Exploring unconventional attributes of red blood cells and their potential applications in biomedicine

References

[1] Aarts PA, Heethaar RM, Sixma JJ. Red blood cell deformability influences platelets–vessel wall interaction in flowing blood. Blood 1984; 64:1228–1233.

[2] Abd Elhadi S, Grigoletto J, Poli M et al. alpha-Synuclein in blood cells differentiates Parkinson’s disease from healthy controls. Ann Clin Transl Neurol 2019; 6:2426–2436.

[3] Ahlqvist KJ, Leoncini S, Pecorelli A et al. MtDNA mutagenesis impairs elimination of mitochondria during erythroid maturation leading to enhanced erythrocyte destruction. Nat Commun 2015; 6:6494.

[4] Al-Abed Y, Dabideen D, Aljabari B et al. ISO-1 binding to the tautomerase active site of MIF inhibits its pro-inflammatory activity and increases survival in severe sepsis. J Biol Chem 2005; 280:36541–36544.

[5] Alimohamadi H, Smith AS, Nowak RB et al. Non-uniform distribution of myosin-mediated forces governs red blood cell membrane curvature through tension modulation. PLoS Comput Biol 2020; 16:e1007890.

[6] Anastasiadi AT, Paronis EC, Arvaniti VZ et al. The post- storage performance of RBCs from beta-thalassemia trait donors is related to their storability profile. Int J Mol Sci 2021a; 22:12281.

[7] Anastasiadi AT, Tzounakas VL, Arvaniti VZ et al. Red blood cell proteasome in beta-thalassemia trait: topology of activity and networking in blood bank conditions. Membranes (Basel) 2021b; 11:11.

[8] Anderson HL, Brodsky IE, Mangalmurti NS. The evolving erythrocyte: red blood cells as modulators of innate immunity. J Immunol 2018; 201:1343–1351.

[9] Angay O, Friedrich M, Pinnecker J et al. Image-based modeling and scoring of Howell-Jolly Bodies in human erythrocytes. Cytometry A 2018; 93:305–313.

[10] Artmann GM, Sung KL, Horn T et al. Micropipette aspiration of human erythrocytes induces echinocytes via membrane phospholipid translocation. Biophys J 1997; 72:1434–1441.

[11] Asher DR, Cerny AM, Finberg RW. The erythrocyte viral trap: transgenic expression of viral receptor on erythrocytes attenuates coxsackievirus B infection. Proc Natl Acad Sci USA 2005; 102:12897–12902.

[12] Ataga KI, Smith WR, De Castro LM et al. ICA-17043-05 Investigators. Efficacy and safety of the Gardos channel blocker, senicapoc (ICA-17043), in patients with sickle cell anemia. Blood 2008; 111:3991–3997.

[13] Badior KE, Casey JR. Molecular mechanism for the red blood cell senescence clock. IUBMB Life 2018; 70:32–40.

[14] Barbour R, Kling K, Anderson JP et al. Red blood cells are the major source of alpha-synuclein in blood. Neurodegener Dis 2008; 5:55–59.

[15] Barshtein G, Pries AR, Goldschmidt N et al. Deformability of transfused red blood cells is a potent determinant of transfusion-induced change in recipient’s blood flow. Microcirculation 2016; 23:479–486.

[16] Barshtein G, Goldschmidt N, Pries AR et al. Deformability of transfused red blood cells is a potent effector of transfusion-induced hemoglobin increment: a study with beta-thalassemia major patients. Am J Hematol 2017; 92:E559–E560.

[17] Bartels T, Choi JG, Selkoe DJ. alpha-Synuclein occurs physiologically as a helically folded tetramer that resists aggregation. Nature 2011; 477:107–110.

[18] Baum J, Ward RH, Conway DJ. Natural selection on the erythrocyte surface. Mol Biol Evol 2002; 19:223–229.

[19] Bax BE, Levene M, Bain MD et al. Erythrocyte encapsulated thymidine phosphorylase for the treatment of patients with mitochondrial neurogastrointestinal encephalomyopathy: study protocol for a multi-centre, multiple dose, open label trial. J Clin Med 2019; 8:1096.

[20] Blackshear PJ, Perera L. Phylogenetic distribution and evolution of the linked RNA-binding and NOT1-binding domains in the tristetraprolin family of tandem CCCH zinc finger proteins. J Interferon Cytokine Res 2014; 34:297–306.

[21] Bouchla A, Kriebardis AG, Georgatzakou HT et al. Red blood cell abnormalities as the mirror of SARS-CoV-2 disease severity: a pilot study. Front Physiol 2021; 12:825055.

[22] Brenner JS, Pan DC, Myerson JW et al. Red blood cell-hitchhiking boosts delivery of nanocarriers to chosen organs by orders of magnitude. Nat Commun 2018; 9:2684.

[23] Brum WS, Cullen NC, Janelidze S et al. A two-step workflow based on plasma p-tau217 to screen for amyloid beta positivity with further confirmatory testing only in uncertain cases. Nat Aging 2023; 3:1079–1090.

