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2000
Volume 32, Issue 23
  • ISSN: 0929-8673
  • E-ISSN: 1875-533X

Abstract

Aims

The aims of this study are to discover dysregulated adipocytokine signaling pathway and pyroptosis-related genes to predict neonatal hypoxic-ischemic encephalopathy (HIE) occurrence.

Background

HIE is an important cause of infant death and long-term neurological sequelae. Current treatment options for HIE are relatively limited and the pathogenesis of HIE remains to be fully explored. This study investigated the alterations of adipocytokine signaling pathway and pyroptosis in neonatal HIE.

Objective

To reveal the alterations of adipocytokine signaling pathway and pyroptosis relevant to HIE occurrence.

Methods

Data on neonatal HIE were downloaded from the Gene Expression Omnibus (GEO) database. Pathway analyses of single-sample gene set enrichment analysis (ssGSEA) and GSEA were performed on the adipocytokine signaling pathway and pyroptosis. Proportions of immune cells in a single sample were also calculated by ssGSEA and CIBERSORT algorithm. The relationship between the adipocytokine signaling pathway and pyroptosis was analyzed according to Pearson correlation analysis.

Results

The activities of KEGG pathways changed after the occurrence of HIE, and adipocytokine signaling pathway was activated with related overexpressed genes. For the three energy metabolisms, carbohydrate metabolism was enhanced; lipid metabolism showed increased fatty acids metabolism and decreased ability of fatty acids synthesis; metabolic levels of phosphate and phenylalanine in amino acid metabolism were elevated. Enhanced pyroptosis and relevant overexpressed genes were accompanied by increased immune cells. A positive connection between adipocytokine signaling pathway and pyroptosis was observed.

Conclusion

These results indicated that the adipocytokine signaling pathway may promote HIE occurrence by upregulating the expression of pyroptosis-related genes, providing a novel mechanism for HIE.

© 2025 Bentham Science Publishers
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2024-02-16
2025-10-22

