Effects and Reversibility of Pre- and Post-natal Iron and Omega-3 Fatty Acid Deficiency, Alone and in Combination, on Bone Development in Rats

Both iron and omega-3 (n-3) polyunsaturated fatty acids may play an important role in bone development. The aim of this study was to investigate the effects of pre- and post-natal iron and n-3 fatty acid deficiency (FAD), alone and in combination, on bone development in rats, and to determine whether effects are reversible when a sufficient diet is provided post-weaning. Using a 2×2-factorial design, 56 female Wistar rats were allocated to one of four diets: (1) control, (2) iron deficient (ID), (3) n-3 FAD or (4) ID and n-3 FAD, and were maintained on the respective diets throughout gestation and lactation. At weaning (post-natal day [PND] 21), offspring (n = 24/group; male:female=1:1) were randomly allocated to either continue with their respective diets or to switch to the control diet until PND 42-45. Bone mineral density (BMD) and bone strength were determined using dual X-ray absorptiometry and three-point bending tests, respectively. Pre- and post-natal ID resulted in significantly lower BMD in the spine and bone strength in the left femur. Both ID and n-3 FAD resulted in lower BMD in the right femur, with an additive reduction in the combined ID and n-3 FAD group vs. controls. While negative effects of pre- and post-natal ID alone were reversed in offspring switched to a control diet post-weaning, lower BMD and bone strength persisted in offspring with combined ID and n-3 FAD during the prenatal and early post-natal period. Effects were not sex-specific. These results indicate that ID during early life may negatively influence bone development, with potential additive effects of n-3 FAD. While the effects of ID alone seem reversible, a combined ID and n-3 FAD may result in irreversible deficits in bone development.

Developmental iron deficiency dysregulates TET activity and DNA hydroxymethylation in the rat hippocampus and cerebellum

Iron deficiency (ID) during neurodevelopment is associated with lasting cognitive and socioemotional deficits, and increased risk for neuropsychiatric disease throughout the lifespan. These neurophenotypical changes are underlain by gene dysregulation in the brain that outlasts the period of ID; however, the mechanisms by which ID establishes and maintains gene expression changes are incompletely understood. The epigenetic modification 5-hydroxymethylcytosine (5hmC), or DNA hydroxymethylation, is one candidate mechanism because of its dependence on iron-containing TET enzymes. The aim of the present study was to determine the effect of fetal-neonatal ID on regional brain TET activity, Tet expression, and 5hmC in the developing rat hippocampus and cerebellum, and to determine whether changes are reversible with dietary iron treatment. Timed pregnant Sprague-Dawley rats were fed iron deficient diet (ID; 4 mg/kg Fe) from gestational day (G)2 to generate iron deficient anemic (IDA) offspring. Control dams were fed iron sufficient diet (IS; 200 mg/kg Fe). At postnatal day (P)7, a subset of ID-fed litters was randomized to IS diet, generating treated IDA (TIDA) offspring. At P15, hippocampus and cerebellum were isolated for subsequent analysis. TET activity was quantified by ELISA from nuclear proteins. Expression of Tet1, Tet2, and Tet3 was quantified by qPCR from total RNA. Global %5hmC was quantified by ELISA from genomic DNA. ID increased DNA hydroxymethylation (p=0.0105), with a corresponding increase in TET activity (p<0.0001) and Tet3 expression (p<0.0001) in the P15 hippocampus. In contrast, ID reduced TET activity (p=0.0016) in the P15 cerebellum, with minimal effect on DNA hydroxymethylation. Neonatal dietary iron treatment resulted in partial normalization of these changes in both brain regions. These results demonstrate that the TET/DNA hydroxymethylation system is disrupted by developmental ID in a brain region-specific manner. Differential regional disruption of this epigenetic system may contribute to the lasting neural circuit dysfunction and neurobehavioral dysfunction associated with developmental ID.