[24] Brun JF, Varlet-Marie E, Myzia J et al. Metabolic influences modulating erythrocyte deformability and eryptosis. Metabolites 2021; 12:4.

[25] Burger P, Hilarius-Stokman P, De Korte D et al. CD47 functions as a molecular switch for erythrocyte phagocytosis. Blood 2012; 119:5512–5521.

[26] Byon JC, Padilla SM, Papayannopoulou T. Deletion of Dicer in late erythroid cells results in impaired stress erythropoiesis in mice. Exp Hematol 2014; 42:852–6.e1.

[27] Cahalan SM, Lukacs V, Ranade SS et al. Piezo1 links mechanical forces to red blood cell volume. Elife 2015; 4:e07370.

[28] Caielli S, Cardenas J, De Jesus AA et al. Erythroid mitochondrial retention triggers myeloid-dependent type I interferon in human SLE. Cell 2021; 184:4464–4479.e19.

[29] Catala A, Youssef LA, Reisz JA et al. Metabolic reprogramming of mouse bone marrow derived macrophages following erythrophagocytosis. Front Physiol 2020; 11:396.

[30] Catala A, Stone M, Busch MP et al. Reprogramming of red blood cell metabolism in Zika virus-infected donors. Transfusion 2022; 62:1045–1064.

[31] Caulier A, Jankovsky N, Gautier EF et al. Red blood cell proteomics reveal remnant protein biosynthesis and folding pathways in PIEZO1-related hereditary xerocytosis. Front Physiol 2022; 13:960291.

[32] Chang TL, Cubillos FF, Kakhniashvili DG et al. Band 3 is a target protein of spectrin’s E2/E3 activity: implication for sickle cell disease and normal red blood cell aging. Cell Mol Biol (Noisy-le-grand) 2004; 50:171–177.

[33] Chang TL, Kakhniashvili DG, Goodman SR. Spectrin’s E2/E3 ubiquitin conjugating/ligating activity is diminished in sickle cells. Am J Hematol 2005; 79:89–96.

[34] Chen SY, Wang Y, Telen MJ et al. The genomic analysis of erythrocyte microRNA expression in sickle cell diseases. PLoS One 2008; 3:e2360.

[35] Chen PH, Hong J, Chi JT. Discovery, genomic analysis, and functional role of the erythrocyte RNAs. Curr Pathobiol Rep 2017; 5:43–48.

[36] Chen M, Leng Y, He C et al. Red blood cells: a potential delivery system. J Nanobiotechnology 2023; 21:288.

[37] Chessa L, Leuzzi V, Plebani A et al. Intra-erythrocyte infusion of dexamethasone reduces neurological symptoms in ataxia teleangiectasia patients: results of a phase 2 trial. Orphanet J Rare Dis 2014; 9:5.

[38] Ciccoli L, De Felice C, Paccagnini E et al. Erythrocyte shape abnormalities, membrane oxidative damage, and beta-actin alterations: an unrecognized triad in classical autism. Mediators Inflamm 2013; 2013:432616.

[39] Cilek N, Ugurel E, Goksel E et al. Signaling mechanisms in red blood cells: a view through the protein phosphorylation and deformability. J Cell Physiol 2023:1–17.

[40] Claver JA, Quaglia AIE. Comparative morphology, development, and function of blood cells in nonmammalian vertebrates. J Exot Pet Med 2009; 18:87–97.

[41] Cortese-Krott MM, Kelm M. Endothelial nitric oxide synthase in red blood cells: key to a new erythrocrine function? Redox Biol 2014; 2:251–258.

[42] Cyrus C. The role of miRNAs as therapeutic tools in sickle cell disease. Medicina (Kaunas) 2021; 57:1106.

[43] D’alessandro A, Hod EA. Red blood cell storage: from genome to exposome towards personalized transfusion medicine. Transfus Med Rev 2023; 37:150750.

[44] D’alessandro A, Dzieciatkowska M, Nemkov T et al. Red blood cell proteomics update: is there more to discover? Blood Transfus 2017a; 15:182–187.

[45] D’alessandro A, Nemkov T, Yoshida T et al. Citrate metabolism in red blood cells stored in additive solution-3. Transfusion 2017b; 57:325–336.

[46] D’alessandro A, Fu X, Kanias T et al. Recipient Epidemiology and Donor Evaluation Study-III (REDS III). Donor sex, age and ethnicity impact stored red blood cell antioxidant metabolism through mechanisms in part explained by glucose 6-phosphate dehydrogenase levels and activity. Haematologica 2021; 106:1290–1302.

[47] D’alessandro A, Anastasiadi AT, Tzounakas VL et al. Red blood cell metabolism in vivo and in vitro. Metabolites 2023a; 13:793.

[48] D’alessandro A, Lukens JR, Zimring JC. The role of PIMT in Alzheimer’s disease pathogenesis: a novel hypothesis. Alzheimers Dement 2023b; 19:5296–5302.

