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2000
Volume 25, Issue 21
  • ISSN: 1568-0266
  • E-ISSN: 1873-4294

Abstract

Background

Gefitinib is associated with various adverse reactions, with diarrhea being prevalent. It is mainly managed through lifestyle changes and symptomatic pharmacological interventions, but these approaches have limited effectiveness and frequent recurrence. Qi Yin San Liang San Decoction (QYSLS) shows promise in relieving gefitinib-induced diarrhea, but its mechanisms are unclear.

Objective

This study aims to explore the pathological mechanisms underlying gefitinib-induced diarrhea and to elucidate the molecular pathways through which QYSLS mediates its therapeutic effects.

Methods

RNA-seq identified differentially expressed genes (DEGs) in colon samples from control and gefitinib-induced diarrhea rats. Network pharmacology was employed to predict the bioactive components and potential targets of QYSLS. A protein-protein interaction (PPI) network was utilized to explore the interactions among these targets, while GO, KEGG, and GSEA enrichment analyses were conducted to reveal the signaling pathways associated with these targets. RNA-seq was used to detect DEGs in QYSLS-mediated relieving of gefitinib-induced diarrhea; the intersection with potential targets was further analyzed to identify key genes. The expression of hub genes was validated through immunohistochemistry and RT-qPCR.

Results

RNA-seq and network pharmacology identified 103 bioactive components of QYSLS, with 84 potential targets in QYSLS relieving gefitinib-induced diarrhea. The DEGs in QYSLS relieving gefitinib-induced diarrhea and 84 potential targets were intersected, resulting in the identification of 26 key genes. Further analysis highlighted three central hub genes (CCL20, CCL25, NOS2), which were enriched in pathways related to innate immune response. Furthermore, immunohistochemistry and RT-qPCR confirmed that the expression of CCL25 was reduced by QYSLS in gefitinib-induced diarrhea rats.

Conclusion

These results indicate that QYSLS may exert its therapeutic effect on gefitinib-induced diarrhea the modulation of chemokines and innate immune responses.

© 2025 Bentham Science Publishers
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References

