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J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Gastrointestinal acute radiation syndrome (GI-ARS) is a deadly consequence of radiation exposure. We hypothesized that the peptide ghrelin is enteroprotective after radiation injury, and that ghrelin promotes intestinal stem cell regeneration via the vagus nerve. We subjected mice to 12-Gy partial body irradiation (PBI) with 5% bone marrow sparing. Some mice were vagotomized prior to PBI. We then injected the mice with human ghrelin (6 nmol\/mouse) or vehicle at 24, 48, and 72 h post-irradiation, and collected blood and tissues at 96 h. PBI caused an 80% reduction in plasma citrulline, 32% shorter villi, 59% fewer crypts, a 14-fold increase in TUNEL+ cells, a 9-fold increase in intestinal permeability (FD4), and 4- to 30-fold increases in bacterial translocation (16S rRNA) to the liver and mesentery. Ghrelin significantly improved all these parameters. Remarkably, vagotomy attenuated ghrelin\u2019s protective effects by 22\u201358%. Mechanistically, ghrelin increased proliferating crypt cells by 2.3-fold, Lgr5+ active stem cells by 2.6-fold, Clu+ revival stem cells by 3.3-fold (immunofluorescence), and Clu mRNA by 1.6-fold compared to PBI alone, and all these effects were significantly diminished by vagotomy. Thus, ghrelin mitigates GI-ARS through vagus nerve-dependent activation of Clu+ revival stem cells and Lgr5+ stem cells, identifying a novel vagal-dependent neuroenteric pathway that regulates intestinal crypt regeneration after radiation injury.<\/jats:p>","DOI":"10.3390\/ijms27156781","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T08:16:52Z","timestamp":1785313012000},"page":"6781","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ghrelin Induces Clu+ Revival Stem Cells and Regenerates Lgr5+ Stem Cells via the Vagus Nerve to Mitigate Gastrointestinal Acute Radiation Syndrome"],"prefix":"10.3390","volume":"27","author":[{"given":"Fangming","family":"Zhang","sequence":"first","affiliation":[{"name":"Center for Immunology and Inflammation, The Feinstein Institutes for Medical Research, Manhasset, NY 11030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Jin","sequence":"additional","affiliation":[{"name":"Center for Immunology and Inflammation, The Feinstein Institutes for Medical Research, Manhasset, NY 11030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaifeng","family":"Ma","sequence":"additional","affiliation":[{"name":"Center for Immunology and Inflammation, The Feinstein Institutes for Medical Research, Manhasset, NY 11030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8280-8999","authenticated-orcid":false,"given":"Asha","family":"Jacob","sequence":"additional","affiliation":[{"name":"Center for Immunology and Inflammation, The Feinstein Institutes for Medical Research, Manhasset, NY 11030, USA"},{"name":"Departments of Surgery and Molecular Medicine, Zucker School of Medicine at Hofstra\/Northwell, Manhasset, NY 11030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1557-0394","authenticated-orcid":false,"given":"Ping","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for Immunology and Inflammation, The Feinstein Institutes for Medical Research, Manhasset, NY 11030, USA"},{"name":"Departments of Surgery and Molecular Medicine, Zucker School of Medicine at Hofstra\/Northwell, Manhasset, NY 11030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8010-148X","authenticated-orcid":false,"given":"Max","family":"Brenner","sequence":"additional","affiliation":[{"name":"Center for Immunology and Inflammation, The Feinstein Institutes for Medical Research, Manhasset, NY 11030, USA"},{"name":"Departments of Surgery and Molecular Medicine, Zucker School of Medicine at Hofstra\/Northwell, Manhasset, NY 11030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1089\/hs.2023.0106","article-title":"Findings and Recommendations From a Series of Workshops on Hospital Emergency Responses to an Improvised Nuclear Device Detonation","volume":"22","author":"Maiello","year":"2024","journal-title":"Health Secur."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/S0140-6736(15)61106-0","article-title":"Health effects of radiation and other health problems in the aftermath of nuclear accidents, with an emphasis on Fukushima","volume":"386","author":"Hasegawa","year":"2015","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1554","DOI":"10.1056\/NEJMra000365","article-title":"Major radiation exposure\u2014What to expect and how to respond","volume":"346","author":"Mettler","year":"2002","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1093\/jrr\/rrac108","article-title":"Comparison between external and internal doses to the thyroid after the Fukushima Daiichi Nuclear Power Plant accident","volume":"64","author":"Ishikawa","year":"2023","journal-title":"J. Radiat. