Efficacy of polysaccharide iron complex in IDA rats: A comparative study with iron protein succinylate and ferrous succinate.

Iron deficiency anemia (IDA) is the most common nutrient-related health problem in the world. There is still a lack of comprehensive comparative study on the efficacies of commonly used iron supplements such as polysaccharide iron complex (PIC), iron protein succinylate (IPS) and ferrous succinate (FS) for IDA. In this study, we compared the PIC, IPS and FS efficacies in IDA rats via intragastric administration. The results showed that the three iron supplements had similar efficacies. PIC/IPS/FS at a dose of 15 mg Fe/kg/d for 10 d increased the hematological and serum biochemical parameters to 2.15/2.12/2.18 (Hb), 1.71/1.67/1.69 (RBC), 2.10/2.11/2.12 (HCT), 1.26/1.22/1.22 (MCV), all 1.34 (MCH), 1.15/1.15/1.14 (MCHC), 1.94/1.82/1.91 (SF), 9.75/9.67/9.53 (SI), and 23.30/22.68/21.64 (TS) times, and reduced TIBC to 0.42/0.43/0.44 times, compared to untreated IDA rats. PIC performed slightly better than IPS and FS in restoring MCV level. Meanwhile, the heart, spleen and kidney coefficients reduced to 67%/74%/65% (heart), all 59% (spleen) and 87%/88%/88% (kidney), and the liver coefficient increased to 116%/115%/116%, compared to untreated IDA rats. The liver iron content was found to be more affected by IDA than the spleen iron content. PIC/IPS/FS at 15 mg Fe/kg/d increased organ iron contents to 4.20/3.97/4.03 times (liver) and 1.36/1.24/1.41 times (spleen) within 10 d compared to untreated IDA rats, and PIC-H and FS were slightly better than IPS in restoring spleen iron content. The results of this study can provide useful data information for the comparison of three iron supplements, PIC, IPS and FS.

Characterization of Oyster Protein Hydrolysate-Iron Complexes and their In Vivo Protective Effects against Iron Deficiency-Induced Symptoms in Mice.

Iron is one of the trace mineral elements, and iron deficiency is a common phenomenon that negatively influences human health. Food-derived iron supplements were considered excellent candidates for improving this syndrome. In this work, oyster-protein hydrolysates (OPH) and ferrous chloride successfully formed the OPH-Fe complex (6 mg/mL, 40 °C, 30 min), where the main binding sites involved were the carboxyl and amino groups. The OPH-Fe complex showed no obvious changes in the secondary structure, while the iron changed the morphological appearance and also showed fluorescence quenching, an ultraviolet shift, and an increase in size distribution. The OPH-Fe complex showed better dynamic absorption of iron (64.11 µmol/L) than ferrous sulfate (46.90 µmol/L), and the medium dose had better protective effects against iron-deficiency anemia in vivo. Three representative peptides (DGKGKIPEE, FAGDDAPRA, and VLDSGDGVTH) that were absorbed intact were identified. This experiment provided a theoretical foundation for further study of the digestion and absorption of the OPH-Fe complex.

Effects of food-derived oligopeptide iron chelates on liver injury and gut microbiota homeostasis in iron-deficiency anemia female rats: a pilot study.

Iron deficiency (ID) is the biggest cause of anemia. This pilot study aimed to investigate the effects of food-derived oligopeptide iron chelates on ameliorating liver injury and restoring gut microbiota homeostasis in iron-deficiency anemia (IDA) female rats. Female Sprague-Dawley rats at 21 days old were selected and randomly divided into a control group (N = 4) and an ID model group (N = 16). The ID model group was fed an iron-deficient diet containing 4 mg kg-1 iron for 28 days to generate the IDA rat model and then randomly subdivided into four groups (N = 4 for each group): ID group, ferrous sulfate group, marine fish oligopeptide iron chelate (MCOP-Fe) group, and whey protein oligopeptide iron chelate (WPP-Fe) group. Iron supplements were given to rats in the three intervention groups once per day via intragastric administration for three weeks. After iron supplementation, the hemoglobin levels in the three intervention groups were significantly improved, with the MCOP-Fe and WPP-Fe groups returning to normal. The ALT and AST levels in the ID group increased significantly, while levels in all intervention groups decreased to normal levels. Liver glutathione in the WPP-Fe group was increased, while the activity of superoxide dismutase also tended to be higher. In addition, 16S rRNA gene sequencing showed that IDA resulted in changes to intestinal microbiota. After intervention, the WPP-Fe group showed increased alpha diversity of intestinal microbes. Therefore, MCOP-Fe and WPP-Fe may improve the iron status of IDA female rats as well as ameliorate liver damage, with WPP-Fe showing a greater potential in improving gut microbiota imbalance.

