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15 pages, 3126 KB  
Article
Green Tea Catechins Significantly Reduce Zika Virus in RBCs Through Viral Inactivation
by Xipeng Yan, Jinlian Li, Xiaoqiong Duan, Limin Chen, Yujia Li and Chunhui Yang
Pathogens 2026, 15(3), 334; https://doi.org/10.3390/pathogens15030334 - 20 Mar 2026
Viewed by 178
Abstract
Background: Despite significant improvements in blood safety, the risk of transfusion-transmitted infections persists, particularly from emerging and re-emerging viruses. For red blood cell (RBC) products, this risk is exacerbated by the fact that there is no routine testing for many of these pathogens, [...] Read more.
Background: Despite significant improvements in blood safety, the risk of transfusion-transmitted infections persists, particularly from emerging and re-emerging viruses. For red blood cell (RBC) products, this risk is exacerbated by the fact that there is no routine testing for many of these pathogens, and effective, commercially available pathogen inactivation technologies specifically for RBCs are still lacking. This gap in the safety framework means that viruses capable of establishing an asymptomatic viremia—a characteristic of many arboviruses like Zika, dengue, and West Nile virus—present a tangible threat to the blood supply, highlighting the need for broad-spectrum countermeasures. Study Design and Methods: This study aims to investigate the antiviral activity of green tea extract (GTE) and its key catechins, epigallocatechin gallate (EGCG) and epicatechin gallate (ECG), against ZIKV in both cellular models and red blood cell (RBC) products. In vitro antiviral activity was assessed using A549 cells treated with GTE (150 μg/mL) or purified EGCG/ECG (20 μM). Mechanistic studies focused on viral attachment inhibition. Additionally, ZIKV-spiked RBC products were co-incubated with GTE (300 μg/mL) for 1 h to evaluate virucidal effects. Erythrocyte integrity was confirmed via hemolysis assays. Results: Co-treatment with GTE or catechins suppressed ZIKV replication by ≥3.64 logs (p < 0.001) in A549 cells. GTE and catechins primarily inhibited viral attachment. In RBCs, GTE reduced viral infectivity by 99.99% (4-log reduction) without compromising erythrocyte membrane integrity or cellular viability. Furthermore, RBCs with added GTE demonstrated a lower hemolysis rate during storage for up to 60 days. Conclusions: GTE exhibits potent virucidal activity against ZIKV in blood matrices, highlighting its potential as a pathogen reduction agent to enhance transfusion safety. Further development of GTE-based additive solutions or technologies is warranted. Full article
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17 pages, 2170 KB  
Article
Comparative Evaluation of Commercial Bulk-Fill Resin-Based Composites: Flexural Properties, Roughness, Water Sorption and Solubility, and Color Stability
by Khalid S. Almulhim, Sarah M. Alghamdi, Raghad S. Alqahtani, Jood K. Alsahiem, Afnan O. Al-Zain, Mohammed M. Gad and Abdulrahman A. Balhaddad
Dent. J. 2026, 14(2), 117; https://doi.org/10.3390/dj14020117 - 14 Feb 2026
Viewed by 349
Abstract
Background/Objectives: Bulk-fill (BF) resin-based composites (RBCs) have become increasingly popular due to their efficient placement. However, there is a lack of comprehensive performance comparisons among commercially available BF RBCs. In standardized curing conditions, this study aimed to compare the mechanical performance, water [...] Read more.
