Remote ischemic conditioning counteracts the intestinal damage of necrotizing enterocolitis by improving intestinal microcirculation.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
02 10 2020
02 10 2020
Historique:
received:
15
01
2019
accepted:
09
09
2020
entrez:
3
10
2020
pubmed:
4
10
2020
medline:
21
10
2020
Statut:
epublish
Résumé
Necrotizing enterocolitis (NEC) is a devastating disease of premature infants with high mortality rate, indicating the need for precision treatment. NEC is characterized by intestinal inflammation and ischemia, as well derangements in intestinal microcirculation. Remote ischemic conditioning (RIC) has emerged as a promising tool in protecting distant organs against ischemia-induced damage. However, the effectiveness of RIC against NEC is unknown. To address this gap, we aimed to determine the efficacy and mechanism of action of RIC in experimental NEC. NEC was induced in mouse pups between postnatal day (P) 5 and 9. RIC was applied through intermittent occlusion of hind limb blood flow. RIC, when administered in the early stages of disease progression, decreases intestinal injury and prolongs survival. The mechanism of action of RIC involves increasing intestinal perfusion through vasodilation mediated by nitric oxide and hydrogen sulfide. RIC is a viable and non-invasive treatment strategy for NEC.
Identifiants
pubmed: 33009377
doi: 10.1038/s41467-020-18750-9
pii: 10.1038/s41467-020-18750-9
pmc: PMC7532542
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4950Subventions
Organisme : CIHR
ID : 162208
Pays : Canada
Organisme : CIHR
ID : 353857
Pays : Canada
Organisme : CIHR
ID : PJT-149046
Pays : Canada
Références
Alganabi, M., Lee, C., Bindi, E., Li, B. & Pierro, A. Recent advances in understanding necrotizing enterocolitis. F1000Res 8, https://doi.org/10.12688/f1000research.17228.1 (2019).
Neu, J. & Walker, W. A. Necrotizing enterocolitis. N. Engl. J. Med. 364, 255–264 (2011).
pubmed: 21247316
pmcid: 3628622
doi: 10.1056/NEJMra1005408
Rees, C. M., Pierro, A. & Eaton, S. Neurodevelopmental outcomes of neonates with medically and surgically treated necrotizing enterocolitis. Arch. Dis. Child Fetal Neonatal Ed. 92, F193–F198 (2007).
pubmed: 16984980
doi: 10.1136/adc.2006.099929
pmcid: 16984980
Nino, D. F. et al. Cognitive impairments induced by necrotizing enterocolitis can be prevented by inhibiting microglial activation in mouse brain. Sci. Transl. Med. 10, https://doi.org/10.1126/scitranslmed.aan0237 (2018).
Squires, R. H. et al. Natural history of pediatric intestinal failure: initial report from the Pediatric Intestinal Failure Consortium. J. Pediatr. 161, 723–728 e722 (2012).
pubmed: 22578586
pmcid: 3419777
doi: 10.1016/j.jpeds.2012.03.062
Robinson, J. R. et al. Surgical necrotizing enterocolitis. Semin. Perinatol. 41, 70–79 (2017).
pubmed: 27836422
doi: 10.1053/j.semperi.2016.09.020
pmcid: 27836422
Chen, Y. et al. Formula feeding and systemic hypoxia synergistically induce intestinal hypoxia in experimental necrotizing enterocolitis. Pediatr. Surg. Int. 32, 1115–1119 (2016).
pubmed: 27815640
doi: 10.1007/s00383-016-3997-8
pmcid: 27815640
Hsueh, W. et al. Neonatal necrotizing enterocolitis: clinical considerations and pathogenetic concepts. Pediatr. Dev. Pathol. 6, 6–23 (2003).
pubmed: 12424605
doi: 10.1007/s10024-002-0602-z
pmcid: 12424605
Chen, Y. et al. The role of ischemia in necrotizing enterocolitis. J. Pediatr. Surg. 51, 1255–1261 (2016).
pubmed: 26850908
doi: 10.1016/j.jpedsurg.2015.12.015
pmcid: 26850908
Chen, Y. et al. Formula feeding and immature gut microcirculation promote intestinal hypoxia, leading to necrotizing enterocolitis. Dis. Model Mech. 12, https://doi.org/10.1242/dmm.040998 (2019).
