Iron Status Research Articles

Longitudinal evaluation of iron status during pregnancy: a prospective cohort study in a high-resource setting

BackgroundIron deficiency affects a large proportion of pregnant women worldwide, with potentially serious consequences for perinatal and infant outcomes, but well-powered, comprehensive analyses of longitudinal iron status during pregnancy are scarce. ObjectivesThis study aimed to evaluate the longitudinal changes in iron biomarkers across pregnancy and prevalence of iron deficiency in primiparous women in a high-resource setting and propose early pregnancy iron status cutoffs that predict iron deficiency in the third trimester. MethodsIn a prospective cohort of primiparous women with low-risk, singleton pregnancies in Ireland, iron [ferritin, soluble transferrin receptors (sTfR), total body iron (TBI)] and inflammatory markers (C-reactive protein, α-glycoprotein) were measured at 3 study visits: 15, 20, and 33 wk of gestation. Women with anemia (hemoglobin < 110g/L) at their first routine antenatal visit were excluded from this analysis. ResultsParticipants (N = 629) were Caucasian (98.2%) and born in Ireland (80.6%). The prevalence of iron deficiency (ferritin < 15 μg/L) increased throughout pregnancy, at 4.5%, 13.7% and 51.2% at 15, 20, and 33 wk of gestation, respectively. Using a ferritin threshold of <30 μg/L, rates of deficiency were 20.7%, 43.7%, and 83.8% across these time points, respectively. Application of sTfR of >4.4 mg/L generated similar prevalence data as ferritin of <15 μg/L at 7.2%, 12.6%, and 60.9%, respectively. Using TBI of <0 mg/kg, deficiency rates were lower than using ferritin or sTfR (P < 0.001). Using a cutpoint analysis method (area under the curve = 0.750), ferritin of <60 μg/L emerged as the ferritin threshold at 15 wk that predicted the presence of iron deficiency (ferritin < 15 μg/L) at 33 wk. Iron-containing supplements (mainly multivitamins) taken prepreganancy/early pregnancy was associated with reduced risk of deficiency throughout pregnancy, including the third trimester (odds ratio: 0.57; 95% confidence interval: 0.39, 0.82; P = 0.002). ConclusionsPregnancy places a remarkable strain on maternal iron status even in a high-resource, generally iron-supplemented population. Women should be screened early in pregnancy for iron status, with a suggested target ferritin concentration of >60 μg/L.This trial was registered at clinicaltrials.gov as NCT01891240 (IMPROvED Study; ==https://www.clinicaltrials.gov/study/NCT01891240?cond=NCT01891240&rank=1).

Pollution load and dynamics of phytoplankton communities in relation to environment variables in Lake Babogay, Ethiopia

ABSTRACT The objective of this study was to investigate the water quality of Lake Babogaya in Ethiopia. Water samples were collected from six different sites, and analyzed for total coliform (TC), fecal coliforms (FC), and Escherichia coli (E.coli) content. Additionally, potential of hydrogen (pH), dissolved oxygen (DO), total dissolved solids (TDS), electrical conductivity (EC), and Secchi depth were measured. Nutrients and heavy metals were determined using standard methods. The abundance of phytoplankton was estimated by calculating the biovolume of the species. The results indicated that pH, TDS, DO, and turbidity ranged from 8.78 + 0.31 to 9.52 + 0.04, 129 + 4 to 419 + 3 ppm, 5.50 to 7.25 mg/l, and 0.96 to 17.29 NTU, respectively. TC bacteria exceeded the World Health Organization (WHO) standards at all sites, while FC levels exceeded in most samples. Cadmium and chromium were low in both seasons, whereas lead in the dry season exceeded the WHO limits. The levels of iron were high across all sites in the dry season and low in most sites in the wet season. Five major taxonomic phytoplankton groups were identified, comprising a total of 31 species with highest richness of green algae, blue-green algae, and diatoms species.