Background/Objectives: Bulk-fill (BF) resin-based composites (RBCs) have become increasingly popular due to their efficient placement. However, there is a lack of comprehensive performance comparisons among commercially available BF RBCs. In standardized curing conditions, this study aimed to compare the mechanical performance, water sorption and solubility, surface roughness, and color stability of commercially available BF RBCs with different consistencies (flowable and packable). Methods: Ten BF RBCs, along with a conventional RBC (control), were evaluated. Flexural strength and elastic modulus were measured using a three-point bending test. Water sorption and solubility were assessed after 28-day water storage. Color (ΔE00) and surface roughness (ΔRa) changes were measured after 28-day immersion in water, Pepsi, or coffee. One-way ANOVA and Tukey’s tests analyzed the data. Results: 3M Flow, Shofu Bulk, and Ivoclar Flow revealed lower strength (p < 0.001) compared to 3M Bulk (132.17 ± 12.54 MPa) and the control (124.56 ± 15.60 MPa). Shofu Bulk (24.68 ± 12.55 µg/mm3) and Ivoclar Flow (27.11 ± 6.27 µg/mm3) were the least affected by water sorption. While Shofu Bulk (13.98 ± 11.39 µg/mm3), Ivoclar Flow (20.28 ± 6.64 µg/mm3), and SDR (20.84 ± 9.74 µg/mm3) exhibited the lowest solubility (p < 0.01). After water and Pepsi immersion, FGM Bulk showed a significant color change compared to 3M Bulk and Ivoclar Bulk (p < 0.05). Following coffee immersion, Shofu Bulk (17.38 ± 1.82) revealed significant color changes (p < 0.001). Increased surface roughness was observed in 3M Bulk and Ivoclar Bulk after water immersion, Shofu Bulk after Pepsi immersion, and FGM Bulk after coffee immersion. Conclusions: BF RBCs exhibit notable variability in their intrinsic properties. 3M Bulk and Control showed the highest strength, while Shofu Bulk had significant color changes. Full article
(This article belongs to the Section Dental Materials)
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12 pages, 1500 KB  
Article
Ex Vivo Evaluation of CD3+CD8+ T Cell Subpopulations in Red Blood Cell Concentrates: Does Storage Time Play an Important Role?
by Salih Haldun Bal, Levent Tufan Kumas, Lacin Cevhertas, Izel Yilmaz, Pinar Hiz-Ellergezen, Ferah Budak-Sener, Yasemin Heper and Haluk Barbaros Oral
J. Clin. Med. 2026, 15(3), 1178; https://doi.org/10.3390/jcm15031178 - 3 Feb 2026
Viewed by 349
Abstract
Background/Objectives: Our study was designed to explore the potential role of allogeneic CD8+ T lymphocytes present in red blood cell concentrates (RBCs) in the development of transfusion-related immunomodulation (TRIM) and the effect of storage time on these cells. Methods: From [...] Read more.
Background/Objectives: Our study was designed to explore the potential role of allogeneic CD8+ T lymphocytes present in red blood cell concentrates (RBCs) in the development of transfusion-related immunomodulation (TRIM) and the effect of storage time on these cells. Methods: From six units of whole blood, donated by volunteers, RBCs were obtained and each one was divided into three equal parts to provide the samples for storage days 0, 21, and 42. On related days, mononuclear cells (MNCs) were isolated from these RBC samples. MNCs were cultured, and phytohemagglutinin was added to half of the culture wells to stimulate the cells and achieve T cell division. Supernatants and MNCs were obtained from stimulated (STI) and unstimulated (US) wells. Supernatants were used for cytokine analyses, while MNCs were used to investigate the T cells and transcription factors. Results: The frequency of CD8+ T lymphocytes (Tc), their subgroups (Tc1, Tc2, and Tc17), specific transcription factors, and effector cytokines decreased during the storage time, but cell viability increased. CD3+CD8+TNF-α+ cells were significantly higher in the STI group on day 0 compared to the US group. Other cells did not respond to the mitogen (phytohemagglutinin) stimulation. Conclusions: During storage, the number of Tc cells and their ability to respond to mitogens decreased over time. The unresponsiveness was not recovered in ex vivo cell culture. Our findings suggest that transfused Tc cells are unlikely to be primary mediators of TRIM. Full article
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9 pages, 717 KB  
Communication
Mentha piperita Essential Oil in Olive Oil: Extending Erythrocyte Viability and Limiting Bacterial Growth Under Serum-Free Conditions
by Tina Novaković, Emina Mehmedović, Maja Krstić Ristivojević, Ivana Prodić, Vesna Jovanović, Milica Aćimović and Katarina Smiljanić
Molecules 2026, 31(3), 516; https://doi.org/10.3390/molecules31030516 - 2 Feb 2026
Viewed by 406
Abstract
Background: Serum-free culture of red blood cells (RBCs) typically leads to rapid loss of viability, limiting experimental and translational applications. Lipid-rich formulations and essential oils may provide biocompatible support for RBC integrity while limiting microbial overgrowth. Methods: RBCs from nine healthy adult donors [...] Read more.
