Tremendous progress has been made in the field of ferroptosis since this regulated cell death process was first named in 2012. Ferroptosis is initiated upon redox imbalance and driven by excessive phospholipid peroxidation. Levels of multiple intracellular nutrients (iron, selenium, vitamin E and coenzyme Q10) are intimately related to the cellular antioxidant system and participate in the regulation of ferroptosis. Dietary intake of monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA) regulates ferroptosis by directly modifying the fatty acid composition in cell membranes. In addition, amino acids and glucose (energy stress) manipulate the ferroptosis pathway through the nutrient-sensitive kinases mechanistic target of rapamycin complex 1 (mTORC1) and AMP-activated protein kinase (AMPK). Understanding the molecular interaction between nutrient signals and ferroptosis sensors might help in the identification of the roles of ferroptosis in normal physiology and in the development of novel pharmacological targets for the treatment of ferroptosis-related diseases.

Adequate iron supply in pregnancy is important for both the woman and the fetus, but iron status is often assessed late in first trimester, if assessed at all. Therefore, identification of factors associated with iron status is important to target vulnerable groups with increased risk of deficiency. Our objectives were to (1) describe iron status in mid-pregnancy and (2) identify sociodemographic and lifestyle predictors of pregnancy iron status. This cross-sectional study uses data from The Norwegian Mother, Father and Child Cohort Study (collected 2002–2008) and The Medical Birth Registry of Norway. Iron status was measured as non-fasting plasma ferritin (P-Fe) and transferrin in gestational week (GW) 18 (n 2990), and by lowest reported Hb in GW 0–30 (n 39 322). We explored predictors of iron status with elastic net, linear and log-binomial regression models. Median P-Fe was 33 μg/l, and 14 % had depleted iron stores (P-Fe <15 μg/l). P-Fe below 30 μg/l was associated with reduced Hb. We identified eleven predictors, with interpregnancy interval (IPI) and parity among the most important. Depleted iron stores was more common among women with IPI < 6 months (56 %) and 6–11 months (33 %) than among those with IPI 24–59 months (19 %) and among nulliparous women (5 %). Positively associated factors with iron status included hormonal contraceptives, age, BMI, smoking, meat consumption and multi-supplement use. Our results highlight the importance of ferritin measurements in women of childbearing age, especially among women not using hormonal contraceptives and women with previous and recent childbirths.

Mammalian neonates undergo rapid transitions from a sterile uterine environment with a continuous intravenous supply of nutrients to a microbe-rich environment with intermittent ingesting of colostrum/milk via the gut. Currently, little is known about the colostrum-induced alterations of intestinal mucosal proteins in piglets with intra-uterine growth restriction (IUGR). In this study, we sought to investigate the innate differences and effects of colostrum on alterations in small-intestinal proteomes of IUGR piglets. Two IUGR (approximately 0·9 kg) and two normal-birth weight (NBW; approximately 1·3 kg) piglets were obtained from each of six sows at birth. One half (n 12; 6 IUGR v. 6 NBW) of the selected newborn piglets were killed to obtain jejunum samples, and the other half (n 12; 6 IUGR v. 6 NBW) of the newborn piglets were allowed to suckle colostrum from their own mothers for 24 h before jejunum sample collection. On the basis of proteomic analysis, we identified thirty-one differentially expressed proteins in the jejunal mucosa between IUGR and normal neonates before or after colostrum consumption. The intestinal proteins altered by colostrum feeding play important roles in the following: (1) increasing intestinal integrity, transport of nutrients, energy metabolism, protein synthesis, immune response and, therefore, cell proliferation; and (2) decreasing oxidative stress, and therefore cell apoptosis, in IUGR neonates. However, colostrum only partially ameliorated the inferior status of the jejunal mucosa in IUGR neonates. These findings provide the first evidence in intestinal protein alterations of IUGR neonates in response to colostrum ingestion, and thus render new insights into the mechanisms responsible for impaired growth in IUGR neonates and into new nutritional intervention strategies.

