Reduced Serum Brain-Derived Neurotrophic Factor in Infants Affected by Severe Bronchiolitis


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Abstract

Background:Bronchiolitis is an acute viral infection of the lower respiratory tract, typical of infants in their first year of life and causing hypoxia in the most serious cases. Bronchiolitis recognizes various demographic risk factors that are associated with greater clinical severity; however, no laboratory factors are yet able to correlate with the clinical severity. Neurotrophins as Brain-Derived Neurotrophic Factor (BDNF) are mediators of neuronal plasticity. BDNF is constitutively expressed in smooth muscle cells and epithelium of the lower respiratory tract, and as it is released during inflammatory conditions, serum levels may have a relevant role in the prognosis of infants with bronchiolitis.

Objective:In the present pilot study, we aimed to disclose the presence of serum BDNF in infants hospitalized with bronchiolitis at discharge as a disease severity indicator.

Methods and Results:Serum BDNF, measured at hospital discharge, was significantly lower in severe bronchiolitis (expressed as O2-supplemented infants). Furthermore, no changes were disclosed for the Tropomyosin receptor kinase B, the main BDNF receptor and neurofilament light chain, a biomarker of neuronal degeneration.

Conclusion:Low serum BDNF in infants with severe bronchiolitis could be associated with a higher utilization by lung cells or with an altered production by lung cells. Therefore, further research is required to study if a decreased production or increased consumption of this biomarker is at the base of the above-mentioned findings.

About the authors

Raffaella Nenna

Department of Experimental Medicine, Medical Faculty, Sapienza University of Rome

Email: info@benthamscience.net

Carla Petrella

Department of Sense Organs, Medical Faculty, Institute of Biochemistry and Cell Biology (IBBC-CNR), Sapienza University of Rome

Email: info@benthamscience.net

Enea Bonci

Department of Experimental Medicine, Medical Faculty, Sapienza University of Rome

Email: info@benthamscience.net

Paola Papoff

Department of Experimental Medicine, Medical Faculty, Sapienza University of Rome

Email: info@benthamscience.net

Margherita Jorgi

Department of Experimental Medicine, Medical Faculty, Sapienza University of Rome,

Email: info@benthamscience.net

Laura Petrarca

Department of Experimental Medicine, Medical Faculty, Sapienza University of Rome

Email: info@benthamscience.net

Maria Conti

Department of Experimental Medicine, Medical Faculty, Sapienza University of Rome

Email: info@benthamscience.net

Christian Barbato

Department of Sense Organs, Medical Faculty, Institute of Biochemistry and Cell Biology (IBBC-CNR), Sapienza University of Rome

Email: info@benthamscience.net

Alessandra Pietrangeli

Virology Laboratory, Department of Molecular Medicine, Sapienza" University

Email: info@benthamscience.net

Marco Fiore

Department of Sense Organs, Medical Faculty, Institute of Biochemistry and Cell Biology (IBBC-CNR), Sapienza University of Rome

Author for correspondence.
Email: info@benthamscience.net

Fabio Midulla

Department of Maternal Infantile and Urological Sciences, Sapienza University of Rome

Author for correspondence.
Email: info@benthamscience.net

BROME Group

Department of Experimental Medicine, Medical Faculty,, Sapienza University of Rome

