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The impact of bio-remediation agent nZVI on environment is still inadequately understood, especially on aquatic food web. The study presented here has therefore considered both chemical (CS) and biological (BS) synthetic origins of nZVI and their effects on both algae and daphnia. The study is unique in its attempt to explore the possibility of trophic transfer from algae to its immediate higher niche (daphnia as the model). An equal weightage of the effects of both CS and BS nZVI on algae and daphnia has been explored here; hence it allows us to compare the capping of nZVI on toxicity. To examine the causes of observed lethality- ROS generation, effects on the activity of oxidative enzymes, membrane damage and biouptake of nZVI was analysed. The overall outcome of CS and BS nZVI on lethality was significantly different in algae and daphnia, where daphnia demonstrated relatively higher sensitivity against CS nZVI. Algae demonstrated considerable differences in CS and BS nZVI toxicity only at higher concentration. This study did not show a probable biomagnification and trophic transfer from algae to daphnia under the experimental conditions even at the highest exposure concentration. The study instigates the importance of trophic transfer to understand the possible biomagnification of nZVI among organisms of different trophic levels and eventually the consequences on environment., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The relationship between iron and β-cell dysfunction has long been recognized as individuals with iron overload display an increased incidence of diabetes. This link is usually attributed to the accumulation of excess iron in β-cells leading to cellular damage and impaired function. Yet, the molecular mechanism(s) by which human β-cells take up iron has not been determined. In the present study, we assessed the contribution of the metal-ion transporters ZRT/IRT-like protein 14 and 8 (ZIP14 and ZIP8) and divalent metal-ion transporter-1 (DMT1) to iron uptake by human β-cells. Iron was provided to the cells as nontransferrin-bound iron (NTBI), which appears in the plasma during iron overload and is a major contributor to tissue iron loading. We found that overexpression of ZIP14 and ZIP8, but not DMT1, resulted in increased NTBI uptake by βlox5 cells, a human β-cell line. Conversely, siRNA-mediated knockdown of ZIP14, but not ZIP8, resulted in 50% lower NTBI uptake in βlox5 cells. In primary human islets, knockdown of ZIP14 also reduced NTBI uptake by 50%. Immunofluorescence analysis of islets from human pancreatic sections localized ZIP14 and DMT1 nearly exclusively to β-cells. Studies in primary human islets suggest that ZIP14 protein levels do not vary with iron status or treatment with IL-1β. Collectively, these observations identify ZIP14 as a major contributor to NTBI uptake by β-cells and suggest differential regulation of ZIP14 in primary human islets compared with other cell types such as hepatocytes., (Copyright © 2017 the American Physiological Society.)

Iron is required for many biological processes but is also toxic in excess; thus, body iron balance is maintained through sophisticated regulatory mechanisms. The lack of a regulated iron excretory mechanism means that body iron balance is controlled at the level of absorption from the diet. Iron absorption is regulated by the hepatic peptide hormone hepcidin. Hepcidin also controls iron release from cells that recycle or store iron, thus regulating plasma iron concentrations. Hepcidin exerts its effects through its receptor, the cellular iron exporter ferroportin. Important regulators of hepcidin, and therefore of systemic iron homeostasis, include plasma iron concentrations, body iron stores, infection and inflammation, and erythropoiesis. Disturbances in the regulation of hepcidin contribute to the pathogenesis of many iron disorders: hepcidin deficiency causes iron overload in hereditary hemochromatosis and nontransfused β-thalassemia, whereas overproduction of hepcidin is associated with iron-restricted anemias seen in patients with chronic kidney disease, chronic inflammatory diseases, some cancers, and inherited iron-refractory iron deficiency anemia. This review summarizes our current understanding of the molecular mechanisms and signaling pathways involved in the control of hepcidin synthesis in the liver, a principal determinant of plasma hepcidin concentrations., Competing Interests: 3 Author disclosures: V Sangkhae, no conflicts of interest. E Nemeth is a consultant to and stockholder of Intrinsic LifeSciences, Merganser Biotech, and Silarus Therapeutics., (© 2017 American Society for Nutrition.)

The mineral body exploited in Salafossa (Eastern Dolomites) was one of the largest lead/zinc-containing mineral deposits in Europe. Both metals were mainly present as sulphides (sphalerite, ZnS and galena, PbS). Mining activity started around 1550, but it was only around 1960 that the richest veins of the minerals were discovered. The mine closed in 1985, and concentrations of several trace metals, such as thallium (Tl), iron (Fe), manganese (Mn), lead (Pb) and zinc (Zn), were detected in the soils and plant samples (Biscutella laevigata L.) that were collected from eighteen sites selected outside the mine. B. laevigata is a pseudometallophyta species, and it often grows near mining areas where the soil's metal concentrations are significantly higher than those of soil with a natural geochemical background. The total metal concentrations in the plant tissue (roots and leaves of Biscutella laevigata) and in the soil samples - both bulk-soil and the B. laevigata root system (rhizo-soil) - were determined through Inductively Coupled Plasma Optical Emission Spectrometry (ICP-OES). The metal extractability and leachability of the soil samples were estimated using soil extractions with DTPA (Diethylenetriaminepentaacetic acid). In addition, metal mobility caused by rainwater runoff was estimated by using a leaching test with a dilute solution of H 2 SO 4 and HNO 3 . The results showed that metals were present in a chemical form available for uptake by the plants' roots. In fact, high concentrations of the metals were also found in the plant tissue (roots and leaves) of B. laevigata, and these concentrations were higher than those whose soils present natural geochemical background levels in the corresponding rhizo-soil. Thus, B. laevigata has shown a marked ability to bioaccumulate trace metals, especially Tl and, to a lesser extent, Zn, Pb, Fe and Mn, and it can influence metal mobility in the rhizo-soil. To assess the uptake and translocation processes of the trace metals, resulting in their bioaccumulation, two different indices were calculated: the enrichment factor in roots (EFr), as the ratio between the metal concentration in belowground biomass and in the respective rhizo-soil, and the translocation factor (TF), as the ratio between the metal concentration in the leaves and the corresponding roots. For both indices, values > 1 denoted enrichment of the metal in the roots or its translocation to the upper tissues. The results showed that EFr and TF were considerably high only for Tl, reaching a maximum value of 60 for EFr and 11.6 for TF. Conversely, the other investigated metals did not show significant bioaccumulation (EFr < 1), and they showed TF > 1 only at a few sites., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Four resected specimens of hepatic angiomyolipoma in which uptake of Sonazoid was observed in the postvascular phase of Sonazoid-enhanced ultrasonography were analyzed. Macrophage localization in the tumor was revealed pathologically by immunohistochemical staining for CD68. CD68-positive cells were observed in the tumor in all cases. The density of CD68-positive cells was 100/mm2, and the ratio of CD68-positive cell density in the tumor to that in the surrounding parenchyma was 32-171%. These results suggested that the uptake of the contrast agent Sonazoid was related to the density of CD68-positive cells., (© 2016 S. Karger AG, Basel.)

Nearly all iron dissolved in the ocean is complexed by strong organic ligands of unknown composition. The effect of ligand composition on microbial iron acquisition is poorly understood, but amendment experiments using model ligands show they can facilitate or impede iron uptake depending on their identity. Here we show that siderophores, organic compounds synthesized by microbes to facilitate iron uptake, are a dynamic component of the marine ligand pool in the eastern tropical Pacific Ocean. Siderophore concentrations in iron-deficient waters averaged 9 pM, up to fivefold higher than in iron-rich coastal and nutrient-depleted oligotrophic waters, and were dominated by amphibactins, amphiphilic siderophores with cell membrane affinity. Phylogenetic analysis of amphibactin biosynthetic genes suggests that the ability to produce amphibactins has transferred horizontally across multiple Gammaproteobacteria, potentially driven by pressures to compete for iron. In coastal and oligotrophic regions of the eastern Pacific Ocean, amphibactins were replaced with lower concentrations (1-2 pM) of hydrophilic ferrioxamine siderophores. Our results suggest that organic ligand composition changes across the surface ocean in response to environmental pressures. Hydrophilic siderophores are predominantly found across regions of the ocean where iron is not expected to be the limiting nutrient for the microbial community at large. However, in regions with intense competition for iron, some microbes optimize iron acquisition by producing siderophores that minimize diffusive losses to the environment. These siderophores affect iron bioavailability and thus may be an important component of the marine iron cycle., Competing Interests: The authors declare no conflict of interest.