To investigate the effects of maternal dietary protein restriction on offspring Fe metabolism, twenty-four second-parity Landrace×Yorkshire sows were randomly allocated to standard-protein (SP) and low-protein (LP) groups. The SP sows were fed diets containing 15 and 18 % crude protein throughout pregnancy and lactation, respectively, whereas the LP sows were subjected to 50 % dietary protein restriction. Offspring birth weight was not affected, but the body weight at weaning (P=0·06) and average daily gain (P=0·01) of the female piglets were significantly decreased. Serum Fe level in the LP piglets was markedly decreased at weaning, especially in males (P=0·03). Serum ferritin level (P=0·08) tended to be lower, yet serum transferrin was greatly higher (P=0·01) in male weaning piglets of the LP group. Duodenal expression of the divalent metal transporter 1 (DMT1) and ferroportin (FPN) was surprisingly reduced (P<0·05) at the level of protein, but not at the mRNA level, in male weaning piglets of the LP group. Male weaning piglets born to the LP sows exhibited higher hepatic hepcidin levels (P=0·09), lower hepatic expression of transferrin (P<0·01) and transferrin receptor 1 (P<0·05) at the level of mRNA. However, no significant differences were observed for hepatic Fe storage, ferritin, transferrin and transferrin receptor 1 protein expression in male weaning piglets of the two groups. These results indicate that maternal protein restriction during pregnancy and lactation influences growth of female offspring at weaning, reduces duodenal expression of Fe transporters (DMT1 and FPN) and decreases serum Fe level in male weaning piglets.

This review examines the importance of the placenta in iron metabolism during development and the effect of iron deficiency on maternal and fetal physiology. Iron is an essential micronutrient, required for a wide variety of biological processes. During pregnancy, the mother has to deplete her iron stores in order to provide the baby with adequate amounts. Trans-placental iron transfer involves binding transferrin (Tf)-bound iron to the Tf receptor, uptake into an endosome, acidification, release of iron through divalent metal transporter 1, efflux across the basolateral membrane through ferroportin and oxidation of Fe(II) by zyklopen. An additional haem transport system has been hypothesised, which may explain why certain gene knockouts are not lethal for the developing fetus. Iron deficiency is a common phenomenon during pregnancy, and the placenta adapts by up-regulating its transfer systems, maintaining iron at the expense of the mother. Despite these adaptations, deficiency cannot be completely prevented, and the offspring suffers both short- and long-term consequences. Some of these, at least, may arise from decreased expression of genes involved in the cell cycle and altered expression of transcription factors, such as c-myc, which in turn can produce, for example, kidneys with reduced numbers of nephrons. The mechanism whereby these changes are induced is not certain, but may simply be as a result of the reduced availability of iron resulting in decreased enzyme activity. Since these changes are so significant, and because some of the changes are irreversible, we believe that iron prophylaxis should be considered in all pregnancies.

Iron is almost ubiquitous in living organisms due to the utility of its redox chemistry. It is also dangerous as it can catalyse the formation of reactive free radicals – a classical double-edged sword. In this review, we examine the uptake and usage of iron by trypanosomatids and discuss how modulation of host iron metabolism plays an important role in the protective response. Trypanosomatids require iron for crucial processes including DNA replication, antioxidant defence, mitochondrial respiration, synthesis of the modified base J and, in African trypanosomes, the alternative oxidase. The source of iron varies between species. Bloodstream-form African trypanosomes acquire iron from their host by uptake of transferrin, and Leishmania amazonensis expresses a ZIP family cation transporter in the plasma membrane. In other trypanosomatids, iron uptake has been poorly characterized. Iron-withholding responses by the host can be a major determinant of disease outcome. Their role in trypanosomatid infections is becoming apparent. For example, the cytosolic sequestration properties of NRAMP1, confer resistance against leishmaniasis. Conversely, cytoplasmic sequestration of iron may be favourable rather than detrimental to Trypanosoma cruzi. The central role of iron in both parasite metabolism and the host response is attracting interest as a possible point of therapeutic intervention.

