Skip to content
2000
  1. Home
  2. A-Z Publications
  3. Current Pharmaceutical Design
  4. Volume 30, Issue 38
  5. Article
Volume 30, Issue 38
  • ISSN: 1381-6128
  • E-ISSN: 1873-4286

Abstract

Aims

This study aims to explore the potential mechanism by which Botulinum toxin type A (BoNT/A) inhibits microglial inflammatory activation through P2X7 receptors (P2X7R).

Background

BoNT/A is a promising analgesic drug, and previous studies have established that it alleviates Neuropathic Pain (NP) by inhibiting microglial inflammatory activation. This study examined the biomarkers and potential mechanisms by which BoNT/A relieves neuropathic pain by mediating microglial P2X7R and analyzing transcriptome sequencing data from mouse BV-2 microglial cells.

Objective

The P2X7R agonist Bz-ATP was used to induce microglial inflammatory activation, whilst RNA-seq technology was used to explore the biomarkers and potential mechanisms through which BoNT/A suppresses microglial inflammation.

Methods

RNA sequencing was performed on three BV-2 cell samples treated with a P2X7R specific activator (Bz-ATP) and three BV-2 cell samples pre-treated with BoNT/A. Only data that successfully passed quality control measures were included in subsequent analysis. Initially, Differentially Expressed Genes (DEGs) were identified from BoNT/A and control samples, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Biomarkers were then identified by constructing a Protein-Protein Interaction (PPI) network and utilizing the CytoHubba plug-in in Cytoscape software. Lastly, enrichment analysis and regulatory network analysis were performed to elucidate the potential mechanism of BoNT/A in the treatment of NP.

Results

93 DEGs related to the “cell component size regulation” GO term and enriched in the “axon guidance” KEGG pathway were identified. Subsequently, 6 biomarkers were identified, namely PTPRF, CHDH, CKM, Ky, Sema3b, and Sema3f, which were enriched in pathways related to biosynthesis and metabolism, disease progression, signal transduction, and organelle function, including the “ribosome” and “Wnt signaling pathway.” Finally, a competing endogenous RNA (ceRNAs) network was constructed from 6 mRNAs, 66 miRNAs, and 31 lncRNAs, forming a complex relationship network.

Conclusion

Six genes (PTPRF, Sema3b, Sema3f, CHDH, CKM, and Ky) were identified as biomarkers of microglial inflammatory activation following BoNT/A treatment. This finding may provide a valuable reference for the relief and treatment of neuropathic pain.

© 2024 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cpd/10.2174/0113816128318908240730093036
2024-11-01
2025-01-10

