New Approaches to the Diagnosis and Management of Anemia and Malaria

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Hematology".

Deadline for manuscript submissions: closed (25 April 2023) | Viewed by 11709

Special Issue Editor


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Guest Editor
Department of Medical Technology and Sciences, International University of Health and Welfare, Ohkawa, Fukuoka 831-8501, Japan
Interests: anemia; thalassemia; myelodysplastic syndrome; malaria; biomarker; iron metabolism; gene therapy; extracellular vesicle; epigenetics
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Special Issue Information

Dear Colleagues,

Red blood cells are the most abundant blood cells that carry oxygen and bicarbonate to keep gas exchange stable throughout the body. Almost 2 kg of circulating RBC mass is maintained under balance between daily production and destruction. Anemia is caused by a heterogenous mechanisms. For example, thalassemia is one of most common human hereditary diseases characterized by chronic ineffective erythropoiesis and hemolysis caused by genetic abnormalities of globin genes. Thalassemia is mainly limited to people in tropical areas. However, globalization of human activities has resulted in it becoming more common in non-tropical countries around the world. Thus, the prevention and control of thalassemia is a world-wide assignment. The effective clinical evaluation of the severity of thalassemia is essential for planning life-long treatment strategies. This Special Issue focuses on new tools for the diagnosis and management of thalassemia.

Progress in the understanding of the molecular mechanism of erythropoiesis has given us much new information on the pathophysiology of erythropoiesis-related infectious diseases such as malaria and parvovirus infection, in which pathogens attack erythroid cells. In this Special Issue, we wish to focus on malaria, the distribution of which overlaps with thalassemia in tropical areas.

To yield a comprehensive overview of the diagnosis and therapy of this disease based on the current knowledge, this Special Issue will accept any kind of studies from basic reviews to clinical papers.

Prof. Dr. Tsukuru Umemura
Guest Editor

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Keywords

  • anemia
  • thalassemia
  • myelodysplastic syndrome
  • malaria
  • biomarker
  • iron metabolism
  • gene therapy
  • extracellular vesicle
  • epigenetics

Published Papers (5 papers)