[49] Dao M, Lim CT, Suresh S. Mechanics of the human red blood cell deformed by optical tweezers. J Mech Phys Solids 2003; 51:2259–2280.

[50] Darbonne WC, Rice GC, Mohler MA et al. Red blood cells are a sink for interleukin 8, a leukocyte chemotaxin. J Clin Invest 1991; 88:1362–1369.

[51] Dawkins R. The Blind Watchmaker. Essex/England: Harlow, Longman Scientific & Technical, 1986.

[52] De Almeida JP, Saldanha C. Nonneuronal cholinergic system in human erythrocytes: biological role and clinical relevance. J Membr Biol 2010; 234:227–234.

[53] Domenech C, Thomas X, Chabaud S et al. l-asparaginase loaded red blood cells in refractory or relapsing acute lymphoblastic leukaemia in children and adults: results of the GRASPALL 2005-01 randomized trial. Br J Haematol 2011; 153:58–65.

[54] Doss JF, Corcoran DL, Jima DD et al. A comprehensive joint analysis of the long and short RNA transcriptomes of human erythrocytes. BMC Genomics 2015; 16:952.

[55] Dzandu JK, Johnson RM. Membrane protein phosphorylation in intact normal and sickle cell erythrocytes. J Biol Chem 1980; 255:6382–6386.

[56] Esperti S, Nader E, Stier A et al. Increased retention of functional mitochondria in mature sickle red blood cells is associated with increased sickling tendency, hemolysis and oxidative stress. Haematologica 2023; 108:3086–3094.

[57] Faoro C, Ataide SF. Noncanonical functions and cellular dynamics of the mammalian signal recognition particle components. Front Mol Biosci 2021; 8:679584.

[58] Fauvet B, Mbefo MK, Fares MB et al. alpha-Synuclein in central nervous system and from erythrocytes, mammalian cells, and Escherichia coli exists predominantly as disordered monomer. J Biol Chem 2012; 287:15345–15364.

[59] Fenk S, Melnikova EV, Anashkina AA et al. Hemoglobin is an oxygen-dependent glutathione buffer adapting the intracellular reduced glutathione levels to oxygen availability. Redox Biol 2022; 58:102535.

[60] Fukuma N, Akimitsu N, Hamamoto H et al. A role of the Duffy antigen for the maintenance of plasma chemokine concentrations. Biochem Biophys Res Commun 2003; 303:137–139.

[61] Gajecki D, Gawrys J, Szahidewicz-Krupska E et al. Role of erythrocytes in nitric oxide metabolism and paracrine regulation of endothelial function. Antioxidants (Basel) 2022; 11:943.

[62] Gambhir KK, Agarwal VR. Red blood cell insulin receptors in health and disease. Biochem Med Metab Biol 1991; 45:133–153.

[63] Gao X, Yue T, Tian F et al. Erythrocyte membrane skeleton inhibits nanoparticle endocytosis. AIP Adv 2017; 7:065303.

[64] Ghashghaeinia M, Toulany M, Saki M et al. The NFkB pathway inhibitors Bay 11-7082 and parthenolide induce programmed cell death in anucleated Erythrocytes. Cell Physiol Biochem 2011; 27:45–54.

[65] Ghashghaeinia M, Toulany M, Saki M et al. Potential roles of the NFkappaB and glutathione pathways in mature human erythrocytes. Cell Mol Biol Lett 2012; 17:11–20.

[66] Ghashghaeinia M, Wesseling MC, Ramos E et al. Trifluoperazine-induced suicidal erythrocyte death and S-nitrosylation inhibition, reversed by the nitric oxide donor sodium nitroprusside. Cell Physiol Biochem 2017; 42:1985–1998.

[67] Giacometti G, Ferreri C, Sansone A et al. High predictive values of RBC membrane-based diagnostics by biophotonics in an integrated approach for Autism Spectrum Disorders. Sci Rep 2017; 7:9854.

[68] Gladwin MT, Schechter AN, Kim-Shapiro DB et al. The emerging biology of the nitrite anion. Nat Chem Biol 2005; 1:308–314.

[69] Goodman SR, Petrofes Chapa R, Zimmer WE. Spectrin’s chimeric E2/E3 enzymatic activity. Exp Biol Med (Maywood) 2015; 240:1039–1049.

[70] Goskel E, Ugurel E, Nader E et al. A preliminary study of Phosphodiesterases and Adenylyl Cyclase Signaling Pathway on red blood cell deformability of sickle cell patients. Front Physiol 2023; 14:1215835.

[71] Gratzer W. Cell biology. More red than dead. Nature 1984; 310:368–369.

[72] Gratzer WB. From helix to haemolysis. Nat Struct Biol 1994; 1:78–79.

[73] Greenwalt TJ. The Ernest Witebsky memorial lecture. Red but not dead: not a hapless sac of hemoglobin. Immunol Invest 1995; 24:3–21.

[74] Groen K, Maltby VE, Sanders KA et al. Erythrocytes in multiple sclerosis - forgotten contributors to the pathophysiology? Mult Scler J Exp Transl Clin 2016; 2:2055217316649981.