Lif-deficiency promote systemic Iron metabolism disorders and increases the susceptibility of osteoblasts to ferroptosis

Leukemia inhibitory factor (LIF) is a multifunctional cytokine that plays a crucial role in various biological processes. However, LIF involvement in iron metabolism remains almost unexplored. This study aimed to explore the impact of LIF on systemic iron transportation and its potential role in ferroptosis in osteoblasts. We observed that the Lif-deficient (Lif−/−) mice is characterized by a reduction in bone mass and a decrease in bone mineral density compared with wild-type (WT) mice. Energy-dispersive X-ray spectroscopy revealed a marked increase in iron content on the surface of femurs from Lif−/− mice. Meanwhile, iron stores test lower iron levels in the spleens and higher levels in the femurs of Lif−/− mice. Besides, Lif−/− mice display increased levels of serum iron, total iron-binding capacity, unsaturated iron-binding capacity, and transferrin saturation and serum ferritin relative to WT mice. Hepcidin mRNA expression reduction in the liver of Lif−/− mice. It also holds true in the AML-12 hepatocyte cell line after Lif-knockdown. Immunohistochemistry and RT-PCR revealed elevated ferroportin (FPN) in duodenal cells of Lif−/− mice. Lif-deficiency decreases SLC7A11 levels in osteoblasts. In addition, overexpression of LIF downregulates CD71, DCYTB, and DMT1, thereby reducing iron uptake in iron-overloaded cells. Femur immunohistochemistry (IHC) revealed increased ACSL4 and decreased GPX4 and SLC7A11, indicating an increase in ferroptosis of osteoblasts in Lif−/− mice. Whole-transcriptome sequencing showed gene expression changes after Lif-knockdown, exhibiting a negative correlation with genes involved in long-chain fatty acid transport, mitochondrial organization, and the p38 MAPK signaling pathway. These results demonstrate that Lif-deficiency alter systemic iron metabolism and increases the susceptibility of osteoblasts to ferroptosis.

Methods established for the detection of mineral levels in whole blood by the dried blood spot technique

Mineral are intimately related to human health and disease, and detection of mineral content in the body is of great significance for the diagnosis and prevention of diseases. In this study, we validated the method developed to detect magnesium (Mg), copper (Cu), iron (Fe), zinc (Zn), and selenium (Se) levels in dried blood spots (DBS). In accordance with the requirements of the guidelines for the Bioanalytical Method Validation Guidance for Industry, we evaluate the linearity, sensitivity, precision, accuracy and selectivity of the developed methods. In addition, Mg, Cu, Fe, Zn and Se were quantified in 195 older adults using DBS technique, and its accuracy was assessed by comparing the results to those detected by inductively coupled plasma-mass spectrometry (ICP-MS). The method has excellent sensitivity and linear range to cover the concentration range of mineral elements in the general population with the required precision, accuracy and selectivity. The correlation coefficients of Mg, Cu, Fe, Zn and Se levels in blood detected by the DBS technique and ICP-MS were 0.638, 0.823, 0.463, 0.728 and 0.751, respectively (all P < 0.05), which indicated that there was a strong correlation between the detection results of the two methods. More than 95 % of the sample results in the Bland-Altman consistency test were within the acceptable limits of agreement (LOA) range, indicating that they had good consistency. DBS technique has good accuracy and reliability in detecting blood mineral levels in the elderly, suggesting potential in the quantification of mineral level in blood.

Prevalence of Hypothyroidism in Children with Transfusion Dependent Thalassemia Patient Attending in A Tertiary Care Hospital of Bangladesh

