Of mitochondrion and COVID-19

References

• Davis I, Doolittle L, Guttridge D, et al. H1N1 influenza A virus infection of mice induces the warburg effect in ATII cells. Am J Respir Crit Care Med 2020;201:A3842.
   Web of Science ®Google Scholar
• Yu Y, Clippinger AJ, Alwine JC. Viral effects on metabolism: changes in glucose and glutamine utilization during human cytomegalovirus infection. Trends Microbiol 2011;19:360–7.
   PubMed Web of Science ®Google Scholar
• Darekar S, Georgiou K, Yurchenko M, et al. Epstein-barr virus immortalization of human B-cells leads to stabilization of hypoxia-induced factor 1 alpha, congruent with the Warburg effect. PLoS One 2012;7:e42072.
   PubMed Web of Science ®Google Scholar
• Ripoli M, D'Aprile A, Quarato G, et al. Hepatitis C virus-linked mitochondrial dysfunction promotes hypoxia-inducible factor 1α-mediated glycolytic adaptation. J Virol 2010;84:647–60.
   PubMed Web of Science ®Google Scholar
• Gabaldón T, Huynen MA. From endosymbiont to host-controlled organelle: the hijacking of mitochondrial protein synthesis and metabolism. Subramaniam S, ed. PLoS Comput Biol 2007;3:e219.
   PubMed Web of Science ®Google Scholar
• Pittis AA, Gabaldón T. Late acquisition of mitochondria by a host with chimaeric prokaryotic ancestry. Nature 2016;531:101–4.
   PubMed Web of Science ®Google Scholar
• Yan XJ, Yu X, Wang XP, et al. Mitochondria play an important role in the cell proliferation suppressing activity of berberine. Sci Rep 2017;7:41712.
   PubMed Web of Science ®Google Scholar
• Vakifahmetoglu-Norberg H, Ouchida AT, Norberg E. The role of mitochondria in metabolism and cell death. Biochem Biophys Res Commun 2017;482:426–31.
   PubMed Web of Science ®Google Scholar
• Handy DE, Loscalzo J. Redox regulation of mitochondrial function. Antioxid Redox Signal 2012;16:1323–67.
   PubMed Web of Science ®Google Scholar
• Reshi L, Wang H-V, Hong J-R. Modulation of mitochondria during viral infections. In: Taskin E, Guven C, eds. Mitochondrial diseases. London: InTech; 2018.
   Google Scholar
• Khan M, Syed GH, Kim SJ, et al. Mitochondrial dynamics and viral infections: a close nexus. Biochim Biophys Acta 2015;1853:2822–33.
   PubMed Web of Science ®Google Scholar
• Tiku V, Tan MW, Dikic I. Mitochondrial functions in infection and immunity. Trends Cell Biol 2020;30:263–75.
   PubMed Web of Science ®Google Scholar
• Young LS, Rickinson AB. Epstein-Barr virus: 40 years on. Nat Rev Cancer 2004;4:757–68.
   PubMed Web of Science ®Google Scholar
• Kramer T, Enquist LW. Alphaherpesvirus infection disrupts mitochondrial transport in neurons. Cell Host Microbe 2012;11:504–14.
   PubMed Web of Science ®Google Scholar
• Takada S, Shirakata Y, Kaneniwa N, et al. Association of hepatitis B virus X protein with mitochondria causes mitochondrial aggregation at the nuclear periphery, leading to cell death. Oncogene 1999;18:6965–73.
   PubMed Web of Science ®Google Scholar
• Hennet T, Peterhans E, Stocker R. Alterations in antioxidant defences in lung and liver of mice infected with influenza A virus. J General Virol 1992;73:39–46.
   PubMed Web of Science ®Google Scholar
• Henkler F, Hoare J, Waseem N, et al. Intracellular localization of the hepatitis B virus HBx protein. J General Virol 2001;82:871–82.
   PubMed Web of Science ®Google Scholar
• Heinze G, Schemper M. A solution to the problem of separation in logistic regression. Stat Med 2002;21:2409–19.