[75] Gu X, Nardone C, Kamitaki N et al. The midnolin-proteasome pathway catches proteins for ubiquitination-independent degradation. Science 2023; 381:eadh5021.

[76] Guizouarn H, Barshtein G. Editorial: red blood cell vascular adhesion and deformability. Front Physiol 2020; 11:657.

[77] Haase VH. Regulation of erythropoiesis by hypoxia-inducible factors. Blood Rev 2013; 27:41–53.

[78] Hammel P, Fabienne P, Mineur L et al. Erythrocyteencapsulated asparaginase (eryaspase) combined with chemotherapy in second-line treatment of advanced pancreatic cancer: an open-label, randomized Phase IIb trial. Eur J Cancer 2020; 124:91–101.

[79] Helms C, Kim-Shapiro DB. Hemoglobin-mediated nitric oxide signaling. Free Radic Biol Med 2013; 61:464–472.

[80] Henslee EA, Crosby P, Kitcatt SJ et al. Rhythmic potassium transport regulates the circadian clock in human red blood cells. Nat Commun 2017; 8:1978.

[81] Hertz L, Flormann D, Birnbaumer L et al. Evidence of in vivo exogen protein uptake by red blood cells: a putative therapeutic concept. Blood Adv 2023; 7:1033–1039.

[82] Hoffmann MG, Kieffer C, Bjorkman PJ. In vitro characterization of engineered red blood cells as viral traps against HIV-1 and SARS-CoV-2. Mol Ther Methods Clin Dev 2021; 21:161–170.

[83] Horuk R, Wang ZX, Peiper SC et al. Identification and characterization of a promiscuous chemokine-binding protein in a human erythroleukemic cell line. J Biol Chem 1994; 269:17730–17733.

[84] Hotz MJ, Qing D, Shashaty MGS et al. Red blood cells homeostatically bind mitochondrial DNA through TLR9 to maintain quiescence and to prevent lung injury. Am J Respir Crit Care Med 2018; 197:470–480.

[85] Huang Z, Hearne L, Irby CE et al. Kinetics of increased deformability of deoxygenated sickle cells upon oxygenation. Biophys J 2003; 85:2374–2383.

[86] Huang Z, Shiva S, Kim-Shapiro DB et al. Enzymatic function of hemoglobin as a nitrite reductase that produces NO under allosteric control. J Clin Invest 2005; 115:2099–2107.

[87] Huisjes R, Bogdanova A, Van Solinge WW et al. Squeezing for life - Properties of red blood cell deformability. Front Physiol 2018; 9:656.

[88] Imberty A, Varrot A. Microbial recognition of human cell surface glycoconjugates. Curr Opin Struct Biol 2008; 18:567–576.

[89] Issaian A, Hay A, Dzieciatkowska M et al. The interactome of the N-terminus of band 3 regulates red blood cell metabolism and storage quality. Haematologica 2021; 106:2971–2985.

[90] Jagadeeswaran R, Vazquez BA, Thiruppathi M et al. Pharmacological inhibition of LSD1 and mTOR reduces mitochondrial retention and associated ROS levels in the red blood cells of sickle cell disease. Exp Hematol 2017; 50:46–52.

[91] Jain V, Yang WH, Wu J et al. Single cell RNA-Seq analysis of human red cells. Front Physiol 2022; 13:828700.

[92] Jaskiewicz E, Jodlowska M, Kaczmarek R et al. Erythrocyte glycophorins as receptors for Plasmodium merozoites. Parasit Vectors 2019; 12:317.

[93] Jia L, Bonaventura C, Bonaventura J et al. S-nitrosohaemoglobin: a dynamic activity of blood involved in vascular control. Nature 1996; 380:221–226.

[94] Joly E, Hudrisier D. What is trogocytosis and what is its purpose? Nat Immunol 2003; 4:815.

[95] Kalani Roy M, La Carpia F, Cendali F et al. Irradiation causes alterations of polyamine, purine, and sulfur metabolism in red blood cells and multiple organs. J Proteome Res 2022; 21:519–534.

[96] Kanayama A, Inoue J, Sugita-Konishi Y et al. Oxidation of Ikappa Balpha at methionine 45 is one cause of taurine chloramine-induced inhibition of NF-kappa B activation. J Biol Chem 2002; 277:24049–24056.

[97] Kar D, Sellamuthu K, Kumar SD et al. Induction of translational readthrough across the thalassemia-causing premature stop codon in beta-globin-encoding mRNA. Biochemistry 2020; 59:80–84.

[98] Karsten E, Breen E, Herbert BR. Red blood cells are dynamic reservoirs of cytokines. Sci Rep 2018a; 8:3101.

[99] Karsten E, Hill CJ, Herbert BR. Red blood cells: the primary reservoir of macrophage migration inhibitory factor in whole blood. Cytokine 2018b; 102:34–40.

[100] Kaul DK, Koshkaryev A, Artmann G et al. Additive effect of red blood cell rigidity and adherence to endothelial cells in inducing vascular resistance. Am J Physiol Heart Circ Physiol 2008; 295:H1788–H1793.