This study evaluated the effect of chia on the iron bioavailability and gene expression of proteins involved in iron metabolism in animals fed with a high fat diet and a standard diet. Four experimental groups were tested (n = 8): standard diet + ferrous sulfate (SD + FS), standard diet + chia (SD + C), high fat diet + ferrous sulfate (HFD + FS), high fat diet + chia (HFD + C). The hemoglobin gain, hemoglobin regeneration efficiency, biological relative value of HRE, serum ferritin and transferrin, liver iron concentration and gene expression of proteins were evaluated. The SD + C group showed lower transferrin expression when compared to the control group. The control group showed serum transferrin concentration higher than the other groups. Serum ferritin and liver iron concentration did not differ among the animals that received chia ferritin and hephaestin expression was lower in experimental groups when compared with the control group. The peroxisome proliferator activated receptor expression was higher in animals fed with SD + C than in the control group. The expression of duodenal cytochrome B and divalent metal transporter 1 in the HFD + C group was higher and ferroportin was lower in the groups containing chia. Animals fed with chia showed similar iron bioavailability compared to animals fed with ferrous sulfate.

Objective: To study the therapeutic efficacy of an oral iron retard preparation in patients with iron deficiency anemia., Methods: In an investigator-initiated open study, 28 patients with iron deficiency anemia were treated with an iron sulfate sustained-release preparation (80 mg iron ions per tablet). The bioavailability was determined from the increase in the haemoglobin value under therapy and the measured blood loss. For the quantification of individual blood losses, a 59 Fe labeling method was used and the 59 Fe whole body retention in the observation period was measured with a whole body counter. This established method provides reliable data on the bioavailability of an oral iron preparation used., Results: In all patients the increased iron loss (average 6.6 ± 5.9 mg/d) was easily compensated by the amount of iron (average 11.7 ± 6.6 mg/d) taken with a daily dose of 80 mg of iron. During the observation period of 6-10 weeks there was a significant increase in haemoglobin (Hb) and ferritin concentration (mean increase of Hb from 10.2 ± 1.6 to 12.5 ± 1.5 g/dl and from ferritin from 9 ± 11 to 31 ± 23 μg/L)., Conclusions: Our results show that the iron sulfate retardant preparation used has a high bioavailability for iron. In all patients the anemia could be treated effectively. These findings seem to indicate that patients with chronic iron deficiency anemia can also receive therapeutically administered iron from the distal intestine sections.

Subcutaneous injection of Oxacom with glutathione-bound dinitrosyl iron complex as the active principle produced a slower drop of mean BP and longer accumulation of protein-bound dinitrosyl iron complexes in whole blood and tissues than intravenous injection of this drug, while durations of hypotensive effect in both cases were practically identical. In contrast to intravenous injection of the drug, its subcutaneous administration was not characterized by a high concentration of protein-bound dinitrosyl iron complexes in the blood at the onset of experiment; in addition, accumulation of these NO forms in the lungs was more pronounced after subcutaneous injection than after intravenous one.

l-lysine (Lys) is an essential amino acid that is added to foods and dietary supplements. Lys may interact with mineral nutrients and affect their metabolism. This study examined the effect of dietary Lys supplementation on the bioavailability of copper (Cu) and iron (Fe). Weanling male Sprague-Dawley rats were fed one of five diets (20% casein) for 4 weeks containing normal Cu and Fe (control) or low Cu or Fe without (LCu, LFe) or with (LCu+Lys, LFe+Lys) addition of 1.5% Lys. Final body weights, body weight gains and food consumption of the rats did not differ (P≥0.05) among diet groups. Rats fed the low Cu or Fe diets showed changes in nutritional biomarkers compared to control rats, demonstrating reduced Cu and Fe status, respectively. Hematological parameters, serum ceruloplasmin activity and Cu and Fe concentrations in serum, liver, kidney and intestinal mucosa were unaffected (P≥0.05) by Lys supplementation. These results indicate that in the context of an adequate protein diet, Lys supplementation at a relatively high level does not affect Cu or Fe bioavailability in rats., (Crown Copyright © 2016. Published by Elsevier GmbH. All rights reserved.)

The distribution of iron-carbon nanoparticles in FeC-DSPE-PEG-2000 modification (micellar particles with structure (Fe) core-carbon shell; PEG-based coating) is studied. The greater part of the nanoparticles accumulated in the spleen and liver, a small amount in the lungs, and the minimum amount in the thymus. The structural changes in the lymphoid organs were minor and involved only the microcirculatory bed. Analysis of the peripheral blood showed manifest anemia, thrombocytopenia, and leukocytosis.

Interest in the consumption of insects (entomophagy) as an alternative environmentally sustainable source of protein in the diet of humans has recently witnessed a surge. Knowledge of the nutrient composition and, in particular, the bioavailability of minerals from insects is currently sparse. This study evaluated the availability of Fe, Ca, Cu, Mg, Mn, and Zn from four commonly eaten insects and compared these to sirloin beef. Soluble iron from the samples was measured by inductively coupled plasma optical emission spectrometry (ICP-OES). Iron bioavailability was determined using an in vitro simulated peptic-pancreatic digestion, followed by measurement of ferritin (a surrogate marker for iron absorption) in Caco-2 cells. Cricket and sirloin beef had comparably higher levels of Fe, Ca, and Mn than grasshopper, meal, and buffalo worms. However, iron solubility was significantly higher from the insect samples than from beef. The complementation of whole-wheat flour with insect or beef protein resulted in overall decreases in mineral content and iron solubility in the composite mixtures. Collectively, the data show that grasshopper, cricket, and mealworms contain significantly higher chemically available Ca, Cu, Mg, Mn, and Zn than sirloin. However, buffalo worms and sirloin exhibited higher iron bioavailability comparable to that of FeSO 4 . Commonly consumed insect species could be excellent sources of bioavailable iron and could provide the platform for an alternative strategy for increased mineral intake in the diets of humans.

Heavy metal contamination of agricultural soil has become a serious global problem. This study was aimed to evaluate the effects of two chromium (Cr) tolerant plant growth promoting bacteria (PGPB) in combination with salicylic acid (SA) on plant growth, physiological, biochemical responses and heavy metal uptake under Cr contamination. A pot experiment (autoclaved sand as growing medium) was performed using maize (Zea mays L.) as a test crop under controlled conditions. Cr toxicity significantly reduced plant growth, photosynthetic pigment, carbohydrates metabolism and increased H 2 O 2 , MDA, relative membrane permeability, proline and Cr contents in maize leaves. However, inoculation with selected PGPB (T2Cr and CrP450) and SA application either alone or in combination alleviated the Cr toxicity and promoted plant growth by decreasing Cr accumulation, H 2 O 2 and MDA level in maize. Furthermore, dual PGPB inoculation with SA application also improved plant performance under Cr-toxicity. Results obtained from this study indicate that PGPB inoculation and SA application enhanced Cr tolerance in maize seedlings by decreasing Cr uptake from root to shoot. Additionally, combination of both PGPB and SA also reduced oxidative stress by elevating the activities of enzymatic and non-enzymatic antioxidant, also indicated by improved carbohydrate metabolism in maize plant exposed to Cr contamination. Comparatively, alleviation effects were more pronounced in PGPB inoculated plants than SA applied plants alone. The results suggest that combined use of PGPB and SA application may be exploited for improving production potential of maize in metal (Cr) contaminated soil., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Unlabelled: The hepatotoxin microcystin (MCYST) is produced by a variety of freshwater cyanobacterial species, including Microcystis aeruginosa Interestingly, MCYST-producing M. aeruginosa strains have been shown to outcompete their nontoxic counterparts under iron-limiting conditions. However, the reasons for this are unclear. Here we examined the proteomic response of M. aeruginosa PCC 7806 continuous cultures under different iron and growth regimes. Iron limitation was correlated with a global reduction in levels of proteins associated with energy metabolism and photosynthesis. These proteomic changes were consistent with physiological observations, including reduced chlorophyll a content and reduced cell size. While levels of MCYST biosynthesis proteins did not fluctuate during the study period, both intra- and extracellular toxin quotas were significantly higher under iron-limiting conditions. Our results support the hypothesis that intracellular MCYST plays a role in protecting the cell against oxidative stress. Further, we propose that extracellular MCYST may act as a signaling molecule, stimulating MCYST production under conditions of iron limitation and enhancing the fitness of bloom populations., Importance: Microcystin production in water supply reservoirs is a global public health problem. Understanding the ecophysiology of hepatotoxic cyanobacteria, including their responses to the presence of key micronutrient metals such as iron, is central to managing harmful blooms. To our knowledge, this was the first study to examine proteomic and physiological changes occurring in M. aeruginosa continuous cultures under conditions of iron limitation at different growth rates., (© Crown copyright 2016.)

