Iron Status Research Articles

Iron Metabolism in Pediatric Living related Liver Transplantation

Abstract Introduction Iron deficiency is a frequent cause of anemia in liver transplant recipients, especially children. Rejection and infection are incriminated causes for occurrence of anemia after liver transplantation (LR). Aim of the Work We aimed to assess iron homeostasis in children who have undergone living related LT (LRLT) and its correlation with occurrence of rejection and infection. Patients and Methods The study was conducted on 35 children who have undergone LRLT. The patient characteristics, frequency of infection and rejection episodes, laboratory investigations including complete blood picture (CBC) and Iron profile (total iron binding capacity (TIBC),serum iron and ferritin) during the patient follow up visits were reported. Results Males were 68.58% of the studied patients and females were 31.42%. Their ages ranged from 1.3-15 years at time of LT with mean (SD) of 7.18 (3.8)years. The mean (SD) duration since LT was 4.83 (4.2) years. The commonest indication to LT was highgamma-glutamyl transferase (GGT) cholestasis (34.7%) followed by biliary atresia (21.7 %). Thirteen percent of patients had low hemoglobin (Hb) of whom 4.3% had normocytic normochromic anemia and 8.7% had microcytic hypochromic anemia. Serum iron was normal in 79.6% of patients and low in 20.4%, and ferritin was normal in 58.7% of patients and low in 41.3% while TIBC was normal in 82.6% of patients and low in 17.4%. Only serum iron showed significant negative correlation with white blood cells (WBCs) (P < 0.05). The iron parameters levels were not different in patients with no rejection or only one attack of rejection and the patients with multiple rejection episodes (P > 0.05). Conclusion Anemia is a reported complication after pediatric LT. Further studies are needed to assess the long term effect of post-LT anemia on patient outcome after LT.

Immunophenotypic Evaluation of Circulating Monocyte Subsets in Beta Thalassemia Major Patients

Abstract Background β-thalassemia is a major public health problem in Egypt with particularly high incidence due to strong cultural preference for consanguineous marriages, and the high carrier rate. Iron overload, which is caused by increased gut iron absorption secondary to ineffective erythropoiesis, and regular blood transfusion is linked to accumulation within different organs with subsequent organ dysfunction. Monocytes are important lineages of innate immunity which activate the adaptive immune response and play a pivotal role in the host response to pathogens. Human blood monocyte subsets classification is based on the expression of CD14 and CD16 cell surface receptors. Aim of the Work To evaluate the circulating monocyte subsets in β-thalassemia major (β-TM) patients and its potential role in prediction of iron overload and chronic inflammation in β- thalassemia major patients. Patients and Methods A Case-Control study conducted on 40 previously diagnosed beta thalassemia major patients attending the outpatient clinic of Ain Shams University Pediatric Hospital, and 20 age and sex matched healthy control subjects. CBC, iron profile, CRP and immunophenotyping for monocyte subsets classification were done. Results Non classical monocytes were found statistically significantly higher in thalassemic patients especially in those with serum ferritin level < 1000 ng/ml (P value < 0.01). In addition, classical monocytes were found to be statistically significantly lower among the patients’ group (P value < 0.01). A negative correlation was found between intermediate monocytes and Transferrin saturation percent (TS%) suggesting its protective role in iron overload thalassemia patients. By using ROC curve, non- classical monocytes predicted ferritin < 1000 ng/ml at a cutoff point of 17.8 % and 0.05 x 10∧9/L for relative and absolute counts respectively. Conclusion All monocyte subsets proposed to have role in predicting iron overload and chronic inflammation β-TM patients. We recommend further studies on β-TM patients with the engagement of activity assays of monocyte subsets to clarify the co-regulatory role in iron hemostasis and chronic inflammation.