Influence of exopolysaccharide EPSKar1-iron complexation on iron bioavailability and alleviating iron deficiency anaemia in Wistar rats.

The prevalence of iron deficiency anaemia is a significant issue worldwide, affecting individuals of all ages and often associated with inadequate iron bioavailability. Despite the use of ferrous salt supplements to address anaemia, their limited bioaccessibility and bioavailability in human GIT and adverse impact on food properties remain significant challenges. Hence, this study aims to explore the iron chelation mechanism of an exopolysaccharide EPSKar1 to enhance iron bioaccessibility, bioavailability, and anti-anaemic effects using cell culture and an anaemic rat model. EPSKar1 was extracted from Lacticaseibacillus rhamnosus Kar1 and complexed with FeSO4 to form "EPSKar1-iron". This novel complex, besides being bio-accessible after in vitro gastric digestion, demonstrated 61.27 ± 1.96% iron bioavailability to the Caco-2 cells. In line with these in vitro findings, intragastric administration of the EPSKar1-iron complex to anaemic Wistar rats at 25 and 50 mg per kg body weight significantly restored blood haemoglobin levels and re-established the morphological features of red blood cells. Furthermore, the apparent digestibility co-efficient and iron uptake improved significantly without adversely affecting the serum biochemical parameters in these anaemic rats. The levels of iron-transport proteins including serum transferrin and ferritin in tissue and plasma have increased remarkably upon oral administration of EPSKar1-iron at a higher dose of 50 mg per kg body weight. Oral supplementation of EPSKar1-iron did not foster adverse histological changes in the liver, kidneys, and spleen. In fact, the treatment with the EPSKar1-iron complex had a restitution effect on the tissue architecture, thereby ameliorating the tissue lesions. These findings collectively indicate that the EPSKar1-iron complex shows nutraceutical potential in enhancing the bioavailability of iron and could be a promising approach to tackle iron deficiency anaemia.

Iron from nanostructured ferric phosphate: absorption and biodistribution in mice and bioavailability in iron deficient anemic women.

Food fortification with iron nanoparticles (NPs) could help prevent iron deficiency anemia, but the absorption pathway and biodistribution of iron-NPs and their bioavailability in humans is unclear. Dietary non-heme iron is physiologically absorbed via the divalent metal transporter-1 (DMT1) pathway. Using radio- iron isotope labelling in mice with a partial knockdown of intestine-specific DMT1, we assessed oral absorption and tissue biodistribution of nanostructured ferric phosphate (FePO4-NP; specific surface area [SSA] 98 m2g-1) compared to to ferrous sulfate (FeSO4), the reference compound. We show that absorption of iron from FePO4-NP appears to be largely DMT1 dependent and that its biodistribution after absorption is similar to that from FeSO4, without abnormal deposition of iron in the reticuloendothelial system. Furthermore, we demonstrate high bioavailability from iron NPs in iron deficient anemic women in a randomized, cross-over study using stable-isotope labelling: absorption and subsequent erythrocyte iron utilization from two 57Fe-labeled FePO4-NP with SSAs of 98 m2g-1 and 188 m2g-1 was 2.8-fold and 5.4-fold higher than from bulk FePO4 with an SSA of 25 m2g-1 (P < 0.001) when added to a rice and vegetable meal consumed by iron deficient anemic women. The FePO4-NP 188 m2g-1 achieved 72% relative bioavailability compared to FeSO4. These data suggest FePO4-NPs may be useful for nutritional applications.

Iron supplementation ameliorates aloin-induced iron deficiency anemia in rats.