  1. HuangJ. DengY. TinM.S. LokV. NgaiC.H. ZhangL. Lucero-PrisnoD.E. XuW. ZhengZ.J. ElcarteE. WithersM. WongM.C.S. Distribution, risk factors, and temporal trends for lung cancer incidence and mortality.Chest202216141101111110.1016/j.chest.2021.12.655 35026300
     [Google Scholar]
  2. SungH. FerlayJ. SiegelR.L. LaversanneM. SoerjomataramI. JemalA. BrayF. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.CA Cancer J. Clin.202171320924910.3322/caac.21660 33538338
     [Google Scholar]
  3. OxnardG.R. ChenR. PharrJ.C. KoellerD.R. BertramA.A. DahlbergS.E. RainvilleI. Shane-CarsonK. TaylorK.A. Sable-HuntA. ShollL.M. TeerlinkC.C. ThomasA. Cannon-AlbrightL.A. FayA.P. Ashton-ProllaP. YangH. SalvatoreM.M. AddarioB.J. JänneP.A. CarboneD.P. WiesnerG.L. GarberJ.E. Germline EGFR mutations and familial Lung cancer.J. Clin. Oncol.202341345274528410.1200/JCO.23.01372 37579253
     [Google Scholar]
  4. HarrisonP.T. VyseS. HuangP.H. Rare epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer.Semin. Cancer Biol.20206116717910.1016/j.semcancer.2019.09.015 31562956
     [Google Scholar]
  5. PassaroA. JänneP.A. MokT. PetersS. Overcoming therapy resistance in EGFR-mutant lung cancer.Nat. Can.20212437739110.1038/s43018‑021‑00195‑8 35122001
     [Google Scholar]
  6. FuK. XieF. WangF. FuL. Therapeutic strategies for EGFR-mutated non-small cell lung cancer patients with osimertinib resistance.J. Hematol. Oncol.202215117310.1186/s13045‑022‑01391‑4 36482474
     [Google Scholar]
  7. BlackhallF. RansonM. ThatcherN. Where next for gefitinib in patients with lung cancer?Lancet Oncol.20067649950710.1016/S1470‑2045(06)70725‑2 16750500
     [Google Scholar]
  8. BarnfieldP.C. EllisP.M. Second-line treatment of non-small cell lung cancer: New developments for tumours not harbouring targetable oncogenic driver mutations.Drugs201676141321133610.1007/s40265‑016‑0628‑6 27557830
     [Google Scholar]
  9. MokT.S. ChengY. ZhouX. LeeK.H. NakagawaK. NihoS. ChawlaA. RosellR. CorralJ. MigliorinoM.R. PluzanskiA. NoonanK. TangY. PastelM. WilnerK.D. WuY.L. Updated overall survival in a randomized study comparing dacomitinib with gefitinib as first-line treatment in patients with advanced non-small-cell lung cancer and EGFR-Activating Mutations.Drugs202181225726610.1007/s40265‑020‑01441‑6 33331989
     [Google Scholar]
  10. MiyauchiE. MoritaS. NakamuraA. HosomiY. WatanabeK. IkedaS. SeikeM. FujitaY. MinatoK. KoR. HaradaT. HagiwaraK. KobayashiK. NukiwaT. InoueA. Updated analysis of NEJ009: Gefitinib-alone versus gefitinib plus chemotherapy for non–small-cell lung cancer with mutated EGFR.J. Clin. Oncol.202240313587359210.1200/JCO.21.02911 35960896
     [Google Scholar]
  11. FukuokaM. YanoS. GiacconeG. TamuraT. NakagawaK. DouillardJ.Y. NishiwakiY. VansteenkisteJ. KudohS. RischinD. EekR. HoraiT. NodaK. TakataI. SmitE. AverbuchS. MacleodA. FeyereislovaA. DongR.P. BaselgaJ. Multi-institutional randomized phase II trial of Gefitinib for previously treated patients with advanced non–small-cell lung cancer.J. Clin. Oncol.20234161162117110.1200/JCO.22.02499 36791474
     [Google Scholar]
  12. RodriguesD. HerpersB. FerreiraS. JoH. FisherC. CoyleL. ChungS.W. KleinjansJ.C.S. JennenD.G.J. de KokT.M. A transcriptomic approach to elucidate the mechanisms of gefitinib-induced toxicity in healthy human intestinal organoids.Int. J. Mol. Sci.2022234221310.3390/ijms23042213 35216325
     [Google Scholar]