Downard, C. D. et al. Altered intestinal microcirculation is the critical event in the development of necrotizing enterocolitis. J. Pediatr. Surg. 46, 1023–1028 (2011).
pubmed: 21683192
doi: 10.1016/j.jpedsurg.2011.03.023
pmcid: 21683192
Yazji, I. et al. Endothelial TLR4 activation impairs intestinal microcirculatory perfusion in necrotizing enterocolitis via eNOS-NO-nitrite signaling. Proc. Natl. Acad. Sci. USA 110, 9451–9456 (2013).
pubmed: 23650378
doi: 10.1073/pnas.1219997110
pmcid: 23650378
Yu, X., Radulescu, A., Zorko, N. & Besner, G. E. Heparin-binding EGF-like growth factor increases intestinal microvascular blood flow in necrotizing enterocolitis. Gastroenterology 137, 221–230 (2009).
pubmed: 19361505
pmcid: 2704259
doi: 10.1053/j.gastro.2009.03.060
Good, M. et al. The human milk oligosaccharide 2′-fucosyllactose attenuates the severity of experimental necrotising enterocolitis by enhancing mesenteric perfusion in the neonatal intestine. Br. J. Nutr. 116, 1175–1187 (2016).
pubmed: 27609061
pmcid: 5124125
doi: 10.1017/S0007114516002944
Drucker, N. A., Jensen, A. R., Ferkowicz, M. & Markel, T. A. Hydrogen sulfide provides intestinal protection during a murine model of experimental necrotizing enterocolitis. J. Pediatr. Surg. 53, 1692–1698 (2018).
pubmed: 29338840
doi: 10.1016/j.jpedsurg.2017.12.003
pmcid: 29338840
Drucker, N. A., Jensen, A. R., Te Winkel, J. P. & Markel, T. A. Hydrogen Sulfide Donor GYY4137 acts through endothelial nitric oxide to protect intestine in murine models of necrotizing enterocolitis and intestinal ischemia. J. Surg. Res. 234, 294–302 (2019).
pubmed: 30527488
doi: 10.1016/j.jss.2018.08.048
pmcid: 30527488
Murry, C. E., Jennings, R. B. & Reimer, K. A. Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation 74, 1124–1136 (1986).
pubmed: 3769170
doi: 10.1161/01.CIR.74.5.1124
pmcid: 3769170
Kanoria, S., Jalan, R., Seifalian, A. M., Williams, R. & Davidson, B. R. Protocols and mechanisms for remote ischemic preconditioning: a novel method for reducing ischemia reperfusion injury. Transplantation 84, 445–458 (2007).
pubmed: 17713425
doi: 10.1097/01.tp.0000228235.55419.e8
pmcid: 17713425
Tapuria, N. et al. Remote ischemic preconditioning: a novel protective method from ischemia reperfusion injury—a review. J. Surg. Res. 150, 304–330 (2008).
pubmed: 19040966
doi: 10.1016/j.jss.2007.12.747
pmcid: 19040966
Lim, S. Y. & Hausenloy, D. J. Remote ischemic conditioning: from bench to bedside. Front. Physiol. 3, 27 (2012).
pubmed: 22363297
pmcid: 3282534
Brzozowski, T. et al. Ischemic preconditioning of remote organs attenuates gastric ischemia-reperfusion injury through involvement of prostaglandins and sensory nerves. Eur. J. Pharmacol. 499, 201–213 (2004).
pubmed: 15363968
pmcid: 15363968
Wang, G. L., Jiang, B. H., Rue, E. A. & Semenza, G. L. Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. Proc. Natl. Acad. Sci. USA 92, 5510–5514 (1995).
pubmed: 7539918
pmcid: 7539918
Choi, Y. H. et al. Doppler sonographic findings in an experimental rabbit model of necrotizing enterocolitis. J. Ultrasound Med. 29, 379–386 (2010).
pubmed: 20194934
pmcid: 20194934
Faingold, R. et al. Necrotizing enterocolitis: assessment of bowel viability with color doppler US. Radiology 235, 587–594 (2005).
