Elevated Iron Levels Research Articles

Peripheral and Central Iron Measures in Alcohol Use Disorder and Aging: A Quantitative Susceptibility Mapping Pilot Study.

Chronic excessive alcohol use has neurotoxic effects, which may contribute to cognitive decline and the risk of early-onset dementia. Elevated peripheral iron levels have been reported in individuals with alcohol use disorder (AUD), but its association with brain iron loading has not been explored. We evaluated whether (1) serum and brain iron loading are higher in individuals with AUD than non-dependent healthy controls and (2) serum and brain iron loading increase with age. A fasting serum iron panel was obtained and a magnetic resonance imaging scan with quantitative susceptibility mapping (QSM) was used to quantify brain iron concentrations. Although serum ferritin levels were higher in the AUD group than in controls, whole-brain iron susceptibility did not differ between groups. Voxel-wise QSM analyses revealed higher susceptibility in a cluster in the left globus pallidus in individuals with AUD than controls. Whole-brain iron increased with age and voxel-wise QSM indicated higher susceptibility with age in various brain areas including the basal ganglia. This is the first study to analyze both serum and brain iron loading in individuals with AUD. Larger studies are needed to examine the effects of alcohol use on iron loading and its associations with alcohol use severity, structural and functional brain changes, and alcohol-induced cognitive impairments.

Effect of standard phlebotomy on myocardial and hepatic iron levels in newly diagnosed cardiac asymptomatic hereditary hemochromatosis subjects with C282Y homozygosity.

Effect of standard phlebotomy on myocardial and hepatic iron levels in newly diagnosed cardiac asymptomatic hereditary hemochromatosis subjects with C282Y homozygosity.

A pilot study to evaluate clinical factors associated with iron and ferritin elevations during pediatric extracorporeal membrane oxygenation.

Introduction: Elevations in serum ferritin and serum iron occur during pediatric extracorporeal membrane oxygenation (ECMO). Previous reports attribute the elevation to frequent red blood cell transfusions and/or hemolysis. Chronic transfusion can cause iron deposition in tissues leading to multisystem organ dysfunction. This study aims identify clinical factors associated with elevated ferritin and iron in pediatric ECMO patients, along with post-decannulation magnetic resonance imaging (MRI) assessment of iron deposition in liver and brain.Methods: Prospective, pilot study, using descriptive statistics to investigate potential associations between patient characteristics, serum ferritin and iron levels, and post-decannulation hepatic and basal ganglia iron deposition.Results: In this study, nine patients (100%) had elevated serum ferritin levels during ECMO. High ferritin levels were more common with veno-arterial than with veno-venous cannulation (p = 0.026) and were also associated with high plasma free hemoglobin levels (p < 0.001). Five patients presented with elevated serum iron levels. High serum iron levels were associated with higher daily (p = 0.016) and cumulative transfusion volumes (p = 0.013) as well ECMO duration beyond 7days. MRI scans were performed on three patients with no evidence of abnormal iron deposition detected in the liver or brain.Conclusions: This pilot study shows that during pediatric ECMO, elevations in serum ferritin and serum iron occur and those elevations may be related to the cannulation modality, ECMO duration, amount of hemolysis, and volume of red blood cell transfusions. Further investigation is warranted to fully understand the implications of elevated serum iron and ferritin in pediatric ECMO.

Comparison of Tuttha Bhasma Prepared by Two Different Methods: A Pharmaceutico-analytical Study

