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Metabolites
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Advances in Iron Metabolism and Anemia
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Advances in Iron Metabolism and Anemia

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Cell Metabolism".

Deadline for manuscript submissions: closed (15 April 2022) | Viewed by 22949

Special Issue Editors

Dr. Immacolata Andolfo

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Guest Editor
Dip. di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, Naples, Italy
Interests: red blood cell membrane defects; iron metabolism; molecular genetics; hereditary anemias; cell signaling; pathophysiologic mechanisms of hereditary anemias; dehydrated hereditary stomatocytosis; PIEZO1
Special Issues, Collections and Topics in MDPI journals
Dr. Roberta Russo

E-Mail Website
Guest Editor
1. Department of Molecular Medicine and Medical Biotechnologies, University Federico II of Naples, 80136 Napoli, Italy
2. CEINGE, Biotecnologie Avanzate, 80145 Napoli, Italy
Interests: congenital dyserythropoietic anemias; erythropoiesis; abnormal erythropoiesis; hereditary anemias; molecular genetics; genomics of hereditary anemias
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Iron is essential for hemoglobin synthesis and crucial for all cells for the production of heme and iron–sulfur clusters, which are components of the proteins/enzymes involved in vital biological processes, such as respiration, nucleic acid replication and repair, metabolic reactions and host defense. Research in this field has made great strides in the last few years and has clarified the role of iron in physiology and diseases. Iron is indispensable for life, but excess iron is toxic. The ability to accept/release electrons explains the tendency of iron to damage cell components and is the reason why body iron must be finely regulated. The disorders associated with alterations of iron metabolism span from iron overload to iron deficiency. The studies of genetic and acquired iron disorders have identified novel iron genes, proteins and pathways and revealed the essential role of the hepcidin–ferroportin axis in systemic iron homeostasis.

The aim of this issue is to achieve an overview of the diseases associated with iron metabolism alterations. We will focus on genetic conditions characterized by iron overload without anemia (hereditary hemochromatosis); iron-loading hereditary anemias (thalassemia syndromes, congenital sideroblastic anemia, congenital dyserythropoietic anemia, hypotransferrinemia, DMT1 mutations, dehydrated hereditary stomatocytosis); genetic iron deficiency (IRIDA); genetic regional iron-ferritin accumulation (hyperferritinemia-cataract syndrome, ferritinopathy); acquired iron overload (chronic blood transfusions); acquired iron-loading anemias (ringed sideroblast myelodysplastic syndrome); acquired absolute iron deficiency; acquired functional iron deficiency (anemia of inflammation). We also aim to highlight new methods allowing the detection of links between disease and iron metabolism.

Dr. Immacolata Andolfo
Dr. Roberta Russo
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Metabolites is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • iron overload
  • iron deficiency
  • pathogenic mechanisms of alteration of iron metabolism
  • physiology of iron metabolism.

Published Papers (6 papers)

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Editorial

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3 pages, 194 KiB  
Editorial
Novel Insights and Future Perspective in Iron Metabolism and Anemia
by Immacolata Andolfo and Roberta Russo
Metabolites 2022, 12(2), 138; https://doi.org/10.3390/metabo12020138 - 02 Feb 2022
Viewed by 1236
Abstract
Iron is an essential element for nearly all living organisms [...] Full article
(This article belongs to the Special Issue Advances in Iron Metabolism and Anemia)

