Iron overload

We have previously reported the design of a portable 109Cd x-ray fluorescence (XRF) skin iron measurement system with a low detection limit of 1.35 μg Fe per g of tissue, which delivers a skin surface dose of 1.1 mSv in iron overload and iron deficiency disease. The system has been found to be precise but must also provide accurate measurements of iron levels in the skin. 
This article describes testing of the system's accuracy. Ten pigskin samples were measured using both the portable XRF system and ICP-MS analysis...

Obesity is associated with dysfunctions in hypothalamic neurons that regulate metabolism, including agouti-related protein (AgRP)-expressing neurons. In a recent article, Zhang et al. demonstrated that either diet- or genetically induced obesity promoted iron accumulation specifically in AgRP neurons. Preventing iron overload in AgRP neurons mitigated diet-induced obesity and related comorbidities in male mice.

Iron is essential for all the lives and mitochondria integrate iron into heme and Fe-S clusters for diverse use as cofactors. Here we screened mitochondrial proteins in KU812 human chronic myelogenous leukemia cells by glutathione S- transferase pulldown assay with PCBP2 to identify mitochondrial receptors for PCBP2, a major cytosolic Fe(II) chaperone. LC-MS analyses identified TOM20, sideroflexin-3 (SFXN3), SFXN1 and TOM70 in the affinity-score sequence. Stimulated emission depletion microscopy and proteinase-K digestion of mitochondria in HeLa cells revealed that TOM20 is located in the outer membrane of mitochondria whereas SFXN3 is located in the inner membrane...

BACKGROUND AND AIMS: Iron overload, oxidative stress and ferroptosis are associated with liver injury in alcohol-associated liver disease (ALD), however, the crosstalk among these regulatory pathways in ALD development is unclear. METHODS: ALD mouse model and general control of amino acid synthesis 5 like 1 (GCN5L1) liver knockout mice were generated to investigate the role of GCN5L1 in ALD development. Proteomic screening tests were performed to identify the key factors mediating GCN5L1 loss-induced ALD...

JOURNAL/nrgr/04.03/01300535-202412000-00027/figure1/v/2024-04-08T165401Z/r/image-tiff Thalamic hemorrhage can lead to the development of central post-stroke pain. Changes in histone acetylation levels, which are regulated by histone deacetylases, affect the excitability of neurons surrounding the hemorrhagic area. However, the regulatory mechanism of histone deacetylases in central post-stroke pain remains unclear. Here, we show that iron overload leads to an increase in histone deacetylase 2 expression in damaged ventral posterolateral nucleus neurons...

PURPOSE: Accurate quantification of liver iron concentration (LIC) can be achieved via magnetic resonance imaging (MRI). Maps of liver T2*/R2* are provided by commercially available, vendor-provided, 3-dimensional (3D) multiecho Dixon sequences and allow automated, inline postprocessing, which removes the need for manual curve fitting associated with conventional 2-dimensional (2D) gradient echo (GRE)-based postprocessing. The main goal of our study was to investigate the relationship among LIC estimates generated by 3D multiecho Dixon sequence to values generated by 2D GRE-based R2* relaxometry as the reference standard...

Hemolytic disease of the fetus and newborn (HDFN) may cause severe cholestasis with direct bilirubin concentrations reaching up to 50 times the upper limit of normal. This case report describes twins whose highest direct bilirubin concentrations were 32.2 mg/dL and 50.2 mg/dL, with no significant signs of hepatic impairment. The index pregnancy was complicated by Rhesus factor immunization with anti-D antibodies present in maternal serum, which caused fetal anemia requiring intrauterine blood transfusions. Complementary tests demonstrated Rhesus D alloimmunization as the sole cause of cholestasis...

BACKGROUND: We prospectively evaluated the predictive value of multiparametric cardiac magnetic resonance (CMR) for cardiovascular complications in non-transfusion-dependent β-thalassemia (β-NTDT) patients who started regular transfusions in late childhood/adulthood (neo β-TDT). METHODS: We considered 180 patients (38.25 ± 11.24 years; 106 females). CMR was used to quantify cardiac iron overload, biventricular function, and atrial dimensions, and to detect left ventricular (LV) replacement fibrosis...

Hemojuvelin (HJV) is a GPI-anchored protein of the repulsive guidance molecule (RGM) family acting as a bone morphogenetic protein (BMP) co-receptor to induce the hepatic iron regulatory protein hepcidin. Hepcidin causes ubiquitination and degradation of the sole known iron exporter ferroportin thereby limiting iron availability. The detailed signaling mechanism of HJV in vivo has yet to be investigated. In the current manuscript, we used an established model of adeno-associated virus (AAV) mediated liver-specific overexpression of HJV in murine models of hepatocyte-specific deficiency of the BMP type I receptors Alk2 or Alk3...

Hereditary hemolytic anemia associated with pyruvate kinase deficiency is a rare hematological disorder that affects the glycolic pathway within red blood cells. The standard of care includes splenectomy, transfusions, and hematopoietic stem cell transplantation. However, these treatments can lead to common iatrogenic side effects such as infections, surgical complications, and iron overload. The novel drug therapy Mitapivat has shown promising results in terms of both efficacy and safety, but it can cause rare side effects such as fractures...

We evaluated the impact of the genotype on clinical and hematochemical features, hepatic and cardiac iron levels, and endocrine, hepatic, and cardiovascular complications in non-transfusion-dependent (NTD) β-thalassemia intermedia (TI) patients. Sixty patients (39.09 ± 11.11 years, 29 females) consecutively enrolled in the Myocardial Iron Overload in Thalassemia project underwent Magnetic Resonance Imaging to quantify iron overload, biventricular function parameters, and atrial areas and to detect replacement myocardial fibrosis...