   PubMed Web of Science ®Google Scholar
• Chen H, Guo J, Wang C, et al. Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records. Lancet 2020;395:809–15.
   PubMed Web of Science ®Google Scholar
• Anon. WHO Coronavirus Disease (COVID-19) Dashboard | WHO Coronavirus Disease (COVID-19) Dashboard. https://covid19.who.int/ [accessed 5 Dec 2020].
   Google Scholar
• Guan W, Ni Z, Hu Y, et al. Clinical characteristics of coronavirus disease 2019 in China. New Engl J Med 2020;382:1708–20.
   PubMed Web of Science ®Google Scholar
• Sánchez-Recalde Á, Solano-López J, Miguelena-Hycka J, et al. COVID-19 and cardiogenic shock. Different cardiovascular presentations with high mortality. Revista Española de Cardiología 2020;73:669–72.
   Web of Science ®Google Scholar
• Du R-H, Liang L-R, Yang C-Q, et al. Predictors of mortality for patients with COVID-19 pneumonia caused by SARS-CoV-2: a prospective cohort study. Eur Respir J 2020;55:2000524.
   PubMed Web of Science ®Google Scholar
• Yang HJ, Zhang YM, Yang M, et al. Predictors of mortality for patients with COVID-19 pneumonia caused by SARS-CoV-2. Eur Respir J 2020;56:2002439.
   PubMedGoogle Scholar
• Ciceri F, Ruggeri A, Lembo R, et al. Decreased in-hospital mortality in patients with COVID-19 pneumonia. Pathogens Global Health 2020;114:281–2.
   PubMed Web of Science ®Google Scholar
• Paek JH, Kim Y, Park WY, et al. Severe acute kidney injury in COVID-19 patients is associated with in-hospital mortality. Hirst JA, ed. PLoS One 2020;15:e0243528.
   PubMedGoogle Scholar
• Malas MB, Naazie IN, Elsayed N, et al. Thromboembolism risk of COVID-19 is high and associated with a higher risk of mortality: a systematic review and meta-analysis. EClinicalMedicine 2020;29-30:100639.
   Google Scholar
• Guo T, Fan Y, Chen M, et al. Cardiovascular implications of fatal outcomes of patients with coronavirus disease 2019 (COVID-19). JAMA Cardiol 2020;5:811–8.
   PubMed Web of Science ®Google Scholar
• Bhatraju PK, Ghassemieh BJ, Nichols M, et al. Covid-19 in Critically ill patients in the seattle region – case series. New Engl J Med 2020;382:2012–22.
   PubMed Web of Science ®Google Scholar
• Zheng S, Fan J, Yu F, et al. Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang province, China, January. Retrospective cohort study. BMJ 2020;369:m1443.
   PubMed Web of Science ®Google Scholar
• Coperchini F, Chiovato L, Croce L, et al. The cytokine storm in COVID-19: an overview of the involvement of the chemokine/chemokine-receptor system. Cytokine Growth Factor Rev 2020;53:25–32.
   PubMed Web of Science ®Google Scholar
• Mittal M, Siddiqui MR, Tran K, et al. Reactive oxygen species in inflammation and tissue injury. Antioxid Redox Signal 2014;20:1126–67.
   PubMed Web of Science ®Google Scholar
• Naha PC, Davoren M, Lyng FM, et al. Reactive oxygen species (ROS) induced cytokine production and cytotoxicity of PAMAM dendrimers in J774A.1 cells. Toxicol Appl Pharmacol 2010;246:91–9.
   PubMed Web of Science ®Google Scholar
• Yang D, Elner SG, Bian ZM, et al. Pro-inflammatory cytokines increase reactive oxygen species through mitochondria and NADPH oxidase in cultured RPE cells. Exp Eye Res 2007;85:462–72.
   PubMed Web of Science ®Google Scholar
• Kamata H, Honda SI, Maeda S, et al. Reactive oxygen species promote TNFα-induced death and sustained JNK activation by inhibiting MAP kinase phosphatases. Cell 2005;120:649–61.
   PubMed Web of Science ®Google Scholar
• Murphy MP. How mitochondria produce reactive oxygen species. Biochem J 2009;417:1–13.