The Paediatric Iron Deficiency Assessment with Reticulocyte Haemoglobin Equivalent (Ret-He) in Comparison with Biochemical Markers of Serum Ferritin and Transferrin Saturation

Diagnosis of iron deficiency anaemia (IDA) is a challenge as the conventional methods often diagnose the disease at the later stage. Haemoglobin content of reticulocytes is useful to identify IDA at earlier stage. The objective of this study was to evaluate reticulocyte-haemoglobin equivalent (Ret-He) in diagnosing IDA in children and to compare it with other conventional methods. This prospective study was conducted on 120 paediatric patients aged 12 years and below, who attended Hospital Sultanah Aminah Johor Bahru, Malaysia with haemoglobin <12 g/dL. Ret-He and serum iron, ferritin and transferrin saturation were measured. Using a cut-off point of 20% for transferrin saturation, 81 out of 120 subjects (67.5%) were found as iron deficient. Based on the diagnosis of IDA, cut-off value for Ret-He using the Receiver Operating Characteristics (ROC) curve analysis was found as 22.65 pg. Ret-He showed a good sensitivity and specificity of 77.8% and 66.7%, respectively. As compared with Ret-He, serum ferritin showed a sensitivity of only 18.9%. However, a good specificity of 100% suggest it is useful for ruling in the disease but not suitable for screening. Transferrin saturation showed a good sensitivity and specificity, but it is biologically variable and not cost effective as a screening tool. Correlation study showed serum iron and transferrin saturation have significant positive correlation with Ret-He (r=0.415 to 0.518). However, there was no correlation between Ret-He and serum ferritin (r=0.051, p=0.578). This study shows that Ret-He at a cut-off point of 22.65 pg has a better sensitivity and potentially be useful as a screening tool in the paediatric population.

Nanostructured LaFeO3 /Si Thin Films Grown by Pulsed Laser Deposition

The orthorhombic LaFeO3 thin films grown by pulsed laser deposition on silicon showed nano-structuration of their surface and preferential crystallographic exposed facets, depending on the deposition temperature. The LaFeO3 film deposited at 850°C has two types of grain termination, flat or tip-like, corresponding to two different growth directions, respectively [110] and [200]. Due to the shape of the termination, the same {110} facets are exposed. The LaFeO3 is iron deficient and consequently contains oxygen vacancies, the exact chemical formula being LaFe0.82O3-delta.

Regulation and Functional Complexity of the Chlorophyll-Binding Protein IsiA

As the oldest known lineage of oxygen-releasing photosynthetic organisms, cyanobacteria play the key roles in helping shaping the ecology of Earth. Iron is an ideal transition metal for redox reactions in biological systems. Cyanobacteria frequently encounter iron deficiency due to the environmental oxidation of ferrous ions to ferric ions, which are highly insoluble at physiological pH. A series of responses, including architectural changes to the photosynthetic membranes, allow cyanobacteria to withstand this condition and maintain photosynthesis. Iron-stress-induced protein A (IsiA) is homologous to the cyanobacterial chlorophyll (Chl)-binding protein, photosystem II core antenna protein CP43. IsiA is the major Chl-containing protein in iron-starved cyanobacteria, binding up to 50% of the Chl in these cells, and this Chl can be released from IsiA for the reconstruction of photosystems during the recovery from iron limitation. The pigment–protein complex (CPVI-4) encoded by isiA was identified and found to be expressed under iron-deficient conditions nearly 30years ago. However, its precise function is unknown, partially due to its complex regulation; isiA expression is induced by various types of stresses and abnormal physiological states besides iron deficiency. Furthermore, IsiA forms a range of complexes that perform different functions. In this article, we describe progress in understanding the regulation and functions of IsiA based on laboratory research using model cyanobacteria.