BACKGROUND: β-Thalassemia major (BTM) is one of the most common hereditary anemias worldwide. Patients suffer from iron overload that results from repeated blood transfusion This in turn leads to multiple organ damage and endocrinopathies. This study aims to assess the prevalence of growth retardation, hypothyroidism, and diabetes mellitus in children and adolescents with BTM treated at Dubai Thalassemia Centre. METHODS: A total of 105 children and adolescents were included in this retrospective observational study...

To assess and validate the gene expression profile of SIRTs (SIRT1, SIRT2, SIRT3, SIRT4, SIRT5, SIRT6, and SIRT7) in relation to the pathogenesis and prognostic progression of Myelodysplastic neoplasm (MDS). Eighty bone marrow samples of patients with de novo MDS were diagnosed according to WHO 2022 and IPSS-R criteria. Ten bone marrow samples were obtained from elderly healthy volunteers and used as control samples. Gene expression levels of all SIRTs were assessed using RT-qPCR assays. Downregulation of SIRT2 (p = 0...

PURPOSE: Bone is susceptible to fluctuations in iron homeostasis, as both iron deficiency and overload are linked to poor bone strength in humans. In mice, however, inconsistent results have been reported, likely due to different diet setups or genetic backgrounds. Here, we assessed the effect of different high and low iron diets on bone in six inbred mouse strains (C57BL/6J, A/J, BALB/cJ, AKR/J, C3H/HeJ, and DBA/2J). METHODS: Mice received a high (20,000 ppm) or low-iron diet (~10 ppm) after weaning for 6-8 weeks...

Previous studies have demonstrated that the underlying mechanisms of myocardial ischemia/reperfusion injury (MIRI) are complex and involve multiple types of regulatory cell death, including ferroptosis, apoptosis, and autophagy. Thus, we aimed to identify the mechanisms underlying MIRI and validate the protective role of epigallocatechin-3-gallate (EGCG) and its related mechanisms in MIRI. An in vivo and in vitro models of MIRI were constructed. The results showed that pretreatment with EGCG could attenuate MIRI, as indicated by increased cell viability, reduced lactate dehydrogenase (LDH) activity and apoptosis, inhibited iron overload, abnormal lipid metabolism, preserved mitochondrial function, decreased infarct size, maintained cardiac function, decreased reactive oxygen species (ROS) level, and reduced TUNEL-positive cells...

Chronic liver diseases are complications of thalassemia with iron overload. Iron chelators are required to remove excessive iron, and antioxidants are supplemented to diminish harmful reactive oxygen species (ROS), purposing to ameliorate oxidative liver damage and dysfunctions. The deferiprone-resveratrol hybrid (DFP-RVT) is a synthetic iron chelator possessing anti-β-amyloid peptide aggregation, anti-malarial activity, and hepatoprotection in plasmodium-infected mice. The study focuses on investigating the antioxidant, cytotoxicity, iron-chelating, anti-lipid peroxidation, and antioxidant defense properties of DFP-RVT in iron-loaded human hepatocellular carcinoma (Huh7) cells...

OBJECTIVES: This study aims to clarify the effect of ferroptosis by P. gingivalis on periodontal epithelium impairment and potential mechanisms. MATERIALS AND METHODS: The expression of epithelial junction proteins (CDH1, OCLN, ZO-1), FTL and GPX4 in healthy and periodontitis tissues was analyzed using bioinformatics analysis and validated in vivo. An in vitro model was constructed to evaluate ferroptosis by mitochondria morphology, content of iron and GSH, and level of lipid peroxidation, FTL, GPX4 and SLC7A11...

BACKGROUND: Beta thalassemia is a lifelong disease involving malformed red blood cells (RBC). One of the disease's complications is hypogonadism, in which adults tend to exhibit regression in sexual characteristics, experience sexual dysfunction, and therefore have a lower quality of life. Around 3-10% of the Indonesian population carries the beta-thalassemia gene. This study aimed to see the proportions of hypogonadism in transfusion-dependent thalassemia patients and its contributing factors...

BACKGROUND: Amorphous silica nanoparticles (SiNPs) have been gradually proven to threaten cardiac health, but pathogenesis has not been fully elucidated. Ferroptosis is a newly defined form of programmed cell death that is implicated in myocardial diseases. Nevertheless, its role in the adverse cardiac effects of SiNPs has not been described. RESULTS: We first reported the induction of cardiomyocyte ferroptosis by SiNPs in both in vivo and in vitro. The sub-chronic exposure to SiNPs through intratracheal instillation aroused myocardial injury, characterized by significant inflammatory infiltration and collagen hyperplasia, accompanied by elevated CK-MB and cTnT activities in serum...

The present study aimed to explore how resveratrol (Res) confers myocardial protection by attenuating ferroptosis. In vivo and in vitro myocardial ischemia/reperfusion injury (MIRI) models were established, with or without Res pretreatment. The results showed that Res pretreatment effectively attenuated MIRI, as evidenced by increased cell viability, reduced lactate dehydrogenase activity, decreased infarct size, and maintained cardiac function. Moreover, Res pretreatment inhibited MIRI-induced ferroptosis, as shown by improved mitochondrial integrity, increased glutathione level, decreased prostaglandin-endoperoxide synthase 2 level, inhibited iron overload, and abnormal lipid peroxidation...