Iron in airway macrophages and infective exacerbations of chronic obstructive pulmonary disease

Background Excess pulmonary iron has been implicated in the pathogenesis of lung disease, including asthma and COPD. An association between higher iron content in sputum macrophages and infective exacerbations of COPD has previously been demonstrated. Objectives To assess the mechanisms of pulmonary macrophage iron sequestration, test the effect of macrophage iron-loading on cellular immune function, and prospectively determine if sputum hemosiderin index can predict infectious exacerbations of COPD. Methods Intra- and extracellular iron was measured in cell-line-derived and in freshly isolated sputum macrophages under various experimental conditions including treatment with exogenous IL-6 and hepcidin. Bacterial uptake and killing were compared in the presence or absence of iron-loading. A prospective cohort of COPD patients with defined sputum hemosiderin indices were monitored to determine the annual rate of severe infectious exacerbations. Results Gene expression studies suggest that airway macrophages have the requisite apparatus of the hepcidin-ferroportin axis. IL-6 and hepcidin play roles in pulmonary iron sequestration, though IL-6 appears to exert its effect via a hepcidin-independent mechanism. Iron-loaded macrophages had reduced uptake of COPD-relevant organisms and were associated with higher growth rates. Infectious exacerbations were predicted by sputum hemosiderin index (β = 0.035, p = 0.035). Conclusions We demonstrate in-vitro and population-level evidence that excess iron in pulmonary macrophages may contribute to recurrent airway infection in COPD. Specifically, IL-6-dependent iron sequestration by sputum macrophages may result in immune cell dysfunction and ultimately lead to increased frequency of infective exacerbation.

NCOA4-Mediated Ferritinophagy: A Vicious Culprit in COVID-19 Pathogenesis?

Coronavirus disease 2019 (COVID-19) is a global pandemic that has caused widespread loss of life. Notably, in this disease, severe inflammatory reactions characterized by cytokine storms are caused by severe acute respiratory syndrome coronavirus 2. The cytokine storms may promote hyper-ferritinemia which can further intensify the inflammation. Moreover, elevated ferritin levels trigger nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy, in which ferritin is degraded and iron is released. Excess iron released from ferritinophagy can promote ferroptosis and cellular damage. Therefore, we propose that NCOA4-mediated ferritinophagy can be targeted to limit the ferroptosis and prevent the multi-organ damage and severity in COVID-19 patients.

Evaluating and Enhancing Iron Removal via Filterable Iron Precipitates Formation during Coal-Waste Bioleaching

Iron removal via jarosite precipitate formation is a commonly used technique in various hydrometallurgical processes. Excess iron removal often becomes essential to an overall metal recovery circuit. This is particularly important to processes involving iron-bearing minerals. A technique, which involved the use of pyrite to generate acid for leaching, for iron removal is critical to enabling the process. Iron removal using CaO or similar reagents is expensive and often results in lost product. In the present study, various compounds that facilitate jarosite formation, namely Na2SO4, NH4OH, KCl, and KOH, were utilized and their effect in precipitation was observed. Visual Minteq assisted simulations were run in order to evaluate favorable conditions for iron removal. Morphology and elemental composition of precipitates were analyzed using scanning electron microscopy equipped with energy-dispersive X-ray spectroscopy, and the phase purity was identified using X-ray diffraction analysis.

A Novel Insight Into the Fate of Cardiomyocytes in Ischemia-Reperfusion Injury: From Iron Metabolism to Ferroptosis

Ischemia-reperfusion injury (IRI), critically involved in the pathology of reperfusion therapy for myocardial infarction, is closely related to oxidative stress the inflammatory response, and disturbances in energy metabolism. Emerging evidence shows that metabolic imbalances of iron participate in the pathophysiological process of cardiomyocyte IRI [also termed as myocardial ischemia-reperfusion injury (MIRI)]. Iron is an essential mineral required for vital physiological functions, including cellular respiration, lipid and oxygen metabolism, and protein synthesis. Nevertheless, cardiomyocyte homeostasis and viability are inclined to be jeopardized by iron-induced toxicity under pathological conditions, which is defined as ferroptosis. Upon the occurrence of IRI, excessive iron is transported into cells that drive cardiomyocytes more vulnerable to ferroptosis by the accumulation of reactive oxygen species (ROS) through Fenton reaction and Haber–Weiss reaction. The increased ROS production in ferroptosis correspondingly leads cardiomyocytes to become more sensitive to oxidative stress under the exposure of excess iron. Therefore, ferroptosis might play an important role in the pathogenic progression of MIRI, and precisely targeting ferroptosis mechanisms may be a promising therapeutic option to revert myocardial remodeling. Notably, targeting inhibitors are expected to prevent MIRI deterioration by suppressing cardiomyocyte ferroptosis. Here, we review the pathophysiological alterations from iron homeostasis to ferroptosis together with potential pathways regarding ferroptosis secondary to cardiovascular IRI. We also provide a comprehensive analysis of ferroptosis inhibitors and initiators, as well as regulatory genes involved in the setting of MIRI.