Aloin, an anthraquinone glycoside, is one of other C-glycosides found in the leaf exudate of Aloe plant. Aloin possesses several biologic activities, including antitumor activity in vitro and in vivo. However, aloin treatment has shown iron deficiency anemia and erythropoiesis in vivo. The present study was undertaken to verify if iron supplementation could alleviate these perturbations, compared to doxorubicin, an anthracycline analog. Oral iron supplementation (20.56 mg elemental Fe/kg bw) to aloin-treated rats normalized red blood corpuscles count, hemoglobin concentration, and serum levels of total iron binding capacity and saturated transferrin, as well as hepatic iron content, hepcidin level, and mRNA expression of ferritin heavy chain (Ferr-H) and transferrin receptor-1 (TfR-1) genes. Although, serum hyperferremia, and leukocytosis were maintained, yet the spleen iron overload was substantially modulated. However, combined aloin and iron treatment increased iron storage levels in the heart and bone marrow, compared to aloin treatment per se. On other hand, oral iron supplementation to rats treated with doxorubicin (15 mg/kg bw) lessened the increase in the spleen iron content concomitantly with hepatic hepcidin level, rebound hepatic iron content to normal level, and by contrast augmented serum levels of iron and transferrin saturation. Also, activated Ferr-H mRNA expression and repressed TfR-1 mRNA expression were recorded, compared to doxorubicin treatment per se. Histopathological examination of the major body iron stores in rats supplemented with iron along with aloin or doxorubicin showed an increase in extramedullary hematopoiesis. In conclusion, iron supplementation restores the disturbances in iron homeostasis and erythropoiesis induced by aloin treatment.

The Use of Iron-Enriched Yeast for the Production of Flatbread.

The most common cause of iron deficiency is an improperly balanced diet, in which the body's need for iron cannot be met by absorption of this element from food. Targeted iron supplementation and food fortification may be the main treatments for iron deficiency in the population. However, many iron-rich supplements and foods have low bioavailability of this element. In our study, we used yeast enriched with iron ions to produce flatbread. The yeast cells accumulated iron ions from the medium supplemented with Fe(NO3)3·9H2O, additionally one of the cultures was treated with pulsed electric field in order to increase the accumulation. The potential bioavailability of iron from flatbread containing 385.8 ± 4.12 mg of iron in 100 g dry mass was 10.83 ± 0.94%. All the flatbreads had a moderate glycemic index. There were no significant differences in antioxidant activity against DPPH• between flatbread with iron-enriched and non-iron-enriched yeast. Sensory evaluation showed that this product is acceptable to consumers since no metallic aftertaste was detected. Iron enriched flatbread can potentially be an alternative to dietary supplements in iron deficiency states.

Iron distribution in different tissues of homozygous Mask (msk/msk) mice and the effects of oral iron treatments.

Iron-refractory iron deficiency anemia (IRIDA) is an autosomal recessive disorder caused by genetic mutations on TMPRSS6 gene which encodes Matriptase2 (MT2). An altered MT2 cannot appropriately suppress hepatic BMP6/SMAD signaling in case of low iron, hence hepcidin excess blocks dietary iron absorption, leading to a form of anemia resistant to oral iron supplementation. In this study, using the IRIDA mouse model Mask, we characterized homozygous (msk/msk) compared to asymptomatic heterozygous (msk/wt) mice, assessing the major parameters of iron status in different organs, at different ages in both sexes. The effect of carbonyl iron diet was analyzed as control iron supplementation being used for many studies in mice. It resulted effective in both anemic control and msk/msk mice, as expected, even if there is no information about its mechanism of absorption. Then, we mainly compared two forms of oral iron supplement, largely used for humans: ferrous sulfate and Sucrosomial iron. In anemic control mice, the two oral formulations corrected hemoglobin levels from 11.40 ± 0.60 to 15.38 ± 1.71 g/dl in 2-4 weeks. Interestingly, in msk/msk mice, ferrous sulfate did not increase hemoglobin likely due to ferroportin/hepcidin-dependent absorption, whereas Sucrosomial iron increased it from 11.50 ± 0.60 to 13.53 ± 0.64 g/dl mainly in the first week followed by a minor increase at 4 weeks with a stable level of 13.30 ± 0.80 g/dl, probably because of alternative absorption. Thus, Sucrosomial iron, already used in other conditions of iron deficiency, may represent a promising option for oral iron supplementation in IRIDA patients.

Flipside of the Coin: Iron Deficiency and Colorectal Cancer.

