Iron Status Research Articles

In-Gel Activity Assay of Mammalian Mitochondrial and Cytosolic Aconitases, Surrogate Markers of Compartment-Specific Oxidative Stress and Iron Status.

Two aconitase isoforms are present in mammalian cells: the mitochondrial aconitase (ACO2) that catalyzes the reversible isomerization of citrate to isocitrate in the citric acid cycle, and the bifunctional cytosolic enzyme (ACO1), which also plays a role as an RNA-binding protein in the regulation of intracellular iron metabolism. Aconitase activities in the different subcellular compartments can be selectively inactivated by different genetic defects, iron depletion, and oxidative or nitrative stress. Aconitase contains a [4Fe-4S]2+ cluster that is essential for substrate coordination and catalysis. Many Fe-S clusters are sensitive to oxidative stress, nitrative stress, and reduced iron availability, which forms the basis of redox- and iron-mediated regulation of intermediary metabolism via aconitase and other Fe-S cluster-containing metabolic enzymes, such as succinate dehydrogenase. As such, ACO1 and ACO2 activities can serve as compartment-specific surrogate markers of oxygen levels, reactive oxygen species (ROS), reactive nitrogen species (RNS), iron bioavailability, and the status of intermediary and iron metabolism. Here, we provide a protocol describing a non-denaturing polyacrylamide gel electrophoresis (PAGE)-based procedure that has been successfully used to monitor ACO1 and ACO2 aconitase activities simultaneously in human and mouse cells and tissues. Key features • Monitoring aconitase activity changes in the mitochondria and cytosol simultaneously in response to oxidative or nitrative stress, iron depletion, and various pathophysiological conditions. • Optimized for human and mouse cell lines and tissue samples. • Semi-quantitative detection of aconitase isoforms with different states of phosphorylation and/or post-translational modification.

Sleeve gastrectomy plus single anastomosis sleeve ileal bipartition versus sleeve gastrectomy alone: The role of bipartition.

Sleeve gastrectomy (SG) with single anastomosis sleeve ileal bipartition (SASI) is a novel procedure for increasing the anti-metabolic efficacy of SG in severely people with obesity. This study aimed to compare 1-year results between SASI and SG, thereby assessing the role of bipartition. The study was conducted at the Medical University hospital. Between November 2021 and December 2022, 39 patients received an SG + SASI surgery, a total of 35 patients completed 1-year follow-up after the surgery. They were matched with a group of 70 patients with SG that were equal in age, sex, and body mass index (BMI). Operative risk, weight loss, and remission of comorbidities were evaluated after 12 months. The operation time of the SASI group was significantly longer than the SG group (140.3 ± 22.8 vs. 114.9 ± 21.6 min; p < .001). At 12 months after surgery, the SASI group had better weight loss (total weight loss: 37.0% vs. 29.7%; p = .001) and achieved a lower BMI than SG (23.4 ± 2.6 kg/m2 vs. 24.6 ± 2.9 kg/m2; p = .046). Reduction of A1C and remission of T2D was greater in the SASI group. The SASI group had a higher reduction in uric acid, low-density lipoprotein, total cholesterol, and triglyceride levels after operation than the SG group. However, the SG group is superior to the SASI group in mean corpuscular volume, calcium, and iron levels. In this study, adding an ileum bipartition to SG increases the weight loss, glycemic, and blood lipid control of SG only.

Iron deficiency and diastolic function in heart failure with preserved ejection fraction

Background. Despite the high prevalence of iron deficiency (ID) in heart failure with preserved ejection fraction (HFpEF), relationship between iron status indicators with the presence of the disease and parameters of diastolic function and myocardial strain have been insufficiently studied.Aim: To evaluate association of iron status indicators with the disease and parameters of diastolic function and myocardial strain in HFpEF patients.Material and Methods. According to diastolic stress test (DST) 67 patients with EF &gt; 50% (65.8 ± 5.5 years) were divided into 2 groups: Gr.1 with HFpEF (n = 41), Gr.2 without HFpEF (n = 26). Parameters of diastolic function, left atrial reservoir strain (LASr), global longitudinal strain (GLS), diastolic reserve as per DST, serum iron (Fe), ferritin, iron transferrin saturation coefficient (ITSC) , hemoglobin (Hb), N-terminal pro B-type natriuretic peptide (NT-proBNP), C-reactive protein (CRP), creatinine, estimated glomerular filtration rate (eGFR) were assessed. Spearman method was used to study the relationships between iron status indicators and parameters of diastolic function, LASr, GLS; the cut-off point for ITSC was found by ROC analysis; factors associated with HFpEF were assessed via regression analysis.Results. In group 1, FCII (NYHA) was revealed more frequent with trends to greater prevalence in women, obesity, higher values of peak E, NT-proBNP, CRP &gt; 3.0 mg/ml, lower values of E/e΄, LASr, Hb, ITSC. As per DST, differences between groups in all variables related elevation left ventricular filling pressure were registered; supreme load and heart rate were lowest in Gr1. Anemia was detected in 6 (9%) patients: 5 (12.2%) vs 1 (3.8%), respectively, p = 0.238; Iron deficiency in 27(40.3%): 18 (43.9%) vs 9 (34.6%), p = 0.157. Correlations were defined between Fe and ITSC with supreme load with DST and diastolic function parameters, but not with LASr and GLS. New cut-off point for ITSC = 29.2% (AUC = 0.699, p = 0.009; sensitivity = 71%, specificity = 69%) associated with HFpEF risk (OR 5.029 95% CI 1.575–16.055; p = 0.006) was revealed.Conclusion: Regardless of HFpEF, ID prevailed in patients aged over 60 years old, which determined the necessity of its screening study for the purpose of timely correction. Association between ITSC reduction less than 29.2% and the disease presence was found: risk of having HFpEF concurrently increased by five times. Interactions were registered between Fe and ITSC with supreme load and diastolic function parameters, but not with LASr and GLS. Higher incidence of CRP &gt; 3.0 mg/ml with HFpEF confirmed pro-inflammatory status of the disease.