The instability and low bioavailability of polyphenols limit their applications in food industries. In this study, epigallocatechin gallate (EGCG) and soybean seed ferritin deprived of iron (apoSSF) were fabricated as a combined double shell material to encapsulate rutin flavonoid molecules. Firstly, due to the reversible assembly characteristics of phytoferritin, rutin was successfully encapsulated within apoSSF to form a ferritin-rutin complex (FR) with an average molar ratio of 28.2: 1 (rutin/ferritin). The encapsulation efficiency and loading capacity of rutin were 18.80 and 2.98 %, respectively. EGCG was then bound to FR to form FR-EGCG composites (FRE), and the binding number of EGCG was 27.30 ± 0.68 with a binding constant K of (2.65 ± 0.11) × 10(4) M(-1). Furthermore, FRE exhibited improved rutin stability, and displayed prolonged release of rutin in simulated gastrointestinal tract fluid, which may be attributed to the external attachment of EGCG to the ferritin cage potentially reducing enzymolysis in GI fluid. In summary, this work demonstrates a novel nanocarrier for stabilization and sustained release of bioactive polyphenols.

Different metabolic pathways of supplemental and fortification Fe, or inhibition of Zn absorption by Fe, may explain adverse effects of supplemental Fe in Fe-sufficient infants. We determined whether the mode of oral Fe administration or the amount habitually consumed affects Fe absorption and systemic Fe utilisation in infants, and assessed the effects of these interventions on Zn absorption, Fe and Zn status, and growth. Fe-sufficient 6-month-old infants (n 72) were randomly assigned to receive 6·6 mg Fe/d from a high-Fe formula, 1·3 mg Fe/d from a low-Fe formula or 6·6 mg Fe/d from Fe drops and a formula with no added Fe for 45 d. Fractional Fe absorption, Fe utilisation and fractional Zn absorption were measured with oral (57Fe and 67Zn) and intravenous (58Fe and 70Zn) isotopes. Fe and Zn status, infection and growth were measured. At 45 d, Hb was 6·3 g/l higher in the high-Fe formula group compared with the Fe drops group, whereas serum ferritin was 34 and 35 % higher, respectively, and serum transferrin 0·1 g/l lower in the high-Fe formula and Fe drops groups compared with the low-Fe formula group (all P<0·05). No intervention effects were observed on Fe absorption, Fe utilisation, Zn absorption, other Fe status indices, plasma Zn or growth. We concluded that neither supplemental or fortification Fe nor the amount of Fe habitually consumed altered Fe absorption, Fe utilisation, Zn absorption, Zn status or growth in Fe-sufficient infants. Consumption of low-Fe formula as the only source of Fe was insufficient to maintain Fe stores.

Superparamagnetic iron oxide nanoparticles (SPIONs) are widely used as contrast agents for stem cell tracking using magnetic resonance imaging (MRI). The total mass of iron oxide that can be internalised into cells without altering their viability or phenotype is an important criterion for the generation of contrast, with SPIONs designed for efficient labelling of stem cells allowing for an increased sensitivity of detection. Although changes in the ratio of polymer and iron salts in co-precipitation reactions are known to affect the physicochemical properties of SPIONs, particularly core size, the effects of these synthesis conditions on stem cell labelling and magnetic resonance (MR) contrast have not been established. Here, we synthesised a series of cationic SPIONs with very similar hydrodynamic diameters and surface charges, but different polymer content. We have investigated how the amount of polymer in the co-precipitation reaction affects core size and modulates not only the magnetic properties of the SPIONs but also their uptake into stem cells. SPIONs with the largest core size and lowest polymer content presented the highest magnetisation and relaxivity. These particles also had the greatest uptake efficiency without any deleterious effect on either the viability or function of the stem cells. However, for all particles internalised in cells, the T 2 and T 2 * relaxivity was independent of the SPION's core size. Our results indicate that the relative mass of iron taken up by cells is the major determinant of MR contrast generation and suggest that the extent of SPION uptake can be regulated by the amount of polymer used in co-precipitation reactions. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

Renal glomerular and tubular dysfunctions have been reported with high prevalence in β-thalassemia. Iron toxicity is implicated in the kidney damage, which may be reversed by iron chelation therapy. To mimic heavy iron overload and evaluate the efficacy of iron chelators in the patients, iron dextran (180mg iron/mouse) was intraperitoneally (i.p.) injected in heterozygous β-globin knockout mice ((muβth-3/+), BKO) and wild type mice (C57BL/6J, WT) over a period of 2 weeks, followed by daily i.p. injection of deferoxamine (DFO) or deferiprone (L1) for 1 week. In BKO mice, iron preferentially accumulated in the proximal tubule with a grading score of 0-1 and increased to grade 3 after iron loading. In contrast, iron mainly deposited in the glomerulus and interstitial space in iron overloaded WT mice. Increased levels of kidney lipid peroxidation, glomerular and medullar damage and fibrosis in iron overloaded mice were reversed by treatment with iron chelators. L1 showed higher efficacy than DFO in reduction of glomerular iron, which was supported by a significantly decreased the amount of glomerular damage. Notably, DFO and L1 demonstrated a distinct pattern of iron distribution in the proximal tubule of BKO mice. In conclusion, chelation therapy has beneficial effects in iron-overloaded kidneys. However, the defect of kidney iron metabolism in thalassemia may be a determining factor of the treatment outcome in individual patients., (Copyright © 2016 Elsevier GmbH. All rights reserved.)