Background: Serum-free culture of red blood cells (RBCs) typically leads to rapid loss of viability, limiting experimental and translational applications. Lipid-rich formulations and essential oils may provide biocompatible support for RBC integrity while limiting microbial overgrowth. Methods: RBCs from nine healthy adult donors were cultured in serum-free RPMI under four conditions: control, vehicle (olive oil, 1:100 v/v), genuine adenosine triphosphate (ATP)-oil® (1:100 v/v), and laboratory oil, “mimicking” ATP-oil®. Cultures were maintained for 18 days. Viability was assessed by light microscopy and trypan blue exclusion; bacterial contamination was qualitatively observed on day 18. Results: Genuine ATP-oil® maintained 35–45% RBC viability at day 18, whereas control and vehicle cultures declined rapidly. The mimicking preparation did not reproduce these effects. ATP-oil® immersion was associated with a qualitative reduction in bacterial contamination versus control, consistent with a dual action on RBC preservation and microbial suppression under serum-free conditions. Conclusions: Supplementation with ATP-oil® substantially prolongs RBC survival and limits bacterial overgrowth in vitro, outperforming commonly used serum or plasma supplements on a per-volume basis. These findings suggest potential applications for improving ex vivo handling or storage of blood components and for reducing background contamination in diagnostic microbiology. Further studies with larger cohorts are warranted to reveal underlying mechanisms and to define active constituents in order to standardize production. Full article
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17 pages, 2629 KB  
Article
Simulated Oxygen Supply Efficiency Assessment to Represent Stored Red Blood Cells Quality
by Zongtang Chu, Guoxing You, Weidan Li, Peilin Shu, Dong Qin, Lian Zhao, Hong Zhou and Ying Wang
Life 2026, 16(2), 205; https://doi.org/10.3390/life16020205 - 26 Jan 2026
Viewed by 331
Abstract
Hemolysis rate is usually used as the acceptance criterion for stored red blood cells (RBCs) in clinical practice. However, there is a current lack of parameters for the characterization of hemoglobin quality. This study aimed to incorporate oxygen affinity, cooperativity, and the Bohr [...] Read more.
Hemolysis rate is usually used as the acceptance criterion for stored red blood cells (RBCs) in clinical practice. However, there is a current lack of parameters for the characterization of hemoglobin quality. This study aimed to incorporate oxygen affinity, cooperativity, and the Bohr effect into a parameter system to monitor oxygen supply efficiency in stored RBCs, potentially serving as a basis for quality assessment. Han Chinese blood from plains, Tibetan blood from plateau, bovine hemoglobin (bHb), and a dextran–bovine hemoglobin conjugate (Dex20-bHb) were analyzed using the BLOODOX-2018. Oxygen affinity (P50) was determined by oxygen dissociation curves (ODCs) at pH = 7.4. Cooperativity was assessed through the Hill coefficient, calculated from the fitting range of the Hill equation. The Bohr effect was evaluated by the acid-base sensitivity index (SI) under simulated pH conditions of the lungs (pH = 7.6) and tissues (pH = 7.2) to calculate corresponding P50 values. Oxygen partial pressures (PO2) simulating lungs (PO2 = 100 mmHg for plains and 60 mmHg for plateau) and tissues (PO2 = 40 mmHg for plains and 30 mmHg for plateau) were used to calculate theoretical oxygen-release capacities in both environments. Multiple regression analysis explored relationships among parameters, constructing a system to assess changes in rat RBCs during storage. Optimized test methods determined P50, Hill coefficient, SI, and theoretical oxygen-release capacities for Han Chinese blood, Tibetan blood, bHb, and Dex20-bHb samples in various environments. We constructed a parameter system to characterize blood’s oxygen supply efficiency, revealing the significant influence of the Bohr effect. This influence varied with environmental changes in oxygen affinity. We validated the system using stored rat RBCs, finding consistent P50 trends with predictions, and initial increases in Hill coefficient and SI followed by decreases. Theoretical oxygen-release capacities varied significantly between plateau and plain environments. These results support using oxygen supply efficiency to assess RBC storage quality for developing transfusion strategies. P50, Hill coefficient, SI, and theoretical oxygen-release capacity in different environments can be incorporated into blood oxygen supply efficiency characterization systems to assess the quality changes in RBCs during storage. Full article
(This article belongs to the Section Physiology and Pathology)
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24 pages, 7353 KB  
Article
Parametric Optimization of RBC-PTES System: Impact on Round-Trip Efficiency and LCOS
by Paul Tafur-Escanta, Franco Cabrera-Ortega, Robert Valencia-Chapi, Luis Garzón-Pérez, Solimar Andrade-Terán and Javier Muñoz-Antón
Energies 2025, 18(24), 6594; https://doi.org/10.3390/en18246594 - 17 Dec 2025
Viewed by 469
Abstract
This study presents a comprehensive thermo-economic evaluation of a pumped thermal energy storage (PTES) system based on a supercritical carbon dioxide (s-CO2) recompression Brayton cycle (RBC). A multiparametric analysis was conducted through systematic parameterization of key design variables, including mass fractions [...] Read more.
