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Impaired bone marrow microenvironment and stem cells in transfusion-dependent beta-thalassemia.
Zhou, X, Huang, L, Wu, J, Qu, Y, Jiang, H, Zhang, J, Qiu, S, Liao, C, Xu, X, Xia, J, et al
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2022;:112548
Abstract
Beta-thalassemia (BT) is a hereditary disease caused by abnormal hemoglobin synthesis with consequent ineffective erythropoiesis. Patients with thalassemia major are dependent on long-term blood transfusions with associated long-term complications such as iron overload (IO). This excess iron can result in tissue damage, impaired organ function, and increased morbidity. Growing evidence has demonstrated that IO contributes to impairment of the bone marrow (BM) microenvironment that largely impacts the function of BM mesenchymal stem cells, hematopoietic stem cells, and endothelial cells. In this article, we review recent progress in the understanding of iron metabolism and the perniciousness induced by IO. We highlight the importance of understanding the cross-talk between BM stem cells and the BM microenvironment, particularly the pathological effect of IO on BM stem cells and BT-associated complications. We also provide an update on recent novel therapies to cure transfusion-dependent beta-thalassemia and iron overload-induced complications for their future clinical application.
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Ferroptosis: mechanisms and links with diseases.
Yan, HF, Zou, T, Tuo, QZ, Xu, S, Li, H, Belaidi, AA, Lei, P
Signal transduction and targeted therapy. 2021;(1):49
Abstract
Ferroptosis is an iron-dependent cell death, which is different from apoptosis, necrosis, autophagy, and other forms of cell death. The process of ferroptotic cell death is defined by the accumulation of lethal lipid species derived from the peroxidation of lipids, which can be prevented by iron chelators (e.g., deferiprone, deferoxamine) and small lipophilic antioxidants (e.g., ferrostatin, liproxstatin). This review summarizes current knowledge about the regulatory mechanism of ferroptosis and its association with several pathways, including iron, lipid, and cysteine metabolism. We have further discussed the contribution of ferroptosis to the pathogenesis of several diseases such as cancer, ischemia/reperfusion, and various neurodegenerative diseases (e.g., Alzheimer's disease and Parkinson's disease), and evaluated the therapeutic applications of ferroptosis inhibitors in clinics.
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3.
GDF15: an emerging modulator of immunity and a strategy in COVID-19 in association with iron metabolism.
Rochette, L, Zeller, M, Cottin, Y, Vergely, C
Trends in endocrinology and metabolism: TEM. 2021;(11):875-889
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic of respiratory and cardiovascular diseases, known as coronavirus disease 2019 (COVID-19). SARS-CoV-2 encodes the structural proteins spike (S), envelope (E), membrane (M), and nucleocapsid (N). The receptor-binding domain on the surface subunit S1 is responsible for attachment of the virus to angiotensin (Ang)-converting enzyme 2 (ACE2), which is highly expressed in host cells. The cytokine storm observed in patients with COVID-19 contributes to the endothelial vascular dysfunction, which can lead to acute respiratory distress syndrome, multiorgan failure, alteration in iron homeostasis, and death. Growth and differentiation factor 15 (GDF15), which belongs to the transforming growth factor-β (TGF-β) superfamily of proteins, has a pivotal role in the development and progression of diseases because of its role as a metabolic regulator. In COVID-19, GDF15 activity increases in response to tissue damage. GDF15 appears to be a strong predictor of poor outcomes in patients critically ill with COVID-19 and acts as an 'inflammation-induced central mediator of tissue tolerance' via its metabolic properties. In this review, we examine the potential properties of GDF15 as an emerging modulator of immunity in COVID-19 in association with iron metabolism. The virus life cycle in host cell provides potential targets for drug therapy.
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4.
Iron at the Interface of Hepatocellular Carcinoma.
