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Molecular Mechanism of CTLA4 -Ig Improving Brain Dysfunction in EAMG Rats LI Shuang-yan, ZHANG Xing-chi, ZHAO Qiao-miao, HOU Yi-bing, RAN Zi-heng, TIAN Ying, XUE Zhan-xia 2022, 12 (4):  1-9.  DOI: 10.3969/j.issn.2095-1396.2022.04.001 Abstract ( 9 )   PDF (1709KB) ( 4 )   Objective：To study the effects and possible mechanisms of CTLA4-Ig on brain dysfunction in EAMG rats. Methods：An experimental autoimmune myasthenia gravis （EAMG） was initially established by immunization of Lewis rats with acetylcholine receptor （AChR） a97- 116 peptide. Then the rats were treated with dexamethasone and CTLA4-Ig. Serum levels of AChR IgG and AChR IgG2b and the content of AChR in hindlimbs were then detected using ELISA. Lennon clinical score was used to evaluate the clinical symptoms of rats in each group.The changes of spatial learning and memory in rats were observed by dark avoidance test. The content of MDA，activities of SOD，Caspases-3，Caspases-9 and Caspases-12 in hippocampus were measured by ultraviolet spectrophotometry. Caspases-3，Caspases-9，Caspases-12 and Trx-1 mRNA expression in hippocampus were measured by RT-PCR and the protein expression of Trx-1 was detected by western blot. Results：CTLA4-Ig and dexamethasone were found to significantly improve clinical symptoms of EAMG rats，reduce serum levels of AChR IgG，AChR IgG2b in peripheral blood，and enhance AChR content in the muscle；CTLA4-Ig and dexamethasone could also prolonge the latency，and reduce the error counts per second. Meanwhile ruduce MDA content，Caspases-3，Caspases-9，Caspases-12 activity and increase SOD activity，and significantly induced Trx-1 mRNA and protein expression upregulation and Caspases-3，Caspases-9， Caspases-12 mRNA expression downregulation and activity of them decreased in hippocampus. Conclusion：EAMG rats can be complicated with brain dysfunction. Oxidative stress and apoptosis mediated by down-regulation of Trx-1 expression may be one of the main causes of CNS damage. CTLA4-Ig can improve the dysfunction of oxidative/antioxidant system and inhibit apoptosis in hippocampus of EAMG rats by up-regulating the mRNA expression of Trx-1. Related Articles | Metrics

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Mechanism of Xiao’er Qingre Zhike Koufuye in Treatment of Fever in Children Based on Network Pharmacology and Molecular Docking Technology WU Wei, XU Zi-xuan, ZHAO Wen-yu, LI Zi-rou, CUI Xiao-yan, ZHANG Su-ping, YU Yong-zhou 2022, 12 (4):  10-22.  DOI: 10.3969/j.issn.2095-1396.2022.04.002 Abstract ( 12 )   PDF (20880KB) ( 4 )   Objective：By constructing the interaction networks between the compositions of Xiao’er Qingre Zhike Koufuye and target networks and proteins，we conducted the enrichment analysis to determine the biological processes and involved pathways，we also studied the potential action mechanism of fever in children. Methods：The active components of Xiao’er Qingre Zhike Koufuye were selected and the target points were predicted by searching TCMSP database，and the potential action targets were obtained by crossing Genecards database with Drug Bank database of the fever-related targets. After processing the comparison results，the targets were input into Cytoscape3.7.2 software to build the “Xiao’er Qingre Zhike Koufuye ingredientscompounds- fever targets” network，and the String database and Cytoscape3.7.2 database were used to construct the protein interaction network and to obtain the key targets. The GO biofunction and KEGG pathway enrichment analysis were later performed through the DAVID v6.8 database and the enrichment results were visualized with Cytoscape3.7.2. Finally，the molecular docking of the key compounds and the targets were performed. Results：160 active components， 584 active component targets，and 4 137 known fever in children-related target genes were obtained. The interaction of disease genes and drug targets yielded 346 intersection targets，and 18 core targets were obtained by the protein interaction network and topological analysis. Enrichment analysis showed that the main pathways focused on neuroactive ligand-receptor-related pathways，immune inflammation pathways，and other pathways such as neurotoxin addiction and viral infection. Further screening of core targets and compounds for molecular docking showed that Casp3，CREB1，Fos，IL-1B，IL-6，INS，Jun，and MYC as core target proteins could stably bind to small molecules such as D-norpseudoephedrine，beta-sitosterol，matrine and ephedrine. Conclusion：Through network pharmacology and molecular docking，our study found the possible active ingredients of Xiao’er Qingre Zhike Koufuye and the potential targets of fever in children and predicted the key ways to treat fever in children. It provided a theoretical basis for explaining the action mechanism of Xiao’er Qingre Zhike Koufuye in children and new methods for further studying the molecular action mechanism. Besides，it supplied a new idea for drug development of children fever. Related Articles | Metrics