  13. Garcia-CampeloR. ArrietaO. MassutiB. Rodriguez-AbreuD. GranadosA.L.O. MajemM. VicenteD. LianesP. Bosch-BarreraJ. InsaA. DómineM. ReguartN. GuiradoM. SalaM.Á. Vázquez-EstevezS. CaroR.B. DrozdowskyjA. VerdúA. KarachaliouN. Molina-VilaM.A. RosellR. Combination of gefitinib and olaparib versus gefitinib alone in EGFR mutant non-small-cell lung cancer (NSCLC): A multicenter, randomized phase II study (GOAL).Lung Cancer2020150626910.1016/j.lungcan.2020.09.018 33070053
     [Google Scholar]
  14. AwD.C.W. TanE.H. ChinT.M. LimH.L. LeeH.Y. SooR.A. Management of epidermal growth factor receptor tyrosine kinase inhibitor‐related cutaneous and gastrointestinal toxicities.Asia Pac. J. Clin. Oncol.2018141233110.1111/ajco.12687 28464435
     [Google Scholar]
  15. ChuC. Rotondo-TrivetteS. MichailS. Chronic diarrhea.Curr. Probl. Pediatr. Adolesc. Health Care202050810084110.1016/j.cppeds.2020.100841 32863166
     [Google Scholar]
  16. JohnT. GrohéC. GoldmanJ.W. ShepherdF.A. de MarinisF. KatoT. WangQ. SuW.C. ChoiJ.H. SriuranpongV. MelottiB. FidlerM.J. ChenJ. AlbayatyM. StachowiakM. TaggartS. WuY.L. TsuboiM. HerbstR.S. MajemM. Three-year safety, tolerability, and health-related quality of life outcomes of adjuvant osimertinib in patients with resected stage IB to IIIA EGFR-mutated NSCLC: Updated analysis from the phase 3 ADAURA trial.J. Thorac. Oncol.20231891209122110.1016/j.jtho.2023.05.015 37236398
     [Google Scholar]
  17. ZhaoY. ChengB. ChenZ. LiJ. LiangH. ChenY. ZhuF. LiC. XuK. XiongS. LuW. ChenZ. ZhongR. ZhaoS. XieZ. LiuJ. LiangW. HeJ. Toxicity profile of epidermal growth factor receptor tyrosine kinase inhibitors for patients with lung cancer: A systematic review and network meta-analysis.Crit. Rev. Oncol. Hematol.202116010330510.1016/j.critrevonc.2021.103305 33757838
     [Google Scholar]
  18. DongS. WangP. ZhangL. ZhangX. LiX. WangJ. CuiX. LanT. GaoC. ShiY. WangW. WangJ. JiangM. The Qi Yin San Liang San decoction enhances anti-CD19 CAR-T cell function in the treatment of B-cell lymphomas.J. Ethnopharmacol.2024319Pt 111710910.1016/j.jep.2023.117109 37657771
     [Google Scholar]
  19. ZhangY.L. WangY.L. YanK. LiH. ZhangX. EssolaJ.M. DingC. ChangK. QingG. ZhangF. TanY. PengT. WangX. JiangM. LiangX.J. HuaQ. Traditional Chinese Medicine formulae QY305 reducing cutaneous adverse reaction and diarrhea by its nanostructure.Adv. Sci. (Weinh.)2024115230614010.1002/advs.202306140 38044276
     [Google Scholar]
  20. WangY. ZhangY. DingC. JiaC. ZhangH. PengT. ChengS. ChenW. TanY. WangX. LiuZ. WeiP. WangX. JiangM. HuaQ. Exploration of the potential mechanism of Qi Yin San Liang San Decoction in the treatment of EGFRI-related adverse skin reactions using network pharmacology and in vitro experiments.Front. Oncol.20221279071310.3389/fonc.2022.790713 35372072
     [Google Scholar]
  21. ZhangP. ZhangD. ZhouW. WangL. WangB. ZhangT. LiS. Network pharmacology: Towards the artificial intelligence-based precision traditional Chinese medicine.Brief. Bioinform.2023251bbad51810.1093/bib/bbad518 38197310
     [Google Scholar]
  22. WangS. ZhangY. HuC. ZhangN. GribskovM. YangH. Shiny-DEG: A Web application to analyze and visualize differentially expressed genes in RNA-seq.Interdiscip. Sci.202012334935410.1007/s12539‑020‑00383‑7 32666343
     [Google Scholar]
  23. HeD.D. ZhangX.K. ZhuX.Y. HuangF.F. WangZ. TuJ.C. Network pharmacology and RNA-sequencing reveal the molecular mechanism of Xuebijing injection on COVID-19-induced cardiac dysfunction.Comput. Biol. Med.202113110429310.1016/j.compbiomed.2021.104293 33662681
     [Google Scholar]
