensatory mechanisms in Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is affecting 5 million people worldwide, but the response mechanisms of the striatum are still unclear. Therefore, identification of gene expression alterations in the striatum will greatly assist the development of novel therapy strategies. METHODS: We performed a comprehensive gene expression analysis in 15 PD patients and 15 normal controls to identify differentially expressed genes (DEGs) using the expression profile GSE20291 from Gene Expression Omnibus (GEO). Gene Ontology (GO) analysis and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway enrichment analysis were used to define functions and pathways altered in PD. Protein-protein interaction network was constructed to find out the modules with close interactions. RESULTS: Total715 DEGs including 268 up-regulated and 447 down-regulated genes were obtained. GO functional enrichment analysis indicated that the genes related with neurons function and cell morphogenesis might be changed upon PD. KEGG pathway enrichment analysis showed that most of the genes were enriched in the nodes of Gap junction, calcium signaling pathway, phosphatidylinositol signaling system, long-term potentiation, Alzheimer's disease and GnRH signaling pathway. Protein-protein interaction network and module analysis suggested that some apoptosis related genes, such as PRKCA, CDC42 and BCL2 may play critical roles in striatal neurons growth. CONCLUSION: Intrinsic striatal tyrosine hydroxylase interneurons growth may be promoted by changes in several genes expression and thus reduce the functional excitatory synapses.

Standard-Dose Atorvastatin Treatment in Patients With Symptomatic Middle Cerebral Artery Atherosclerotic Stenosis: A Vessel Wall Magnetic Resonance Imaging Study.

Background and Purpose: Ischemic stroke can be caused by atherosclerotic lesions of the middle cerebral artery (MCA). Some studies have described the effects of statin treatment on carotid artery plaques, but little is known about the effects of statin treatment on MCA plaques. The purpose of this study was to validate the efficacy of standard-dose atorvastatin (20 mg/day) in patients with symptomatic MCA atherosclerotic stenosis (SMAS) in northern China. Materials and Methods: This study is a prospective, single-arm, single-center, 12-month follow-up observational study monitoring imaging, and clinical outcomes of standard-dose atorvastatin treatment among patients with SMAS. The primary outcomes were changes in vessel wall magnetic resonance imaging (VWMRI) and serum lipid profiles before and after (1, 3, 6, and 12 months) statin treatment. Results: A total of 46 patients were recruited for this study, and 24 patients completed the follow-up. During the follow-up period, serum non-high-density lipoprotein cholesterol concentrations gradually decreased in the patients. Fourteen patients (54.33%) had a reversal of MCA plaques and 10 patients (41.67%) had no significant progression of MCA plaques and remained stable at the follow-up endpoint. At the 12 months follow-up time-point, the treatment did not reverse vascular remodeling or change the shape and distribution of plaques. Altered serum low-density lipoprotein cholesterol (LDL-C) concentrations in patients were strongly associated with plaque reversal. Conclusion: Vessel wall magnetic resonance imaging could accurately characterize changes in MCA plaques after lipid-lowering therapy. Standard-dose atorvastatin treatment could stabilize and reverse plaques in northern Chinese patients with SMAS.

Correlations of MCP-1 -2518A>G polymorphism and serum levels with cerebral infarction risk: a meta-analysis.

This meta-analysis was performed to evaluate the relationships between the monocyte chemoattractant protein-1 (MCP-1) -2518A>G (rs1024611 A>G) polymorphism and its serum levels, and the risk of cerebral infarction. The PubMed, CISCOM, CINAHL, Web of Science, Google Scholar, EBSCO, Cochrane Library, and CBM databases were searched for relevant articles published before October 1st, 2013 without language restrictions. Meta-analysis was conducted using the STATA 12.0 software. Crude odds ratios (ORs) or standardized mean difference (SMD) with their 95% confidence intervals (95% CIs) were calculated. Twelve case-control studies that met all the inclusion criteria were included in this meta-analysis. A total of 1272 patients with cerebral infarction and 1210 healthy control subjects were involved in this meta-analysis. Our meta-analysis results reveal that the MCP-1 -2518A>G polymorphism might increase the risk of cerebral infarction (A allele vs. G allele: OR=1.37, 95% CI: 1.18-1.60, p<0.001; GA+AA vs. GG: OR=1.33, 95% CI: 1.09-1.62, p=0.005; respectively). Furthermore, cerebral infarction patients had higher levels of serum MCP-1 than did healthy control subjects (SMD=2.96, 95% CI: 2.00-3.92, p<0.001). Statistical analysis revealed no evidence of publication bias in this meta-analysis (all p>0.05). Our findings indicate that the MCP-1 -2518A>G polymorphism and serum MCP-1 levels may contribute to the development of cerebral infarction. Thus, the MCP-1 -2518A>G polymorphism and serum MCP-1 levels could be potential biomarkers for the early detection of cerebral infarction.