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1097\/01.CCM.0000257328.31668.22","article-title":"The 9-11 Commission\u2019s invitation to imagine: A pathophysiology-based approach to critical care of nuclear explosion victims","volume":"35","author":"Manthous","year":"2007","journal-title":"Crit. Care Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"031002","DOI":"10.1088\/1361-6498\/ac7d18","article-title":"Medical management of acute radiation syndrome","volume":"42","author":"Dainiak","year":"2022","journal-title":"J. Radiol. Prot."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1097\/HP.0000000000001319","article-title":"A systematic review of the hematopoietic acute radiation syndrome (H-ARS) in canines and non-human primates: Acute mixed neutron\/gamma vs. reference quality radiations","volume":"119","author":"MacVittie","year":"2020","journal-title":"Health Phys."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1126\/science.1095956","article-title":"Medicine. Modulation of radiation injury","volume":"304","author":"Coleman","year":"2004","journal-title":"Science"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Dorr, H., and Meineke, V. (2011). Acute radiation syndrome caused by accidental radiation exposure\u2014Therapeutic principles. BMC Med., 9.","DOI":"10.1186\/1741-7015-9-126"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1667\/RADE-23-00196.1","article-title":"Gastrointestinal acute radiation syndrome: Mechanisms, models, markers, and medical countermeasures","volume":"201","author":"Winters","year":"2024","journal-title":"Radiat. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"S32","DOI":"10.1001\/dmp.2011.17","article-title":"Radiation injury after a nuclear detonation: Medical consequences and the need for scarce resources allocation","volume":"5","author":"DiCarlo","year":"2011","journal-title":"Disaster Med. Public Health Prep."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1080\/09553002.2023.2181999","article-title":"Where are the medical countermeasures against the ARS and DEARE? A current topic relative to an animal model research platform, radiation exposure context, the acute and delayed effects of acute exposure, and the FDA animal rule","volume":"99","author":"MacVittie","year":"2023","journal-title":"Int. J. Radiat. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1348","DOI":"10.1053\/j.gastro.2018.08.016","article-title":"Reserve stem cells in intestinal homeostasis and injury","volume":"155","author":"Bankaitis","year":"2018","journal-title":"Gastroenterology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1038\/nature06196","article-title":"Identification of stem cells in small intestine and colon by marker gene Lgr5","volume":"449","author":"Barker","year":"2007","journal-title":"Nature"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/S0968-4328(01)00013-0","article-title":"Morphological aspects of ionizing radiation response of small intestine","volume":"33","author":"Somosy","year":"2002","journal-title":"Micron"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1097\/HP.0000000000000903","article-title":"The gastrointestinal subsyndrome of the acute radiation syndrome in rhesus macaques: A systematic review of the lethal dose-response relationship with and without medical management","volume":"116","author":"MacVittie","year":"2019","journal-title":"Health Phys."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3018","DOI":"10.1038\/s41467-024-47124-8","article-title":"p53 promotes revival stem cells in the regenerating intestine after severe radiation injury","volume":"15","author":"Morral","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1038\/s41586-019-1154-y","article-title":"Single-cell transcriptomes of the regenerating intestine reveal a revival stem cell","volume":"569","author":"Ayyaz","year":"2019","journal-title":"Nature"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1097\/MED.0000000000000610","article-title":"Ghrelin-cell physiology and role in the gastrointestinal tract","volume":"28","author":"Sakata","year":"2021","journal-title":"Curr. Opin. Endocrinol. Diabetes Obes."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1016\/j.cmet.2018.02.008","article-title":"The homeostatic force of ghrelin","volume":"27","author":"Yanagi","year":"2018","journal-title":"Cell Metab."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.molmet.2018.09.007","article-title":"Ghrelin transport across the blood-brain barrier can occur independently of the growth hormone secretagogue receptor","volume":"18","author":"Rhea","year":"2018","journal-title":"Mol. Metab."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1002\/cne.20823","article-title":"Expression of ghrelin receptor mRNA in the rat and the mouse brain","volume":"494","author":"Zigman","year":"2006","journal-title":"J. Comp. Neurol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"48","DOI":"10.3181\/0706-RM-169","article-title":"Suppression of intestinal mucosal apoptosis by ghrelin in fasting rats","volume":"233","author":"Park","year":"2008","journal-title":"Exp. Biol. