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Current Pediatric Reviews

Author(s): Xue Cai, Heather L. Liebe, Alena Golubkova, Tyler Leiva and Catherine J. Hunter*

DOI: 10.2174/1573396318666220805110947

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A Review of the Diagnosis and Treatment of Necrotizing Enterocolitis

Page: [285 - 295] Pages: 11

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Abstract

Necrotizing enterocolitis (NEC) is a devastating disease that primarily affects the gastrointestinal tract of premature neonates. The diagnosis and treatment of NEC remain challenging. New biomarkers and potential treatments for NEC have emerged in recent years, leading to the potential of earlier therapeutic intervention and improved outcomes. This paper aims to provide a review of the most recent diagnostic indicators and therapeutics of NEC along with a brief overview of future directions of research into this disease.

Keywords: Necrotizing enterocolitis, biomarkers, neonates, apolipoproteins, probiotics, necrosis.

Graphical Abstract

[1]
Meister AL, Doheny KK, Travagli RA. Necrotizing enterocolitis: It’s not all in the gut. Exp Biol Med (Maywood) 2020; 245(2): 85-95.
[http://dx.doi.org/10.1177/1535370219891971] [PMID: 31810384]
[2]
Rich BS, Dolgin SE. Necrotizing enterocolitis. Pediatr Rev 2017; 38(12): 552-9.
[http://dx.doi.org/10.1542/pir.2017-0002] [PMID: 29196510]
[3]
Neu J, Walker WA. Necrotizing enterocolitis. N Engl J Med 2011; 364(3): 255-64.
[http://dx.doi.org/10.1056/NEJMra1005408] [PMID: 21247316]
[4]
Gephart SM, Gordon PV, Penn AH, et al. Changing the paradigm of defining, detecting, and diagnosing NEC: Perspectives on Bell’s stages and biomarkers for NEC. Semin Pediatr Surg 2018; 27(1): 3-10.
[http://dx.doi.org/10.1053/j.sempedsurg.2017.11.002] [PMID: 29275814]
[5]
Goldstein GP, Sylvester KG. Biomarker discovery and utility in necrotizing enterocolitis. Clin Perinatol 2019; 46(1): 1-17.
[http://dx.doi.org/10.1016/j.clp.2018.10.001] [PMID: 30771811]
[6]
Ng PC. An update on biomarkers of necrotizing enterocolitis. Semin Fetal Neonatal Med 2018; 23(6): 380-6.
[http://dx.doi.org/10.1016/j.siny.2018.07.006] [PMID: 30082194]
[7]
Terrin G, Stronati L, Cucchiara S, De Curtis M. Serum markers of necrotizing enterocolitis: A systematic review. J Pediatr Gastroenterol Nutr 2017; 65(6): e120-32.
[http://dx.doi.org/10.1097/MPG.0000000000001588] [PMID: 28379923]
[8]
Shelby RD, Raab R, Besner GE, McElroy SJ. Hope on the horizon: Promising novel therapies for necrotizing enterocolitis. Pediatr Res 2020; 88 (Suppl. 1): 30-4.
[http://dx.doi.org/10.1038/s41390-020-1077-1] [PMID: 32855510]
[9]
Niño DF, Sodhi CP, Hackam DJ. Necrotizing enterocolitis: New insights into pathogenesis and mechanisms. Nat Rev Gastroenterol Hepatol 2016; 13(10): 590-600.
[http://dx.doi.org/10.1038/nrgastro.2016.119] [PMID: 27534694]
[10]
Agakidou E, Agakidis C, Gika H, Sarafidis K. Emerging biomarkers for prediction and early diagnosis of necrotizing enterocolitis in the era of metabolomics and proteomics. Front Pediatr 2020; 8, 602255.
[http://dx.doi.org/10.3389/fped.2020.602255] [PMID: 33425815]
[11]
Ramasamy I. Recent advances in physiological lipoprotein metabolism. Clin Chem Lab Med 2014; 52(12): 1695-727.
[http://dx.doi.org/10.1515/cclm-2013-0358] [PMID: 23940067]
[12]
Chatziioannou AC, Wolters JC, Sarafidis K, et al. Targeted LC-MS/MS for the evaluation of proteomics biomarkers in the blood of neo-nates with necrotizing enterocolitis and late-onset sepsis. Anal Bioanal Chem 2018; 410(27): 7163-75.