Chemical genetic interactions of New Zealand bee products in Saccharomyces cerevisiae

<p>Propolis, bee venom and bee pollen all have been used by humans traditionally for various medicinal purposes. Studies of these products have been limited primarily to antimicrobial, antifungal, anticancer and free radical scavenging properties. The mechanisms of action of these products remain largely unknown. This study investigates the biological effects of propolis, bee venom and bee pollen using chemical genomics and the yeast model organism. These products are screened against genome-wide yeast mutant libraries to determine the genes, proteins, and pathways that are targets of these products. I identified that propolis chelates iron and consequently creates an iron-deficient condition, which results in the upregulation of plasma membrane and vacuolar high-affinity iron transporters to maximise iron acquisition. Bee venom inhibited the biosynthesis of phosphatidylcholine via Opi3p that catalyses the final two steps of phosphatidylcholine biosynthesis within the CDP-ethanolamine pathway. Bee pollen showed a potential effect on GDP-mannose transport in which the GDP-mannose transport mutants confer hypersensitivity against bee pollen treatment.</p>

Association of SNPs within TMPRSS6 and BMP2 genes with iron deficiency status in Saudi Arabia

Background Globally, iron-deficiency anemia (IDA) remains a major health obstacle. This health condition has been identified in 47% of pre-school students (aged 0 to 5 years), 42% of pregnant females, and 30% of non-pregnant females (aged 15 to 50 years) worldwide according to the WHO. Environmental and genetic factors play a crucial role in the development of IDA; genetic testing has revealed the association of a number of polymorphisms with iron status and serum ferritin. Aim The current study aims to reveal the association of TMPRSS6 rs141312 and BMP2 rs235756 with the iron status of females in Saudi Arabia. Methods A cohort of 108 female university students aged 18–25 years was randomly selected to participate: 50 healthy and 58 classified as iron deficient. A 3–5 mL sample of blood was collected from each one and analyzed based on hematological and biochemical iron status followed by genotyping by PCR. Results The genotype distribution of TMPRSS6 rs141312 was 8% (TT), 88% (TC) and 4% (CC) in the healthy group compared with 3.45% (TT), 89.66% (TC) and 6.89% (CC) in the iron-deficient group (P = 0.492), an insignificant difference in the allelic distribution. The genotype distribution of BMP2 rs235756 was 8% (TT), 90% (TC) and 2% (CC) in the healthy group compared with 3.45% (TT), 82.76% (TC) and 13.79% (CC) in iron-deficient group (P = 0.050) and was significantly associated with decreased ferritin status (P = 0.050). In addition, TMPRSS6 rs141312 is significantly (P<0.001) associated with dominant genotypes (TC+CC) and increased risk of IDA while BMP2 rs235756 is significantly (P<0.026) associated with recessive homozygote CC genotypes and increased risk of IDA. Conclusion Our finding potentially helps in the early prediction of iron deficiency in females through the genetic testing.

Chemical genetic interactions of New Zealand bee products in Saccharomyces cerevisiae

<p>Propolis, bee venom and bee pollen all have been used by humans traditionally for various medicinal purposes. Studies of these products have been limited primarily to antimicrobial, antifungal, anticancer and free radical scavenging properties. The mechanisms of action of these products remain largely unknown. This study investigates the biological effects of propolis, bee venom and bee pollen using chemical genomics and the yeast model organism. These products are screened against genome-wide yeast mutant libraries to determine the genes, proteins, and pathways that are targets of these products. I identified that propolis chelates iron and consequently creates an iron-deficient condition, which results in the upregulation of plasma membrane and vacuolar high-affinity iron transporters to maximise iron acquisition. Bee venom inhibited the biosynthesis of phosphatidylcholine via Opi3p that catalyses the final two steps of phosphatidylcholine biosynthesis within the CDP-ethanolamine pathway. Bee pollen showed a potential effect on GDP-mannose transport in which the GDP-mannose transport mutants confer hypersensitivity against bee pollen treatment.</p>