Background: Blood transfusions and iron chelation are standard treatments for β-thalassemia major and Hb E-Beta-Thalassemia. However, repeated transfusions raise body iron levels, leading to secondary hemosiderosis and complications in the heart, endocrine system, and liver. Thyroid dysfunction results from gland infiltration, chronic hypoxia, free radical damage, and iron overload. This study aimed to find out the prevalence of hypothyroidism in transfusion-dependent thalassemic children attending Bangladesh Shishu Hospital &amp; Institute. Methods: A descriptive cross-sectional study was conducted at the Thalassemia Centre, Department of Hematology and Oncology, Bangladesh Shishu Hospital &amp; Institute, from December 2019 to November 2020. The study included 140 children with thalassemia, aged 5 to 16 years, who were receiving blood transfusions. Data were collected using a structured questionnaire with participant consent. Statistical analysis was performed using SPSS version 23.0. Results: In this study, hypothyroidism was observed in 26.2% of patients, with 23.5% having subclinical and 2.9% overt hypothyroidism. In most of the patients (n=85), aged 11-16 years, 58.3% had normal thyroid function, 36.5% had subclinical, and 4.7% had overt hypothyroidism, which was statistically significant (p&lt;0.05). Of the 91 patients with hemoglobin levels below 11.5 g/dL, 85.7% had normal thyroid function, 13.2% had subclinical hypothyroidism, and 1.1% had overt hypothyroidism, also significant (p&lt;0.05). In the group with ferritin levels of 1200-2000 ng/mL, 78.1% had normal thyroid function, 18.8% had subclinical hypothyroidism, and 3.1% had overt hypothyroidism, which was not statistically significant (p&gt;0.05). Conclusion: Subclinical hypothyroidism is commonly seen in thalassemia patients aged 5 to 16 years who undergo regular blood transfusions. Regular physical exams and thyroid function assessments are crucial to detect overt hypothyroidism early. Timely hormone replacement can

Association between cord blood telomere length and iron status in South Canara region

Association between cord blood telomere length and iron status in South Canara region

Association between serum iron levels and atherosclerotic cardiovascular diseases among American older adults: a cross-sectional study based on the National Health and Nutrition Examination Survey, 2009-2018.

There is controversy regarding the relationship between serum iron levels and atherosclerotic cardiovascular disease (ASCVD). To investigate the relationship between serum iron levels and ASCVD among older adults using data from the 2009-2018 National Health and Nutrition Examination Survey (NHANES). We performed a cross-sectional analysis involving 8,682 participants aged 60 years and older, with complete data on serum iron levels and confirmed ASCVD status, sourced from the 2009-2018 National Health and Nutrition Examination Survey (NHANES). Multivariable logistic regression models were used to examine the association between serum iron levels and ASCVD. To assess the consistency of this association across different demographic groups, subgroup analyses, and interaction tests were performed. The group with the highest serum iron levels (fourth quartile, 100-369 μg/dL) exhibited several distinct characteristics: they were the youngest on average (69.57 ± 6.91 years), had the highest proportion of males (61.42%), and the highest hemoglobin levels (14.43 ± 1.33 g/dL). This group also showed the lowest iron supplement usage (19.71 ± 12.85 mg/30 days), white blood cell counts (6.73 ± 2.41 1,000 cells/μL), and serum creatinine levels (0.98 ± 0.45 mg/dL). Moreover, they had higher levels of education and income, a higher likelihood of being married, and a lower body mass index (BMI). Additionally, they had significantly lower rates of diabetes, hypertension, stroke, and heart attacks (all p < 0.05). After adjusting for potential confounders, a linear relationship between serum iron levels and ASCVD was initially observed (OR = 0.97; 95% CI, 0.95-0.99, p < 0.05). However, further analysis using a two-part logistic regression model with an inflection point at 131 μg/dL revealed more nuanced results. For serum iron levels below 131 μg/dL, each 10 μg/dL increase was associated with a 4% decrease in the odds of ASCVD (OR = 0.96; 95% CI, 0.93-0.98, p < 0.001). Conversely, for serum iron levels above 131 μg/dL, each 10 μg/dL increase corresponded to a 1% increase in the odds of ASCVD, though this finding was not statistically significant (OR = 1.01; 95% CI, 0.98-1.08, p > 0.05). In the US elderly population, serum iron levels are negatively associated with ASCVD, particularly when serum iron levels are below 131 μg/dL.