[http://dx.doi.org/10.1007/s00216-018-1320-3] [PMID: 30141021]
[13]
Ng PC, Ang IL, Chiu RW, et al. Host-response biomarkers for diagnosis of late-onset septicemia and necrotizing enterocolitis in preterm infants. J Clin Invest 2010; 120(8): 2989-3000.
[http://dx.doi.org/10.1172/JCI40196] [PMID: 20592468]
[14]
Fawley J, Gourlay DM. Intestinal alkaline phosphatase: A summary of its role in clinical disease. J Surg Res 2016; 202(1): 225-34.
[http://dx.doi.org/10.1016/j.jss.2015.12.008] [PMID: 27083970]
[15]
Heinzerling NP, Liedel JL, Welak SR, et al. Intestinal alkaline phosphatase is protective to the preterm rat pup intestine. J Pediatr Surg 2014; 49(6): 954-60.
[http://dx.doi.org/10.1016/j.jpedsurg.2014.01.031] [PMID: 24888842]
[16]
Whitehouse JS, Riggle KM, Purpi DP, et al. The protective role of intestinal alkaline phosphatase in necrotizing enterocolitis. J Surg Res 2010; 163(1): 79-85.
[http://dx.doi.org/10.1016/j.jss.2010.04.048] [PMID: 20599220]
[17]
Heath M, Buckley R, Gerber Z, et al. Association of intestinal alkaline phosphatase with necrotizing enterocolitis among premature infants. JAMA Netw Open 2019; 2(11), e1914996.
[http://dx.doi.org/10.1001/jamanetworkopen.2019.14996] [PMID: 31702803]
[18]
Kampanatkosol R, Thomson T, Habeeb O, et al. The relationship between reticulated platelets, intestinal alkaline phosphatase, and ne-crotizing enterocolitis. J Pediatr Surg 2014; 49(2): 273-6.
[http://dx.doi.org/10.1016/j.jpedsurg.2013.11.037] [PMID: 24528965]
[19]
Mohr AM, Mott JL. Overview of microRNA biology. Semin Liver Dis 2015; 35(1): 3-11.
[http://dx.doi.org/10.1055/s-0034-1397344] [PMID: 25632930]
[20]
Ng PC, Chan KY, Leung KT, et al. Comparative MiRNA expressional profiles and molecular networks in human small bowel tissues of necrotizing enterocolitis and spontaneous intestinal perforation. PLoS One 2015; 10(8), e0135737.
[http://dx.doi.org/10.1371/journal.pone.0135737] [PMID: 26274503]
[21]
Ng PC, Chan KYY, Yuen TP, et al. Plasma miR-1290 is a novel and specific biomarker for early diagnosis of necrotizing enterocolitis-biomarker discovery with prospective cohort evaluation. J Pediatr 2019; 205: 83-90.e10.
[http://dx.doi.org/10.1016/j.jpeds.2018.09.031] [PMID: 30529132]
[22]
Pergialiotis V, Konstantopoulos P, Karampetsou N, et al. Calprotectin levels in necrotizing enterocolitis: A systematic review of the litera-ture. Inflamm Res 2016; 65(11): 847-52.
[http://dx.doi.org/10.1007/s00011-016-0963-9] [PMID: 27328832]
[23]
MacQueen BC, Christensen RD, Yost CC, et al. Elevated fecal calprotectin levels during necrotizing enterocolitis are associated with acti-vated neutrophils extruding neutrophil extracellular traps. J Perinatol 2016; 36(10): 862-9.
[http://dx.doi.org/10.1038/jp.2016.105] [PMID: 27388941]
[24]
Thuijls G, Derikx JP, van Wijck K, et al. Non-invasive markers for early diagnosis and determination of the severity of necrotizing entero-colitis. Ann Surg 2010; 251(6): 1174-80.
[http://dx.doi.org/10.1097/SLA.0b013e3181d778c4] [PMID: 20485148]
[25]
Bin-Nun A, Booms C, Sabag N, Mevorach R, Algur N, Hammerman C. Rapid fecal calprotectin (FC) analysis: Point of care testing for diagnosing early necrotizing enterocolitis. Am J Perinatol 2015; 32(4): 337-42.
[http://dx.doi.org/10.1055/s-0034-1384640] [PMID: 25111039]
[26]
MacQueen BC, Christensen RD, Yost CC, et al. Reference intervals for stool calprotectin in preterm neonates and their utility for the diag-nosis of necrotizing enterocolitis. J Perinatol 2018; 38(10): 1379-85.
