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Biomedicines
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Advances in Iron Deficiency and Iron-Related Disorders
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Advances in Iron Deficiency and Iron-Related Disorders

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Endocrinology and Metabolism Research".

Deadline for manuscript submissions: 30 June 2024 | Viewed by 6031

Special Issue Editor

Dr. Alireza Morovat

E-Mail Website
Guest Editor
Department of Clinical Biochemistry, Oxford University Hospitals, Oxford OX3 9DU, UK
Interests: biomarkers; mitochondrial diseases; dementia; iron pathophysiology; liver allograft function

Special Issue Information

Dear Colleagues,

Iron status influences a vast array of cellular processes.  Iron imbalance or dysregulation can have adverse, clinically-significant  effects on gene regulation, enzyme activities, mitochondrial function, stress response and even cell viability.  Absolute or functional iron deficiency can lead to morbidity, impairs neurobehavioural development in early life, predisposes to immune dysfunction, and is associated with adverse outcomes in patients with cancer, heart failure or those undergoing surgery.  At the other end of the spectrum, iron has been associated with inflammatory processes, oxidative stress, mitochondrial dysfunction and ferroptosis.  Some of these and related cellular events have implications for neurodegenerative, cardiovascular, pulmonary, hepatic and other disorders.  The expanding knowledge of the involvement of iron in cellular function has encouraged exciting avenues of research that are increasing our understanding of the pathogenic mechanisms of some common diseases, and may pave the way for interventions that would alleviate those conditions or improve clinical outcomes.

It gives me great pleasure to invite researchers who are studying cellular processes and mechanisms of disease in which iron plays a significant role to submit their original research or review papers for this special issue of Biomedicines.  The aim of this special issue is to offer emerging knowledge or overviews of the pathophysiological mechanisms through which iron imbalance may bring about clinical effects.  Research involving clinical studies or the use of human cells are especially, but not exclusively, welcome.

Dr. Alireza Morovat
Guest Editor

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. Biomedicines 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 2600 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 deficiency
  • iron overload
  • pathophysiology
  • inflammation
  • organ disorders
  • cancer
  • neurodegenerative disease
  • immune function
  • therapy

Published Papers (5 papers)