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References

  1. GrecoP. NenciniG. PivaI. SciosciaM. VoltaC.A. SpadaroS. NeriM. BonaccorsiG. GrecoF. CoccoI. SorrentinoF. D’AntonioF. NappiL. Pathophysiology of hypoxic–ischemic encephalopathy: A review of the past and a view on the future.Acta Neurol. Belg.2020120227728810.1007/s13760‑020‑01308‑332112349
     [Google Scholar]
  2. KurinczukJ.J. KoningW.M. BadawiN. Epidemiology of neonatal encephalopathy and hypoxic–ischaemic encephalopathy.Early Hum. Dev.201086632933810.1016/j.earlhumdev.2010.05.01020554402
     [Google Scholar]
  3. LawnJ. ShibuyaK. SteinC. No cry at birth: Global estimates of intrapartum stillbirths and intrapartum-related neonatal deaths.Bull. World Health Organ.200583640941715976891
     [Google Scholar]
  4. BlackR.E. CousensS. JohnsonH.L. LawnJ.E. RudanI. BassaniD.G. JhaP. CampbellH. WalkerC.F. CibulskisR. EiseleT. LiuL. MathersC. Global, regional, and national causes of child mortality in 2008: A systematic analysis.Lancet201037597301969198710.1016/S0140‑6736(10)60549‑120466419
     [Google Scholar]
  5. MontaldoP. PauliahS.S. LallyP.J. OlsonL. ThayyilS. Cooling in a low-resource environment: Lost in translation.Semin. Fetal Neonatal Med.2015202727910.1016/j.siny.2014.10.00425457083
     [Google Scholar]
  6. HigginsR.D. RajuT. EdwardsA.D. AzzopardiD.V. BoseC.L. ClarkR.H. FerrieroD.M. GuilletR. GunnA.J. HagbergH. HirtzD. InderT.E. JacobsS.E. JenkinsD. JuulS. LaptookA.R. LuceyJ.F. MazeM. PalmerC. PapileL. PfisterR.H. RobertsonN.J. RutherfordM. ShankaranS. SilversteinF.S. SollR.F. ThoresenM. WalshW.F. Hypothermia and other treatment options for neonatal encephalopathy: An executive summary of the Eunice Kennedy Shriver NICHD workshop.J. Pediatr.20111595851858.e110.1016/j.jpeds.2011.08.00421875719
     [Google Scholar]
  7. ZorenaK. DudaJ.O. ŚlęzakD. RobakowskaM. MrugaczM. Adipokines and obesity. Potential link to metabolic disorders and chronic complications.Int. J. Mol. Sci.20202110357010.3390/ijms2110357032443588
     [Google Scholar]
  8. FengE. JiangL. Peptidomic analysis of hippocampal tissue for explore leptin neuroprotective effect on the preterm ischemia-hypoxia brain damage model rats.Neuropharmacology202016210780310.1016/j.neuropharm.2019.10780331580838
     [Google Scholar]
  9. XuN. ZhangY. DoychevaD.M. DingY. ZhangY. TangJ. GuoH. ZhangJ.H. Adiponectin attenuates neuronal apoptosis induced by hypoxia-ischemia via the activation of AdipoR1/APPL1/LKB1/AMPK pathway in neonatal rats.Neuropharmacology201813341542810.1016/j.neuropharm.2018.02.02429486166
     [Google Scholar]
  10. ZhangY. XuN. DingY. DoychevaD.M. ZhangY. LiQ. FloresJ. HaghighiabyanehM. TangJ. ZhangJ.H. Chemerin reverses neurological impairments and ameliorates neuronal apoptosis through ChemR23/CAMKK2/AMPK pathway in neonatal hypoxic–ischemic encephalopathy.Cell Death Dis.20191029710.1038/s41419‑019‑1374‑y30718467
     [Google Scholar]
  11. SerdarM. KempeK. RizazadM. HerzJ. BendixI. MüserF.U. SabirH. Early pro-inflammatory microglia activation after inflammation-sensitized hypoxic-ischemic brain injury in neonatal rats.Front. Cell. Neurosci.20191323710.3389/fncel.2019.0023731178702
     [Google Scholar]
  12. CuiX. PengM. ChenH. The emerging role of lymphocyte activation gene 3 in the cancer immunotherapy.Oncologie202224466567810.32604/oncologie.2022.023641
     [Google Scholar]
  13. RoqueN. MatiasD. SilvaB.J. FerrerP.V. PessoaS.L. de SpohrS.C.L.T. The interface of cancer, their microenvironment and nanotechnology.Oncologie202224337141110.32604/oncologie.2022.024035
     [Google Scholar]
  14. WangC. ZhangP. LiY. WangX. GuoL. LiJ. JiaoH. Downregulation of TRIM27 alleviates hypoxic-ischemic encephalopathy through inhibiting inflammation and microglia cell activation by regulating STAT3/HMGB1 axis.J. Chem. Neuroanat.202312910225110.1016/j.jchemneu.2023.10225136796734
     [Google Scholar]
  15. CarrerasN. ArnaezJ. VallsA. AgutT. SierraC. Garcia-AlixA. CSF neopterin and beta-2-microglobulin as inflammation biomarkers in newborns with hypoxic–ischemic encephalopathy.Pediatr. Res.20239351328133510.1038/s41390‑022‑02011‑035388137
     [Google Scholar]
  16. FrankD. VinceJ.E. Pyroptosis versus necroptosis: Similarities, differences, and crosstalk.Cell Death Differ.20192619911410.1038/s41418‑018‑0212‑630341423
     [Google Scholar]