pubmed: 15858098
pmcid: 15858098
Watkins, D. J. & Besner, G. E. The role of the intestinal microcirculation in necrotizing enterocolitis. Semin. Pediatr. Surg. 22, 83–87 (2013).
pubmed: 23611611
pmcid: 3646103
Poot, M., Gibson, L. L. & Singer, V. L. Detection of apoptosis in live cells by MitoTracker red CMXRos and SYTO dye flow cytometry. Cytometry 27, 358–364 (1997).
pubmed: 9098628
pmcid: 9098628
Dyson, R. M. et al. A role for H2S in the microcirculation of newborns: the major metabolite of H2S (thiosulphate) is increased in preterm infants. PLoS ONE 9, e105085 (2014).
pubmed: 25121737
pmcid: 4133363
Dyson, R. M. et al. Interactions of the gasotransmitters contribute to microvascular tone (dys)regulation in the preterm neonate. PLoS ONE 10, e0121621 (2015).
pubmed: 25807236
pmcid: 4373676
Hatoum, O. A., Binion, D. G., Otterson, M. F. & Gutterman, D. D. Acquired microvascular dysfunction in inflammatory bowel disease: loss of nitric oxide-mediated vasodilation. Gastroenterology 125, 58–69 (2003).
pubmed: 12851871
pmcid: 12851871
Zani, A. et al. Captopril reduces the severity of bowel damage in a neonatal rat model of necrotizing enterocolitis. J. Pediatr. Surg. 43, 308–314 (2008).
pubmed: 18280280
doi: 10.1016/j.jpedsurg.2007.10.022
pmcid: 18280280
Doherty, N. S. & Hancock, A. A. Role of alpha-2 adrenergic receptors in the control of diarrhea and intestinal motility. J. Pharmacol. Exp. Ther. 225, 269–274 (1983).
pubmed: 6132991
pmcid: 6132991
Feather-Schussler, D. N. & Ferguson, T. S. A battery of motor tests in a neonatal mouse model of cerebral palsy. J. Vis. Exp. https://doi.org/10.3791/53569 (2016).
Kitagawa, K., Saitoh, M., Ishizuka, K. & Shimizu, S. Remote limb ischemic conditioning during cerebral ischemia reduces infarct size through enhanced collateral circulation in murine focal cerebral ischemia. J. Stroke Cerebrovasc. Dis. 27, 831–838 (2018).
pubmed: 29395650
doi: 10.1016/j.jstrokecerebrovasdis.2017.09.068
pmcid: 29395650
Ren, C. et al. Limb ischemic conditioning improved cognitive deficits via eNOS-dependent augmentation of angiogenesis after chronic cerebral hypoperfusion in rats. Aging Dis. 9, 869–879 (2018).
pubmed: 30271664
pmcid: 6147592
doi: 10.14336/AD.2017.1106
Zheng, Y., Lu, X., Li, J., Zhang, Q. & Reinhardt, J. D. Impact of remote physiological ischemic training on vascular endothelial growth factor, endothelial progenitor cells and coronary angiogenesis after myocardial ischemia. Int. J. Cardiol. 177, 894–901 (2014).
pubmed: 25453408
doi: 10.1016/j.ijcard.2014.10.034
pmcid: 25453408
Kono, Y. et al. Remote ischemic conditioning improves coronary microcirculation in healthy subjects and patients with heart failure. Drug Des. Dev. Ther. 8, 1175–1181 (2014).
Ito, Y. et al. Intestinal microcirculatory dysfunction during the development of experimental necrotizing enterocolitis. Pediatr. Res. 61, 180–184 (2007).
pubmed: 17237719
doi: 10.1203/pdr.0b013e31802d77db
pmcid: 17237719
Zani, A. et al. Amniotic fluid stem cells improve survival and enhance repair of damaged intestine in necrotising enterocolitis via a COX-2 dependent mechanism. Gut. 63, 300–309 (2014).
pubmed: 23525603
doi: 10.1136/gutjnl-2012-303735
pmcid: 23525603
Fan, W. Q., Smolich, J. J., Wild, J., Yu, V. Y. & Walker, A. M. Nitric oxide modulates regional blood flow differences in the fetal gastrointestinal tract. Am. J. Physiol. 271, G598–G604 (1996).