Iron deficiency, with or without anemia, is the most frequent hematological manifestation in individuals with cancer, and is especially common in patients with colorectal cancer. Iron is a vital micronutrient that plays an essential role in many biological functions, in the context of which it has been found to be intimately linked to cancer biology. To date, however, whereas a large number of studies have comprehensively investigated and reviewed the effects of excess iron on cancer initiation and progression, potential interrelations of iron deficiency with cancer have been largely neglected and are not well-defined. Emerging evidence indicates that reduced iron intake and low systemic iron levels are associated with the pathogenesis of colorectal cancer, suggesting that optimal iron intake must be carefully balanced to avoid both iron deficiency and iron excess. Since iron is vital in the maintenance of immunological functions, insufficient iron availability may enhance oncogenicity by impairing immunosurveillance for neoplastic changes and potentially altering the tumor immune microenvironment. Data from clinical studies support these concepts, showing that iron deficiency is associated with inferior outcomes and reduced response to therapy in patients with colorectal cancer. Here, we elucidate cancer-related effects of iron deficiency, examine preclinical and clinical evidence of its role in tumorigenesis, cancer progression and treatment response. and highlight the importance of adequate iron supplementation to limit these outcomes.

Prediction of anemia at delivery.

We aimed to assess risk factors for anemia at delivery by conducting a secondary analysis of a prospective cohort study database including 1527 women who delivered vaginally ≥ 36 gestational weeks. Anemia (Hemoglobin (Hb) < 10.5 g/dL) was assessed at delivery. A complete blood count results during pregnancy as well as maternal and obstetrical characteristics were collected. The primary endpoint was to determine the Hb cutoff between 24 and 30 gestational weeks that is predictive of anemia at delivery by using the area under the curve (AUC) of the receiver operating characteristic curve. Independent risk factors for anemia at delivery were assessed using stepwise multivariable logistic regression. Hb and infrequent iron supplement treatment were independent risk factors for anemia at delivery (OR 0.3 95%CI [0.2-0.4] and OR 2.4 95%CI [1.2-4.8], respectively; C statistics 83%). Hb 10.6 g/dL was an accurate cutoff to predict anemia at delivery (AUC 80% 95%CI 75-84%; sensitivity 75% and specificity 74%). Iron supplement was beneficial to prevent anemia regardless of Hb value. Altogether, Hb should be routinely tested between 24 and 30 gestational weeks to screen for anemia. A flow chart for anemia screening and treatment during pregnancy is proposed in the manuscript.Trial registration: ClinicalTrials.gov Identifier: NCT02434653.

Gut Microbial and Metabolic Profiling Reveal the Lingering Effects of Infantile Iron Deficiency Unless Treated with Iron.

SCOPE: Iron deficiency (ID) compromises the health of infants worldwide. Although readily treated with iron, concerns remain about the persistence of some effects. Metabolic and gut microbial consequences of infantile ID were investigated in juvenile monkeys after natural recovery (pID) from iron deficiency or post-treatment with iron dextran and B vitamins (pID+Fe). METHODS AND RESULTS: Metabolomic profiling of urine and plasma is conducted with 1 H nuclear magnetic resonance (NMR) spectroscopy. Gut microbiota are characterized from rectal swabs by amplicon sequencing of the 16S rRNA gene. Urinary metabolic profiles of pID monkeys significantly differed from pID+Fe and continuously iron-sufficient controls (IS) with higher maltose and lower amounts of microbial-derived metabolites. Persistent differences in energy metabolism are apparent from the plasma metabolic phenotypes with greater reliance on anaerobic glycolysis in pID monkeys. Microbial profiling indicated higher abundances of Methanobrevibacter, Lachnobacterium, and Ruminococcus in pID monkeys and any history of ID resulted in a lower Prevotella abundance compared to the IS controls. CONCLUSIONS: Lingering metabolic and microbial effects are found after natural recovery from ID. These long-term biochemical derangements are not present in the pID+Fe animals emphasizing the importance of the early detection and treatment of early-life ID to ameliorate its chronic metabolic effects.

Global look at nutritional and functional iron deficiency in infancy.

