Ferritin

Crystals of E. coli cytochrome b1, alias bacterioferritin, were grown fr om a low ionic strength solution. The resulting monoclniic P21 structure was solved by molecular replacement and refined using noncrystallographi c symmetries applied to the fundamental unit, consisting of two protein subunits and a single haem. From the Patterson self-rotation results it was shown that the asymmetric unit of the monoclinic crystal consists of 12 such dimers and corresponds to a complete, nearly spherical, molecule of bacterioferritin (M4 = 450 kDa) of 432 point-group symmetry. It is thus the most symmetrical cytochrome. As previously determined for the tetragonal form, the haem is located in a special position on a local twofold axis of the dimer. A bimetal centre is also observed within the four-helix bundle of each monomer; a metal-binding site is located on the fourfold axis.

Competing Interests: The authors have declared that no competing interests exist. Copyright: 2014 Verma M et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Iron deficiency (ID) is an urgent public health problem that has devastating effects on maternal and child health. However, due to poor access and affordability, screening and diagnosis for ID is often limited to proxy hemoglobin measurements alone. Here, we report the development and validation of ironPhone, a mobile-device coupled portable diagnostics for quantification of serum ferritin concentrations, an iron status biomarker, within a few minutes, from a drop of fingerprick blood. The ironPhone diagnostic platform comprises of a smartphone accessory, an app, and a disposable lateral flow immunoassay test strip to quantify serum ferritin. For initial validation in the lab, we optimized and evaluated the performance of ironPhone with known ferritin concentrations in spiked buffer and serum samples. Following lab validation, we performed a human validation by collecting fingerprick whole blood samples from 20 participants to assess iron status using ironPhone and compared the results with the laboratory standard IMMULITE 2000 analyzer. Findings from the ironPhone for the buffer and spiked serum samples provided a calibration curve with R 2 values of 0.97 (n=27) and 0.93 (n=12), respectively. On comparison with the laboratory standard IMMULITE analyzer in whole blood samples, a correlation of 0.92 (P < 0.0001) was observed with a sensitivity of over 90% for predicting ID (ferritin < 15.0 µg/L) via the ironPhone, demonstrating its promise for iron status assessment at the point-of-care.

In this excerpt from Inflammation Mastery, 4th Edition (InflammationMastery.com) and Textbook of Clinical Nutrition and Functional Medicine, Dr Vasquez provides pages discussing "Iron Deficiency, Interpretation of Serum Ferritin Table, Management Diagram"

A comparative study of ferrous gluconate as well as fresh and outdated tablets
of Ascofer® was carried out usingM¨ossbauer spectroscopy with a high velocity resolution.
The obtained results revealed the presence of three ferrous and one ferric component in
all investigated samples which may be related to ferrous gluconate molecules and ferric
contamination and/or aging effect

Background: Tick control is an essential aspect of controlling the spread of tick-borne diseases affecting humans and animals, but it presently faces several challenges. Development of an anti-tick vaccine is aimed at designing cost-effective and environmentally friendly protection against ticks and tick-borne diseases as an alternative to the use of chemical acaricides. A single vaccine from the tick midgut protein Bm86 is currently available for field applications, but its efficacy is limited to only some tick species. Identification of candidate vaccine antigens that can affect multiple tick species is highly desirable. The hard tick Haemaphysalis longicornis has two kinds of the iron-binding protein ferritin (HlFER), an intracellular HlFER1 and a secretory HlFER2, and RNA interference experiments showed that these are physiologically important in blood feeding and reproduction and in protection against oxidative stress. Here we investigated the potential of targeting HlFERs for tick control by immunizing the host with recombinant HlFERs (rHlFER1 and rHlFER2).
Methods: Rabbits were immunized with rHlFERs three times subcutaneously at two-week intervals. Antisera were collected before the first immunization and a week after each immunization to confirm the antigen-specific serum antibody titer by serum ELISA. Two weeks after the final immunization, the rabbits were challenged with tick infestation. After dropping, tick feeding and reproduction parameters were evaluated to determine vaccine efficacy. To demonstrate the effects of antibodies, oxidative stress was detected in the eggs and larvae.
Results: The antibody titer of rHlFER-immunized rabbits greatly increased after the second immunization. Antibodies exhibited cross-reactivity with rHlFERs and reacted with tick native HlFERs in Western blot analysis.  Significantly lower bodyweight was observed in the ticks infested from the rHlFER2-immunized rabbit compared to those from the control rabbit. Reduced oviposition and hatching rate were observed in both rHlFER-immunized groups. rHlFER2 showed a higher vaccine efficacy. The antibodies against rHlFERs were detected in the eggs, and higher levels of oxidative stress biomarkers in the eggs and larvae, of ticks from rHlFER vaccinated rabbits.
Conclusion: Collectively, these results showed that HlFER2 has a good potential as an anti-tick vaccine antigen that may affect multiple tick species.

