Changes In Iron Metabolism Research Articles

Integrating multi-omics techniques and in vitro experiments reveals that GLRX3 regulates the immune microenvironment and promotes hepatocellular carcinoma cell proliferation and invasion through iron metabolism pathways

BackgroundHepatocellular carcinoma (HCC) is a common malignancy worldwide, and its development is closely related to abnormalities in iron metabolism. This study aims to systematically analyze changes in iron metabolism in the tumor microenvironment of HCC using single-cell sequencing technology, and investigate the potential mechanisms by which iron metabolism regulation affects the survival of liver cancer patients.Materials and methodsSingle-cell sequencing data from hepatocellular carcinoma patients were obtained from the GEO database. By iron metabolism genomic scoring, we assessed differences in iron metabolism levels in hepatocellular carcinoma samples. By cell communication analysis as well as GO and KEGG enrichment analysis, we determined the functional role of iron metabolism in different cell types. We used survival analysis and Kaplan-Meier curves to assess the impact of iron metabolism levels on patient prognosis. In addition, we identified and analyzed the expression profile of the GLRX3 gene, investigated its key regulatory role in iron metabolism, and validated its clinical value as a prognostic marker. Finally, we explored the effect of GLRX3 on hepatocellular carcinoma phenotype by in vitro experiments such as PCR, transwell, CCK8, and wound healing assay.ResultsBioinformatics results and experimental validation confirmed the dysregulation of iron metabolism in the development of hepatocellular carcinoma, revealing iron’s regulatory influence across various cell types. Additionally, GLRX3 was identified as a key regulatory factor in iron metabolism, and the mechanism by which GLRX3 regulates tumor cell proliferation and immune evasion was determined. Furthermore, experiments verified GLRX3’s role in facilitating tumor cell proliferation and invasion.ConclusionThis study highlights the critical role of iron metabolism in the progression of hepatocellular carcinoma, particularly the regulatory mechanism of the GLRX3 gene in tumor cell proliferation and immune evasion. Iron metabolism abnormalities are not only drivers of liver cancer development but also key indicators of patient prognosis.

Hepcidin Exacerbates Iron Metabolism Imbalance in Septic Mice.

Sepsis is a life-threatening condition associated with acute organ dysfunction. Iron is an essential trace element for multicellular organisms and almost all microorganisms, and its role in sepsis has been increasingly recognized. The aim of this study was to investigate the changes in iron metabolism in caecal ligation and puncture solution (CLP) -induced septic mice and the effects of hepcidin pretreatment on serum inflammatory marker levels and liver iron metabolism in CLP-induced septic mice. C57BL/6 mice were given normal saline, CLP (peritonitis model) or 100μg of hepcidin via intraperitoneal injection. The experimental animals were divided into 4 groups: the control group, model group (CLP), hepcidin pretreatment Groups CLP+hepcidin-2h and CLP+hepcidin-24h. Blood samples were collected at 6, 12 and 24hours after CLP surgery, and the mice were euthanized and livers were obtained. ELISA revealed that hepcidin pretreatment, especially 2hours in advance (p<0.01), increased the serum hepcidin, TNF-a and IL-6 in CLP-induced septic mice; the serum iron content of CLP-related septic mice decreased (P<0.01), while the liver iron content increased (P<0.01); Hepcidin pretreatment reduced the serum iron (P<0.05) at 6h and 12h and liver iron concentrations (P<0.01) at 6h, 12h and 24h in CLP-related septic mice. Western blotting revealed that the hepatic iron absorption-related proteins transferrin receptor-2 (TFR2), ZRT/IRT-like protein 14 (ZIP14) and divalent meta lion transporter-1 (DMT1) were elevated (P<0.01); The iron-exporting protein ferroportin (SLC40A1) was decreased (P<0.01) throughout CLP and CLP+hepcidin sepsis. Compared with CLP group, the protein expressions in the CLP+ hepcidin-2h group were more obvious than that in the CLP+ hepcidin-24h group. Hepcidin has proinflammatory effect. Hepcidin exacerbates iron metabolism imbalances in sepsis by influencing the expression of iron absorption-related proteins and iron export-related proteins.