   PubMed Web of Science ®Google Scholar
• Saleh J, Peyssonnaux C, Singh KK, et al. Mitochondria and microbiota dysfunction in COVID-19 pathogenesis. Mitochondrion 2020;54:1–7.
   PubMed Web of Science ®Google Scholar
• Mariathasan S, Newton K, Monack DM, et al. Differential activation of the inflammasome by caspase-1 adaptors ASC and Ipaf. Nature 2004;430:213–8.
   PubMed Web of Science ®Google Scholar
• Broz P, Dixit VM. Inflammasomes: mechanism of assembly, regulation and signalling. Nat Rev Immunol 2016;16:407–20.
   PubMed Web of Science ®Google Scholar
• Martinon F, Burns K, Tschopp J. The Inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-β. Mol Cell 2002;10:417–26.
   PubMed Web of Science ®Google Scholar
• Sui A, Chen X, Shen J, et al. Inhibiting the NLRP3 inflammasome with MCC950 ameliorates retinal neovascularization and leakage by reversing the IL-1β/IL-18 activation pattern in an oxygen-induced ischemic retinopathy mouse model. Cell Death Dis 2020;11:901.
   PubMed Web of Science ®Google Scholar
• Shaw MH, Reimer T, Kim YG, et al. NOD-like receptors (NLRs): bona fide intracellular microbial sensors. Curr Opin Immunol 2008;20:377–82.
   PubMed Web of Science ®Google Scholar
• Swanson KV, Deng M, Ting JPY. The NLRP3 inflammasome: molecular activation and regulation to therapeutics. Nat Rev Immunol 2019;19:477–89.
   PubMed Web of Science ®Google Scholar
• Kauppinen A. Mitochondria-associated inflammasome activation and its impact on aging and age-related diseases. In: Fulop T, Franceschi C, Hirokawa K, Pawelec G, eds. Handbook of immunosenescence. Cham: Springer International Publishing; 2018:1–20.
   Google Scholar
• Ouyang L, Gong J. Mitochondrial-targeted ubiquinone: a potential treatment for COVID-19. Med Hypotheses 2020;144:110161.
   PubMed Web of Science ®Google Scholar
• Singh KK, Chaubey G, Chen JY, et al. Decoding sars-cov-2 hijacking of host mitochondria in covid-19 pathogenesis. Am J Physiol Cell Physiol 2020;319:C258–C267.
   PubMed Web of Science ®Google Scholar
• Ganji R, Reddy PH. Impact of COVID-19 on mitochondrial-based immunity in aging and age-related diseases. Front Aging Neurosci 2020;12:614650.
   PubMed Web of Science ®Google Scholar
• Zhao N, Enns CA. Iron transport machinery of human cells, players and their interactions. In: Orlov S, ed. Current topics in membranes. Vol. 69. San Diego: Academic Press Inc.; 2012:67–93.
   Google Scholar
• Collins JF, Anderson GJ. Molecular mechanisms of intestinal iron transport. In: Johnson LR, ed. Physiology of the gastrointestinal tract. Vol. 2. London: Elsevier Inc.; 2012:1921–1947.
   Google Scholar
• Garrick MD. Human iron transporters. Genes Nutr 2011;6:45–54.
   PubMed Web of Science ®Google Scholar
• Liuzzi JP, Aydemir F, Nam H, et al. Zip14 (Slc39a14) mediates non-transferrin-bound iron uptake into cells. Proc Natl Acad Sci USA 2006;103:13612–7.
   PubMed Web of Science ®Google Scholar
• McKie AT, Barrow D, Latunde-Dada GO, et al. An iron-regulated ferric reductase associated with the absorption of dietary iron. Science 2001;291:1755–9.
   PubMed Web of Science ®Google Scholar
• Ji C, Kosman DJ. Molecular mechanisms of non-transferrin-bound and transferring-bound iron uptake in primary hippocampal neurons. J Neurochem 2015;133:668–83.
   PubMed Web of Science ®Google Scholar
• Vargas JD, Herpers B, McKie AT, et al. Stromal cell-derived receptor 2 and cytochrome b561 are functional ferric reductases. Biochim Biophys Acta 2003;1651:116–23.