This study presents a comprehensive thermo-economic evaluation of a pumped thermal energy storage (PTES) system based on a supercritical carbon dioxide (s-CO2) recompression Brayton cycle (RBC). A multiparametric analysis was conducted through systematic parameterization of key design variables, including mass fractions directed to the recompressor during charging and to the high-pressure turbine during discharging, as well as compressor inlet pressure and temperature and turbine inlet temperature. Performance optimization focused on two main indicators: round-trip efficiency (ηRT) and levelized cost of storage (LCOS), enabling identification of trade-offs between thermodynamic and economic performance. Results show that minimizing LCOS yields 148.72 $/MWh with an ηRT of 57.1%, whereas maximizing efficiency achieves 61.5% at an LCOS of 158.4 $/MWh. Exergy destruction analysis highlights the strategic role of the main compressor and thermal storage tanks in overall irreversibility distribution. These findings confirm the technical feasibility of the s-CO2 recompression Brayton cycle as a competitive solution for long-duration thermal energy storage. Full article
(This article belongs to the Special Issue Solar Energy Conversion and Storage Technologies)
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16 pages, 1058 KB  
Review
When Blood Remembers Its Sex: Toward Truly Personalized Transfusion Medicine
by Sotirios P. Fortis, Styliani Kokoris, Pavlos Kelepousidis, Georgios Dryllis, Maria-Aspasia Kosma, Theodoros Pittaras, Anastasios G. Kriebardis and Serena Valsami
J. Pers. Med. 2025, 15(12), 592; https://doi.org/10.3390/jpm15120592 - 3 Dec 2025
Viewed by 864
Abstract
Background: Biological sex differences are well-recognized as non-negligible factors in implementing precision medicine practice. Sex chromosomes influence protein expression and signaling, and thus cellular pathways are often regulated differently. Additionally, the importance of sex as a biological variable has gained significant traction [...] Read more.
Background: Biological sex differences are well-recognized as non-negligible factors in implementing precision medicine practice. Sex chromosomes influence protein expression and signaling, and thus cellular pathways are often regulated differently. Additionally, the importance of sex as a biological variable has gained significant traction in biomedical research, including transfusion medicine. Regarding transfusion medicine, several studies reveal the role of gender in blood transfusion, blood donors’ behavior towards donation, blood products’ composition and storage, transfusion therapy, and possibly post-transfusion patient outcomes. Methods: In this review, the role of sex and gender in the whole transfusion chain (from the blood donor to the blood product and the patient) is assessed and summarized using data from observational studies, registry analyses, and randomized trials. Results: Female donors face higher deferral rates due to biological factors (iron deficiency, low hemoglobin, pregnancy) and sociocultural factors (caregiving responsibilities, misinformation). However, women are more likely to donate based on empathy, moral duty, or community responsibility and are more consistent in sustaining voluntary donation during crises. Men donate more frequently, typically driven by external motivators, and provide red blood cell (RBC) products with higher hemoglobin content, whereas RBCs from female donors exhibit greater metabolic stability and reduced hemolysis during storage. Plasma from multiparous women possibly contains alloantibodies associated with adverse transfusion reactions, namely transfusion-related acute lung injury (TRALI). Platelet function also varies by sex, though its possible clinical impact is still unknown. Although observational studies suggest sex-mismatched transfusions are associated with increased morbidity and mortality—particularly in transfusions from female donors to male recipients—large registries and randomized controlled trials show inconsistent or negligible effect on survival. Conclusions: Donor and recipient sex are emerging variables of possible clinical importance in transfusion practice. Incorporating sex-informed insights into donor recruitment, blood product handling and transfusion policies may improve safety while advancing precision medicine. Further large-scale trials are needed to elucidate the impact of sex in transfusion, identify and eliminate possible risks, and bridge the gap between biological insights and clinical practice. Full article
(This article belongs to the Special Issue Advances in Transfusion Medicine and Immunological Research)
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22 pages, 3025 KB  
Article
Osmotic Fragility in Leukodepleted Stored Red Blood Cells: Implications for Neurocritical Care Transfusion Strategies
by Marta Peris, Maria A. Poca, Ana Ortuño, Verónica Pons, Nuria Rodríguez-Borrero, Desiree Jurado, Rafael Parra-López, Marina Rierola and Juan Sahuquillo
Cells 2025, 14(21), 1726; https://doi.org/10.3390/cells14211726 - 3 Nov 2025
Viewed by 1754
Abstract
Background: Anemia is frequent in critically ill patients with traumatic brain injury (TBI) and worsens neurological outcomes. Red blood cell (RBC) transfusion is a cornerstone of management, but storage-related biochemical and structural changes may impair oxygen delivery. This study examined the effect [...] Read more.