Horse-spleen apoferritin is known to crystallize in three different space groups, cubic F432, tetragonal P42(1)2 and orthorhombic P2(1)2(1)2. A structure comparison of the cubic and tetragonal forms is presented here. Both crystal forms were obtained by the vapor-diffusion technique and data were collected at 2.26 A (cubic crystal) and 2.60 A (tetragonal crystal) resolution. Two main differences were observed between these crystal structures: (i) whereas intermolecular contacts only involve salt-bridge type interactions via cadmium ions in the cubic structure, two types of interactions are observed in the tetragonal crystal (cadmium-ion-mediated salt bridges and hydrogen-bonding interactions) and (ii) cadmium ions bound in the threefold axes of ferritin molecules exhibit lower site-occupation factors in the tetragonal structure than in the cubic one.

This WHO guideline on use of ferritin concentrations to assess iron status in individuals and populations is an update of, and supersedes, previous recommendations in the World Health Organization (WHO)/Centers for Disease Control and Prevention (CDC) publication, Assessing the iron status of population, first published in 2004), and recommendations related to ferritin in Iron deficiency anaemia: assessment, prevention and control, a guide for programme managers (2001).
In order to produce this guideline, the rigorous procedures described in the WHO handbook for guideline development were followed. This document presents the direct and indirect evidence, as well as the qualitative reviews that served to inform the recommendations herein.

OBJECTIVE—We examined the relationship among iron stores, the metabolic syndrome, and insulin resistance. RESEARCH DESIGN AND METHODS—We conducted a cross-sectional study of 6,044 adults &gt;20 years of age who participated in the Third National Health and Nutrition Examination Survey. Metabolic syndrome was defined as the presence of at least three of the following: elevated blood pressure, low HDL cholesterol, elevated serum triglycerides, elevated plasma glucose, and abdominal obesity. Insulin resistance was estimated using homeostasis model assessment (for insulin resistance), fasting insulin, and triglyceride–to–HDL cholesterol ratio. RESULTS—After excluding individuals with likely hemochromatosis, mean serum ferritin values in premenopausal women, postmenopausal women, and men were 33.6, 93.4, and 139.9 μg/l, respectively. Metabolic syndrome was more common in those with the highest compared with the lowest levels of serum ferritin in premenopausal women (14.9 vs. 6.4%, P = 0....

World Health Organization. (‎2020)‎. Serum ferritin concentrations for the assessment of iron status in individuals and populations: technical brief. World Health Organization. https://apps.who.int/iris/handle/10665/337666. License: CC BY-NC-SA 3.0 IGO

Crystals of recombinant mouse L-chain apoferritin were obtained by the hanging-drop technique using ammonium sulfate as precipitant. Two crystal forms were observed in the same drop. The crystals belong to either the P2 monoclinic or to the P42(1)2 tetragonal space group. The monoclinic crystals diffracted to beyond 2.4 A resolution but were systematically twinned, while the tetragonal crystals diffracted to beyond 2.9 A. These crystallization conditions in the absence of metal salts should facilitate the study of the interaction between L-chain ferritins and heavy metals, particularly the iron core.

Cubic F432 crystals of recombinant mouse L-chain apoferritin were obtained by the hanging-drop technique with ammonium sulfate and cadmium sulfate as precipitants. The structure was refined to 2.1 and 1.6 A resolution from data obtained at room temperature and under cryogenic conditions, respectively. The structure of an eight-amino-acid loop insertion in the mouse sequence is found to be highly disordered both at room temperature and at low temperature.

