الملخص
BACKGROUND:In the process of exploring the mechanism of Alzheimer's disease,the important role of bioinformatics for common target screening has been revealed,enabling the use of its screening results as a basis for exploring the therapeutic effects of drugs on the disease. OBJECTIVE:To predict the targets of liraglutide,a glucagon-like peptide-1 receptor agonist,in the treatment of Alzheimer's disease by bioinformatics and molecular biology. METHODS:DisGeNET database and SEA database were used to obtain the common genes of Alzheimer's disease and liraglutide.GO/KEGG enrichment analysis of common targets was conducted using DAVID online database.Protein-protein interaction networks were constructed using STRING database.The optimal dosage of liraglutide was determined using cell counting kit-8 assay.Expression of key proteins was analyzed using immunofluorescence and immunoblotting techniques.The mouse hippocampal neuron HT22 cell line was used for ex vivo experiments,and the cells were randomly divided into three groups:HT22 group,HT22+Aβ group,and HT22+Aβ+Lir group.No special treatment was done in the HT22 group,while Aβ1-42 was used to intervene in the HT22 cell line for 24 hours to construct an Aβ injury cell model in the HT22+Aβ group.In additional to modeling,liraglutide was added to the HT22+Aβ+Lir group for 12 hours. RESULTS AND CONCLUSION:A total of 3 333 genes associated with Alzheimer's disease were screened from DisGeNET database.Then 147 potential targets of liraglutide were obtained from SEA database.Finally,64 common targets of Alzheimer's disease and Liraglutide were determined using R packets.GO/KEGG analysis of common targets using DAVID online database suggested that common targets were mainly enriched in the following biological processes:neuroactive ligand-receptor interaction,renin-angiotensin system,bladder cancer,endopeptidase activity,peptide receptor activity,G protein-coupled peptide receptor activity,and transport vesicles.The obtained 64 common target proteins were imported into SRTING online database for protein-protein interaction network construction,and the top three genes,matrix metalloproteinases 2,9 and interleukin 1β,were obtained.The activity of cultured cells was detected by the cell counting kit-8 kit.Liraglutide at 100 nmol/L was the optimal concentration for antagonizing Aβ1-42.In the western blot and immunofluorescence assays,the expression of matrix metalloproteinases 2,9 and interleukin 1β was significantly increased in the HT22+Aβ group compared with the HT22 group(P<0.05)but significantly decreased in the HT22+Aβ+Lir group compared with the HT22+Aβ group(P<0.05).To conclude,the above bioinformatics data and secondary validation of differential genes in the GEO database suggest that both matrix metalloproteinases 2,9 and interleukin 1β could be potential targets of liraglutide in the treatment of Alzheimer's disease.
الملخص
The content of optical isomerism is the difficult point of organic chemistry teaching, and so case-based learning (CBL), theoretical-experimental integration teaching method and micro class teaching methods are tried to be used in classroom teaching according to the actual teaching situations. For CBL teaching method, the course is guided by the step of introduction-question-discussion and summary-exten-sions; For theoretical-experimental integration teaching method, combined with the theory class, the two experiments including the determination of optical rotation and organic molecular model are set for the opti-cal isomer content, to enhance the students' understanding of theoretical knowledge through the hands-on operation;For micro class teaching method, the key and difficult points of this chapter are dug out and about 10 minutes of video are recorded by using common video software before class, which are introduced in the classroom or provided to students after class for repeated watching, to deepen the students' understanding of the concept and phenomenon of optical isomers. In brief, it is important to combine various teaching method to improve the classroom instructing effectively and stimulate the students' interest in organic chemistry.
الملخص
ObjectiveTo investigate the correlation of hippocampal synaptic plasticity with spatial learning and memory under normal and pathological condition,and provide experimental evidence for the coincidence of hippocampal late-phase long-term potentiation (L-LTP) and behavioral experiments.Methods 38 SD rats were randomly divided into two groups,control and AD model.First,Morris water maze was used to test the ability of spatial learning and memory of rats.The escape latencies for rats to search for an underwater platform in 5 days of navigation tests and the swimming time percentage in target qtuadrant on the 6th day after withdrawing the platform in probe trails were recorded.Then,in vivo hippocampus L-LTP of field excitatory postsynaptic potential (fEPSP)in CA1 region was recorded after delivering high frequency stimulation (HFS).ResultsBilateral intrahippocampal injection of 4 nmol amyloid β peptide ( Aβ 25-35 ) significantly impaired spatial learning and memory of rats in water maze tests,as well as in vivo hippocampal L-LTP.In control group,there was a significant negative correlation between the amplitude of fEPSP and the escape latency ( r =-0.8306,P < 0.01 ) and a significant positive correlation between the amplitude of fEPSP and the swimming time percentage in target quadrant ( r=0.7709,P<0.01 ).In AD model group,similar correlations were found,with a correlation coefficient of r =-0.7675 (P <0.01 ) and r =0.8049 (P < 0.01 ),respectively.When putting all data from the two groups together,the hippocampal L-LTP was more correlated with escape latency ( r =-0.9124,P < 0.01 ) and swimming time percentage ( r=0.9745,P<0.01).ConclusionThere is very close correlation between the hippocampal L-LTP and the spatial learning and memory behavior in rats,suggesting that the hippocampal L-LTP may be involved in the electrophysiological mechanism of spatial learning and memory in rats,and the impairment of L-LTP could partly represent the deficits in cognitive function of animals.
الملخص
In order to synthetically train students to do scientific researches independently,inspire their enthusiasm and go-aheadism about study,and improve the quality of experimental teaching,we have been exploring to update experimental content and reform experimental system for many years,and have commenced a number of "Series Experiments".The setup of"Series Experiments" which means several separate experiments are organized together by their internal relations has already showed us a favorable effect.
الملخص
Aim To observe the effects of flavonoids,including galangin(G),kaempferol(K),apigenin(A),morin(M),quercetin(Q) and myricetin(MY),on myocardial apoptosis induced by H2O2,and explore the possible mechanism.Methods Primary cultured cardiocytes of neonatal rat were randomly divided into normal group,model group,and flavonoids group.Fluorescent staining,electrophoresis and Western-blot were employed to observe the cardiocyte apoptosis and proteins expression.Results Exposure to 100 ?mol?L-1 H2O2 for 16 h resulted in myocardial apoptosis significantly(P