Email: info@benthamscience.net

References

  1. Midulla, F.; Petrarca, L.; Frassanito, A.; Di Mattia, G.; Zicari, A.M.; Nenna, R. Bronchiolitis clinics and medical treatment. Minerva Pediatr., 2018, 70(6), 600-611. doi: 10.23736/S0026-4946.18.05334-3 PMID: 30334624
  2. Shi, T.; McAllister, D.A.; O’Brien, K.L.; Simoes, E.A.F.; Madhi, S.A.; Gessner, B.D.; Polack, F.P.; Balsells, E.; Acacio, S.; Aguayo, C.; Alassani, I.; Ali, A.; Antonio, M.; Awasthi, S.; Awori, J.O.; Azziz-Baumgartner, E.; Baggett, H.C.; Baillie, V.L.; Balmaseda, A.; Barahona, A.; Basnet, S.; Bassat, Q.; Basualdo, W.; Bigogo, G.; Bont, L.; Breiman, R.F.; Brooks, W.A.; Broor, S.; Bruce, N.; Bruden, D.; Buchy, P.; Campbell, S.; Carosone-Link, P.; Chadha, M.; Chipeta, J.; Chou, M.; Clara, W.; Cohen, C.; de Cuellar, E.; Dang, D.A.; Dash-yandag, B.; Deloria-Knoll, M.; Dherani, M.; Eap, T.; Ebruke, B.E.; Echavarria, M.; de Freitas, L.E.C.C.; Fasce, R.A.; Feikin, D.R.; Feng, L.; Gentile, A.; Gordon, A.; Goswami, D.; Goyet, S.; Groome, M.; Halasa, N.; Hirve, S.; Homaira, N.; Howie, S.R.C.; Jara, J.; Jroundi, I.; Kartasasmita, C.B.; Khuri-Bulos, N.; Kotloff, K.L.; Krishnan, A.; Libster, R.; Lopez, O.; Lucero, M.G.; Lucion, F.; Lupisan, S.P.; Marcone, D.N.; McCracken, J.P.; Mejia, M.; Moisi, J.C.; Montgomery, J.M.; Moore, D.P.; Moraleda, C.; Moyes, J.; Munywoki, P.; Mutyara, K.; Nicol, M.P.; Nokes, D.J.; Nymadawa, P.; da Costa Oliveira, M.T.; Oshitani, H.; Pandey, N.; Paranhos-Baccalà, G.; Phillips, L.N.; Picot, V.S.; Rahman, M.; Rakoto-Andrianarivelo, M.; Rasmussen, Z.A.; Rath, B.A.; Robinson, A.; Romero, C.; Russomando, G.; Salimi, V.; Sawatwong, P.; Scheltema, N.; Schweiger, B.; Scott, J.A.G.; Seidenberg, P.; Shen, K.; Singleton, R.; Sotomayor, V.; Strand, T.A.; Sutanto, A.; Sylla, M.; Tapia, M.D.; Thamthitiwat, S.; Thomas, E.D.; Tokarz, R.; Turner, C.; Venter, M.; Waicharoen, S.; Wang, J.; Watthanaworawit, W.; Yoshida, L.M.; Yu, H.; Zar, H.J.; Campbell, H.; Nair, H. Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in young children in 2015: A systematic review and modelling study. Lancet, 2017, 390(10098), 946-958. doi: 10.1016/S0140-6736(17)30938-8 PMID: 28689664
  3. Manti, S.; Staiano, A.; Orfeo, L.; Midulla, F.; Marseglia, G.L.; Ghizzi, C.; Zampogna, S.; Carnielli, V.P.; Favilli, S.; Ruggieri, M.; Perri, D.; Di Mauro, G.; Gattinara, G.C.; D’Avino, A.; Becherucci, P.; Prete, A.; Zampino, G.; Lanari, M.; Biban, P.; Manzoni, P.; Esposito, S.; Corsello, G.; Baraldi, E. UPDATE - 2022 Italian guidelines on the management of bronchiolitis in infants. Ital. J. Pediatr., 2023, 49(1), 19. doi: 10.1186/s13052-022-01392-6 PMID: 36765418
  4. Øymar, K.; Skjerven, H.O.; Mikalsen, I.B. Acute bronchiolitis in infants, a review. Scand. J. Trauma Resusc. Emerg. Med., 2014, 22(1), 23. doi: 10.1186/1757-7241-22-23 PMID: 24694087