Effect of annealing on the structural and superconducting properties of FeSe1−xTex

<p><b>The term 'high-temperature superconductivity' has long been synonymous with copper oxide-based superconductors (cuprates) up until the recent discovery of the iron-based superconductors in 2008. This new family of superconductors exhibits fundamentally interesting properties such as the interplay between magnetism and superconductivity as well as the very recently discovered topological properties of FeSe1−xTex. Furthermore, from an application point of view, iron-based superconductors have the potential to become the new norm for low-temperature, high-field applications such as MRI and nuclear fusion.</b></p> <p>However, some of the post-processing procedures required to obtain high-quality samples, like the annealing process of FeSe1−xTex, are yet to be fully understood.</p> <p>This thesis reports on the effect of annealing on the structure and composition of FeSe1−xTex and how they manifest as changes in the superconducting properties.</p> <p>Overall, air annealing is shown to improve the critical temperature and critical current density of FeSe1−xTex for almost all investigated doping concentrations.</p> <p>These improvements are the result of a decrease in excess iron driven by the formation of thin iron oxide layers on exposed surfaces of the crystal.</p> <p>Further analysis suggests that the reduction in the excess iron concentration is largest in the region right underneath the oxide layers. Consequently, the improvement in the superconducting properties is also found to be largest in these regions. In terms of the annealing atmosphere, even in nitrogen and low-vacuum atmospheres, annealing still leads to the formation of an iron oxide layer and an improvement in the superconducting properties due to the presence of residual oxygen. In rare cases, annealing was found to induce asymmetric magnetic hysteresis loops as a result of weak bulk pinning and strong surface pinning. Whilst asymmetric hysteresis loops have occasionally been reported in the cuprates and polycrystalline iron-based superconductors, this work reports the first observation of such behaviour in FeSe1−xTex single crystals. This work has deepened the understanding of the annealing process on the intrinsic properties of FeSe1−xTexand facilitates the study of additional post-processing procedures that will further improve the properties of this family of superconductors.</p>

Effect of annealing on the structural and superconducting properties of FeSe1−xTex

<p><b>The term 'high-temperature superconductivity' has long been synonymous with copper oxide-based superconductors (cuprates) up until the recent discovery of the iron-based superconductors in 2008. This new family of superconductors exhibits fundamentally interesting properties such as the interplay between magnetism and superconductivity as well as the very recently discovered topological properties of FeSe1−xTex. Furthermore, from an application point of view, iron-based superconductors have the potential to become the new norm for low-temperature, high-field applications such as MRI and nuclear fusion.</b></p> <p>However, some of the post-processing procedures required to obtain high-quality samples, like the annealing process of FeSe1−xTex, are yet to be fully understood.</p> <p>This thesis reports on the effect of annealing on the structure and composition of FeSe1−xTex and how they manifest as changes in the superconducting properties.</p> <p>Overall, air annealing is shown to improve the critical temperature and critical current density of FeSe1−xTex for almost all investigated doping concentrations.</p> <p>These improvements are the result of a decrease in excess iron driven by the formation of thin iron oxide layers on exposed surfaces of the crystal.</p> <p>Further analysis suggests that the reduction in the excess iron concentration is largest in the region right underneath the oxide layers. Consequently, the improvement in the superconducting properties is also found to be largest in these regions. In terms of the annealing atmosphere, even in nitrogen and low-vacuum atmospheres, annealing still leads to the formation of an iron oxide layer and an improvement in the superconducting properties due to the presence of residual oxygen. In rare cases, annealing was found to induce asymmetric magnetic hysteresis loops as a result of weak bulk pinning and strong surface pinning. Whilst asymmetric hysteresis loops have occasionally been reported in the cuprates and polycrystalline iron-based superconductors, this work reports the first observation of such behaviour in FeSe1−xTex single crystals. This work has deepened the understanding of the annealing process on the intrinsic properties of FeSe1−xTexand facilitates the study of additional post-processing procedures that will further improve the properties of this family of superconductors.</p>