  24. WardmanR. KelesM. PachkivI. HemannaS. GreinS. SchwarzJ. SteinF. OlaR. DobrevaG. HentzeM.W. HeinekeJ. RNA-Binding proteins regulate post-transcriptional responses to TGF-β to coordinate function and mesenchymal activation of murine endothelial cells.Arterioscler. Thromb. Vasc. Biol.202343101967198910.1161/ATVBAHA.123.319925 37650327
     [Google Scholar]
  25. HongD.C. YangJ. SunC. LiuY.T. ShenL.J. XuB.S. QueY. XiaX. ZhangX. Genomic profiling of radiation-induced sarcomas reveals the immunologic characteristics and its response to immune checkpoint blockade.Clin. Cancer Res.202329152869288410.1158/1078‑0432.CCR‑22‑3567 37184976
     [Google Scholar]
  26. LoveM.I. HuberW. AndersS. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2.Genome Biol.2014151255010.1186/s13059‑014‑0550‑8 25516281
     [Google Scholar]
  27. McDermaidA. MonierB. ZhaoJ. LiuB. MaQ. Interpretation of differential gene expression results of RNA-seq data: Review and integration.Brief. Bioinform.20192062044205410.1093/bib/bby067 30099484
     [Google Scholar]
  28. KuonenF. LiN.Y. HaenselD. PatelT. GaddamS. YerlyL. RiegerK. AasiS. OroA.E. c-FOS drives reversible basal to squamous cell carcinoma transition.Cell Rep.202137110977410.1016/j.celrep.2021.109774 34610301
     [Google Scholar]
  29. KanehisaM. FurumichiM. TanabeM. SatoY. MorishimaK. KEGG: new perspectives on genomes, pathways, diseases and drugs.Nucleic Acids Res.201745D1D353D36110.1093/nar/gkw1092 27899662
     [Google Scholar]
  30. GillespieM. JassalB. StephanR. MilacicM. RothfelsK. Senff-RibeiroA. GrissJ. SevillaC. MatthewsL. GongC. DengC. VarusaiT. RagueneauE. HaiderY. MayB. ShamovskyV. WeiserJ. BrunsonT. SanatiN. BeckmanL. ShaoX. FabregatA. SidiropoulosK. MurilloJ. ViteriG. CookJ. ShorserS. BaderG. DemirE. SanderC. HawR. WuG. SteinL. HermjakobH. D’EustachioP. The reactome pathway knowledgebase 2022.Nucleic Acids Res.202250D1D687D69210.1093/nar/gkab1028 34788843
     [Google Scholar]
  31. RuJ. LiP. WangJ. ZhouW. LiB. HuangC. LiP. GuoZ. TaoW. YangY. XuX. LiY. WangY. YangL. TCMSP: A database of systems pharmacology for drug discovery from herbal medicines.J. Cheminform.2014611310.1186/1758‑2946‑6‑13 24735618
     [Google Scholar]
  32. WuY. ZhangF. YangK. FangS. BuD. LiH. SunL. HuH. GaoK. WangW. ZhouX. ZhaoY. ChenJ. SymMap: An integrative database of traditional Chinese medicine enhanced by symptom mapping.Nucleic Acids Res.201947D1D1110D111710.1093/nar/gky1021 30380087
     [Google Scholar]
  33. ShangL. WangY. LiJ. ZhouF. XiaoK. LiuY. ZhangM. WangS. YangS. Mechanism of Sijunzi decoction in the treatment of colorectal cancer based on network pharmacology and experimental validation.J. Ethnopharmacol2023302Pt A11587610.1016/j.jep.2022.11587636343798
     [Google Scholar]
  34. UniProt: The universal protein knowledgebase.Nucleic Acids Res.201745D1D158D16910.1093/nar/gkw1099 27899622
     [Google Scholar]
  35. BarshirR. FishilevichS. Iny-SteinT. ZeligO. MazorY. Guan-GolanY. SafranM. LancetD. GeneCaRNA: A comprehensive gene-centric database of Human Non-coding RNAs in the GeneCards Suite.J. Mol. Biol.20214331116691310.1016/j.jmb.2021.166913 33676929
     [Google Scholar]
  36. AmbergerJ.S. BocchiniC.A. SchiettecatteF. ScottA.F. HamoshA. OMIM.org: Online Mendelian Inheritance in Man (OMIM®), an online catalog of human genes and genetic disorders.Nucleic Acids Res.201543D1D789D79810.1093/nar/gku1205 25428349
     [Google Scholar]
  37. JiX.Y. LeiC.J. KongS. LiH.F. PanS.Y. ChenY.J. ZhaoF.R. ZhuT.T. Hydroxy-safflower yellow a mitigates vascular remodeling in rat pulmonary arterial hypertension.Drug Des. Devel. Ther.20241847549110.2147/DDDT.S439686 38405578