Hepcidin: A missing link at the interface of malaria and hypertension

Malaria and hypertension are seemingly unrelated communicable and non-communicable diseases, both highly pervasive in the global south. There is a debate about the potential connection between these two disorders beyond any obvious factors. The emerging evidence suggests an emerging genetic selection pressure for hypertension in malaria-endemic regions. Furthermore, the impact of the liver hormone hepcidin, which has been overlooked, is significant in the development of hypertension due to malaria. Malaria exposure leads to changes in iron metabolism through the regulation of hepcidin, resulting in iron deficiency and, consequently, the development of hypertension.

Iron chelation by oral deferoxamine treatment decreased brain iron and iron signaling proteins.

Deferoxamine (DFO) and other iron chelators are clinically used for cancer and stroke. They may also be useful for Alzheimers disease (AD) to diminish iron from microbleeds. DFO may also stimulate antioxidant membrane repair which is impaired during AD. DFO, and other chelators do enter the brain despite some contrary reports. Low dose, oral DFO was given in lab chow to wildtype (WT) C57BL/6 mice to evaluate potential impact on iron levels, iron-signaling and storage proteins, and amyloid precursor protein (APP) and processing enzymes. Young WT mice do not have microbleeds or disrupted blood-brain barrier of AD mice. Iron was measured by MRI and chemically after two weeks of dietary DFO. Cerebral cortex was examined for changes in iron metabolism, antioxidant signaling, and APP processing by Western blot. DFO decreased brain iron by 18% (MRI) and decreased seven major proteins that mediate iron metabolism by at least 25%. The iron storage proteins ferritin light and heavy chain decreased by at least 30%. APP and secretase enzymes also decreased by 30%. WT mice respond to DFO with decreased APP, amyloid processing enzymes, and antioxidant repair. Potential DFO treatment for early-stage AD by DFO should consider the benefits of lowered APP and secretase enzymes.

Effect of Single High-Dose Vitamin D3 Supplementation on Post-Ultra Mountain Running Heart Damage and Iron Metabolism Changes: A Double-Blind Randomized Controlled Trial.

Exercise-induced inflammation can influence iron metabolism. Conversely, the effects of vitamin D3, which possesses anti-inflammatory properties, on ultramarathon-induced heart damage and changes in iron metabolism have not been investigated. Thirty-five healthy long-distance semi-amateur runners were divided into two groups: one group received 150,000 IU of vitamin D3 24 h prior to a race (n = 16), while the other group received a placebo (n = 19). Serum iron, hepcidin (HPC), ferritin (FER), erythroferrone (ERFE), erythropoietin (EPO), neopterin (NPT), and cardiac troponin T (cTnT) levels were assessed. A considerable effect of ultramarathon running on all examined biochemical markers was observed, with a significant rise in serum levels of ERFE, EPO, HPC, NPT, and cTnT detected immediately post-race, irrespective of the group factor. Vitamin D3 supplementation showed a notable interaction with the UM, specifically in EPO and cTnT, with no other additional changes in the other analysed markers. In addition to the correlation between baseline FER and post-run ERFE, HPC was modified by vitamin D. The ultramarathon significantly influenced the EPO/ERFE/HPC axis; however, a single substantial dose of vitamin D3 had an effect only on EPO, which was associated with the lower heart damage marker cTnT after the run.

Prognostic Impact of Iron Metabolism Changes in Patients with Acute Coronary Syndrome and its Correlation with TIMI Risk Score and 6-month Left Ventricular Performance