pubmed: 8897878
pmcid: 8897878
Schmidt, M. R. et al. Intermittent peripheral tissue ischemia during coronary ischemia reduces myocardial infarction through a KATP-dependent mechanism: first demonstration of remote ischemic perconditioning. Am. J. Physiol. Heart Circ. Physiol. 292, H1883–H1890 (2007).
pubmed: 17172279
doi: 10.1152/ajpheart.00617.2006
pmcid: 17172279
Shan, H. et al. Exogenous hydrogen sulfide offers neuroprotection on intracerebral hemorrhage injury through modulating endogenous H2S metabolism in mice. Front. Cell. Neurosci. 13, 349 (2019).
pubmed: 31440142
pmcid: 6693577
doi: 10.3389/fncel.2019.00349
Wu, W. et al. H2S donor NaHS changes the production of endogenous H2S and NO in D-galactose-induced accelerated ageing. Oxid. Med. Cell. Longev. 2017, 5707830 (2017).
pubmed: 28512525
pmcid: 5420433
Lei, S., Cao, Y., Sun, J., Li, M. & Zhao, D. H2S promotes proliferation of endometrial stromal cells via activating the NF-kappaB pathway in endometriosis. Am. J. Transl. Res. 10, 4247–4257 (2018).
pubmed: 30662667
pmcid: 6325523
Förstermann, U., Boissel, J.-P. & Kleinert, H. Expressional control of the ‘constitutive’ isoforms of nitric oxide synthase (NOS I and NOS III). FASEB J. 12, 773–790 (1998).
pubmed: 9657518
doi: 10.1096/fasebj.12.10.773
pmcid: 9657518
Connelly, L., Jacobs, A. T., Palacios-Callender, M., Moncada, S. & Hobbs, A. J. Macrophage endothelial nitric-oxide synthase autoregulates cellular activation and pro-inflammatory protein expression. J. Biol. Chem. 278, 26480–26487 (2003).
pubmed: 12740377
doi: 10.1074/jbc.M302238200
pmcid: 12740377
Przyklenk, K., Bauer, B., Ovize, M., Kloner, R. A. & Whittaker, P. Regional ischemic ‘preconditioning’ protects remote virgin myocardium from subsequent sustained coronary occlusion. Circulation 87, 893–899 (1993).
pubmed: 7680290
doi: 10.1161/01.CIR.87.3.893
pmcid: 7680290
Kerendi, F. et al. Remote postconditioning. Brief renal ischemia and reperfusion applied before coronary artery reperfusion reduces myocardial infarct size via endogenous activation of adenosine receptors. Basic Res. Cardiol. 100, 404–412 (2005).
pubmed: 15965583
doi: 10.1007/s00395-005-0539-2
pmcid: 15965583
Souza Filho, M. V. et al. Hind limb ischemic preconditioning induces an anti-inflammatory response by remote organs in rats. Braz. J. Med. Biol. Res. 42, 921–929 (2009).
pubmed: 19738981
doi: 10.1590/S0100-879X2009005000025
pmcid: 19738981
Ren, C., Gao, X., Steinberg, G. K. & Zhao, H. Limb remote-preconditioning protects against focal ischemia in rats and contradicts the dogma of therapeutic time windows for preconditioning. Neuroscience 151, 1099–1103 (2008).
pubmed: 18201834
doi: 10.1016/j.neuroscience.2007.11.056
pmcid: 18201834
Kuzuya, T. et al. Delayed effects of sublethal ischemia on the acquisition of tolerance to ischemia. Circ. Res. 72, 1293–1299 (1993).
pubmed: 8495557
pmcid: 8495557
Jiang, Q. et al. Systemic redistribution of the intramyocardially injected mesenchymal stem cells by repeated remote ischaemic post-conditioning. J. Cell. Mol. Med. 22, 417–428 (2018).
pubmed: 28944999
doi: 10.1111/jcmm.13331
pmcid: 28944999
Lee, J. S. & Polin, R. A. Treatment and prevention of necrotizing enterocolitis. Semin. Neonatol. 8, 449–459 (2003).
pubmed: 15001117
pmcid: 7128229
doi: 10.1016/S1084-2756(03)00123-4
Walsh, M. C. & Kliegman, R. M. Necrotizing enterocolitis: treatment based on staging criteria. Pediatr. Clin. N. Am. 33, 179–201 (1986).