Influence of Biological Sex and Congenital Iron Deficiency on Neonatal Cytokine Responses.

Stimulated cord blood mononuclear cell (CBMC) cytokine responses were previously shown to predict the risk of childhood atopic disease. Iron deficiency (ID) at birth may also program atopic disease. Males are at a higher risk of pediatric atopic disease, but it is not known whether congenital ID impacts CBMC immune responses differentially by sex. Cord blood (CB) samples were collected from healthy term or near-term neonates after elective cesarean deliveries. A transferrin saturation ≤ 25% defined congenital ID. CBMCs were stimulated with either phytohemagglutinin (PHA) or PHA plus an iron chelator. Of the 85 neonates, the 26 neonates with congenital ID exhibited lower plasma tumor necrosis factor-α (TNF-α), as well as higher CBMC TNF-α and IL-8 responses than iron-sufficient neonates (p = 0.017, p = 0.013, and p = 0.007, respectively). Higher CBMC TNF-α responses were seen in both males and females with congenital ID. However, females with congenital ID also had lower plasma IL-6, lower plasma TNF-α, and higher CBMC interleukin (IL)-8 responses. Additionally, iron chelation during culture influenced stimulated CBMC IFN-γ and CBMC TNF-α responses. Congenital ID may influence stimulated CBMC cytokine responses, but results point to a sex-specific regulation of immune balance at birth. Because males are more prone to infantile ID and more likely to develop early childhood asthma, future studies should further investigate how fetal sex and congenital iron status impacts childhood immune responsiveness to infections and antigenic stimulation from the rearing environment.

Enhancing Lettuce (Lactuca sativa) Productivity: Foliar Sprayed Fe-Alg-CaCO3 MPs as Fertilizers for Aquaponics Cultivation.

Aquaponics is an innovative agricultural method combining aquaculture and hydroponics. However, this balance can lead to the gradual depletion of essential micronutrients, particularly iron. Over time, decreasing iron levels can negatively impact plant health and productivity, making the monitoring and management of iron in aquaponic systems vital. This study investigates the use of Fe-Alg-CaCO3 microparticles (MPs) as foliar fertilizer on lettuce plants in an aquaponic system. The research investigated Lactuca sativa L. cv. Foglia di Quercia Verde plants as the experimental cultivar. Three iron concentrations (10, 50, and 250 ppm) were tested, with 15 plants per treatment group, plus a control group receiving only sterile double-distilled water. The Fe-Alg-CaCO3 MPs and ultrapure water were applied directly to the leaves using a specialized nebulizer. Foliar nebulization was chosen for its precision and minimal resource use, aligning with the sustainability goals of aquaponic cultivation. The research evaluated rosette diameter, root length, fresh weight, soluble solids concentration, levels of photosynthetic pigments, and phenolic and flavonoid content. The 250 ppm treatment produced the most notable enhancements in both biomass yield and quality, highlighting the potential of precision fertilizers to boost sustainability and efficiency in aquaponic systems. In fact, the most significant increases involved biomass production, particularly in the edible portions, along with photosynthetic pigment levels. Additionally, the analysis of secondary metabolite content, such as phenols and flavonoids, revealed no reduction compared to the control group, meaning that the proposed fertilizer did not negatively impact the biosynthetic pathways of these bioactive compounds. This study opens new possibilities in aquaponics cultivation, highlighting the potential of precision fertilizers to enhance sustainability and productivity in soilless agriculture.

