Temporal changes in erythroid progenitors in critically ill patients: a prospective cohort study.

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Why cells need iron: a compendium of iron utilisation.

Iron deficiency is globally prevalent, causing an array of developmental, haematological, immunological, neurological, and cardiometabolic impairments, and is associated with symptoms ranging from chronic fatigue to hair loss. Within cells, iron is utilised in a variety of ways by hundreds of different proteins. Here, we review links between molecular activities regulated by iron and the pathophysiological effects of iron deficiency.

Effects of Iron Status on Adaptive Immunity and Vaccine Efficacy: A Review.

Vaccines can prevent infectious diseases, but their efficacy varies, and factors impacting vaccine effectiveness remain unclear. Iron deficiency is the most common nutrient deficiency, affecting >2 billion individuals. It is particularly common in areas with high infectious disease burden and in groups that are routinely vaccinated, such as infants, pregnant women, and the elderly.

Iron dysregulation and inflammatory stress erythropoiesis associates with long-term outcome of COVID-19.

Persistent symptoms following SARS-CoV-2 infection are increasingly reported, although the drivers of post-acute sequelae (PASC) of COVID-19 are unclear. Here we assessed 214 individuals infected with SARS-CoV-2, with varying disease severity, for one year from COVID-19 symptom onset to determine the early correlates of PASC. A multivariate signature detected beyond two weeks of disease, encompassing unresolving inflammation, anemia, low serum iron, altered iron-homeostasis gene expression and emerging stress erythropoiesis; differentiated those who reported PASC months later, irrespective of COVID-19 severity.

Novel role of bone morphogenetic protein 9 in innate host responses to HCMV infection.

Herpesviruses modulate immune control to secure lifelong infection. The mechanisms Human Cytomegalovirus (HCMV) employs in this regard can reveal unanticipated aspects of cellular signaling involved in antiviral immunity. Here, we describe a novel relationship between the TGF-β family cytokine BMP9 and HCMV infection.

Another iron in C. difficile's fire.

Iron is arguably the most important nutrient in the ongoing battle between hosts and bacteria. Recently in Nature, a unique iron storage organelle, the ferrosome, was discovered in the human pathogen Clostridioides difficile. But what is the role of ferrosomes and how do they affect bacterial behavior and infection?

Iron overload induces dysplastic erythropoiesis and features of myelodysplasia in Nrf2-deficient mice.

Iron overload (IOL) is hypothesized to contribute to dysplastic erythropoiesis. Several conditions, including myelodysplastic syndrome, thalassemia and sickle cell anemia, are characterized by ineffective erythropoiesis and IOL. Iron is pro-oxidant and may participate in the pathophysiology of these conditions by increasing genomic instability and altering the microenvironment.

Cellular iron governs the host response to malaria.

Malaria and iron deficiency are major global health problems with extensive epidemiological overlap. Iron deficiency-induced anaemia can protect the host from malaria by limiting parasite growth. On the other hand, iron deficiency can significantly disrupt immune cell function.

Ancient genomic linkage couples metabolism with erythroid development.

Generation of mature cells from progenitors requires tight coupling of differentiation and metabolism. During erythropoiesis, erythroblasts are required to massively upregulate globin synthesis then clear extraneous material and enucleate to produce erythrocytes. has remained in synteny with the α-globin genes for >500 million years, and harbours the majority of the α-globin enhancers.

Iron deficiency and the effectiveness of the BNT162b2 vaccine for SARS-CoV-2 infection: A retrospective, longitudinal analysis of real-world data.

Background: Iron plays a key role in human immune responses; however, the influence of iron deficiency on the coronavirus disease 2019 (COVID-19) vaccine effectiveness is unclear.

Aim: To assess the effectiveness of the BNT162b2 messenger RNA COVID-19 vaccine in preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19-related hospitalization and death in individuals with or without iron deficiency.

Methods: This large retrospective, longitudinal cohort study analyzed real-world data from the Maccabi Healthcare Services database (covering 25% of Israeli residents).

Defective iron homeostasis and hematological abnormalities in Niemann-Pick disease type C1.

: Niemann-Pick disease type C1 (NPC1) is a neurodegenerative lysosomal storage disorder characterized by the accumulation of multiple lipids in the late endosome/lysosomal system and reduced acidic store calcium. The lysosomal system regulates key aspects of iron homeostasis, which prompted us to investigate whether there are hematological abnormalities and iron metabolism defects in NPC1. : Iron-related hematological parameters, systemic and tissue metal ion and relevant hormonal and proteins levels, expression of specific pro-inflammatory mediators and erythrophagocytosis were evaluated in an authentic mouse model and in a large cohort of NPC patients.

Iron, glucose and fat metabolism and obesity: an intertwined relationship.

