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Blood Cells in Human Health and Disease

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: 28 February 2026 | Viewed by 3213

Special Issue Editor


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Guest Editor
1. Galilee Research Institute (MIGAL), Kiryat Shmona, Israel
2. Faculty of Sciences, Tel Hai Academic College, Upper Galilee, Israel
Interests: physiological; biophysical; red blood cells; RBCs; metabolic complications

Special Issue Information

Dear Colleagues,

Red blood cells (RBCs, or erythrocytes) are phenomenal cells whose functional responsibility is far from limited to oxygen delivery to the tissues of our body. The unique properties of the RBC membrane and cytoskeleton components, as well as the molecular interactions and regulation of hemoglobin and other cytosolic molecules, precisely determine their unique functionality in transporting respiratory gases and physiological regulations. It is evident that RBC physiological and biophysical features are drastically altered under numerous inherited and pathological conditions (e.g., congenital hemoglobinopathies, cardiovascular and metabolic abnormalities, infections) and aging (in vivo and during storage). These aspects are at the top of dynamic, interdisciplinary, and multifaceted RBC research. We are pleased to share that we have opened a Special Issue dedicated to novel studies of the biochemical, hemodynamic, and biophysical properties of RBCs. State-of-the-art novel findings about the interaction of erythrocytes with external factors and the implications of this exposure in health will be welcome. These issues can be discussed from an experimental, clinical, or numerical point of view.

Dr. Leonid Livshits
Guest Editor

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Keywords

  • red blood cell
  • RBC membrane
  • RBC biophysical properties
  • RBC rheology
  • RBC mechanical properties
  • RBC membrane vesiculation
  • RBC clearance
  • RBC in diabetes
  • hemoglobinopathies
  • RBC storage
 

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Published Papers (3 papers)