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Research

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13 pages, 449 KiB  
Article
Prevalence and Characteristics of Metabolic Hyperferritinemia in a Population-Based Central-European Cohort
by Sophie Gensluckner, Bernhard Wernly, Florian Koutny, Georg Strebinger, Stephan Zandanell, Lars Stechemesser, Bernhard Paulweber, Bernhard Iglseder, Eugen Trinka, Vanessa Frey, Patrick Langthaler, Georg Semmler, Luca Valenti, Elena Corradini, Christian Datz and Elmar Aigner
Biomedicines 2024, 12(1), 207; https://doi.org/10.3390/biomedicines12010207 - 17 Jan 2024
Viewed by 794
Abstract
Background: Hyperferritinemia (HF) is a common finding and can be considered as metabolic HF (MHF) in combination with metabolic diseases. The definition of MHF was heterogenous until a consensus statement was published recently. Our aim was to apply the definition of MHF to [...] Read more.
Background: Hyperferritinemia (HF) is a common finding and can be considered as metabolic HF (MHF) in combination with metabolic diseases. The definition of MHF was heterogenous until a consensus statement was published recently. Our aim was to apply the definition of MHF to provide data on the prevalence and characteristics of MHF in a Central-European cohort. Methods: This study was a retrospective analysis of the Paracelsus 10,000 study, a population-based cohort study from the region of Salzburg, Austria. We included 8408 participants, aged 40–77. Participants with HF were divided into three categories according to their level of HF and evaluated for metabolic co-morbidities defined by the proposed criteria for MHF. Results: HF was present in 13% (n = 1111) with a clear male preponderance (n = 771, 69% of HF). Within the HF group, 81% (n = 901) of subjects fulfilled the metabolic criteria and were defined as MHF, of which 75% (n = 674) were characterized by a major criterion. In the remaining HF cohort, 52% (n = 227 of 437) of subjects were classified as MHF after application of the minor criteria. Conclusion: HF is a common finding in the general middle-aged population and the majority of cases are classified as MHF. The new classification provides useful criteria for defining MHF. Full article
(This article belongs to the Special Issue Advances in Iron Deficiency and Iron-Related Disorders)
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14 pages, 1276 KiB  
Article
Factors Governing the Erythropoietic Response to Intravenous Iron Infusion in Patients with Chronic Kidney Disease: A Retrospective Cohort Study
by Chukwuma A. Chukwu, Helen Gilbody, Olivia Wickens, Craig Carroll, Sunil Bhandari and Philip A. Kalra
Biomedicines 2023, 11(9), 2417; https://doi.org/10.3390/biomedicines11092417 - 29 Aug 2023
Viewed by 985
Abstract
Background: Limited knowledge exists about factors affecting parenteral iron response. A study was conducted to determine the factors influencing the erythropoietic response to parenteral iron in iron-deficient anaemic patients whose kidney function ranged from normal through all stages of chronic kidney disease (CKD) [...] Read more.
Background: Limited knowledge exists about factors affecting parenteral iron response. A study was conducted to determine the factors influencing the erythropoietic response to parenteral iron in iron-deficient anaemic patients whose kidney function ranged from normal through all stages of chronic kidney disease (CKD) severity. Methods: This retrospective cohort study included parenteral iron recipients who did not receive erythropoiesis-stimulating agents (ESA) between 2017 and 2019. The study cohort was derived from two groups of patients: those managed by the CKD team and patients being optimised for surgery in the pre-operative clinic. Patients were categorized based on their kidney function: Patients with normal kidney function [estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m2] were compared to those with CKD stages 3–5 (eGFR < 60 mL/min/1.73 m2). Patients were further stratified by the type of iron deficiency [absolute iron deficiency (AID) versus functional iron deficiency (FID)]. The key outcome was change in hemoglobin (∆Hb) between pre- and post-infusion haemoglobin (Hb) values. Parenteral iron response was assessed using propensity-score matching and multivariate linear regression. The impact of kidney impairment versus the nature of iron deficiency (AID vs. FID) in response was explored. Results: 732 subjects (mean age 66 ± 17 years, 56% females and 87% White) were evaluated. No significant differences were observed in the time to repeat Hb among CKD stages and FID/AID patients. The Hb rise was significantly lower with lower kidney function (non-CKD and CKD1–2; 13 g/L, CKD3–5; 7 g/L; p < 0.001). When groups with different degrees of renal impairment were propensity-score matched according to whether iron deficiency was due to AID or FID, the level of CKD was found not to be relevant to Hb responses [unmatched (∆Hb) 12.1 vs. 8.7 g/L; matched (∆Hb) 12.4 vs. 12.1 g/L in non-CKD and CKD1–2 versus CKD3–5, respectively]. However, a comparison of patients with AID and FID, while controlling for the degree of CKD, indicated that patients with FID exhibited a diminished Hb response regardless of their level of kidney impairment. Conclusion: The nature of iron deficiency rather than the severity of CKD has a stronger impact on Hb response to intravenous iron with an attenuated response seen in functional iron deficiency irrespective of the degree of renal impairment. Full article
(This article belongs to the Special Issue Advances in Iron Deficiency and Iron-Related Disorders)
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15 pages, 5731 KiB  
Article
High Hepcidin Levels Promote Abnormal Iron Metabolism and Ferroptosis in Chronic Atrophic Gastritis
by Yashuo Zhao, Jianing Zhao, Hongyu Ma, Yan Han, Weichao Xu, Jie Wang, Yanru Cai, Xuemei Jia, Qingzhong Jia and Qian Yang
Biomedicines 2023, 11(9), 2338; https://doi.org/10.3390/biomedicines11092338 - 22 Aug 2023
Cited by 1 | Viewed by 1334
Abstract
Background: Chronic atrophic gastritis (CAG) is a chronic inflammatory disease and premalignant lesion of gastric cancer. As an antimicrobial peptide, hepcidin can maintain iron metabolic balance and is susceptible to inflammation. Objectives: The objective of this study was to clarify whether hepcidin is [...] Read more.
Background: Chronic atrophic gastritis (CAG) is a chronic inflammatory disease and premalignant lesion of gastric cancer. As an antimicrobial peptide, hepcidin can maintain iron metabolic balance and is susceptible to inflammation. Objectives: The objective of this study was to clarify whether hepcidin is involved in abnormal iron metabolism and ferroptosis during CAG pathogenesis. Methods: Non-atrophic gastritis (NAG) and chronic atrophic gastritis (CAG) patient pathology slides were collected, and related protein expression was detected by immunohistochemical staining. The CAG rat model was established using MNNG combined with an irregular diet. Results: CAG patients and rats exhibited iron deposition in gastric tissue. CAG-induced ferroptosis in the stomach was characterized by decreased GPX4 and FTH levels and increased 4-HNE levels. Hepcidin, which is mainly located in parietal cells, was elevated in CAG gastric tissue. The high gastric level of hepcidin inhibited iron absorption in the duodenum by decreasing the protein expression of DMT1 and FPN1. In addition, the IL-6/STAT3 signaling pathway induced hepcidin production in gastric tissue. Conclusion: Our results showed that the high level of gastric hepcidin induced ferroptosis in the stomach but also inhibited iron absorption in the intestines. Inhibiting hepcidin might be a new strategy for the prevention of CAG in the future. Full article
(This article belongs to the Special Issue Advances in Iron Deficiency and Iron-Related Disorders)
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Review