doi: 10.1016/S0031-3955(16)34975-6
Bell, M. J. et al. Neonatal necrotizing enterocolitis. Therapeutic decisions based upon clinical staging. Ann. Surg. 187, 1–7 (1978).
pubmed: 413500
pmcid: 1396409
doi: 10.1097/00000658-197801000-00001
Eitel, I. et al. Cardioprotection by combined intrahospital remote ischaemic perconditioning and postconditioning in ST-elevation myocardial infarction: the randomized LIPSIA CONDITIONING trial. Eur. Heart J. 36, 3049–3057 (2015).
pubmed: 26385956
doi: 10.1093/eurheartj/ehv463
pmcid: 26385956
Botker, H. E. et al. Remote ischaemic conditioning before hospital admission, as a complement to angioplasty, and effect on myocardial salvage in patients with acute myocardial infarction: a randomised trial. Lancet 375, 727–734 (2010).
pubmed: 20189026
doi: 10.1016/S0140-6736(09)62001-8
pmcid: 20189026
Gaspar, A. et al. Randomized controlled trial of remote ischaemic conditioning in ST-elevation myocardial infarction as adjuvant to primary angioplasty (RIC-STEMI). Basic Res. Cardiol. 113, 14 (2018).
pubmed: 29516192
doi: 10.1007/s00395-018-0672-3
pmcid: 29516192
Kang, Z. et al. Remote ischemic preconditioning upregulates microRNA-21 to protect the kidney in children with congenital heart disease undergoing cardiopulmonary bypass. Pediatr. Nephrol. 33, 911–919 (2018).
pubmed: 29197999
doi: 10.1007/s00467-017-3851-9
pmcid: 29197999
Zhong, H. et al. Cardioprotective effect of remote ischemic postconditioning on children undergoing cardiac surgery: a randomized controlled trial. Paediatr. Anaesth. 23, 726–733 (2013).
pubmed: 23668330
doi: 10.1111/pan.12181
pmcid: 23668330
Luo, W., Zhu, M., Huang, R. & Zhang, Y. A comparison of cardiac post-conditioning and remote pre-conditioning in paediatric cardiac surgery. Cardiol. Young. 21, 266–270 (2011).
pubmed: 21262079
pmcid: 21262079
Zhou, W. et al. Limb ischemic preconditioning reduces heart and lung injury after an open heart operation in infants. Pediatr. Cardiol. 31, 22–29 (2010).
pubmed: 19787388
pmcid: 19787388
Cheung, M. M. et al. Randomized controlled trial of the effects of remote ischemic preconditioning on children undergoing cardiac surgery: first clinical application in humans. J. Am. Coll. Cardiol. 47, 2277–2282 (2006).
pubmed: 16750696
pmcid: 16750696
Zhao, J. J. et al. Remote ischemic postconditioning for ischemic stroke: a systematic review and meta-analysis of randomized controlled trials. Chin. Med. J. 131, 956–965 (2018).
pubmed: 29664057
pmcid: 5912063
Hausenloy, D. J. et al. Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial. Lancet 394, 1415–1424 (2019).
pubmed: 31500849
pmcid: 6891239
Meybohm, P. et al. A multicenter trial of remote ischemic preconditioning for heart surgery. N. Engl. J. Med. 373, 1397–1407 (2015).
pubmed: 26436208
pmcid: 26436208
Hausenloy, D. J. et al. Remote ischemic preconditioning and outcomes of cardiac surgery. N. Engl. J. Med. 373, 1408–1417 (2015).
pubmed: 26436207
pmcid: 26436207
Struck, R. et al. Effect of remote ischemic preconditioning on intestinal ischemia-reperfusion injury in adults undergoing on-pump CABG surgery: a randomized controlled pilot trial. J. Cardiothorac. Vasc. Anesth. 32, 1243–1247 (2018).
pubmed: 29429928
pmcid: 29429928
McCrindle, B. W. et al. Remote ischemic preconditioning in children undergoing cardiac surgery with cardiopulmonary bypass: a single-center double-blinded randomized trial. J. Am. Heart Assoc. 3, https://doi.org/10.1161/JAHA.114.000964 (2014).