Background: Anemia is frequent in critically ill patients with traumatic brain injury (TBI) and worsens neurological outcomes. Red blood cell (RBC) transfusion is a cornerstone of management, but storage-related biochemical and structural changes may impair oxygen delivery. This study examined the effect of storage duration on osmotic fragility (OF) and free hemoglobin (fHb) in leukodepleted packed RBCs (pRBCs) as indicators of membrane stability and hemolysis. Methods: Twenty-four leukodepleted pRBC units in SAGM (saline, adenine, glucose, and mannitol) solution were analyzed from Day 3 to Day 42. OF was assessed by Beutler’s method with H50 values derived from logistic models, and fHb was quantified spectrophotometrically. Flow cytometry with phosphate-buffered saline (PBS)-induced osmotic stress provided complementary OF data. Results: OF increased significantly beyond 28 days, with Week 6 H50 values exceeding those at Weeks 2 and 4 (p < 0.0001). fHb rose progressively with storage: 7.3 ± 4.3 µmol/L (Week 2), 14.6 ± 7.9 (Week 4), and 25.7 ± 12.1 (Week 6) (p < 0.0001). Hemolysis remained below the 0.8% threshold but increased from 0.09% to 0.29% (p < 0.0001). Conclusions: pRBC storage beyond 28 days leads to greater OF and fHb release, reflecting reduced membrane stability. These changes may compromise transfusion efficacy and oxygen delivery in neurocritical care. Full article
(This article belongs to the Special Issue Highlights in Red Blood Cell Research)
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12 pages, 975 KB  
Article
Validation of Using Multiplex PCR with Sex Markers SSM4 and ALLWSex2 in Long-Term Stored Blood Samples to Determine Sex of the North American Shortnose Sturgeon (Acipenser brevirostrum)
by Hajar Sadat Tabatabaei Pozveh, Salar Dorafshan, Tillmann J. Benfey, Jason A. Addison and Matthew K. Litvak
Fishes 2025, 10(10), 478; https://doi.org/10.3390/fishes10100478 - 25 Sep 2025
Cited by 1 | Viewed by 1159
Abstract
Sex-specific information is crucial for sturgeon culture, conservation, and fisheries management. However, identifying their sex is difficult outside the spawning season. Two recently identified female-specific loci (AllWSex2 and SSM4) are conserved across many Acipenserid species, but they have not been validated for all [...] Read more.
Sex-specific information is crucial for sturgeon culture, conservation, and fisheries management. However, identifying their sex is difficult outside the spawning season. Two recently identified female-specific loci (AllWSex2 and SSM4) are conserved across many Acipenserid species, but they have not been validated for all species within this family. This study aimed to (1) determine whether SSM4 can be used to sex shortnose sturgeon, (2) develop and test a multiplex PCR technique using both ALLWSex2 and SSM4 for sexing shortnose sturgeon, (3) determine if long-term stored blood samples can be used to sex shortnose sturgeon, and (4) test the effect of storage temperature on DNA degradation. DNA was extracted from frozen RBC samples from 36 previously sexed fish. A multiplex PCR was set up using three pairs of primers: AllWSex2 and SSM4, as female-specific loci, and mtDNA, as an internal control. AllWSex2 and SSM4 allowed for perfect discrimination of sex. While long-term storage and storage temperature did cause DNA degradation, the signal was still strong enough after 8 years of cold storage for reliable sex determination. This suggests that researchers now have the ability to re-examine archived/frozen samples to determine the sex of their sturgeon. Full article
(This article belongs to the Section Genetics and Biotechnology)
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16 pages, 4967 KB  
Article
Pathogen-Reduced Low-Titer Group O Whole Blood for Managing Massive Blood Loss in Prehospital and Early Hospital Settings: An In Vitro Study
by Ekaterina Sherstyukova, Julia Semenova, Snezhanna Kandrashina, Alina Bogdanova, Ilya Vinogradov, Vladimir Inozemtsev, Mikhail Shvedov, Alexander Grechko, Maxim Dokukin, Artem Kuzovlev, Elena Klychnikova, Andrey Bulanov, Alexander Kostin and Viktoria Sergunova
J. Clin. Med. 2025, 14(17), 6292; https://doi.org/10.3390/jcm14176292 - 5 Sep 2025
Viewed by 1498
Abstract
Background/Objectives: Leukoreduced low-titer group O whole blood (LTOWB) is a promising option for early transfusion in massive hemorrhages, by providing red blood cells (RBCs), plasma, and platelets in a single unit. This study aimed to assess the effects of pathogen reduction (PR) [...] Read more.