In most animals, the acquisition of the essential trace metal iron (Fe) is achieved by the gut, but in hagfishes, the skin is a nutrient absorbing epithelium, and thus may also play a role in Fe uptake. In the current study, the absorption of Fe, as Fe(II), across the intestinal and cutaneous epithelia of Pacific hagfish (Eptatretus cirrhatus) was investigated. Both epithelia absorbed Fe, with saturation at lower tested concentrations, superseded by a diffusive component at higher Fe exposure concentrations. Affinity constants (Km) of 9.4 and 137μM, and maximal Fe transport rates (Jmax) of 0.81 and 0.57nmolcm(-2)h(-1) were determined for the skin and the gut, respectively. This characterises the skin as a relatively high-affinity Fe transport epithelium. The majority of the absorbed Fe in the skin remained in the tissue, whereas in the gut, most absorbed Fe was found in the serosal fluid, suggesting distinct mechanisms of Fe handling between the two epithelia. To determine if reduced dissolved oxygen altered Fe transport, hagfish were subjected to hypoxia for 24h, before Fe transport was again assessed. Hypoxia had no effect on Fe transport across gut or skin, likely owing to the relative lack of change in haematological variables, and thus an unaltered Fe demand under such conditions. These data are the first to kinetically characterise the absorption of a nutritive trace metal across the epithelia of hagfish and add to the growing understanding of the role of the skin in nutritive transport in this group., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Advanced, metastatic, castration resistant and chemo-resistant prostate cancer has triggered change in the drug development landscape against prostate cancer. Bovine lactoferrin (bLf) is currently attracting attention in clinics for its anti-cancer properties and proven safety profile. bLf internalises into cancer cells via receptor mediated endocytosis, boosts immunity and complements chemotherapy. We employed bLf as an excellent functional carrier protein for delivering doxorubicin (Dox) into DU145 cells, CD44+/EpCAM+ double positive enriched DU145 3D prostaspheres and drug resistant ADR1000-DU145 cells, thus circumventing Dox efflux, to overcome chemo-resistance. Successful bLf-Dox conjugation with iron free or iron saturated bLf forms did not affect the integrity and functionality of bLf and Dox. bLf-Dox internalised into DU145 cells within 6 h, enhanced nuclear Dox retention up to 24 h, and proved significantly effective (p < 0.001) in reducing LC50 value of Dox from 5.3 μM to 1.3 μM (4 fold). Orally fed iron saturated bLf-Dox inhibited tumour development, prolonged survival, reduced Dox induced general toxicity, cardiotoxicity, neurotoxicity in TRAMP mice and upregulated serum levels of anti-cancer molecules TNF-α, IFN-γ, CCL4 and CCL17. The study identifies promising potential of a novel and safer bLf-Dox conjugate containing a conventional cytotoxic drug along with bLf protein to target drug resistance.

While replacing electrolytic iron with NaFeEDTA in multi-micronutrient fortification-mixes is a popular option, there is no information about the effect on the iron and zinc availabilities in African staple foods. This study evaluated the effects of adding a multi-micronutrient fortification-mix, with no iron, electrolytic iron or NaFeEDTA on the availabilities of iron and zinc from thick and fermented special-grade maize porridges using a Caco-2 cell model. Replacing electrolytic iron with NaFeEDTA significantly (p ⩽ 0.05) increased iron and, importantly zinc, availabilities in both the thick (2.16% vs. 1.45% and 2.51% vs. 2.29%, respectively) and fermented (3.35% vs. 2.66% and 3.04% vs. 2.61%, respectively) porridges. Some of the NaFeEDTA complexes perhaps partially dissociated because of pH changes during simulated digestion, binding with zinc and increasing its availability. NaFeEDTA in a multi-micronutrient fortification-mix, added to less refined, high phytate maize meal, would be more effective than electrolytic iron in addressing both iron and zinc deficiencies in low socio-economic populations of sub-Saharan Africa., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The influence of the composition of calcium (Ca(2+)), magnesium (Mg(2+)), and iron (Fe(3+)) ions in two concentration levels (low-500 mg/L of CaCl2, 125 mg/L of MgCl2, and 10 mg/L of FeCl3 and high-2,500 mg/L of CaCl2, 625 mg/L of MgCl2, and 50 mg/L of FeCl3) contained in water on the pharmacokinetics (PK) of oxytetracycline (OTC) was determined. OTC hydrochloride was administered at a dose of 25 mg/kg of body weight to broiler chickens divided into four groups of nine birds each, including 3 oral groups (in deionized water -control, in water with low ion concentration, and in water with high ion concentration) and 1 intravenous group. OTC concentrations in plasma were determined using liquid chromatography-tandem mass spectrometry, after which non-compartmental pharmacokinetic analysis was conducted.The absolute bioavailability of OTC in the group of birds exposed to higher ions concentration was reduced (8.68% ± 2.56) as compared to the control (13.71% ± 2.60). Additionally, in this group, decrease in PK parameters such as: area under the concentration-time curve from 0 to infinity (15.36 μg × h/mL ± 4.36), from 0 to t (14.78 μg × h/mL ± 4.37), area under the first moment of curve from 0 to t (107.54 μg × h/mL ± 36.48), and maximum plasma concentration (2.13 μg/mL ± 0.32) were also observed. It is noteworthy, all mentioned parameters demonstrated a downward trend with high correlation coefficient (P = 0.004, P = 0.002, P = 0.005, P = 0.004, P = 0.011, respectively), reflecting the influence of increasing concentrations of Ca(2+), Mg(2+), and Fe(3+) ions on the decreasing absorption rate of OTC.Based on the current research results, it can be assumed that high concentrations of several ions applied concomitantly are able to decrease the absorption of OTC from gastrointestinal tract in broiler chickens. This occurrence might impair the drug's clinical efficacy toward some pathogenic microorganisms. It implies that using OTC on a farm may require administration of higher doses than the routine one when infections are caused by less sensitive pathogens., (© 2016 Poultry Science Association Inc.)

Fe fortification of centrally manufactured and frequently consumed condiments such as bouillon cubes could help prevent Fe deficiency in developing countries. However, Fe compounds that do not cause sensory changes in the fortified product, such as ferric pyrophosphate (FePP), exhibit low absorption in humans. Tetra sodium pyrophosphate (NaPP) can form soluble complexes with Fe, which could increase Fe bioavailability. Therefore, the aim of this study was to investigate Fe bioavailability from bouillon cubes fortified with either FePP only, FePP+NaPP, ferrous sulphate (FeSO4) only, or FeSO4+NaPP. We first conducted in vitro studies using a protocol of simulated digestion to assess the dialysable and ionic Fe, and the cellular ferritin response in a Caco-2 cell model. Second, Fe absorption from bouillon prepared from intrinsically labelled cubes (2·5 mg stable Fe isotopes/cube) was assessed in twenty-four Fe-deficient women, by measuring Fe incorporation into erythrocytes 2 weeks after consumption. Fe bioavailability in humans increased by 46 % (P<0·005) when comparing bouillons fortified with FePP only (4·4 %) and bouillons fortified with FePP+NaPP (6·4 %). Fe absorption from bouillons fortified with FeSO4 only and with FeSO4+NaPP was 33·8 and 27·8 %, respectively (NS). The outcome from the human study is in agreement with the dialysable Fe from the in vitro experiments. Our findings suggest that the addition of NaPP could be a promising strategy to increase Fe absorption from FePP-fortified bouillon cubes, and if confirmed by further research, for other fortified foods with complex food matrices as well.

Strategies that enhance the Fe bioavailability of the bean are of keen interest to nutritionists, bean breeders and growers. In beans, the cotyledons contain 75-80% of the total seed Fe, most of which appears to be located within the cotyledon cells. The cotyledon cell walls are known to be resistant to digestion in the stomach and the upper small intestine. Therefore, given the above and the general belief that the primary site for human Fe absorption is the upper small intestine, the present study was designed to determine if the cotyledon cell walls represent a barrier to Fe absorption from the bean. To do so, we utilized high pressure to rupture bean cotyledon cells. The iron bioavailability of cooked bean samples was assessed using an in vitro digestion/Caco-2 cell culture model. Microscopy analyses confirmed that the cotyledon cell walls are highly resistant to pepsin, the low pH of the stomach, and the pancreatic enzymes, indicating that the walls are a barrier to Fe absorption from the bean. Relatively high intracellular pressure (>4000 psi) was required to initiate cell wall rupture. Surprisingly, the lysis of cotyledon cells did not result in a consistent or strong enhancement of bioavailable Fe, suggesting that the liberated intracellular starch and protein influenced the Fe bioavailability by creating a matrix that inhibited the exchange of Fe with the cell transport mechanism. Such observations warrant further pursuit in vivo as the confirmation of these effects would reshape strategies to enhance Fe absorption from beans.