Attenuation of TNF-α and Iron Levels in Renal Hemosiderosis by Phaleria macrocarpa (Scheff.) Boerl Extract in a Rat Iron Overload Model

Regular blood transfusions are typically used to treat the genetic anemia known as thalassemia, which can lead to an increase in the body's total iron levels. The condition of excess iron can be toxic to the body due to the formation of free radicals that are harmful and can damage cells and tissues. So the availability of free iron will form the basis of iron toxicity because it accelerates the Fenton reaction to produce an increase in the amount of ROS that cannot be suppressed so that saturation of the antioxidant system can occur. Excess iron has been known to be a risk factor for organ dysfunction and damage that results in various organ diseases such as liver, heart and kidney, diabetes mellitus, and neurodegenerative diseases. Mangiferin is an active compound has been shown to act as an iron chelating agent by forming complexes with iron. The complex formed can reduce iron accumulation in thalassemia patients who receive blood transfusions on a regular basis. Mahkota Dewa (Phaleria macrocarpa) is a well-known medicinal plant native to Papua, Indonesia, and it also includes the active ingredient mangiferin. This study aims to determine the effectiveness of the ethanolic extract of Phaleria macrocarpa fruit as an iron chelating agent observed in the kidneys in a rat model of excess iron

Ablation of mitophagy receptor FUNDC1 accentuates septic cardiomyopathy through ACSL4-dependent regulation of ferroptosis and mitochondrial integrity

Sepsis evokes compromised myocardial function prompting heart failure albeit target therapy remains dismal. Our study examined the possible role of mitophagy receptor FUNDC1 in septic cardiomyopathy. A sepsis model was established using cecal ligation and puncture (CLP) in FUNDC1 knockout (FUNDC1−/−) and WT mice prior to the evaluation of cardiac morphology, echocardiographic and cardiomyocyte contractile, oxidative stress, apoptosis, necroptosis, and ferroptosis. RNAseq analysis depicted discrepant patterns in mitophagy, oxidative stress and ferroptosis between CLP-challenged and control murine hearts. Septic patients displayed cardiac injury alongside low plasma FUNDC1 and iron levels. CLP evoked interstitial fibrosis, cardiac dysfunction (lowered ejection fraction, fractional shortening, shortening/relengthening velocity, peak shortening and electrically-stimulated intracellular Ca2+ rise, alongside increased LV end systolic diameter and relengthening duration), O2− buildup, apoptosis, necroptosis, and ferroptosis (downregulated GPX4 and SLC7A11), the responses of which were accentuated by FUNDC1 ablation. In particular, levels of lipid peroxidation enzyme acyl-CoA synthetase long-chain family member 4 (ACSL4) were upregulated following CLP procedure, with a more pronounced response in FUNDC1−/− mice. Co-immunoprecipitation and interaction interface revealed an evident interaction between FUNDC1 and ACSL4. In vitro studies revealed that the endotoxin lipopolysaccharide provoked cardiomyocyte contractile and lipid peroxidation anomalies, the responses were reversed by the mitophagy inducer oleanolic acid, inhibition of ACSL4 and ferroptosis. These findings favor a role for FUNDC1-ACSL4-ferroptosis cascade in septic cardiomyopathy.

Quantifying Remyelination Using χ-Separation in White Matter and Cortical Multiple Sclerosis Lesions.

