{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,11]],"date-time":"2026-11-11T15:54:03Z","timestamp":1794412443217,"version":"4.9.0"},"reference-count":89,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,2,27]],"date-time":"2023-02-27T00:00:00Z","timestamp":1677456000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81700497"],"award-info":[{"award-number":["81700497"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81873848"],"award-info":[{"award-number":["81873848"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Despite the significant progress that has been made in terms of understanding the pathophysiology and risk factors of Hirschsprung-associated enterocolitis (HAEC), the morbidity rate has remained unsatisfactorily stable, and clinical management of the condition continues to be challenging. Therefore, in the present literature review, we summarized the up-to-date advances that have been made regarding basic research on the pathogenesis of HAEC. Original articles published between August 2013 and October 2022 were searched in a number of databases, including PubMed, Web of Science, and Scopus. The keywords \u201cHirschsprung enterocolitis\u201d, \u201cHirschsprung\u2019s enterocolitis\u201d, \u201cHirschsprung\u2019s-associated enterocolitis\u201d, and \u201cHirschsprung-associated enterocolitis\u201d were selected and reviewed. A total of 50 eligible articles were obtained. The latest findings of these research articles were grouped into gene, microbiome, barrier function, enteric nervous system, and immune state categories. The present review concludes that HAEC is shown to be a multifactorial clinical syndrome. Only deep insights into this syndrome, with an accrual of knowledge in terms of understanding its pathogenesis, will elicit the necessary changes that are required for managing this disease.<\/jats:p>","DOI":"10.3390\/ijms24054602","type":"journal-article","created":{"date-parts":[[2023,2,27]],"date-time":"2023-02-27T03:29:48Z","timestamp":1677468588000},"page":"4602","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Update on the Pathogenesis of the Hirschsprung-Associated Enterocolitis"],"prefix":"10.3390","volume":"24","author":[{"given":"Shuai","family":"Li","sequence":"first","affiliation":[{"name":"Department of Pediatric Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yichun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuiqing","family":"Chi","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaotao","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1016\/S0140-6736(17)32284-5","article-title":"Advances in paediatric gastroenterology","volume":"390","author":"Tam","year":"2017","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1016\/j.jpedsurg.2019.01.026","article-title":"Factors influencing the incidence of Hirschsprung associated enterocolitis (HAEC)","volume":"54","author":"Piche","year":"2019","journal-title":"J. Pediatr. Surg."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1016\/j.jpedsurg.2014.02.042","article-title":"Transanal rectal mucosectomy and partial internal anal sphincterectomy for Hirschsprung\u2019s disease","volume":"49","author":"Zhang","year":"2014","journal-title":"J. Pediatr. Surg."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1007\/s00383-017-4065-8","article-title":"Guidelines for the diagnosis and management of Hirschsprung-associated enterocolitis","volume":"33","author":"Gosain","year":"2017","journal-title":"Pediatr. Surg. Int."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1007\/s00383-017-4066-7","article-title":"Guidelines for the management of postoperative obstructive symptoms in children with Hirschsprung disease","volume":"33","author":"Langer","year":"2017","journal-title":"Pediatr. Surg. Int."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"6443","DOI":"10.1172\/JCI126584","article-title":"Intestinal proinflammatory macrophages induce a phenotypic switch in interstitial cells of Cajal","volume":"130","author":"Chen","year":"2020","journal-title":"J. Clin. Investig."},{"key":"ref_7","first-page":"1089","article-title":"Role of Janus kinase2-signal transducer and activator of transcription3 signal transduction pathway in hirschsprung\u2019s disease associated enterocolitis","volume":"37","author":"Chen","year":"2020","journal-title":"Chin. J. Exp. Surg."},{"key":"ref_8","first-page":"1123","article-title":"Role of NF-kappaB signal transduction pathway in Hirschsprung\u2019s disease associated enterocolitis","volume":"41","author":"Chen","year":"2020","journal-title":"Chin. J. Pediatr. Surg."