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Research

18 pages, 2211 KB  
Article
Pyruvate Kinase Deficiency: Markedly Decreased Reticulocyte PK Activity and Limited Specificity of the PK/HK Ratio
by Larisa Koleva, Ivan A. Dolgikh, Aleksandra V. Kryukova, Dmitry S. Prudinnik, Elizaveta A. Bovt, Soslan S. Shakhidzhanov, Svetlana G. Mann, Nataliya S. Smetanina, Fazoil I. Ataullakhanov and Elena I. Sinauridze
Int. J. Mol. Sci. 2025, 26(17), 8606; https://doi.org/10.3390/ijms26178606 - 4 Sep 2025
Viewed by 452
Abstract
Diagnosis of pyruvate kinase deficiency (PKD) remains challenging in clinical practice. The pyruvate kinase (PK) to hexokinase (HK) activity ratio (PK/HK) was proposed to reduce the confounding effect of reticulocytosis on PK activity measurement. However, decreased PK activity and PK/HK ratios have also [...] Read more.
Diagnosis of pyruvate kinase deficiency (PKD) remains challenging in clinical practice. The pyruvate kinase (PK) to hexokinase (HK) activity ratio (PK/HK) was proposed to reduce the confounding effect of reticulocytosis on PK activity measurement. However, decreased PK activity and PK/HK ratios have also been observed in other anemias, raising doubts about their diagnostic value. We assessed the diagnostic accuracy of PK/HK ratio versus PK activity in differentiating PKD from other hereditary anemias. This study included 41 patients with molecularly confirmed PKD and 62 patients with other anemias. We also evaluated the influence of reticulocytosis and transfusions on erythrocyte PK activity. The PK/HK ratio showed 73% specificity, while PK activity alone achieved 95%. In PKD patients, reticulocytosis did not affect PK activity because reticulocyte PK activity was already markedly reduced (23-fold) compared with controls. In other anemias, decreases in PK activity were present in both reticulocytes and erythrocytes, but to a lesser extent. Transfusions contribute more to the false-normal result of PK activity than reticulocytosis. Measuring reticulocyte-specific PK activity during regular transfusions provided reliable results, as only patient-derived reticulocytes are present in the blood. PK activity demonstrates higher specificity than PK/HK ratio in diagnosing PKD. Reticulocytosis is not a confounder, while transfusions remain the main limitation. Reticulocyte-specific PK activity measurement may improve diagnostic accuracy in transfused patients. Full article
(This article belongs to the Special Issue Blood Cells in Human Health and Disease)
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16 pages, 3978 KB  
Article
Cepharanthine Promotes Ca2+-Independent Premature Red Blood Cell Death Through Metabolic Insufficiency and p38 MAPK/CK1α/COX/MLKL/PKC/iNOS Signaling
by Shaymah H. Alruwaili, Jawaher Alsughayyir and Mohammad A. Alfhili
Int. J. Mol. Sci. 2025, 26(15), 7250; https://doi.org/10.3390/ijms26157250 - 27 Jul 2025
Viewed by 526
Abstract
Nonspecific toxicity to normal and malignant cells restricts the clinical utility of many anticancer drugs. In particular, anemia in cancer patients develops due to drug-induced toxicity to red blood cells (RBCs). The anticancer alkaloid, cepharanthine (CEP), elicits distinct forms of cell death including [...] Read more.
Nonspecific toxicity to normal and malignant cells restricts the clinical utility of many anticancer drugs. In particular, anemia in cancer patients develops due to drug-induced toxicity to red blood cells (RBCs). The anticancer alkaloid, cepharanthine (CEP), elicits distinct forms of cell death including apoptosis and autophagy, but its cytotoxicity to RBCs has not been investigated. Colorimetric and fluorometric techniques were used to assess eryptosis and hemolysis in control and CEP-treated RBCs. Cells were labeled with Fluo4/AM and annexin-V-FITC to measure Ca2+ and phosphatidylserine (PS) exposure, respectively. Forward scatter (FSC) was detected to estimate cell size, and extracellular hemoglobin along with lactate dehydrogenase and aspartate transaminase activities were assayed to quantify hemolysis. Physiological manipulation of the extracellular milieu and various signaling inhibitors were tested to dissect the underlying mechanisms of CEP-induced RBC death. CEP increased PS exposure and hemolysis indices and decreased FSC in a concentration-dependent manner with prominent membrane blebbing. Although no Ca2+ elevation was detected, chelation of intracellular Ca2+ by BAPTA-AM reduced hemolysis. Whereas SB203580, D4476, acetylsalicylic acid, necrosulfonamide, and melatonin inhibited both PS exposure and hemolysis, staurosporin, L-NAME, ascorbate, caffeine, adenine, and guanosine only prevented hemolysis. Interestingly, sucrose had a unique dual effect by exacerbating PS exposure and reversing hemolysis. Of note, blocking KCl efflux augmented PS exposure while aggravating hemolysis only under Ca2+-depleted conditions. CEP activates Ca2+-independent pathways to promote eryptosis and hemolysis. The complex cytotoxic profile of CEP can be mitigated by targeting the identified modulatory pathways to potentiate its anticancer efficacy. Full article
(This article belongs to the Special Issue Blood Cells in Human Health and Disease)
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17 pages, 5434 KB  
Article
An Evaluation of the Safety of Intravenous Injections of the Natural Extracellular Hemoglobin M101 in Dogs and Monkeys
by Elisabeth Leize-Zal, Leïla Demini, Benoît Barrou and Franck Zal
Int. J. Mol. Sci. 2025, 26(2), 842; https://doi.org/10.3390/ijms26020842 - 20 Jan 2025
Cited by 1 | Viewed by 1322
Abstract
Hemoglobin-based oxygen carriers have been developed to compensate the needs of blood for transfusions. Most of them were based on intracellular hemoglobin extracted from bovine or human blood, but unfortunately, this type of hemoglobin did not pass through the last steps of clinical [...] Read more.
Hemoglobin-based oxygen carriers have been developed to compensate the needs of blood for transfusions. Most of them were based on intracellular hemoglobin extracted from bovine or human blood, but unfortunately, this type of hemoglobin did not pass through the last steps of clinical trials. In this context, HEMARINA discovered a natural extracellular hemoglobin, possessing several advantages avoiding intracellular hemoglobin-related side effects. Many preclinical studies assessed the safety of M101 used in intravenous (IV) injection in rodents. To explore the safety of IV injections of M101 in large mammals, six dogs received each a single injection of liquid M101 according to a dose escalation with a 48 h follow-up. Then, two monkeys received multiple IV injections of the same dose of M101 every hour for seven hours. This study showed that single and multiple IV injections in dogs and monkeys did not cause clinical or histological lesions, nor did they induce immunological reactions. This makes M101 the best candidate to date for human use in emergency situations requiring blood and, in several diseases, causing hypoxia problems. Full article
(This article belongs to the Special Issue Blood Cells in Human Health and Disease)
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