Antimicrobial proteins are active against protozoans, fungi, viruses as well as gram-positive and gram-negative bacteria. In many cases, antimicrobial proteins are present as components of innate immunity and are capable of evading bacterial resistance mechanisms. Due to these characteristics, these proteins represent an appealing alternative to conventional antibiotic drugs. Considerable research has been conducted on antimicrobial proteins from invertebrate and mammalian sources. Within the last decade, over 20 novel antimicrobial proteins have been isolated from avian systems. The majority of these proteins has been isolated from the domestic chicken and therefore represents a minuscule fraction of the avian antimicrobial proteins that are potentially awaiting discovery. In this review, we elaborate on these discoveries and on the future of avian antimicrobial protein research.

Background: Alterations in iron metabolism have been suggested as potential pathological markers in patients with manifest depression. No data on the association between iron and depression exist from population-based studies, in which milder forms of depressive symptoms are much more common. The aim of this study was to analyze the relationship between six parameters of iron metabolism and depressive mood in a population-based cross-sectional study in Germany.

Methods: A total of 374 participants, aged 65–83 years, of the Memory and Morbidity in Augsburg Elderly (MEMO) Study were assessed using the Center for Epidemiologic Studies – Depression Scale (CES-D) for depression. Iron, ferritin, transferrin, soluble transferrin receptor, iron binding capacity, transferrin saturation and C-reactive protein were analyzed with standard laboratory methods. Linear and logistic regression analyses were applied to evaluate the relationship between iron parameters and depressive mood.

Results: The 7-day prevalence of depressive mood was 10.2%, with a higher risk in women compared to men [odds ratio (OR) = 2.04; 95% confidence interval (95% CI) = 1.04–4.0]. Correlation and linear regression analyses adjusted for age, gender, hypertension and smoking yielded no significant relationship between any of the iron parameters and the CES-D scores. In gender-stratified analyses a statistically significant association between serum iron and depressive mood was observed in men only. This finding disappeared after applying a Bonferroni correction for multiple testing.

Conclusions: The lack of association of iron metabolism and depressive mood reported in this population-based study does not support previous findings in patients with major depression. This negative finding in milder forms of depression in elderly people indicates either the absence or a more complex nature of the interactions between iron metabolism, low-grade inflammation and depression.

Sixty children aged 1-3 years with protein malnutrition were involved in the present study. Measurements were made of plasma transferrin receptor (TfR), haemoglobin (Hb), ferritin, transferrin and Fe in comparison with twenty apparently healthy age- and sex-matched reference children in Nigeria. Plasma TfR was measured by an immunofluorometric assay. The mean plasma concentrations of both albumin (37 g/l) and transferrin (1·88 g/l) were within reference ranges in the ‘healthy’ children. The malnourished children had severe protein deficiency as indicated by their significantly lower mean plasma albumin (24·4-28·2 g/l; P < 0·0001) and transferrin (1·24-1·53 g/l; P < 0·0001) concentrations in comparison with the reference children. In the reference children, the traditional indicators of Fe nutrition (plasma Fe, transferrin Fe saturation and Hb) were within the reference ranges, but ferritin values were raised, indicating acute or chronic infection and/or inflammation. The mean concentrations of plasma TW (4·2-5-2 mg/l) in the malnourished group were significantly lower than the mean (6·1 mgn) of the reference children (P=0·0009). In the children with severe malnutrition, none of the indicators of Fe status except Hb (81·5-86·7 g/l; P<0·0001) showed Fe deficiency, including the serum concentration of TfR and the TfR : ferritin ratio, although the Fe status was lower than in the reference children (for Fe P = 0·009; and ferritin P=0·0004). In the absence of haemodilution, the low Hb values are a clear indication that the malnourished children were Fe deficient; none of the other indices was indicative of Fe deficiency. This is the first report of TfR levels in malnourished and healthy African children.