ABSTRACT Introduction: This research study focuses on the standardization and chemical characterization of Tuttha Bhasma, an essential component of Ayurvedic medicine. Tuttha, a mineral substance, is utilized for its therapeutic properties but requires purification before use to prevent adverse effects. The study aims to standardize two distinct preparation methods (Method A and Method B) for Tuttha Bhasma following traditional procedures and assess their chemical properties for potential therapeutic efficacy. Materials and Methods: Raw materials including Tuttha, Nimbu, Lakucha, Shodhit Gandhaka, and Shodhit Tankana were procured and used in the preparation processes. The study involved Nirmalikarana (cleansing), Tuttha Shodhana (purification), and Tuttha Marana (incineration) through both methods. Organoleptic tests and Bhasma Pariksha tests were conducted alongside modern atomic absorption spectroscopy to analyze Tuttha Bhasma’s physical characteristics and chemical composition. Results: Tuttha Bhasma prepared using both methods and passed classical Ayurvedic tests, indicating successful preparation. Analysis revealed substantial changes in chemical composition during Tuttha Bhasma preparation. Method A exhibited a significant increase in copper content (65.85%) while Method B displayed elevated copper (67.23%), sulfur (8.51%), and iron (1.76%) levels. Method B’s Tuttha Bhasma exhibited higher proportions of macro- and microminerals. Conclusion: The study successfully standardizes Tuttha Bhasma preparation methods and characterizes their chemical properties. Both methods yield Bhasma conforming to classical Ayurvedic tests, indicating their potential efficacy. Method B, involving Gandhaka and Tankana for Marana, results in Tuttha Bhasma with enhanced mineral content, suggesting greater therapeutic potential. These findings contribute to the advancement of Ayurvedic medicine, offering standardized Tuttha Bhasma preparation methods and insights into its chemical composition for future therapeutic exploration.

Iron and glucose-regulated protein 78: fundamental components in the coinfection of Rhizopus oryzae and SARS-CoV-2

Along with the growing number of fatalities and lack of specific treatment at the time, the increasing incidence of mucormycosis worried world health agencies, as it ran the risk of more threatening outcomes for COVID-19 patients. In this context, this review aims to assemble case reports of COVID-19 associated mucormycosis and discuss virulence and host factors involved in the progress of these infections – key aspects that might unveil biological targets and pharmacological approaches to treat these infections. Recently, elevated serum iron levels during SARS-CoV-2 infection have been reported in the literature. Besides being a clinical characteristic of diabetic patients, iron overload is described as a risk factor for Rhizopus oryzae infection. Furthermore, the increased expression of human heat-shock protein GRP78 during iron overload and coronavirus infection display a crucial role as a mediator in Mucorales invasion. These remarkable mechanisms might explain the high incidence of mucormycosis in COVID-19 patients with diabetes and, therefore, suggest regulation of GRP78 expression, management of glycemia and glucocorticoid treatment as potential therapeutic targets of this severe coinfection.

Upregulation of Nrf2 Signalling and the Inhibition of Erastin-Induced Ferroptosis by Ferulic Acid in MIN6 Cells.

Ferroptosis is a regulated cell death process characterised by the iron-dependent accumulation of oxidised polyunsaturated fatty acid-containing phospholipids. Its initiation is complicated and involves reactive oxygen species (ROS) and a loss of the activity of the lipid repair enzyme glutathione peroxidase 4 (GPX4). These play critical roles in the development of ferroptotic cell damage by lipid peroxidation. Antioxidant therapy is a promising therapeutic strategy to prevent or even reverse the progression of ferroptosis. This study was designed to demonstrate the protective effect of ferulic acid (FA) against oxidative stress and erastin-mediated ferroptosis in murine MIN6 cells. Cells were treated with FA or its metabolite ferulic acid 4-O-sulfate disodium salt (FAS) and 20 μM of erastin. Cell viability was determined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assay, iron levels were measured by inductively coupled plasma mass spectrometry (ICP-MS), ROS levels were determined by a dihydrodichlorofluorescein (H2DCF) cell-permeant probe, and glutathione and lipid peroxidation were assayed with commercially available kits. The phenolic acids enhanced cell viability in erastin-treated MIN6 cells in a dose-dependent manner. Furthermore, MIN6 cells exposed to erastin alone showed elevated levels of iron and ROS, glutathione (GSH) depletion, and lipid peroxidation (p < 0.05) compared to cells that were protected by co-treatment with FA or FAS. The treatment of MIN6 cells with FA or FAS following exposure to erastin increased the nuclear translocation of nuclear factor erythroid-2-related factor 2 (Nrf2) protein levels. Consequently, levels of its downstream antioxidant proteins, HO-1, NQO1, GCLC, and GPX4, increased. FA and FAS greatly decreased erastin-induced ferroptosis in the presence of the Nrf2 inhibitor, ML385, through the regulation of Nrf2 response genes. In conclusion, these results show that FA and FAS protect MIN6 cells from erastin-induced ferroptosis by the Nrf2 antioxidant protective mechanism.