Pre-Clinical Insights into the Iron and Breast Cancer Hypothesis

Population studies, systematic reviews, and meta-analyses have revealed no relationship between iron status and breast cancer, a weak positive association, or a small protective effect of low iron status. However, in those studies, the authors concluded that further investigation was merited. The set of experiments reported here used preclinical models to assess the likely value of further investigation. The effects of iron status on the initiation and promotion stage of mammary carcinogenesis are reported. Using the classical model of cancer initiation in the mammary gland, 7,12 dimethyl-benz[α]anthracene-induced carcinogenesis was unaffected by iron status. Similarly, excess iron intake showed no effect on the promotion stage of 1-methyl-1-nitrosurea-induced mammary carcinogenesis, though iron deficiency exerted a specific inhibitory effect on the carcinogenic process. Though iron-mediated cellular oxidation is frequently cited as a potential mechanism for effects on breast cancer, no evidence of increased oxidative damage to DNA attributable to excess iron intake was found. The reported preclinical data fail to provide convincing evidence that the further evaluation of the iron–breast cancer risk hypotheses is warranted and underscore the value of redefining the referent group in population-based studies of iron–cancer hypotheses in other tissues.

Sulphate reduction determines the long-term effect of iron amendments on phosphorus retention in lake sediments

Purpose This field study aimed to guide the planning of iron amendments for phosphorus retention by investigating the long-term fate of iron added to two urban lakes (Plötzensee and Groß Glienicker See) in Berlin, Germany. The contributions of iron dosing to improve lake status as well as the relevance of competing processes for management success were evaluated. Methods Sediment stratigraphy, as well as occurrence of iron minerals, and fluxes between water and sediment were examined using geochemical analyses (i.e. element composition, sequential extraction, X-ray diffraction, and pore water analyses). A one-box lake model was used to relate these fluxes to monitoring data from the water column and to sediment inventories. Results In both lakes, the added iron was preserved in the sediment. Whereas phosphorus retention increased following the addition of iron to Groß Glienicker See, sulphur was retained by the excess iron in Plötzensee. This contrasting effect is attributed to significantly different sulphate reduction rates in two lakes (Wilcoxon rank sum test: W = 25, p = 0.008). According to the one-box model, sulphate reduction explained both the decrease in measured sulphate concentrations after iron application as well as the observed increase in sulphur deposition in the sediments. Conclusion Management interventions involving iron amendments to enhance phosphorus retention must consider the competing process of iron sulphide formation during the entire management plan period, and additional iron may need to be applied to account for this effect.

Bioinformatics and wet laboratory analysis of rs1800562 to predict genetic aetiology of iron overload in Nigeria

Introduction/Objective The most reported single nucleotide polymorphism (SNP) of the HFE gene is rs1800562, representing the substitution of Adenine for Guanine at position 847 of the HFE gene. This has been widely implicated in hereditary haemochromatosis and other conditions like altered cholesterol balance, Alzheimer’s disease and cutaneous photosensitivity. Abnormal HFE protein resulting from the mutant HFE gene leads to formation of excess iron which has been postulated as likely mechanism for these diseases. Although there is evidence of iron overload in Africans, only few studies have explored possible genetic causes, and prevalence of rs1800562 is not known in West African population. Hence the need to determine the prevalence of rs1800562 in Nigeria using computational and wet laboratory approach. Methods/Case Report Details of rs1800562 were retrieved from Ensembl Genome Browser version 99. Severity of the consequences of this SNP on protein product was determined using bioinformatics tools including SIFT, Polyphen, Mutation Assessor, HOPE, I-mutant and MutPred2. Genotyping of rs1800562 was done In silico using restriction fragment length polymorphism (RFLP). Primer3plus was used for primer design, NCBI BLAST and SMS were used for primer validation. We used Webcutter 2.0 to determine suitable restriction enzymes. The genotyping was simulated using USCS virtual PCR and RestrictionMapper. Whole blood samples were obtained from 200 participants selected randomly from a pool of blood donors. DNA was extracted and flanking region of rs1800562 was amplified. The amplified product was digested by RSA1and fragments examined on agarose gel electrophoresis. Results (if a Case Study enter NA) The MAF was found to be 0.01 globally and 0.02 in Africa. In the two Nigerian population examined (Yoruba and Esan population), MAF was 0.00. Mutation Assessor and SIFT Polyphen consistently predicted the mutation to be of severe consequences. Analysis on HOPE, I-mutant and Mutpred2 revealed loss of protein stability, change in net charges affecting the HFE protein localization and its interaction with other proteins. All the participants in the wet laboratory analysis were homozygous for the wild type allele of rs1800562 (MAF=0). Conclusion This study confirmed the In silico prediction of the absence of rs1800562 in Nigeria. Future studies should focus on other SNPs of the HFE gene as well as other gene involved in iron metabolism.