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1.
The diagnostic and prognostic value of red cell distribution width in cardiovascular disease; current status and prospective.
Parizadeh, SM, Jafarzadeh-Esfehani, R, Bahreyni, A, Ghandehari, M, Shafiee, M, Rahmani, F, Parizadeh, MR, Seifi, S, Ghayour-Mobarhan, M, Ferns, GA, et al
BioFactors (Oxford, England). 2019;(4):507-516
Abstract
The red blood cell distribution width (RDW) is an index of the heterogeneity of circulating red blood cell size, which along with other standard complete blood count (CBC) parameters are used to identify hematological system diseases. Besides hematological disorders, several clinical studies have shown that an increased in the RDW may be associated with other diseases including acute pancreatitis, chronic kidney disease, gastrointestinal disorders, cancer, and of special interest in this review, cardiovascular disease (CVD). The diagnostic and prognostic value of RDW in different CVD (acute coronary syndrome, ischemic cerebrovascular disease, peripheral artery disease, atrial fibrillation, heart failure, and acute ischemic stroke) has been reviewed in this article, to provide an understanding how its measurement may be applied to improve the management of these conditions.
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2.
MPP1-based mechanism of resting state raft organization in the plasma membrane. Is it a general or specialized mechanism in erythroid cells?
Trybus, M, Niemiec, L, Biernatowska, A, Hryniewicz-Jankowska, A, Sikorski, AF
Folia histochemica et cytobiologica. 2019;(2):43-55
Abstract
Biological membranes are organized in various microdomains, one of the best known being called membrane rafts. The major function of these is thought to organize signaling partners into functional complexes. An important protein found in membrane raft microdomains of erythroid and other blood cells is MPP1 (membrane palmitoylated protein 1)/p55. MPP1 (p55) belongs to the MAGUK (membrane-associated guanylate kinase homolog) family and it is a major target of palmitoylation in the red blood cells (RBCs) membrane. The well-known function of this protein is to participate in formation of the junctional complex of the erythrocyte mem-brane skeleton. However, its function as a "raft organizer" is not well understood. In this review we focus on recent reports concerning MPP1 participation in membrane rafts organization in erythroid cells, including its role in signal transduction. Currently it is not known whether MPP1 could have a similar role in cell types other than erythroid lineage. We present also preliminary data regarding the expression level of MPP1 gene in several non-erythroid cell lines.
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3.
The long and winding road to pathogen reduction of platelets, red blood cells and whole blood.
Rebulla, P
British journal of haematology. 2019;(5):655-667
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Abstract
Pathogen reduction technologies (PRTs) have been developed to further reduce the current very low risks of acquiring transfusion-transmitted infections and promptly respond to emerging infectious threats. An entire portfolio of PRTs suitable for all blood components is not available, but the field is steadily progressing. While PRTs for plasma have been used for many years, PRTs for platelets, red blood cells (RBC) and whole blood (WB) were developed more slowly, due to difficulties in preserving cell functions during storage. Two commercial platelet PRTs use ultra violet (UV) A and UVB light in the presence of amotosalen or riboflavin to inactivate pathogens' nucleic acids, while a third experimental PRT uses UVC light only. Two PRTs for WB and RBC have been tested in experimental clinical trials with storage limited to 21 or 35 days, due to unacceptably high RBC storage lesion beyond these time limits. This review summarizes pre-clinical investigations and selected outcomes from clinical trials using the above PRTs. Further studies are warranted to decrease cell storage lesions after PRT treatment and to test PRTs in different medical and surgical conditions. Affordability remains a major administrative obstacle to PRT use, particularly so in geographical regions with higher risks of transfusion-transmissible infections.
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When might transferrin, hemopexin or haptoglobin administration be of benefit following the transfusion of red blood cells?
Buehler, PW, Karnaukhova, E
Current opinion in hematology. 2018;(6):452-458
Abstract
PURPOSE OF REVIEW After transfusion, a percentage of red blood cells undergo hemolysis within macrophages. Intravascular exposures to hemin and hemoglobin (Hb) can occur after storage bag hemolysis, some transfusion reactions, during use of medical assist devices and in response to bacterial hemolysins. Proteins that regulate iron, hemin and Hb either become saturated after iron excess (transferrin, Tf) or depleted after hemin (hemopexin, Hpx) and Hb (haptoglobin, Hp) excess. Protein saturation or stoichiometric imbalance created by transfusion increases exposure to non-Tf bound iron, hemin and Hb. Tf, Hpx and Hp are being developed for hematological disorders where iron, hemin and Hb contribute to pathophysiology. However, complexed to their ligands, each represents a potential iron source for pathogens, which may complicate the use of these proteins. RECENT FINDINGS Erythrophagocytosis by macrophages and processes of cell death that lead to reactive iron exposure are increasingly described. In addition, the effects of transfusion introduced circulatory hemin and Hb are described in the literature, particularly following large volume transfusion, infection and during concomitant medical device use. SUMMARY Supplementation with Tf, Hpx and Hp suggests therapeutic potential in conditions of extravascular/intravascular hemolysis. However, their administration following transfusion may require careful assessment of concomitant disease.