Objectives: Iron is vital for human metabolism and function. One major cause of anemia is a shortage of iron. On the other hand, a low blood iron level does not always indica te an abnormal hemoglobin concentration. Left ventricular function, ferritin, and blood iron levels were investigated 6 months following the acute coronary syndrome (ACS) index event. In addition, we searched for correlations between thrombolysis in myocardial infarction (TIMI) risk score, cytokines such as C-reactive protein (CRP), and serum iron content. Materials and Methods: From August 2021 to July 2022, 100 consecutive patients with ACS who were requesting admission to the critical care unit of the Cardiology Department at SCB Medical College in Cuttack, Odisha, were the subject of this study. Participants in our research with ST-elevation or non-ST-elevation myocardial infarction (ST elevation myocardial infarction [STEMI] or Non ST elevation myocardial infarction [NSTEMI]) ranged in age from 18 to 70 years. We measured CRP, transferrin saturation, total iron binding capacity, ferritin, and blood iron at baseline. The left ventricular ejection fraction (LVEF %) difference was assessed 6 months after baseline echocardiography and follow-up. Various factors were considered while calculating the short- and long-term prognoses, including the patient’s heart failure at admission and any deaths that took place in hospitals within 6 months after the index event. Results: There was no improvement in LVEF for 56.25% of patients (36 out of 66) 6 months after the index event; however, for 43.75% (28 patients) of the 66 STEMI patients, LVEF improved. Out of 34 NSTEMI patients, 14 (42.42%) improved their LVEF 6 months after ACS, whereas 19 (57.58%) did not. Serum iron levels and LVEF at 6 months were shown to be significantly correlated in all patients (overall P &lt; 0.001, STEMI P &lt; 0.001, and NSTEMI P = 0.001). Serum iron levels are positively correlated with improvements in LVEF after 6 months in both patients with STEMI; P &lt; 0.001, and NSTEMI P = 0.006. Serum iron levels and hospitalized STEMI patients’ TIMI risk scores showed a significant connection (P &lt; 0.001). Conclusion: Regardless of hemoglobin content, patients with &lt;10% improvement in LVEF from baseline had considerably lower blood iron levels. Six months after their initial ACS incident, patients with ACS who had lower blood iron concentrations at baseline recovered less well in terms of left ventricular systolic function. In our study, 48% of men and 68% of women were found to be iron deficient. In addition to being an indicator of inflammation, hypoferremia may be the target of a novel biomarker with potential applications in medicine in the near future. It could be useful in predicting left ventricular function following ACS.

Iron accumulation in ovarian microenvironment damages the local redox balance and oocyte quality in aging mice

Accumulating oxidative damage is a primary driver of ovarian reserve decline along with aging. However, the mechanism behind the imbalance in reactive oxygen species (ROS) is not yet fully understood. Here we investigated changes in iron metabolism and its relationship with ROS disorder in aging ovaries of mice. We found increased iron content in aging ovaries and oocytes, along with abnormal expression of iron metabolic proteins, including heme oxygenase 1 (HO-1), ferritin heavy chain (FTH), ferritin light chain (FTL), mitochondrial ferritin (FTMT), divalent metal transporter 1 (DMT1), ferroportin1(FPN1), iron regulatory proteins (IRP1 and IRP2) and transferrin receptor 1 (TFR1). Notably, aging oocytes exhibited enhanced ferritinophagy and mitophagy, and consistently, there was an increase in cytosolic Fe2+, elevated lipid peroxidation, mitochondrial dysfunction, and augmented lysosome activity. Additionally, the ovarian expression of p53, p21, p16 and microtubule-associated protein tau (Tau) were also found to be upregulated. These alterations could be phenocopied with in vitro Fe2+ administration in oocytes from 2-month-old mice but were alleviated by deferoxamine (DFO). In vivo application of DFO improved ovarian iron metabolism and redox status in 12-month-old mice, and corrected the alterations in cytosolic Fe2+, ferritinophagy and mitophagy, as well as related degenerative changes in oocytes. Thereby in the whole, DFO delayed the decline in ovarian reserve and significantly increased the number of superovulated oocytes with reduced fragmentation and aneuploidy. Together, our findings suggest that aging-related disturbance in ovarian iron homeostasis contributes to excessive ROS production and that iron chelation may improve ovarian redox status, and efficiently delay the decline in ovarian reserve and oocyte quality in aging mice. These data propose a novel intervention strategy for preserving the ovarian reserve function in elderly women.

Addressing Inequality in the COVID-19 Pandemic in Africa: A Snapshot from Clinical Symptoms to Vaccine Distribution

On 30 January 2020, WHO declared COVID-19 a public health emergency of global concern. COVID-19 became pandemic on 11 March 2020, and spread unprecedently. No country was prepared to face its impact. Major fears started to be expressed for Africa, where dramatic consequences were expected, due to the weakness of health systems. In this review, we related major concerns, at that time but still present, regarding the limited resources in terms of qualified physicians and researchers, as well as the scarce funds to purchase essential medical equipment and improve hospital infrastructures. The difficulties to provide proper care became an undeniable mark of inequality, highlighting the need to empower local capacity and raise preparedness against infection outbreaks. The transmissibility of genetic variants affecting African nations, the immunopathology underlying comorbidities, sequelae, and pre-existing conditions, often related to changes in iron metabolism and enhancing COVID-19 severity, were described. The obstacles in adopting standardized prevention measures were highlighted, along with testing capacity biases and inequity of healthcare access and vaccine distribution. By providing a better understanding of the COVID-19 pandemic in Africa, we draw attention to the need for collaborative efforts to leverage the quality of healthcare and research in this continent.