[http://dx.doi.org/10.1038/s41372-018-0108-9] [PMID: 29740189]
[27]
Qu Y, Xu W, Han J, Zhou W, Wu H. Diagnostic value of fecal calprotectin in necrotizing enterocolitis: A meta-analysis. Early Hum Dev 2020; 151, 105170.
[http://dx.doi.org/10.1016/j.earlhumdev.2020.105170] [PMID: 32919106]
[28]
van Zoonen AGJF, Hulzebos CV, Muller Kobold AC, Kooi EMW, Bos AF, Hulscher JBF. Serial fecal calprotectin in the prediction of necrotizing enterocolitis in preterm neonates. J Pediatr Surg 2019; 54(3): 455-9.
[http://dx.doi.org/10.1016/j.jpedsurg.2018.04.034] [PMID: 29859621]
[29]
Shores DR, Fundora J, Go M, et al. Normative values for circulating intestinal fatty acid binding protein and calprotectin across gestational ages. BMC Pediatr 2020; 20(1): 250.
[http://dx.doi.org/10.1186/s12887-020-02142-5] [PMID: 32456678]
[30]
Shen L, Weber CR, Raleigh DR, Yu D, Turner JR. Tight junction pore and leak pathways: A dynamic duo. Annu Rev Physiol 2011; 73(1): 283-309.
[http://dx.doi.org/10.1146/annurev-physiol-012110-142150] [PMID: 20936941]
[31]
Ravisankar S, Tatum R, Garg PM, Herco M, Shekhawat PS, Chen YH. Necrotizing enterocolitis leads to disruption of tight junctions and increase in gut permeability in a mouse model. BMC Pediatr 2018; 18(1): 372.
[http://dx.doi.org/10.1186/s12887-018-1346-x] [PMID: 30482190]
[32]
Bein A, Eventov-Friedman S, Arbell D, Schwartz B. Intestinal tight junctions are severely altered in NEC preterm neonates. Pediatr Neonatol 2018; 59(5): 464-73.
[http://dx.doi.org/10.1016/j.pedneo.2017.11.018] [PMID: 29276042]
[33]
Ares G, Buonpane C, Sincavage J, Yuan C, Wood DR, Hunter CJ. Caveolin 1 is associated with upregulated claudin 2 in necrotizing enter-ocolitis. Sci Rep 2019; 9(1): 4982.
[http://dx.doi.org/10.1038/s41598-019-41442-4] [PMID: 30899070]
[34]
P Blackwood M D B, R Wood B S D, Y Yuan B S C, et al.. Urinary claudin-2 measurements as a predictor of necrotizing enterocolitis: A pilot study. J Neonatal Surg 2015; 4(4): 43.
[http://dx.doi.org/10.47338/jns.v4.457] [PMID: 26500853]
[35]
Griffiths V, Al Assaf N, Khan R. Review of claudin proteins as potential biomarkers for necrotizing enterocolitis. Iran J Med Sci 2021; 190(4): 1465-72.
[http://dx.doi.org/10.1007/s11845-020-02490-2] [PMID: 33492576]
[36]
Hwang M, Tierradentro-García LO, Dennis RA, Anupindi SA. The role of ultrasound in necrotizing enterocolitis. Pediatr Radiol 2022; 52(4): 702-15.
[PMID: 34654968]
[37]
Fonseca EKUN, Ponte MPTR, Sameshima YT. “Zebra pattern” in necrotizing enterocolitis. Abdom Radiol (NY) 2017; 42(11): 2776-7.
[http://dx.doi.org/10.1007/s00261-017-1191-7] [PMID: 28528387]
[38]
Faingold R, Daneman A, Tomlinson G, et al. Necrotizing enterocolitis: Assessment of bowel viability with color doppler US. Radiology 2005; 235(2): 587-94.
[http://dx.doi.org/10.1148/radiol.2352031718] [PMID: 15858098]
[39]
Al-Hamad S, Hackam DJ, Goldstein SD, Huisman TAGM, Darge K, Hwang M. Contrast-enhanced ultrasound and near-infrared spectros-copy of the neonatal bowel: Novel, bedside, noninvasive, and radiation-free imaging for early detection of necrotizing enterocolitis. Am J Perinatol 2018; 35(14): 1358-65.