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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.
Nemkov, T, Reisz, JA, Xia, Y, Zimring, JC, D'Alessandro, A
Expert review of proteomics. 2018;(11):855-864
Abstract
Recently, the classification of two 'novel' organs, the mesentere and interstitium, was saluted as a scientific breakthrough and disseminated into mainstream media. The novelty of these findings did not pertain to the characterization of some previously unexplored phenomena, rather to the appreciation that well-established tissues may play some hitherto unexplored functions critical to system homeostasis. Areas covered: Here we provocatively comment on the potential classification of red blood cells - by far the most abundant host cell in the human body (~ 83% of the total cells) - as an organ involved in many functions beyond gas transport. In this perspective article, we describe some of these functions with a special emphasis on the role erythrocytes play with respect to systemic metabolic homeostasis. We thus focus on how these functions modulate the cross talk of red blood cells among each other and with other cell types including immune cells. Expert commentary: The appreciation of RBCs as an organ impacting systemic metabolic homeostasis and other cell functions while engaging in complex metabolic activity beyond oxygen transport can foster the development of novel therapeutic interventions in pathologic hypoxemia, inflammation, neurodgenerative diseases, aging, and cancer.
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Development, validation, and potential applications of biotinylated red blood cells for posttransfusion kinetics and other physiological studies: evidenced-based analysis and recommendations.
Mock, DM, Nalbant, D, Kyosseva, SV, Schmidt, RL, An, G, Matthews, NI, Vlaar, APJ, van Bruggen, R, de Korte, D, Strauss, RG, et al
Transfusion. 2018;(8):2068-2081
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Abstract
The current reference method in the United States for measuring in vivo population red blood cell (RBC) kinetics utilizes chromium-51 (51 Cr) RBC labeling for determining RBC volume, 24-hour posttransfusion RBC recovery, and long-term RBC survival. Here we provide evidence supporting adoption of a method for kinetics that uses the biotin-labeled RBCs (BioRBCs) as a superior, versatile method for both regulatory and investigational purposes. RBC kinetic analysis using BioRBCs has important methodologic, analytical, and safety advantages over 51 Cr-labeled RBCs. We critically review recent advances in labeling human RBCs at multiple and progressively lower biotin label densities for concurrent, accurate, and sensitive determination of both autologous and allogeneic RBC population kinetics. BioRBC methods valid for RBC kinetic studies, including successful variations used by the authors, are presented along with pharmacokinetic modeling approaches for the accurate determination of RBC pharmacokinetic variables in health and disease. The advantages and limitations of the BioRBC method-including its capability of determining multiple BioRBC densities simultaneously in the same individual throughout the entire RBC life span-are presented and compared with the 51 Cr method. Finally, potential applications and limitations of kinetic BioRBC determinations are discussed.
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FADS Polymorphism, Omega-3 Fatty Acids and Diabetes Risk: A Systematic Review.
Brayner, B, Kaur, G, Keske, MA, Livingstone, KM
Nutrients. 2018;(6)
Abstract
The role of n-3 long chain polyunsaturated fatty acids (LC n-3 PUFA) in reducing the risk of type 2 diabetes (T2DM) is not well established. The synthesis of LC n-3 PUFA requires fatty acid desaturase enzymes, which are encoded by the FADS gene. It is unclear if FADS polymorphism and dietary fatty acid intake can influence plasma or erythrocyte membrane fatty acid profile and thereby the risk of T2DM. Thus, the aim of this systematic review was to assess the current evidence for an effect of FADS polymorphism on T2DM risk and understand its associations with serum/erythrocyte and dietary LC n-3 PUFA. A systematic search was performed using PubMed, Embase, Cochrane and Scopus databases. A total of five studies met the inclusion criteria and were included in the present review. This review identified that FADS polymorphism may alter plasma fatty acid composition and play a protective role in the development of T2DM. Serum and erythrocyte LC n-3 PUFA levels were not associated with risk of T2DM, while dietary intake of LC n-3 PUFA was associated with lower risk of T2DM in one study only. The effect of LC n-3 PUFA consumption on associations between FADS polymorphism and T2DM warrants further investigation.