Glioblastoma multiforme influence on the elemental homeostasis of the distant organs: the results of inter-comparison study carried out with TXRF method

Glioblastoma (GBM) is a fast-growing and aggressive brain tumor which invades the nearby brain tissue but generally does not spread to the distant organs. Nonetheless, if untreated, GBM can result in patient death in time even less than few months from the diagnosis. The influence of the tumor progress on organs other than brain is obvious but still not well described. Therefore, we examined the elemental abnormalities appearing in selected body organs (kidney, heart, spleen, lung) in two rat models of GBM. The animals used for the study were subjected to the implantation of human GBM cell lines (U87MG and T98G) characterized by different levels of invasiveness. The elemental analysis of digested organ samples was carried out using the total reflection X-ray fluorescence (TXRF) method, independently, in three European laboratories utilizing various commercially available TXRF spectrometers. The comparison of the data obtained for animals subjected to T98G and U87MG cells implantation showed a number of elemental anomalies in the examined organs. What is more, the abnormalities were found for rats even if neoplastic tumor did not develop in their brains. The most of alterations for both experimental groups were noted in the spleen and lungs, with the direction of the found element changes in these organs being the opposite. The observed disorders of element homeostasis may result from many processes occurring in the animal body as a result of implantation of cancer cells or the development of GBM, including inflammation, anemia of chronic disease or changes in iron metabolism. Tumor induced changes in organ elemental composition detected in cooperating laboratories were usually in a good agreement. In case of elements with higher atomic numbers (Fe, Cu, Zn and Se), 88% of the results were classified as fully compliant. Some discrepancies between the laboratories were found for lighter elements (P, S, K and Ca). However, also in this case, the obtained results fulfilled the requirements of full (the results from three laboratories were in agreement) or partial agreement (the results from two laboratories were in agreement).

Dysfunctional iron metabolism in pressure injuries is related to aberrant CD163 and Homx-1 signal transduction.

Dysregulation of iron metabolism has been associated with impaired chronic wound healing. However, changes in iron metabolism have yet to be reported in pressure injuries, a type of chronic wound. In this study, we aimed to investigate changes in iron metabolism and associated regulatory mechanisms in pressure injuries. We collected tissue biopsies and data from 20 consenting stage IV-pressure injuries patients and 5 non-pressure injuries patients hospitalised at the Affiliated Hospital of Qingdao University between March 2021 and June 2021. In addition, we measured the iron content by inductively coupled plasma mass spectrometry and Prussian blue staining in deep tissue pressure injury mouse models. An Enzyme-linked immune sorbent assay measured the expression of ferritin, ferroportin-1 and transferrin. Immunofluorescence staining, high-throughput transcriptome sequencing, Western blot and RT-qPCR further analysed the fundamental mechanisms regulating iron metabolism. In this study, we observed numerous inflammatory cells infiltrating the marginal tissues of stage IV pressure injury patients and in deep tissue pressure injury models. The expression levels of pro-inflammatory factors, such as inducible nitric oxide synthase and interleukin-6, were significantly increased (p < 0.05). The iron level was proportional to the degree of progression, with the most significant change appearing on the third day in deep tissue pressure injury models (p < 0.05). Enzyme-linked immune sorbent assay results suggested abnormal gene expression was related to iron metabolism, including a substantial increase in ferritin and a significant decrease in the expression of ferroportin-1 (p < 0.05). In addition, immunofluorescence staining and Western blot showed that the expression of macrophage membrane receptor CD163 was abnormally elevated (p < 0.05). Both high-throughput transcriptome sequencing and qRT-PCR results suggested aberrant expression of the CD163/Homx-1-mediated signalling pathway. Dysfunctional iron metabolism was suggested to be related to the aberrant CD163/Homx-1 signalling pathway in deep tissue pressure injury models.