[http://dx.doi.org/10.1055/s-0038-1655768] [PMID: 29852509]
[40]
Patel AK, Lazar DA, Burrin DG, et al. Abdominal near-infrared spectroscopy measurements are lower in preterm infants at risk for ne-crotizing enterocolitis. Pediatr Crit Care Med 2014; 15(8): 735-41.
[http://dx.doi.org/10.1097/PCC.0000000000000211] [PMID: 25068253]
[41]
Chen W, Sun J, Kappel SS, Gormsen M, Sangild PT, Aunsholt L. Gut transit time, using radiological contrast imaging, to predict early signs of necrotizing enterocolitis. Pediatr Res 2021; 89(1): 127-33.
[http://dx.doi.org/10.1038/s41390-020-0871-0] [PMID: 32244249]
[42]
Denning TL, Bhatia AM, Kane AF, Patel RM, Denning PW. Pathogenesis of NEC: Role of the innate and adaptive immune response. Semin Perinatol 2017; 41(1): 15-28.
[http://dx.doi.org/10.1053/j.semperi.2016.09.014] [PMID: 27940091]
[43]
Nolan LS, Rimer JM, Good M. The role of human milk oligosaccharides and probiotics on the neonatal microbiome and risk of necrotiz-ing enterocolitis: A narrative review. Nutrients 2020; 12(10), E3052.
[http://dx.doi.org/10.3390/nu12103052] [PMID: 33036184]
[44]
Lönnerdal B. Infant formula and infant nutrition: Bioactive proteins of human milk and implications for composition of infant formulas. Am J Clin Nutr 2014; 99(3): 712S-7S.
[http://dx.doi.org/10.3945/ajcn.113.071993] [PMID: 24452231]
[45]
Telang S. Lactoferrin: A critical player in neonatal host defense. Nutrients 2018; 10(9), E1228.
[http://dx.doi.org/10.3390/nu10091228] [PMID: 30181493]
[46]
Liu J, Zhu H, Li B, et al. Lactoferrin reduces necrotizing enterocolitis severity by upregulating intestinal epithelial proliferation. Eur J Pediatr Surg 2020; 30(1): 90-5.
[http://dx.doi.org/10.1055/s-0039-1693728] [PMID: 31344710]
[47]
Liu Y, Perego M, Xiao Q, et al. Lactoferrin-induced myeloid-derived suppressor cell therapy attenuates pathologic inflammatory condi-tions in newborn mice. J Clin Invest 2019; 129(10): 4261-75.
[http://dx.doi.org/10.1172/JCI128164] [PMID: 31483289]
[48]
Wu RY, Li B, Koike Y, et al. Human milk oligosaccharides increase mucin expression in experimental necrotizing enterocolitis. Mol Nutr Food Res 2019; 63(3), e1800658.
[PMID: 30407734]
[49]
Li B, Wu RY, Horne RG, et al. Human milk oligosaccharides protect against necrotizing enterocolitis by activating intestinal cell differenti-ation. Mol Nutr Food Res 2020; 64(21), e2000519.
[http://dx.doi.org/10.1002/mnfr.202000519] [PMID: 32926533]
[50]
Sodhi CP, Wipf P, Yamaguchi Y, et al. The human milk oligosaccharides 2′-fucosyllactose and 6′-sialyllactose protect against the devel-opment of necrotizing enterocolitis by inhibiting toll-like receptor 4 signaling. Pediatr Res 2021; 89(1): 91-101.
[http://dx.doi.org/10.1038/s41390-020-0852-3] [PMID: 32221473]
[51]
Warner BB, Deych E, Zhou Y, et al. Gut bacteria dysbiosis and necrotising enterocolitis in very low birthweight infants: A prospective case-control study. Lancet 2016; 387(10031): 1928-36.
[http://dx.doi.org/10.1016/S0140-6736(16)00081-7] [PMID: 26969089]
[52]
Wang Y, Hoenig JD, Malin KJ, et al. 16S rRNA gene-based analysis of fecal microbiota from preterm infants with and without necrotizing enterocolitis. ISME J 2009; 3(8): 944-54.
[http://dx.doi.org/10.1038/ismej.2009.37] [PMID: 19369970]
[53]
Robertson C, Savva GM, Clapuci R, et al. Incidence of necrotising enterocolitis before and after introducing routine prophylactic Lactoba-cillus and Bifidobacterium probiotics. Arch Dis Child Fetal Neonatal Ed 2020; 105(4): 380-6.