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1007\/s00383-020-04784-z","article-title":"Predictive factors for the development of postoperative Hirschsprung-associated enterocolitis in children operated during infancy","volume":"37","author":"Sakurai","year":"2021","journal-title":"Pediatr. Surg. Int."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Yulianda, D., Sati, A.I., Makhmudi, A. (2019). Risk factors of preoperative Hirschsprung-associated enterocolitis. BMC Proc., 13.","DOI":"10.1186\/s12919-019-0172-y"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1007\/s00383-013-3353-1","article-title":"Hirschsprung-associated enterocolitis: Pathogenesis, treatment and prevention","volume":"29","author":"Demehri","year":"2013","journal-title":"Pediatr. Surg. Int."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1056\/NEJMoa1706594","article-title":"Molecular Genetic Anatomy and Risk Profile of Hirschsprung\u2019s Disease","volume":"380","author":"Tilghman","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1016\/S2352-4642(22)00193-6","article-title":"Regenerative medicine: Postnatal approaches","volume":"6","author":"Tam","year":"2022","journal-title":"Lancet Child Adolesc."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2001","DOI":"10.1016\/j.jpedsurg.2016.09.026","article-title":"Enterocolitis and bowel function in children with Hirschsprung disease and trisomy 21","volume":"51","author":"Kwendakwema","year":"2016","journal-title":"J. Pediatr. Surg."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1016\/j.jss.2019.06.086","article-title":"Does Hirschsprung-Associated Enterocolitis Differ in Children With and Without Down Syndrome?","volume":"245","author":"Halleran","year":"2020","journal-title":"J. Surg. Res."},{"key":"ref_16","first-page":"522","article-title":"Diagnosis, treatment and prognosis of Mowat-Wilson syndrome with Hirschsprung\u2019s disease","volume":"43","author":"Li","year":"2022","journal-title":"Chin. J. Pediatr. Surg."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Bachetti, T., Rosamilia, F., Bartolucci, M., Santamaria, G., Mosconi, M., Sartori, S., De Filippo, M.R., Di Duca, M., Obino, V., and Avanzini, S. (2021). The OSMR Gene Is Involved in Hirschsprung Associated Enterocolitis Susceptibility through an Altered Downstream Signaling. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22083831"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Zhang, H., Zhao, J.L., Zheng, Y., Xie, X.L., Huang, L.H., Li, L., Zhu, Y., Lu, L.F., Hu, T.Q., and Zhong, W. (2021). Correlation analysis of IL-11 polymorphisms and Hirschsprung disease subtype susceptibility in Southern Chinese Children. BMC Med. Genom., 14.","DOI":"10.1186\/s12920-020-00867-x"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"BSR20182290","DOI":"10.1042\/BSR20182290","article-title":"Associations of SLC6A20 genetic polymorphisms with Hirschsprung\u2019s disease in a Southern Chinese population","volume":"39","author":"Xie","year":"2019","journal-title":"Biosci. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.5958\/0976-5506.2019.02029.1","article-title":"ITGB2 (CD18) mRNA expression in hirschsprung-associated enterocolitis (HAEC)","volume":"10","author":"Mariana","year":"2019","journal-title":"Indian J. Public Health Res. Dev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1038\/nature09944","article-title":"Enterotypes of the human gut microbiome","volume":"473","author":"Arumugam","year":"2011","journal-title":"Nature"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.1016\/j.jpedsurg.2014.01.060","article-title":"Intestinal dysbiosis and bacterial enteroinvasion in a murine model of Hirschsprung\u2019s disease","volume":"49","author":"Pierre","year":"2014","journal-title":"J. Pediatr. Surg."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"30","DOI":"10.3389\/fsurg.2018.00030","article-title":"Bacterial Microbiome Dynamics in Post Pull-Through Hirschsprung-Associated Enterocolitis (HAEC): An Experimental Study Employing the Endothelin Receptor B-Null Mouse Model","volume":"5","author":"Cheng","year":"2018","journal-title":"Front. Surg."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Li, Y., Poroyko, V., Yan, Z., Pan, L., Feng, Y., Zhao, P., Xie, Z., and Hong, L. (2016). Characterization of Intestinal Microbiomes of Hirschsprung\u2019s Disease Patients with or without Enterocolitis Using Illumina-MiSeq High-Throughput Sequencing. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0162079"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41420-022-01015-3","article-title":"Overabundance of Veillonella parvula promotes intestinal inflammation by activating macrophages via LPS-TLR4 pathway","volume":"8","author":"Zhan","year":"2022","journal-title":"Cell Death Discov."