Continuous training in young athletes decreases hepcidin secretion and is positively correlated with serum 25(OH)D and ferritin.

Iron deficiency is known to impair muscle function and reduce athletic performance, while vitamin D has been reported to induce iron deficiency. However, the mechanism underlying exercise-induced changes in iron metabolism and the involvement of vitamins in this mechanism are unclear. The present study examined changes in biological iron metabolism induced by continuous training and the effects of vitamin D on these changes. Diet, physical characteristics, and blood test data were collected from 23 female high school students in a dance club on the last day of each of a 2-month continuous training period and a 2-week complete rest periods. Serum hepcidin-25 levels were significantly lower during the training period than the rest period (p = 0.013), as were the red blood cell count, hemoglobin, and hematocrit (all p < 0.001). Serum erythropoietin was significantly higher (p = 0.001) during the training period. Significant positive correlations were observed between 25(OH)D levels and serum iron, serum ferritin, and transferrin saturation during the training period. Multiple regression analysis with serum 25(OH)D level as the dependent variable and serum ferritin and iron levels as independent variables during the training period revealed a significant association with serum ferritin. Continuous training may promote hemolysis and erythropoiesis, contributing to the suppression of hepcidin expression. The relationship between serum 25(OH)D and iron in vivo may be closely related to metabolic changes induced by the exercise load.

Amyotrophic lateral sclerosis associated disturbance of iron metabolism is blunted by swim training-role of AKT signaling pathway

Swim training has increased the life span of the transgenic animal model of amyotrophic lateral sclerosis (ALS). Conversely, the progress of the disease is associated with the impairment of iron metabolism and insulin signaling.We used transgenic hmSOD1 G93A (ALS model) and non-transgenic mice in the present study. The study was performed on the muscles taken from trained (ONSET and TERMINAL) and untrained animals at three stages of the disease: BEFORE, ONSET, and TERMINAL. In order to study the molecular mechanism of changes in iron metabolism, we used SH-SY5Y and C2C12 cell lines expression vector pcDNA3.1 and transiently transfected with specific siRNAs.The progress of ALS resulted in decreased P-Akt/Akt ratio, which is associated with increased proteins responsible for iron storage ferritin L, ferritin H, PCBP1, and skeletal muscle iron at ONSET. Conversely, proteins responsible for iron export- TAU significantly decrease. The training partially reverses changes in proteins responsible for iron metabolism. AKT silencing in the SH-SY5Y cell line decreased PCBP2 and ferroportin and increased ferritin L, H, PCBP1, TAU, transferrin receptor 1, and APP. Moreover, silencing APP led to an increase in ferritin L and H.Our data suggest that swim training in the mice ALS model is associated with significant changes in iron metabolism related to AKT activity. Down-regulation of AKT mainly upregulates proteins involved in iron import and storage but decreases proteins involved in iron export.