[http://dx.doi.org/10.1136/archdischild-2019-317346] [PMID: 31666311]
[54]
Baranowski JR, Claud EC. Necrotizing enterocolitis and the preterm infant microbiome. Adv Exp Med Biol 2019; 1125: 25-36.
[http://dx.doi.org/10.1007/5584_2018_313] [PMID: 30680646]
[55]
Hallab JC, Leach ST, Zhang L, et al. Molecular characterization of bacterial colonization in the preterm and term infant’s intestine. Indian J Pediatr 2013; 80(1): 1-5.
[http://dx.doi.org/10.1007/s12098-012-0753-5] [PMID: 22576294]
[56]
Underwood MA, German JB, Lebrilla CB, Mills DA. Bifidobacterium longum subspecies infantis: Champion colonizer of the infant gut. Pediatr Res 2015; 77(1-2): 229-35.
[http://dx.doi.org/10.1038/pr.2014.156] [PMID: 25303277]
[57]
Bi LW, Yan BL, Yang QY, Li MM, Cui HL. Probiotic strategies to prevent necrotizing enterocolitis in preterm infants: A meta-analysis. Pediatr Surg Int 2019; 35(10): 1143-62.
[http://dx.doi.org/10.1007/s00383-019-04547-5] [PMID: 31420743]
[58]
Soltan Dallal MM, Mojarrad M, Baghbani F, Raoofian R, Mardaneh J, Salehipour Z. Effects of probiotic Lactobacillus acidophilus and Lactobacillus casei on colorectal tumor cells activity (CaCo-2). Arch Iran Med 2015; 18(3): 167-72.
[PMID: 25773690]
[59]
Rao SC, Athalye-Jape GK, Deshpande GC, Simmer KN, Patole SK. Probiotic supplementation and late-onset sepsis in preterm infants: A meta-analysis. Pediatrics 2016; 137(3), e20153684.
[http://dx.doi.org/10.1542/peds.2015-3684] [PMID: 26908700]
[60]
Patel RM, Underwood MA. Probiotics and necrotizing enterocolitis. Semin Pediatr Surg 2018; 27(1): 39-46.
[http://dx.doi.org/10.1053/j.sempedsurg.2017.11.008] [PMID: 29275816]
[61]
Underwood MA, Arriola J, Gerber CW, et al. Bifidobacterium longum subsp. infantis in experimental necrotizing enterocolitis: Alterations in inflammation, innate immune response, and the microbiota. Pediatr Res 2014; 76(4): 326-33.
[http://dx.doi.org/10.1038/pr.2014.102] [PMID: 25000347]
[62]
Cuna A, Yu W, Menden HL, et al. NEC-like intestinal injury is ameliorated by Lactobacillus rhamnosus GG in parallel with SIGIRR and A20 induction in neonatal mice. Pediatr Res 2020; 88(4): 546-55.
[http://dx.doi.org/10.1038/s41390-020-0797-6] [PMID: 32053825]
[63]
Lin PW, Nasr TR, Berardinelli AJ, Kumar A, Neish AS. The probiotic Lactobacillus GG may augment intestinal host defense by regulating apoptosis and promoting cytoprotective responses in the developing murine gut. Pediatr Res 2008; 64(5): 511-6.
[http://dx.doi.org/10.1203/PDR.0b013e3181827c0f] [PMID: 18552706]
[64]
Bron PA, Kleerebezem M, Brummer RJ, et al. Can probiotics modulate human disease by impacting intestinal barrier function? Br J Nutr 2017; 117(1): 93-107.
[http://dx.doi.org/10.1017/S0007114516004037] [PMID: 28102115]
[65]
Blackwood BP, Yuan CY, Wood DR, Nicolas JD, Grothaus JS, Hunter CJ. Probiotic Lactobacillus species strengthen intestinal barrier function and tight junction integrity in experimental necrotizing enterocolitis. J Probiotics Health 2017; 5(1): 159.
[http://dx.doi.org/10.4172/2329-8901.1000159] [PMID: 28638850]
[66]
Hoyos AB. Reduced incidence of necrotizing enterocolitis associated with enteral administration of Lactobacillus acidophilus and Bifidobacterium infantis to neonates in an intensive care unit. Int J Infect Dis 1999; 3(4): 197-202.