Vascular Aging and Damage in Patients with Iron Metabolism Disorders.

Vascular aging is a physiological, multifactorial process that involves every type of vessel, from large arteries to microcirculation. This manifests itself as impaired vasomotor function, altered secretory phenotype, deteriorated intercellular transport function, structural remodeling, and aggravated barrier function between the blood and the vascular smooth muscle layer. Iron disorders, particularly iron overload, may lead to oxidative stress and, among other effects, vascular aging. The elevated transferrin saturation and serum iron levels observed in iron overload lead to the formation of a non-transferrin-bound iron (NTBI) fraction with high pro-oxidant activity. NTBI can induce the production of reactive oxygen species (ROS), which induce lipid peroxidation and mediate iron-related damage as the elements of oxidative stress in many tissues, including heart and vessels' mitochondria. However, the available data make it difficult to precisely determine the impact of iron metabolism disorders on vascular aging; therefore, the relationship requires further investigation. Our study aims to present the current state of knowledge on vascular aging in patients with deteriorated iron metabolism.

Sec14-like-Lipid-Binding-4 Enables Hemoglobin Clearance By Liver Sinusoidal Endothelial Cells

Hemolysis of banked red blood cells (RBC storage lesion) contributes to lack of therapeutic benefit and higher mortality following transfusion therapy in patients. However, the molecular mechanism underlying storage lesion remains poorly understood. Using a multiple-ancestry genome-wide association analysis among blood donors, our group has recently identified Sec14-like-lipid-binding-4 (Sec14L4) protein to be associated with increased rate of hemolysis following blood storage. Although Sec14L4 is highly similar to yeast phosphatidylinositol transfer protein Sec14, which is known to be involved in the synthesis of golgi-derived transport vesicles, the exact function of Sec14L4 and how it promotes RBC storage lesions remains unknown. Our initial studies using fluorescence microscopy in our newly generated Sec14L4 null mice revealed significant enrichment of Sec14L4 in the live sinusoidal endothelial cells (LSECs), which positively correlated with elevated levels of iron in the liver. Scanning and transmission electron micrographs revealed impaired actin cytoskeleton organization in LSECs of Sec14L4 null mice, which was associated with upregulation of major GTPases RhoA, RhoB and Rac1 activity. The impairment of actin cytoskeletal organization in Sec14L4 null mice lead to impaired vesicle trafficking in LSECs and higher retention of RBCs in the liver sinusoids compared to control mice. These data are the first to demonstrate a previously unrecognized role for Sec14L4 protein in LSEC mediated endocytic trafficking by promoting actin polymerization. These findings also suggest that Sec14L4 may regulate RBC storage lesion through impaired hemoglobin clearance by LSECs secondary to cytoskeletal impairment.