Genetic polymorphisms in the ESR1 gene and cerebral infarction risk: a meta-analysis.

A number of studies have documented that estrogen receptor α (ESR1) may play an important role in the development and progression of cerebral infarction, but many existing studies have yielded inconclusive results. This meta-analysis was performed to evaluate the relationships between ESR1 genetic polymorphisms and cerebral infarction risk. The PubMed, CISCOM, CINAHL, Web of Science, Google Scholar, EBSCO, Cochrane Library, and CBM databases were searched for relevant articles published before October 1, 2013, without any language restrictions. Meta-analysis was conducted using the STATA 12.0 software. Seven case-control studies were included with a total of 1471 patients with cerebral infarction and 4688 healthy control subjects. Two common single-nucleotide polymorphisms (SNPs) in the ESR1 gene (rs2234693 T>C and rs9340799 A>G) were assessed. Our meta-analysis results revealed that ESR1 genetic polymorphisms might increase the risk of cerebral infarction. Subgroup analysis by SNP type indicated that both rs2234693 and rs9340799 polymorphisms in the ESR1 gene were strongly associated with an increased risk of cerebral infarction. Further subgroup analysis by ethnicity showed significant associations between ESR1 genetic polymorphisms and increased risk of cerebral infarction among both Asians and Caucasians. In the stratified subgroup analysis by gender, the results suggested that ESR1 genetic polymorphisms were associated with an increased risk of cerebral infarction in the female population. However, there were no statistically significant associations between ESR1 genetic polymorphisms and cerebral infarction risk in the male population. Meta-regression analyses also confirmed that gender might be a main source of heterogeneity. Our findings indicate that ESR1 genetic polymorphisms may contribute to the development of cerebral infarction, especially in the female population.

Hypoxia increases Aß-induced tau phosphorylation by calpain and promotes behavioral consequences in AD transgenic mice.

Chronic hypoxia has been reported to contribute to the development of Alzheimer's disease (AD). However, the mechanism of hypoxia in the pathogenesis of AD remains unclear. The purpose of this study was to investigate the effects of chronic hypoxia treatment on ß-amyloid, tau pathologies, and the behavioral consequences in the double transgenic (APP/PS1) mice. Double transgenic mice (APP/PS1 mice) were treated with hypoxia, and spatial learning and memory abilities of mice were assessed in the Morris water maze. ß-amyloid level and plaque level in APP/PS1 double transgenic mice were detected by immunohistochemistry. Protein tau, p35/p25, cyclin-dependent kinase 5 (CDK5), and calpain were detected by western blotting analysis. Chronic hypoxia treatment decreased memory and cognitive function in AD mice. In addition, chronic hypoxia treatment resulted in increased senile plaques, accompanying with increased tau phosphorylation. The hypoxia-induced increase in the tau phosphorylation was associated with a significant increase in the production of p35 and p25 and upregulation of calpain, suggesting that hypoxia induced aberrant CDK5/p25 activation via upregulation of calpain. Our results showed that chronic hypoxia exposure accelerates not only amyloid pathology but also tau pathology via calpain-mediated tau hyperphosphorylation in an AD mouse model. These pathological changes possibly contribute to the hypoxia-induced behavioral change in AD mice.

Metformin inhibits glioma cell U251 invasion by downregulation of fibulin-3.

Fibulin-3 has been considered as a regulator of glioma cell invasion, but little is known about the molecules regulating fibulin-3 expression. Metformin, an oral antidiabetic drug in the biguanide class, is known to inhibit proliferation and metastasis in a variety of cancer cells. In the present study, we determined the effect of metformin on the expression of fibulin-3 in U251 Human glioma cells. Metformin potently suppressed U251 cell adhesion and invasion. Metformin inhibited the expression of fibulin-3 at the transcriptional level. Moreover, metformin abolished the protein expression of fibulin-3 in a concentration-dependent manner. Furthermore, this compound suppressed the expression of matrix metalloproteinase-2, a key effector of glioma cell invasion, regulated by fibulin-3. Taken together, our results suggest that metformin abolishes fibulin-3 expression and subsequently inhibits invasion of glioma cells.