     [Google Scholar]
  38. DonchevaN.T. MorrisJ.H. HolzeH. KirschR. NastouK.C. Cuesta-AstrozY. RatteiT. SzklarczykD. von MeringC. JensenL.J. Cytoscape stringApp 2.0: Analysis and visualization of heterogeneous biological networks.J. Proteome Res.202322263764610.1021/acs.jproteome.2c00651 36512705
     [Google Scholar]
  39. SzklarczykD. KirschR. KoutrouliM. NastouK. MehryaryF. HachilifR. GableA.L. FangT. DonchevaN.T. PyysaloS. BorkP. JensenL.J. von MeringC. The STRING database in 2023: protein–protein association networks and functional enrichment analyses for any sequenced genome of interest.Nucleic Acids Res.202351D1D638D64610.1093/nar/gkac1000 36370105
     [Google Scholar]
  40. ZhengY. ChenY. DingX. WongK.H. CheungE. Aquila: A spatial omics database and analysis platform.Nucleic Acids Res.202351D1D827D83410.1093/nar/gkac874 36243967
     [Google Scholar]
  41. ZhuH. ChangM. WangQ. ChenJ. LiuD. HeW. Identifying the potential of miRNAs in Houttuynia cordata-derived exosome-like nanoparticles against respiratory RNA viruses.Int. J. Nanomedicine2023185983600010.2147/IJN.S425173 37901360
     [Google Scholar]
  42. Gene Ontology Consortium. Gene Ontology Consortium: Going forward.Nucleic Acids Res.201543Database issueD1049D105610.1093/nar/gku117925428369
     [Google Scholar]
  43. DennisG. ShermanB.T. HosackD.A. YangJ. GaoW. LaneH.C. LempickiR.A. DAVID: Database for annotation, visualization, and integrated discovery.Genome Biol.200345310.1186/gb‑2003‑4‑5‑p3 12734009
     [Google Scholar]
  44. HeQ. LiuC. WangX. RongK. ZhuM. DuanL. ZhengP. MiY. Exploring the mechanism of curcumin in the treatment of colon cancer based on network pharmacology and molecular docking.Front. Pharmacol.202314110258110.3389/fphar.2023.1102581 36874006
     [Google Scholar]
  45. MingS. YinH. LiX. GongS. ZhangG. WuY. GITR promotes the polarization of TFH-Like Cells in Helicobacter pylori-Positive gastritis.Front. Immunol.20211273626910.3389/fimmu.2021.736269 34589088
     [Google Scholar]
  46. BourgonjeA.R. HuS. SpekhorstL.M. ZhernakovaD.V. Vich VilaA. LiY. VoskuilM.D. van BerkelL.A. Bley FollyB. CharroutM. MahfouzA. ReindersM.J.T. van HeckJ.I.P. JoostenL.A.B. VisschedijkM.C. van DullemenH.M. FaberK.N. SamsomJ.N. FestenE.A.M. DijkstraG. WeersmaR.K. The effect of phenotype and genotype on the plasma proteome in patients with inflammatory bowel disease.J. Crohn’s Colitis202216341442910.1093/ecco‑jcc/jjab157 34491321
     [Google Scholar]
  47. LiuX. LiuK. WangY. MengX. WangQ. TaoS. XuQ. ShenX. GaoX. HongS. JinH. WangJ.Q. WangD. LuL. MengZ. WangL. SWI/SNF chromatin remodeling factor BAF60b restrains inflammatory diseases by affecting regulatory T cell migration.Cell. Rep202443711445810.1016/j.celrep.2024.114458 38996070
     [Google Scholar]
  48. HsuW.H. YangJ.C.H. MokT.S. LoongH.H. Overview of current systemic management of EGFR-mutant NSCLC.Ann Oncol.201829i3i9Suppl. 110.1093/annonc/mdx70229462253
     [Google Scholar]
  49. ZhangX. QiuH. LiC. CaiP. QiF. The positive role of traditional Chinese medicine as an adjunctive therapy for cancer.Biosci. Trends202115528329810.5582/bst.2021.01318 34421064
     [Google Scholar]
  50. LiX. LiuZ. LiaoJ. ChenQ. LuX. FanX. Network pharmacology approaches for research of Traditional Chinese Medicines.Chin. J. Nat. Med.202321532333210.1016/S1875‑5364(23)60429‑7 37245871
     [Google Scholar]