METTL16 epigenetically enhances GPX4 expression via m6A modification to promote breast cancer progression by inhibiting ferroptosis

Breast cancer is malignant cancer that severely threatens the life quality of female patients. N6-methyladenosine (m6A) is a prevalent modification of RNA. METTL16 is an important methyltransferase. This work aims to study the role of METTL16 in breast cancer cell death. The expression of METTL16 in clinical breast cancer specimens was analyzed by qPCR assay. The in vitro and in vivo breast cancer cell proliferation was measured by CCK8, colony formation, and xenograft mouse model. Cell ferroptosis was assessed by measuring the accumulation of iron, Fe2+, and lipid ROS. The mechanistic study was performed by RNA degradation, qPCR, and Western blotting assay. METTL16 was overexpressed in tumor tissues from breast cancer patients compared with the para-tumor tissues. Knockdown of METTL16 suppressed in vitro cell proliferation and in vivo tumor growth of breast cancer cells. Meanwhile, METTL16 silencing led to elevated intracellular levels of iron, Fe2+, and lipid ROS, indicating the incidence of ferroptosis. Furthermore, siMETTL16 decreased m6A methylation and enhanced the degradation of GPX4 RNA. METTL16-regulated m6A methylation of GPX4 stimulates proliferation and suppresses ferroptosis of breast cancer cells. Therefore, we concluded that METTL16 epigenetically enhanced GPX4 expression via m6A modification to promote breast cancer progression by inhibiting ferroptosis.

Tycho Brahe’s Health and Death: What Can We Learn from the Trace Element Levels Found in His Hair and Bone Samples?

Abstract Based on the analysis of Tycho Brahe’s hair and bones for the presence of elevated levels of the elements iron (Fe), cobalt (Co), arsenic (As), silver (Ag) and gold (Au), this paper tries to find their likely sources and to judge whether the unusual concentrations in which they were found could have been due to some form of medication. On the basis of an osteopathological study, an attempt is made moreover to arrive at a comprehensive picture of Brahe’s health. As a possible source of the elements in question, his three elixirs and their compositions are discussed. Additionally, further inorganic medicines of the period containing the above-mentioned elements are presented and, where possible, their medical usage is discussed. While a combination of pathological data and probable medication is used to draw a general picture of Brahe’s health and potential illnesses, some questions cannot be conclusively answered, however, until more data about the astronomer’s health conditions come to light.

Iron-dependent BMP6 Regulation in Liver Sinusoidal Endothelial Cells Is Instructed by Hepatocyte-derived Secretory Signals.

Iron-dependent BMP6 Regulation in Liver Sinusoidal Endothelial Cells Is Instructed by Hepatocyte-derived Secretory Signals.

Iron Profile in Patients with Type II Diabetes Mellitus in — A study in a Tertiary Care Hospital

Abstract Background: The most prevalent metabolic condition, type 2 diabetes mellitus, is characterized by persistent hyperglycemia caused by abnormalities in insulin production, insulin action, or both. Iron, a transitional metal, has been demonstrated to play a key role in the pathophysiology of Type 2 Diabetes Mellitus, with a bidirectional link in which iron influences glucose metabolism, which in turn influences the iron metabolic pathways. The current study aimed to estimate the iron profile in Type 2 diabetes mellitus cases. Methods: This cross-sectional study was done in the Department of Biochemistry, Prathima Institute of Medical Sciences, Naganoor, Karimnagar. A total of n=100 cases of type II diabetes mellitus were included in the study and age and sex-matched healthy controls were also included in the study. Laboratory investigations included Fasting Blood glucose, Serum ferritin, Total iron-binding capacity, serum iron, and serum transferrin saturation. Results: The fasting blood glucose was found to be significantly higher in the diabetes mellitus cases. The serum ferritin mean values were 105.32 µgm/dl. In the controls, the range of ferritin levels was 145 µgm/dl. The serum ferritin levels were found to be significantly reduced in the study cases as compared to the controls. Similarly, the total iron-binding capacity (TIBC) of the cases was found to be significantly increased as compared to the controls. The serum transferrin levels were also found to be elevated in the study cases as compared to the controls. Conclusion: Iron is closely related to the development of diabetes mellitus. Elevated iron and ferritin levels are risk factors for diabetes and can lead to a variety of problems. Conversely in chronic diabetics, there is a tendency to develop iron deficiency anemia and other nutritional deficiency anemias as observed by the results of the current study. As a result, iron profile evaluation can be a valuable output of the expected investigations on diabetes and related problems.