   PubMed Web of Science ®Google Scholar
• Mackenzie EL, Iwasaki K, Tsuji Y. Intracellular iron transport and storage: from molecular mechanisms to health implications. Antioxid Redox Signal 2008;10:997–1030.
   PubMed Web of Science ®Google Scholar
• Arosio P, Elia L, Poli M. Ferritin, cellular iron storage and regulation. IUBMB Life 2017;69:414–22.
   PubMed Web of Science ®Google Scholar
• De Domenico I, McVey Ward D, Kaplan J. Regulation of iron acquisition and storage: consequences for iron-linked disorders. Nat Rev Mol Cell Biol 2008;9:72–81.
   PubMed Web of Science ®Google Scholar
• Bystrom LM, Guzman ML, Rivella S. Iron and reactive oxygen species: friends or foes of cancer cells? Antioxid Redox Signal 2014;20:1917–24.
   PubMed Web of Science ®Google Scholar
• Dixon SJ, Stockwell BR. The role of iron and reactive oxygen species in cell death. Nat Chem Biol 2014;10:9–17.
   PubMed Web of Science ®Google Scholar
• Cairo G, Recalcati S. Iron-regulatory proteins: molecular biology and pathophysiological implications. Exp Rev Mol Med 2007;9:1–13.
   PubMedGoogle Scholar
• Zhou ZD, Tan EK. Iron regulatory protein (IRP)-iron responsive element (IRE) signaling pathway in human neurodegenerative diseases. Mol Neurodegener 2017;12:1–12.
   PubMed Web of Science ®Google Scholar
• Yanatori I, Richardson DR, Imada K, et al. Iron export through the transporter ferroportin 1 is modulated by the iron chaperone PCBP2. J Biol Chem 2016;291:17303–18.
   PubMed Web of Science ®Google Scholar
• Daru J, Colman K, Stanworth SJ, et al. Serum ferritin as an indicator of iron status: what do we need to know? Am J Clin Nutr 2017;106:1634S–9S. Vol
   PubMed Web of Science ®Google Scholar
• Paradkar PN, Zumbrennen KB, Paw BH, et al. Regulation of mitochondrial iron import through differential turnover of mitoferrin 1 and mitoferrin 2. Mol Cell Biol 2009;29:1007–16.
   PubMed Web of Science ®Google Scholar
• Shaw GC, Cope JJ, Li L, et al. Mitoferrin is essential for erythroid iron assimilation. Nature 2006;440:96–100.
   PubMed Web of Science ®Google Scholar
• Gao G, Chang YZ. Mitochondrial ferritin in the regulation of brain iron homeostasis and neurodegenerative diseases. Front Pharmacol 2014;5:19.
   PubMed Web of Science ®Google Scholar
• Chen C, Paw BH. Cellular and mitochondrial iron homeostasis in vertebrates. Biochim Biophys Acta 2012;1823:1459–67.
   PubMed Web of Science ®Google Scholar
• Walter PB, Knutson MD, Paler-Martinez A, et al. Iron deficiency and iron excess damage mitochondria and mitochondrial DNA in rats. Proc Natl Acad Sci USA 2002;99:2264–9.
   PubMed Web of Science ®Google Scholar
• Vlahakos VD, Marathias KP, Arkadopoulos N, et al. Hyperferritinemia in patients with COVID‐19: an opportunity for iron chelation? Artif Organs 2021;45:163–7. aor.
   PubMed Web of Science ®Google Scholar
• Abobaker A. Can iron chelation as an adjunct treatment of COVID-19 improve the clinical outcome? Eur J Clin Pharmacol 2020;76:1619–20.
   PubMed Web of Science ®Google Scholar
• Alfarouk KO, Verduzco D, Rauch C, et al. Glycolysis, tumor metabolism, cancer growth and dissemination. A new pH-based etiopathogenic perspective and therapeutic approach to an old cancer question. Oncoscience 2014;1:777–802.