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.17219\/acem\/109342","article-title":"Is intestinal stasis sufficient by itself in promoting enterocolitis in a non-genetic rat model of Hirschsprung\u2019s disease?","volume":"28","author":"Mitroudi","year":"2019","journal-title":"Adv. Clin. Exp. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.jpedsurg.2020.06.018","article-title":"A piglet model of iatrogenic rectosigmoid hypoganglionosis reveals the impact of the enteric nervous system on gut barrier function and microbiota postnatal development","volume":"56","author":"Arnaud","year":"2021","journal-title":"J. Pediatr. Surg."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.1007\/s00383-022-05191-2","article-title":"A pilot study characterizing longitudinal changes in fecal microbiota of patients with Hirschsprung-associated enterocolitis","volume":"38","author":"Parker","year":"2022","journal-title":"Pediatr. Surg. Int."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1007\/s00383-014-3543-5","article-title":"The impact of Clostridium difficile on paediatric surgical practice: A systematic review","volume":"30","author":"Friedmacher","year":"2014","journal-title":"Pediatr. Surg. Int."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Frykman, P.K., Nordenskojld, A., Kawaguchi, A., Hui, T.T., Granstrom, A.L., Cheng, Z., Tang, J., Underhill, D.M., Iliev, I., and Funari, V.A. (2015). Characterization of Bacterial and Fungal Microbiome in Children with Hirschsprung Disease with and without a History of Enterocolitis: A Multicenter Study. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0124172"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"326","DOI":"10.3389\/fped.2019.00326","article-title":"A Metagenomics Study on Hirschsprung\u2019s Disease Associated Enterocolitis: Biodiversity and Gut Microbial Homeostasis Depend on Resection Length and Patient\u2019s Clinical History","volume":"7","author":"Prato","year":"2019","journal-title":"Front. Pediatr."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.bbrc.2014.01.104","article-title":"Characterization of the intestinal microbiome of Hirschsprung\u2019s disease with and without enterocolitis","volume":"445","author":"Yan","year":"2014","journal-title":"Biochem. Bioph. Res. Co."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1080\/19490976.2015.1134082","article-title":"Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism","volume":"7","author":"Morrison","year":"2016","journal-title":"Gut Microbes"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.jpedsurg.2015.10.012","article-title":"Altered fecal short chain fatty acid composition in children with a history of Hirschsprung-associated enterocolitis","volume":"51","author":"Demehri","year":"2016","journal-title":"J. Pediatr. Surg."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"16167","DOI":"10.1038\/s41598-021-95589-0","article-title":"Disparities in the gut metabolome of post-operative Hirschsprung\u2019s disease patients","volume":"11","author":"Plekhova","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1016\/j.tem.2020.02.012","article-title":"Gut Microbial Metabolites of Aromatic Amino Acids as Signals in Host-Microbe Interplay","volume":"31","author":"Liu","year":"2020","journal-title":"Trends Endocrin. Met."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1080\/19490976.2020.1711685","article-title":"Prospective study reveals a microbiome signature that predicts the occurrence of post-operative enterocolitis in Hirschsprung disease (HSCR) patients","volume":"11","author":"Tang","year":"2020","journal-title":"Gut Microbes"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Thiagarajah, J.R., Yildiz, H., Carlson, T., Thomas, A.R., Steiger, C., Pieretti, A., Zukerberg, L.R., Carrier, R.L., and Goldstein, A.M. (2014). Altered Goblet Cell Differentiation and Surface Mucus Properties in Hirschsprung Disease. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0099944"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1002\/mabi.201400473","article-title":"Mucus Barriers to Microparticles and Microbes are Altered in Hirschsprung\u2019s Disease","volume":"15","author":"Yildiz","year":"2015","journal-title":"Macromol. Biosci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"21725","DOI":"10.1038\/s41598-020-78340-z","article-title":"Analysis of enteric nervous system and intestinal epithelial barrier to predict complications in Hirschsprung\u2019s disease","volume":"10","author":"Dariel","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1038\/s41575-022-00675-x","article-title":"The role of goblet cells and mucus in intestinal homeostasis","volume":"19","author":"Gustafsson","year":"2022","journal-title":"Nat. Rev. Gastro. Hepat."