  5. Bukiya, A.N. Fetal cerebral artery mitochondrion as target of prenatal alcohol exposure. Int. J. Environ. Res. Public Health, 2019, 16(9), 1586. doi: 10.3390/ijerph16091586 PMID: 31067632
  6. de Sonnaville, E.S.V.; Oosterlaan, J.; Ghiassi, S.A.; van Leijden, O.; van Ewijk, H.; Knoester, H.; van Woensel, J.B.M.; Kӧnigs, M. Long-term neurocognitive outcomes after pediatric intensive care: Exploring the role of drug exposure. Pediatr. Res., 2023, 94(2), 603-610. doi: 10.1038/s41390-022-02460-7 PMID: 36694029
  7. Shein, S.L.; Slain, K.N.; Clayton, J.A.; McKee, B.; Rotta, A.T.; Wilson-Costello, D. Neurologic and functional morbidity in critically ill children with bronchiolitis. Pediatr. Crit. Care Med., 2017, 18(12), 1106-1113. doi: 10.1097/PCC.0000000000001337 PMID: 28930814
  8. Andrade, C.A.; Kalergis, A.M.; Bohmwald, K. Potential neurocognitive symptoms due to respiratory syncytial virus infection. Pathogens, 2021, 11(1), 47. doi: 10.3390/pathogens11010047 PMID: 35055995
  9. Nenna, R.; Cutrera, R.; Frassanito, A.; Alessandroni, C.; Nicolai, A.; Cangiano, G.; Petrarca, L.; Arima, S.; Caggiano, S.; Ullmann, N.; Papoff, P.; Bonci, E.; Moretti, C.; Midulla, F. Modifiable risk factors associated with bronchiolitis. Ther. Adv. Respir. Dis., 2017, 11(10), 393-401. doi: 10.1177/1753465817725722 PMID: 28812472
  10. Di Mattia, G.; Nenna, R.; Mancino, E.; Rizzo, V.; Pierangeli, A.; Villani, A.; Midulla, F. During the COVID‐19 pandemic where has respiratory syncytial virus gone? Pediatr. Pulmonol., 2021, 56(10), 3106-3109. doi: 10.1002/ppul.25582 PMID: 34273135
  11. Nenna, R.; Evangelisti, M.; Frassanito, A.; Scagnolari, C.; Pierangeli, A.; Antonelli, G.; Nicolai, A.; Arima, S.; Moretti, C.; Papoff, P.; Villa, M.P.; Midulla, F. Respiratory syncytial virus bronchiolitis, weather conditions and air pollution in an Italian urban area: An observational study. Environ. Res., 2017, 158, 188-193. doi: 10.1016/j.envres.2017.06.014 PMID: 28647513
  12. Panickar, J.R.; Dodd, S.R.; Smyth, R.L.; Couriel, J.M. Trends in deaths from respiratory illness in children in England and Wales from 1968 to 2000. Thorax, 2005, 60(12), 1035-1038. doi: 10.1136/thx.2005.044750 PMID: 16143582
  13. Be’er, M.; Bushmitz, S.; Cahal, M.; Sadot, E.; Yochpaz, S.; Besor, O.; Amirav, I.; Lavie, M. Asthma risk after a pediatric intensive care unit admission for respiratory syncytial virus bronchiolitis. Pediatr. Pulmonol., 2022, 57(7), 1677-1683. doi: 10.1002/ppul.25953 PMID: 35579122
  14. Jartti, T.; Mäkelä, M.J.; Vanto, T.; Ruuskanen, O. The link between bronchiolitis and asthma. Infect. Dis. Clin. North Am., 2005, 19(3), 667-689. doi: 10.1016/j.idc.2005.05.010 PMID: 16102655
  15. Nenna, R.; Ferrara, M.; Nicolai, A.; Pierangeli, A.; Scagnolari, C.; Papoff, P.; Antonelli, G.; Moretti, C.; Midulla, F. Viral load in infants hospitalized for respiratory syncytial virus bronchiolitis correlates with recurrent wheezing at thirty-six-month follow-up. Pediatr. Infect. Dis. J., 2015, 34(10), 1131-1132. doi: 10.1097/INF.0000000000000825 PMID: 26132826