Background/Objectives: Leukoreduced low-titer group O whole blood (LTOWB) is a promising option for early transfusion in massive hemorrhages, by providing red blood cells (RBCs), plasma, and platelets in a single unit. This study aimed to assess the effects of pathogen reduction (PR) on the LTOWB quality and its suitability for emergency transfusions, including its post-thaw RBC usability. Methods: Whole blood from 24 donors was processed and analyzed over seven days, including post-thaw assessments. Hematological and coagulation parameters, along with atomic force microscopy, were used to assess the RBCs’ morphology, cytoskeletal integrity, and nanomechanical properties. Results: The PR reduced the leukocyte content while preserving platelet counts at the level of the control group. Although certain clotting factors, such as fibrinogen (p < 0.001) and factor VIII (p < 0.001), were diminished after the PR, thromboelastometry results remained within reference ranges, indicating a maintained hemostatic potential. Morphological changes in RBCs were observed, but the membrane elasticity remained stable throughout storage and after thawing, indicating preserved macromechanical properties essential for hemostasis. Conclusions: These findings demonstrate that LTOWB treated with partial a leukoreduction and PR maintains functional and structural integrity, supporting its potential utility as a safe and effective transfusion product for managing acute blood loss. Full article
(This article belongs to the Section Hematology)
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13 pages, 1151 KB  
Article
Time-Dependent Changes in Malondialdehyde and Free-Hemoglobin in Leukoreduced and Non-Leukoreduced Canine Packed Red Blood Cells Units During Storage
by Arianna Miglio, Aurora Barbetta, Valentina Cremonini, Olimpia Barbato, Giovanni Ricci, Valeria Toppi, Luca Avellini, Valentina Cavani and Maria Teresa Antognoni
Vet. Sci. 2025, 12(9), 838; https://doi.org/10.3390/vetsci12090838 - 30 Aug 2025
Viewed by 1242
Abstract
Storage of Blood units determines the accumulation of harmful substances, such as malondialdehyde (MDA) and free hemoglobin (fHb). These may lead to several complications, including cardiovascular, neurodegenerative, and metabolic disorders in recipients. The objective of this study was to evaluate the concentrations of [...] Read more.
Storage of Blood units determines the accumulation of harmful substances, such as malondialdehyde (MDA) and free hemoglobin (fHb). These may lead to several complications, including cardiovascular, neurodegenerative, and metabolic disorders in recipients. The objective of this study was to evaluate the concentrations of MDA and fHb in canine leukoreduced (LR) and non-leukoreduced (NLR) packed red blood cells (pRBC) during the storage period of six weeks. Blood samples were collected from six healthy adult Weimaraner dogs (three females and three males). Whole blood was stored in citrate-phosphate-dextrose saline-adenine-glucose-mannitol additive solution (CPD-SAGM) bags and, for each donor, two pRBC units (one NLR and one LR) were produced and stored at 4 °C for 42 days. Samples were collected on days 0, 7, 14, 21, 28, 35, and 42, and analyzed for malondialdehyde (MDA) using a canine-specific ELISA method, and for free hemoglobin (fHb) using the Harboe direct spectrophotometric method. The results demonstrated a statistically significant reduction in MDA accumulation in LR-pRBC compared to NLR-pRBC blood units and lower values of fHb in LR at T6. However, no significant difference in fHb levels were demonstrated. These findings suggest that leukoreduction may limit oxidative stress during blood storage, reducing the potential adverse effects of transfusions related to oxidative damage. Full article
(This article belongs to the Section Veterinary Internal Medicine)
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24 pages, 1850 KB  
Review
Pathophysiological Associations and Measurement Techniques of Red Blood Cell Deformability
by Minhui Liang, Dawei Ming, Jianwei Zhong, Choo Sheriel Shannon, William Rojas-Carabali, Kajal Agrawal, Ye Ai and Rupesh Agrawal
Biosensors 2025, 15(9), 566; https://doi.org/10.3390/bios15090566 - 28 Aug 2025
Cited by 3 | Viewed by 3714
Abstract
Red blood cell (RBC), accounting for approximately 45% of total blood volume, are essential for oxygen delivery and carbon dioxide removal. Their unique biconcave morphology, high surface area-to-volume ratio, and remarkable deformability enable them to navigate microvessels narrower than their resting diameter, ensuring [...] Read more.
