AIM: To investigate the effects of a Chinese herb compound prescription, Wen-Jin-Tong(WJT), on the deposition of advanced glycation end products (AGEs) ,the expression of receptor for AGEs(RAGE)and ICAM-1 in cardiovascular tissues of diabetic rats. METHODS: The diabetic rat model was induced by injection of streptozotocin. The quantity of AGEs accumulation, the expressions of RAGE and ICAM-1 in aorta and cardiac tissues were detected using fluorescence method, RT-PCR and in situ hybridization techniques. RESULTS: AGEs accumulation in aorta and cardiac tissues of rats treated with Wen-Jin-Tong was lower than that of diabetic model rats(P

Objective: To observe the effects of manganese( Ⅲ ) meso-tetrakis (N, N'-diethylimidazolium-2-yl) porphyrin (MnTDM) in treatment of early Parkinson's disease(PD) mouse model induced by subcutaneous injection of 1-methyl-4-phenyl1, 2, 3, 6-tetrahydropyridine(MPTP) and to discuss its possible mechanism. Methods:Forty male C57BL/6 mice were evenly randomized into 4 groups: MPTP model group(subcutaneous injection of 25 mg/kg MPTP for 3 days), MnTDM+ MPTP group (15 mg/kg MnTDM was subcutaneously injected 1 h before MPTP injection), MnTDM control group, and normal saline group. Performance of animals in the pole and swimming test was observed 3 days after the last injection. Levels of dopamine (DA) and its metabolites(3,4-dihydroxyphenylacetic acid [DOPAC] and homovanillic acid [HVA]) in the striatum of animals were measured by high-performance liquid chromatography with an electrochemical detector(HPLC-ECD). Thiobarbituric acid (TBA) method was used to examine the levels of malondialdehyde(MDA). Results: Acute injection of MPTP could be used for establishment of PD model. The striatal levels of DA, DOPAC and HVA in MPTP group were significantly lower(P＜0.01)and the striatal level of MDA was significantly higher(P＜0.05) than those of the control group. MPTP had no obvious effect on the behavioral performance of the animals in a short term. MnTDM could partly inhibit the above effects of MPTP. Compared with MPTP group, MnTDM+ MPTP group had significantly higher DA, DOPAC, and HVA levels and significantly lower MDA level(all P＜0.05). There was no significant difference in the behavioral indices of animals between the 4 groups. Conclusion:MnTDM can inhibit lipid peroxidation and promote DA production; it has preventive and therapeutic effects on MPTP induced PD.

Objective To construct Neuropilins-2 eukaryotic expression vector for RNA interference.Methods Recombinant targeting on gene NRP2 was designed and established with plasmid pGenSil-1 based on NRP2 cDNA equences of Genomes.Two pairs of oligonucleotides were synthesized according to the Tuschl and inserted into plasmid pGenSil-l to generate siRNA eukaryotic expression vector,DH5? strains were transformed,plasmid were extracted,and recombinant vectors were identified by the restriction map and the sequence analysis.The recombinant plasmid(pGenSil-NRP2) was transfected into the cultured LOVO cells.At 48 h after transfection,the whole cell protein was extracted,and the protein level was detected by Western blotting with mouse-anti-human NRP2 monoclonal antibody.Results Recombinant plasmids were completely coincided with the designs by the restriction map and the sequence analysis.pGenSil-NRP2 expression vector into LOVO cells down-regulated the protein level of NRP2 at 48 h after transfection.The recombinant eukaryotic expression vector were constructed successfully.Conclusion siRNA recombinant can be constructed successfully by RNAi technique for inhibiting NRP2 expression.

OBJECTIVETo investigate the effect of risperidone, an antipsychotic drug, on the Akt-GSK3β pathway and the role of PI3K in dopamine D2 receptor (DRD2) expression and Akt-GSK3β signal pathway.

METHODSHuman glioma cells (U251) were cultured in vitro. Cells without any treatment as control, Western blotting was used for measuring the expression of Akt (Thr308 and Ser473) and GSK3β (Ser9) protein phosphorylation by risperidone and LY294002 in U251 cell, and real-time PCR was used for detecting the expression of DRD2 mRNA.