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e14561","DOI":"10.1111\/nmo.14561","article-title":"The ghrelin agonist, HM01 activates central vagal and enteric cholinergic neurons and reverses gastric inflammatory and ileus responses in rats","volume":"35","author":"Yuan","year":"2023","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1038\/s41575-020-0271-2","article-title":"Enteric nervous system: Sensory transduction, neural circuits and gastrointestinal motility","volume":"17","author":"Spencer","year":"2020","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.regpep.2011.11.007","article-title":"The effects of enteral ghrelin administration on the remodeling of the small intestinal mucosa in neonatal piglets","volume":"174","author":"Slupecka","year":"2012","journal-title":"Regul. Pept."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2039","DOI":"10.1016\/j.jpedsurg.2016.09.035","article-title":"Ghrelin improves intestinal mucosal atrophy during parenteral nutrition: An experimental study","volume":"51","author":"Yamada","year":"2016","journal-title":"J. Pediatr. Surg."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"153424","DOI":"10.1016\/j.phymed.2020.153424","article-title":"Ghrelin reverts intestinal stem cell loss associated with radiation-induced enteropathy by activating Notch signaling","volume":"81","author":"Kwak","year":"2021","journal-title":"Phytomedicine"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1186\/s10020-025-01399-9","article-title":"Ghrelin mitigates partial body irradiation-induced gastrointestinal acute radiation syndrome by promoting intestinal stem cell regeneration","volume":"31","author":"Yamaga","year":"2025","journal-title":"Mol. Med."},{"key":"ref_30","first-page":"332","article-title":"The effect of whole-body radiation on blood levels of gastrointestinal peptides in the rat","volume":"1","author":"Katanyutanon","year":"2008","journal-title":"Int. J. Clin. Exp. Med."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Wang, Z., Yang, W.L., Jacob, A., Aziz, M., and Wang, P. (2015). Human ghrelin mitigates intestinal injury and mortality after whole body irradiation in rats. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0118213"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Chaung, W., Jacob, A., Wang, Z., Yang, W.L., Brenner, M., and Wang, P. (2026). Human ghrelin improves vascular integrity and survival after total body irradiation. Cells, 15.","DOI":"10.3390\/cells15070586"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2421","DOI":"10.1097\/CCM.0b013e3181a557a2","article-title":"Orexigenic hormone ghrelin ameliorates gut barrier dysfunction in sepsis in rats","volume":"37","author":"Wu","year":"2009","journal-title":"Crit. Care Med."},{"key":"ref_34","first-page":"777","article-title":"Ghrelin clearance is reduced at the late stage of polymicrobial sepsis","volume":"12","author":"Wu","year":"2003","journal-title":"Int. J. Mol. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1097\/SLA.0b013e3181ad85d6","article-title":"Ghrelin hyporesponsiveness contributes to age-related hyperinflammation in septic shock","volume":"250","author":"Wu","year":"2009","journal-title":"Ann. Surg."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Wu, R., Dong, W., Ji, Y., Zhou, M., Marini, C.P., Ravikumar, T.S., and Wang, P. (2008). Orexigenic hormone ghrelin attenuates local and remote organ injury after intestinal ischemia-reperfusion. PLoS ONE, 3.","DOI":"10.1371\/journal.pone.0002026"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"407","DOI":"10.2119\/molmed.2009.00100","article-title":"Human ghrelin ameliorates organ injury and improves survival after radiation injury combined with severe sepsis","volume":"15","author":"Shah","year":"2009","journal-title":"Mol. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3033","DOI":"10.3748\/wjg.v13.i22.3033","article-title":"Biomarkers for radiation-induced small bowel epithelial damage: An emerging role for plasma citrulline","volume":"13","author":"Lutgens","year":"2007","journal-title":"World J. Gastroenterol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1667\/RR14305.1","article-title":"Citrulline as a biomarker for gastrointestinal-acute radiation syndrome: Species differences and experimental condition effects","volume":"186","author":"Bujold","year":"2016","journal-title":"Radiat. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1038\/nrgastro.2014.46","article-title":"Radiation enteropathy\u2014Pathogenesis, treatment and prevention","volume":"11","author":"Denham","year":"2014","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1016\/j.celrep.2018.06.110","article-title":"Ki67 is a graded rather than a binary marker of proliferation versus quiescence","volume":"24","author":"Miller","year":"2018","journal-title":"Cell Rep."