Red blood cell (RBC), accounting for approximately 45% of total blood volume, are essential for oxygen delivery and carbon dioxide removal. Their unique biconcave morphology, high surface area-to-volume ratio, and remarkable deformability enable them to navigate microvessels narrower than their resting diameter, ensuring efficient microcirculation. RBC deformability is primarily determined by membrane viscoelasticity, cytoplasmic viscosity, and cell geometry, all of which can be altered under various physiological and pathological conditions. Reduced deformability is a hallmark of numerous diseases, including sickle cell disease, malaria, diabetes mellitus, sepsis, ischemia–reperfusion injury, and storage lesions in transfused blood. As these mechanical changes often precede overt clinical symptoms, RBC deformability is increasingly recognized as a sensitive biomarker for disease diagnosis, prognosis, and treatment monitoring. Over the past decades, diverse techniques have been developed to measure RBC deformability. These include single-cell methods such as micropipette aspiration, optical tweezers, atomic force microscopy, magnetic twisting cytometry, and quantitative phase imaging; bulk approaches like blood viscometry, ektacytometry, filtration assays, and erythrocyte sedimentation rate; and emerging microfluidic platforms capable of high-throughput, physiologically relevant measurements. Each method captures distinct aspects of RBC mechanics, offering unique advantages and limitations. This review synthesizes current knowledge on the pathophysiological significance of RBC deformability and the methods for its measurement. We discuss disease contexts in which deformability is altered, outline mechanical models describing RBC viscoelasticity, and provide a comparative analysis of measurement techniques. Our aim is to guide the selection of appropriate approaches for research and clinical applications, and to highlight opportunities for developing robust, clinically translatable diagnostic tools. Full article
(This article belongs to the Special Issue Microfluidics for Sample Pretreatment)
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16 pages, 1064 KB  
Article
Variability in the Deformability of Red Blood Cells: Application to Treating Premature Newborns with Blood Transfusion
by Dan Arbell, Alexander Gural, Gregory Barshtein, Sinan Abu-Leil, Lisandro Luques, Benny Gazer and Saul Yedgar
Int. J. Mol. Sci. 2025, 26(17), 8144; https://doi.org/10.3390/ijms26178144 - 22 Aug 2025
Viewed by 1625
Abstract
Blood units are routinely collected from adult donors and stored as packed red blood cells (PRBC). The quality of PRBC, including their deformability, decreases during storage. Since PRBC transfusion has been reported to promote circulatory issues in premature neonates (PNs), they typically receive [...] Read more.
Blood units are routinely collected from adult donors and stored as packed red blood cells (PRBC). The quality of PRBC, including their deformability, decreases during storage. Since PRBC transfusion has been reported to promote circulatory issues in premature neonates (PNs), they typically receive freshly stored units. To test the hypothesis that freshly stored PRBCs can provide red blood cells (RBCs) with appropriate deformability for PN recipients, we compared the deformability of PRBCs transfused to PNs with that of cord blood RBCs (CRBCs), which are known to have deformability equivalent to that of newborn RBCs (PN-RBC). We found that, on average, CRBC deformability was higher than that of PRBCs. However, both showed significant variability with overlapping ranges. A highly significant correlation was observed between cell deformability and the combined levels of specific membrane proteins (ezrin, stomatin, flotillins) and membrane-bound hemoglobin (Pearson coefficient > 0.70, p < 0.02). This study indicates that the storage duration is inadequate for selecting PRBCs for PN recipients. PRBCs with deformability similar to that of PN-RBCs could enable safer and more effective transfusions for PN patients. Measuring membrane proteins alongside membrane-bound hemoglobin can serve as a useful method for selecting appropriate PRBC units for transfusion to PNs. Full article
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14 pages, 387 KB  
Review
Red Blood Cells and Human Aging: Exploring Their Biomarker Potential
by Roula P. Kyriacou and Sapha Shibeeb
Diagnostics 2025, 15(16), 1993; https://doi.org/10.3390/diagnostics15161993 - 8 Aug 2025
Cited by 5 | Viewed by 3580
Abstract
Aging is a complex biological process marked by progressive physiological decline with increasing vulnerability to diseases such as cardiovascular disorders, neurodegenerative conditions, and metabolic syndromes. Identifying reliable biomarkers of aging is essential for assessing biological age, predicting health outcomes, and guiding interventions to [...] Read more.