Using magnetic resonance relaxometry to evaluate the safety and quality of induced pluripotent stem cell-derived spinal cord progenitor cells

BackgroundThe emergence of induced pluripotent stem cells (iPSCs) offers a promising approach for replacing damaged neurons and glial cells, particularly in spinal cord injuries (SCI). Despite its merits, iPSC differentiation into spinal cord progenitor cells (SCPCs) is variable, necessitating reliable assessment of differentiation and validation of cell quality and safety. Phenotyping is often performed via label-based methods including immunofluorescent staining or flow cytometry analysis. These approaches are often expensive, laborious, time-consuming, destructive, and severely limits their use in large scale cell therapy manufacturing settings. On the other hand, cellular biophysical properties have demonstrated a strong correlation to cell state, quality and functionality and can be measured with ingenious label-free technologies in a rapid and non-destructive manner.MethodIn this study, we report the use of Magnetic Resonance Relaxometry (MRR), a rapid and label-free method that indicates iron levels based on its readout (T2). Briefly, we differentiated human iPSCs into SCPCs and compared key iPSC and SCPC cellular markers to their intracellular iron content (Fe3+) at different stages of the differentiation process.ResultsWith MRR, we found that intracellular iron of iPSCs and SCPCs were distinctively different allowing us to accurately reflect varying levels of residual undifferentiated iPSCs (i.e., OCT4+ cells) in any given population of SCPCs. MRR was also able to predict Day 10 SCPC OCT4 levels from Day 1 undifferentiated iPSC T2 values and identified poorly differentiated SCPCs with lower T2, indicative of lower neural progenitor (SOX1) and stem cell (Nestin) marker expression levels. Lastly, MRR was able to provide predictive indications for the extent of differentiation to Day 28 spinal cord motor neurons (ISL-1/SMI-32) based on the T2 values of Day 10 SCPCs.ConclusionMRR measurements of iPSCs and SCPCs has clearly indicated its capabilities to identify and quantify key phenotypes of iPSCs and SCPCs for end-point validation of safety and quality parameters. Thus, our technology provides a rapid label-free method to determine critical quality attributes in iPSC-derived progenies and is ideally suited as a quality control tool in cell therapy manufacturing.

Relationship Between Whole Blood Iron Levels and Lipid Profile Parameters in the General Population: Findings from Routine Physical Examination Report.

Dyslipidemia is related to the occurrence and development of many diseases and is a common problem among the general population. A significant link has been identified between dyslipidemia and ferroptosis. Lipid profile parameters are important indicators of dyslipidemia. Iron is the main cause of ferroptosis. However, the relationship between blood lipid parameters and whole blood iron levels has remained unclear. Based on a community population, the study aimed to explore the relationship between whole blood iron levels and blood lipids in Taizhou, China. The blood samples were collected from 1917 community residents, and levels of total cholesterol, triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and whole blood iron were measured. Pearson correlation was used to analyze the correlation between whole blood iron levels and lipids profile parameters. The results of the study showed that for both men and women, whole blood iron concentration was positively correlated with total cholesterol, triglycerides, and low-density lipoprotein cholesterol (P < 0.001), but not with high-density lipoprotein cholesterol (P = 0.618, P = 0.083). The positive correlation between whole blood iron and triglycerides was the most significant (P < 0.001, r = 0.138). The above trends were more pronounced among men than among women. Therefore, the study suggested that regulating whole blood iron levels of populations in Taizhou, China, may be a potential strategy for regulating triglycerides, total cholesterol, and low-density lipoprotein. The potential for controlling triglycerides by regulating whole blood iron is more apparent. The result of the study has some implications for the prevention and diagnosis of dyslipidemia among medical staff and residents, especially male residents.

A Review of the Association Between Dietary Intake and Brain Iron Levels in Older Adults: Preliminary Findings and Future Directions.

Background/Objectives: Non-heme iron is essential for critical neuronal functions such as ATP generation, synaptogenesis, neurotransmitter synthesis, and myelin formation. However, as non-heme iron accumulates with age, excessive levels can contribute to oxidative stress, potentially disrupting neuronal integrity and contributing to cognitive decline. Despite growing evidence linking high brain iron with poorer cognitive performance, there are currently no proven methods to reduce brain iron accumulation in aging or to protect cognitive function from iron's negative effects. Recent studies suggest that nutrition may influence brain iron levels, though the evidence remains limited and mixed. Methods: In this review, we explore recent findings, including our own cross-sectional and longitudinal studies, to evaluate the potential effectiveness of healthy diets and specific nutrients in mitigating brain iron accumulation during aging. We also briefly assess the roles of age and gender as factors in the relationship between dietary factors and brain iron load. Results: The limited findings in the literature indicate that dietary choices may impact brain iron levels. In particular, nutrients such as vitamins, antioxidants, iron-chelators, and polyunsaturated fatty acids may slow brain iron accumulation in older adults. Conclusions: Our review highlights the multiple gaps in current knowledge and underscores a critical need for additional research on this important topic.