КЛИНИКО-ДИАГНОСТИЧЕСКОЕ ЗНАЧЕНИЕ ГЕПСИДИНА В РЕГУЛЯЦИИ ОБМЕНА ЖЕЛЕЗА У ПАЦИЕНТОВ С ЮВЕНИЛЬНЫМ ИДИОПАТИЧЕСКИМ АРТРИТОМ

Introduction. Anemia in juvenile idiopathic arthritis (JIA), as a rule, has a multifactorial genesis, which is based on an immune-mediated mechanism: cytokines during inflammation cause changes in iron metabolism, which leads to changes in the production of red blood cells and their precursors, reticulocytes; An increase in hepcidin content causes disturbances in iron metabolism. The purpose of the study was to study hepcidin levels in patients with JIA and determine its prognostic value for the development of anemia. Material and methods. A total of 65 patients with JIA who were undergoing inpatient treatment at the 2nd State Children's Clinical Hospital in Minsk were examined. All patients underwent a general blood test using a hematological analyzer “Sysmex XS-800i” (Japan) with determination of erythrocyte, reticulocyte, and platelet parameters. A biochemical blood test included determination of iron metabolism indicators. The enzyme immunoassay method was used to study the content of cytokines: interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), interleukin-4 (IL-4), interleukin-1β (IL-1β) and γ-interferon (γ-IFN). Results. All patients were divided into two groups according to the median hepcidin value. The first group, in which the values were less than 4760.0 pg/ml, included 31 patients, the second group, in which the values were more than 4760.0 pg/ml, included 34 patients. An increase in hepcidin content was accompanied by an increase in the incidence of anemia (χ² = 4.55; p = 0.03). Based on the results of the Pearson correlation analysis (r), a number of statistically significant relationships between the concentration of hepcidin and the level of IL-6 were identified (r = 0.27; p &lt; 0.05); hemoglobin (r= - 0.28; p&lt;0.05); hemoglobin content in the erythrocyte (r = - 0.29; p &lt; 0.05 and erythropoietin (r = 0.32; p &lt; 0.05). Conclusions. In children with juvenile idiopathic arthritis, increased levels of hepcidin in the blood are accompanied by an increased risk of developing anemia. The earliest markers of the development of this anemia are a decrease in the hemoglobin content in the erythrocyte, a decrease in the average volume of the erythrocyte, and an increase in the synthesis of immature forms of reticulocytes. Hepcidin acts as a marker of both the activity of the inflammatory process in children with JIA and affects the distribution of iron between its storage and the functionally active pool.

Dysregulated iron homeostasis in dystrophin-deficient cardiomyocytes: correction by gene editing and pharmacological treatment.

Duchenne muscular dystrophy (DMD)-associated cardiomyopathy is a serious life-threatening complication, the mechanisms of which have not been fully established, and therefore no effective treatment is currently available. The purpose of the study was to identify new molecular signatures of the cardiomyopathy development in DMD. For modelling of DMD-associated cardiomyopathy, we prepared three pairs of isogenic control and dystrophin-deficient human induced pluripotent stem cell (hiPSC) lines. Two isogenic hiPSC lines were obtained by CRISPR/Cas9-mediated deletion of DMD exon 50 in unaffected cells generated from healthy donor and then differentiated into cardiomyocytes (hiPSC-CM). The latter were subjected to global transcriptomic and proteomic analyses followed by more in-depth investigation of selected pathway and pharmacological modulation of observed defects. Proteomic analysis indicated a decrease in the level of mitoNEET protein in dystrophin-deficient hiPSC-CM, suggesting alteration in iron metabolism. Further experiments demonstrated increased labile iron pool both in the cytoplasm and mitochondria, a decrease in ferroportin level and an increase in both ferritin and transferrin receptor in DMD hiPSC-CM. Importantly, CRISPR/Cas9-mediated correction of the mutation in the patient-derived hiPSC reversed the observed changes in iron metabolism and restored normal iron levels in cardiomyocytes. Moreover, treatment of DMD hiPSC-CM with deferoxamine (DFO, iron chelator) or pioglitazone (mitoNEET stabilizing compound) decreased the level of reactive oxygen species in DMD hiPSC-CM. To our knowledge, this study demonstrated for the first time impaired iron metabolism in human DMD cardiomyocytes, and potential reversal of this effect by correction of DMD mutation or pharmacological treatment. This implies that iron overload-regulating compounds may serve as novel therapeutic agents in DMD-associated cardiomyopathy.

Clinical and pathological features of brain iron metabolism in neurodegerative and demyelinating disorders

The results of many modern studies show the significance of the role of changes in iron metabolism and its increased accumulation in the pathogenesis of neurodegenerative and demyelinating diseases. Determining the role of iron metabolism and the characteristics of its distribution in strategically important areas of the brain in diseases of the nervous system is important from a diagnostic point of view, since it can help determine the rate of disease progression and, accordingly, correction of therapy. The article presents modern literature data describing the main disorders of iron metabolism in the structure of the pathogenesis of neurodegenerative diseases (Alzheimer’s disease and Parkinson’s disease), and demyelinating diseases, in particular, multiple sclerosis. Attention is drawn to the role of changes in iron metabolism in the pathogenesis of the process of regulated cell death, ferroptosis, accompanied by depletion of intracellular glutathione, decreased activity of the enzyme glutathione peroxidase-4 and the subsequent process of lipid peroxidation caused by a decrease in the protective antioxidant system of cells and the accumulation of reactive oxygen species. Attention is drawn to the role of the Fenton reaction in the accumulation of free radicals, the oxidation of iron and, as a consequence, its excessive deposition in brain structures. Information is provided on the features of the pathogenesis of neuronal iron accumulation, modern diagnostic capabilities for assessing iron content in strategically important areas of the brain using various methods, and the possibility of various options for therapeutic treatment of these conditions is considered. Attention is drawn to the patterns of iron distribution in normal brain structures depending on age, as well as in the specified nosologies. Data are presented on the connection between an increase in the amount of iron content in brain cells and the severity of clinical manifestations of diseases. Attention is drawn to the relationship between the progression of disease severity and the increase in metal content in the cells of strategically significant areas of the brain. When writing the article, modern materials and meta-analyses were used, containing the results of a significant number of studies devoted to the problem considered in this review.

