4.6 Review

Iron Chelation as a Potential Therapeutic Approach in Acute Lung Injury

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Iron deficiency and cardiovascular disease

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Summary: Iron deficiency is common in patients with cardiovascular disease, especially coronary artery disease and heart failure. Various factors contribute to the development of iron deficiency, such as inadequate dietary iron, chronic inflammation, and increased blood loss. For patients with heart failure, iron deficiency is an important therapeutic target, even in the absence of anemia.

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Lipocalin-2 promotes acute lung inflammation and oxidative stress by enhancing macrophage iron accumulation

Hyeong Seok An et al.

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Review Chemistry, Multidisciplinary

Ferroptosis in viral infection: the unexplored possibility

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Summary: Viral infections can lead to redistribution of iron and increased cellular iron content in host cells, resulting in ferroptosis, a characteristic form of cell death. Viruses can disrupt iron uptake and the antioxidant response system, as well as utilize iron transporter proteins as receptors.

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Article Cell Biology

The role of ferroptosis in acute lung injury

Xin Liu et al.

Summary: This review summarizes the recent discoveries on the role of ferroptosis in acute lung injury/acute respiratory distress syndrome (ALI/ARDS) to provide new strategies for its prevention and treatment.

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Ameliorating effects of probiotics on alterations in iron homeostasis and inflammation in COVID-19

Eman M. El-Sayed et al.

Summary: COVID-19, caused by SARS-COV-2, continues to pose a global threat with increased mortality rates. The pathogenesis of the virus involves excessive inflammation leading to a cytokine storm, changes in immunity, and disturbances in iron metabolism. Studies suggest that using probiotics as an adjuvant therapy can improve symptoms and outcomes of COVID-19 by ameliorating iron and immunity changes.

MOLECULAR BIOLOGY REPORTS (2022)

Article Respiratory System

Excess iron promotes emergence of foamy macrophages that overexpress ferritin in the lungs of silicosis patients

Christian Anthony Aloe et al.

Summary: This study evaluated iron-related and inflammatory markers in stone benchtop industry workers with silicosis. The results showed significantly elevated iron levels in the blood of silicosis patients, which were strongly correlated with serum ferritin levels. Inflammatory markers were not increased in silicosis patients. Additionally, foamy macrophages were observed in the bronchoalveolar lavage fluid of silicosis patients. Ferritin may represent an early disease marker for silicosis and may contribute to fibrotic lung remodeling.

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Iron overload in alcoholic liver disease: underlying mechanisms, detrimental effects, and potential therapeutic targets

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Review Cell Biology

Interaction between macrophages and ferroptosis

Yan Yang et al.

Summary: Ferroptosis is a newly discovered iron-dependent cell death pathway characterized by lipid peroxidation and GSH depletion, participating in the development of various diseases. Macrophages, as immune cells, play crucial roles in regulating iron, lipid, and amino acid metabolisms, and recent studies target their polarization to induce ferroptosis in cancer cells for treatment.

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Ambient Availability of Amino Acids, Proteins, and Iron Impacts Copper Resistance of Aspergillus fumigatus

Annie Yap et al.

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Association Between Iron Metabolism and Acute Kidney Injury in Critically Ill Patients With Diabetes

Manqiu Mo et al.

Summary: This study investigated the relationship between iron metabolism and acute kidney injury (AKI) in patients with diabetes. The results showed that increased serum ferritin (SF) levels were associated with a higher risk of AKI and all-cause death.

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Iron overload promotes intervertebral disc degeneration via inducing oxidative stress and ferroptosis in endplate chondrocytes

Wenchao Wang et al.

Summary: Iron overload is strongly associated with the onset and development of intervertebral disc degeneration (IVDD) through oxidative stress and ferroptosis.

FREE RADICAL BIOLOGY AND MEDICINE (2022)

Article Biochemistry & Molecular Biology

Anti-Inflammatory Effects of the Iron Chelator, DIBI, in Experimental Acute Lung Injury

Christian Lehmann et al.