Association between serum iron status and the risk of colorectal cancer in US adults: a cross-sectional analysis of NHANES 2001–2020

BackgroundMaintaining iron homeostasis is crucial for preventing the development of colorectal cancer (CRC). However, Evidence regarding the correlation between serum iron status and CRC has been inconsistent. This population-based study aims to explore the potential association between serum iron status and CRC risk.MethodsUsing data from the National Health and Nutrition Examination Survey (NHANES) registry spanning from 2001 to 2020, a cross-sectional study involving 9504 participants was performed to assess the relationship between serum iron status and CRC risk. The study encompassed men and women of various racial backgrounds, aged 20 to 80, from across the United States. Participants’ characteristics were presented using mean or proportion. The possible risk factor for CRC was examined using both univariable and multivariable analysis. A logistic regression model was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) of CRC in accordance with each quantile increment in serum iron item levels.ResultsAfter making full adjustment, our analysis did not reveal a statistically significant association between serum iron, ferritin, transferrin saturation (TSAT), total iron-binding capacity (TIBC) and the risk of CRC. While there was no statistically significant difference observed, an increasing ferritin concentration appeared to be associated with a decreased CRC risk when compared to the lowest quantile. Specifically, the ORs and 95% CIs for the second, third, and fourth quantiles (Q2, Q3, and Q4) versus the lowest quantile (Q1) were as follows: Q2 (vs. Q1) OR 0.403, 95% CI 0.063–2.568; Q3 (vs. Q1) OR 0.316, 95% CI 0.059–1.687; Q4 (vs. Q1) OR 0.250, 95% CI 0.050–1.258. However, this trend did not reach statistical significance (P for trend = 0.381).ConclusionOur analyze did not demonstrate a statistically significant correlation between serum iron status and the risk of CRC.

Detection of PD-L1 expression levels in malignant pleural mesothelioma with a targeted MRI nanoprobe in vivo.

Immune checkpoint inhibitors (ICIs) have demonstrated potential in inhibiting the growth of malignant pleural mesothelioma (MPM), and their efficacy is associated with the expression of programmed death-ligand 1(PD-L1). This study evaluated a PD-L1-targeted nanoprobe for detecting PD-L1 expression in a nude mouse model of malignant pleural mesothelioma (MPM). A PD-L1-binding peptide (WL-12) was conjugated with superparamagnetic iron oxide nanoparticles (SPIONs) to create the nanoprobe WL-12@Fe₃O₄. The nanoprobe's stability, biotoxicity, targeting ability, and in vivo magnetic resonance (MR) imaging effects were assessed and compared to non-targeted Fe₃O₄ nanoparticles. ΔT2 values and PD-L1 expression were measured in H226 and MSTO-211H tumor tissues over 4 weeks to analyze correlations. The WL-12@Fe₃O₄ nanoprobe demonstrated uniform distribution and a spherical shape, with a larger size (43.82nm) and lower surface potential (-9.34 ± 0.54mV) compared to Fe₃O₄ (32.67nm, -20.20 ± 0.88mV, P < 0.05). The XPS and FT-IR analysis results indicate the successful coupling of WL-12 with Fe3O4. It was well dispersed in serum and saline and showed no cytotoxicity or organ damage in vivo. The probe selectively accumulated in PD-L1-expressing MPM cells, especially MSTO-211H, and exhibited significantly higher uptake in high PD-L1-expressing H460 cells (930.22 ± 11.75ng/mL) compared to low PD-L1-expressing A549 cells (254.89 ± 17.33ng/mL, P < 0.05). Tumor iron levels in the WL-12@Fe₃O₄ group were significantly elevated (141.02 ± 17.33μg/g) compared to controls (36.43 ± 3.56μg/g, P < 0.05), with no significant differences in other organs (P > 0.05). The T2 values of H226 and MSTO-211H tumors decreased after probe injection, with ΔT2 values significantly higher in the targeted group than the nontargeted group (P < 0.05). ΔT2 values increased over 4weeks, correlating strongly with PD-L1 expression (P < 0.05). The PD-L1-targeted nanoprobe with MRI is a promising tool for noninvasive, real-time assessment of PD-L1 expression in MPM.

Effect of iron status on myocardial infarction: A two-sample mendelian randomization study