Triapine has been investigated as anticancer drug in multiple clinical phase I/II trials. Although promising anti-leukemic activity was observed, Triapine was ineffective against solid tumors. The reasons are currently widely unknown. The biological activity of Triapine is strongly connected to its iron complex (Fe-Triapine) which is pharmacologically not investigated. Here, novel analytical tools for Triapine and Fe-Triapine were developed and applied for cell extracts and body fluids of treated mice. Triapine and its iron complex showed a completely different behavior: for Triapine, low protein binding was observed in contrast to fast protein adduct formation of Fe-Triapine. Notably, both drugs were rapidly cleared from the body (serum half-life time <1h). Remarkably, in contrast to Triapine, where (in accordance to clinical data) basically no renal excretion was found, the iron complex was effectively excreted via urine. Moreover, no Fe-Triapine was detected in serum or cytosolic extracts after Triapine treatment. Taken together, our study will help to further understand the biological behavior of Triapine and its Fe-complex and allow the development of novel thiosemicarbazones with pronounced activity against solid tumor types., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The causes and consequences of geophagy, the craving and consumption of earth, remain enigmatic, despite its recognition as a behavior with public health implications. Iron deficiency has been proposed as both a cause and consequence of geophagy, but methodological limitations have precluded a decisive investigation into this relationship. Here we present a novel in vivo model for assessing the impact of geophagic earth on iron status: Gallus gallus (broiler chicken). For four weeks, animals were gavaged daily with varying dosages of geophagic material or pure clay mineral. Differences in haemoglobin (Hb) across treatment groups were assessed weekly and differences in liver ferritin, liver iron, and gene expression of the iron transporters divalent metal transporter 1 (DMT1), duodenal cytochrome B (DcytB) and ferroportin were assessed at the end of the study. Minimal impact on iron status indicators was observed in all non-control groups, suggesting dosing of geophagic materials may need refining in future studies. However, this model shows clear advantages over prior methods used both in vitro and in humans, and represents an important step in explaining the public health impact of geophagy on iron status.

Introduction and Objective: Oyster mushroom Pleurotus ostreatus is good source of iron. However, there is a limited data concerning bioavailability of iron from oyster mushroom and also cereal products containing this mushroom. The aim of this study was to assess bioavailability of iron from products with an addition of Pleurotus ostreatus in male rats with anaemia., Material and Methods: Investigations were conducted in two stages. In the first stage iron deficiency was developed in rats. For this purpose 6 weeks old 36 male Wistar rats were fed a AIN-93M diet deficient in iron and 6 males received a standard AIN-93M diet. In the second stage of the study the assessment of Fe bioavailability from cereal products enriched with dried Pleurotus ostreatus. After experiment the animals were killed and blood and heart, liver, spleen and kidneys were collected for biochemical tests., Results: Feeding male Wistar rats supplemented with dried Pleurotus ostreatus mushrooms diets resulted in the restitution of the systemic Fe level, as manifested by an increase of the level comparable to the control group for: iron transferrin saturation rate, haemoglobin and mean corpuscular volume. Values of hematocrit, mean corpuscular haemoglobin and mean corpuscular haemoglobin concentration in animals fed products supplemented with Pleurotus ostreatus were significantly higher compared to animals fed products with no Fe added. The highest MCV value was recorded when 20% of dried oyster mushrooms were added. Iron levels in the blood serum, the liver and kidneys in animals fed cereal products considerably exceeded values recorded at the beginning of the experiment and were similar to the control values., Conclusions: Product may be a valuable source of iron in the nutrition of individuals with a deficiency of this element, first of all patients with absorption and metabolism disorders, but also may add variety to the traditional daily diet.

Twenty-four organic Fe sources were evaluated by polarographic analysis and via solubility in buffers (pH 5 and 2) and deionized water. Organic Fe sources included 6 Fe-Met complexes (Fe-Met), 10 Fe-Gly complexes, 1 Fe-Lys complex, 4 Fe proteinates, and 3 Fe-AA complexes (Fe-AA). Sources varied considerably in chemical characteristics. Chelation strengths (quotient of formation [Q] values) ranged from weak (Q = 1.08) to extremely strong strength (Q = 8,590). A total of 1,170 1-d-old Arbor Acres male broilers were randomly allotted to 6 replicate cages (15 chicks/cage) for each of 13 treatments in a completely randomized design involving a 4 × 3 factorial arrangement of treatments (4 Fe sources × 3 added Fe levels) plus a control with no added Fe. Dietary treatments included a corn-soybean meal basal diet (control; 55.8 mg Fe/kg) and the basal diet supplemented with 20, 40, or 60 mg Fe/kg as iron sulfate (FeSO∙7HO); an Fe-Met with weak chelation strength (Fe-Met W; Q = 1.37; 14.7% Fe); an iron proteinate with moderate chelation strength (Fe-Prot M; Q = 43.6; 14.2% Fe); or an iron proteinate with extremely strong chelation strength (Fe-Prot ES; Q = 8,590; 10.2% Fe). The growth performance, Fe concentrations, hematological indices, and activities and gene expressions of 2 Fe-containing enzymes in tissues of broilers at 7, 14, and 21 d of age were determined in the present study. Transferrin saturation in plasma on 14 d; bone Fe on d 7 and 14; liver Fe on d 7, 14, and 21; kidney Fe on d 14; succinate dehydrogenase activities in the liver on d 21 and in the kidney on d 7 and 21; mRNA levels in the kidney and heart on d 14; and mRNA levels in the liver and kidney on d 21 linearly increased ( < 0.05) as added Fe levels increased. However, differences in bioavailabilities among Fe sources were detected ( < 0.05) only for the mRNA levels in the liver and kidney on d 21. Based on slope ratios from the multiple linear regression of mRNA level in the liver or kidney of broilers on d 21 on daily dietary analyzed Fe intake, the bioavailabilities of Fe-Met W, Fe-Prot M, and Fe-Prot ES relative to iron sulfate (100%) were 129 ( = 0.18), 164 ( < 0.003), and 174% ( < 0.001) or 102 ( = 0.95), 143 ( = 0.09), and 174% ( < 0.004), respectively. These results indicated that the relative bioavailabilities of organic Fe sources were closely related to their Q values and organic Fe sources with greater Q values showed higher Fe bioavailabilities.

Iron (Fe) is an essential trace element for marine fish. However, our knowledge of Fe requirements at different development stages of marine fish is still limited. Here, we reported the efficient Fe absorption strategies adopted by larval fish under different dietary Fe supplementary levels (i.e., 0-640 mg/kg). Biokinetically, the larval fish controlled their dietary Fe assimilation efficiency (AE, 1.6-18.5%), and enhanced their waterborne Fe uptake (ca. 2.5 fold change of uptake rate constant) once the dietary Fe was deficient (i.e., 27.4 mg Fe/kg feed). Transcriptionally, the expression of hepcidin1 (hep1; Fe regulator; i.e., 2.3-15.7 fold change) in larval fish was positively correlated with the Fe supplementary levels. Comparatively, the female adult fish were poor in assimilating the added Fe source (i.e., ferric form) with similar life-sustainable levels of Fe (i.e., 0.046-0.12 μg/g/d assimilated for Fe supplementary levels of 27.4, 162 and 657 mg Fe/kg feed). The overall feeding experiments suggested that dietary net Fe flux sufficient for the normal growth of larval medaka was 0.71-1.75 μg/g/d (i.e., 83.9 mg Fe/kg feed), consistent with the modeled value (i.e., 1.09-2.16 μg/g/d). In female adults, the estimated essential net Fe flux was 0.88-0.90 μg/g/d.

In this study, the influence of soil types on the effect of the commercial form of C-nZVI on tissue concentrations, cellular component, reproduction outcome in Eisenia fetida, and the soil health was investigated. C-nZVI at concentration level of 3 g kg(-1) soil showed no effect on the survival of E. fetida in the three soil types. However, varying effects such as concentration-dependent increase in tissue iron concentration, lipid peroxidation, and damage to DNA molecules by C-nZVI were observed. C-nZVI at an exposure concentration of 60 mg kg(-1) soil induced oxidative stress in E. fetida. Tissue Fe concentration appeared correlated to the DNA damage. Oxidative stress and DNA damage may explain the toxicity mechanisms of nZVI to E. fetida. Graphical Abstract Reactive oxygen species induced by nZVI.