  51. SuM. PanT. ChenQ.Z. ZhouW.W. GongY. XuG. YanH.Y. LiS. ShiQ.Z. ZhangY. HeX. JiangC.J. FanS.C. LiX. CairnsM.J. WangX. LiY.S. Data analysis guidelines for single-cell RNA-seq in biomedical studies and clinical applications.Mil. Med. Res.2022916810.1186/s40779‑022‑00434‑8 36461064
     [Google Scholar]
  52. JingS. ChenH. LiuE. ZhangM. ZengF. ShenH. FangY. MuhitdinovB. HuangY. Oral pectin/oligochitosan microspheres for colon-specific controlled release of quercetin to treat inflammatory bowel disease.Carbohydr. Polym.202331612102510.1016/j.carbpol.2023.121025 37321723
     [Google Scholar]
  53. BatihaG.E.S. BeshbishyA.M. IkramM. MullaZ.S. El-HackM.E.A. TahaA.E. AlgammalA.M. ElewaY.H.A. The pharmacological activity, biochemical properties, and pharmacokinetics of the major natural polyphenolic flavonoid: Quercetin.Foods20209337410.3390/foods9030374 32210182
     [Google Scholar]
  54. BianY. DongY. SunJ. SunM. HouQ. LaiY. ZhangB. Protective effect of Kaempferol on LPS-induced inflammation and barrier dysfunction in a coculture model of intestinal epithelial cells and intestinal microvascular endothelial cells.J. Agric. Food Chem.202068116016710.1021/acs.jafc.9b06294 31825618
     [Google Scholar]
  55. ZhangL. XieQ. LiX. Esculetin: A review of its pharmacology and pharmacokinetics.Phytother. Res.202236127929810.1002/ptr.7311 34808701
     [Google Scholar]
  56. LiY. WangG. LiY. Therapeutic potential of natural coumarins in autoimmune diseases with underlying mechanisms.Front. Immunol.202415143284610.3389/fimmu.2024.1432846 39544933
     [Google Scholar]
  57. TanimotoA. WitaicenisA. CarusoÍ.P. PivaH.M.R. AraujoG.C. MoraesF.R. FosseyM.C. CornélioM.L. SouzaF.P. Di StasiL.C. 4-Methylesculetin, a natural coumarin with intestinal anti-inflammatory activity, elicits a glutathione antioxidant response by different mechanisms.Chem. Biol. Interact.202031510887610.1016/j.cbi.2019.108876 31669340
     [Google Scholar]
  58. KaminskaP. TempesA. ScholzE. MalikA.R. Cytokines on the way to secretion.Cytokine Growth Factor Rev.202479526510.1016/j.cytogfr.2024.08.003 39227243
     [Google Scholar]
  59. CambierS. GouwyM. ProostP. The chemokines CXCL8 and CXCL12: Molecular and functional properties, role in disease and efforts towards pharmacological intervention.Cell. Mol. Immunol.202320321725110.1038/s41423‑023‑00974‑6 36725964
     [Google Scholar]
  60. LeeA.Y.S. EriR. LyonsA.B. GrimmM.C. KornerH. CC chemokine ligand 20 and its cognate receptor CCR6 in Mucosal T Cell immunology and inflammatory bowel disease: Odd couple or axis of evil?Front. Immunol.2013419410.3389/fimmu.2013.00194 23874340
     [Google Scholar]
  61. KadomotoS. IzumiK. MizokamiA. The CCL20-CCR6 axis in cancer progression.Int. J. Mol. Sci.20202115518610.3390/ijms21155186 32707869
     [Google Scholar]
  62. MeiteiH.T. JadhavN. LalG. CCR6-CCL20 axis as a therapeutic target for autoimmune diseases.Autoimmun. Rev.202120710284610.1016/j.autrev.2021.102846 33971346
     [Google Scholar]
  63. BlázquezAB. KnightAK. GetachewH A functional role for CCR6 on proallergic T cells in the gastrointestinal tract.Gastroenterology2010138127510.1053/j.gastro.2009.09.016
     [Google Scholar]
  64. HannaD.N. SmithP.M. NovitskiyS.V. WashingtonM.K. ZiJ. WeaverC.J. HamaamenJ.A. LewisK.B. ZhuJ. YangJ. LiuQ. BeauchampR.D. MeansA.L. SMAD4 suppresses colitis-associated carcinoma through inhibition of CCL20/CCR6-mediated inflammation.Gastroenterology2022163513341350.e1410.1053/j.gastro.2022.07.016 35863523
     [Google Scholar]
  65. HuangY. WangD. WangX. ZhangY. LiuT. ChenY. TangY. WangT. HuD. HuangC. Abrogation of CC chemokine receptor 9 ameliorates ventricular remodeling in mice after myocardial infarction.Sci. Rep.2016613266010.1038/srep32660 27585634