Quantifying Brain Iron in Hereditary Hemochromatosis Using R2* and Susceptibility Mapping.

Brain iron dyshomeostasis is increasingly recognized as an important contributor to neurodegeneration. Hereditary hemochromatosis is the most commonly inherited disorder of systemic iron overload. Although there is an increasing interest in excessive brain iron deposition, there is a paucity of evidence showing changes in brain iron exceeding that in healthy controls. Quantitative susceptibility mapping and R2* mapping are established MR imaging techniques that we used to noninvasively quantify brain iron in subjects with hereditary hemochromatosis. Fifty-two patients with hereditary hemochromatosis and 47 age- and sex-matched healthy controls were imaged using a multiecho gradient-echo sequence at 3T. Quantitative susceptibility mapping and R2* data were generated, and regions within the deep gray matter were manually segmented. Mean susceptibility and R2* relaxation rates were calculated for each region, and iron content was compared between the groups. We noted elevated iron levels in patients with hereditary hemochromatosis compared with healthy controls using both R2* and QSM methods in the caudate nucleus, putamen, pulvinar thalamus, red nucleus, and dentate nucleus. Additionally, the substantia nigra showed increased susceptibility while the thalamus showed an increased R2* relaxation rate compared with healthy controls, respectively. Both quantitative susceptibility mapping and R2* showed abnormal levels of brain iron in subjects with hereditary hemochromatosis compared with controls. Quantitative susceptibility mapping and R2* can be acquired in a single MR imaging sequence and are complementary in quantifying deep gray matter iron.

The Role of Microglia in Alzheimer's Disease From the Perspective of Immune Inflammation and Iron Metabolism.

Alzheimer’s disease (AD), the most common type of senile dementia, includes the complex pathogenesis of abnormal deposition of amyloid beta-protein (Aβ), phosphorylated tau (p-tau) and neuroimmune inflammatory. The neurodegenerative process of AD triggers microglial activation, and the overactivation of microglia produces a large number of neuroimmune inflammatory factors. Microglia dysfunction can lead to disturbances in iron metabolism and enhance iron-induced neuronal degeneration in AD, while elevated iron levels in brain areas affect microglia phenotype and function. In this manuscript, we firstly discuss the role of microglia in AD and then introduce the role of microglia in the immune-inflammatory pathology of AD. Their role in AD iron homeostasis is emphasized. Recent studies on microglia and ferroptosis in AD are also reviewed. It will help readers better understand the role of microglia in iron metabolism in AD, and provides a basis for better regulation of iron metabolism disorders in AD and the discovery of new potential therapeutic targets for AD.

Serum Ferritin in Metabolic Syndrome-Mechanisms and Clinical Applications.

Metabolic syndrome (MS) is a cluster of conditions including central obesity, hypertriglyceridemia, low HDL cholesterol, hyperglycaemia, and hypertension with a prevalence rate of 20–25% of the world’s adult population. Metabolic syndrome is often characterized by insulin resistance, which some have suggested is a major supportive connection between physical inactivity and MS. Various studies suggest that moderately elevated iron and ferritin levels are associated with an increased prevalence of metabolic syndrome and are markers of insulin resistance. Increased body iron stores are associated with the development of glucose intolerance, type 2 diabetes mellitus, and insulin resistance syndrome (IRS). This is a hospital-based cross-sectional observational study, which was conducted in the department of internal medicine of a tertiary care hospital in northern India. The study was conducted from 1 January 2019 to 30 June 2020 and included 100 patients and 100 controls. All subjects in the age group of 35–65 years were enrolled and investigated as per the study design. Metabolic syndrome patients were diagnosed according to the modified National Cholesterol Education Program Adult Treatment Panel-III (NCEP ATP-III) with BMI > 23 kg/m2. All baseline investigations were undertaken, including serum ferritin levels. Insulin resistance (IR) was calculated using the homeostasis model assessment IR (HOMA-IR) formula. We found a positive association between an increase in serum ferritin with the prevalence of metabolic syndrome and its clinical parameter. The serum ferritin level was positively correlated with the level of insulin resistance and inversely correlated with the insulin level of the patients.