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/s41575-018-0081-y","article-title":"Tales from the crypt: New insights into intestinal stem cells","volume":"16","author":"Gehart","year":"2019","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1186\/s13578-020-00425-z","article-title":"Ghrelin, a novel therapy, corrects cytokine and NF-kappaB-AKT-MAPK network and mitigates intestinal injury induced by combined radiation and skin-wound trauma","volume":"10","author":"Kiang","year":"2020","journal-title":"Cell Biosci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e13745","DOI":"10.14814\/phy2.13745","article-title":"Evidence for a direct effect of the autonomic nervous system on intestinal epithelial stem cell proliferation","volume":"6","author":"Davis","year":"2018","journal-title":"Physiol. Rep."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"G193","DOI":"10.1152\/ajpgi.00239.2020","article-title":"Neuronal innervation of the intestinal crypt","volume":"320","author":"Seppen","year":"2021","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/1478-811X-7-20","article-title":"Cholinergic receptor pathways involved in apoptosis, cell proliferation and neuronal differentiation","volume":"7","author":"Resende","year":"2009","journal-title":"Cell Commun. Signal"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1097\/SHK.0b013e318299e9c0","article-title":"Vagus nerve stimulation attenuates intestinal epithelial tight junctions disruption in endotoxemic mice through alpha7 nicotinic acetylcholine receptors","volume":"40","author":"Zhou","year":"2013","journal-title":"Shock"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1097\/TA.0b013e31825debd3","article-title":"Vagal nerve stimulation modulates gut injury and lung permeability in trauma-hemorrhagic shock","volume":"73","author":"Levy","year":"2012","journal-title":"J. Trauma. Acute Care Surg."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1038\/s41392-020-0150-x","article-title":"DNA damage response signaling pathways and targets for radiotherapy sensitization in cancer","volume":"5","author":"Huang","year":"2020","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1177\/1535370220938375","article-title":"The M1 muscarinic acetylcholine receptor in the crypt stem cell compartment mediates intestinal mucosal growth","volume":"245","author":"Greig","year":"2020","journal-title":"Exp. Biol. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"106984","DOI":"10.1016\/j.intimp.2020.106984","article-title":"Upregulated nicotinic ACh receptor signaling contributes to intestinal stem cell function through activation of Hippo and Notch signaling pathways","volume":"88","author":"Takahashi","year":"2020","journal-title":"Int. Immunopharmacol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"C525","DOI":"10.1152\/ajpcell.00739.2025","article-title":"Selective modulation of murine intestinal M1 and M3 muscarinic receptor expression has divergent effects on specialized epithelial cells and body weight","volume":"330","author":"Schledwitz","year":"2026","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"17057","DOI":"10.2147\/JIR.S539407","article-title":"Muscarinic Receptor-Mediated Electroacupuncture Modulation of Reactive Enteric Glial Cells Ameliorates Postoperative Ileus","volume":"18","author":"He","year":"2025","journal-title":"J. Inflamm. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"RP95267","DOI":"10.7554\/eLife.95267","article-title":"Nicotine enhances the stemness and tumorigenicity in intestinal stem cells via Hippo-YAP\/TAZ and Notch signal pathway","volume":"13","author":"Isotani","year":"2025","journal-title":"eLife"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"jjaf038","DOI":"10.1093\/ecco-jcc\/jjaf038","article-title":"Epithelial genetic muscarinic receptor 3 ablation induces sex-specific modulation of colonic intestinal progenitor cells and response to intestinal injury","volume":"19","author":"Ragab","year":"2025","journal-title":"J. Crohns Colitis"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.stem.2013.11.008","article-title":"Lgr5+ stem cells are indispensable for radiation-induced intestinal regeneration","volume":"14","author":"Metcalfe","year":"2014","journal-title":"Cell Stem Cell"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1093\/jrr\/rrab124","article-title":"Mechanisms modulating the activities of intestinal stem cells upon radiation or chemical agent exposure","volume":"63","author":"Liao","year":"2022","journal-title":"J. Radiat. Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1186\/s13578-025-01434-6","article-title":"Regulation of revival stem cell differentiation by CREPT\/RPRD1B during intestinal regeneration","volume":"15","author":"Lan","year":"2025","journal-title":"Cell Biosci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1826","DOI":"10.1210\/jc.2012-4247","article-title":"Clinical review: The human experience with ghrelin administration","volume":"98","author":"Garin","year":"2013","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_60","unstructured":"FDA, CBER (2026, May 26). Guidance for Industry: Animal Models-Essential Elements to Address Efficacy Under the Animal Rule, Available online: http:\/\/www.fda.gov\/downloads\/Drugs\/GuidanceComplianceRegulatoryInformation\/Guidances\/ucm078923.pdf."