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1111\/imr.12182","article-title":"The mucus and mucins of the goblet cells and enterocytes provide the first defense line of the gastrointestinal tract and interact with the immune system","volume":"260","author":"Pelaseyed","year":"2014","journal-title":"Immunol. Rev."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.arcmed.2019.03.004","article-title":"Intestinal Trefoil Factor 3 Alleviates the Intestinal Barrier Function Through Reducing the Expression of TLR4 in Rats with Nonalcoholic Steatohepatitis","volume":"50","author":"Wang","year":"2019","journal-title":"Arch. Med. Res."},{"key":"ref_44","first-page":"2914","article-title":"SPDEF is required for mouse pulmonary goblet cell differentiation and regulates a network of genes associated with mucus production","volume":"119","author":"Chen","year":"2009","journal-title":"J. Clin. Investig."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/j.ydbio.2010.11.001","article-title":"Altered intestinal epithelial homeostasis in mice with intestine-specific deletion of the Kruppel-like factor 4 gene","volume":"349","author":"Ghaleb","year":"2011","journal-title":"Dev. Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1007\/s00383-017-4178-0","article-title":"Altered goblet cell function in Hirschsprung\u2019s disease","volume":"34","author":"Nakamura","year":"2018","journal-title":"Pediatr. Surg. Int."},{"key":"ref_47","first-page":"655","article-title":"Gfra1 Underexpression Causes Hirschsprung\u2019s Disease and Associated Enterocolitis in Mice","volume":"7","author":"Porokuokka","year":"2019","journal-title":"Cell. Mol. Gastroenter"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1016\/j.jpedsurg.2016.02.060","article-title":"Altered expression of ATP-sensitive K+ channels in Hirschsprung\u2019s disease","volume":"51","author":"Tomuschat","year":"2016","journal-title":"J. Pediatr. Surg."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1038\/pr.2016.140","article-title":"Altered expression of a two-pore domain (K2P) mechano-gated potassium channel TREK-1 in Hirschsprung\u2019s disease","volume":"80","author":"Tomuschat","year":"2016","journal-title":"Pediatr. Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1038\/cmi.2014.137","article-title":"Regulation of TWIK-related potassium channel-1 (Trek1) restitutes intestinal epithelial barrier function","volume":"13","author":"Huang","year":"2016","journal-title":"Cell. Mol. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.molimm.2019.09.020","article-title":"Curcumin inhibits LPS-induced neuroinflammation by promoting microglial M2 polarization via TREM2\/ TLR4\/ NF-kappaB pathways in BV2 cells","volume":"116","author":"Zhang","year":"2019","journal-title":"Mol. Immunol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.3389\/fphys.2019.01455","article-title":"Activation of Cofilin Increases Intestinal Permeability via Depolymerization of F-Actin During Hypoxia in vitro","volume":"10","author":"Song","year":"2019","journal-title":"Front. Physiol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"168","DOI":"10.3892\/mmr.2022.12684","article-title":"E. coli JM83 damages the mucosal barrier in Ednrb knockout mice to promote the development of Hirschsprung-associated enterocolitis via activation of TLR4\/p-p38\/NF-\u03baB signaling","volume":"25","author":"Zheng","year":"2022","journal-title":"Mol. Med. Rep."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1488","DOI":"10.1016\/j.jpedsurg.2019.11.009","article-title":"Increased protease activated receptors in the colon of patients with Hirschsprung\u2019s disease","volume":"55","author":"Tomuschat","year":"2020","journal-title":"J. Pediatr. Surg."},{"key":"ref_55","first-page":"507","article-title":"Lack of Mucosal Cholinergic Innervation Is Associated With Increased Risk of Enterocolitis in Hirschsprung\u2019s Disease","volume":"12","author":"Keck","year":"2021","journal-title":"Cell. Mol. Gastroenter"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.jpedsurg.2015.10.006","article-title":"Roles of nitric oxide and intestinal microbiota in the pathogenesis of necrotizing enterocolitis","volume":"51","author":"Grishin","year":"2016","journal-title":"J. Pediatr. Surg."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1053\/j.semperi.2008.01.002","article-title":"The role of nitric oxide in intestinal epithelial injury and restitution in neonatal necrotizing enterocolitis","volume":"32","author":"Chokshi","year":"2008","journal-title":"Semin. Perinatol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1007\/s00383-019-04505-1","article-title":"Altered expression of caveolin-1 in the colon of patients with Hirschsprung\u2019s disease","volume":"35","author":"Nakamura","year":"2019","journal-title":"Pediatr. Surg. Int."