OBJECTIVE To evaluate these activities of Rg1 in the 1-methyl-4-phenyl-1,2,3,6-tetrahy?dropyridine (MPTP)/probenecid (MPTP/p)-induced PD mouse model for the first time and to elucidate the underlying mechanisms. METHODS Male C57BL/6 mice were randomly assigned to six groups. One hour prior to MPTP/p injection, Group Ⅲ-Ⅵ mice received 10 mg·kg-1, 20 mg·kg-1, or 40 mg·kg-1 Rg1 or 3 mg·kg-1 selegiline, respectively, orally from D (-3) to D49. Group Ⅰ-Ⅱ mice received solvent water. Subsequently, GroupⅡ-Ⅵ mice received by injection MPTP-HCl (25 mg·kg- 1 bw dissolved in 0.9% saline, sc) on a 40-d schedule at intervals of 4 d between consecutive doses in combination with an adjuvant drug, probenecid (250 mg·kg- 1 bw in 0.03 mL of DMSO, ip); GroupⅠ mice were injected with saline and probenecid. Behavioral performance was assessed in the open field test, pole test and rotarod test. Neurotransmitters in the striatum were detected using HPLC. Protein levels were measured by Western blot. Pathological characteristics were examined by immunohistochemistry. Ultrastructure changes were observed by electron microscopy. RESULTS Oral treatment with Rg1 significantly attenuated the high MPTP-induced mortality, behavior defects, loss of dopamine neurons and abnormal ultrastructure changes in the SNpc. Other assays indicated that the protective effect of Rg1 may be mediated by its anti-neuroinflammatory properties. Rg1 regulated MPTP-induced reactive astrocytes and microglia and decreased the release of cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-1b (IL-1b) in the SNpc. Rg1 also alleviated the unusual MPTP induced increase in oligomeric, phosphorylated and disease-related a-synuclein in the SNpc. CONCLUSION Rg1 protects dopaminergic neurons, most likely by reducing aberrant a-synuclein-mediated neuroinflammation, and holds promise for Parkinson disease therapeutics.

OBJECTIVE Glioblastoma multiforme (GBM) is the most malignant primary tumor of the central nervous system and is associated with a very poor prognosis. No further improvements in outcomes have been reported since radiotherapy-temozolomide therapy was introduced.Therefore,de-veloping new agents to treat GBM is important. This study aimed to evaluate the anti-tumor effect of evodiamine (Evo) on GBM cells, and to determine the underlying mechanisms involved. METHODS U251,LN229,HEB and PC12 cells were treated with various concentrations of evodiamine for 24 and 48 hours,cell viability was measured by MTT assay.The U251 and LN229 cells were treated with evo-diamine(0-10 μmol·L-1)for 24 h,and then stained with Hoechst 33258.An Annexin V-FITC Apoptosis Detection Kit was used to detect apoptosis in the cells.Reactive oxygen species(ROS)production was detected using dichlorofluorescein diacetate (DCFH-DA) staining. The changes in mitochondrial mem-brane potential (MMP) were assessed by JC-1 after cells were treated with evodiamine. The expres-sion levels of p-PI3K,PI3K,p-Akt,Akt,Bax,Bcl-2,p-p38,p38,p-JNK,JNK,p-ERK,ERK,Cytochrome c, Caspase-3, cleaved Caspase-3, PRAP, and cleaved PARP were measured by Western blot analy-ses. RESULTS According to MTT assay results, Evo significantly inhibited the cell proliferation in a time- and dose-dependent manner. Fluorescence microscopy and flow cytometry analyses revealed that Evo induced cell apoptosis in a concentration-dependent manner.Moreover,Evo induced reactive oxygen species (ROS) production and mitochondrial membrane potential (MMP) disruption. Finally, Evo induced apoptosis in cancer cells by suppressing PI3K/AKT signaling and inducing MAPK phos-phorylation(p38 and JNK,but not ERK)to regulate apoptotic proteins(Bax,Bcl-2,Cytochrome c,Cas-pase-3, and PARP). CONCLUSION In summary, Evo inhibits cell proliferation by inducing cellular apoptosis via suppressing PI3K/AKT and activating MAPK in GBM;these results indicate that Evo may be regarded as a new approach for GBM treatment.

