Bibliometric Analysis And Bioinformatics Analysis Of Calcium Channels In Epilepsy

Objective: Ca2+ channel is a transmembrane glycoprotein on the cell membrane,and its activation can promote the increase of intracellular Ca2+ concentration.At present,the regulatory role of Ca2+ in a variety of life activities has been gradually elucidated,among which epilepsy one of the common diseases is caused by the imbalance of Ca2+ homeostasis.In clinical practice,classic antiepileptic drugs(such as phenytoin and levetiracetam)mainly act by targeting calcium channels,which are also regarded as the most promising targets for drug therapy.Accompanied by this is the emergence of a large number of such documents,but the scientometric information characteristics related to this are still unknown.In addition,although the Ca2+ channel is the initiating factor of epilepsy,it is also a good target for anti-epileptic therapy.However,no studies have revealed its dysregulated genes,mRNA-miRNA network and diagnostic biomarkers in epilepsy.Therefore,we will use this as an opportunity to explore these two aspects.In the part of scientific analysis of calcium channels in epilepsy(part 1),we use Citespace and Vosviewer to analyze to analyze the bibliometric information and explore the scientometric characteristics of calcium channels in epilepsy.In the part of the study of the mechanism of calcium channels in epilepsy(Part 2),we established an animal model of post traumatic epilepsy(PTE)and identified the dysregulated genes,mRNA-miRNA network and diagnostic biomarkers related to calcium channels in PTE.Finally,we will lay a theoretical foundation for targeted therapy of epilepsy.Method:In the part of scientific analysis of calcium channels in epilepsy(part 1),this study retrieved the core collection of the web of science database of 2010-2020 for the research article and review of epilepsy as the research sample.There are 589 articles included in the literature set and they are downloaded and stored as TXT format.VOSviewer and Cite Space software were used to perform bibliometric analysis and knowledge mappings.Co-operative network,co-occurrence keywords,and reference co-citation were constructed.In the part of the study of the mechanism of calcium channels in epilepsy(Part 2),this study established a PTE rat model and took the rat brain tissue forRNA-seq.Bioinformatics tools(KEGG pathway,GO enrichment,etc.)were used to identify dysregulated genes and mRNA-miRNA networks in PTE.Through comprehensive analysis of mRNA and miRNA expression profiles,the diagnostic biomarkers related to calcium channels in PTE were determined,verified by RT-qPCR,and the molecular regulation mechanism of these dysregulated genes in PTE was explored.Result: In the part of scientific analysis of calcium channels in epilepsy(part 1),This study found that the research focus of calcium channel in epilepsy in the past ten years has been mainly orientated to examining danio rerio,t-type calcium channel antagonist tta-a2,quantitative trait locus,neuronal excitability,t-type calcium channel antagonist z944,and homozygous missense variant.Among many subfamily members of voltage-gated calcium channels,CaV2.3,CaV3,and auxiliary subunit ?2?-1 resulted as potentially good drug targets in antiepileptic therapy.In the part of the study of the mechanism of calcium channels in epilepsy(Part 2),this study showed that compared with the control group,there were 431 dysregulated genes in the PTE group.The results of bioinformatics analysis show that there are a total of 10 mRNAs and 21 dysregulated microRNAs in PTE that are related to calcium channels.And we have further constructed the mRNA-microRNA network related to calcium channels in PTE.This network suggests that there are multiple sets of dysregulated mRNA-miRNAs in the calcium channels of PTE.Real-time RT-PCR results confirmed their expression changes and negative correlation.Finally,from the analysis of the three types of information integration of mRNA-microRNA network,interaction mechanism and miRNA expression profile,mi R-449a-5p,mi R-377-3p and mi R-494-3p are extremely specific and may be potential diagnostic biomarkers and therapeutic targets for PTE.