Background There is no recommendation to screen ferritin level in blood donors, even though several studies have noted the high prevalence of iron deficiency after blood donation, particularly among menstruating females. Furthermore, some clinical trials have shown that non-anaemic women with unexplained fatigue may benefit from iron supplementation. Our objective is to determine the clinical effect of iron supplementation on fatigue in female blood donors without anaemia, but with a mean serum ferritin ≤ 30 ng/ml. Methods/Design In a double blind randomised controlled trial, we will measure blood count and ferritin level of women under age 50 yr, who donate blood to the University Hospital of Lausanne Blood Transfusion Department, at the time of the donation and after 1 week. One hundred and forty donors with a ferritin level ≤ 30 ng/ml and haemoglobin level ≥ 120 g/l (non-anaemic) a week after the donation will be included in the study and randomised. A one-month course of oral fe...

Background: In recent years, the use of ferritins as nano-vehicles for drug delivery is taking center stage. Compared to other similar nanocarriers, Archaeoglobus fulgidus ferritin is particularly interesting due to its unique ability to assemble-disassemble under very mild conditions. Recently this ferritin was engineered to get a chimeric protein targeted to human CD71 receptor, typically overexpressed in cancer cells. Results: Archaeoglobus fulgidus chimeric ferritin was used to generate a self-assembling hybrid nanoparticle hosting an aminic dendrimer together with a small nucleic acid. The positively charged dendrimer can indeed establish electrostatic interactions with the chimeric ferritin internal surface, allowing the formation of a protein-dendrimer binary system. The 4 large triangular openings on the ferritin shell represent a gate for negatively charged small RNAs, which access the internal cavity attracted by the dense positive charge of the dendrimer. This ternary protein-dendrimer-RNA system is efficiently uptaken by acute myeloid leukemia cells, typically difficult to transfect. As a proof of concept, we used a microRNA whose cellular delivery and induced phenotypic effects can be easily detected. In this article we have demonstrated that this hybrid nanoparticle successfully delivers a pre-miRNA to leukemia cells. Once delivered, the nucleic acid is released into the cytosol and processed to mature miRNA, thus eliciting phenotypic effects and morphological changes similar to the initial stages of granulocyte differentiation. Conclusion: The results here presented pave the way for the design of a new family of protein-based transfecting agents that can specifically target a wide range of diseased cells.

Background: In recent years, the use of ferritins as nano-vehicles for drug delivery is taking center stage. Compared to other similar nanocarriers, Archaeoglobus fulgidus ferritin is particularly interesting due to its unique ability to assemble-disassemble under very mild conditions. Recently this ferritin was engineered to get a chimeric protein targeted to human CD71 receptor, typically overexpressed in cancer cells. Results: Archaeoglobus fulgidus chimeric ferritin was used to generate a self-assembling hybrid nanoparticle hosting an aminic dendrimer together with a small nucleic acid. The positively charged dendrimer can indeed establish electrostatic interactions with the chimeric ferritin internal surface, allowing the formation of a protein-dendrimer binary system. The 4 large triangular openings on the ferritin shell represent a gate for negatively charged small RNAs, which access the internal cavity attracted by the dense positive charge of the dendrimer. This ternary protein-dendrimer-RNA system is efficiently uptaken by acute myeloid leukemia cells, typically difficult to transfect. As a proof of concept, we used a microRNA whose cellular delivery and induced phenotypic effects can be easily detected. In this article we have demonstrated that this hybrid nanoparticle successfully delivers a pre-miRNA to leukemia cells. Once delivered, the nucleic acid is released into the cytosol and processed to mature miRNA, thus eliciting phenotypic effects and morphological changes similar to the initial stages of granulocyte differentiation. Conclusion: The results here presented pave the way for the design of a new family of protein-based transfecting agents that can specifically target a wide range of diseased cells.

Background and Objective: Increased ferritin levels have been implicated in the pathogenesis of diabetes. This study was done to determine the effect of continuous and interval aerobic exercise training on serum ferritin and iron level of induced diabetic rats. Methods: In this experimental study, 32 wistar rats weighing 205±54 g were randomly allocated into four groups including healthy control, diabetic control, diabetic interval training and diabetic continuous training. The diabetic training groups were received 10 weeks of training following one week after the induction of diabetes by streptozotocin and nicotinamide. Fasting blood sugar ferritin and iron level was measured in each animal. Results: Induction of diabetes significantly increased serum ferritin and iron levels in diabetic control group compared to healthy control group (P<0.05). Serum ferritin and iron levels and fasting blood sugar significantly reduced in interval aerobic exercise and continuous aerobic training groups compared to diabetic control group (P<0.05). There was not any significant difference in the dependent variables between interval aerobic exercise and continuous aerobic training. Conclusion: In conclusion, it seems the training of two methods of aerobic interval and continuous training in induced diabetic rats with reduction of serum ferritin and iron levels, as well as improving fasting blood glucose and serum insulin seems to reduce insulin resistance index and improve glycemic status in induced diabetic rats.