This paper reviewed the advances on effective constituents and biological activities of coumarins in recent ten years. Coumarins are a group of important natural compounds, and have been found to have multi-biological activities such as anti-HIV, anti-tumor, anti-hypertension, anti-arrhythmia, anti-osteoporosis, assuaging pain, preventing asthma and antisepsis. Therefore, further investigation should emphasize on improving techniques for extraction and separation, searching the effective precursory compound, and synthesizing and screening out courmarin derivatives with high activity and low toxicity.
Animals ; Anti-Arrhythmia Agents ; pharmacology ; Anti-HIV Agents ; pharmacology ; Antihypertensive Agents ; pharmacology ; Antineoplastic Agents, Phytogenic ; pharmacology ; Coumarins ; isolation & purification ; pharmacology ; Humans ; Plants, Medicinal ; chemistry

OBJECTIVETo establish malignant progression associated gene expression profiles in human brain glioma.

METHODSThe primary (WHO grade II), recurrent (WHO grade III) and re-recurrent (WHO grade IV) glioma specimens were sequentially collected from one single patient. Gene expression of different tumor specimens and normal brain tissue of the same patient was compared by microarrary techniques.

RESULTS197 differentially expressed genes with differential ratio > or = 3 were observed when compared with normal brain tissue. When the specimens (3 tumor, 1 normal brain) were paired with each other, 7 groups containing 489 genes (upregulated 193, downregulated 296) were observed. According to the descending frequency of the 109 genes with known function, they were the genes associated with development, metabolism, differentiation, signal transduction, DNA binding transcription, cellular receptor, immunity, ion-channel transportation, protein translation, cell backbone motion, stress, protooncogene and anti-oncogene and cell apoptosis, respectively.

CONCLUSIONFrom the 197 differentially expressed genes found in one glioma patient experiencing tumor malignant progression, 17 genes screened out by bioinformatics assay, may offer valuable information on molecular mechanisms on genesis and malignant progression of glioma.

Brain Neoplasms ; genetics ; pathology ; Gene Expression Profiling ; Glioma ; genetics ; pathology ; Humans ; Oligonucleotide Array Sequence Analysis

Objective To determine whether atorvastatin will induce depressive symptoms in patients with cerebral infarction. Methods The clinical data of 404 patients with large artery atherosclerotic cerebral infarction, admitted to our hospital from June 2009 to December 2010, were clinically analyzed; these patients were divided into common treatment group (atorvastatin ([7.72±3.01])mg/d,n=151) and intensive lipid lowering group (atorvastatin [18.58±9.93] mg/d,n=201) and control group (n=52); 189 males and 163 females accepted lipid-lowering treatment.Hamilton Depression Rating Scale (HAMD) was employed before treatment and 3 months after the treatment and statistical analysis was performed on their scores. Results No significant deviation in scores of HAMD before and after treatment was noted in these patients (P＞0.05).No significant deviation in scores of HAMD was noted neither between intensive lipid lowering group and control group,nor between common treatment group and control group (P＞0.05). No significant deviation in HAMD was observed between the treatment groups with mild/no depression symptoms and control group (P＞0.05).The scores of HAMD in female patients were significantly higher than that in male patients 3 months after treatment (P＜0.05),but no significant deviations in the level of cholesterol, the lowering degree of cholesterol and the dosage of atorvastatin were observed between female and male patients (P＞0.05). Conclusion The lipid-lowering treatment with atorvastatin will not induce depressive symptoms in patients with cerebral infarction.The depressive symptoms of female is not related with the level of cholesterol,the lowering degree of cholesterol and the dosage ofatorvastatin.

OBJECTIVETo understand the prevalence of Epstein-Barr virus (EBV) infection in urban and rural areas of Beijing using the serological method.

METHODSTotally 589 serum samples were collected from children in Beijing urban and rural areas who were 0--14 years old and tested with Viron-Seron ELISA classic EBV virus capsid antigen IgG antibody (EBV VCA IgG) kit. Optical density of serum samples was obtained at the wavelength of 405 nanometers. Sero-positive or negative samples were determined according to standard curve and cut-off attached in ELISA classic EBV VCA IgG kits. The activity of EBV VCA IgG was calculated by using special formula. The percentage and activity of EBV VCA IgG from Beijing children were compared with SPSS 13.0 between the urban and rural areas.

RESULTSThe percentage of EBV VCA IgG seropositive samples was 83.6%, and 80.8% in those from urban and 86.2% in those from rural areas. The peak value of EBV infection was 71% seen among children under the age of 3 years, and in urban area the rate was 67.7%, which was lower than that in the rural area (75.3%), and was 82.5% by the age of 6, which was lower than the data (up to 90%) reported 30 years ago. There was a significant difference in EBV infection rate and VCA IgG activities in children at different ages between urban and rural areas (P < 0.05).