Summary: The iron chelator, DIBI, exhibits beneficial anti-inflammatory effects in experimental acute lung injury by reducing histopathological damage, inflammatory mediator levels, and NF-kappa B p65 activation.

MOLECULES (2022)

Review Biochemistry & Molecular Biology

Targeting Ferroptosis as a Promising Therapeutic Strategy for Ischemia-Reperfusion Injury

Yihang Pan et al.

Summary: Ischemia-reperfusion (I/R) injury is a significant challenge in perioperative medicine, and ferroptosis has been identified as a potential therapeutic target for this devastating disease.

ANTIOXIDANTS (2022)

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Macrophage ferroportin serves as a therapeutic target against bacteria-induced acute lung injury by promoting barrier restoration

Hanbin Wang et al.

Summary: This study found that pulmonary macrophages from patients with acute respiratory distress syndrome (ARDS) and mice infected with bacteria showed increased expression of ferroportin (FPN). Deleting FPN in myeloid cells enhanced resistance to bacterial infection in mice, reducing bacterial growth and preserving lung barrier integrity. Macrophage FPN deficiency limited iron availability to bacteria and promoted tissue restoration through iron-activated Yes-associated protein signaling.

ISCIENCE (2022)

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STAT6 inhibits ferroptosis and alleviates acute lung injury via regulating P53/SLC7A11 pathway

Youjing Yang et al.

Summary: This study identified STAT6 as a critical regulator of epithelial ferroptosis during acute lung injury (ALI). STAT6 negatively regulates ferroptosis by competitively binding with CBP, inhibiting P53 acetylation and restoring SLC7A11 expression. Overexpression of STAT6 attenuated ALI-induced lung injury. STAT6 may be a potential therapeutic target for the treatment of ALI.

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Targeting ferroptosis as a vulnerability in pulmonary diseases

Li Yang et al.

Summary: This review discusses the role of ferroptosis in the pathogenesis of pulmonary diseases and suggests that targeting ferroptosis could be a potential treatment for drug-resistant lung cancer or antibiotic-resistant pulmonary infections.

CELL DEATH & DISEASE (2022)

Review Immunology

The role of neutrophil extracellular traps in acute lung injury

Davide Scozzi et al.

Summary: Acute lung injury (ALI) is a serious inflammatory condition with high mortality rates. Neutrophils and neutrophil extracellular traps (NETs) are important factors in the development of ALI, with defective NET release contributing to increased infection risk and lung tissue damage. Intervention with DNase and selective NET inhibitors may help reduce lung injury.

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YAP1 alleviates sepsis-induced acute lung injury via inhibiting ferritinophagy-mediated ferroptosis

Jing Zhang et al.

Summary: YAP1 can inhibit ferroptosis and alleviate sepsis-induced acute lung injury (ALI) by disrupting ferritinophagy and regulating key genes and pathways.

FRONTIERS IN IMMUNOLOGY (2022)

Review Medicine, General & Internal

Role of Iron and Iron Overload in the Pathogenesis of Invasive Fungal Infections in Patients with Hematological Malignancies

Toni Valkovic et al.

Summary: Iron plays an important role in the survival and reproduction of fungal pathogens, and there is evidence linking invasive fungal infections to iron or iron overload. Understanding the association between iron and iron overload with susceptibility to invasive fungal infections is crucial, especially for patients with hematological malignancies.

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Antimicrobial Activity of the Iron-Chelator, DIBI, against Multidrug-Resistant Canine Methicillin-Susceptible Staphylococcus pseudintermedius: A Preliminary Study of Four Clinical Strains

Francesca Paola Nocera et al.

Summary: Staphylococcus pseudintermedius is an important pathogen in dogs and also poses a potential threat to human health. A compound called DIBI shows potential as a non-antibiotic treatment for antimicrobial-resistant canine S. pseudintermedius otitis.

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Iron Overload and Breast Cancer: Iron Chelation as a Potential Therapeutic Approach

Sufia Islam et al.

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Iron overload, oxidative stress and vascular dysfunction: Evidences from clinical studies and animal models

Leonardo dos Santos et al.