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Research

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12 pages, 3330 KiB  
Article
In Vitro Study of Ineffective Erythropoiesis in Thalassemia: Diverse Intrinsic Pathophysiological Features of Erythroid Cells Derived from Various Thalassemia Syndromes
by Woratree Kaewsakulthong, Thunwarat Suriyun, Sukanya Chumchuen, Usanarat Anurathapan, Suradej Hongeng, Suthat Fucharoen and Orapan Sripichai
J. Clin. Med. 2022, 11(18), 5356; https://doi.org/10.3390/jcm11185356 - 13 Sep 2022
Cited by 3 | Viewed by 1620
Abstract
Defective hemoglobin production and ineffective erythropoiesis contribute to the pathophysiology of thalassemia syndromes. Previous studies in the field of erythropoiesis mainly focused on the severe forms of thalassemia, such as β-thalassemia major, while mechanisms underlying the pathogenesis of other thalassemia syndromes remain largely [...] Read more.
Defective hemoglobin production and ineffective erythropoiesis contribute to the pathophysiology of thalassemia syndromes. Previous studies in the field of erythropoiesis mainly focused on the severe forms of thalassemia, such as β-thalassemia major, while mechanisms underlying the pathogenesis of other thalassemia syndromes remain largely unexplored. The current study aimed to investigate the intrinsic pathophysiological properties of erythroid cells derived from the most common forms of thalassemia diseases, including α-thalassemia (hemoglobin H and hemoglobin H-Constant Spring diseases) and β-thalassemia (homozygous β0-thalassemia and β0-thalassemia/hemoglobin E diseases), under an identical in vitro erythroid culture system. Cell proliferation capacity, differentiation velocity, cell death, as well as globin synthesis and the expression levels of erythropoiesis modifying factors were determined. Accelerated expansion was found in erythroblast cells derived from all types of thalassemia, with the highest degree in β0-thalassemia/hemoglobin E. Likewise, all types of thalassemia showed limited erythroid cell differentiation, but each of them manifested varying degrees of erythroid maturation arrest corresponding with the clinical severity. Robust induction of HSP70 transcripts, an erythroid maturation-related factor, was found in both α- and β-thalassemia erythroid cells. Increased cell death was distinctly present only in homozygous β0-thalassemia erythroblasts and associated with the up-regulation of pro-apoptotic (Caspase 9, BAD, and MTCH1) genes and down-regulation of the anti-apoptotic BCL-XL gene. Full article
(This article belongs to the Special Issue New Approaches to the Diagnosis and Management of Anemia and Malaria)
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21 pages, 2784 KiB  
Article
Extracellular Vesicles Derived from Early and Late Stage Plasmodium falciparum-Infected Red Blood Cells Contain Invasion-Associated Proteins
by Sinmanus Vimonpatranon, Sittiruk Roytrakul, Narumon Phaonakrop, Kittima Lekmanee, Anyapat Atipimonpat, Narinee Srimark, Kasama Sukapirom, Kesinee Chotivanich, Ladawan Khowawisetsut and Kovit Pattanapanyasat
J. Clin. Med. 2022, 11(14), 4250; https://doi.org/10.3390/jcm11144250 - 21 Jul 2022
Cited by 10 | Viewed by 2531
Abstract
In infectious diseases, extracellular vesicles (EVs) released from a pathogen or pathogen-infected cells can transfer pathogen-derived biomolecules, especially proteins, to target cells and consequently regulate these target cells. For example, malaria is an important tropical infectious disease caused by Plasmodium spp. Previous studies [...] Read more.
In infectious diseases, extracellular vesicles (EVs) released from a pathogen or pathogen-infected cells can transfer pathogen-derived biomolecules, especially proteins, to target cells and consequently regulate these target cells. For example, malaria is an important tropical infectious disease caused by Plasmodium spp. Previous studies have identified the roles of Plasmodium falciparum-infected red blood cell-derived EVs (Pf-EVs) in the pathogenesis, activation, and modulation of host immune responses. This study investigated the proteomic profiles of Pf-EVs isolated from four P. falciparum strains. We also compared the proteomes of EVs from (i) different EV types (microvesicles and exosomes) and (ii) different parasite growth stages (early- and late-stage). The proteomic analyses revealed that the human proteins carried in the Pf-EVs were specific to the type of Pf-EVs. By contrast, most of the P. falciparum proteins carried in Pf-EVs were common across all types of Pf-EVs. As the proteomics results revealed that Pf-EVs contained invasion-associated proteins, the effect of Pf-EVs on parasite invasion was also investigated. Surprisingly, the attenuation of parasite invasion efficiency was found with the addition of Pf-MVs. Moreover, this effect was markedly increased in culture-adapted isolates compared with laboratory reference strains. Our evidence supports the concept that Pf-EVs play a role in quorum sensing, which leads to parasite growth-density regulation. Full article
(This article belongs to the Special Issue New Approaches to the Diagnosis and Management of Anemia and Malaria)
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8 pages, 791 KiB  
Article
Impaired Terminal Erythroid Maturation in β0-Thalassemia/HbE Patients with Different Clinical Severity
by Thunwarat Suriyun, Pranee Winichagoon, Suthat Fucharoen and Orapan Sripichai
J. Clin. Med. 2022, 11(7), 1755; https://doi.org/10.3390/jcm11071755 - 22 Mar 2022
Cited by 1 | Viewed by 1835
Abstract
Anemia in β-thalassemia is associated with ineffective erythropoiesis and a shortened lifespan of erythroid cells. The limited differentiation of β-thalassemic erythroblasts has been documented, but the characteristic feature of terminal erythroid maturation and its physiological relevance are not clearly described in β-thalassemias. Here, [...] Read more.
Anemia in β-thalassemia is associated with ineffective erythropoiesis and a shortened lifespan of erythroid cells. The limited differentiation of β-thalassemic erythroblasts has been documented, but the characteristic feature of terminal erythroid maturation and its physiological relevance are not clearly described in β-thalassemias. Here, the red blood cell and reticulocyte cellular characteristics were determined in patients with β0-thalassemia/HbE in comparison to patients with iron deficiency anemia and healthy normal subjects. Severely affected β0-thalassemia/HbE patients showed the highest increase in immature reticulocytes, but the number of total erythrocytes was the lowest. Despite similar ranges of hemoglobin levels, β0-thalassemia/HbE patients had a higher number of reticulocytes and a greater proportion of immature fraction than patients with iron deficiency anemia did. In vitro CD34+ hematopoietic progenitor cells’ culture and flow cytometry analysis were conducted to investigate the erythroid maturation and mitochondrial clearance in β0-thalassemia/HbE erythroid cells as compared to normal cells. The delayed erythroid maturation and evidence of impaired mitochondria clearance were observed in β0-thalassemia/HbE cells at the terminal stage of differentiation. Additionally, increased transcript levels of genes related to erythroid mitophagy, BNIP3L and PINK1, were revealed in β0-thalassemia/HbE erythroblasts. The findings indicate that the erythroid maturation is physiologically relevant, and that the restoration of terminal maturation represents a potential therapeutic target for β-thalassemias. Full article
(This article belongs to the Special Issue New Approaches to the Diagnosis and Management of Anemia and Malaria)
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10 pages, 7476 KiB  
Article
Pre-Analytical Modification of Serum miRNAs: Diagnostic Reliability of Serum miRNAs in Hemolytic Diseases
by Yukichi Takada, Tatsuki Shibuta, Mayu Hatano, Kenichi Sato, Mari Koga, Ayaka Ishibashi, Tetsuhiro Harada, Takashi Hisatomi, Hanae Shimura, Noriyasu Fukushima, Kamonlak Leecharoenkiat, Supat Chamnanchanunt, Saovaros Svasti, Suthat Fucharoen and Tsukuru Umemura
J. Clin. Med. 2021, 10(21), 5045; https://doi.org/10.3390/jcm10215045 - 28 Oct 2021
Cited by 2 | Viewed by 1654
Abstract
Circulating microRNAs (miRNAs) are useful biomarkers of hemolysis. Since blood cells are the main origins of circulating miRNAs, we evaluated blood cell-related pre-analytical modification of the miRNA signatures during blood drawing and serum processing. The levels of miRNA before and after ex vivo [...] Read more.
Circulating microRNAs (miRNAs) are useful biomarkers of hemolysis. Since blood cells are the main origins of circulating miRNAs, we evaluated blood cell-related pre-analytical modification of the miRNA signatures during blood drawing and serum processing. The levels of miRNA before and after ex vivo blood drawing were analyzed with the reverse transcriptase-based polymerase chain reaction method. Furthermore, the changes of miRNA signatures caused by different time-lag between blood drawing and serum preparation by 24 h were evaluated. Finally, we compared the miRNA levels between leftover samples and samples of hemolytic diseases. Blood drawing procedure induced increments of red blood cell (RBC)-related miRNAs (miR-451a, miR-486) about 2-fold. One hour standing of blood samples before serum separation induced almost the same increases in RBC-related miRNAs. To test the clinical usefulness of miR-451a as a biomarker of hemolytic diseases, we analyzed miRNAs of samples from 10 normal subjects, 30 leftover samples in the clinical laboratory, and 20 samples from patients with hemolytic diseases. Serum miR-451a significantly increased in patients with hemolytic anemia more than the levels of pre-analytical modification. In conclusion, the pre-analytical modification of serum miRNAs did not disturb the usefulness of RBC-derived miRNAs as biomarkers of hemolytic diseases. Full article
(This article belongs to the Special Issue New Approaches to the Diagnosis and Management of Anemia and Malaria)
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Review