Iron-deficiency anemia (IDA) affects many infants in low- and middle-income countries (LMICs) and may impair cognitive development and adaptive immunity. Effective interventions to improve iron intakes for infants in LMICs are urgently needed. However, absorption of oral iron fortificants and supplements is low, usually <10%, and most of the iron passes into the colon unabsorbed. In randomized controlled trials, provision of iron to infants in LMICs adversely affects their gut microbiome and increases pathogenic Escherichia coli, gut inflammation, and diarrhea. To minimize these detrimental effects of iron, it is important to provide the lowest effective dosage and maximize fractional iron absorption. Prebiotic galacto-oligosaccharides and apo-lactoferrin may prove useful in iron formulations in LMICs because they increase absorption of fortificant iron and at the same time may mitigate the adverse effects of unabsorbed iron on the infant gut. Providing well-absorbed iron early in infancy may improve immune function. Recent data from a Kenyan birth cohort suggest IDA at the time of infant vaccination impairs the response to diphtheria, pertussis, and pneumococcus vaccines. A randomized trial follow-up study reported that providing iron to Kenyan infants at the time of measles vaccination increased antimeasles immunoglobulin G (IgG), seroconversion, and IgG avidity. Because IDA is so common among infants in LMICs and because the vaccine-preventable disease burden is so high, even if IDA only modestly reduces immunogenicity of vaccines, its prevention could have major benefits.

Using Volatile Organic Compounds to Investigate the Effect of Oral Iron Supplementation on the Human Intestinal Metabolome.

Patients with iron deficiency anaemia are treated with oral iron supplementation, which is known to cause gastrointestinal side effects by likely interacting with the gut microbiome. To better study this impact on the microbiome, we investigated oral iron-driven changes in volatile organic compounds (VOCs) in the faecal metabolome. Stool samples from patients with iron deficiency anaemia were collected pre- and post-treatment (n = 45 and 32, respectively). Faecal headspace gas analysis was performed by gas chromatography-mass spectrometry and the changes in VOCs determined. We found that the abundance of short-chain fatty acids and esters fell, while aldehydes increased, after treatment. These changes in pre- vs. post-iron VOCs resemble those reported when the gut is inflamed. Our study shows that iron changes the intestinal metabolome, we suggest by altering the structure of the gut microbial community.

[Moderate anaemia refractory to oral iron in a pregnant woman with a history of bariatric surgery]. / Anemia moderada refractaria al hierro oral en una gestante con antecedente de cirugía bariátrica.

INTRODUCTION: Introduction: bariatric surgery involves nutritional and trace element deficiencies that may have a negative impact if not treated properly, especially in situations such as pregnancy. Case report: a patient who underwent biliopancreatic diversion surgery without subsequent therapeutic adherence consults due to edema; findings included 29-week gestation (type 1 intrauterine growth restriction) and moderate anemia. Vitamin supplementation, oligoelements, enteral nutrition, and intravenous iron were restarted. Due to poor hemoglobin response with repleted iron deposits, recombinant human erythropoietin was associated. Discussion: the most frequent nutritional deficiencies after malabsorptive bariatric surgery are sideropenia and hypoproteinemia. Sideropenia and anemia increase the risk of preterm delivery, low weight, and perinatal mortality. In patients with inadequate response to intravenous iron, treatment with recombinant human erythropoietin may be considered, although its use in pregnant women without chronic renal failure has no indication in the prescribing information of this drug.

INTRODUCCIÓN: Introducción: la cirugía bariátrica (CB) implica déficits nutricionales y de oligoelementos que pueden tener una repercusión negativa en caso de no tratarse adecuadamente, especialmente en situaciones como la gestación. Caso clínico: paciente sometida a CB del tipo de la derivación biliopancreática, sin adherencia terapéutica posterior, que acude por edemas, confirmándose la presencia de una gestación de 29 semanas (feto CIR de tipo I) y de anemia moderada. Se reinició la suplementación de vitaminas, oligoelementos, nutrición enteral y hierro intravenoso (FEIV). Debido a la escasa respuesta de la hemoglobina con depósitos de hierro repletados, se asoció eritropoyetina humana recombinante (rHuEPO). Discusión: los déficits nutricionales más frecuentes tras una CB malabsortiva son la ferropenia y la hipoproteinemia. La ferropenia y la anemia incrementan el riesgo del parto pretérmino, el bajo peso y la mortalidad perinatal. En las pacientes sin adecuada respuesta al FEIV puede plantearse el tratamiento con rHuEPO, aunque su uso en gestantes sin insuficiencia renal crónica no dispone de indicación en la ficha técnica.