World Health Organization. (‎2020)‎. Serum ferritin concentrations for the assessment of iron status in individuals and populations: technical brief. World Health Organization. https://apps.who.int/iris/handle/10665/337666. License: CC BY-NC-SA 3.0 IGO

The research aims at understanding the molecular mechanisms underlying the protective role played by Dps proteins and ferritins in the bacterial response to iron-induced stress conditions. Iron is an essential element for most organisms, but is potentially toxic due to the low solubility of the stable oxidation state, Fe(III), and to the tendency of Fe(II) to potentiate the production of highly reactive oxygen species (ROS) e.g. through the Fenton reaction. All organisms have developed strategies that allow them to acquire iron, and to solubilize and store it in a non toxic, readily available form. Typically, intracellular iron is sequestered reversibly in ferritin, the ubiquitous iron storage protein (1). In bacteria, given the very limited availability of free Fe(II), the Dps proteins, expressed by bacteria under a variety of stress conditions, have been recognized to possess not only the capacity to accumulate iron in a soluble form similarly to ferritin, but also a specific ability to decrease ROS production induced by Fe(II) and hydrogen peroxide, which is used as physiological oxidant (2, 3). In addition, some members of the Dps family have structural elements that permit the interaction with DNA in a sequence-aspecific manner and thereby protect it physically (4).

Some biologic indices characterizing the state of 50 patients with homozygous β-thalassaemia treated in 3 University Hospitals in our country are studied. In the study not only routine methods for investigation of haematologic and haemoglobin indices but also methods for statistical processing are used, including variational analyses with t-test for comparison of mean quantities, correlational and regressional analyses. The results show difference between blood-group belonging of patients with thalassaemia and healthy population. Still some patients do not receive optimal transfusion regimen. Chelating therapy is also insuficient in a part of the patients. Desferioxamine is still the main chelating medicine. Medical knowledge about the essence of illness and methods for treatment are insuficient in patients and their parents. Combined efforts are necessary - from medical staff, patients and their parents for overcoming of established disadvantages in the treatment of patients with homozygous β- thalassaemia.

We refined the structure of the tetragonal form of recombinant horse L-chain apoferritin to 2.0 A and we compared it with that of the cubic form previously refined to the same resolution. The major differences between the two structures concern the cadmium ions bound to the residues E130 at the threefold axes of the molecule. Taking advantage of the significant anomalous signal (f" = 3.6 e-) of cadmium at 1.375 A, the wavelength used here, we performed anomalous Fourier difference maps with the refined model phases. These maps reveal the positions of anomalous scatterers at different locations in the structure. Among these, some are found near residues that were known previously to bind metal ions, C48, E57, C126, D127, E130, and H132. But new cadmium binding sites are evidenced near residues E53, E56, E57, E60, and H114, which were suggested to be involved in the iron loading process. The quality of the anomalous Fourier difference map increases significantly with noncrystallographic symmetry map averaging. Such maps reveal density peaks that fit the positions of Met and Cys sulfur atoms, which are weak anomalous scatterers (f" = 0.44 e-)

Background & Objective: Female athletes are at an increasing risk of depleting their iron stores and iron deficiency. It has recently been suggested that hepcidin may be an important regulator of wholebody iron homeostasis. Then, the purpose of the present study was to investigate the effects of exhaustive exercises on hepcidin hormone, iron, ferritin, and hemoglobin of female athletes. Materials & Methods: 30 female athletes were selected for the study and were randomly assigned to experimental and control groups. The participants&#39; fasting blood samples were taken 2 h before exercise (including 3*6 repetition), just 3 and 24 hours after exhaustive exercise. Data analysis was carried out using repeated measure and ANOVA. Results: The results showed that hepcidin increased significantly after the exercise in the experimental group (P= 0.001) and the highest increase was 3 hours after exercise (P= 0.004). Also Iron (P= 0.001), ferritin (P= 0.001) and hemoglobin (P= 0.001) increase...