  • From This Site

    /content/journals/cpd/10.2174/0113816128318908240730093036
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. KimY. KwonS.Y. JungH.S. ParkY.J. KimY.S. InJ.H. ChoiJ.W. KimJ.A. JooJ.D. Amitriptyline inhibits the MAPK/ERK and CREB pathways and proinflammatory cytokines through A3AR activation in rat neuropathic pain models.Korean J. Anesthesiol.2019721606710.4097/kja.d.18.0002229969887
     [Google Scholar]
  2. GangadharanV. ZhengH. TabernerF.J. LandryJ. NeesT.A. PistolicJ. AgarwalN. MännichD. BenesV. HelmstaedterM. OmmerB. LechnerS.G. KunerT. KunerR. Neuropathic pain caused by miswiring and abnormal end organ targeting.Nature2022606791213714510.1038/s41586‑022‑04777‑z35614217
     [Google Scholar]
  3. KogaK. KobayashiK. TsudaM. KubotaK. KitanoY. FurueH. Voltage-gated calcium channel subunit α2δ-1 in spinal dorsal horn neurons contributes to aberrant excitatory synaptic transmission and mechanical hypersensitivity after peripheral nerve injury.Front. Mol. Neurosci.202316109992510.3389/fnmol.2023.109992537033377
     [Google Scholar]
  4. PickeringG. MartinE. TiberghienF. DelormeC. MickG. Localized neuropathic pain: An expert consensus on local treatments.Drug Des. Devel. Ther.2017112709271810.2147/DDDT.S14263029066862
     [Google Scholar]
  5. ChuQ. AnJ. LiuP. SongY. ZhaiX. YangR. NiuJ. YangC. LiB. Repurposing a tricyclic antidepressant in tumor and metabolism disease treatment through fatty acid uptake inhibition.J. Exp. Med.20232203e2022131610.1084/jem.2022131636520461
     [Google Scholar]
  6. ZaccaraG. PeruccaP. LoiaconoG. GiovannelliF. VerrottiA. The adverse event profile of lacosamide: A systematic review and meta-analysis of randomized controlled trials.Epilepsia2013541667410.1111/j.1528‑1167.2012.03589.x22779776
     [Google Scholar]
  7. YuanX. HanS. ManyandeA. GaoF. WangJ. ZhangW. TianX. Spinal voltage-gated potassium channel Kv1.3 contributes to neuropathic pain via the promotion of microglial M1 polarization and activation of the NLRP3 inflammasome.Eur. J. Pain202327228930210.1002/ejp.205936440534
     [Google Scholar]
  8. YinY. WeiL. CaseleyE.A. Lopez-CharcasO. WeiY. LiD. MuenchS.P. RogerS. WangL. JiangL.H. Leveraging the ATP-P2X7 receptor signalling axis to alleviate traumatic CNS damage and related complications.Med. Res. Rev.20234351346137310.1002/med.2195236924449
     [Google Scholar]
  9. HuS. HuJ. ZouF. LiuJ. LuoH. HuD. WuL. ZhangW. P2X7 receptor in inflammation and pain.Brain Res. Bull.202218719920910.1016/j.brainresbull.2022.07.00635850190
     [Google Scholar]
  10. GuiX. WangH. WuL. TianS. WangX. ZhengH. WuW. Botulinum toxin type A promotes microglial M2 polarization and suppresses chronic constriction injury-induced neuropathic pain through the P2X7 receptor.Cell Biosci.20201014510.1186/s13578‑020‑00405‑332211150
     [Google Scholar]
  11. ClarkA.K. D’AquistoF. GentryC. MarchandF. McMahonS.B. MalcangioM. Rapid co-release of interleukin 1β and caspase 1 in spinal cord inflammation.J. Neurochem.200699386888010.1111/j.1471‑4159.2006.04126.x16942597
     [Google Scholar]
  12. HuangQ. MaoX.F. WuH.Y. LiuH. SunM.L. WangX. WangY.X. Cynandione A attenuates neuropathic pain through p38β MAPK-mediated spinal microglial expression of β-endorphin.Brain Behav. Immun.201762647710.1016/j.bbi.2017.02.00528189715
     [Google Scholar]
  13. BorstK. DumasA.A. PrinzM. Microglia: Immune and non-immune functions.Immunity202154102194220810.1016/j.immuni.2021.09.01434644556
     [Google Scholar]
  14. Villasana-SalazarB. VezzaniA. Neuroinflammation microenvironment sharpens seizure circuit.Neurobiol. Dis.202317810602710.1016/j.nbd.2023.10602736736598
     [Google Scholar]