     [Google Scholar]
  66. PathakM. LalG. The regulatory function of CCR9+ dendritic cells in inflammation and autoimmunity.Front. Immunol.20201153632610.3389/fimmu.2020.536326 33123124
     [Google Scholar]
  67. LinL. DaiF. WeiJ.J. TangX.Y. ChenZ. SunG.B. Allergic inflammation is exacerbated by allergen-induced type 2 innate lymphoid cells in a murine model of allergic rhinitis.Rhinology201755433934710.4193/Rhin17.065 28689218
     [Google Scholar]
  68. López-PachecoC. SoldevilaG. Du PontG. Hernández-PandoR. García-ZepedaE.A. CCR9 is a key regulator of early phases of allergic airway inflammation.Mediators Inflamm.2016201611610.1155/2016/3635809 27795621
     [Google Scholar]
  69. BrunnerP.M. Suárez-FariñasM. HeH. MalikK. WenH.C. GonzalezJ. ChanT.C.C. EstradaY. ZhengX. KhattriS. DattolaA. KruegerJ.G. Guttman-YasskyE. The atopic dermatitis blood signature is characterized by increases in inflammatory and cardiovascular risk proteins.Sci. Rep.201771870710.1038/s41598‑017‑09207‑z 28821884
     [Google Scholar]
  70. CamposJ. Osorio-BarriosF. VillaneloF. Gutierrez-MaldonadoS.E. VargasP. Pérez-AcleT. PachecoR. Chemokinergic and dopaminergic signalling collaborates through the heteromer formed by CCR9 and Dopamine receptor D5 increasing the migratory speed of effector CD4+ T-cells to infiltrate the colonic mucosa.Int. J. Mol. Sci.202425181002210.3390/ijms251810022 39337509
     [Google Scholar]
  71. GaoW. WangY. BiJ. ChenX. LiN. WangY. TangH. MaoJ. Impaired CCR9/CCL25 signalling induced by inefficient dendritic cells contributes to intestinal immune imbalance in nonalcoholic steatohepatitis.Biochem. Biophys. Res. Commun.2021534344010.1016/j.bbrc.2020.12.007 33310185
     [Google Scholar]
  72. JaradeA. GarciaZ. MarieS. DemeraA. PrinzI. BoussoP. Di SantoJ.P. SerafiniN. Inflammation triggers ILC3 patrolling of the intestinal barrier.Nat. Immunol.20222391317132310.1038/s41590‑022‑01284‑1 35999393
     [Google Scholar]
  73. SomasundaramV. GilmoreA.C. BasudharD. PalmieriE.M. ScheiblinD.A. HeinzW.F. ChengR.Y.S. RidnourL.A. Altan-BonnetG. LockettS.J. McVicarD.W. WinkD.A. Inducible nitric oxide synthase-derived extracellular nitric oxide flux regulates proinflammatory responses at the single cell level.Redox Biol.20202810135410.1016/j.redox.2019.101354 31683257
     [Google Scholar]
  74. CinelliM.A. DoH.T. MileyG.P. SilvermanR.B. Inducible nitric oxide synthase: Regulation, structure, and inhibition.Med. Res. Rev.202040115818910.1002/med.21599 31192483
     [Google Scholar]
  75. AlarfajS.J. MostafaS.A. NegmW.A. El-MasryT.A. KamalM. ElsaeedM. El NakibA.M. Mucosal genes expression in inflammatory bowel disease patients: New insights.Pharmaceuticals202316232410.3390/ph16020324 37259466
     [Google Scholar]
/content/journals/ctmc/10.2174/0115680266393963250611142026
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Qi Yin San Liang San Decoction Relieves Gefitinib-Induced Diarrhea via the Modulation of Chemokines and Innate Immune Responses
Curr. Top. Med. Chem. 25, 2543 (2025); https://doi.org/10.2174/0115680266393963250611142026
/content/journals/ctmc/10.2174/0115680266393963250611142026
/content/journals/ctmc/10.2174/0115680266393963250611142026
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  • Article Type:     Research Article
Keyword(s): diarrhea; gefitinib; network pharmacology; QYSLS; RNA-seq

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