Paganoni, R, Lechel, A, Vujic Spasic, M
International journal of molecular sciences. 2021;(8)
Abstract
Cancer incidence and mortality are rapidly growing, with liver cancer being the sixth most diagnosed cancer worldwide and the third leading cause of cancer death in 2020. A number of risk factors have been identified that trigger the progression to hepatocellular carcinoma. In this review, we focus on iron as a potential risk factor for liver carcinogenesis. Molecules involved in the regulation of iron metabolism are often upregulated in cancer cells, in order to provide a supply of this essential trace element for all stages of tumor development, survival, proliferation, and metastasis. Thus, cellular and systemic iron levels must be tightly regulated to prevent or delay liver cancer progression. Disorders associated with dysregulated iron metabolism are characterized with increased susceptibility to hepatocellular carcinoma. This review discusses the association of iron with metabolic disorders such as hereditary hemochromatosis, non-alcoholic fatty liver disease, obesity, and type 2 diabetes, in the background of hepatocellular carcinoma.
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5.
Iron in immune cell function and host defense.
Haschka, D, Hoffmann, A, Weiss, G
Seminars in cell & developmental biology. 2021;:27-36
Abstract
The control over iron availability is crucial under homeostatic conditions and even more in the case of an infection. This results from diverse properties of iron: first, iron is an important trace element for the host as well as for the pathogen for various cellular and metabolic processes, second, free iron catalyzes Fenton reaction and is therefore producing reactive oxygen species as a part of the host defense machinery, third, iron exhibits important effects on immune cell function and differentiation and fourth almost every immune activation in turn impacts on iron metabolism and spatio-temporal iron distribution. The central importance of iron in the host and microbe interplay and thus for the course of infections led to diverse strategies to restrict iron for invading pathogens. In this review, we focus on how iron restriction to the pathogen is a powerful innate immune defense mechanism of the host called "nutritional immunity". Important proteins in the iron-host-pathogen interplay will be discussed as well as the influence of iron on the efficacy of innate and adaptive immunity. Recently described processes like ferritinophagy and ferroptosis are further covered in respect to their impact on inflammation and infection control and how they impact on our understanding of the interaction of host and pathogen.
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The possible effects of iron loss from bloodletting on mortality from pneumonia in the nineteenth century.
Brabin, B
Journal of clinical epidemiology. 2021;:139-146
Abstract
OBJECTIVE To estimate iron losses and disease severity following 19th century bloodletting in patients with pneumonia. STUDY DESIGN AND SETTING Benefits of bloodletting in pneumonia patients were contested during the 19th century. Although large blood volumes during infection were removed there was no systematic data collection assessing efficacy and knowledge of iron composition of blood was rudimentary. This observational analysis of historical data quantifies iron losses in pneumonia cases in relation to disease severity. RESULTS Based on one detailed case series average blood volume removed for survivors was 830 mL (range 114-2272 mL), and mean recovery times were shorter in patients bled within 2 days of illness (P < 0.001). Average iron removed was 446 mg with phlebotomy done ≤2 days of illness presentation and 347 mg after >2 days of illness (P = 0.012). Across several European hospitals average case fatality in pneumonia patients receiving phlebotomy was higher than in those treated without phlebotomy (19.9% vs. 12.8%, OR 1.55, 95% CI 1.38-1.74, P < 0.001). CONCLUSION Variable efficacy for bloodletting could at least in part be explained by altered iron status.
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Complementary Feeding and Iron Status: "The Unbearable Lightness of Being" Infants.