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1016\/j.jpedsurg.2017.01.046","article-title":"NOS-interacting protein (NOSIP) is increased in the colon of patients with Hirschsprungs\u2019s disease","volume":"52","author":"Tomuschat","year":"2017","journal-title":"J. Pediatr. Surg."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1834","DOI":"10.1016\/j.jpedsurg.2016.08.001","article-title":"Bowel dysfunction following pullthrough surgery is associated with an overabundance of nitrergic neurons in Hirschsprung disease","volume":"51","author":"Cheng","year":"2016","journal-title":"J. Pediatr. Surg."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1053\/j.gastro.2012.06.034","article-title":"Gut microbial products regulate murine gastrointestinal motility via Toll-like receptor 4 signaling","volume":"143","author":"Anitha","year":"2012","journal-title":"Gastroenterology"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1053\/j.gastro.2013.08.047","article-title":"Toll-like receptor 2 regulates intestinal inflammation by controlling integrity of the enteric nervous system","volume":"145","author":"Brun","year":"2013","journal-title":"Gastroenterology"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1188","DOI":"10.1016\/j.jpedsurg.2017.01.065","article-title":"Cotransplantation of neuroepithelial stem cells with interstitial cells of Cajal improves neuronal differentiation in a rat aganglionic model","volume":"52","author":"Zhang","year":"2017","journal-title":"J. Pediatr. Surg."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1","DOI":"10.5457\/p2005-114.251","article-title":"Altered Distribution of Interstitial Cells of Cajal in Normoganglionic and Transitional Zone of Hirschsprung Disease and Their Clinical Significance","volume":"16","author":"Jankovic","year":"2020","journal-title":"Cent. Eur. J. Paediatr."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.intimp.2016.07.020","article-title":"Hydrogen sulfide improves colonic barrier integrity in DSS-induced inflammation in Caco-2 cells and mice","volume":"39","author":"Zhao","year":"2016","journal-title":"Int. Immunopharmacol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/j.jpedsurg.2017.06.011","article-title":"Reduction of hydrogen sulfide synthesis enzymes cystathionine-beta-synthase and cystathionine-gamma-lyase in the colon of patients with Hirschsprungs disease","volume":"53","author":"Tomuschat","year":"2018","journal-title":"J. Pediatr. Surg."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Turula, H., and Wobus, C.E. (2018). The Role of the Polymeric Immunoglobulin Receptor and Secretory Immunoglobulins during Mucosal Infection and Immunity. Viruses, 10.","DOI":"10.3390\/v10050237"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Gosain, A., Barlow-Anacker, A.J., Erickson, C.S., Pierre, J.F., Heneghan, A.F., Epstein, M.L., and Kudsk, K.A. (2015). Impaired Cellular Immunity in the Murine Neural Crest Conditional Deletion of Endothelin Receptor-B Model of Hirschsprung\u2019s Disease. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0128822"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1002\/eji.201444737","article-title":"Enterocolitis causes profound lymphoid depletion in endothelin receptor B- and endothelin 3-null mouse models of Hirschsprung-associated enterocolitis","volume":"45","author":"Frykman","year":"2015","journal-title":"Eur. J. Immunol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1146\/annurev-physiol-022516-034339","article-title":"Macrophage Polarization","volume":"79","author":"Murray","year":"2017","journal-title":"Annu. Rev. Physiol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.anai.2018.05.010","article-title":"The role of gastrointestinal permeability in food allergy","volume":"121","author":"Samadi","year":"2018","journal-title":"Ann. Allerg. Asthma Im."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"7615","DOI":"10.1096\/fj.201801913R","article-title":"B-lymphocyte-intrinsic and -extrinsic defects in secretory immunoglobulin A production in the neural crest-conditional deletion of endothelin receptor B model of Hirschsprung-associated enterocolitis","volume":"33","author":"Medrano","year":"2019","journal-title":"FASEB J."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1097\/MPG.0000000000002358","article-title":"Inflammatory Bowel Disease Serological Immune Markers Anti-Saccharomyces cerevisiae Mannan Antibodies and Outer Membrane Porin C are Potential Biomarkers for Hirschsprung-associated Enterocolitis","volume":"69","author":"Frykman","year":"2019","journal-title":"J. Pediatr. Gastr. Nutr."