BackgroundIn observational studies, connections have been identified between iron status and myocardial infarction (MI). The significance of changes in iron status as either a risk factor or a result of MI remains unclear. MethodsWe obtained our instrumental variables from a meta-analysis of three GWASs in Iceland, the UK, and Denmark, which discovered 62 independent sequence variants across 56 loci linked to blood iron levels, ferritin, total iron binding capacity (TIBC), transferrin saturation (TSAT), and the Genetics of Iron Status (GIS) database for transferrin. To evaluate the connection between iron status markers and myocardial infarction (MI), we used three GWAS datasets focused on MI outcomes. The chosen datasets included one representing the European population (ebi-a-GCST011364: n case=14,825, n control=380,970; finn-b-I9_MI: n case=12,801, n control=187,840) and another with a mixed population (ieu-a-798: n case=43,676, n control=128,199). The primary method used in our study was inverse variance-weighting, while we also assessed heterogeneity and horizontal pleiotropy to enhance the robustness of our findings. ResultsThe main analysis with the inverse variance-weighted method showed no significant impact of iron marker levels on MI risk in the ebi-a-GCST011364 and finn-b-I9-MI cohorts. In contrast, the ieu-a-798 cohort indicated that higher ferritin levels had a protective effect against MI (OR = 0.87, 95% CI 0.78-0.98, P=0.03). Additionally, TSAT showed an association with decreased MI risk (OR = 0.91, 95% CI 0.84-0.98, P=0.01). No significant correlations were observed for other iron status traits examined in this study. Evaluations of horizontal pleiotropy and heterogeneity showed no abnormalities, further strengthening the reliability of our results. ConclusionsOur multi-cohort MR analysis suggests a potential protective effect of higher ferritin levels and TSAT against MI risk. These findings contribute to our understanding of the relationship between iron status markers and cardiovascular health, offering insights for future research and potential therapeutic interventions.

Elevated iron levels in the older adult brain are associated with higher R2 relaxation rate in gray matter and more white matter hyperintensities: An ex‐vivo MRI, pathology and mass spectrometry study

AbstractBackgroundElevated iron in brain is a source of free radicals that causes oxidative stress which has been linked to neuropathologies and cognitive impairment among older adults. The aim of this study was to investigate the association of iron levels with transverse relaxation rate, R2, and white matter hyperintensities (WMH), independent of the effects of other metals and age‐related neuropathologies.MethodCerebral hemispheres from 437 older adults participating in the Rush Memory and Aging Project study (Table 1) were imaged ex‐vivo using 3T MRI scanners. R2 maps were generated from multi‐echo spin‐echo data and then registered to an ex‐vivo brain template. WMH were segmented based on T2‐weighted images. WMH volume was normalized by the total hemisphere volume and then log‐transformed. Following ex‐vivo MRI, all hemispheres underwent neuropathologic assessment including Aß plaques, neurofibrillary tangles, LATE‐NC, hippocampal sclerosis, Lewy bodies, cerebral amyloid angiopathy, gross infarcts, microscopic infarcts, atherosclerosis, and arteriolosclerosis (Table 1). Inductively coupled plasma mass spectrometry was used to measure brain trace metal levels. The assessed metals included iron, boron, titanium, manganese, copper, zinc, selenium, rubidium, molybdenum, and mercury (Table 1). Linear regression was used to test the association of R2 and WMH burden with iron levels. All models were controlled for all other metals and neuropathologies listed above, demographics (age at death, sex, years of education), the presence of the APOE‐e4 allele, postmortem interval to fixation and to imaging, and scanner. Statistical analysis was performed using PALM, with tail‐accelerated 5,000 permutations. Statistical significance was set at p&lt;0.05 after family wise error rate correction.ResultThe voxel‐wise analysis revealed a spatial pattern of higher R2 for higher iron levels, particularly in gray matter (Fig. 1). The pattern included basal ganglia structures such as the globus pallidus and putamen, and cortical regions including the precentral, postcentral and cuneus cortex (Fig. 1). Higher lobar and total WMH burden were also associated with higher iron levels (Fig. 2). No negative associations were observed.ConclusionThis investigation combined ex‐vivo MRI, neuropathology and mass spectrometry in a community‐based older adults and showed that higher iron levels were independently associated with higher R2 in gray matter and higher WMH burden.

Postpartum maternal and infant haematological effects of second-trimester ferric carboxymaltose versus standard-of-care oral iron in Malawi: longitudinal follow-up of a randomised controlled trial