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.semcdb.2023.07.009","article-title":"Vagal sensory pathway for the gut-brain communication","volume":"156","author":"Cao","year":"2024","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1136\/gutjnl-2012-302550","article-title":"The vagal innervation of the gut and immune homeostasis","volume":"62","author":"Matteoli","year":"2013","journal-title":"Gut"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Yamamoto, T., Kodama, T., Lee, J., Utsunomiya, N., Hayashi, S., Sakamoto, H., Kuramoto, H., and Kadowaki, M. (2014). Anti-allergic role of cholinergic neuronal pathway via alpha7 nicotinic ACh receptors on mucosal mast cells in a murine food allergy model. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0085888"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1111\/joa.14178","article-title":"Transauricular vagal nerve stimulation suppresses inflammatory responses in the gut and brain in an inflammatory bowel disease model","volume":"246","author":"Atalar","year":"2025","journal-title":"J. Anat."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"e14294","DOI":"10.14814\/phy2.14294","article-title":"Sacral nerve stimulation prompts vagally-mediated amelioration of rodent colitis","volume":"8","author":"Pasricha","year":"2020","journal-title":"Physiol. Rep."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1410","DOI":"10.1038\/s41416-018-0118-6","article-title":"Targeting LGR5 in colorectal cancer: Therapeutic gold or too plastic?","volume":"118","author":"Morgan","year":"2018","journal-title":"Br. J. Cancer"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"34389","DOI":"10.18632\/oncotarget.5360","article-title":"Clusterin, a gene enriched in intestinal stem cells, is required for L1-mediated colon cancer metastasis","volume":"6","author":"Shapiro","year":"2015","journal-title":"Oncotarget"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1007\/s10555-024-10173-y","article-title":"Clusterin: A marker and mediator of chemoresistance in colorectal cancer","volume":"43","author":"Hlavca","year":"2024","journal-title":"Cancer Metastasis Rev."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1097\/01.sla.0000251614.42290.ed","article-title":"Ghrelin down-regulates proinflammatory cytokines in sepsis through activation of the vagus nerve","volume":"245","author":"Wu","year":"2007","journal-title":"Ann. Surg."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1097\/SHK.0b013e3181f48a37","article-title":"Ghrelin suppresses inflammation and neuronal nitric oxide synthase in focal cerebral ischemia via the vagus nerve","volume":"35","author":"Cheyuo","year":"2011","journal-title":"Shock"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.surg.2011.06.027","article-title":"Human ghrelin protects animals from renal ischemia-reperfusion injury through the vagus nerve","volume":"151","author":"Rajan","year":"2012","journal-title":"Surgery"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1097\/SLA.0000000000000328","article-title":"Ghrelin protects rats against traumatic brain injury and hemorrhagic shock through upregulation of UCP2","volume":"260","author":"Qi","year":"2014","journal-title":"Ann. Surg."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Rana, M., Fei-Bloom, Y., Son, M., La Bella, A., Ochani, M., Levine, Y.A., Chiu, P.Y., Wang, P., Chavan, S.S., and Volpe, B.T. (2018). Constitutive vagus nerve activation modulates immune suppression in sepsis survivors. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.02032"},{"key":"ref_74","first-page":"19","article-title":"Development of a multi-organ radiation injury model with precise dosimetry with focus on GI-ARS","volume":"201","author":"Kumar","year":"2024","journal-title":"Radiat. Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"22186","DOI":"10.1038\/s41598-023-49499-y","article-title":"Human cell-expressed tag-free rhMFG-E8 as an effective radiation mitigator","volume":"13","author":"Chaung","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/bs.mcb.2021.12.017","article-title":"Methods for induction and assessment of intestinal permeability in rodent models of radiation injury","volume":"168","author":"Ewing","year":"2022","journal-title":"Methods Cell Biol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/15\/6781\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T08:22:34Z","timestamp":1785313354000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/15\/6781"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,29]]},"references-count":76,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["ijms27156781"],"URL":"https:\/\/doi.org\/10.3390\/ijms27156781","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,29]]}}}