Background: It has been reported that R2* is a sensitive marker for iron deposition. The aim of this study was to quantitatively assess iron deposition in Parkinson's disease (PD) using changes of R2* in enhanced T2 star-weighted angiography (ESWAN) and to discuss the value of ESWAN for PD., Methods: Fifty-four primary PD patients and twenty-eight healthy individuals were examined by ESWAN in the 3·0 T magnetic resonance imaging system. The R2* values were measured from the deep gray nuclei (including the substantia nigra [SN], red nuclei, globus pallidus, putamina, caudate nuclei, and thalami). The unified PD rating scale (UPDRS) III assessment, the nonmotor symptoms scale (NMSS), and the mini mental state examination (MMSE) were used to rate all the patients., Results: The comparison of the R* values between the deep gray nuclei on the same side of the PD patients and the control group revealed significant differences in the SN and red nuclei (P < 0.05). There was a significant difference between Hoehn and Yahr (HY) 1 and HY2-4 patients in terms of the values of the SN. There was a slight correlation between the R* values of the SN of the PD patients (HY >1) and the UPDRS III ratings. No correlation between the R* signal values in the PD patients and the NMSS and MMSE scales was found., Conclusion: Iron concentrations in the regions of interest may represent the severity of the PD motor symptoms, and whether they are related to the nonmotor symptoms remains a question for further investigation. ESWAN offers special advantages in determining iron depositions in the brain and in enabling a sensitive diagnosis of PD, although further study is necessary.

Background: Iron fortification of rice is a promising strategy for improving iron nutrition. However, it is technically challenging because rice is consumed as intact grains, and ferric pyrophosphate (FePP), which is usually used for rice fortification, has low bioavailability., Objective: We investigated whether the addition of a citric acid/trisodium citrate (CA/TSC) mixture before extrusion increases iron absorption in humans from FePP-fortified extruded rice grains., Design: We conducted an iron absorption study in iron-sufficient young women (n = 20), in which each participant consumed 4 different meals (4 mg Fe/meal): 1) extruded FePP-fortified rice (No CA/TSC); 2) extruded FePP-fortified rice with CA/TSC added before extrusion (CA/TSC extruded); 3) extruded FePP-fortified rice with CA/TSC solution added after cooking and before consumption (CA/TSC solution); and 4) nonextruded rice fortified with a FeSO4 solution added after cooking and before consumption (reference). Iron absorption was calculated from erythrocyte incorporation of stable iron isotopes 14 d after administration. In in vitro experiments, we assessed the soluble and dialyzable iron from rice meals in which CA/TSC was added at different preparation stages and from meals with different iron:CA:TSC ratios., Results: Fractional iron absorption was significantly higher from CA/TSC-extruded meals (3.2%) than from No CA/TSC (1.7%) and CA/TSC solution (1.7%; all P < 0.05) and was not different from the FeSO4 reference meal (3.4%). In vitro solubility and dialyzability were higher in CA/TSC-extruded rice than in rice with No CA/TSC and CA/TSC solution, and solubility increased with higher amounts of added CA and TSC in extruded rice., Conclusions: Iron bioavailability nearly doubled when CA/TSC was extruded with FePP into fortified rice, resulting in iron bioavailability comparable to that of FeSO4 We attribute this effect to an in situ generation of soluble FePP citrate moieties during extrusion and/or cooking because of the close physical proximity of FePP and CA/TSC in the extruded rice matrix. This trial was registered at clinicaltrials.gov as NCT02176759., (© 2016 American Society for Nutrition.)

Purpose: To investigate the effects of the consumption of Maillard reaction products (MRPs) from bread crust (BC) on iron, copper and zinc body retention and tissue distribution, determining whether these effects are related to the molecular weight of browning products., Methods: During an 88-day study period, rats were fed a Control diet or diets containing BC as source of MRPs, its soluble high or low molecular weight fractions (BC, LMW or HMW diets). A mineral balance was conducted throughout the experiment to determine iron, copper and zinc retention. At day 88, animals were killed, blood was drawn for haemoglobin determination and some organs removed to analyse minerals., Results: Copper and zinc balances were unchanged, and scant modification detected in their body delivery. However, the Fe retention rate from the diet increased (13, 22 and 32 % for BC, LMW and HMW diets), and a parallel higher Fe body concentration was observed (13-18 % higher than the Control group). Incoming iron accumulated particularly in the liver, femur and small intestine, but functional iron tended to decrease, as reflected by haemoglobin levels., Conclusions: The long-term intake of BC or derivatives did not produce a notable effect on copper or zinc balances, although slightly increased iron retention rate and the body concentration of this mineral were observed. Iron accumulated in some organs, but the production of haemoglobin was not improved. In view of the differences observed between the effects of BC and its derivatives, our results underline the importance of working with real food matrices, where the joint presence of different components modulates the in vivo final effects.

Background: Traits such as bird-, insect- and mould-resistance are the focus in selecting improved sorghum varieties, but this often increases the tannin content, which can negatively affect iron bioavailability. The grain characteristics, nutrient retention, and the fate of iron-binding polyphenols (IBPs) during injera processing, an Ethiopian traditional fermented pancake, were investigated using agriculturally improved tannin-free (TFC) and high-tannin (HTC) sorghum cultivars., Results: The HTC had significantly higher IBP contents than the TFC (P < 0.05). Decortication led to iron (24-27%), calcium (18-43%), IBP (catechol 35-41%, galloyl 35-42%), and tannin (12-35%) losses. Sourdough fermentation reduced the IBP and tannin concentrations in HTC, but had no effect on the IBP concentrations in TFC. The modified injera processing that included pre-soaking resulted in the highest IBP reductions (galloyl 73% and catechol 71%)., Conclusion: Nutrient retention in HTC and TFC processing was different. Including a pre-soaking step during injera processing of HTC could counter the negative effects of IBP on iron absorption, while benefiting from the agronomic features of HTC., (© 2015 Society of Chemical Industry.)

Background: Biofortified beans have been produced with higher nutrient concentrations. The objective was to evaluate the in vitro and in vivo iron and zinc bioavailability of common beans Pontal (PO), targeted for biofortification, compared with conventional Perola (PE) and their effects on the iron and zinc nutritional status of preschool children., Results: In Caco-2 cells, PO and PE beans did not show differences in ferritin (PO, 13.1 ± 1.4; PE, 13.6 ± 1.4 ng mg(-1) protein) or zinc uptake (PO, 15.9 ± 1.5; PE, 15.5 ± 3.5 µmol mg(-1) protein). In the rat, PO and PE beans presented high iron bioavailability (PO, 109.6 ± 29.5; PE, 110.7 ± 13.9%). In preschool children, no changes were observed in iron and zinc nutritional status comparing before and after PO consumption (ferritin, 41.2 ± 23.2 and 28.9 ± 40.4 µg L(-1) ; hemoglobin, 13.7 ± 2.2 and 13.1 ± 3.2 g dL(-1) ; plasma zinc, 119.2 ± 24.5 and 133.9 ± 57.7 µg dL(-1) ; erythrocyte zinc, 53.5 ± 13.8 and 59.4 ± 17.1 µg g(-1) hemoglobin)., Conclusion: Iron and zinc bioavailability in PO and PE beans was not statistically different using either cell culture, animal or human models. Efforts should focus on increasing mineral bioavailability of beans targeted for biofortification., (© 2015 Society of Chemical Industry.)

To develop an iron supplement that is effectively absorbed and utilized, thiolated human-like collagen was created to improve the iron binding capacity of human-like collagen. A thiolated human-like collagen-iron complex was prepared in a phosphate buffer, and one mole of thiolated human-like collagen-iron possessed approximately 28.83 moles of iron. The characteristics of thiolated human-like collagen-iron were investigated by ultraviolet-visible absorption spectroscopy, Fourier transform infrared spectroscopy, circular dichroism, and differential scanning calorimetry. The results showed that the thiolated human-like collagen-iron complex retained the secondary structure of human-like collagen and had greater thermodynamic stability than human-like collagen, although interactions between iron ions and human-like collagen occurred during the formation of the complex. In addition, to evaluate the bioavailability of thiolated human-like collagen-iron, an in vitro Caco-2 cell model and an in vivo iron deficiency anemia mouse model were employed. The data demonstrated that the thiolated human-like collagen-iron complex exhibited greater bioavailability and was more easily utilized than FeSO4, ferric ammonium citrate, or ferrous glycinate. These results indicated that the thiolated human-like collagen-iron complex is a potential iron supplement in the biomedical field., (© The Author(s) 2016.)