Iron homeostasis disorder in piglet intestine.

Iron plays an essential role in preventing iron deficiency anemia and ensuring the healthy growth of animals. The special physiological condition of piglets is the main cause of iron deficiency. Iron metabolism in the intestine is the basis for understanding the effects of iron on the health of piglets. In order to scientifically evaluate dietary iron supplementation doses, it is necessary to recognize the effects of iron deficiency and iron overload on piglet intestinal health. Besides, iron as a cofactor is essential for the growth of microorganisms, and microorganisms compete with the host to absorb iron. Under the stress of iron deficiency and iron overload, various control schemes (such as precise nutrition, element balance, elimination of oxidation, etc.) are effective measures to eliminate adverse effects. In this review, we comprehensively review recent findings on the effects of iron deficiency and iron overload on intestinal health. This review will provide a rational design strategy to achieve a reasonable iron supplement, which will guide the use of iron in animal husbandry.

The development of lentil derived protein-iron complexes and their effects on iron deficiency anemia in vitro.

Iron deficiency anemia (IDA) is the most common nutrient-dependent health problem in the world and could be reversed by commercially available iron supplementation. The form of iron supplement is important due to its toxicity on the gastrointestinal system (GI), so the development of new dietary strategies might be important for the prevention of IDA. It has been shown that plant-based proteins bind to iron and might decrease the free form of iron before absorption and increase iron bioavailability. Thus, we aimed to form lentil derived protein-iron complexes and to test the functional properties of hydrolysed protein-iron complexes in anemic Caco-2 cell line. Our main findings were that (i) lentil derived proteins had the capacity to chelate iron minerals and (ii) hydrolysed protein-iron complexes significantly reduced the mRNA levels of iron regulated divalent metal transporter-1 (DMT1), transferrin receptor (TFR), and ankyrin repeat domain 37 (ANKRD37) marker genes that were induced by iron deficiency anemia. The current findings suggest that hydrolysed protein-iron complexes might have functional properties in iron deficiency anemia in vitro. Further in vivo studies are necessary to show lentil derived proteins and iron might be used as supplements or food additives to reduce the risk of iron deficiency anemia.

Fractional iron absorption from enteric-coated ferrous sulphate tablet.

Background & objectives: Iron supplementation is widely used public health measure to manage iron deficiency anaemia. In India, enteric-coated iron tablets are administered to adolescent boys and girls to avoid adverse effects such as gastritis, which reduces compliance, but this may result in poor iron absorption. Data on the absorption of iron from enteric-coated ferrous sulphate tablets are lacking. The present study using stable isotopic approach was aimed to measure iron absorption in iron deficient women. Methods: Iron absorption was measured from stable isotope-labelled enteric-coated ferrous sulphate ([57]Fe, ECFS) and uncoated ferrous sulphate ([58]Fe, UCFS) tablets in iron-deficient (n=9) women, aged 18-40 yr with no infection or inflammation. The two types of tablets (ECFS and UCFS) were administered on consecutive days, 60 min after breakfast, and the sequence being random. Blood samples were collected before dosing, and on day 15, to measure iron absorption from the shift in iron isotopic ratios in haemoglobin. Results: Eight women completed the iron absorption study. Iron absorption was found to be significantly lower in ECFS compared to UCFS (3.5 vs. 12%, P <0.05) consumption. Interpretation & conclusions: Our study showed poor iron bioavailability from ECFS, and supplementation programmes may consider UCFS tablets for better haematological outcomes.

Metabolic effect of AOS-iron in rats with iron deficiency anemia using LC-MS/MS based metabolomics.