Prognostic Impact of Iron Metabolism Changes in Patients with Acute Coronary Syndrome and its Correlation with TIMI Risk Score and 6 Month Left Ventricular Performance

Prognostic Impact of Iron Metabolism Changes in Patients with Acute Coronary Syndrome and its Correlation with TIMI Risk Score and 6 Month Left Ventricular Performance

Beneficial effects of the combination of BCc1 and Hep-S nanochelating-based medicines on IL-6 in hospitalized moderate COVID-19 adult patients: a randomized, double-blind, placebo-controlled clinical trial

BackgroundIn the severe forms of COVID-19 and many other infectious diseases, the patients develop a cytokine storm syndrome (CSS) where pro-inflammatory cytokines such as IL-6 and TNF-α play a key role in the development of this serious process. Selenium and iron are two important trace minerals, and their metabolism is tightly connected to immune system function. Numerous studies highlight the role of selenium and iron metabolism changes in the procedure of COVID-19 inflammation. The immunomodulator effect of nanomedicines that are synthesized based on nanochelating technology has been proved in previous studies. In the present study, the effects of the combination of BCc1(with iron-chelating property) and Hep-S (containing selenium) nanomedicines on mentioned cytokines levels in hospitalized moderate COVID-19 patients were evaluated.MethodsLaboratory-confirmed moderate COVID-19 patients were enrolled to participate in a randomized, double-blind, placebo-controlled study in two separate groups: combination of BCc1 and Hep-S (N = 62) (treatment) or placebo (N = 60) (placebo). The blood samples were taken before medications on day zero, at discharge, and 28 days after consumption to measure hematological and biochemical parameters and cytokine levels. The clinical symptoms of all the patients were recorded according to an assessment questionnaire before the start of the treatment and on days 3 and discharge day.ResultsThe results revealed that consumption of the nanomedicines led to a significant decrease in the mean level of IL-6 cytokine, and at the end of the study, there was a 77% downward trend in IL-6 in the nanomedicine group, while an 18% increase in the placebo group (p < 0.05). In addition, the patients in the nanomedicines group had lower TNF-α levels; accordingly, there was a 21% decrease in TNF-α level in the treatment group, while a 31% increase in this cytokine level in the placebo was observed (p > 0.05). On the other hand, in nanomedicines treated groups, clinical scores of coughing, fatigue, and need for oxygen therapy improved.ConclusionsIn conclusion, the combination of BCc1 and Hep-S inhibits IL-6 as a highly important and well-known cytokine in COVID-19 pathophysiology and presents a promising view for immunomodulation that can manage CSS.Trial registrationIranian Registry of Clinical Trials RCT20170731035423N2. Registered on June 12, 2020.

Seasonal and fasting induced changes in iron metabolism in Djungarian hamsters

Djungarian hamsters are small rodents that show pronounced physiological acclimations in response to changes in photoperiod, and unfavorable environmental conditions such as reduced food availability and low external temperature. These include substantial adjustments, such as severe body weight loss and the use of daily torpor. Torpor is a state of decreased physiological activity in eutherms, usually marked by low metabolic rate and a reduced body temperature. In this study, we investigated the effects of photoperiodic acclimation and food deprivation on systemic iron metabolism in Djungarian hamsters. Our study illustrates the association between liver iron levels and the incidence of torpor expression during the course of the experiment. Moreover, we show that both, acclimation to short photoperiods and long-term food restriction, associated with iron sequestration in the liver. This effect was accompanied with hypoferremia and mild reduction in the expression of principal iron-hormone, hepcidin. In addition to iron, the levels of manganese, selenium, and zinc were increased in the liver of hamsters under food restriction. These findings may be important factors for regulating physiological processes in hamsters, since iron and other trace elements are essential for many metabolic and physiological processes.