  15. BradesiS SvenssonCI SteinauerJ PothoulakisC YakshTL MayerEA Role of spinal microglia in visceral hyperalgesia and NK1R up-regulation in a rat model of chronic stress.Gastroenterology20091364133948
     [Google Scholar]
  16. TsudaM. P2 receptors, microglial cytokines and chemokines, and neuropathic pain.J. Neurosci. Res.20179561319132910.1002/jnr.2381627376880
     [Google Scholar]
  17. XieJ. LiuS. WuB. LiG. RaoS. ZouL. YiZ. ZhangC. JiaT. ZhaoS. SchmalzingG. HausmannR. NieH. LiG. LiangS. The protective effect of resveratrol in the transmission of neuropathic pain mediated by the P2X7 receptor in the dorsal root ganglia.Neurochem. Int.2017103243510.1016/j.neuint.2016.12.00628027922
     [Google Scholar]
  18. Martel-GallegosG. Casas-PrunedaG. Ortega-OrtegaF. Sánchez-ArmassS. Olivares-ReyesJ.A. DieboldB. Pérez-CornejoP. ArreolaJ. Oxidative stress induced by P2X7 receptor stimulation in murine macrophages is mediated by c-Src/Pyk2 and ERK1/2.Biochim. Biophys. Acta, Gen. Subj.20131830104650465910.1016/j.bbagen.2013.05.02323711511
     [Google Scholar]
  19. ChenS. Clinical uses of botulinum neurotoxins: Current indications, limitations and future developments.Toxins (Basel)201241091393910.3390/toxins410091323162705
     [Google Scholar]
  20. NovisS.A. De MattosJ.P. De RossoA.L. Botulinum toxin in blepharospasm, in hemifacial spasm, and in cervical dystonia: Results in 33 patients.Arq. Neuropsiquiatr.1995533-A40341010.1590/S0004‑282X19950003000068540813
     [Google Scholar]
  21. SchaeferS. GottschalkC. JabbariB. Treatment of chronic migraine with focus on botulinum neurotoxins.Toxins (Basel)2015772615262810.3390/toxins707261526184313
     [Google Scholar]
  22. PearlC. MoxleyB. PerryA. DemianN. Dallaire-GirouxC. Management of trigeminal neuralgia with botulinum toxin Type A: Report of two cases.Dent J (Basel)20221011207
     [Google Scholar]
  23. PengF. XiaT.B. Effects of intradermal botulinum toxin injections on herpes zoster related neuralgia.Infect. Drug Resist.2023162159216510.2147/IDR.S40197237077249
     [Google Scholar]
  24. SandriniG. De IccoR. TassorelliC. SmaniaN. TamburinS. Botulinum neurotoxin type A for the treatment of pain: Not just in migraine and trigeminal neuralgia.J. Headache Pain20171813810.1186/s10194‑017‑0744‑z28324318
     [Google Scholar]
  25. PapagiannopoulouD. VardouliL. DimitriadisF. ApostolidisA. Retrograde transport of radiolabelled botulinum neurotoxin type A to the CNS after intradetrusor injection in rats.BJU Int.2016117469770410.1111/bju.1316325912438
     [Google Scholar]
  26. KimD.W. LeeS.K. AhnnJ. Botulinum toxin as a pain killer: Players and actions in antinociception.Toxins (Basel)2015772435245310.3390/toxins707243526134255
     [Google Scholar]
  27. JiangF. ZhongH. HongY. ZhaoG. Use of a tourniquet in total knee arthroplasty: A systematic review and meta-analysis of randomized controlled trials.J. Orthop. Sci.201520111012310.1007/s00776‑014‑0664‑625373840
     [Google Scholar]
  28. MaiarùM. LeeseC. CertoM. Echeverria-AltunaI. MangioneA.S. ArsenaultJ. DavletovB. HuntS.P. Selective neuronal silencing using synthetic botulinum molecules alleviates chronic pain in mice.Sci. Transl. Med.201810450eaar738410.1126/scitranslmed.aar738430021888
     [Google Scholar]
  29. de Sena BrandineG. SmithA.D. Falco: High-speed FastQC emulation for quality control of sequencing data.F1000 Res.20198187410.12688/f1000research.21142.133552473
     [Google Scholar]
  30. KimD. PaggiJ.M. ParkC. BennettC. SalzbergS.L. Graph-based genome alignment and genotyping with HISAT2 and HISAT-genotype.Nat. Biotechnol.201937890791510.1038/s41587‑019‑0201‑431375807
     [Google Scholar]