Research

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9 pages, 273 KiB  
Article
Associated Effect of SLC40A1 and TMPRSS6 Polymorphisms on Iron Overload
by Lorena Duca, Francesca Granata, Elena Di Pierro, Valentina Brancaleoni, Giovanna Graziadei and Isabella Nava
Metabolites 2022, 12(10), 919; https://doi.org/10.3390/metabo12100919 - 29 Sep 2022
Viewed by 1332
Abstract
Mutations in the ferroportin (FPN) gene SLC40A1 alter iron recycling and cause disturbances in iron homeostasis. The variants of TMPRSS6 contribute to the development of iron deficiencies. In this study, we determined the role of FPN and TMPRSS6 gene polymorphisms in the modulation [...] Read more.
Mutations in the ferroportin (FPN) gene SLC40A1 alter iron recycling and cause disturbances in iron homeostasis. The variants of TMPRSS6 contribute to the development of iron deficiencies. In this study, we determined the role of FPN and TMPRSS6 gene polymorphisms in the modulation of iron homeostasis based on biochemical parameters. PCR analysis and sequencing were performed to determine the single nucleotide polymorphisms (SNPs) SLC40A1 c.44–24G>C (rs1439816), SLC40A1 c.663T>C (rs2304704), and TMPRSS6 c.2207T>C (rs855791). Hemoglobin concentration and iron status were determined by standard procedures. We studied 79 iron-loaded individuals for SLC40A1 polymorphisms. Interestingly, 35/79 individuals with SLC40A1 SNPs also carried a TMPRSS6 c.2207T>C polymorphism. The biochemical values of the iron overloaded individuals were compared to those of the individuals carrying TMPRSS6 SNPs and the healthy individuals (wild-type group). The ferritin concentration, transferrin saturation % (TS%), and hemoglobin concentration were significantly higher in the participants with FPN SNPs than in the other three groups. The ferritin concentration and TS% were higher in participants with both SLC40A1 and TMPRSS6 SNPs than in the TMPRSS6 and wild-type groups, while hemoglobin concentration was significantly higher than that in the TMPRSS6 SNP group only. The participants with TMPRSS6 SNPs had significantly lower ferritin concentration, TS%, and hemoglobin concentration than all the other groups. SLC40A1 and TMPRSS6 SNPs might act in the opposite direction, preventing the development of severe iron overload, and the modulation of the iron status by TMPRSS6 SNPs might provide protection. Full article
(This article belongs to the Special Issue Advances in Iron Metabolism and Anemia)
15 pages, 1470 KiB  
Article
The Impact of Iron Dyshomeostasis and Anaemia on Long-Term Pulmonary Recovery and Persisting Symptom Burden after COVID-19: A Prospective Observational Cohort Study
by Thomas Sonnweber, Philipp Grubwieser, Sabina Sahanic, Anna Katharina Böhm, Alex Pizzini, Anna Luger, Christoph Schwabl, Sabine Koppelstätter, Katharina Kurz, Bernhard Puchner, Barbara Sperner-Unterweger, Katharina Hüfner, Ewald Wöll, Manfred Nairz, Gerlig Widmann, Ivan Tancevski, Judith Löffler-Ragg and Günter Weiss
Metabolites 2022, 12(6), 546; https://doi.org/10.3390/metabo12060546 - 14 Jun 2022
Cited by 11 | Viewed by 3114
Abstract
Coronavirus disease 2019 (COVID-19) is frequently associated with iron dyshomeostasis. The latter is related to acute disease severity and COVID-19 convalescence. We herein describe iron dyshomeostasis at COVID-19 follow-up and its association with long-term pulmonary and symptomatic recovery. The prospective, multicentre, observational cohort [...] Read more.
Coronavirus disease 2019 (COVID-19) is frequently associated with iron dyshomeostasis. The latter is related to acute disease severity and COVID-19 convalescence. We herein describe iron dyshomeostasis at COVID-19 follow-up and its association with long-term pulmonary and symptomatic recovery. The prospective, multicentre, observational cohort study “Development of Interstitial Lung Disease (ILD) in Patients With Severe SARS-CoV-2 Infection (CovILD)” encompasses serial extensive clinical, laboratory, functional and imaging evaluations at 60, 100, 180 and 360 days after COVID-19 onset. We included 108 individuals with mild-to-critical acute COVID-19, whereas 75% presented with severe acute disease. At 60 days post-COVID-19 follow-up, hyperferritinaemia (35% of patients), iron deficiency (24% of the cohort) and anaemia (9% of the patients) were frequently found. Anaemia of inflammation (AI) was the predominant feature at early post-acute follow-up, whereas the anaemia phenotype shifted towards iron deficiency anaemia (IDA) and combinations of IDA and AI until the 360 days follow-up. The prevalence of anaemia significantly decreased over time, but iron dyshomeostasis remained a frequent finding throughout the study. Neither iron dyshomeostasis nor anaemia were related to persisting structural lung impairment, but both were associated with impaired stress resilience at long-term COVID-19 follow-up. To conclude, iron dyshomeostasis and anaemia are frequent findings after COVID-19 and may contribute to its long-term symptomatic outcome. Full article
(This article belongs to the Special Issue Advances in Iron Metabolism and Anemia)
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12 pages, 3055 KiB  
Article
Intestinal Absorption Study of a Granular Form of Ferric Pyrophosphate
by Marta Micheletto, Elisa Gaio, Erik Tedesco, Giovanni Di Maira, Etienne Mantovan, Michela Zanella, Paolo Pastore, Marco Roverso, Gabriella Favaro and Federico Benetti
Metabolites 2022, 12(5), 463; https://doi.org/10.3390/metabo12050463 - 21 May 2022
Cited by 3 | Viewed by 2309
Abstract
Iron deficiency is one of the most prevalent nutritional disorders worldwide. The standard treatment involves iron supplementation, but this task is challenging because of poor solubility and organoleptic issues. Moreover, the need to increase iron bioavailability represents a challenge for treating iron-related disorders. [...] Read more.
Iron deficiency is one of the most prevalent nutritional disorders worldwide. The standard treatment involves iron supplementation, but this task is challenging because of poor solubility and organoleptic issues. Moreover, the need to increase iron bioavailability represents a challenge for treating iron-related disorders. In this study, gastroresistance and iron intestinal absorption of an innovative granular formulation composed of ferric pyrophosphate, modified starch and phospholipids branded as Ferro Fosfosoma® was investigated. Gastroresistant properties were studied using standard protocols, and a bioaccessible fraction was obtained by exposing a food supplement to in vitro digestion. This fraction was used for investigating iron absorption in Caco-2 and human follicle-associated intestinal epithelium (FAE) models. Ferro Fosfosoma® showed an improved resistance to gastric digestion and higher intestinal absorption than ferric pyrophosphate salt used as a control in both models. In the FAE model, Ferro Fosfosoma® induces larger iron absorption than in the Caco-2 monolayer, most likely due to the transcytosis ability of M cells. The larger iron absorption in the Ferro Fosfosoma®-treated FAE model corresponds to higher ferritin level, proving physiological iron handling that was once delivered by granular formulation. Finally, the formulation did not induce any alterations in viability and barrier integrity. To conclude, Ferro Fosfosoma® favors iron absorption and ferritin expression, while preserving any adverse effects. Full article
(This article belongs to the Special Issue Advances in Iron Metabolism and Anemia)
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Review