Iron deficiency anemia (IDA) is a worldwide nutritional problem. The metabolic mechanism of IDA is still unclear. So, the underlying metabolic mechanism of iron supplementation has not been reported even if various iron supplements to treat IDA have been studied. The present study aimed to investigate the metabolic mechanisms of IDA and agar oligosaccharide-iron complex (AOS-iron) supplementation in IDA rats by assessing the changes of endogenous metabolites in serum and liver using LC-MS/MS metabolomics approach. Orthogonal partial least-squares discriminant analysis (OPLS-DA) score plots showed significant separation of metabolites in serum and liver among the normal, anemia model and AOS-iron groups. Seventeen and eight metabolites were identified from serum and liver, respectively. Pathway enrichment analysis suggested that potential biomarkers were strongly involved in the biosynthesis of saturated and unsaturated fatty acids, sphingolipid metabolism, glycerophospholipid metabolism, linoleic acid metabolism, Fcγ receptor (FcγR)-mediated phagocytosis, pancreatic cancer metabolism, regulation of autophagy, gonadotropin releasing hormone (GnRH) signaling pathway, fatty acid metabolism, pantothenate and CoA biosynthesis, glutathione metabolism and primary bile acid biosynthesis. After supplementing 2 mg Fe/kg·bw AOS-iron for 4 weeks, the major metabolites in related pathways disrupted by IDA were restored to normal levels. Therefore, AOS-iron effectively treated IDA by regulating metabolic disorders.

Anemia and iron deficiency in Crohn's disease.

Introduction: Anemia is a common extraintestinal complication of Crohn's disease (CD) mainly caused by iron deficiency, that affects the quality of life in CD patients. Elucidation of the etiology and pathology of iron-deficiency anemia (IDA) and anemia of chronic diseases (ACD) has developed in recent years. Common biochemical parameters of iron status are insufficient for assessment of patients with anemia and CD. Thus, novel iron indices are required for accurate assessment in IDA patients with CD. Oral iron supplementation for IDA treatment is common and is associated with minor gastrointestinal side effects. Intravenous substitution improves safety profiles but may be not tolerable in some patients. Fortunately, additional therapies for anemia of active CD have emerged in recent years.Area covered: Here, we propose the review article on the link among anemia, iron deficiency, and Crohn's disease. We discuss the current diagnosis and therapy of anemia and iron deficiency in CD and propose the new directions for future research.Expert commentary: Exploring pathogeneses and treatments of anemia and iron deficiency in Crohn's disease will develop potential tools for early diagnosis and effective treatment of anemia in CD patients, and improve their life quality.

Sevoflurane anesthesia during pregnancy in mice induces cognitive impairment in the offspring by causing iron deficiency and inhibiting myelinogenesis.

Maternal anesthetic exposure during pregnancy is associated with an increased risk of cognitive impairment in offspring. The balance of cerebral iron metabolism is essential for the development of brain tissue. Iron deficiency affects the myelinogenesis and nerve tissue development, especially in fetus or infant, which has a key role in cognitive function. We aimed to investigate whether maternal sevoflurane (Sev) exposure caused cognitive impairment in offspring through inducing iron deficiency and inhibiting myelinogenesis. Pregnant mice (gestation stage day 14) were treated with 2% Sev for 6 h. Cognitive function of offspring mice was determined by the Morris water maze and Context fear conditioning test. Iron levels were assayed by Perl's iron staining and synchrotron imaging. Hippocampus and cortex tissues or cerebral microvascular endothelial cells of offspring mice (postnatal day 35) were harvested and subjected to Western blot and/or immunhistochemistry to assess ferritin, transferrin receptor 1(TfR1), Ferroportin-1 (FpN1), myelin basic protein (MBP), tight junction protein ZO-1, occludin, and claudin-5 levels. Beginning with postnatal day 30, the offspring were treated with iron therapy for 30 days, and the indicators above were tested. Our results showed Sev dramatically decreased the iron levels of brain and impaired cognitive function in offspring mice. Sev decreased the expression of heavy chain ferritin (FtH), light chain ferritin (FtL), MBP, ZO-1, occludin, claudin-5, and FpN1, and increased TfR1 in hippocampus and cortex or cerebral microvascular endothelial cells of offspring mice, indicating that Sev caused the iron deficiency and impaired the myelinogenesis in the brain of offspring. Interestingly, iron therapy prompted the myelinogenesis and improved impaired cognitive function at postnatal day 60. Our research uncovered a new mechanism which showed that iron deficiency induced by Sev and myelin formation disorder due to decreased iron of brain may be an important risk factor for cognitive impairment in offspring. It was necessary for offspring to be supplied iron supplement whose mother suffered exposure to sevoflurane during pregnancy.