[101] Kay MM, Goodman J, Goodman S et al. Membrane protein band 3 alteration associated with neurologic disease and tissuereactive antibodies. Exp Clin Immunogenet 1990; 7:181–199.

[102] Kerkela E, Lahtela J, Larjo A et al. Exploring transcriptomic landscapes in red blood cells, in their extracellular vesicles and on a single-cell level. Int J Mol Sci 2022; 23:12897.

[103] King ML. I have a dream; speech at the March on Washington, n.p, 1963.

[104] Koleva L, Bovt E, Ataullakhanov F et al. Erythrocytes as carriers: from drug delivery to biosensors. Pharmaceutics 2020; 12:276.

[105] Kumar SD, Kar D, Akhtar MN et al. Evidence for low-level translation in human erythrocytes. Mol Biol Cell 2022; 33:br21.

[106] Lam LKM, Murphy S, Kokkinaki D et al. DNA binding to TLR9 expressed by red blood cells promotes innate immune activation and anemia. Sci Transl Med 2021; 13:eabj1008.

[107] Leo F, Hutzler B, Ruddiman CA et al. Cellular microdomains for nitric oxide signaling in endothelium and red blood cells. Nitric Oxide 2020; 96:44–53.

[108] Li X, Wu Z, Wang Y et al. Characterization of adult alphaand beta-globin elevated by hydrogen peroxide in cervical cancer cells that play a cytoprotective role against oxidative insults. PLoS One 2013; 8:e54342.

[109] Liang N, Jiao Z, Zhang C et al. Mature red blood cells contain long DNA fragments and could acquire DNA from lung cancer tissue. Adv Sci (Weinh) 2023; 10:e2206361.

[110] Lippi G, Plebani M. Red blood cell distribution width (RDW) and human pathology. One size fits all. Clin Chem Lab Med 2014; 52:1247–1249.

[111] Liu J, Niu N, Li X et al. The life cycle of polyploid giant cancer cells and dormancy in cancer: opportunities for novel therapeutic interventions. Semin Cancer Biol 2022; 81:132–144.

[112] Loyd MR, Okamoto Y, Randall MS et al. Role of AP1/NFE2 binding sites in endogenous alpha-globin gene transcription. Blood 2003; 102:4223–4228.

[113] Madeddu C, Neri M, Sanna E et al. Experimental drugs for chemotherapy- and cancer-related anemia. J Exp Pharmacol 2021; 13:593–611.

[114] Mantel PY, Hoang AN, Goldowitz I et al. Malaria-infected erythrocyte-derived microvesicles mediate cellular communication within the parasite population and with the host immune system. Cell Host Microbe 2013; 13:521–534.

[115] Maor G, Dubreuil RR, Feany MB. alpha-Synuclein promotes neuronal dysfunction and death by disrupting the binding of Ankyrin to beta-Spectrin. J Neurosci 2023; 43:1614–1626.

[116] Marengo-Rowe AJ. Structure-function relations of human hemoglobins. Proc (Bayl Univ Med Cent) 2006; 19:239–245.

[117] Mei Y, Liu Y, Ji P. Understanding terminal erythropoiesis: an update on chromatin condensation, enucleation, and reticulocyte maturation. Blood Rev 2021; 46:100740.

[118] Minetti G, Egee S, Morsdorf D et al. Red cell investigations: art and artefacts. Blood Rev 2013; 27:91–101.

[119] Moriconi C, Dzieciatkowska M, Roy M et al. Retention of functional mitochondria in mature red blood cells from patients with sickle cell disease. Br J Haematol 2022; 198:574–586.

[120] Moura PL, Hawley BR, Mankelow TJ et al. Non-muscle myosin II drives vesicle loss during human reticulocyte maturation. Haematologica 2018; 103:1997–2007.

[121] Mulatie Z, Aynalem M, Getawa S. MicroRNAs as quality assessment tool in stored packed red blood cell in blood banks. J Blood Med 2023; 14:99–106.

[122] Nemkov T, Reisz JA, Xia Y et al. Red blood cells as an organ? How deep omics characterization of the most abundant cell in the human body highlights other systemic metabolic functions beyond oxygen transport. Expert Rev Proteomics 2018a; 15:855–864.

[123] Nemkov T, Sun K, Reisz JA et al. Hypoxia modulates the purine salvage pathway and decreases red blood cell and supernatant levels of hypoxanthine during refrigerated storage. Haematologica 2018b; 103:361–372.

[124] Nemkov T, Stefanoni D, Bordbar A et al. Recipient Epidemiology and Donor Evaluation Study III Red Blood Cell–Omics (REDS-III RBC-Omics) Study. Blood donor exposome and impact of common drugs on red blood cell metabolism. JCI Insight 2021; 6:e146175.

[125] Nemkov T, Stephenson D, Erickson C et al. Regulation of kynurenine metabolism by blood donor genetics and biology impacts red cell hemolysis in vitro and in vivo. Blood 2023; 143:456–472.