Myelin and iron play essential roles in remyelination processes of multiple sclerosis (MS) lesions. χ-separation, a novel biophysical model applied to multiecho T2*-data and T2-data, estimates the contribution of myelin and iron to the obtained susceptibility signal. We used this method to investigate myelin and iron levels in lesion and nonlesion brain areas in patients with MS and healthy individuals. This prospective MS cohort study included patients with MS fulfilling the McDonald Criteria 2017 and healthy individuals, aged 18 years or older, with no other neurologic comorbidities. Participants underwent MRI at baseline and after 2 years, including multiecho GRE-(T2*) and FAST-(T2) sequences. Using χ-separation, we generated myelin-sensitive and iron-sensitive susceptibility maps. White matter lesions (WMLs), cortical lesions (CLs), surrounding normal-appearing white matter (NAWM), and normal-appearing gray matter were segmented on fluid-attenuated inversion recovery and magnetization-prepared 2 rapid gradient echo images, respectively. Cross-sectional group comparisons used Wilcoxon rank-sum tests, longitudinal analyses applied Wilcoxon signed-rank tests. Associations with clinical outcomes (disease phenotype, age, sex, disease duration, disability measured by Expanded Disability Status Scale [EDSS], neurofilament light chain levels, and T2-lesion number and volume) were assessed using linear regression models. Of 168 patients with MS (median [interquartile range (IQR)] age 47.0 [21.7] years; 101 women; 6,898 WMLs, 775 CLs) and 103 healthy individuals (age 33.0 [10.5] years, 57 women), 108 and 62 were followed for a median of 2 years, respectively (IQR 0.1; 5,030 WMLs, 485 CLs). At baseline, WMLs had lower myelin (median 0.025 [IQR 0.015] parts per million [ppm]) and iron (0.017 [0.015] ppm) than the corresponding NAWM (myelin 0.030 [0.012]; iron 0.019 [0.011] ppm; both p < 0.001). After 2 years, both myelin (0.027 [0.014] ppm) and iron had increased (0.018 [0.015] ppm; both p < 0.001). Younger age (p < 0.001, b = -5.111 × 10-5), lower disability (p = 0.04, b = -2.352 × 10-5), and relapsing-remitting phenotype (RRMS, 0.003 [0.01] vs primary progressive 0.002 [IQR 0.01], p < 0.001; vs secondary progressive 0.0004 [IQR 0.01], p < 0.001) at baseline were associated with remyelination. Increment of myelin correlated with clinical improvement measured by EDSS (p = 0.015, b = -6.686 × 10-4). χ-separation, a novel mathematical model applied to multiecho T2*-images and T2-images shows that young RRMS patients with low disability exhibit higher remyelination capacity, which correlated with clinical disability over a 2-year follow-up.

DEHP regulates ferritinophagy to promote testicular ferroptosis via suppressing SIRT1/PGC-1α pathway

To increase elasticity and flexibility, di-2-ethylhexyl phthalate (DEHP) is used in a variety of industrial products, but excessive exposure to it can pose a threat to human health. In epidemiological studies of population exposure to DEHP, attention has been paid to damage to the male reproductive system. However, the toxicological mechanism of DEHP regarding testicular injury is not well understood. We used Western blot analysis, transmission electron microscopy, fluorescence staining, transient transfection and assay kit to detect relevant indicators, and the results were as follows: After DEHP exposure, the expression levels of ACSL4, COX2, TF, FTH1, LC3, AMPK, p-AMPK, ULK1, p-ULK1, serum iron, tissue iron and MDA in the exposure group were significantly increased. The expression levels of GPX4, NCOA4, p62, SIRT1, and PGC-1α, as well as the contents of GSH and ATP, decreased. Electron microscopy showed that more autophagosomes were observed. Our findings suggest that exposure to DEHP induced ferritinophagy and ferroptosis in the testis. In vitro, the promoting effect of ferritinophagy on ferroptosis was verified by applying the autophagy inhibitor (3-MA) and si-NCOA4. Moreover, Mono-(2-ethylhexyl) phthalate (MEHP) inhibited the mitochondrial regulatory protein SIRT1/PGC-1α, leading to mitochondrial dysfunction. Changes in mitochondrial reactive oxygen species (MtROS) and energy over-activated AMPK/ULK1 autophagy pathway, and then promoted ferritinophagy, which increased the sensitivity of TM4 cells to ferroptosis. This research offers a theoretical framework for the prevention and management of DEHP-induced harm.

Iron Deficiency Is Associated with Elevated Parathormone Levels, Low Vitamin D Status, and Risk of Bone Loss in Omnivores and Plant-Based Diet Consumers.