   PubMedGoogle Scholar
• Alfarouk KO. Tumor metabolism, cancer cell transporters, and microenvironmental resistance. J Enzyme Inhibit Med Chem 2016;31:859–8.
   PubMed Web of Science ®Google Scholar
• Hertz L, Dienel GA. Lactate transport and transporters: general principles and functional roles in brains cells. J Neurosci Res 2005;79:11–8.
   PubMed Web of Science ®Google Scholar
• Bosshart PD, Kalbermatter D, Bonetti S, et al. Mechanistic basis of L-lactate transport in the SLC16 solute carrier family. Nature Commun 2019;10:2649.
   PubMed Web of Science ®Google Scholar
• Haas R, Smith J, Rocher-Ros V, et al. Lactate regulates metabolic and proinflammatory circuits in control of T cell migration and effector functions. PLoS Biol 2015;13:e1002202.
   PubMed Web of Science ®Google Scholar
• Pucino V, Bombardieri M, Pitzalis C, et al. Lactate at the crossroads of metabolism, inflammation, and autoimmunity. Eur J Immunol 2017;47:14–21.
   PubMed Web of Science ®Google Scholar
• Gerner RR, Klepsch V, Macheiner S, et al. NAD metabolism fuels human and mouse intestinal inflammation. Gut 2018;67:1813–23.
   PubMed Web of Science ®Google Scholar
• Adriouch S, Hubert S, Pechberty S, et al. NAD + released during inflammation participates in T cell homeostasis by inducing ART2-mediated death of naive T cells in vivo. J Immunol 2007;179:186–94.
   PubMed Web of Science ®Google Scholar
• Henry BM, Aggarwal G, Wong J, et al. Lactate dehydrogenase levels predict coronavirus disease 2019 (COVID-19) severity and mortality: a pooled analysis. Am J Emerg Med 2020;38:1722–6.
   PubMed Web of Science ®Google Scholar
• Booth AL, Abels E, McCaffrey P. Development of a prognostic model for mortality in COVID-19 infection using machine learning. Modern Pathol 2021;34:522–31.
   PubMed Web of Science ®Google Scholar
• Romero-Garcia S, Prado-Garcia H. Mitochondrial calcium: transport and modulation of cellular processes in homeostasis and cancer (Review). Int J Oncol 2019;54:1155–67.
   PubMed Web of Science ®Google Scholar
• Paupe V, Prudent J. New insights into the role of mitochondrial calcium homeostasis in cell migration. Biochem Biophys Res Commun 2018;500:75–86.
   PubMed Web of Science ®Google Scholar
• Contreras L, Drago I, Zampese E, et al. Mitochondria: the calcium connection. Biochim Biophys Acta 2010;1797:607–18.
   PubMed Web of Science ®Google Scholar
• Gandhi S, Wood-Kaczmar A, Yao Z, et al. PINK1-associated Parkinson’s disease is caused by neuronal vulnerability to calcium-induced cell death. Mol Cell 2009;33:627–38.
   PubMed Web of Science ®Google Scholar
• Dagda RK, Cherra SJ, Kulich SM, et al. Loss of PINK1 function promotes mitophagy through effects on oxidative stress and mitochondrial fission. J Biol Chem 2009;284:13843–55.
   PubMed Web of Science ®Google Scholar
• Gelmetti V, De Rosa P, Torosantucci L, et al. PINK1 and BECN1 relocalize at mitochondria-associated membranes during mitophagy and promote ER-mitochondria tethering and autophagosome formation. Autophagy 2017;13:654–69.
   PubMed Web of Science ®Google Scholar
• Jouaville LS, Pinton P, Bastianutto C, et al. Regulation of mitochondrial ATP synthesis by calcium: evidence for a long-term metabolic priming. Proc Natl Acad Sci USA 1999;96:13807–12.
   PubMed Web of Science ®Google Scholar
• Kennedy ED, Rizzuto R, Theler JM, et al. Glucose-stimulated insulin secretion correlates with changes in mitochondrial and cytosolic Ca2+ in aequorin-expressing INS-1 cells. J Clin Invest 1996;98:2524–38.