  16. Kneyber, M.C.J.; Steyerberg, E.W.; de Groot, R.; Moll, H.A. Long‐term effects of respiratory syncytial virus (RSV) bronchiolitis in infants and young children: A quantitative review. Acta Paediatr., 2000, 89(6), 654-660. doi: 10.1111/j.1651-2227.2000.tb00359.x PMID: 10914957
  17. Vanker, A.; Gie, R.P.; Zar, H.J. The association between environmental tobacco smoke exposure and childhood respiratory disease: A review. Expert Rev. Respir. Med., 2017, 11(8), 661-673. doi: 10.1080/17476348.2017.1338949 PMID: 28580865
  18. Frassanito, A.; Nenna, R.; Arima, S.; Petrarca, L.; Pierangeli, A.; Scagnolari, C.; Di Mattia, G.; Mancino, E.; Matera, L.; Porta, D.; Rusconi, F.; Midulla, F. Modifiable environmental factors predispose term infants to bronchiolitis but bronchiolitis itself predisposes to respiratory sequelae. Pediatr. Pulmonol., 2022, 57(3), 640-647. doi: 10.1002/ppul.25794 PMID: 34918490
  19. Brown, P.M.; Schneeberger, D.L.; Piedimonte, G. Biomarkers of respiratory syncytial virus (RSV) infection: specific neutrophil and cytokine levels provide increased accuracy in predicting disease severity. Paediatr. Respir. Rev., 2015, 16(4), 232-240. doi: 10.1016/j.prrv.2015.05.005 PMID: 26074450
  20. Fiore, M.; Triaca, V.; Amendola, T.; Tirassa, P.; Aloe, L. Brain NGF and EGF administration improves passive avoidance response and stimulates brain precursor cells in aged male mice. Physiol. Behav., 2002, 77(2-3), 437-443. doi: 10.1016/S0031-9384(02)00875-2 PMID: 12419420
  21. Carito, V.; Ceccanti, M.; Ferraguti, G.; Coccurello, R.; Ciafrè, S.; Tirassa, P.; Fiore, M. NGF and BDNF alterations by prenatal alcohol exposure. Curr. Neuropharmacol., 2019, 17(4), 308-317. doi: 10.2174/1570159X15666170825101308 PMID: 28847297
  22. Ricci, A.; Felici, L.; Mariotta, S.; Mannino, F.; Schmid, G.; Terzano, C.; Cardillo, G.; Amenta, F.; Bronzetti, E. Neurotrophin and neurotrophin receptor protein expression in the human lung. Am. J. Respir. Cell Mol. Biol., 2004, 30(1), 12-19. doi: 10.1165/rcmb.2002-0110OC PMID: 12791675
  23. Ricci, A.; Graziano, P.; Bronzetti, E.; Saltini, C.; Sciacchitano, S.; Cherubini, E.; Renzoni, E.; Du Bois, R.M.; Grutters, J.C.; Mariotta, S. Increased pulmonary neurotrophin protein expression in idiopathic interstitial pneumonias. Sarcoidosis Vasc. Diffuse Lung Dis., 2007, 24(1), 13-23. PMID: 18069415
  24. Stoll, P.; Wuertemberger, U.; Bratke, K.; Zingler, C.; Virchow, C.J.; Lommatzsch, M. Stage-dependent association of BDNF and TGF-β1 with lung function in stable COPD. Respir. Res., 2012, 13(1), 116. doi: 10.1186/1465-9921-13-116 PMID: 23245944