CONCLUSIONThe rate of EBV infection in children living in urban area was lower by the age of 6 years. The primary infection of EBV occurred late in part of children lived in urban area.

Adolescent ; Age Factors ; Antigens, Viral ; immunology ; Capsid Proteins ; immunology ; Child ; Child, Preschool ; China ; epidemiology ; Cities ; epidemiology ; Epstein-Barr Virus Infections ; epidemiology ; immunology ; Herpesvirus 4, Human ; immunology ; Humans ; Immunoglobulin G ; analysis ; immunology ; Infant ; Infant, Newborn ; Rural Population ; statistics & numerical data ; Serologic Tests

OBJECTIVETo determine independent factors correlated with clinical effects of DK crush and classical crush technique with drug-eluting stents on bifurcation lesions.

METHODS311 patients with bifurcation lesions were randomized to classical (C, n = 156) or double kissing (DK) crush (n = 155) stent implantation group. The primary endpoints included major adverse cardiac events (MACE).

RESULTSFinal kissing balloon inflation (FKBI) success rate was 76% in C and 100% in DK groups (P < 0.001). DK crush procedure was characterized by lower unsatisfactory FKBI rate (27.6% vs.6.3%, P < 0.01). Clinical follow-up was available in 100% and angiographic follow-up in 82% patients. The overall restenosis rate was 32.3% in C and 20.3% in DK groups (P = 0.01), respectively. Cumulative 8-month MACE was 35.9% in without-FKBI and 19.7% in with-FKBI sub-groups, and 11.4% in DK group (P = 0.02). The incidence of stent thrombosis was 3.2% in C group (5.1% without vs. 1.7% with FKBI) and 1.3% in DK group (P > 0.05). The predictive factors of MACE included minimal side branch stent lumen diameter and lack of DK crush technique.

CONCLUSIONDK crush technique is an alternative of double stenting techniques in terms of improvement of restenosis and clinical outcomes.

Aged ; Angioplasty, Balloon, Coronary ; methods ; Coronary Artery Disease ; therapy ; Coronary Stenosis ; therapy ; Drug-Eluting Stents ; Female ; Humans ; Male ; Middle Aged ; Prospective Studies ; Stents

OBJECTIVE: To screen differentially expressed gene (DEG) related to myelodysplastic syndrome (MDS) based on Gene Expression Omnibus (GEO) database, and explore the core genes and pathogenesis of MDS by analyzing the biological functions and related signaling pathways of DEG. METHODS: The expression profiles of GSE4619, GSE19429, GSE58831 including MDS patients and normal controls were downloaded from GEO database. The gene expression analysis tool (GEO2R) of GEO database was used to screen DEG according to | log FC (fold change) |≥1 and P<0.01. David online database was used to annotate gene ontology function (GO). Metascape online database was used to enrich and analyze differential genes in Kyoto Encyclopedia of Genes and Genomes (KEGG). The protein-protein interaction network (PPI) was constructed by using STRING database. CytoHubba and Mcode plug-ins of Cytoscape were used to analyze the key gene clusters and hub genes. R language was used to diagnose hub genes and draw the ROC curve. GSEA enrichment analysis was performed on GSE19429 according to the expression of LEF1. RESULTS: A total of 74 co-DEG were identified, including 14 up-regulated genes and 60 down regulated genes. GO enrichment analysis indicated that BP of down regulated genes was mainly enriched in the transcription and regulation of RNA polymerase II promoter, negative regulation of cell proliferation, and immune response. CC of down regulated genes was mainly enriched in the nucleus, transcription factor complexes, and adhesion spots. MF was mainly enriched in protein binding, DNA binding, and β-catenin binding. KEGG pathway was enriched in primary immunodeficiency, Hippo signaling pathway, cAMP signaling pathway, transcriptional mis-regulation in cancer and hematopoietic cell lineage. BP of up-regulated genes was mainly enriched in type I interferon signaling pathway and viral response. CC was mainly enriched in cytoplasm. MF was mainly enriched in RNA binding. Ten hub genes and three important gene clusters were screened by STRING database and Cytoscape software. The functions of the three key gene clusters were closely related to immune regulation. ROC analysis showed that the hub genes had a good diagnostic significance for MDS. GSEA analysis indicated that LEF1 may affect the normal function of hematopoietic stem cells by regulating inflammatory reaction, which further revealed the pathogenesis of MDS. CONCLUSION Bioinformatics can effectively screen the core genes and key signaling pathways of MDS, which provides a new strategy for the diagnosis and treatment of MDS.
Computational Biology ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Gene Ontology ; Humans ; Myelodysplastic Syndromes/genetics*