  17. ShiJ. ZhaoY. WangK. ShiX. WangY. HuangH. ZhuangY. CaiT. WangF. ShaoF. Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death.Nature2015526757566066510.1038/nature1551426375003
     [Google Scholar]
  18. KayagakiN. StoweI.B. LeeB.L. O’RourkeK. AndersonK. WarmingS. CuellarT. HaleyB. GirmaR.M. PhungQ.T. LiuP.S. LillJ.R. LiH. WuJ. KummerfeldS. ZhangJ. LeeW.P. SnipasS.J. SalvesenG.S. MorrisL.X. FitzgeraldL. ZhangY. BertramE.M. GoodnowC.C. DixitV.M. Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling.Nature2015526757566667110.1038/nature1554126375259
     [Google Scholar]
  19. HuangJ. LuW. DoychevaD.M. GamdzykM. HuX. LiuR. ZhangJ.H. TangJ. IRE1α inhibition attenuates neuronal pyroptosis via miR-125/NLRP1 pathway in a neonatal hypoxic-ischemic encephalopathy rat model.J. Neuroinflammation202017115210.1186/s12974‑020‑01796‑332375838
     [Google Scholar]
  20. LvY. SunB. LuX. LiuY. LiM. XuL.X. FengC.X. DingX. FengX. The role of microglia mediated pyroptosis in neonatal hypoxic-ischemic brain damage.Biochem. Biophys. Res. Commun.2020521493393810.1016/j.bbrc.2019.11.00331718799
     [Google Scholar]
  21. DongX. ZhuangS. HuangY. YangX. FuY. YuL. ZhaoY. Expression profile of circular RNAs in the peripheral blood of neonates with hypoxic-ischemic encephalopathy.Mol. Med. Rep.2020221879610.3892/mmr.2020.1109132468058
     [Google Scholar]
  22. DongX. ZhaoY. HuangY. YuL. YangX. GaoF. Analysis of long noncoding RNA expression profiles in the whole blood of neonates with hypoxic-ischemic encephalopathy.J. Cell. Biochem.201912058499850910.1002/jcb.2813830474258
     [Google Scholar]
  23. ShenW. SongZ. ZhongX. HuangM. ShenD. GaoP. QianX. WangM. HeX. WangT. LiS. SongX. Sangerbox: A comprehensive, interaction-friendly clinical bioinformatics analysis platform.iMeta202213e3610.1002/imt2.36
     [Google Scholar]
  24. CharoentongP. FinotelloF. AngelovaM. MayerC. EfremovaM. RiederD. HacklH. TrajanoskiZ. Pan-cancer immunogenomic analyses reveal genotype-immunophenotype relationships and predictors of response to checkpoint blockade.Cell Rep.201718124826210.1016/j.celrep.2016.12.01928052254
     [Google Scholar]
  25. WangY. ChenW. LiK. WuG. ZhangW. MaP. FengS. Tissue-based metabolomics reveals metabolic signatures and major metabolic pathways of gastric cancer with help of transcriptomic data from TCGA.Biosci. Rep.20214110BSR2021147610.1042/BSR2021147634549263
     [Google Scholar]
  26. SubramanianA. TamayoP. MoothaV.K. MukherjeeS. EbertB.L. GilletteM.A. PaulovichA. PomeroyS.L. GolubT.R. LanderE.S. MesirovJ.P. Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles.Proc. Natl. Acad. Sci.200510243155451555010.1073/pnas.050658010216199517
     [Google Scholar]
  27. BindeaG. MlecnikB. TosoliniM. KirilovskyA. WaldnerM. ObenaufA.C. AngellH. FredriksenT. LafontaineL. BergerA. BrunevalP. FridmanW.H. BeckerC. PagèsF. SpeicherM.R. TrajanoskiZ. GalonJ. Spatiotemporal dynamics of intratumoral immune cells reveal the immune landscape in human cancer.Immunity201339478279510.1016/j.immuni.2013.10.00324138885
     [Google Scholar]
  28. ChenB. KhodadoustM.S. LiuC.L. NewmanA.M. AlizadehA.A. Profiling tumor infiltrating immune cells with CIBERSORT.Methods Mol. Biol.2018171124325910.1007/978‑1‑4939‑7493‑1_1229344893
     [Google Scholar]
  29. NewmanA.M. LiuC.L. GreenM.R. GentlesA.J. FengW. XuY. HoangC.D. DiehnM. AlizadehA.A. Robust enumeration of cell subsets from tissue expression profiles.Nat. Methods201512545345710.1038/nmeth.333725822800
     [Google Scholar]
  30. BuysseJ. KhanR. AldossO. VijayakumarN. NijresB.M. Neonatal myocardial infarction.J. Am. Coll. Cardiol.202177182758275810.1016/S0735‑1097(21)04113‑9
     [Google Scholar]
  31. JacobsS.E. BergM. HuntR. Tarnow-MordiW.O. InderT.E. DavisP.G. Cooling for newborns with hypoxic ischaemic encephalopathy.Cochrane Libr.201320131CD00331110.1002/14651858.CD003311.pub323440789
     [Google Scholar]
  32. ZengY. WangY.C. XuJ. Le XuX. Overexpression of retinoid X receptor beta provides protection against oxidized low-density lipoprotein-induced inflammation via regulating PGC1α-dependent mitochondrial homeostasis in endothelial cells.Biochem. Pharmacol.202118811455910.1016/j.bcp.2021.11455933872571
     [Google Scholar]
  33. ZengY. CaoJ. LiCX. WangCY. WuRM. XuXL. MDM2-mediated ubiquitination of RXRβ contributes to mitochondrial damage and related inflammation in atherosclerosis.Int. J. Mol. Sci.20222310576610.3390/ijms23105766
     [Google Scholar]