  25. Braun, A.; Lommatzsch, M.; Neuhaus-Steinmetz, U.; Quarcoo, D.; Glaab, T.; McGregor, G.P.; Fischer, A.; Renz, H. Brain‐derived neurotrophic factor (BDNF) contributes to neuronal dysfunction in a model of allergic airway inflammation. Br. J. Pharmacol., 2004, 141(3), 431-440. doi: 10.1038/sj.bjp.0705638 PMID: 14718253
  26. Rochlitzer, S.; Nassenstein, C.; Braun, A. The contribution of neurotrophins to the pathogenesis of allergic asthma. Biochem. Soc. Trans., 2006, 34(4), 594-599. doi: 10.1042/BST0340594 PMID: 16856870
  27. Joachim, R.A.; Noga, O.; Sagach, V.; Hanf, G.; Fliege, H.; Kocalevent, R.D.; Peters, E.M.; Klapp, B.F. Correlation between immune and neuronal parameters and stress perception in allergic asthmatics. Clin. Exp. Allergy, 2008, 38(2), 283-290. doi: 10.1111/j.1365-2222.2007.02899.x PMID: 18070153
  28. Lommatzsch, M.; Niewerth, A.; Klotz, J.; Schulte-Herbrüggen, O.; Zingler, C.; Schuff-Werner, P.; Virchow, J.C. Platelet and plasma BDNF in lower respiratory tract infections of the adult. Respir. Med., 2007, 101(7), 1493-1499. doi: 10.1016/j.rmed.2007.01.003 PMID: 17317133
  29. Tortorolo, L.; Langer, A.; Polidori, G.; Vento, G.; Stampachiacchere, B.; Aloe, L.; Piedimonte, G. Neurotrophin overexpression in lower airways of infants with respiratory syncytial virus infection. Am. J. Respir. Crit. Care Med., 2005, 172(2), 233-237. doi: 10.1164/rccm.200412-1693OC PMID: 15879412
  30. Chmielewska, N.; Szyndler, J.; Makowska, K.; Wojtyna, D.; Maciejak, P.; Płaźnik, A. Looking for novel, brain-derived, peripheral biomarkers of neurological disorders. Neurol. Neurochir. Pol., 2018, 52(3), 318-325. doi: 10.1016/j.pjnns.2018.02.002 PMID: 29478670
  31. Giovannoni, G. Peripheral blood neurofilament light chain levels: The neurologist’s C-reactive protein? Brain, 2018, 141(8), 2235-2237. doi: 10.1093/brain/awy200 PMID: 30060019
  32. Nayani, K.; Naeem, R.; Munir, O.; Naseer, N.; Feroze, A.; Brown, N.; Mian, A.I. The clinical respiratory score predicts paediatric critical care disposition in children with respiratory distress presenting to the emergency department. BMC Pediatr., 2018, 18(1), 339. doi: 10.1186/s12887-018-1317-2 PMID: 30376827
  33. Destino, L.; Weisgerber, M.C.; Soung, P.; Bakalarski, D.; Yan, K.; Rehborg, R.; Wagner, D.R.; Gorelick, M.H.; Simpson, P. Validity of respiratory scores in bronchiolitis. Hosp. Pediatr., 2012, 2(4), 202-209. doi: 10.1542/hpeds.2012-0013 PMID: 24313026
  34. Nenna, R.; Fedele, G.; Frassanito, A.; Petrarca, L.; Di Mattia, G.; Pierangeli, A.; Scagnolari, C.; Papoff, P.; Schiavoni, I.; Leone, P.; Moretti, C.; Midulla, F. Increased T-helper Cell 2 response in infants with respiratory syncytial virus bronchiolitis hospitalized outside epidemic peak. Pediatr. Infect. Dis. J., 2020, 39(1), 61-67. doi: 10.1097/INF.0000000000002505 PMID: 31815840