The Neisseria gonorrhoeae type IV pilus promotes resistance to hydrogen peroxide- and LL-37-mediated killing by modulating the availability of intracellular, labile iron.

The Neisseria gonorrhoeae Type IV pilus is a multifunctional, dynamic fiber involved in host cell attachment, DNA transformation, and twitching motility. We previously reported that the N. gonorrhoeae pilus is also required for resistance against hydrogen peroxide-, antimicrobial peptide LL-37-, and non-oxidative, neutrophil-mediated killing. We tested whether the hydrogen peroxide, LL-37, and neutrophil hypersensitivity phenotypes in non-piliated N. gonorrhoeae could be due to elevated iron levels. Iron chelation in the growth medium rescued a nonpiliated pilE mutant from both hydrogen peroxide- and antimicrobial peptide LL-37-mediated killing, suggesting these phenotypes are related to iron availability. We used the antibiotic streptonigrin, which depends on free cytoplasmic iron and oxidation to kill bacteria, to determine whether piliation affected intracellular iron levels. Several non-piliated, loss-of-function mutants were more sensitive to streptonigrin killing than the piliated parental strain. Consistent with the idea that higher available iron levels in the under- and non-piliated strains were responsible for the higher streptonigrin sensitivity, iron limitation by desferal chelation restored resistance to streptonigrin in these strains and the addition of iron restored the sensitivity to streptonigrin killing. The antioxidants tiron and dimethylthiourea rescued the pilE mutant from streptonigrin-mediated killing, suggesting that the elevated labile iron pool in non-piliated bacteria leads to streptonigrin-dependent reactive oxygen species production. These antioxidants did not affect LL-37-mediated killing. We confirmed that the pilE mutant is not more sensitive to other antibiotics showing that the streptonigrin phenotypes are not due to general bacterial envelope disruption. The total iron content of the cell was unaltered by piliation when measured using ICP-MS suggesting that only the labile iron pool is affected by piliation. These results support the hypothesis that piliation state affects N. gonorrhoeae iron homeostasis and influences sensitivity to various host-derived antimicrobial agents.

Diagnosing microbiologically influenced corrosion at a crude oil pipeline facility leak site – A multiple lines of evidence approach

In crude oil transmission pipelines, some parts of the system receive minimal or no fluid flow (‘dead legs’), which can on occasion lead to under deposit corrosion wherein a mixture of sediments, hydrocarbons, water, and microorganisms collectively contribute to an integrity failure. However, the microbial contribution to this phenomenon in crude oil transmission pipelines is poorly characterized. To better understand this process, we used a multiple lines of evidence approach to examine a dead leg failure event using sludge samples collected from at andnear the leak location and from non-corroded areas on the same pipe segment. Chemical analyses revealed elevated levels of acetate, total iron, and FeCO3 at the leak locations compared to non-corroded areas. Electrochemical techniques showed increased evidence for corrosion in leak site samples compared to non-corroded samples, while corrosion coupon analysis revealed many localized pits of up to 20 μm deep in leak location samples compared to fewer pits that were up to 4 μm deep from the non-corroded sample after incubating the samples for 30 days. 16S rRNA gene analysis revealed sulfide-producers, acetogens, and methanogens in all collected samples. The lack of detection of FeS as a corrosion product, no significant differences in sulfate and sulfide concentrations across all samples, and elevated levels of acetate at the leak location suggested that acetogens and/or fermentative bacteria contributed to this pipeline leak. This study highlights the use of a multiple lines of evidence approach that can be used to garner evidence to determine the contribution of MIC to failures in dead leg pipeline segments.