A cross-sectional study was performed in healthy adults (mean age 28 y, 67% women) whose habitual diet was an omnivore, lacto-ovo vegetarian, or vegan diet. The total sample (n = 297) was divided into two groups according to the parathormone (PTH) cut-off value of 65 pg/mL of either normal-PTH (n = 228) or high-PTH (n = 69). Vitamin D status (25-hydroxycholecalciferol, 25-OHD), PTH, and bone formation (bone alkaline phosphatase, BAP) and bone resorption (N-telopeptides of type I collagen, NTx) markers were determined. Hematocrit, erythrocytes, hemoglobin, platelets, serum iron, serum transferrin, transferrin saturation, and serum ferritin were also measured. In the total sample, 25-OHD and PTH were negatively correlated, and all subjects with high PTH presented vitamin D insufficiency (25-OHD < 75 nmol/L). High bone remodeling was observed in the high-PTH group, with significantly higher NTx and marginally higher BAP compared to the normal-PTH group. Hematocrit and ferritin were significantly lower in the high-PTH compared to the normal-PTH group. However, serum iron was higher in the high-PTH group, which was only observed for the lacto-ovo vegetarian and vegan subjects. It is concluded that both low vitamin D and low iron status are associated with elevated PTH and bone resorption, more in vegetarians than omnivores, which is in line with the hypothesis that chronic iron deficiency in adulthood mainly predisposes to osteoporosis in postmenopausal women and the elderly.

A Study of the Clinical Profile of Iron Deficiency Anemia in Children With Sickle Cell Disease in a Tertiary Care Center.

Background Sickle cell disease (SCD) and iron deficiency anemia (IDA) are significant global health concerns, particularly in pediatric populations. This study investigates the prevalence, clinical impact, and management challenges of IDA in children with SCD. Methods A prospective observational study was conducted at the Department of Pediatrics, Jawaharlal Nehru Medical College(JNMC) and Acharya Vinoba Bhave Rural Hospital (AVBRH), Sawangi, from June 2022 to May 2024. The study included 60 children diagnosed with SCD. Comprehensive assessments were performed, including medical histories, physical examinations, and hematological investigations. Diagnosis of IDA was based on hemoglobin levels, mean corpuscular volume (MCV), red cell distribution width (RDW), peripheral blood smears, serum iron levels,and serum ferritin concentrations. Results Of the 60 participants, 15% exhibited iron deficiency. No significant gender differences were found in iron deficiency status. A significant association was observed between SCD type and the presence of pallor (p = 0.025) and sickle cell crises (p = 0.023). The study also found no significant association between SCD type and the presence of organomegaly (p = 0.079) or iron deficiency status (p = 0.675). The mean hemoglobin levels varied across SCD types, with sickle cell anemia patients showing lower levels than those with sickle cell trait or disease. Conclusion Diagnosing and managing IDA in children with SCD is complex due to overlapping hematological features and the risk of iron overload from frequent transfusions. Tailored diagnostic and therapeutic approaches are essential to improving hemoglobin levels, reducing complications, and enhancing the quality of life for affected children. This study provides valuable insights for refining clinical practices and emphasizes the need for a multidisciplinary approach to managing these intertwined conditions.

Zinc and Ferritin Levels and Their Associations with Functional Disorders and/or Thyroid Autoimmunity: A Population-Based Case-Control Study.

Population zinc and iron status appear to be associated with an increased risk of thyroid function abnormalities and thyroid autoimmunity (AITD). In the present study, we aimed to determine whether zinc and/or iron levels (assessed by ferritin levels) were associated with the presence of AITD and with alterations in thyroid function. A population-based case-control study (n = 1048) was conducted (cases: n = 524; controls: n = 524). Participants were measured for blood concentrations of zinc and ferritin, TSH, FT4, FT3, and thyroid autoantibodies. No significant differences were found in relation to ferritin levels between cases and controls. Among cases, the prevalence of low zinc levels in those with hypothyroidism (both subclinical and overt) was 49.1% [odds ratio (OR) of low zinc levels: 5.926; 95% CI: 3.756-9.351]. The prevalence of low zinc levels in participants with hyperthyroidism (both subclinical and overt) was 37.5% [OR of low zinc levels: 3.683; 95% CI: 1.628-8.33]. The zinc value that best discriminated the highest frequency of AITD was 70.4 µg/dL [sensitivity: 0.947, 1-specificity: 0.655, specificity: 0.345]. The highest frequency of AITD was calculated based on a zinc value <70 µg/dL (relative to a normal value), with this frequency being significantly higher in cases than in controls [OR: 9.3; 95% CI: 6.1-14.3 (p = 0.001)]. In conclusion, the results of our study suggest that zinc deficiency is associated with an increased frequency of functional thyroid disorders and thyroid autoimmunity.