  35. Tore, F.; Tonchev, A.; Fiore, M.; Tuncel, N.; Atanassova, P.; Aloe, L.; Chaldakov, G. From adipose tissue protein secretion to adipopharmacology of disease. Immunol. Endocr. Metab. Agents Med. Chem., 2007, 7(2), 149-155. doi: 10.2174/187152207780363712
  36. Yano, H.; Chao, M.V. Neurotrophin receptor structure and interactions. Pharm. Acta Helv., 2000, 74(2-3), 253-260. doi: 10.1016/S0031-6865(99)00036-9 PMID: 10812966
  37. Pramanik, S.; Sulistio, Y.A.; Heese, K. Neurotrophin signaling and stem cells—implications for neurodegenerative diseases and stem cell therapy. Mol. Neurobiol., 2017, 54(9), 7401-7459. doi: 10.1007/s12035-016-0214-7 PMID: 27815842
  38. Ebadi, M.; Bashir, R.M.; Heidrick, M.L.; Hamada, F.M.; El Refaey, E.; Hamed, A.; Helal, G.; Baxi, M.D.; Cerutis, D.R.; Lassi, N.K. Neurotrophins and their receptors in nerve injury and repair. Neurochem. Int., 1997, 30(4-5), 347-374. doi: 10.1016/S0197-0186(96)00071-X PMID: 9106250
  39. Prakash, Y.S.; Martin, R.J. Brain-derived neurotrophic factor in the airways. Pharmacol. Ther., 2014, 143(1), 74-86. doi: 10.1016/j.pharmthera.2014.02.006 PMID: 24560686
  40. Zingaropoli, M.A.; Pasculli, P.; Barbato, C.; Petrella, C.; Fiore, M.; Dominelli, F.; Latronico, T.; Ciccone, F.; Antonacci, M.; Liuzzi, G.M.; Talarico, G.; Bruno, G.; Galardo, G.; Pugliese, F.; Lichtner, M.; Mastroianni, C.M.; Minni, A.; Ciardi, M.R. Biomarkers of neurological damage: From acute stage to post-acute sequelae of COVID-19. Cells, 2023, 12(18), 2270. doi: 10.3390/cells12182270 PMID: 37759493
  41. Petrella, C.; Nenna, R.; Petrarca, L.; Tarani, F.; Paparella, R.; Mancino, E.; Di Mattia, G.; Conti, M.G.; Matera, L.; Bonci, E.; Ceci, F.M.; Ferraguti, G.; Gabanella, F.; Barbato, C.; Di Certo, M.G.; Cavalcanti, L.; Minni, A.; Midulla, F.; Tarani, L.; Fiore, M. Serum NGF and BDNF in Long-COVID-19 adolescents: A pilot study. Diagnostics, 2022, 12(5), 1162. doi: 10.3390/diagnostics12051162 PMID: 35626317
  42. Petrella, C.; Zingaropoli, M.A.; Ceci, F.M.; Pasculli, P.; Latronico, T.; Liuzzi, G.M.; Ciardi, M.R.; Angeloni, A.; Ettorre, E.; Menghi, M.; Barbato, C.; Ferraguti, G.; Minni, A.; Fiore, M. COVID-19 affects serum brain-derived neurotrophic factor and neurofilament light chain in aged men: Implications for morbidity and mortality. Cells, 2023, 12(4), 655. doi: 10.3390/cells12040655 PMID: 36831321
  43. Serafim Junior, V.; Fernandes, G.M.M.; Oliveira-Cucolo, J.G.; Pavarino, E.C.; Goloni-Bertollo, E.M. Role of Tropomyosin-related kinase B receptor and brain-derived neurotrophic factor in cancer. Cytokine, 2020, 136, 155270. doi: 10.1016/j.cyto.2020.155270
  44. Hang, P.Z.; Ge, F.Q.; Li, P.F.; Liu, J.; Zhu, H.; Zhao, J. The regulatory role of the BDNF/TrkB pathway in organ and tissue fibrosis. Histol. Histopathol., 2021, 36(11), 1133-1143. doi: 10.14670/HH-18-368 PMID: 34327702