[126] Neote K, Mak JY, Kolakowski LF Jr et al. Functional and biochemical analysis of the cloned Duffy antigen: identity with the red blood cell chemokine receptor. Blood 1994; 84:44–52.

[127] Newton AC, Cook SL, Huestis WH. Transfer of band 3, the erythrocyte anion transporter, between phospholipid vesicles and cells. Biochemistry 1983; 22:6110–6117.

[128] Nguyen DB, Wagner-Britz L, Maia S et al. Regulation of phosphatidylserine exposure in red blood cells. Cell Physiol Biochem 2011; 28:847–856.

[129] Nirmalraj PN, Schneider T, Felbecker A. Spatial organization of protein aggregates on red blood cells as physical biomarkers of Alzheimer’s disease pathology. Sci Adv 2021; 7:eabj2137.

[130] Ogino T, Hosako M, Hiramatsu K et al. Oxidative modification of IkappaB by monochloramine inhibits tumor necrosis factor alpha-induced NF-kappaB activation. Biochim Biophys Acta 2005; 1746:135–142.

[131] Olumuyiwa-Akeredolu OO, Soma P, Buys AV et al. Characterizing pathology in erythrocytes using morphological and biophysical membrane properties: relation to impaired hemorheology and cardiovascular function in rheumatoid arthritis. Biochim Biophys Acta Biomembr 2017; 1859:2381–2391.

[132] Osakada T, Abe T, Itakura T et al. Hemoglobin in the blood acts as a chemosensory signal via the mouse vomeronasal system. Nat Commun 2022; 13:556.

[133] Paone S, D’alessandro S, Parapini S et al. Characterization of the erythrocyte GTPase Rac1 in relation to Plasmodium falciparum invasion. Sci Rep 2020; 10:22054.

[134] Papadopoulos C. Immunosuppressive function of intratumor red blood cells: an immune-metabolic perspective. Curr Cancer Ther Rev 2022; 18:224–226.

[135] Papadopoulos C, Panopoulou M, Anagnostopoulos K et al. Immune and metabolic interactions of human erythrocytes: a molecular perspective. Endocr Metab Immune Disord Drug Targets 2021a; 21:843–853.

[136] Papadopoulos C, Tentes I, Anagnostopoulos K. Molecular interactions between erythrocytes and the endocrine system. Maedica (Bucur) 2021b; 16:489–492.

[137] Parashar A, Jacob VD, Gideon DA et al. Hemoglobin catalyzes ATP-synthesis in human erythrocytes: a murburn model. J Biomol Struct Dyn 2022; 40:8783–8795.

[138] Patgaonkar M, Aranha C, Bhonde G et al. Identification and characterization of anti-microbial peptides from rabbit vaginal fluid. Vet Immunol Immunopathol 2011; 139:176–186.

[139] Paulus JK, Van Der Hoorn RL. Tricked or trapped-Two decoy mechanisms in host-pathogen interactions. PLoS Pathog 2018; 14:e1006761.

[140] Peixeiro I, Silva AL, Romao L. Control of human beta-globin mRNA stability and its impact on beta-thalassemia phenotype. Haematologica 2011; 96:905–913.

[141] Phan TT, Vy HT, Ho TT et al. Emergence role of nucleated red blood cells in molecular response evaluation for chronic myeloid leukemia. Int J Gen Med 2019; 12:333–341.

[142] Pierige F, Bigini N, Rossi L et al. Reengineering red blood cells for cellular therapeutics and diagnostics. Wiley Interdiscip Rev Nanomed Nanobiotechnol 2017; 9:e1454.

[143] Pikora K, Kretowska-Grunwald A, Krawczuk-Rybak M et al. Diagnostic value and prognostic significance of Nucleated Red Blood Cells (NRBCs) in selected medical conditions. Cells 2023; 12:1817.

[144] Qiang Y, Liu J, Dao M et al. Mechanical fatigue of human red blood cells. Proc Natl Acad Sci USA 2019; 116:19828–19834.

[145] Qiang Y, Liu J, Dao M et al. In vitro assay for single-cell characterization of impaired deformability in red blood cells under recurrent episodes of hypoxia. Lab Chip 2021; 21:3458–3470.

[146] Rab ME, Van Oirschot BA, Kosinski PA et al. AG-348 (Mitapivat), an allosteric activator of red blood cell pyruvate kinase, increases enzymatic activity, protein stability, and ATP levels over a broad range of PKLR genotypes. Haematologica 2021; 106:238–249.

[147] Recktenwald SM, Simionato G, Lopes MGM et al. Cross-talk between red blood cells and plasma influences blood flow and omics phenotypes in severe COVID-19. Elife 2022; 11:e81316.

[148] Regev-Rudzki N, Wilson DW, Carvalho TG et al. Cell-cell communication between malaria-infected red blood cells via exosome-like vesicles. Cell 2013; 153:1120–1133.