Aging is a complex biological process marked by progressive physiological decline with increasing vulnerability to diseases such as cardiovascular disorders, neurodegenerative conditions, and metabolic syndromes. Identifying reliable biomarkers of aging is essential for assessing biological age, predicting health outcomes, and guiding interventions to promote healthy aging. Among various candidate biomarkers, red blood cells (RBCs) offer a unique and accessible window into the aging process due to their abundance, finite lifespan, and responsiveness to systemic changes. This review examines the potential of RBCs as biomarkers of aging by exploring their age-associated morphological, functional, and biochemical alterations. Age-related reduction in key haematological parameters such as RBC count, haemoglobin concentration, and haematocrit, and increases in mean cell volume (MCV) and red cell distribution width (RDW), reflect underlying shifts in erythropoiesis and cellular turnover. Functional changes include reduced oxygen-carrying capacity, decreased deformability, diminished ATP release, and increased RBC aggregation, all of which may impair both macrocirculatory and microcirculatory flow and tissue oxygenation. Biochemically, aging RBCs exhibit altered membrane lipid and protein composition, reduced membrane fluidity, and diminished antioxidant and enzymatic activity, contributing to cellular senescence and clearance. Despite these promising indicators, challenges persist in establishing RBC parameters as definitive biomarkers of aging. Inter-individual and intra-individual variability and storage-related artifacts complicate their use. In conclusion, RBCs present a compelling, though currently underutilized, avenue for aging biomarker research. Further longitudinal validation and mechanistic research are essential to support the clinical utility of RBC parameters as biomarkers of aging. Full article
(This article belongs to the Special Issue Advances in Laboratory Markers of Human Disease)
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Article
Biotype Determines Survival of Yersinia enterocolitica in Red Blood Cell Concentrates
by Katarzyna Morka, Sylwia Banaszkiewicz, Jakub Korkus, Jacek Bania, Jarosław Bystroń, Gabriela Bugla-Płoskońska, Marta Stanek, Urszula Sokalska, Małgorzata Szymczyk-Nużka, Samuel K. Sheppard and Ben Pascoe
Int. J. Mol. Sci. 2025, 26(12), 5775; https://doi.org/10.3390/ijms26125775 - 16 Jun 2025
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Abstract
Red blood cell (RBC) concentrates remain at risk of bacterial contamination during cold storage. Although infrequent, Yersinia enterocolitica poses a significant blood safety risk. This study aimed to assess Y. enterocolitica bioserotype growth in RBC concentrates, serum sensitivity, and genetic diversity including iron [...] Read more.
Red blood cell (RBC) concentrates remain at risk of bacterial contamination during cold storage. Although infrequent, Yersinia enterocolitica poses a significant blood safety risk. This study aimed to assess Y. enterocolitica bioserotype growth in RBC concentrates, serum sensitivity, and genetic diversity including iron metabolism genes. Ten Y. enterocolitica isolates from bioserotypes 1A, 1B/O:8, 4/O:3, and 2/O:9 were incubated in RBC concentrates and counted on days 3, 7, 14, 21, and 28. After incubation, the isolates were tested in human serum (NHS). Eight genomes were sequenced, analyzed using cgMLST, and screened for iron metabolism genes. The isolates formed two clusters, with 186dz (1A) and Ye8 (1B/O:8) as singletons. After 28 days in the RBC concentrates, the bacterial counts ranged from 1.98 × 10⁵ to 1.2 × 10⁹ CFU/mL, with Ye8 (1B/O:8) achieving the highest growth and one 4/O:3 isolate showing the lowest. All isolates survived 15–30 min in NHS, but the 28s isolate did not survive at 60 min. Serum sensitivity increased in two isolates, decreased in three, and remained unchanged in five. Isolates contained 27–42 iron metabolism genes with multiple allelic variants. The iron metabolism gene content or variants may influence the growth of Y. enterocolitica in RBC. Full article
(This article belongs to the Section Molecular Microbiology)
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