Dysregulation of iron metabolism-linked genes at myocardial tissue and cell levels in dilated cardiomyopathy

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Fondazione Gigi &amp; Pupa Ferrari ONLUS Italian Ministry of Health-Ricerca Corrente. Background Heart failure (HF) is defined as one of the main clinical and public health burdens with multifactorial symptoms and high worldwide prevalence. Dilated cardiomyopathy (DCM) is one of the leading causes of HF and is responsible for over half of all left ventricular assist device implantations and heart transplantations. DCM is regarded as a multiple disease entity linked to a number of genetic, nutritional, inflammatory, infective, metabolic, and environmental causes. Among the metabolic processes associated with HF, iron metabolism disorders, ranging from iron deficiency to iron overload, are gaining attention. However, the understanding of iron mechanisms, at cardiac level, involved in HF and particularly in DCM, remains elusive. Purpose We aim to evaluate the possible dysregulation of iron metabolism-linked genes in DCM, through a quantitative analysis of public myocardial gene expression data at tissue and cell levels. Methods Bulk RNA sequencing (RNA-seq) and single-nucleus RNA-seq (snRNA-seq) datasets, respectively of 436 and 38 left ventricle samples from adult non-failed (NF) and DCM subjects, were retrieved from public studies. We defined a list of 272 genes directly related to intramyocardial iron metabolism and performed the differential gene expression analysis both at whole cardiac tissue level and in cardiomyocytes, fibroblasts, myeloid, endocardial, and endothelial cells. Results In the overall myocardial tissue, we found 44 iron-linked genes differentially expressed between DCM and NF subjects. To better understand iron genes abnormalities in the myocardium of DCM patients we deepened the analysis from tissue to single-cell level. Among the five considered cell types (cardiomyocytes, fibroblasts, myeloid, endocardial, and endothelial cells) at least 9% of iron-linked expressed genes were significantly regulated in DCM when compared to NF. Specifically, the iron metabolism in DCM cardiomyocytes is altered at several levels (Figure 1), including: 1) imbalance of Fe3+ internalization (SCARA5 down-regulation) and reduction of internal conversion from Fe3+ to Fe2+ (STEAP3 down-regulation), 2) increase of iron consumption to produce hemoglobin (HBA1/2 up-regulation), 3) higher heme synthesis and externalization (ALAS2 and ABCG2 up-regulation), 4) lower cleavage of heme to Fe2+, biliverdin and carbon monoxide (HMOX2 down-regulation), and 5) positive regulation of hepcidin (BMP6 up-regulation). Conclusions In conclusion, the present study provides significant progress in knowledge of iron metabolism changes in DCM disease, which likely have a clinical meaning. Indeed, our data show that regulation of intracellular iron homeostasis is dysfunctional in DCM patients’ cardiac tissues, supporting, but not providing, the hypothesis of a direct effect of iron in the disease progression.

Oral nutrition supplement improves nutrition and inflammation of cancer patients by regulating iron metabolism

ABSTRACT The relationship between cancer and iron metabolism has received more attention, but there is less research on nutritional support to improve the nutritional and inflammatory status of cancer patients by regulating iron metabolism. A survey was conducted involving 90 patients with lung cancer. The control group was given routine hospitalization diet and the oral nutrition supplement (ONS) group was given oral nutrient solution on the basis of routine hospitalization diet. It lasted for 2 weeks. The changes of iron metabolism, nutritional status, and inflammatory indicators of the two groups were compared. After 2 weeks of intervention, the levels of ALB and PA in the ONS group were increased than that in the control group (P < .05), the inflammation was significantly decreased in the ONS group (P < .05), and the levels of Hb, SI, and TIBC in the ONS group were higher than that in the control group, while the SF was significantly reduced (P < .05). ONS could improve iron metabolism, nutritional status, and inflammatory levels. We speculate that the decrease in inflammation may be due to the changes of iron metabolism, thereby improving nutritional status. It may become a new target for tumor treatment.