[149] Reithmeier RA, Casey JR, Kalli AC et al. Band 3, the human red cell chloride/bicarbonate anion exchanger (AE1, SLC4A1), in a structural context. Biochim Biophys Acta 2016; 1858:1507–1532.

[150] Reynaert NL, Ckless K, Korn SH et al. Nitric oxide represses inhibitory kappaB kinase through S-nitrosylation. Proc Natl Acad Sci USA 2004; 101:8945–8950.

[151] Reynaert NL, Van Der Vliet A, Guala AS et al. Dynamic redox control of NF-kappaB through glutaredoxin-regulated S-glutathionylation of inhibitory kappaB kinase beta. Proc Natl Acad Sci USA 2006; 103:13086–13091.

[152] Robert M, Laperrousaz B, Piedrahita D et al. Multiparametric characterization of red blood cell physiology after hypotonic dialysis based drug encapsulation process. Acta Pharm Sin B 2022; 12:2089–2102.

[153] Sakai T, Antoku Y, Iwashita H et al. Chorea-acanthocytosis: abnormal composition of covalently bound fatty acids of erythrocyte membrane proteins. Ann Neurol 1991; 29:664–669.

[154] Sangokoya C, Telen MJ, Chi JT. microRNA miR-144 modulates oxidative stress tolerance and associates with anemia severity in sickle cell disease. Blood 2010; 116:4338–4348.

[155] Sarchione A, Marchand A, Taymans JM et al. Alpha-synuclein and lipids: the Elephant in the room? Cells 2021; 10:2452.

[156] Satchwell TJ, Toye AM. Band 3, an essential red blood cell hub of activity. Haematologica 2021; 106:2792–2793.

[157] Sbardella D, Tundo GR, Campagnolo L et al. Author correction: retention of mitochondria in mature human red blood cells as the result of autophagy impairment in Rett Syndrome. Sci Rep 2021; 11:12337.

[158] Schafer FQ, Buettner GR. Redox environment of the cell as viewed through the redox state of the glutathione disulfide/glutathione couple. Free Radic Biol Med 2001; 30:1191–1212.

[159] Seidel P, Roth M, Ge Q et al. IkappaBalpha glutathionylation and reduced histone H3 phosphorylation inhibit eotaxin and RANTES. Eur Respir J 2011; 38:1444–1452.

[160] Smith AS, Nowak RB, Zhou S et al. Myosin IIA interacts with the spectrin-actin membrane skeleton to control red blood cell membrane curvature and deformability. Proc Natl Acad Sci USA 2018; 115:E4377–E4385.

[161] Song A, Wen AQ, Wen YE et al. p97 dysfunction underlies a loss of quality control of damaged membrane proteins and promotes oxidative stress and sickling in sickle cell disease. FASEB J 2022; 36:e22246.

[162] Sosale NG, Rouhiparkouhi T, Bradshaw AM et al. Cell rigidity and shape override CD47’s “self”-signaling in phagocytosis by hyperactivating myosin-II. Blood 2015; 125:542–552.

[163] Stachon A, Segbers E, Holland-Letz T et al. Nucleated red blood cells in the blood of medical intensive care patients indicate increased mortality risk: a prospective cohort study. Crit Care 2007; 11:R62.

[164] Sun L, Yu Y, Niu B et al. Red blood cells as potential repositories of MicroRNAs in the circulatory system. Front Genet 2020; 11:442.

[165] Talhouarne GJS, Gall JG. 7SL RNA in vertebrate red blood cells. RNA 2018; 24:908–914.

[166] Thomas T, Stefanoni D, Dzieciatkowska M et al. Evidence of structural protein damage and membrane lipid remodeling in red blood cells from COVID-19 patients. J Proteome Res 2020; 19:4455–4469.

[167] Thomas TA, Qiu A, Kim CY et al. Reticulocytes in donor blood units enhance red blood cell alloimmunization. Haematologica 2023; 108:2639–2651.

[168] Tian C, Liu G, Gao L et al. Erythrocytic alpha-Synuclein as a potential biomarker for Parkinson’s disease. Transl Neurodegener 2019; 8:15.

[169] Toppet M, Fall AB, Ferster A et al. Antisickling activity of sodium cromoglicate in sickle-cell disease. Lancet 2000; 356:309.

[170] Tumburu L, Ghosh-Choudhary S, Seifuddin FT et al. Circulating mitochondrial DNA is a proinflammatory DAMP in sickle cell disease. Blood 2021; 137:3116–3126.

[171] Tzounakas VL, Karadimas DG, Papassideri IS et al. Erythrocyte-based drug delivery in Transfusion Medicine: wandering questions seeking answers. Transfus Apher Sci 2017; 56:626–634.

[172] Tzounakas VL, Anastasiadi AT, Dzieciatkowska M et al. Proteome of stored RBC membrane and vesicles from heterozygous beta thalassemia donors. Int J Mol Sci 2021; 22:3369.

[173] Tzounakas VL, Anastasiadi AT, Stefanoni D et al. Beta thalassemia minor is a beneficial determinant of red blood cell storage lesion. Haematologica 2022a; 107:112–125.