RESULTSRisperidone has significantly enhanced the expression of phosphorylated Akt and phosphorylated GSK3β (P< 0.05), but did not alter the mRNA expression of DRD2. LY294002 could reduce the phosphorylation of Akt and GSK3β (P< 0.01, P< 0.05), and also decrease the DRD2 mRNA (P<0 .05).

CONCLUSIONRisperidone can activate the Akt-GSK3β signaling pathway in the U251 cells, and PI3K is a common regulatory site in Akt-GSK3β signaling and D2 receptor gene expression.

Antipsychotic Agents ; pharmacology ; Cell Line, Tumor ; Glioma ; drug therapy ; genetics ; metabolism ; Glycogen Synthase Kinase 3 ; genetics ; metabolism ; Glycogen Synthase Kinase 3 beta ; Humans ; Phosphatidylinositol 3-Kinases ; genetics ; metabolism ; Phosphorylation ; Proto-Oncogene Proteins c-akt ; genetics ; metabolism ; Risperidone ; pharmacology ; Signal Transduction ; drug effects

OBJECTIVETo explore the association of a functional polymorphism Val158Met of COMT gene and attention and executive function in first-episode treatment-naive patients with schizophrenia and healthy controls.

METHODSTrail making test (TMT) and clinical performances were evaluated in 103 first-episode treatment-naive patients with schizophrenia and 99 healthy controls. Polymorphism of COMT Val158Met was analyzed using polymerase chain reaction-restriction fragment length polymorphism method. A general linear model was used to investigate the effect of genotype subgroups on the attention and executive function.

RESULTSThere was a significant difference between control subjects and patients with schizophrenia on the TMT-A and B. However, no significant difference among Val/Val, Val/Met and Met/Met on the TMT-A and B in control subjects and patients with schizophrenia was detected.

CONCLUSIONThe association among COMT Met variant and trail making testing (attention and executive function) has been replicated. However, no association of COMT Met variant with disruption of dopaminergic influence on neurocognitive function was detected. This may be due to the heterogeneity of population.

Adolescent ; Adult ; Amino Acid Substitution ; Attention ; physiology ; Catechol O-Methyltransferase ; genetics ; Executive Function ; physiology ; Female ; Gene Frequency ; Genotype ; Humans ; Male ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Polymorphism, Restriction Fragment Length ; Schizophrenia ; genetics ; physiopathology ; Schizophrenic Psychology ; Trail Making Test ; Young Adult

Objective: To understand the consistency of ALK Ventana-D5F3 immunohistochemistry (IHC) interpretation in Chinese lung adenocarcinoma among histopathologists from different hospitals, and to recommend solution for the problems found during the interpretation of ALK IHC in real world, with the aim of the precise selection of patients who can benefit from ALK targeted therapy. Methods: This was a multicenter and retrospective study. A total of 109 lung adenocarcinoma cases with ALK Ventana-D5F3 IHC staining were collected from 31 lung cancer centers in RATICAL research group from January to June in 2018. All cases were scanned into digital imaging with Ventana iSCANcoreo Digital Slide Scanning System and scored by 31 histopathologists from different centers according to ALK binary (positive or negative) interpretation based on its manufacturer′s protocol. The cases with high inconsistency rate were further analyzed using FISH/RT-PCR/NGS. Results: There were 49 ALK positive cases and 60 ALK negative cases, confirmed by re-evaluation by the specialist panel. Two cases (No. 2302 and No.2701) scored as positive by local hospitals were rescored as negative, and were confirmed to be negative by RT-PCR/FISH/NGS. The false interpretation rate of these two cases was 58.1% (18/31) and 48.4% (15/31), respectively. Six out of 31 (19.4%) pathologists got 100% accuracy. The minimum consistency between every two pathologists was 75.8%.At least one pathologist gave negative judgement (false negative) or positive judgement (false positive) in the 49 positive or 60 negative cases, accounted for 26.5% (13/49), 41.7% (25/60), respectively, with at least one uncertainty interpretation accounted for 31.2% (34/109). Conclusion There are certain heterogeneities and misclassifications in the real world interpretation of ALK-D5F3 IHC test, which need to be guided by the oncoming expert consensus based on the real world data.