  45. Matera, L.; Nenna, R.; Frassanito, A.; Petrarca, L.; Mancino, E.; Rizzo, V.; Di Mattia, G.; La Regina, D.P.; Pierangeli, A.; Midulla, F. Low lymphocyte count: A clinical severity marker in infants with bronchiolitis. Pediatr. Pulmonol., 2022, 57(7), 1770-1775. doi: 10.1002/ppul.25919 PMID: 35411598
  46. Binns, E.; Tuckerman, J.; Licciardi, P.V.; Wurzel, D. Respiratory syncytial virus, recurrent wheeze and asthma: A narrative review of pathophysiology, prevention and future directions. J. Paediatr. Child Health, 2022, 58(10), 1741-1746. doi: 10.1111/jpc.16197 PMID: 36073299
  47. Nievas-Soriano, B.J.; Martín-Latorre, M.M.; Martín-González, M.; Manzano-Agugliaro, F.; Castro-Luna, G. Worldwide research trends on bronchiolitis in pediatrics. Pediatr. Pulmonol., 2023, 58(8), 2189-2203. doi: 10.1002/ppul.26453 PMID: 37154529
  48. Zang, N.; Li, S.; Li, W.; Xie, X.; Ren, L.; Long, X.; Xie, J.; Deng, Y.; Fu, Z.; Xu, F.; Liu, E. Resveratrol suppresses persistent airway inflammation and hyperresponsivess might partially via nerve growth factor in respiratory syncytial virus-infected mice. Int. Immunopharmacol., 2015, 28(1), 121-128. doi: 10.1016/j.intimp.2015.05.031 PMID: 26044349
  49. Kyo, M.; Zhu, Z.; Nanishi, M.; Shibata, R.; Ooka, T.; Freishtat, R.J.; Mansbach, J.M.; Camargo, C.A., Jr; Hasegawa, K. Association of nasopharyngeal and serum glutathione metabolism with bronchiolitis severity and asthma risk: A prospective multicenter cohort study. Metabolites, 2022, 12(8), 674. doi: 10.3390/metabo12080674 PMID: 35893241
  50. Zhu, Y.; Fan, Q.; Cheng, L.; Chen, B. Diagnostic errors in initial misdiagnosis of foreign body aspiration in children: A retrospective observational study in a tertiary care hospital in China. Front Pediatr., 2021, 9, 694211. doi: 10.3389/fped.2021.694211 PMID: 34722414
  51. Zhu, Z.; Camargo, C.A., Jr; Raita, Y.; Fujiogi, M.; Liang, L.; Rhee, E.P.; Woodruff, P.G.; Hasegawa, K. Metabolome subtyping of severe bronchiolitis in infancy and risk of childhood asthma. J. Allergy Clin. Immunol., 2022, 149(1), 102-112. doi: 10.1016/j.jaci.2021.05.036 PMID: 34119532
  52. Calabrese, V.; Cornelius, C.; Dinkova-Kostova, A.T.; Calabrese, E.J.; Mattson, M.P. Cellular stress responses, the hormesis paradigm, and vitagenes: novel targets for therapeutic intervention in neurodegenerative disorders. Antioxid. Redox Signal., 2010, 13(11), 1763-1811. doi: 10.1089/ars.2009.3074 PMID: 20446769
  53. Calabrese, V.; Mancuso, C.; Calvani, M.; Rizzarelli, E.; Butterfield, D.A.; Stella, A.M. Nitric oxide in the central nervous system: Neuroprotection versus neurotoxicity. Nat. Rev. Neurosci., 2007, 8(10), 766-775. doi: 10.1038/nrn2214 PMID: 17882254
  54. Calabrese, V.; Cornelius, C.; Dinkova-Kostova, A.T.; Calabrese, E.J. Vitagenes, cellular stress response, and acetylcarnitine: Relevance to hormesis. Biofactors, 2009, 35(2), 146-160. doi: 10.1002/biof.22 PMID: 19449442

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