[http://dx.doi.org/10.1016/S1201-9712(99)90024-3] [PMID: 10575148]
[67]
Pell LG, Loutet MG, Roth DE, Sherman PM. Arguments against routine administration of probiotics for NEC prevention. Curr Opin Pediatr 2019; 31(2): 195-201.
[http://dx.doi.org/10.1097/MOP.0000000000000730] [PMID: 30624281]
[68]
Chen W, Wang X, Yan X, Yu Z, Zhang J, Han S. The emerging role of exosomes in the pathogenesis, prognosis and treatment of necrotiz-ing enterocolitis. Am J Transl Res 2020; 12(11): 7020-33.
[PMID: 33312348]
[69]
Matei AC, Antounians L, Zani A. Extracellular vesicles as a potential therapy for neonatal conditions: State of the art and challenges in clinical translation. Pharmaceutics 2019; 11(8), E404.
[http://dx.doi.org/10.3390/pharmaceutics11080404] [PMID: 31405234]
[70]
Jiang L, Shen Y, Guo D, et al. EpCAM-dependent extracellular vesicles from intestinal epithelial cells maintain intestinal tract immune balance. Nat Commun 2016; 7(1): 13045.
[http://dx.doi.org/10.1038/ncomms13045] [PMID: 27721471]
[71]
Miyake H, Lee C, Chusilp S, et al. Human breast milk exosomes attenuate intestinal damage. Pediatr Surg Int 2020; 36(2): 155-63.
[http://dx.doi.org/10.1007/s00383-019-04599-7] [PMID: 31713717]
[72]
Gao R, Zhang R, Qian T, et al. A comparison of exosomes derived from different periods breast milk on protecting against intestinal or-ganoid injury. Pediatr Surg Int 2019; 35(12): 1363-8.
[http://dx.doi.org/10.1007/s00383-019-04562-6] [PMID: 31576466]
[73]
Martin C, Patel M, Williams S, Arora H, Brawner K, Sims B. Human breast milk-derived exosomes attenuate cell death in intestinal epithe-lial cells. Innate Immun 2018; 24(5): 278-84.
[http://dx.doi.org/10.1177/1753425918785715] [PMID: 29991305]
[74]
Dong P, Zhang Y, Yan DY, et al. Protective effects of human milk-derived exosomes on intestinal stem cells damaged by oxidative stress. Cell Transplant 2020; 29, 963689720912690.
[http://dx.doi.org/10.1177/0963689720912690] [PMID: 32193954]
[75]
Pisano C, Galley J, Elbahrawy M, et al. Human breast milk-derived extracellular vesicles in the protection against experimental necrotizing enterocolitis. J Pediatr Surg 2020; 55(1): 54-8.
[http://dx.doi.org/10.1016/j.jpedsurg.2019.09.052] [PMID: 31685268]
[76]
McCulloh CJ, Olson JK, Wang Y, et al. Treatment of experimental necrotizing enterocolitis with stem cell-derived exosomes. J Pediatr Surg 2018; 53(6): 1215-20.
[http://dx.doi.org/10.1016/j.jpedsurg.2018.02.086] [PMID: 29661576]
[77]
Rager TM, Olson JK, Zhou Y, Wang Y, Besner GE. Exosomes secreted from bone marrow-derived mesenchymal stem cells protect the intestines from experimental necrotizing enterocolitis. J Pediatr Surg 2016; 51(6): 942-7.
[http://dx.doi.org/10.1016/j.jpedsurg.2016.02.061] [PMID: 27015901]
[78]
O’Connell JS, Lee C, Farhat N, et al. Administration of extracellular vesicles derived from human amniotic fluid stem cells: A new treat-ment for necrotizing enterocolitis. Pediatr Surg Int 2021; 37(3): 301-9.
[http://dx.doi.org/10.1007/s00383-020-04826-6] [PMID: 33566163]
[79]
Yin Y, Qin Z, Xu X, et al. Inhibition of miR-124 improves neonatal necrotizing enterocolitis via an MYPT1 and TLR9 signal regulation mechanism. J Cell Physiol 2019; 234(7): 10218-24.
[http://dx.doi.org/10.1002/jcp.27691] [PMID: 30480807]
[80]
Nguyen DN, Stensballe A, Lai JC, et al. Elevated levels of circulating cell-free DNA and neutrophil proteins are associated with neonatal sepsis and necrotizing enterocolitis in immature mice, pigs and infants. Innate Immun 2017; 23(6): 524-36.