  31. LiaoY. SmythG.K. ShiW. featureCounts: An efficient general purpose program for assigning sequence reads to genomic features.Bioinformatics201430792393010.1093/bioinformatics/btt65624227677
     [Google Scholar]
  32. LoveM.I. HuberW. AndersS. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2.Genome Biol.2014151255010.1186/s13059‑014‑0550‑825516281
     [Google Scholar]
  33. GustavssonE.K. ZhangD. ReynoldsR.H. Garcia-RuizS. RytenM. ggtranscript : An R package for the visualization and interpretation of transcript isoforms using ggplot2.Bioinformatics202238153844384610.1093/bioinformatics/btac40935751589
     [Google Scholar]
  34. GuZ. HübschmannD. Make interactive complex heatmaps in R.Bioinformatics20223851460146210.1093/bioinformatics/btab80634864868
     [Google Scholar]
  35. YuG. WangL.G. HanY. HeQ.Y. clusterProfiler: An R package for comparing biological themes among gene clusters.OMICS201216528428710.1089/omi.2011.011822455463
     [Google Scholar]
  36. ChengX. DengW. ZhangZ. ZengZ. LiuY. ZhouX. ZhangC. WangG. Novel amino acid metabolism-related gene signature to predict prognosis in clear cell renal cell carcinoma.Front. Genet.20221398216210.3389/fgene.2022.98216236118874
     [Google Scholar]
  37. LiuP. XuH. ShiY. DengL. ChenX. Potential molecular mechanisms of plantain in the treatment of gout and hyperuricemia based on network pharmacology.Evid. Based Complement. Alternat. Med.2020202012010.1155/2020/302312733149752
     [Google Scholar]
  38. ZhengY. GaoW. ZhangQ. ChengX. LiuY. QiZ. LiT. Ferroptosis and autophagy-related genes in the pathogenesis of ischemic cardiomyopathy.Front. Cardiovasc. Med.2022990675310.3389/fcvm.2022.90675335845045
     [Google Scholar]
  39. LiberzonA. BirgerC. ThorvaldsdóttirH. GhandiM. MesirovJ.P. TamayoP. The Molecular Signatures Database (MSigDB) hallmark gene set collection.Cell Syst.20151641742510.1016/j.cels.2015.12.00426771021
     [Google Scholar]
  40. ZhouW. LeiZ. ShiY. GongC. KaiZ. WeiN. WangL. ZhangC. ZhangH. Intrathecal injection of botulinum toxin type A has an analgesic effect in male rats CCI model by inhibiting the activation of spinal P2X4R.Neurochem. Res.202348103099311210.1007/s11064‑023‑03969‑x37336823
     [Google Scholar]
  41. DamoE. SimonettiM. Axon guidance molecules and pain.Cells20221119314310.3390/cells1119314336231105
     [Google Scholar]
  42. Picón-PagèsP. Garcia-BuendiaJ. MuñozF.J. Functions and dysfunctions of nitric oxide in brain.Biochim. Biophys. Acta Mol. Basis Dis.2019186581949196710.1016/j.bbadis.2018.11.00730500433
     [Google Scholar]
  43. SalveminiD. LittleJ.W. DoyleT. NeumannW.L. Roles of reactive oxygen and nitrogen species in pain.Free Radic. Biol. Med.201151595196610.1016/j.freeradbiomed.2011.01.02621277369
     [Google Scholar]
  44. ColesC.H. JonesE.Y. AricescuA.R. Extracellular regulation of type IIa receptor protein tyrosine phosphatases: Mechanistic insights from structural analyses.Semin. Cell Dev. Biol.2015379810710.1016/j.semcdb.2014.09.00725234613
     [Google Scholar]
  45. SarhanA.R. PatelT.R. CreeseA.J. TomlinsonM.G. HellbergC. HeathJ.K. HotchinN.A. CunninghamD.L. Regulation of platelet derived growth factor signaling by Leukocyte Common Antigen-related (LAR) protein tyrosine phosphatase: A quantitative phosphoproteomics study.Mol. Cell. Proteomics20161561823183610.1074/mcp.M115.05365227074791
     [Google Scholar]
  46. McLeodF. SalinasP.C. Wnt proteins as modulators of synaptic plasticity.Curr. Opin. Neurobiol.201853909510.1016/j.conb.2018.06.00329975877
     [Google Scholar]
  47. LiX.H. MiaoH.H. ZhuoM. NMDA receptor dependent long-term potentiation in chronic pain.Neurochem. Res.201944353153810.1007/s11064‑018‑2614‑830109556
     [Google Scholar]