Background: It has been predicted that the global temperature will rise in the future, which means crops including sorghum will likely be grown under higher temperatures, and consequently may affect the nutritional properties., Methods: The effects of two growth temperatures (OT, day/night 32/21°C; HT 38/21°C) on tannin, phytate, mineral, and in vitro iron availability of raw and cooked grains (as porridge) of six sorghum genotypes were investigated., Results: Tannin content significantly decreased across all sorghum genotypes under high growth temperature (P ≤0.05), while the phytate and mineral contents maintained the same level, increased or decreased significantly, depending on the genotype. The in vitro iron availability in most sorghum genotypes was also significantly reduced under high temperature, except for Ai4, which showed a pronounced increase (P ≤0.05). The cooking process significantly reduced tannin content in all sorghum genotypes (P ≤0.05), while the phytate content and in vitro iron availability were not significantly affected., Conclusions: This research provides some new information on sorghum grain nutritional properties when grown under predicted future higher temperatures, which could be important for humans where sorghum grains are consumed as staple food.

The aim of this study was to assess hepatic functional reserve by analyzing the hepatic parenchyma enhancement curve of parenchyma-specific contrast-enhanced ultrasonography (CEUS). Fifty-two patients with cirrhosis who underwent CEUS and indocyanine green tests (ICG) because of a focal liver lesion were enrolled. We evaluated the hemodynamic-related parameters of the time-intensity curve and compared these findings with the ICG retention rate at 15 min (ICG R15). The correlation between the time from peak to one half (s) and ICG R15 was statistically significant and was relatively proportional to the ICG R15. A cut-off value of 149 s was determined for the time from peak to one half for abnormal ICG R15 (>14). The sensitivity and specificity were 85.7% and 92.3%, respectively, for the detection of abnormal ICG R15. In conclusion, the time from peak to one half of the time-intensity curve of parenchyma-specific CEUS of the liver can be a useful parameter to predict the hepatic reserve in liver cirrhosis., (Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Magnetic hyperthermia ablation is a new and minimally invasive modality for localized tumor removal. However, an inadequate ablation dosage can leave a residual tumor or cause a variety of complications. In addition, commonly used magnetic nanoparticles can easily escape from the tumor tissue, which present potential safety problems. In this study, a smart phase transitional and injectable implant based on biocompatible poly lactic-co-glycolic acid (PLGA) implant incorporating magnetic material (Fe powder) and anti-cancer drug (doxorubicin (DOX)) was developed. The magnetic-induced hyperthermia and release efficiency of DOX were evaluated in vitro. Drug release can be controlled under external alternating current magnetic field (AMF). The results of the in vivo tumor therapeutic efficacy showed that when exposed to external AMF, this smart injectable DOX/PLGA-Fe implant could converse magnetic energy into heat and accelerate the release of DOX, which leads to increasing the temperature to achieve tumor coagulative necrosis and accelerating the release of DOX to enhance residual tumor apoptosis. Furthermore, there was no leakage of magnetic material, as demonstrated using real-time ultrasound (US) and computerized tomography (CT) imaging, realizing the guidance and monitoring of tumor therapy. In conclusion, this smart phase transitional and injectable implant DOX/PLGA-Fe has the ability to improve the efficiency of this newly developed minimally invasive magnetic ablation of tumor treatment technique, and will provide a new avenue of developing minimally invasive synergistic tumor therapy., (Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Iron (Fe) is abundant in soils but generally poorly soluble. Plants, with the exception of Graminaceae, take up Fe using an Fe(III)-chelate reductase coupled to an Fe(II) transporter. Whether or not nongraminaceous species can convert scarcely soluble Fe(III) forms into soluble Fe forms has deserved little attention so far. We have used Beta vulgaris, one among the many species whose roots secrete flavins upon Fe deficiency, to study whether or not flavins are involved in Fe acquisition. Flavins secreted by Fe-deficient plants were removed from the nutrient solution, and plants were compared with Fe-sufficient plants and Fe-deficient plants without flavin removal. Solubilization of a scarcely soluble Fe(III)-oxide was assessed in the presence or absence of flavins, NADH (nicotinamide adenine dinucleotide, reduced form) or plant roots, and an Fe(II) trapping agent. The removal of flavins from the nutrient solution aggravated the Fe deficiency-induced leaf chlorosis. Flavins were able to dissolve an Fe(III)-oxide in the presence of NADH. The addition of extracellular flavins enabled roots of Fe-deficient plants to reductively dissolve an Fe(III)-oxide. We concluded that root-secretion of flavins improves Fe nutrition in B. vulgaris. Flavins allow B. vulgaris roots to mine Fe from Fe(III)-oxides via reductive mechanisms., (© 2015 CSIC New Phytologist © 2015 New Phytologist Trust.)

Iron deficiency affects thousands of people worldwide. Biofortification of staple food crops aims to support the reduction of this deficiency. This study evaluates the effect of combinations of common beans and rice, targets for biofortification, with high carotenoid content crops on the iron bioavailability, protein gene expression, and antioxidant effect. Iron bioavailability was measured by the depletion/repletion method. Seven groups were tested (n = 7): Pontal bean (PB); rice + Pontal bean (R + BP); Pontal bean + sweet potato (PB + SP); Pontal bean + pumpkin (PB + P); Pontal bean + rice + sweet potato (PB + R + P); Pontal bean + rice + sweet potato (PB + R + SP); positive control (Ferrous Sulfate). The evaluations included: hemoglobin gain, hemoglobin regeneration efficiency (HRE), gene expression of divalente metal transporter 1 (DMT-1), duodenal citocromo B (DcytB), ferroportin, hephaestin, transferrin and ferritin and total plasma antioxidant capacity (TAC). The test groups, except the PB, showed higher HRE (p < 0.05) than the control. Gene expression of DMT-1, DcytB and ferroportin increased (p < 0.05) in the groups fed with high content carotenoid crops (sweet potato or pumpkin). The PB group presented lower (p < 0.05) TAC than the other groups. The combination of rice and common beans, and those with high carotenoid content crops increased protein gene expression, increasing the iron bioavailability and antioxidant capacity.

This study aimed to assess and compare the in vitro and in vivo bioaccessibility/bioavailability of As and Pb in a mining contaminated soil (As, 2267 mg kg(-1); Pb, 1126 mg kg(-1)), after the addition of conventional (phosphoric acid), opportunistic [water treatment residues (WTRs)], and engineered [nano- and microscale zero valent iron (ZVI)] amendments. Phosphoric acid was the only amendment that could significantly decrease Pb bioaccessibility with respect to untreated soil (41 and 47% in the gastric phase and 2.1 and 8.1% in the intestinal phases, respectively), giving treatment effect ratios (TERs, the bioaccessibility in the amended soil divided by the bioaccessibility in the untreated soil) of 0.25 and 0.87 in the gastric and intestinal phase, respectively. The in vivo bioavailability of Pb decreased in the phosphate treatment relative to the untreated soil (6 and 24%, respectively), and also in the Fe WTR 2% (12%) and nZVI-2 (13%) treatments. The ZVI amendments caused a decrease in As bioaccessibility, with the greatest decrease in the nZVI2-treated soil (TERs of 0.59 and 0.64 in the gastric and intestinal phases, respectively). Arsenic X-ray absorption near-edge spectroscopy analysis indicated that most of the As in the untreated soil was present as As(V) associated with Fe mineral phases, whereas in the treated soil, the proportion of arsenosiderite increased. Arsenite was present only as a minor species (3-5%) in the treated soils, with the exception of an nZVI treatment [∼14% of As(III)], suggesting a partial reduction of As(V) to As(III) caused by nZVI oxidation.