   PubMed Web of Science ®Google Scholar
• Yang C, Ma X, Wu J, et al. Low serum calcium and phosphorus and their clinical performance in detecting COVID‐19 patients. J Med Virol 2021;93:1639–51.
   PubMed Web of Science ®Google Scholar
• Gaffney PJ, Brasher M. Subunit structure of the plasmin-induced degradation products of crosslinked fibrin. BBA 1973;295:308–13.
   PubMedGoogle Scholar
• Gaffney PD. dimer. History of the discovery, characterisation and utility of this and other fibrin fragments. Fibrinol Proteol 1993;7:2–8.
   Google Scholar
• Haverkate F, Timan G. Protective effect of calcium in the plasmin degradation of fibrinogen and fibrin fragments D. Thrombosis Res 1977;10:803–12.
   PubMed Web of Science ®Google Scholar
• Favresse J, Lippi G, Roy P-M, et al. D-dimer: preanalytical, analytical, postanalytical variables, and clinical applications. Crit Rev Clin Lab Sci 2018;55:548–77.
   PubMed Web of Science ®Google Scholar
• Kelly J, Rudd A, Lewis RR, et al. Plasma D-dimers in the diagnosis of venous thromboembolism. Arch Intern Med 2002;162:747–56.
   PubMedGoogle Scholar
• Pulivarthi S, Gurram MK. Effectiveness of D-dimer as a screening test for venous thromboembolism: an update. North Am J Med Sci 2014;6:491–9.
   PubMedGoogle Scholar
• Matsuo H, Nakajima Y, Ogawa T, et al. Evaluation of D-dimer in screening deep vein thrombosis in hospitalized japanese patients with acute medical diseases/Episodes. Ann Vasc Dis 2016;9:193–200.
   PubMedGoogle Scholar
• Cho ES, McClelland PH, Cheng O, et al. Utility of D-dimer for diagnosis of deep vein thrombosis in coronavirus disease-19 infection. J Vasc Surg 2021;9:47–53.
   PubMed Web of Science ®Google Scholar
• Yu HH, Qin C, Chen M, et al. D-dimer level is associated with the severity of COVID-19. Thrombosis Res 2020;195:219–25.
   PubMed Web of Science ®Google Scholar
• Yao Y, Cao J, Wang Q, et al. D-dimer as a biomarker for disease severity and mortality in COVID-19 patients: a case control study. J Intens Care 2020;8:49.
   PubMed Web of Science ®Google Scholar
• Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 2020;395:1054–62.
   PubMed Web of Science ®Google Scholar
• Wang Q, Zennadi R. Oxidative stress and thrombosis during aging: the roles of oxidative stress in RBCS in venous thrombosis. Int J Mol Sci 2020;21:1–22.
   Web of Science ®Google Scholar
• Lee KH, Kim JR. Reactive oxygen species regulate the generation of urokinase plasminogen activator in human hepatoma cells via MAPK pathways after treatment with hepatocyte growth factor. Exp Mol Med 2009;41:180–8.
   PubMed Web of Science ®Google Scholar
• Tykhomyrov AA, Zhernosekov DD, Guzyk MM, et al. Plasminogen modulates formation of reactive oxygen species in human platelets. Ukrain Biochem J 2018;90:31–40.
   Google Scholar
• Wijnker PJM, Sequeira V, Foster DB, et al. Length-dependent activation is modulated by cardiac troponin I bisphosphorylation at Ser23 and Ser24 but not by Thr143 phosphorylation. Am J Physiol 2014;306:H1171–H1181.
   PubMed Web of Science ®Google Scholar
• Sun YB, Lou F, Irving M. Calcium- and myosin-dependent changes in troponin structure during activation of heart muscle. J Physiol 2009;587:155–63.
   PubMed Web of Science ®Google Scholar
• Korff S, Katus HA, Giannitsis E. Differential diagnosis of elevated troponins. Heart 2006;92:987–93.
   PubMed Web of Science ®Google Scholar
• Skeik N, Patel DC. A review of troponins in ischemic heart disease and other conditions. Int J Angiol 2007;16:53–8.