Iron deficiency and high-intensity running interval training do not impact femoral or tibial bone in young female rats

In the US, as many as 20% of recruits sustain stress fractures during basic training. In addition, approximately one-third of female recruits develop iron deficiency upon completion of training. Iron is a cofactor in bone collagen formation and vitamin D activation, thus we hypothesized iron deficiency may be contributing to altered bone microarchitecture and mechanics during 12-weeks of increased mechanical loading. Three-week old female Sprague Dawley rats were assigned to one of four groups: iron adequate sedentary, iron deficient sedentary, iron adequate exercise, and iron deficient exercise. Exercise consisted of high-intensity treadmill running (54 min 3×/week). After 12-weeks, serum bone turnover markers, femoral geometry and microarchitecture, mechanical properties and fracture toughness, and tibiae mineral composition and morphometry were measured. Iron deficiency increased the bone resorption markers C-terminal telopeptide type I collagen and tartate-resistant acid phosphatase 5b (TRAcP 5b). In exercised rats, iron deficiency further increased bone TRAcP 5b, while in iron adequate rats, exercise increased the bone formation marker procollagen type I N-terminal propeptide. In the femur, exercise increased cortical thickness and maximum load. In the tibia, iron deficiency increased the rate of bone formation, mineral apposition, and zinc content. These data show that the femur and tibia structure and mechanical properties are not negatively impacted by iron deficiency despite a decrease in tibiae iron content and increase in serum bone resorption markers during 12-weeks of high-intensity running in young growing female rats.

Impact of Spirulina corn soy blend on Iron deficient children aged 6–23 months in Ndhiwa Sub-County Kenya: a randomized controlled trial

Background Iron deficiency anemia (IDA) remains high in Kenya despite interventions. Twenty-seven percent of children aged 6 months-14 years are anemic, with low iron intake (7%) among children aged 6–23 months. Standard food interventions involve a corn soy blend (CSB), which is limited in micronutrients, and fortifiers are not accessible locally. Moreover, the use of spirulina as a strategy for mitigating IDA has not been adequately documented. This study compared the impact of a spirulina corn soy blend (SCSB) on IDA among children aged 6–23 months. Methods A total of 240 children with IDA were randomly assigned to study groups at a ratio of 1:1:1 through lotteries, and caregivers and research assistants were blinded to group assignment. Dry-take-home SCSB, CSB and placebo flour (1.7 kg) was given to caregivers to prepare porridges using a flour water ratio of 1:4, producing 600 ml–700 ml of porridge to feed children 200 ml of porridge three times a day for 6 months. Impact was assessed as plasma hematocrit at baseline and after the study. Blood drawing, preparation and analysis were performed in accordance with approved procedures by the EthicsResearchCommittee. Monthly follow-up and data collection on dietary intake, anthropometry, morbidity and infant feeding practices were performed using questionnaires. Relative risk, magnitude of change and log-rank tests were used to compare the impact of the intervention, and significant differences were determined at P < 0.05. Results The survival probabilities for children consuming SCSB were significantly higher than those consuming CSB (log-rank-X2 = 0.978; CI: 0.954–1.033, P = 0.001) and the placebo (log-rankX2 = 0.971; CI: 0.943–0.984, P = 0.0001). Children consuming SCSB had a mean recovery time of 8 days (CI: 7–12 days) compared to those consuming CSB (19 days; CI: 20–23 days) and placebo (33 days; CI: 3 1–35 days). The recovery rate was 15.4 per 100 persons per day for children who consumed SCSB as opposed to 4.6 and 1.8 per 100 persons per day for those who consumed CSB and the placebo, respectively. Conclusion Management of IDA with SCSB compared to CSB and the placebo led to faster reversal and large numbers of recoveries from IDA. The recovery rates were above the World Health Organizations (WHO) minimums standards for food interventions. Efforts to realize high and faster recoveries from IDA should be heightened by fortifying CSB with spirulina powder.