The aim of this study is to determine the effect of proteins from cereals and legumes on heme iron (Fe) absorption. The absorption of heme Fe without its native globin was measured. Thirty adult females participated in two experimental studies (15 per study). Study I focused on the effects of cereal proteins (zein, gliadin and glutelin) and study II on the effects of legume proteins (soy, pea and lentil) on heme Fe absorption. When heme was given alone (as a control), study I and II yielded 6.2% and 11.0% heme absorption (p > 0.05). In study I, heme Fe absorption was 7.2%, 7.5% and 5.9% when zein, gliadin and glutelin were added, respectively. From this, it was concluded that cereal proteins did not affect heme Fe absorption. In study II, heme Fe absorption was 7.3%, 8.1% and 9.1% with the addition of soy, pea and lentil proteins, respectively. Only soy proteins decreased heme Fe absorption (p < 0.05). These results suggest that with the exception of soy proteins, which decreased absorption, proteins derived from cereals and legumes do not affect heme Fe absorption.

Background: Fortification of milk formulas with iron is a strategy widely used, but the absorption of non-heme iron is low. The purpose of this study was to measure the bioavailability of two iron fortified milk formulas designed to cover toddlers´ nutritional needs. These milks were fortified with iron sulfate stabilized with maltodextrin and citric acid., Methods: 15 women (33-47 years old) participated in study. They received on different days, after an overnight fast, 200 mL of Formula A; 200 mL of Formula B; 30 mL of a solution of iron and ascorbic acid as reference dose and 200 mL of full fat cow's milk fortified with iron as ferrous sulfate. Milk formulas and reference dose were labeled with radioisotopes (59)Fe or (55)Fe, and the absorption of iron measured by erythrocyte incorporation of radioactive Fe., Results: The geometric mean iron absorption corrected to 40% of the reference dose was 20.6% for Formula A and 20.7% for Formula B, versus 7.5% of iron fortified cow's milk (p < 0.001). The post hoc Sheffé indeed differences between the milk formulas and the cow's milk (p < 0.001)., Conclusion: Formulas A and B contain highly bioavailable iron, which contributes to covering toddlers´ requirements of this micronutrient.

Iron-bioceramic composites have been developed as biodegradable implant materials with tailored degradation behavior and bioactive features. In the current work, in vivo bioactivity of the composites was comprehensively studied by using sheep animal model. Five groups of specimens (Fe-HA, Fe-TCP, Fe-BCP composites, and pure-Fe and SS316L as controls) were surgically implanted into medio proximal region of the radial bones. Real-time ultrasound analysis showed a decreased echo pattern at the peri-implant biodegradation site of the composites indicating minimal tissue response during the wound healing process. Peripheral whole blood biomarkers monitoring showed a normal dynamic change of blood cellular responses and no stress effect was observed. Meanwhile, the released Fe ion concentration was increasing along the implantation period. Histological analysis showed that the composites corresponded with a lower inflammatory giant cell count than that of SS316L. Analysis of the retrieved implants showed a thicker degradation layer on the composites compared with pure-Fe. It can be concluded that the iron-bioceramic composites are bioactive and induce a preferable wound healing process., (© 2014 Wiley Periodicals, Inc.)

In vitro gastrointestinal digestion of babassu mesocarp in the absence and presence of milk and lignin was performed to evaluate the bioaccessibility of Cu, Fe, and Zn. Extractions using NaOH solutions (pH 7 and 12) were carried out to evaluate the interactions of Cu(II), Fe(III), and Zn(II) with the extracted compounds and with the washed mesocarp. Studies using reference solutions showed a decrease in the free concentration of the elements in the presence of mesocarp. Phytate, a component present in the mesocarp, can be the main compound responsible for the elements' interactions with mesocarp. Lignin increases the elements' soluble fractions; however, the elements' concentrations in the dialyzed fractions, representing the bioaccessible portion, were very low. On the other hand, Cu, Fe, and Zn bioaccessibility in milk was not influenced by the mesocarp.

Purpose: To evaluate the impact of the level of inherent hepatic iron deposition on the ability of multiecho T2*-weighted magnetic resonance imaging (T2*WI) to identify hepatocellular carcinoma. This is relevant to the ancillary features described in the Liver Imaging Reporting and Data System reporting system., Methods: This retrospective review identified liver transplant patients with a preoperative magnetic resonance imaging at 1.5 T including gradient-recalled echo T2*WI (echo time, 9.5, 19.3, 29.0 milliseconds). A blinded, randomized reading was performed by a single reader of each of the images at each echo time. Hepatic iron content (HIC) was calculated for each participant and compared with the results of the blinded read., Results: Ninety-eight HCCs were identified on explant pathology in 73 participants. Of these, 57 HCCs (58%) were identified on T2*WI. However, no HCCs were visible in participants with HIC < 1.0 mg/g. For participants with HIC > 1.0 mg/g, 57 (88%) of 65 HCCs were visible., Conclusions: Most of HCCs can be identified on T2*WI without gadolinium; however, performance is significantly affected by background HIC.

Diet is the main source of cadmium (Cd) exposure. Gastrointestinal absorption increases during pregnancy. Cadmium accumulated in the placenta may interfere with nutrient transport to the foetus. Data on the potential of Cd to act as a steroid disruptor of pregnancy are limited. We evaluated the effects of oral Cd exposure during pregnancy on placental function in micronutrient transfer to the foetus and steroidogenesis in Wistar rats (regular 4-day cyclers) that mated with unexposed males. Pregnant rats were randomly assigned to a Cd group exposed orally to 50 mg Cd l(-1) (CdCl(2)xH2O dissolved in demineralized water), ≈ 7.5 mg Cd kg(-1) a day, during 20 days of gestation and control (supplied with demineralized water). Non-pregnant rats were treated under the same experimental conditions. On day 20, all of the rats were killed and samples were taken for element analyses (by electrothermal atomic absorption spectrometry). Progesterone and testosterone were measured in serum and placenta-derived samples (by immunoenzymometric assay and/or enzyme-linked immunosorbent assay). In the exposed rats, Cd increased in blood and organs, more in pregnant rats, and in placenta and foetus whereas zinc increased in liver. Iron decreased in maternal organs and in foetus, whereas zinc decreased in maternal kidney and placenta. Liver copper was lower and kidney copper higher in all pregnant vs. non-pregnant rats. Steroids in serum and placenta did not change. In conclusion, oral Cd exposure during rat pregnancy does not affect progesterone and testosterone at term. Transplacental iron and zinc handover are disrupted, which may put at risk the maintenance of foetal nutrition and viability., (Copyright © 2014 John Wiley & Sons, Ltd.)

Iron deficiency is a major public health problem in the world. Ferritin is being explored as a novel and natural strategy for iron supplementation. The objective of this study was to evaluate iron bioavailability from ferritin isolated from plant and animal sources. The stability of plant ferritin and animal ferritin was studied by in vitro and in vivo digestion to determine whether these ferritins can pass through the gastrointestinal tract in intact form. Results from sodium dodecyl sulfate polyacrylamide gel electrophoresis and Western blot indicate that both plant ferritin and animal ferritin can resist digestion (both under acidic and moderately acidic conditions). Furthermore, ferritin was labeled with (59)Fe, and bioavailability of iron from ferritin was assessed by uptake into Caco-2 cells. Our results indicate that iron is taken up from the ferritins and that iron bioavailability from soybean ferritin (rH-1:rH-2=1:1) is the highest. These results may be explained by the binding of ferritin to Caco-2 cells, which can be attributed to the interaction between ferritin and its putative receptor(s) at the surface of Caco-2 cells. In conclusion, ferritin from plant and animal sources may be developed as an iron source., (Copyright © 2015 Elsevier Inc. All rights reserved.)