   PubMedGoogle Scholar
• Daubert MA, Jeremias A. The utility of troponin measurement to detect myocardial infarction: review of the current findings. Vasc Health Risk Manage 2010;6:691–9.
   PubMedGoogle Scholar
• Okamoto R, Hirashiki A, Cheng XW, et al. Usefulness of serum cardiac troponins T and I to predict cardiac molecular changes and cardiac damage in patients with hypertrophic cardiomyopathy. Int Heart J 2013;54:202–6.
   PubMed Web of Science ®Google Scholar
• Pankuweit S, Richter A. Mitochondrial disorders with cardiac dysfunction: an under-reported aetiology with phenotypic heterogeneity. Eur Heart J. 36:2894–7.
   PubMed Web of Science ®Google Scholar
• Amgalan D, Pekson R, Kitsis RN. Troponin release following brief myocardial ischemia: apoptosis versus necrosis. JACC 2017;2:118–21.
   Google Scholar
• Park KC, Gaze DC, Collinson PO, et al. Cardiac troponins: from myocardial infarction to chronic disease. Cardiovasc Res 2017;113:1708–18.
   PubMed Web of Science ®Google Scholar
• Tersalvi G, Vicenzi M, Calabretta D, et al. Elevated troponin in patients with coronavirus disease 2019: possible mechanisms. J Cardiac Fail 2020;26:470–5.
   PubMed Web of Science ®Google Scholar
• Lombardi CM, Carubelli V, Iorio A, et al. Association of troponin levels with mortality in italian patients hospitalized with coronavirus disease 2019: results of a multicenter study. JAMA Cardiol 2020;5:1274–E7.
   PubMed Web of Science ®Google Scholar
• Mannu GS. The non-cardiac use and significance of cardiac troponins. Scott Med J 2014;59:172–8.
   PubMed Web of Science ®Google Scholar
• Collado S, Arenas MD, Barbosa F, et al. COVID-19 in grade 4–5 chronic kidney disease patients. Kidney Blood Pressure Res 2020;45:768–74.
   PubMed Web of Science ®Google Scholar
• Ajaimy M, Melamed ML. Covid-19 in patients with kidney disease. Clin J Am Soc Nephrol 2020;15:1087–9.
   PubMedGoogle Scholar
• Alfarouk KO, Shayoub MEA, Muddathir AK, et al. Evolution of tumor metabolism might reflect carcinogenesis as a reverse evolution process (dismantling of multicellularity). Cancers 2011;3:3002–17.
   PubMedGoogle Scholar
• Andreux PA, Houtkooper RH, Auwerx J. Pharmacological approaches to restore mitochondrial function. Nat Rev Drug Discovery 2013;12:465–83.
   PubMed Web of Science ®Google Scholar
• Reshkin SJ, Bellizzi A, Caldeira S, et al. Na+/H+ exchanger-dependent intracellular alkalinization is an early event in malignant transformation and plays an essential role in the development of subsequent transformation-associated phenotypes. FASEB J 2000;14:2185–97.
   PubMed Web of Science ®Google Scholar
• Cardone RAR, Alfarouk KOK, Elliott RLR, et al. The role of sodium hydrogen exchanger 1 in dysregulation of proton dynamics and reprogramming of cancer metabolism as a sequela. Int J Mol Sci 2019;20:3694.
   Web of Science ®Google Scholar
• Alvarez BV, Villa-Abrille MC. Mitochondrial NHE1: a newly identified target to prevent heart disease. Front Physiol 2013;4:152.
   PubMed Web of Science ®Google Scholar
• Wilson L, Gage P, Ewart G. Hexamethylene amiloride blocks E protein ion channels and inhibits coronavirus replication. Virology 2006;353:294–306.
   PubMed Web of Science ®Google Scholar
• Haddad JJ, Land SC. Amiloride blockades lipopolysaccharide-induced proinflammatory cytokine biosynthesis in an IκB-α/NF-κB-dependent mechanism: evidence for the amplification of an antiinflammatory pathway in the alveolar epithelium. Am J Respir Cell Mol Biol 2002;26:114–26.