Bile from the hemojuvelin-deficient mouse model of iron excess is enriched in iron and ferritin.

Iron is an essential nutrient but is toxic in excess. Iron deficiency is the most prevalent nutritional deficiency and typically linked to inadequate intake. Iron excess is also common and usually due to genetic defects that perturb expression of hepcidin, a hormone that inhibits dietary iron absorption. Our understanding of iron absorption far exceeds that of iron excretion, which is believed to contribute minimally to iron homeostasis. Prior to the discovery of hepcidin, multiple studies showed that excess iron undergoes biliary excretion. We recently reported that wild-type mice raised on an iron-rich diet have increased bile levels of iron and ferritin, a multi-subunit iron storage protein. Given that genetic defects leading to excessive iron absorption are much more common causes of iron excess than dietary loading, we set out to determine if an inherited form of iron excess known as hereditary hemochromatosis also results in bile iron loading. We employed mice deficient in hemojuvelin, a protein essential for hepcidin expression. Mutant mice developed bile iron and ferritin excess. While lysosomal exocytosis has been implicated in ferritin export into bile, knockdown of Tfeb, a regulator of lysosomal biogenesis and function, did not impact bile iron or ferritin levels. Bile proteomes differed between female and male mice for wild-type and hemojuvelin-deficient mice, suggesting sex and iron excess impact bile protein content. Overall, our findings support the notion that excess iron undergoes biliary excretion in genetically determined iron excess.

Ferroptosis: a new mechanism of traditional Chinese medicine for treating hematologic malignancies.

Ferroptosis is a recently identified form of cell death characterized by lipid peroxidation and elevated iron levels. It is closely associated with hematologic malignancies, including leukemia, multiple myeloma (MM), and myelodysplastic syndromes (MDS). Research indicates that ferroptosis could represent a novel therapeutic target for these hematologic malignancies. Furthermore, traditional Chinese medicine (TCM) has been shown to modulate hematologic malignancies through the ferroptosis pathway. This paper aims to elucidate the mechanisms underlying ferroptosis and summarize the current research advancements regarding ferroptosis in hematologic malignancies, as well as the role of traditional Chinese medicine in the prevention and treatment of ferroptosis, with the goal of enhancing treatment efficacy.

DMT1 knockout abolishes ferroptosis induced mitochondrial dysfunction in C. elegans amyloid β proteotoxicity

Iron is critical for neuronal activity and metabolism, and iron dysregulation alters these functions in age-related neurodegenerative disorders, such as Alzheimer's disease (AD). AD is a chronic neurodegenerative disease characterized by progressive neuronal dysfunction, memory loss and decreased cognitive function. AD patients exhibit elevated iron levels in the brain compared to age-matched non-AD individuals. However, the degree to which iron overload contributes to AD pathogenesis is unclear. Here, we evaluated the involvement of ferroptosis, an iron-dependent cell death process, in mediating AD-like pathologies in C. elegans. Results showed that iron accumulation occurred prior to the loss of neuronal function as worms age. In addition, energetic imbalance was an early event in iron-induced loss of neuronal function. Furthermore, the loss of neuronal function was, in part, due to increased mitochondrial reactive oxygen species mediated oxidative damage, ultimately resulting in ferroptotic cell death. The mitochondrial redox environment and ferroptosis were modulated by pharmacologic processes that exacerbate or abolish iron accumulation both in wild-type worms and worms with increased levels of neuronal amyloid beta (Aβ). However, neuronal Aβ worms were more sensitive to ferroptosis-mediated neuronal loss, and this increased toxicity was ameliorated by limiting the uptake of ferrous iron through knockout of divalent metal transporter 1 (DMT1). In addition, DMT1 knockout completely suppressed phenotypic measures of Aβ toxicity with age. Overall, our findings suggest that iron-induced ferroptosis alters the mitochondrial redox environment to drive oxidative damage when neuronal Aβ is overexpressed. DMT1 knockout abolishes neuronal Aβ−associated pathologies by reducing neuronal iron uptake.