[http://dx.doi.org/10.1177/1753425917719995] [PMID: 28714327]
[81]
Klinke M, Vincent D, Trochimiuk M, et al. Degradation of extracellular DNA significantly ameliorates necrotizing enterocolitis severity in mice. J Surg Res 2019; 235: 513-20.
[http://dx.doi.org/10.1016/j.jss.2018.10.041] [PMID: 30691836]
[82]
Namachivayam K. MohanKumar K, Shores DR, et al Targeted inhibition of thrombin attenuates murine neonatal necrotizing enterocolitis. Proc Natl Acad Sci USA 2020; 117(20): 10958-69.
[http://dx.doi.org/10.1073/pnas.1912357117] [PMID: 32366656]
[83]
Xia X, Wang D, Yu L, et al. Activated M1 macrophages suppress c-kit expression via TNF-α-mediated upregulation of miR-222 in neona-tal necrotizing enterocolitis. Inflamm Res 2021; 70(3): 343-58.
[http://dx.doi.org/10.1007/s00011-021-01441-6] [PMID: 33564933]
[84]
Wei J, Besner GE. M1 to M2 macrophage polarization in heparin-binding epidermal growth factor-like growth factor therapy for necrotiz-ing enterocolitis. J Surg Res 2015; 197(1): 126-38.
[http://dx.doi.org/10.1016/j.jss.2015.03.023] [PMID: 25913486]
[85]
Ren W, Liu G, Chen S, et al. Melatonin signaling in T cells: Functions and applications. J Pineal Res 2017; 62(3), e12394.
[http://dx.doi.org/10.1111/jpi.12394] [PMID: 28152213]
[86]
Ma F, Hao H, Gao X, et al. Melatonin ameliorates necrotizing enterocolitis by preventing Th17/Treg imbalance through activation of the AMPK/SIRT1 pathway. Theranostics 2020; 10(17): 7730-46.
[http://dx.doi.org/10.7150/thno.45862] [PMID: 32685016]
[87]
Cho SX, Rudloff I, Lao JC, et al. Characterization of the pathoimmunology of necrotizing enterocolitis reveals novel therapeutic opportu-nities. Nat Commun 2020; 11(1): 5794.
[http://dx.doi.org/10.1038/s41467-020-19400-w] [PMID: 33188181]
[88]
Liew FY, Girard J-P, Turnquist HR. Interleukin-33 in health and disease. Nat Rev Immunol 2016; 16(11): 676-89.
[http://dx.doi.org/10.1038/nri.2016.95] [PMID: 27640624]
[89]
Leaphart CL, Cavallo J, Gribar SC, et al. A critical role for TLR4 in the pathogenesis of necrotizing enterocolitis by modulating intestinal injury and repair. J Immunol 2007; 179(7): 4808-20.
[http://dx.doi.org/10.4049/jimmunol.179.7.4808] [PMID: 17878380]
[90]
Hackam DJ, Sodhi CP, Good M. New insights into necrotizing enterocolitis: From laboratory observation to personalized prevention and treatment. J Pediatr Surg 2019; 54(3): 398-404.
[http://dx.doi.org/10.1016/j.jpedsurg.2018.06.012] [PMID: 29980346]
[91]
Sodhi CP, Neal MD, Siggers R, et al. Intestinal epithelial Toll-like receptor 4 regulates goblet cell development and is required for necrotiz-ing enterocolitis in mice. Gastroenterology 2012; 143(3): 708-718.e5.
[http://dx.doi.org/10.1053/j.gastro.2012.05.053] [PMID: 22796522]
[92]
Liu T, Zong H, Chen X, Li S, Liu Z, Cui X. Toll-like receptor 4-mediated necroptosis in the development of necrotizing enterocolitis. Pediatr Res 2022; 91(1): 73-82.
[PMID: 33731807]
[93]
Richardson WM, Sodhi CP, Russo A, Siggers RH, Afrazi A, Gribar SC. Nucleotide-binding oligomerization domain-2 inhibits toll-like receptor-4 signaling in the intestinal epithelium. Gastroenterology 2010; 139(3): 904-17.
[http://dx.doi.org/10.1053/j.gastro.2010.05.038]
[94]
Hackam D, Caplan M. Necrotizing enterocolitis: Pathophysiology from a historical context. Semin Pediatr Surg 2018; 27(1): 11-8.
[http://dx.doi.org/10.1053/j.sempedsurg.2017.11.003] [PMID: 29275810]