Anaemia is common in mothers and infants in the first year postpartum, especially in sub-Saharan Africa. We evaluated whether treating anaemia in the second trimester of pregnancy with a single dose of intravenous iron, ferric carboxymaltose, compared with standard-of-care oral iron could alleviate anaemia in postpartum women and their infants. REVAMP (ACTRN12618001268235), an open-label, individually randomised, controlled trial done across nine urban and five rural health centres in Malawi, recruited women if they were in the second trimester of singleton pregnancy, had a capillary haemoglobin concentration of less than 10·0 g/dL, and had a negative malaria rapid diagnostic test. Once enrolled, women were randomly assigned (1:1) to receive intravenous ferric carboxymaltose (20 mg/kg up to 1000 mg) or standard of care (60 mg oral elemental iron twice daily for 90 days); all women received preventive malaria treatment. The primary endpoint of REVAMP was anaemia prevalence at 36 weeks of gestation, with follow-up of mothers and infants until 1 month postpartum. In REVAMP-EXTENDED, women from REVAMP who gave consent, and their infants, were followed up at 3, 6, 9, and 12 months postpartum, and venous blood was collected for haemoglobin, ferritin, and C-reactive protein measurement. Maternal postpartum outcomes comprised prevalence of anaemia (venous haemoglobin concentration <11 g/dL up to and including delivery and <12·0 g/dL postpartum) and haemoglobin concentration, as well as iron status (iron deficiency, defined as serum ferritin <15 μg/L, or <30 μg/L if C-reactive protein >5 mg/L, and iron deficiency anaemia [both iron deficiency and anaemia]). Infant outcomes comprised cord ferritin concentration, and haemoglobin and ferritin concentrations at 1, 3, 6, 9, and 12 months of age. Between Nov 12, 2018, and March 2, 2021, 862 women were randomly assigned in REVAMP, of whom 793 (393 in the ferric carboxymaltose group [376 liveborn infants] and 400 [379 liveborn infants] in the standard-of-care group) provided consent for REVAMP-EXTENDED. At 12 months postpartum, ferritin concentrations were higher (geometric mean ratio 1·47 [95% CI 1·29-1·66], p<0·0001), and prevalence of iron deficiency was lower (prevalence ratio 0·65 [0·48-0·88], p=0·0050), in mothers receiving ferric carboxymaltose than in those receiving standard of care. Anaemia was less common in women who received ferric carboxymaltose than in those who received standard of care at 1 month (prevalence ratio 0·84 [95% CI 0·71-0·98], p=0·027), 3 months (0·75 [0·62-0·91], p=0·0029), and 6 months (0·78 [0·63-0·96], p=0·018) postpartum but not thereafter. There was no evidence of a difference between groups regarding cord ferritin, infant ferritin, or infant haemoglobin concentrations at any timepoint. Benefits on postpartum anaemia were restricted to mothers with baseline iron deficiency. Ferric carboxymaltose treatment in the second trimester protected women from postpartum anaemia and iron deficiency but did not affect infant haematological or iron status. Bill & Melinda Gates Foundation. For the Chichewa translation of the abstract see Supplementary Materials section.

Cefiderocol has immunoregulative effects in LPS-induced vitro experimental model via inhibiting inflammation and ferroptosis

BackgroundCefiderocol is a new catecholamine-containing siderophore cephalosporin. It, however, remains unclear how cefiderocol modulates the immune response of the host. ObjectivesThis study elucidated whether cefiderocol exerts immunoprotective effects in an in vitro experimental model induced with lipopolysaccharide (LPS). MethodsMouse macrophage RAW 264.7 cells were exposed to LPS (100 ng/mL) or LPS + cefiderocol (40 mg/L) to assess the immunomodulatory effect of cefiderocol in vitro. ELISA was performed on cell culture supernatants to estimate cytokine levels. Ferroptosis level was also quantified by detecting intracellular reactive oxygen species (ROS) and iron levels through flow cytometry analysis. Malondialdehyde (MDA) and glutathione (GSH) levels were estimated by ELISA. We conducted western blotting assay for evaluating key ferroptosis pathway proteins. ResultsCefiderocol alleviated LPS-induced inflammation by reducing IL-6, TNF-α, and IL-1β production levels and enhancing the IL-10 production level. Further analysis to determine the underlying mechanism revealed that cefiderocol inhibited ferroptosis; this was confirmed by reduced ROS, MDA, and Fe2+ ion levels; increased GSH levels; upregulated expression of solute carrier family 7 member 11, glutathione peroxidase 4, nuclear factor erythroid 2-related factor 2, and ferroptosis suppressor protein 1; and downregulated expression of acyl-CoA synthetase long-chain family member 4. ConclusionsCefiderocol may play a key role in reducing inflammation by decreasing inflammatory cytokine release and suppressing ferroptosis.

Iron regulatory protein 1-deficient mice exhibit hypospermatogenesis.

Imbalances in testicular iron levels are linked to compromised sperm production and male infertility. Iron regulatory proteins (IRP) 1 and 2 play crucial roles in cellular iron regulation. We investigated the role of IRP1 on spermatogenesis using Irp1-deficient mice (Irp1-/-). Histological analysis of the testis of Irp1-/- mice revealed hypospermatogenesis with a significant reduction in the number of elongated spermatids and daily sperm production compared to wild-type (WT) mice. Flow cytometry of germ cells from WT and Irp1-/- mice showed reduction in spermatocytes and round and elongated spermatids in Irp1-/- mice, which was confirmed by histological and immunofluorescence quantification. Finally, stage VIII of spermatogenesis, crucial for spermatid maturation, was less frequent in Irp1-/- testicular cross-sections. Hypospermatogenesis worsened with age despite unchanged intratesticular iron levels. Mechanistically, this was due to increased oxidative stress indicated by elevated 8-Oxoguanine (8-OxoG) levels, a DNA lesion resulting from reactive oxygen species (ROS). Furthermore, bulk RNA-seq data indicated compromised DNA damage repair and cell cycle processes, including mitosis and meiosis in Irp1-/- mice, which may explain hypospermatogenesis. Our results suggest that IRP1 deletion leads to hypospermatogenesis due to impaired cell cycle progression, decreased DNA damage repair capacity, and oxidative damage. Altogether, this study uncovers a role for IRP1, independent of traditional mechanisms of iron regulation.