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Conversion ratios of n-3 fatty acids between plasma and erythrocytes: a systematic review and meta-regression.
Hu, XF, Sandhu, SK, Harris, WS, Chan, HM
The British journal of nutrition. 2017;(8):1162-1173
Abstract
As biomarkers of dietary intake or disease risk factor, n-3 fatty acid (FA) can be measured in plasma phospholipids (PL), total lipids (TL) or erythrocytes. However, the numeric relationships between n-3 FA in these lipid pools are not clear. Our goal was to derive conversion ratios for plasma and erythrocyte n-3 FA. Potential studies were identified through systematic literature search in PubMed, Embase and the Cochrane Library of Systematic reviews (1950 to October 2014). In all, fifty-six studies reporting n-3 in healthy individuals were included, of which thirty-four articles reported plasma PL and erythrocytes, and twenty-two reported plasma TL and erythrocytes. Meta-regressions were performed to quantify the ratio between plasma and erythrocyte n-3 FA weight percentages, controlling for covariates including age, sex and study design. The conversion ratios from plasma PL to erythrocytes for EPA, DHA, DPA and total n-3 PUFA are 0·75, 1·16, 2·32 and 1·22; the corresponding conversion ratios from plasma TL to erythrocytes are 1·00, 2·10, 3·85 and 2·08, respectively. The conversion ratios were validated using reported values from the literature and measured data from fifty individuals. The relative error of the predicted results were within 10 % of the mean reported values except for EPA, and the individual measured data except for DPA, in plasma TL. The conversion ratios between plasma PL and erythrocytes were more stable compared with plasma TL. Such conversion ratios will be useful for nutritionists or public health professionals to assess FA profiles of different populations using data collected with different methodologies.
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Transfusion-related immunomodulation: a reappraisal.
Youssef, LA, Spitalnik, SL
Current opinion in hematology. 2017;(6):551-557
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Abstract
PURPOSE OF REVIEW This review summarizes current and prior observations regarding transfusion-related immunomodulation (TRIM) and puts these ideas into a modern immunological context, incorporating concepts from innate, adaptive, and nutritional immunity. We propose that TRIM research focus on determining whether there are specific, well-defined immunosuppressive effects from transfusing 'pure' red blood cells (RBCs) themselves, along with the by-products produced by the stored RBCs as a result of the 'storage lesion.' Macrophages are a key cell type involved in physiological and pathological RBC clearance and iron recycling. The plasticity and diversity of macrophages makes these cells potential mediators of immune suppression that could constitute TRIM. RECENT FINDINGS Recent reports identified the capacity of macrophages and monocytes to exhibit 'memory.' Exposure to various stimuli, such as engulfment of apoptotic cells and interactions with ß-glucan and lipopolysaccharide, were found to induce epigenetic, metabolic, and functional changes in certain myeloid cells, particularly macrophages and monocytes. SUMMARY Macrophages may mediate the immunosuppressive aspects of TRIM that arise as a result of transfused RBCs and their storage lesion induced by-products.
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Maintenance and regulation of asymmetric phospholipid distribution in human erythrocyte membranes: implications for erythrocyte functions.
Arashiki, N, Takakuwa, Y
Current opinion in hematology. 2017;(3):167-172
Abstract
PURPOSE OF REVIEW The article summarizes new insights into the molecular mechanisms for the maintenance and regulation of the asymmetric distribution of phospholipids in human erythrocyte membranes. We focus on phosphatidylserine, which is primarily found in the inner leaflet of the membrane lipid bilayer under low Ca conditions (<1 μmol/l) and is exposed to the outer leaflet under elevated Ca concentrations (>1 μmol/l), when cells become senescent. Clarification of the molecular basis of phosphatidylserine flipping and scrambling is important for addressing long-standing questions regarding phosphatidylserine functions. RECENT FINDINGS ATP11C, a P-IV ATPase, has been identified as a major flippase in analyses of patient erythrocytes with a 90% reduction in flippase activity. Phospholipid scramblase 1 (PLSCR1) has been defined as a Ca-activated scramblase that is completely suppressed by membrane cholesterol under low Ca concentrations. SUMMARY For survival, phosphatidylserine surface exposure is prevented by cholesterol-mediated suppression of PLSCR1 under low Ca concentrations, irrespective of flipping by ATP11C. In senescent erythrocytes, PLSCR1 is activated by elevated Ca, resulting in phosphatidylserine exposure, allowing macrophage phagocytosis. These recent molecular findings establish the importance of the maintenance and regulation of phosphatidylserine distribution for both the survival and death of human erythrocytes.