[174] Tzounakas VL, Dzieciatkowska M, Anastasiadi AT et al. Red cell proteasome modulation by storage, redox metabolism and transfusion. Blood Transfus 2022b; 20:27–39.

[175] Ugurel E, Goksel E, Cilek N et al. Proteomic analysis of the role of the Adenylyl Cyclase-cAMP Pathway in red blood cell mechanical responses. Cells 2022; 11:1250.

[176] Ulker P, Sati L, Celik-Ozenci C et al. Mechanical stimulation of nitric oxide synthesizing mechanisms in erythrocytes. Biorheology 2009; 46:121–132.

[177] Van ‘T Erve TJ, Wagner BA, Ryckman KK et al. The concentration of glutathione in human erythrocytes is a heritable trait. Free Radic Biol Med 2013; 65:742–749.

[178] Van Wijk R, Van Solinge WW. The energy-less red blood cell is lost: erythrocyte enzyme abnormalities of glycolysis. Blood 2005; 106:4034–4042.

[179] Villa CH, Anselmo AC, Mitragotri S et al. Red blood cells: supercarriers for drugs, biologicals, and nanoparticles and inspiration for advanced delivery systems. Adv Drug Deliv Rev 2016; 106:88–103.

[180] Von Lindern M, Egee S, Bianchi P et al. The function of ion channels and membrane potential in red blood cells: toward a systematic analysis of the erythroid channelome. Front Physiol 2022; 13:824478.

[181] Waggoner SA, Liebhaber SA. Regulation of alphaglobin mRNA stability. Exp Biol Med (Maywood) 2003; 228:387–395.

[182] Wang M. RBC mitochondria trigger interferon release. Nat Rev Nephrol 2021; 17:707.

[183] Wang C, Ye Y, Sun W et al. Red blood cells for glucose-responsive insulin delivery. Adv Mater 2017; 29:1606617.

[184] Webb KL, Dominelli PB, Baker SE et al. Influence of high hemoglobin-oxygen affinity on humans during hypoxia. Front Physiol 2021; 12:763933.

[185] Wong AJ, Kiehart DP, Pollard TD. Myosin from human erythrocytes. J Biol Chem 1985; 260:46–49.

[186] Wu YW, Goubran H, Seghatchian J et al. Smart blood cell and microvesicle-based Trojan horse drug delivery: merging expertise in blood transfusion and biomedical engineering in the field of nanomedicine. Transfus Apher Sci 2016; 54:309–318.

[187] Wu Y, Leyk S, Torabi H et al. Plasmodium falciparum infection reshapes the human microRNA profiles of red blood cells and their extracellular vesicles. iScience 2023; 26:107119.

[188] Xiao W, Shameli A, Harding CV et al. Late stages of hematopoiesis and B cell lymphopoiesis are regulated by alpha-synuclein, a key player in Parkinson’s disease. Immunobiology 2014; 219:836–844.

[189] Xu P, Chen C, Zhang Y et al. Erythrocyte transglutaminase-2 combats hypoxia and chronic kidney disease by promoting oxygen delivery and carnitine homeostasis. Cell Metab 2022; 34:299–316.e6.

[190] Yamada M, Matsuhira T, Yamamoto K et al. Antioxidative Pseudoenzymatic Mechanism of NAD(P)H coexisting with oxyhemoglobin for suppressed methemoglobin formation. Biochemistry 2019; 58:1400–1410.

[191] Yang W, Li X, Li X et al. Hemoglobin-alpha-synuclein complex exhibited age-dependent alterations in the human striatum and peripheral RBCs. Neurosci Lett 2020; 736:135274.

[192] Zhang ZW, Cheng J, Xu F et al. Red blood cell extrudes nucleus and mitochondria against oxidative stress. IUBMB Life 2011; 63:560–565.

[193] Zhang L, Wang S, Lin J. Clinical and molecular research of neuroacanthocytosis. Neural Regen Res 2013a; 8:833–842.

[194] Zhang S, Mercado-Uribe I, Liu J. Generation of erythroid cells from fibroblasts and cancer cells in vitro and in vivo. Cancer Lett 2013b; 333:205–212.

[195] Zhang H, Wan GZ, Wang YY et al. The role of erythrocytes and erythroid progenitor cells in tumors. Open Life Sci 2022; 17:1641–1656.

[196] Zhao Y, Sun X, Zhang G et al. Interaction of mesoporous silica nanoparticles with human red blood cell membranes: size and surface effects. ACS Nano 2011; 5:1366–1375.

[197] Zhao Z, Ukidve A, Gao Y et al. Erythrocyte leveraged chemotherapy (ELeCt): nanoparticle assembly on erythrocyte surface to combat lung metastasis. Sci Adv 2019; 5:eaax9250.

[198] Zhao Z, Ukidve A, Krishnan V et al. Systemic tumour suppression via the preferential accumulation of erythrocyte- anchored chemokine-encapsulating nanoparticles in lung metastases. Nat Biomed Eng 2021; 5:441–454.

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