Short- and long-term alterations of hematopoietic cell lineages in rats with congenital iron deficiency.

Data support that fetal iron delivery is prioritized to hemoglobin in erythrocytes (RBC). Iron deficiency (ID) during pregnancy can cause congenital ID, i.e., low fetal iron acquisition. Because how congenital ID impacts other fetal hematopoietic cell lineages is unknown our pilot study examined this in a rat congenital ID model. Pregnant dams fed ID diets were compared to iron sufficient (IS) controls. Iron indices, complete cell counts with differentials, and microscopic morphology were studied at birth P2-3, mid-recovery P15 and adolescent post-recovery P45. Compared to IS at birth, ID rats exhibited 350% higher zinc protoporphyrin/heme, 70% lower plasma ferritin, 30% lower hemoglobin, 25% fewer platelets, but nucleated RBC (nRBC) and reticulocytes did not differ. Compared to IS at birth, ID rats exhibited 36% fewer white counts (WBC) but proportionate lymphocytes and granulocytes (all P<0.015). Compared to IS at P45, RBC, platelets, and WBC numbers did not differ, but lymphocytes were relatively lower in ID (P<0.01). Microscopic morphology differed from IS in ID, with persistent differences at P45. Because altered inflammatory programming was previously reported in congenital ID and because this pilot study found altered WBC populations, this model of congenital ID is well situated to investigate long-term developmental programming.

Heavy Metals in Water and Sediments and Their Impact on Water Quality in Andean Micro-watersheds: A Study of the Colorado and Alajua Rivers in the Ambato River Watershed, Tungurahua, Ecuador

The present study aims to characterize the water and sediment quality of the Colorado and Alajua rivers within Ecuador’s Ambato River watershed, with a specific focus on the presence of heavy metals. Measurements were conducted at five sampling points along the upper and lower zones of each river, where both physicochemical and microbiological parameters, as well as concentrations of heavy metals in water and sediments, were analyzed. Most parameters exhibited statistically significant differences, as determined by the analysis of variance (ANOVA), between the values observed in the upper and lower zones of the micro-watersheds. Water quality in the mentioned rivers was assessed using specific water quality indices, WQI, namely the NSF-WQI and Dinius WQI. Additionally, the impact of heavy metal presence in the water and sediments was evaluated using the Heavy Metal Evaluation Index (HEI). While most parameters met the Ecuadorian quality standards for water sources intended for human consumption, concerns emerged regarding elevated levels of total and fecal coliforms along both rivers, which could limit the suitability of these rivers as a water source for human use and consumption. At various sampling points, water quality criteria for the preservation of aquatic life were not met for several heavy metals. For example, the Colorado River exhibited elevated levels of zinc (59-76 μg.L-1), copper (12-47 μg.L-1), lead (1.2-3.9 μg.L-1 ), iron (0.33-0.37 mg.L-1 ), and manganese (0.37-0.47 mg.L-1), while the Alajua River showed excess copper (11 μg.L-1), iron (0.61-0.72 mg.L-1), and manganese (0.62-0.98 mg.L-1). Geological factors likely contribute to the concentration of heavy metals in the upper segments of the rivers, while agricultural runoff may contribute to concentrations in the lower segments. Sediments exhibited higher average values of the Heavy Metal Evaluation Index (HEI) (20.6-26.7) compared to water samples (13.9-15.4), indicating a potential accumulation of heavy metals in the river sediments. Overall, both rivers exhibited contamination levels ranging from regular to moderate, as indicated by the calculated average Water Quality Indices (WQI), with certain areas showing slight contamination or meeting acceptable standards. These results highlight the influence of anthropogenic activities on water quality, emphasizing the necessity of continuous monitoring to assess and control their impact.

Village-level Processing of Pangi (Pangium edule Reinw.) Seeds by the Obu Manuvu Improves the Edibility and Level of Some Nutritional Factors [RESEARCH NOTE

Pangi (Pangium edule Reinw) seed is known to be a poisonous material. However, it becomes safe for consumption after processing. This study determined the effect of village-level processing by the Obu Manuvu community of Marilog District, Davao City, Philippines on the antinutrient and nutritional composition of Pangi seeds. Processing methods involved washing with running water for about 15 s, boiling in water for 30 min, and soaking in flowing water in a nearby river overnight. Results showed that after processing, the levels of antinutrients such as cyanogenic glycosides and oxalates were reduced significantly (p &lt; 0.05) by 99.15% and 78.23%, respectively. Further, the tannin content was also significantly reduced by 96.15%. The crude fat content significantly increased (p &lt; 0.05) by about 54%. Crude ash and fiber decreased, while protein did not change significantly (p &lt; 0.05). Minerals such as calcium and zinc increased (p &lt; 0.05) by 221.43% and 64.39%, respectively while the iron and manganese levels remained unaffected. Findings of the study suggested that the processing method by the Obu Manuvu effectively reduces the level of antinutrients, thereby improving the edibility and safety of Pangi seeds. Further, the processing method improves the level of some nutrients, specifically crude fat, calcium, and zinc.