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/nrrheum.2015.53","article-title":"The IL-23-IL-17 axis in inflammatory arthritis","volume":"11","author":"Lubberts","year":"2015","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1038\/s41590-018-0071-9","article-title":"IL-17-receptor-associated adaptor Act1 directly stabilizes mRNAs to mediate IL-17 inflammatory signaling","volume":"19","author":"Herjan","year":"2018","journal-title":"Nat. Immunol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.1038\/mi.2016.130","article-title":"IL-36gamma is a crucial proximal component of protective type-1-mediated lung mucosal immunity in Gram-positive and -negative bacterial pneumonia","volume":"10","author":"Kovach","year":"2017","journal-title":"Mucosal. Immunol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"34","DOI":"10.4049\/jimmunol.1501312","article-title":"Cutting Edge: IL-36 Receptor Promotes Resolution of Intestinal Damage","volume":"196","author":"Harusato","year":"2016","journal-title":"J. Immunol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1007\/s00383-016-3980-4","article-title":"Increased Act1\/IL-17R expression in Hirschsprung\u2019s disease","volume":"32","author":"Tomuschat","year":"2016","journal-title":"Pediatr. Surg. Int."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1007\/s00383-016-4011-1","article-title":"Altered expression of IL36 gamma and IL36 receptor (IL1RL2) in the colon of patients with Hirschsprung\u2019s disease","volume":"33","author":"Tomuschat","year":"2017","journal-title":"Pediatr. Surg. Int."},{"key":"ref_80","first-page":"504","article-title":"Expressions of Th17-related cytokines in children with Hirschsprung\u2019s disease-associated enterocolitis","volume":"35","author":"Ren","year":"2014","journal-title":"Chin. J. Pediatr. Surg."},{"key":"ref_81","first-page":"263","article-title":"Experimental study of dental pulp stem cells in the treatment of Hirschsprungs disease associated enterocolitis","volume":"40","author":"Meng","year":"2019","journal-title":"Chin. J. Pediatr. Surg."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"e105071","DOI":"10.15252\/embj.2020105071","article-title":"CARD8 inflammasome activation triggers pyroptosis in human T cells","volume":"39","author":"Linder","year":"2020","journal-title":"EMBO J."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/s00383-018-4371-9","article-title":"Altered expression of inflammasomes in Hirschsprung\u2019s disease","volume":"35","author":"Nakamura","year":"2019","journal-title":"Pediatr. Surg. Int."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.1016\/j.jpedsurg.2018.08.059","article-title":"Reduced expression of the NLRP6 inflammasome in the colon of patients with Hirschsprung\u2019s disease","volume":"54","author":"Tomuschat","year":"2019","journal-title":"J. Pediatr. Surg."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"18588","DOI":"10.18632\/aging.103852","article-title":"Lipopolysaccharide upregulates miR-132\/212 in Hirschsprung-associated enterocolitis, facilitating pyroptosis by activating NLRP3 inflammasome via targeting Sirtuin 1 (SIRT1)","volume":"12","author":"Li","year":"2020","journal-title":"Aging"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.semcdb.2015.02.009","article-title":"Exosomes and their roles in immune regulation and cancer","volume":"40","author":"Greening","year":"2015","journal-title":"Semin. Cell. Dev. Biol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1097\/TA.0000000000001296","article-title":"Exosomes, not protein or lipids, in mesenteric lymph activate inflammation: Unlocking the mystery of post-shock multiple organ failure","volume":"82","author":"Kojima","year":"2017","journal-title":"J. Trauma Acute Care"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"15016","DOI":"10.1038\/ncomms15016","article-title":"Exosome-delivered EGFR regulates liver microenvironment to promote gastric cancer liver metastasis","volume":"8","author":"Zhang","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_89","first-page":"4182","article-title":"Circulating exosomal microRNA-18a-5p accentuates intestinal inflammation in Hirschsprung-associated enterocolitis by targeting RORA","volume":"13","author":"Chen","year":"2021","journal-title":"Am. J. Transl. Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/5\/4602\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:43:36Z","timestamp":1760121816000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/5\/4602"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,27]]},"references-count":89,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["ijms24054602"],"URL":"https:\/\/doi.org\/10.3390\/ijms24054602","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,27]]}}}