  48. CaoF.L. XuM. GongK. WangY. WangR. ChenX. ChenJ. Imbalance between excitatory and inhibitory synaptic transmission in the primary somatosensory cortex caused by persistent nociception in rats.J. Pain201920891793110.1016/j.jpain.2018.11.01430742914
     [Google Scholar]
  49. SimonettiM. AgarwalN. StösserS. BaliK.K. KaraulanovE. KambleR. PospisilovaB. KurejovaM. BirchmeierW. NiehrsC. HeppenstallP. KunerR. Wnt-Fzd signaling sensitizes peripheral sensory neurons via distinct noncanonical pathways.Neuron201483110412110.1016/j.neuron.2014.05.03724991956
     [Google Scholar]
  50. LiuS. LiuY.P. HuangZ.J. ZhangY.K. SongA.A. MaP.C. SongX.J. Wnt/Ryk signaling contributes to neuropathic pain by regulating sensory neuron excitability and spinal synaptic plasticity in rats.Pain2015156122572258410.1097/j.pain.000000000000036626407042
     [Google Scholar]
  51. ZhangY. ZhaoD. LiX. GaoB. SunC. ZhouS. MaY. ChenX. XuD. The Wnt/β-Catenin pathway regulated cytokines for pathological neuropathic pain in chronic compression of dorsal root ganglion model.Neural Plast.2021202111010.1155/2021/668019233959159
     [Google Scholar]
  52. HalleskogC. MulderJ. DahlströmJ. MackieK. HortobágyiT. TanilaH. Kumar PuliL. FärberK. HarkanyT. SchulteG. WNT signaling in activated microglia is proinflammatory.Glia201159111913110.1002/glia.2108120967887
     [Google Scholar]
  53. HalleskogC. DijksterhuisJ.P. KilanderM.B.C. Becerril-OrtegaJ. VillaescusaJ.C. LindgrenE. ArenasE. SchulteG. Heterotrimeric G protein-dependent WNT-5A signaling to ERK1/2 mediates distinct aspects of microglia proinflammatory transformation.J. Neuroinflammation20129111110.1186/1742‑2094‑9‑11122647544
     [Google Scholar]
  54. YangY. ZhangZ. Microglia and Wnt pathways: Prospects for inflammation in Alzheimer’s disease.Front. Aging Neurosci.20201211010.3389/fnagi.2020.0011032477095
     [Google Scholar]
  55. HalleskogC. SchulteG. WNT -3A and WNT -5A counteract lipopolysaccharide-induced pro-inflammatory changes in mouse primary microglia.J. Neurochem.2013125680380810.1111/jnc.1225023534675
     [Google Scholar]
  56. O’KorenE.G. YuC. KlingebornM. WongA.Y.W. PriggeC.L. MathewR. KalnitskyJ. MsallamR.A. SilvinA. KayJ.N. Bowes RickmanC. ArshavskyV.Y. GinhouxF. MeradM. SabanD.R. Microglial function is distinct in different anatomical locations during retinal homeostasis and degeneration.Immunity2019503723737.e710.1016/j.immuni.2019.02.00730850344
     [Google Scholar]
  57. MrdjenD. PavlovicA. HartmannF.J. SchreinerB. UtzS.G. LeungB.P. LeliosI. HeppnerF.L. KipnisJ. MerklerD. GreterM. BecherB. High-dimensional single-cell mapping of central nervous system immune cells reveals distinct myeloid subsets in health, aging, and disease.Immunity2018482380395.e610.1016/j.immuni.2018.01.01129426702
     [Google Scholar]
  58. BöttcherC. SchlickeiserS. SneeboerM.A.M. KunkelD. KnopA. PazaE. FidzinskiP. KrausL. SnijdersG.J.L. KahnR.S. SchulzA.R. MeiH.E. HolE.M. SiegmundB. GlaubenR. SpruthE.J. de WitteL.D. PrillerJ. Human microglia regional heterogeneity and phenotypes determined by multiplexed single-cell mass cytometry.Nat. Neurosci.2019221789010.1038/s41593‑018‑0290‑230559476
     [Google Scholar]
  59. WorzfeldT. OffermannsS. Semaphorins and plexins as therapeutic targets.Nat. Rev. Drug Discov.201413860362110.1038/nrd433725082288
     [Google Scholar]
  60. Gilabert-JuanJ. SáezA.R. Lopez-CamposG. Sebastiá-OrtegaN. González-MartínezR. CostaJ. HaroJ.M. CalladoL.F. MeanaJ.J. NacherJ. SanjuánJ. MoltóM.D. Semaphorin and plexin gene expression is altered in the prefrontal cortex of schizophrenia patients with and without auditory hallucinations.Psychiatry Res.2015229385085710.1016/j.psychres.2015.07.07426243375