A bidirectional relationship exists between adipose tissue metabolism and iron regulation. Total body fat, fat distribution and exercise influence iron status and components of the iron-regulatory pathway, including hepcidin and erythroferrone. Conversely, whole body and tissue iron stores associate with fat mass and distribution and glucose and lipid metabolism in adipose tissue, liver, and muscle.

Hepcidin-guided screen-and-treat interventions for young children with iron-deficiency anaemia in The Gambia: an individually randomised, three-arm, double-blind, controlled, proof-of-concept, non-inferiority trial.

Background: Iron deficiency is the most prevalent nutritional disorder worldwide. Iron supplementation has modest efficacy, causes gastrointestinal side-effects that limit compliance, and has been associated with serious adverse outcomes in children across low-income settings. We aimed to compare two hepcidin-guided screen-and-treat regimens designed to reduce overall iron dosage by targeting its administration to periods when children were safe and ready to receive iron supplementation, with WHO's recommendation of universal iron supplementation.

Effects of iron deficiency and iron supplementation at the host-microbiota interface: Could a piglet model unravel complexities of the underlying mechanisms?

Iron deficiency is the most prevalent human micronutrient deficiency, disrupting the physiological development of millions of infants and children. Oral iron supplementation is used to address iron-deficiency anemia and reduce associated stunting but can promote infection risk since restriction of iron availability serves as an innate immune mechanism against invading pathogens. Raised iron availability is associated with an increase in enteric pathogens, especially Enterobacteriaceae species, accompanied by reductions in beneficial bacteria such as Bifidobacteria and lactobacilli and may skew the pattern of gut microbiota development.

Plasma iron controls neutrophil production and function.

Low plasma iron (hypoferremia) induced by hepcidin is a conserved inflammatory response that protects against infections but inhibits erythropoiesis. How hypoferremia influences leukocytogenesis is unclear. Using proteomic data, we predicted that neutrophil production would be profoundly more iron-demanding than generation of other white blood cell types.

Evaluation of perturbed iron-homeostasis in a prospective cohort of patients with COVID-19.

Marked reductions in serum iron concentrations are commonly induced during the acute phase of infection. This phenomenon, termed hypoferremia of inflammation, leads to inflammatory anemia, but could also have broader pathophysiological implications. In patients with coronavirus disease 2019 (COVID-19), hypoferremia is associated with disease severity and poorer outcomes, although there are few reported cohorts.

Dual RNA sequencing reveals dendritic cell reprogramming in response to typhoidal Salmonella invasion.

Salmonella enterica represent a major disease burden worldwide. S. enterica serovar Typhi (S.

Analysis of Iron and Iron-Interacting Protein Dynamics During T-Cell Activation.

Recent findings have shown that iron is a powerful regulator of immune responses, which is of broad importance because iron deficiency is highly prevalent worldwide. However, the underlying reasons of why iron is needed by lymphocytes remain unclear. Using a combination of mathematical modelling, bioinformatic analysis and experimental work, we studied how iron influences T-cells.

Temporal variation of planetary iron as a driver of evolution.

Iron is an irreplaceable component of proteins and enzyme systems required for life. This need for iron is a well-characterized evolutionary mechanism for genetic selection. However, there is limited consideration of how iron bioavailability, initially determined by planetary accretion but fluctuating considerably at global scale over geological time frames, has shaped the biosphere.

Intravenous iron to treat anaemia following critical care: a multicentre feasibility randomised trial.

Background: Anaemia is common and associated with poor outcomes in survivors of critical illness. However, the optimal treatment strategy is unclear.

Methods: We conducted a multicentre, feasibility RCT to compare either a single dose of ferric carboxymaltose 1000 mg i.

Metabolic requirements of NK cells during the acute response against retroviral infection.

Natural killer (NK) cells are important early responders against viral infections. Changes in metabolism are crucial to fuel NK cell responses, and altered metabolism is linked to NK cell dysfunction in obesity and cancer. However, very little is known about the metabolic requirements of NK cells during acute retroviral infection and their importance for antiviral immunity.

Vaccine efficacy and iron deficiency: an intertwined pair?

Vaccines are the most effective measure to prevent deaths and illness from infectious diseases. Nevertheless, the efficacy of several paediatric vaccines is lower in low-income and middle-income countries (LMICs), where mortality from vaccine-preventable infections remains high. Vaccine efficacy can also be decreased in adults in the context of some common comorbidities.

Inclusion of cGAMP within virus-like particle vaccines enhances their immunogenicity.

Cyclic GMP-AMP (cGAMP) is an immunostimulatory molecule produced by cGAS that activates STING. cGAMP is an adjuvant when administered alongside antigens. cGAMP is also incorporated into enveloped virus particles during budding.