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8 pages, 1024 KiB  
Review
Helicobacter pylori Infection and Chronic Immune Thrombocytopenia
by Hiroaki Takeuchi and Aoi Okamoto
J. Clin. Med. 2022, 11(16), 4822; https://doi.org/10.3390/jcm11164822 - 17 Aug 2022
Cited by 12 | Viewed by 3205
Abstract
Approximately half of the world’s population is infected with Helicobacter pylori, which causes gastric disease. Recent systematic reviews and meta-analyses have reported that H. pylori may also have extragastric manifestations such as hematologic diseases, including chronic immune thrombocytopenia (cITP). However, the molecular [...] Read more.
Approximately half of the world’s population is infected with Helicobacter pylori, which causes gastric disease. Recent systematic reviews and meta-analyses have reported that H. pylori may also have extragastric manifestations such as hematologic diseases, including chronic immune thrombocytopenia (cITP). However, the molecular mechanisms by which H. pylori induces cITP remain unclear, and may involve the host immune response, bacterial strain diversity, and delivery of bacterial molecules to the host blood vessels. This review discusses the important pathophysiological mechanisms by which H. pylori potentially contributes to the development of cITP in infected patients. Full article
(This article belongs to the Special Issue New Approaches to the Diagnosis and Management of Anemia and Malaria)
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