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17 pages, 708 KiB  
Review
The Iron Metabolism with a Specific Focus on the Functioning of the Nervous System
by Monika Kulaszyńska, Sebastian Kwiatkowski and Karolina Skonieczna-Żydecka
Biomedicines 2024, 12(3), 595; https://doi.org/10.3390/biomedicines12030595 - 06 Mar 2024
Viewed by 756
Abstract
Iron is the micronutrient with the best-studied biological functions. It is widely distributed in nature, and its involvement in the main metabolic pathways determines the great importance of this metal for all organisms. Iron is required for cellular respiration and various biochemical processes [...] Read more.
Iron is the micronutrient with the best-studied biological functions. It is widely distributed in nature, and its involvement in the main metabolic pathways determines the great importance of this metal for all organisms. Iron is required for cellular respiration and various biochemical processes that ensure the proper functioning of cells and organs in the human body, including the brain. Iron also plays an important role in the production of free radicals, which can be beneficial or harmful to cells under various conditions. Reviews of iron metabolism and its regulation can be found in the literature, and further advances in understanding the molecular basis of iron metabolism are being made every year. The aim of this review is to systematise the available data on the role of iron in the function of the nervous system, especially in the brain. The review summarises recent views on iron metabolism and its regulatory mechanisms in humans, including the essential action of hepcidin. Special attention is given to the mechanisms of iron absorption in the small intestine and the purpose of this small but critically important pool of iron in the brain. Full article
(This article belongs to the Special Issue Advances in Iron Deficiency and Iron-Related Disorders)
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12 pages, 265 KiB  
Review
Is It Time to Alter the Standard of Care for Iron Deficiency/Iron Deficiency Anemia in Reproductive-Age Women?
by Mrutyunjaya B. Bellad, Anmol Patted and Richard J. Derman
Biomedicines 2024, 12(2), 278; https://doi.org/10.3390/biomedicines12020278 - 25 Jan 2024
Viewed by 1098
Abstract
Two billion people worldwide suffer from anemia, with reproductive-age women being disproportionately affected. Iron plays a crucial role in cellular function and impacts cognition, physical function, and quality of life. Iron deficiency (ID) and iron deficiency anemia (IDA) are associated with adverse effects [...] Read more.
Two billion people worldwide suffer from anemia, with reproductive-age women being disproportionately affected. Iron plays a crucial role in cellular function and impacts cognition, physical function, and quality of life. Iron deficiency (ID) and iron deficiency anemia (IDA) are associated with adverse effects on pregnancy and fetal development. Oral iron supplementation has been the standard treatment for decades, often producing sub-optimal outcomes. Many babies are still being born with ID and suffer adverse sequelae due to inadequate iron levels in the mothers. Is it time to consider a broad scale-up of parenteral iron as a new standard of care? Full article
(This article belongs to the Special Issue Advances in Iron Deficiency and Iron-Related Disorders)
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