Kharbanda, R. K. et al. Transient limb ischemia induces remote ischemic preconditioning in vivo. Circulation 106, 2881–2883 (2002).
pubmed: 12460865
pmcid: 12460865
Sylvester, K. G. et al. A novel urine peptide biomarker-based algorithm for the prognosis of necrotising enterocolitis in human infants. Gut 63, 1284–1292 (2014).
pubmed: 24048736
doi: 10.1136/gutjnl-2013-305130
pmcid: 24048736
Ji, J. et al. A data-driven algorithm integrating clinical and laboratory features for the diagnosis and prognosis of necrotizing enterocolitis. PLoS ONE 9, e89860 (2014).
pubmed: 24587080
pmcid: 3938509
doi: 10.1371/journal.pone.0089860
Ballance, W. A., Dahms, B. B., Shenker, N. & Kliegman, R. M. Pathology of neonatal necrotizing enterocolitis: a ten-year experience. J. Pediatr. 117, S6–S13 (1990).
pubmed: 2362230
doi: 10.1016/S0022-3476(05)81124-2
pmcid: 2362230
Wang, Y. et al. Remote ischemic conditioning may improve outcomes of patients with cerebral small-vessel disease. Stroke 48, 3064–3072 (2017).
pubmed: 29042490
doi: 10.1161/STROKEAHA.117.017691
pmcid: 29042490
Pryds, K. et al. Remote ischaemic conditioning and healthcare system delay in patients with ST-segment elevation myocardial infarction. Heart 102, 1023–1028 (2016).
pubmed: 26911520
doi: 10.1136/heartjnl-2015-308980
pmcid: 26911520
Zani, A. et al. A spectrum of intestinal injury models in neonatal mice. Pediatr. Surg. Int. 32, 65–70 (2016).
pubmed: 26552653
doi: 10.1007/s00383-015-3813-x
pmcid: 26552653
Kisanuki, Y. Y. et al. Tie2-Cre transgenic mice: a new model for endothelial cell-lineage analysis in vivo. Dev. Biol. 230, 230–242 (2001).
pubmed: 11161575
doi: 10.1006/dbio.2000.0106
pmcid: 11161575
Chan, K. L. et al. Revisiting ischemia and reperfusion injury as a possible cause of necrotizing enterocolitis: Role of nitric oxide and superoxide dismutase. J. Pediatr. Surg. 37, 828–834 (2002).
pubmed: 12037744
doi: 10.1053/jpsu.2002.32882
pmcid: 12037744
Szabo, C. Hydrogen sulphide and its therapeutic potential. Nat. Rev. Drug Discov. 6, 917–935 (2007).
pubmed: 17948022
doi: 10.1038/nrd2425
pmcid: 17948022
Ran-Ressler, R. R. et al. Branched chain fatty acids reduce the incidence of necrotizing enterocolitis and alter gastrointestinal microbial ecology in a neonatal rat model. PLoS ONE 6, e29032 (2011).
pubmed: 22194981
pmcid: 3237582
doi: 10.1371/journal.pone.0029032
Li, B. et al. Intestinal epithelial injury induced by maternal separation is protected by hydrogen sulfide. J. Pediatr. Surg. 52, 40–44 (2017).
pubmed: 27836362
doi: 10.1016/j.jpedsurg.2016.10.013
pmcid: 27836362
Tang, P. et al. In vivo two-photon imaging of axonal dieback, blood flow, and calcium influx with methylprednisolone therapy after spinal cord injury. Sci. Rep. 5, 9691 (2015).
pubmed: 25989524
pmcid: 4437044
doi: 10.1038/srep09691
Jodal, M. & Lundgren, O. Countercurrent mechanisms in the mammalian gastrointestinal tract. Gastroenterology 91, 225–241 (1986).
pubmed: 3519349
doi: 10.1016/0016-5085(86)90463-4
pmcid: 3519349
Koike, Y. et al. Live imaging of fetal intra-abdominal organs using two-photon laser-scanning microscopy. Methods Mol. Biol. 1752, 63–69 (2018).
pubmed: 29564762
doi: 10.1007/978-1-4939-7714-7_6
pmcid: 29564762