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11 pages, 874 KiB  
Review
The Role of Ferritin in Health and Disease: Recent Advances and Understandings
by Nikhil Kumar Kotla, Priyata Dutta, Sanjana Parimi and Nupur K. Das
Metabolites 2022, 12(7), 609; https://doi.org/10.3390/metabo12070609 - 30 Jun 2022
Cited by 17 | Viewed by 6175
Abstract
Systemic iron homeostasis needs to be tightly controlled, as both deficiency and excess iron cause major global health concerns, such as iron deficiency anemia, hemochromatosis, etc. In mammals, sufficient dietary acquisition is critical for fulfilling the systemic iron requirement. New questions are emerging [...] Read more.
Systemic iron homeostasis needs to be tightly controlled, as both deficiency and excess iron cause major global health concerns, such as iron deficiency anemia, hemochromatosis, etc. In mammals, sufficient dietary acquisition is critical for fulfilling the systemic iron requirement. New questions are emerging about whether and how cellular iron transport pathways integrate with the iron storage mechanism. Ferritin is the intracellular iron storage protein that stores surplus iron after all the cellular needs are fulfilled and releases it in the face of an acute demand. Currently, there is a surge in interest in ferritin research after the discovery of novel pathways like ferritinophagy and ferroptosis. This review emphasizes the most recent ferritin-related discoveries and their impact on systemic iron regulation. Full article
(This article belongs to the Special Issue Advances in Iron Metabolism and Anemia)
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13 pages, 1397 KiB  
Review
New Insights into Iron Deficiency Anemia in Children: A Practical Review
by Carla Moscheo, Maria Licciardello, Piera Samperi, Milena La Spina, Andrea Di Cataldo and Giovanna Russo
Metabolites 2022, 12(4), 289; https://doi.org/10.3390/metabo12040289 - 25 Mar 2022
Cited by 9 | Viewed by 7371
Abstract
Iron deficiency anemia (IDA) is the most frequent hematological disorder in children, with an incidence in industrialized countries of 20.1% between 0 and 4 years of age and 5.9% between 5 and 14 years (39 and 48.1% in developing countries). Although IDA has [...] Read more.
Iron deficiency anemia (IDA) is the most frequent hematological disorder in children, with an incidence in industrialized countries of 20.1% between 0 and 4 years of age and 5.9% between 5 and 14 years (39 and 48.1% in developing countries). Although IDA has been recognized for a long time, there are still uncovered issues and room for improving the management of this condition. New frontiers regarding its diagnosis and therapeutic options emerge every day; recently, innovative formulations of iron have been launched, both for oral and parenteral administration, with the aim of offering treatment schedules with higher efficacy and lower toxicity. As a matter of fact, glycinate and liposomal preparations, while maintaining a satisfying efficacy profile, have significantly fewer side effects, in comparison to the traditional elemental iron salts; parenteral iron, usually considered a second-choice therapy reserved to selected cases, may evolve further, as a consequence of the production of molecules with an interesting clinical profile such as ferrocarboxymaltose, which is already available for adolescents aged >14 years. The present article reports the clinically relevant latest insights regarding IDA in children and offers a practical guide to help pediatricians, particularly to choose the most appropriate prevention and therapy strategies. Full article
(This article belongs to the Special Issue Advances in Iron Metabolism and Anemia)
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