     [Google Scholar]
  61. Mosca-BoidronA.L. GueneauL. HuguetG. GoldenbergA. HenryC. GigotN. Pallesi-PocachardE. FalaceA. DuplombL. ThevenonJ. DuffourdY. ST-OngeJ. ChambonP. RivièreJ.B. Thauvin-RobinetC. CallierP. MarleN. PayetM. RagonC. Goubran BotrosH. BurattiJ. CalderariS. DumasG. DelormeR. LagardeN. PinoitJ.M. RosierA. Masurel-PauletA. CardosoC. MugneretF. Saugier-VeberP. CampionD. FaivreL. BourgeronT. A de novo microdeletion of SEMA5A in a boy with autism spectrum disorder and intellectual disability.Eur. J. Hum. Genet.201624683884310.1038/ejhg.2015.21126395558
     [Google Scholar]
  62. Calderon de AndaF. RosarioA.L. DurakO. TranT. GräffJ. MeletisK. ReiD. SodaT. MadabhushiR. GintyD.D. KolodkinA.L. TsaiL.H. Autism spectrum disorder susceptibility gene TAOK2 affects basal dendrite formation in the neocortex.Nat. Neurosci.20121571022103110.1038/nn.314122683681
     [Google Scholar]
  63. PijuanJ. Ortigoza-EscobarJ.D. OrtizJ. AlcaláA. CalvoM.J. CubellsM. Hernando-DavalilloC. PalauF. HoenickaJ. PLXNA2 and LRRC40 as candidate genes in autism spectrum disorder.Autism Res.20211461088110010.1002/aur.250233749153
     [Google Scholar]
  64. IgeaA. CarvalheiroT. Malvar-FernándezB. Martinez-RamosS. Rafael-VidalC. NiemantsverdrietE. VaradéJ. Fernández-CarreraA. JimenezN. McGarryT. Rodriguez-TrilloA. VealeD. FearonU. CondeC. Pego-ReigosaJ.M. González-FernándezÁ. ReedquistK.A. RadstakeT.R.D.J. van der Helm-Van MilA. GarcíaS. Central role of semaphorin 3B in a serum-induced arthritis model and reduced levels in patients with rheumatoid arthritis.Arthritis Rheumatol.202274697298310.1002/art.4206535001548
     [Google Scholar]
  65. TangM.W. Malvar FernándezB. NewsomS.P. van BuulJ.D. RadstakeT.R.D.J. BaetenD.L. TakP.P. ReedquistK.A. GarcíaS. Class 3 semaphorins modulate the invasive capacity of rheumatoid arthritis fibroblast-like synoviocytes.Rheumatology (Oxford)201857590992010.1093/rheumatology/kex51129471421
     [Google Scholar]
  66. WangQ. ChiuS.L. KoropouliE. HongI. MitchellS. EaswaranT.P. HamiltonN.R. GustinaA.S. ZhuQ. GintyD.D. HuganirR.L. KolodkinA.L. Neuropilin-2/PlexinA3 receptors associate with GluA1 and mediate Sema3F-dependent homeostatic scaling in cortical neurons.Neuron201796510841098.e710.1016/j.neuron.2017.10.02929154130
     [Google Scholar]
  67. ParkS. ChoiS.G. YooS.M. SonJ.H. JungY.K. Choline dehydrogenase interacts with SQSTM1/p62 to recruit LC3 and stimulate mitophagy.Autophagy201410111906192010.4161/auto.3217725483962
     [Google Scholar]
  68. KuaiJ. WuK. HanT. ZhaiW. SunR. LncRNA HOXA10-AS promotes the progression of esophageal carcinoma by regulating the expression of HOXA10.Cell Cycle202322327629010.1080/15384101.2022.210863336588458
     [Google Scholar]
  69. WaldbilligF. BormannF. NeubergerM. EllingerJ. ErbenP. KriegmairM.C. MichelM.S. NuhnP. NientiedtM. An m6A-driven prognostic marker panel for renal cell carcinoma based on the first transcriptome-wide m6A-seq.Diagnostics (Basel)202313582310.3390/diagnostics1305082336899967
     [Google Scholar]
  70. WeiX. SuR. YangM. PanB. LuJ. LinH. ShuW. WangR. XuX. Quantitative proteomic profiling of hepatocellular carcinoma at different serum alpha-fetoprotein level.Transl. Oncol.20222010142210.1016/j.tranon.2022.10142235430532
     [Google Scholar]
  71. ZhangQ. DingL. ZhouT. ZhaiQ. NiC. LiangC. LiJ. A metabolic reprogramming-related prognostic risk model for clear cell renal cell carcinoma: From construction to preliminary application.Front. Oncol.20221298242610.3389/fonc.2022.98242636176391
     [Google Scholar]