Accumulation of Toxic Elements in Fish from Ohrid Lake Under the Influence of Anthropogenic Activities

Abstract Water ecosystems are under intense anthropogenic influence, which leads to an increased presence of pollutants, including a large number of toxic substances, primarily heavy metals, which requires constant monitoring. Fish are one of the most indicative factors for assessing water pollution with harmful elements, and this is important not only for environmental protection but also for the assessment of meat quality and the potential risk to the human population. The main goal of this research was to analyze the level of accumulation of heavy metals and metalloids, such as arsenic (As), iron (Fe), chromium (Cr), copper (Cu), lead (Pb) and zinc (Zn) in the muscle tissue of commercially important fish species from Ohrid Lake, to compare their concentrations in different fish species, to apply the index of heavy metal pollution in the assessment of water pollution, and to make a comparison of the concentrations of accumulated heavy metals and metalloids in the muscle tissue of the examined fish species with the maximal permitted concentrations prescribed by the legal regulations. The research area was in Ohrid Lake, Macedonia. The most important commercial fish species from Ohrid Lake, i.e. common carp, Ohrid trout, and barbel, were sampled for analysis. Statistical analysis of the data showed significant differences (P &lt; 0.05) and significant variations in iron, chromium, copper, and zinc levels between different fish species and sampling months, highlighting the importance of considering species-specific factors such as feeding, habitat preferences, and metabolic processes in understanding the patterns of element accumulation, but also the temporal dynamics of element accumulation in fish. Based on the data on the concentrations of toxic elements (Fe, Cr, Cu, Pb, Zn) in common carp, Ohrid trout, and barbel during the examined months (May, September, December, February), it can be concluded that the obtained values are below the maximum allowed concentrations prescribed on the basis of Commission Regulation (EU) No 1881/2006. This means that the fish species analyzed are safe for consumption and comply with regulatory guidelines, thus ensuring the protection of consumer health.

AEBP1 Silencing Protects Against Cerebral Ischemia/Reperfusion Injury by Regulating Neuron Ferroptosis and Microglia M2 Polarization Through PRKCA-PI3K-Akt Axis.

Cerebral ischemia/reperfusion injury is one of the main causes of neuronal damage. Neuron ferroptosis and microglia polarization are considered as critical processes during cerebral ischemia/reperfusion. Adipocyte enhancer-binding protein 1 (AEBP1) usually acts as a transcriptional repressor which is involved in various diseases. However, it is still remains unknown whether AEBP1 could have important roles in regulating the neuron ferroptosis and microglia polarization in cerebral ischemia/reperfusion injury. The oxygen-glucose deprivation and reperfusion (OGD/R)-treated cells and middle cerebral artery occlusion (MCAO)-treated mice were used as in vitro and in vivo models. The differentially expressed factors were analyzed according to GEO datasets. Relative mRNA and protein expression levels were detected by qRT-PCR and western blot analysis. Cell viability was measured by CCK-8 assay. ROS, GSH and iron contents were detected using specifical assay kits. CD26 and CD206 levels were measured by immunofluorescence assay. Inflammatory cytokines were detected by ELISA. The association between AEBP1 and PRKCA was assessed by luciferase reporter and ChIP analyses. The neuron damage in mice was analyzed by TTC staining and neurological deficit score. Transcription factor AEBP1 was increased in OGD/R-treated HT22 and BV2 cells. AEBP1 silencing attenuated OGD/R-induced HT22 cell ferroptosis through increasing cell viability, GSH and GPX4 levels, and decreasing ROS, iron and ACSL4 levels. AEBP1 knockdown promoted microglia M2 polarization by increasing CD206-positive cells and Arg-1 level, and reducing iNOS, TNF-α, IL-1β and IL-6 levels in BV2 cells. AEBP1 transcriptionally repressed PRKCA expression, and further regulated PI3K/Akt signaling activation. Inhibition of PRKCA or PI3K/Akt reversed the effects of AEBP1 silencing on neuron ferroptosis and microglia M2 polarization. AEBP1 downregulation attenuated neuronal damage by decreasing infarct size and deficit scores in MCAO-treated mice. AEBP1 silencing mitigated neuron ferroptosis and promoted microglia M2 polarization through increasing PRKCA and activating PI3K/Akt signaling, indicating the potentially protective action of AEBP1 knockdown in cerebral ischemia/reperfusion injury.