Miniello, VL, Verga, MC, Miniello, A, Di Mauro, C, Diaferio, L, Francavilla, R
Nutrients. 2021;(12)
Abstract
The complementary feeding (CF) period that takes place between 6 and 24 months of age is of key importance for nutritional and developmental reasons during the transition from exclusively feeding on milk to family meals. In 2021, a multidisciplinary panel of experts from four Italian scientific pediatric societies elaborated a consensus document on CF, focusing in particular on healthy term infants. The aim was to provide healthcare providers with useful guidelines for clinical practice. Complementary feeding is also the time window when iron deficiency (ID) and iron deficiency anemia (IDA) are most prevalent. Thus, it is appropriate to address the problem of iron deficiency through nutritional interventions. Adequate iron intake during the first two years is critical since rapid growth in that period increases iron requirements per kilogram more than at any other developmental stage. Complementary foods should be introduced at around six months of age, taking into account infant iron status.
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Iron Transport across Symbiotic Membranes of Nitrogen-Fixing Legumes.
Day, DA, Smith, PMC
International journal of molecular sciences. 2021;(1)
Abstract
Iron is an essential nutrient for the legume-rhizobia symbiosis and nitrogen-fixing bacteroids within root nodules of legumes have a very high demand for the metal. Within the infected cells of nodules, the bacteroids are surrounded by a plant membrane to form an organelle-like structure called the symbiosome. In this review, we focus on how iron is transported across the symbiosome membrane and accessed by the bacteroids.
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Bacterial Responses to Iron Withholding by Calprotectin.
Obisesan, AO, Zygiel, EM, Nolan, EM
Biochemistry. 2021;(45):3337-3346
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Abstract
Iron (Fe) plays important roles in both essential cellular processes and virulence pathways for many bacteria. Consequently, Fe withholding by the human innate immune system is an effective form of defense against bacterial infection. In this Perspective, we review recent studies that have established a foundation for our understanding of the impact of the metal-sequestering host defense protein calprotectin (CP) on bacterial Fe homeostasis. We also discuss two recently uncovered strategies for bacterial adaptation to Fe withholding by CP. Together, these studies provide insight into how Fe sequestration by CP affects bacterial pathogens that include Pseudomonas aeruginosa, Acinetobacter baumannii, and Staphylococcus aureus. Overall, recent studies suggest that Fe withholding by CP may have implications for bacterial survival and virulence in the host, and further explorations that directly address this possibility present an important area for discovery.
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Heterogeneous Fenton catalysts: A review of recent advances.
Thomas, N, Dionysiou, DD, Pillai, SC
Journal of hazardous materials. 2021;(Pt B):124082
Abstract
Heterogeneous Fenton catalysts are emerging as excellent materials for applications related to water purification. In this review, recent trends in the synthesis and application of heterogeneous Fenton catalysts for the abatement of organic pollutants and disinfection of microorganisms are discussed. It is noted that as the complexity of cell wall increases, the resistance level towards various disinfectants increases and it requires either harsh conditions or longer exposure time for the complete disinfection. In case of viruses, enveloped viruses (e.g. SARS-CoV-2) are found to be more susceptible to disinfectants than the non-enveloped viruses. The introduction of plasmonic materials with the Fenton catalysts broadens the visible light absorption efficiency of the hybrid material, and incorporation of semiconductor material improves the rate of regeneration of Fe(II) from Fe(III). A special emphasis is given to the use of Fenton catalysts for antibacterial applications. Composite materials of magnetite and ferrites remain a champion in this area because of their easy separation and reuse, owing to their magnetic properties. Iron minerals supported on clay materials, perovskites, carbon materials, zeolites and metal-organic frameworks (MOFs) dramatically increase the catalytic degradation rate of contaminants by providing high surface area, good mechanical stability, and improved electron transfer. Moreover, insights to the zero-valent iron and its capacity to remove a wide range of organic pollutants, heavy metals and bacterial contamination are also discussed. Real world applications and the role of natural organic matter are summarised. Parameter optimisation (e.g. light source, dosage of catalyst, concentration of H2O2 etc.), sustainable models for the reusability or recyclability of the catalyst and the theoretical understanding and mechanistic aspects of the photo-Fenton process are also explained. Additionally, this review summarises the opportunities and future directions of research in the heterogeneous Fenton catalysis.