  72. OhnishiT. BalanS. ToyoshimaM. MaekawaM. OhbaH. WatanabeA. IwayamaY. FujitaY. TanY. HisanoY. Shimamoto-MitsuyamaC. NozakiY. EsakiK. NagaokaA. MatsumotoJ. HinoM. MatagaN. Hayashi-TakagiA. HashimotoK. KuniiY. KakitaA. YabeH. YoshikawaT. Investigation of betaine as a novel psychotherapeutic for schizophrenia.EBioMedicine20194543244610.1016/j.ebiom.2019.05.06231255657
     [Google Scholar]
  73. TruongT.T.T. BortolasciC.C. KidnapillaiS. SpoldingB. PanizzuttiB. LiuZ.S.J. WatmuffB. KimJ.H. DeanO.M. RichardsonM. BerkM. WalderK. Common effects of bipolar disorder medications on expression quantitative trait loci genes.J. Psychiatr. Res.202215010511210.1016/j.jpsychires.2022.03.02535366598
     [Google Scholar]
  74. YangQ. ZhangP. HanL. ShiP. ZhaoZ. CuiD. HongK. Mitochondrial-related genes PDK2, CHDH, and ALDH5A1 served as a diagnostic signature and correlated with immune cell infiltration in ulcerative colitis.Aging (Albany NY)20241643803382210.18632/aging.20556138376420
     [Google Scholar]
  75. JohnsonA.R. LaoS. WangT. GalankoJ.A. ZeiselS.H. Choline dehydrogenase polymorphism rs12676 is a functional variation and is associated with changes in human sperm cell function.PLoS One201274e3604710.1371/journal.pone.003604722558321
     [Google Scholar]
  76. WangC. MaC. GongL. DaiS. LiY. Preventive and therapeutic role of betaine in liver disease: A review on molecular mechanisms.Eur. J. Pharmacol.202191217460410.1016/j.ejphar.2021.17460434743980
     [Google Scholar]
  77. MogilnickaI. JaworskaK. KoperM. MaksymiukK. SzudzikM. RadkiewiczM. ChabowskiD. UfnalM. Hypertensive rats show increased renal excretion and decreased tissue concentrations of glycine betaine, a protective osmolyte with diuretic properties.PLoS One2024191e029492610.1371/journal.pone.029492638166023
     [Google Scholar]
  78. ZhangM. WangX.L. ShiH. MengL.Q. QuanH.F. YanL. YangH.F. PengX.D. Betaine inhibits NLRP3 inflammasome hyperactivation and regulates microglial m1/m2 phenotypic differentiation, thereby attenuating lipopolysaccharide-induced depression-like behavior.J. Immunol. Res.2022202211410.1155/2022/931343636339940
     [Google Scholar]
  79. PukaleD.D. LazarenkoD. AryalS.R. KhabazF. ShriverL.P. LeipzigN.D. Osmotic contribution of synthesized betaine by choline dehydrogenase using in vivo and in vitro models of post-traumatic syringomyelia.Cell. Mol. Bioeng.2023161415410.1007/s12195‑022‑00749‑536660584
     [Google Scholar]
  80. MaucherD. SchmidtB. SchumannJ. Loss of endothelial barrier function in the inflammatory setting: Indication for a cytokine-mediated post-transcriptional mechanism by virtue of upregulation of miRNAs miR-29a-3p, miR-29b-3p, and miR-155-5p.Cells20211011284310.3390/cells1011284334831066
     [Google Scholar]
  81. XiaoX. LiW. RongD. XuZ. ZhangZ. YeH. XieL. WuY. ZhangY. WangX. Human umbilical cord mesenchymal stem cells-derived extracellular vesicles facilitate the repair of spinal cord injury via the miR-29b-3p/PTEN/Akt/mTOR axis.Cell Death Discov.20217121210.1038/s41420‑021‑00572‑334381025
     [Google Scholar]
/content/journals/cpd/10.2174/0113816128318908240730093036
Loading
Exploring the Biomarkers and Potential Mechanisms of Botulinum Toxin Type A in the Treatment of Microglial Inflammatory Activation through P2X7 Receptors based on Transcriptome Sequencing
Curr. Pharm. Des. 30, 3038 (2024); https://doi.org/10.2174/0113816128318908240730093036
/content/journals/cpd/10.2174/0113816128318908240730093036
/content/journals/cpd/10.2174/0113816128318908240730093036
Loading

Data & Media loading...

Supplements

file format download Download

  • Article Type:     Research Article
Keyword(s): biomarker; botulinum toxin type A; competitive endogenous RNA, metabolism; gene set enrichment analysis; Neuropathic pain

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test