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Bioinformatics Analysis of the Relationship between Exosomal ceRNA Regulatory Network and Alzheimer’s Disease ZHANG Zhi-qing, ZHANG Yong-cai, LIU Lin-xuan, LI Ren-qing, LIU Ji-jia, DU Jing-kao, JIANG Bei, WEI Huiping, SU Li-ning 2022, 12 (4):  23-40.  DOI: 10.3969/j.issn.2095-1396.2022.04.003 Abstract ( 12 )   PDF (3399KB) ( 5 )   Objective：Exploring the potential relationship between Alzheimer’s disease （AD） and exosomal ceRNA regulatory network to provide a basis for clinical treatment and research targets. Methods：Datas were downloaded in the Gene Expression Omnibus database （GEO）. Then the differentially expressed genes （DEGs） and differentially expressed miRNAs from AD patients and healthy controls were screened to identify biomarkers of AD. DAVID used to carry out functional enrichment analysis of gene ontology （GO）. Kyoto Encyclopedia of Genes and Genomes （KEGG） was used to performed signal pathway analysis on DEGs pathway analysis， Cytoscape was used to construct network between DEGs and differentially expressed miRNAs to identify key node genes. Results：683 DEGs （377 downregulated DEGs and 306 upregulated DEGs） were screened，and 90 AD related DEGs enriched in exosomes and cell vesicles were screened as our target DEGs. The study also screened 748 differentially expressed miRNAs （90 downregulated miRNAs and 658 upregulated miRNAs） and 186 extracellular vesicle miRNAs （147 upregulated miRNAs and 39 downregulated miRNAs）. The database was used to predict the targeting relationship between these miRNAs and target DEGs，the targeting relationship between lncRNA and miRNA，and the targeting relationship between circRNA and miRNA. The lncRNAmiRNA- mRNA and circRNA-miRNA-mRNA ceRNA regulatory networks were constructed， and the important role of some results in AD disease was emphatically discussed. Conclusion： These results indicated that the occurrence of AD is the result of the synergistic action of multiple interacting genes and non coding RNAs. The data of this study provides a new perspective and analysis for the exosomal ceRNA network related to AD. Related Articles | Metrics

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Role of PPARβ/δ in Neurodegenerative Diseases CAI Yu-shan, ZHAO Shuai 2022, 12 (4):  41-48.  DOI: 10.3969/j.issn.2095-1396.2022.04.004 Abstract ( 29 )   PDF (1157KB) ( 15 )   Peroxisome proliferator-activated receptor （PPAR） is a ligand-activated transcription factor in the nuclear hormone receptor family，containing three different subtypes of PPARs，PPARα，PPARβ/δ and PPARγ. PPARβ/δ controls many intracellular metabolic processes，including the metabolism of long-chain fatty acids，cholesterol and sphingolipid. As a transcription factor，PPARβ/δ can be activated by dietary lipids and endogenous ligands （e.g. long-chain saturated and polyunsaturated fatty acids） as well as certain lipid metabolites. It displays transcriptional activity mainly through interacting with the retinoid X receptorα（ RXRα） to regulate glucose and lipid metabolism，mitochondrial function，and cell growth. Despite of its high expression in brain cells and in different brain regions，its role in neurodegeneration and neuroinflammation remains poorly understood. In recent years，the role of PPARβ/δ in neurodegenerative diseases has attracted more and more attention. Based on the structure and biological function of PPARβ/δ，this paper reviews its role in the pathogenesis of neurodegenerative diseases such as Alzheimer’s disease，Parkinson’s disease，Huntington’s disease and multiple sclerosis. Related Articles | Metrics

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Research Progress in Regulation of Central Nervous System Function by Radix Bupleuri and Scutellaria Baicalensis LI Chen-yang, ZHAO Jiao-jiao, ZHANG Wei 2022, 12 (4):  49-57.  DOI: 10.3969/j.issn.2095-1396.2022.04.005 Abstract ( 11 )   PDF (1004KB) ( 4 )   The compatibility of Radix Bupleuri and Scutellaria Baicalensis was common in ancient prescriptions and was recorded in many famous ancient prescriptions. Modern pharmacological studies showed that the combination of Radix Bupleuri and Scutellaria Baicalensis had good effects on the prevention and treatment of epilepsy，depression， Alzheimer’s disease，glioma，and cerebral ischemia-reperfusion. The combination of the two drugs synergistically protected nerves and played a role in the prevention and treatment of central nervous system diseases by regulating nerve cell signaling pathways，inflammatory factor level，cell apoptosis process，neurotransmitter content，and other mechanisms. In this paper，the domestic and foreign research on the prevention and treatment of central nervous system diseases by Radix Bupleuri-Scutellaria baicalensis and its chemical components were reviewed，aiming to provide a reference for better research and development and rational utilization of the two drugs. Related Articles | Metrics

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The Blood-Brain Barrier and Alzheimer’s Disease LV Xue-ying, ZHANG Zheng, LUO Huan-min 2022, 12 (4):  58-64.  DOI: 10.3969/j.issn.2095-1396.2022.04.006 Abstract ( 16 )   PDF (970KB) ( 5 )   Alzheimer’s disease is still a difficult problem in medical field since its discovery. This article reviews the relationship between blood-brain barrier （BBB） and Alzheimer’s disease. A large number of studies have identified elevated BBB leakage in Alzheimer’s disease patients，and ApoE4 is the strongest genetic risk factor for late onset Alzheimer’s disease. This paper focuses on the causes of BBB damage and how to repair BBB to achieve the therapeutic effect of Alzheimer’s disease. Related Articles | Metrics