   PubMed Web of Science ®Google Scholar
• Jankun J, Skrzypczak-Jankun E. Molecular basis of specific inhibition of urokinase plasminogen activator by amiloride. Cancer Biochem Biophys 1999;17:109–23.
   PubMedGoogle Scholar
• Vassalli JD, Belin D. Amiloride selectively inhibits the urokinase-type plasminogen activator. FEBS Lett 1987;214:187–91.
   PubMed Web of Science ®Google Scholar
• Javadov S, Choi A, Rajapurohitam V, et al. NHE-1 inhibition-induced cardioprotection against ischaemia/reperfusion is associated with attenuation of the mitochondrial permeability transition. Cardiovasc Res 2007;77:416–24.
   PubMed Web of Science ®Google Scholar
• Bencze G, Bencze S, Rivera KD, et al. Mito-oncology agent: fermented extract suppresses the Warburg effect, restores oxidative mitochondrial activity, and inhibits in vivo tumor growth. Sci Rep 2020;10:14174.
   PubMed Web of Science ®Google Scholar
• Mueller T, Voigt W. Fermented wheat germ extract – nutritional supplement or anticancer drug? Nutr J 2011;10:89.
   PubMed Web of Science ®Google Scholar
• Sukkar SG, Cella F, Rovera GM, et al. A multicentric prospective open trial on the quality of life and oxidative stress in patients affected by advanced head and neck cancer treated with a new benzoquinone-rich product derived from fermented wheat germ (Avemar). Mediterranean J Nutr Metab 2008;1:37–42.
   Google Scholar
• Jeong H-Y, Choi Y-S, Lee J-K, et al. Anti-inflammatory activity of citric acid-treated wheat germ extract in lipopolysaccharide-stimulated macrophages. Nutrients 2017;9:730.
   Web of Science ®Google Scholar
• Mijnhout GS, Kollen BJ, Alkhalaf A, et al. Alpha lipoic acid for symptomatic peripheral neuropathy in patients with diabetes: a meta-analysis of randomized controlled trials. Int J Endocrinol 2012;2012:2012.
   Web of Science ®Google Scholar
• Zhong M, Sun A, Xiao T, et al. A randomized, single-blind, group sequential, active-controlled study to evaluate the clinical efficacy and safety of α-Lipoic acid for critically ill patients with coronavirus disease 2019 (COVID-19). medRxiv 2020:2020.04.15.20066266.
   Google Scholar
• Schwartz L, Seyfried T, Alfarouk KO, et al. Out of Warburg effect: an effective cancer treatment targeting the tumor specific metabolism and dysregulated pH. Semin Cancer Biol 2017;43:134–8.
   PubMed Web of Science ®Google Scholar
• Schwartz L, Supuran CT, Alfarouk KO. The Warburg effect and the hallmarks of cancer. Anti-Cancer Agents Med Chem 2017;17:164–70.
   PubMed Web of Science ®Google Scholar
• Gendrot M, Andreani J, Duflot I, et al. Methylene blue inhibits replication of SARS-CoV-2 in vitro. Int J Antimicrob Agents 2020;56:106202.
   PubMed Web of Science ®Google Scholar
• Henry M, Summa M, Patrick L, et al. A cohort of cancer patients with no reported cases of SARS-CoV-2 infection: the possible preventive role of Methylene Blue. Substantia 2020;4:888.
   Google Scholar
• Warburg O. On the origin of cancer cells. Science 1956;123:309–14.
   PubMed Web of Science ®Google Scholar
• Vander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 2009;324:1029–1033.
   PubMed Web of Science ®Google Scholar
• Dhup S, Dadhich RK, Porporato PE, et al. Multiple biological activities of lactic acid in cancer: influences on tumor growth, angiogenesis and metastasis. Curr Pharm Des 2012;18:1319–30.
   PubMed Web of Science ®Google Scholar
• Ayres JS. A metabolic handbook for the COVID-19 pandemic. Nat Metab 2020;2:572–585.
   PubMedGoogle Scholar
• Alfarouk KO, Muddathir AK, Shayoub MEA. Tumor acidity as evolutionary spite. Cancers 2011;3:408–414.
   PubMedGoogle Scholar