Summary: Although iron is important for many vital processes in the body, iron overload can cause tissue damage, especially in the cardiovascular system. Recent studies have shown that iron excess can lead to vascular dysfunction, leading to the concept of iron overload vasculopathy. This review summarizes the current knowledge on the impact of iron overload on blood vessels, using evidence from epidemiological studies, animal models, and in vitro cell systems, and highlights potential therapeutic targets.

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Iron Acquisition Mechanisms and Their Role in the Virulence of Acinetobacter baumannii

Shoshana Cook-Libin et al.

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The role of iron in host-microbiota crosstalk and its effects on systemic glucose metabolism

Jordi Mayneris-Perxachs et al.

Summary: Patients with obesity-associated metabolic dysfunction exhibit dysregulation in iron homeostasis and alterations in gut microbiota composition and functionality. This Review discusses the bidirectional relationships between the host and the microbiota in the acquisition of elemental iron and the implications for glucose metabolism.

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ROS-triggered endothelial cell death mechanisms: Focus on pyroptosis, parthanatos, and ferroptosis

Dongdong Zheng et al.

Summary: Endothelial cells act as a physical barrier between the blood and vessel wall in the vascular system, playing a crucial role in maintaining intravascular homeostasis. Dysfunction or death of endothelial cells may lead to the progression of various diseases, mainly associated with oxidative stress.

FRONTIERS IN IMMUNOLOGY (2022)

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The Influence of Viral Infections on Iron Homeostasis and the Potential for Lactoferrin as a Therapeutic in the Age of the SARS-CoV-2 Pandemic

Jeffrey L. Ward et al.

Summary: The association of hyperinflammation and hyperferritinemia with adverse outcomes in SARS-CoV-2-infected patients suggests the importance of iron homeostasis in pathogenesis. Bovine lactoferrin, a multipurpose glycoprotein, has the potential to be a therapeutic adjuvant against SARS-CoV-2.

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Sant-Rayn Pasricha et al.

Summary: Iron deficiency is a major contributor to the global burden of disease, particularly affecting children, premenopausal women, and those in low-income and middle-income countries. Oral iron therapy is usually the first line of treatment, but high-dose oral iron supplementation and iron absorption during inflammation may be limited by hepcidin upregulation.

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The role of iron in the pathogenesis of COVID-19 and possible treatment with lactoferrin and other iron chelators

Hosam M. Habib et al.

Summary: Iron overload is increasingly seen as a contributor to the pathogenesis of COVID-19, triggering inflammation, hypercoagulation, hyperferritinemia, and immune dysfunction. Iron chelators, including the naturally occurring lactoferrin, may hold therapeutic value in COVID-19 by modulating the immune response and blocking the entry of coronaviruses into host cells.

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The Role of Ferroptosis in Acute Respiratory Distress Syndrome

Mengdi Qu et al.

Summary: ?Ferroptosis is a newly discovered type of regulated cell death characterized by iron-dependent lipid peroxidation. It is involved in the pathological development of various diseases and recent studies suggest its potential as a therapeutic target for acute lung injury/acute respiratory distress syndrome.

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Role of Iron in the Molecular Pathogenesis of Diseases and Therapeutic Opportunities

Usama Abbasi et al.

Summary: This article discusses the essential role of iron in the human body, the importance of iron homeostasis, and the effects of iron deficiency and excess on the body. It also explores the use of iron chelation strategies in alleviating the toxicity of excess iron.

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Characterization of a ferroptosis and iron-metabolism related lncRNA signature in lung adenocarcinoma

Jie Yao et al.

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Ferrostatin-1 alleviates lipopolysaccharide-induced acute lung injury via inhibiting ferroptosis

Pengfei Liu et al.

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Lisa Mayr et al.

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The emerging role of ferroptosis in inflammation

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Iron overload causes a mild and transient increase in acute lung injury

Vida Zhang et al.

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Hiroshi Kawabata

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Iron homeostasis and iron-regulated ROS in cell death, senescence and human diseases

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Mitchell D. Knutson

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