  34. TangT. WeiY. KangJ. SheZ.G. KimD. SailorM.J. RuoslahtiE. PangH.B. Tumor-specific macrophage targeting through recognition of retinoid X receptor beta.J. Control. Release2019301425310.1016/j.jconrel.2019.03.00930871996
     [Google Scholar]
  35. ZarateM.A. De DiosR.K. BalasubramaniyanD. ZhengL. SherlockL.G. RozanceP.J. WrightC.J. The acute hepatic NF-κB-mediated proinflammatory response to endotoxemia is attenuated in intrauterine growth-restricted newborn mice.Front. Immunol.20211270677410.3389/fimmu.2021.70677434539638
     [Google Scholar]
  36. PinkoskyS.L. ScottJ.W. DesjardinsE.M. SmithB.K. DayE.A. FordR.J. LangendorfC.G. LingN.X.Y. NeroT.L. LohK. GalicS. HoqueA. SmilesW.J. NgoeiK.R.W. ParkerM.W. YanY. MelcherK. KempB.E. OakhillJ.S. SteinbergG.R. Long-chain fatty acyl-CoA esters regulate metabolism via allosteric control of AMPK β1 isoforms.Nat. Metab.20202987388110.1038/s42255‑020‑0245‑232719536
     [Google Scholar]
  37. NiY. XuZ. LiC. ZhuY. LiuR. ZhangF. ChangH. LiM. ShengL. LiZ. HouM. ChenL. YouH. McManusD.P. HuW. DuanY. LiuY. JiM. Therapeutic inhibition of miR-802 protects against obesity through AMPK-mediated regulation of hepatic lipid metabolism.Theranostics20211131079109910.7150/thno.4935433391522
     [Google Scholar]
  38. YangQ. MaQ. XuJ. LiuZ. MaoX. ZhouY. CaiY. DaQ. HongM. WeintraubN.L. FultonD.J. de ChantemèleB.E.J. HuoY. Endothelial AMPKα1/PRKAA1 exacerbates inflammation in HFD-fed mice.Br. J. Pharmacol.202217981661167810.1111/bph.1574234796475
     [Google Scholar]
  39. KennedyG. GibsonO. T O’HareD. MillsI.G. EvergrenE. The role of CaMKK2 in Golgi-associated vesicle trafficking.Biochem. Soc. Trans.202351133134210.1042/BST2022083336815702
     [Google Scholar]
  40. Pons-TostivintE. LugatA. FontenauJ.F. DenisM.G. BennounaJ. STK11/LKB1 modulation of the immune response in lung cancer: From biology to therapeutic impact.Cells20211011312910.3390/cells1011312934831355
     [Google Scholar]
  41. YangM. LongD. HuL. ZhaoZ. LiQ. GuoY. HeZ. ZhaoM. LuL. LiF. LongH. WuH. LuQ. AIM2 deficiency in B cells ameliorates systemic lupus erythematosus by regulating Blimp-1–Bcl-6 axis-mediated B-cell differentiation.Signal Transduct. Target. Ther.20216134110.1038/s41392‑021‑00725‑x34521812
     [Google Scholar]
  42. MengJ. LiN. LiuX. QiaoS. ZhouQ. TanJ. ZhangT. DongZ. QiX. KijlstraA. MaoL. YangP. HouS. NLRP3 attenuates intraocular inflammation by inhibiting AIM2-mediated pyroptosis through the phosphorylated Salt-Inducible kinase 1/sterol regulatory element binding transcription factor 1 pathway.Arthritis Rheumatol.202375584285510.1002/art.4242036529965
     [Google Scholar]
  43. ChenH. DengY. GanX. LiY. HuangW. LuL. WeiL. SuL. LuoJ. ZouB. HongY. CaoY. LiuY. ChiW. NLRP12 collaborates with NLRP3 and NLRC4 to promote pyroptosis inducing ganglion cell death of acute glaucoma.Mol. Neurodegener.20201512610.1186/s13024‑020‑00372‑w32295623
     [Google Scholar]
  44. JinP. QiD. CuiY. LenahanC. ZhangJ.H. TaoX. DengS. TangJ. Aprepitant attenuates NLRC4-dependent neuronal pyroptosis via NK1R/PKCδ pathway in a mouse model of intracerebral hemorrhage.J. Neuroinflammation202219119810.1186/s12974‑022‑02558‑z35922848
     [Google Scholar]
  45. HouJ. HsuJ.M. HungM.C. Molecular mechanisms and functions of pyroptosis in inflammation and antitumor immunity.Mol. Cell202181224579459010.1016/j.molcel.2021.09.00334562371
     [Google Scholar]
  46. FengX. XiaoJ. BaiL. Role of adiponectin in osteoarthritis.Front. Cell Dev. Biol.20221099276410.3389/fcell.2022.99276436158216
     [Google Scholar]
  47. BaralA. ParkP.H. Leptin induces apoptotic and pyroptotic cell death via NLRP3 inflammasome activation in rat hepatocytes.Int. J. Mol. Sci.202122221258910.3390/ijms22221258934830465
     [Google Scholar]
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Alterations in Adipocytokine Signaling Pathway and Pyroptosis in Neonatal Hypoxic-ischemic Encephalopathy
Curr. Med. Chem. 32, 4805 (2025); https://doi.org/10.2174/0109298673293975240214091034
/content/journals/cmc/10.2174/0109298673293975240214091034
/content/journals/cmc/10.2174/0109298673293975240214091034
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  • Article Type:     Research Article
Keyword(s): adipocytokine signaling pathway; database; energy metabolism; Hypoxic ischemic encephalopathy; immune level; neutrophils; omnibus; pyroptosis

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