Evaluation of Heavy Metal Concentration in Sediments of Rupingazi River, Kenya

Heavy metal concentration (Cu, Zn, Fe, Mn, Ni) was evaluated in sediment samples of Rupingazi river during the wet and dry seasons. In this study, the sediment samples were collected from twenty sampling points along the river. The heavy metal levels were evaluated using Atomic Absorption Spectrphotometer.The obtained data was analyzed using one-way analysis of variance. The range of the concentration of copper was found to be 4.68- 12.69 mg/kg for the wet season and 0.98-24.10mg/kg for the dry season. The mean values of the concentration of iron was found to be 1422-6145.33 mg/kg for the wet season and 1254-5866.67 mg/kg for the dry season. The range of the concentration of Nickel was found to be 0.72- 30.73 mg/kg for the wet season and 2.63-12.48 mg/kg for the dry season. Concentration of manganese was found to be 48.03-411.20 mg/kg for the wet season and 6.15-248.35 mg/kg for the dry season Zinc concentration was found to be 26.29-167.10 mg/kg for the wet season and 4.82-28.39 mg/kg for the dry season. The Zinc, Manganese, Nickel Iron and Copper levels were not beyond the USEPA recommended limits.

SGK1 suppresses ferroptosis in ovarian cancer via NRF2-dependent and -independent pathways.

High-grade serous ovarian cancer (HGSOC) is a highly aggressive disease often developing resistance to current therapies, necessitating new treatment strategies. Our study identifies SGK1, a key effector in the PI3K pathway, as a promising therapeutic target to exploit ferroptosis, a distinct form of cell death induced by iron overload and lipid peroxidation. Importantly, SGK1 activation, whether through high expression or the constitutively active SGK1-S422D mutation, confers resistance to ferroptosis in HGSOC. Conversely, SGK1 inhibition significantly enhances sensitivity to ferroptosis, as shown by increased PTGS2 expression (a ferroptosis marker), lipid peroxidation, and toxic-free iron levels. Remarkably, this enhanced cytotoxicity is reversed by ferrostatin-1 and the iron chelator deferoxamine, highlighting the pivotal roles of lipid peroxidation and iron dysregulation in the process. Mechanistically, SGK1 protects HGSOC cells from ferroptosis via NRF2-dependent pathways, promoting glutathione synthesis and iron homeostasis, and NRF2-independent pathways via mTOR/SREBP1/SCD1-mediated lipogenesis. Notably, pharmacological SGK1 inhibition sensitizes HGSOC xenograft models to ferroptosis induction, highlighting its therapeutic potential. These findings establish SGK1 as a critical regulator of ferroptosis and suggest targeting SGK1 alongside ferroptosis pathways as a potential therapeutic strategy for HGSOC patients.

Health Risk Assessment of Exposure to Iron in Gravity Feed System Water among Indigenous People

This study aims to determine the health risk exposure of iron level in drinking water from gravity feed system among residents at Sungai Mas village, Sungai Lembing, Kuantan Pahang. A cross-sectional research was carried out based on inclusion and exclusion criteria. The purposive sampling method was used to select respondents of Jakun and Semaq Beri tribe. This research had two parts;questionnaire,as well aswater sample collection and analysis. The iron level was determined using Hanna Instruments HI801-02 iris Visible Spectrophotometer, while pH level was determined using EUTECHC Cyberscan pH 310 Series Meter. Median and IQR of iron were 0.080 and 0.030 mg/L, respectively.There was no relationship between iron and pH levels of drinking water samples in the study area. There was no significant difference between iron levels in drinking water and the National Standard for Drinking Water Quality, and the value ranged between 0.030-0.550 mg/L. There was no health risk of iron exposure among respondents. The HQ was &lt;1. Generally, drinking water containing iron had no adverse health effects. The iron in drinking water in this study was not influenced. So there are no carcinogenic effects on the community in Sungai Mas Village, Sungai Lembing.