Immunoinformatic Design of a Multivalent Peptide Vaccine Against Mucormycosis: Targeting FTR1 Protein of Major Causative Fungi.

Mucormycosis is a potentially fatal illness that arises in immunocompromised people due to diabetic ketoacidosis, neutropenia, organ transplantation, and elevated serum levels of accessible iron. The sudden spread of mucormycosis in COVID-19 patients engendered massive concern worldwide. Comorbidities including diabetes, cancer, steroid-based medications, long-term ventilation, and increased ferritin serum concentration in COVID-19 patients trigger favorable fungi growth that in turn effectuate mucormycosis. The necessity of FTR1 gene-encoded ferrous permease for host iron acquisition by fungi has been found in different studies recently. Thus, targeting the transit component could be a potential solution. Unfortunately, no appropriate antifungal vaccine has been constructed as of yet. To date, mucormycosis has been treated with antiviral therapy and surgical treatment only. Thus, in this study, the FTR1 protein has been targeted to design a convenient and novel epitope-based vaccine with the help of immunoinformatics against four different virulent fungal species. Furthermore, the vaccine was constructed using 8 CTL, 2 HTL, and 1 LBL epitopes that were found to be highly antigenic, non-allergenic, non-toxic, and fully conserved among the fungi under consideration. The vaccine has very reassuring stability due to its high pI value of 9.97, conclusive of a basic range. The vaccine was then subjected to molecular docking, molecular dynamics, and immune simulation studies to confirm the biological environment’s safety, efficacy, and stability. The vaccine constructs were found to be safe in addition to being effective. Finally, we used in-silico cloning to develop an effective strategy for vaccine mass production. The designed vaccine will be a potential therapeutic not only to control mucormycosis in COVID-19 patients but also be effective in general mucormycosis events. However, further in vitro, and in vivo testing is needed to confirm the vaccine’s safety and efficacy in controlling fungal infections. If successful, this vaccine could provide a low-cost and effective method of preventing the spread of mucormycosis worldwide.

Assessment of the ecological state of the composition of surface waters and bottom sediments in the Yamalo-Nenets Autonomous Okrug

The article shows the results of analyzes of surface waters and bottom sediments of the Yamalo-Nenets Autonomous Okrug. The following rivers were selected as objects: the Ob, the Taz, the Pur, the Yuribei etc. Sampling was carried out near settlements Salekhard, Nadym, Salemal, Pitlyar etc. Water samples were analyzed for the content of: dissolved oxygen, chemical oxygen demand, concentrations of oil products, iron, copper, zinc, nickel, manganese, sulfate ions, bottom sediment samples - for pH values of water extract, content of oil products, sulfates, iron, nickel, chromium, manganese, copper, mercury, lead, zinc, cadmium. Excesses of concentrations of iron, manganese and copper (relative to standard values) were found in most water samples. Elevated levels of petroleum products, lead, chromium, zinc, nickel, iron, manganese and copper (compared to the approved background values) were detected in many bottom sediment samples.

An anti-diabetic drug targets NEET (CISD) proteins through destabilization of their [2Fe-2S] clusters

Elevated levels of mitochondrial iron and reactive oxygen species (ROS) accompany the progression of diabetes, negatively impacting insulin production and secretion from pancreatic cells. In search for a tool to reduce mitochondrial iron and ROS levels, we arrived at a molecule that destabilizes the [2Fe-2S] clusters of NEET proteins (M1). Treatment of db/db diabetic mice with M1 improved hyperglycemia, without the weight gain observed with alternative treatments such as rosiglitazone. The molecular interactions of M1 with the NEET proteins mNT and NAF-1 were determined by X-crystallography. The possibility of controlling diabetes by molecules that destabilize the [2Fe–2S] clusters of NEET proteins, thereby reducing iron-mediated oxidative stress, opens a new route for managing metabolic aberration such as in diabetes.