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The Mystery of Red Blood Cells Extracellular Vesicles in Sleep Apnea with Metabolic Dysfunction.
Khalyfa, A, Sanz-Rubio, D
International journal of molecular sciences. 2021;(9)
Abstract
Sleep is very important for overall health and quality of life, while sleep disorder has been associated with several human diseases, namely cardiovascular, metabolic, cognitive, and cancer-related alterations. Obstructive sleep apnea (OSA) is the most common respiratory sleep-disordered breathing, which is caused by the recurrent collapse of the upper airway during sleep. OSA has emerged as a major public health problem and increasing evidence suggests that untreated OSA can lead to the development of various diseases including neurodegenerative diseases. In addition, OSA may lead to decreased blood oxygenation and fragmentation of the sleep cycle. The formation of free radicals or reactive oxygen species (ROS) can emerge and react with nitric oxide (NO) to produce peroxynitrite, thereby diminishing the bioavailability of NO. Hypoxia, the hallmark of OSA, refers to a decline of tissue oxygen saturation and affects several types of cells, playing cell-to-cell communication a vital role in the outcome of this interplay. Red blood cells (RBCs) are considered transporters of oxygen and nutrients to the tissues, and these RBCs are important interorgan communication systems with additional functions, including participation in the control of systemic NO metabolism, redox regulation, blood rheology, and viscosity. RBCs have been shown to induce endothelial dysfunction and increase cardiac injury. The mechanistic links between changes of RBC functional properties and cardiovascular are largely unknown. Extracellular vesicles (EVs) are secreted by most cell types and released in biological fluids both under physiological and pathological conditions. EVs are involved in intercellular communication by transferring complex cargoes including proteins, lipids, and nucleic acids from donor cells to recipient cells. Advancing our knowledge about mechanisms of RBC-EVs formation and their pathophysiological relevance may help to shed light on circulating EVs and to translate their application to clinical practice. We will focus on the potential use of RBC-EVs as valuable diagnostic and prognostic biomarkers and state-specific cargoes, and possibilities as therapeutic vehicles for drug and gene delivery. The use of RBC-EVs as a precision medicine for the diagnosis and treatment of the patient with sleep disorder will improve the prognosis and the quality of life in patients with cardiovascular disease (CVD).
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Pharmacogenomics with red cells: a model to study protein variants of drug transporter genes.
Flegel, WA, Srivastava, K, Sissung, TM, Goldspiel, BR, Figg, WD
Vox sanguinis. 2021;(2):141-154
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The PharmacoScan pharmacogenomics platform screens for variation in genes that affect drug absorption, distribution, metabolism, elimination, immune adverse reactions and targets. Among the 1,191 genes tested on the platform, 12 genes are expressed in the red cell membrane: ABCC1, ABCC4, ABCC5, ABCG2, CFTR, SLC16A1, SLC19A1, SLC29A1, ATP7A, CYP4F3, EPHX1 and FLOT1. These genes represent 5 ATP-binding cassette proteins, 3 solute carrier proteins, 1 ATP transport protein and 3 genes associated with drug metabolism and adverse drug reactions. Only ABCG2 and SLC29A1 encode blood group systems, JR and AUG, respectively. We propose red cells as an ex vivo model system to study the effect of heritable variants in genes encoding the transport proteins on the pharmacokinetics of drugs. Altered pharmacodynamics in red cells could also cause adverse reactions, such as haemolysis, hitherto unexplained by other mechanisms.
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Poor Birth Outcomes in Malaria in Pregnancy: Recent Insights Into Mechanisms and Prevention Approaches.
Chua, CLL, Hasang, W, Rogerson, SJ, Teo, A
Frontiers in immunology. 2021;:621382
Abstract
Pregnant women in malaria-endemic regions are susceptible to malaria in pregnancy, which has adverse consequences on birth outcomes, including having small for gestational age and preterm babies. These babies are likely to have low birthweights, which predisposes to infant mortality and lifelong morbidities. During malaria in pregnancy, Plasmodium falciparum-infected erythrocytes express a unique variant surface antigen, VAR2CSA, that mediates sequestration in the placenta. This process may initiate a range of host responses that contribute to placental inflammation and dysregulated placental development, which affects placental vasculogenesis, angiogenesis and nutrient transport. Collectively, these result in the impairment of placental functions, affecting fetal development. In this review, we provide an overview of malaria in pregnancy and the different pathological pathways leading to malaria in pregnancy-associated low birthweight. We also discuss current prevention and management strategies for malaria in pregnancy, and some potential therapeutic interventions that may improve birth outcomes. Lastly, we outline some priorities for future research that could bring us one step closer to reducing this health burden.
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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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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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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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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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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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Transfusion-related immunomodulation: a reappraisal.
Youssef, LA, Spitalnik, SL
Current opinion in hematology. 2017;(6):551-557
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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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Red Blood Cell Distribution Width: A Novel Predictive Indicator for Cardiovascular and Cerebrovascular Diseases.
Li, N, Zhou, H, Tang, Q
Disease markers. 2017;:7089493
Abstract
The red blood cell distribution width (RDW) obtained from a standard complete blood count (CBC) is a convenient and inexpensive biochemical parameter representing the variability in size of circulating erythrocytes. Over the past few decades, RDW with mean corpuscular volume (MCV) has been used to identify quite a few hematological system diseases including iron-deficiency anemia and bone marrow dysfunction. In recent years, many clinical studies have proved that the alterations of RDW levels may be associated with the incidence and prognosis in many cardiovascular and cerebrovascular diseases (CVDs). Therefore, early detection and intervention in time of these vascular diseases is critical for delaying their progression. RDW as a new predictive marker and an independent risk factor plays a significant role in assessing the severity and progression of CVDs. However, the mechanisms of the association between RDW and the prognosis of CVDs remain unclear. In this review, we will provide an overview of the representative literatures concerning hypothetical and potential epidemiological associations between RDW and CVDs and discuss the underlying mechanisms.
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Systematic review of adverse health outcomes associated with high serum or red blood cell folate concentrations.
Colapinto, CK, O'Connor, DL, Sampson, M, Williams, B, Tremblay, MS
Journal of public health (Oxford, England). 2016;(2):e84-97
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Abstract
BACKGROUND To examine the relationship between reported high serum or red blood cell (RBC) folate status and adverse health outcomes. METHODS We systematically searched PubMed/Medline and EMBASE (to May 2013), with no limits by study type, country or population, to identify studies reporting high folate concentrations in association with adverse health outcomes. Two reviewers screened studies and extracted data. Study quality was assessed. RESULTS We included 51 articles, representing 46 studies and 71 847 participants. Quantiles were used by 96% of studies to identify high folate concentrations. Eighty-three percent of serum folate and 50% of RBC folate studies reported a high folate cutoff that corresponded with a clinically normal concentration. Increasing values of reported high folate concentration did not demonstrate a consistent association with risk of adverse health outcomes. Overall, reported high folate concentrations appeared to be associated with a decreased risk of adverse health outcomes, though substantial methodological heterogeneity precluded complex analyses. CONCLUSIONS Our interpretation was complicated by methodological variability. High folate cutoffs varied and often corresponded with normal or desirable blood concentrations. In general, a negative association appeared to exist between reported high folate status and adverse health outcomes. Consistent methods and definitions are needed to examine high folate status and ultimately inform public health interventions.