Study of the Efficacy and Safety of Darbepoetin Alfa versus Epoetin Alfa in the Treatment of Anemia in Pediatric Patients on Regular Hemodialysis

Abstract Background Anemia is a common comorbidity in patients with chronic kidney disease (CKD). That affects the vast majority and can have a significant impact on patient morbidity and mortality. Erythropoiesis-stimulating agents (ESAs) are the main lines in management of anemia in hemodialysis patients. Replacement therapy with recombinant human erythropoietin (r- HuEPO) has provided an effective treatment for patients with renal “Epoetin alfa” is a recombinant erythropoietin with the same amino acid sequence as human erythropoietin (EPO). In comparison to epoetin alfa, darbepoetin alfa (DPO) contains an increased amount of sialic acid-containing carbohydrate chains. It shows a much longer elimination half-life than epoetin alfa, with prolonged erythropoietic effect. Aim of the Work to evaluate whether darbpoetin and epopoetin alpha can be used interchangeably on the same patient, achieving the same desired effect and to detect any difference in the occurrence of side effects between both ESAs. Patient and Methods This was a crossover study that took place in the Pediatrics Dialysis unit, Children’s Hospital, Ain Shams University. The study was conducted on 40 children with end stage renal disease on regular hemodialysis over a period of 6 months. The patients were randomly put into two groups A and B, each group contained 20 patients. Each group received one type of ESA either ( darbpoetin alpha or epopoetin alpha )for 3 months and then shifted to the other type of ESA for another 3 months. The dosage of epoetin alfa used was (200 IU/kg/week) and a conversion rate of EPO: DPO, 300:1. A period of 6 weeks was agreed as a washout period after the first drug given in both groups in which no results were recorded but ESA was not stopped due to its essentiality. Blood tests (hemoglobin (Hb), serum urea, serum creatinine and iron profile; (S. iron, S. ferritin, TIBC, and transferrin saturation)) were withdrawn at the start and the end of the 3 months’ period of each drug. Results We found no difference on the Hb level with both drugs. The interchange between them did not yield any significant drop in the Hb levels. Hb target in both EPO and DPO was reached in 22.5% of total cases, and was not reached in 62.5%. This proved that both drugs give the same effect with nearly negligible difference. No serious Sside effect as convulsions, hypertension, and thrombosis were noticed in both groups. Conclusion The target Hb was not reached in most patients of both groups of ESRD on regular hemodialysis at the unit and none of both drugs showed superior results or less side effects than the other.

P-015 Impaired spermatogenesis in colitis: the role of interferon-γ mediated ferroptosis in sertoli cells by colitic CD4+ T cells

Abstract Study question Does colitis have an impact on spermatogenesis and what could be the potential mechanism? Summary answer Colitis causes sertoli cell ferroptosis and disrupts spermatogenesis in mice due to the migration of colitic CD4+ T cells that produce interferon-γ. What is known already In recent years, there has been a significant increase in rheumatic and inflammatory diseases. Epidemiological data reveals that dysregulated immune conditions can directly or indirectly impact male fertility and sexual function in patients of reproductive age. Inflammatory bowel disease (IBD), which encompasses Crohn’s disease and ulcerative colitis, is a chronic, recurring gastrointestinal inflammatory disorder characterized by bloody stools and weight loss. A study from a Swedish national cohort showed that IBD patients had diminished sperm fertility and increased sperm DNA fragmentation compared to healthy individuals. However, the precise mechanisms underlying male fertility problems in IBD remain unclear. Study design, size, duration In this study, C57BL/6 mice were kept under specific pathogen-free conditions. A murine colitis model that simulates human colitis histological features and symptoms was created using Dextran Sulfate Sodium (DSS). To establish the model, 2-2.5% DSS was added to the mice’s drinking water from days 0 to 7, followed by a three-day recovery period. Participants/materials, setting, methods Testis, epididymis and colon sections were stained with hematoxylin and eosin for histological analysis. The localization and phenotype of infiltrated lymphocytes in epididymis and testis were studied by immunostaining and flow cytometry. Sperm functions including motility, viability, and DNA integrity were assessed by standard assays. Iron, malondialdehyde, and reactive oxygen species (ROS) levels were analysed by commercial kit. Main results and the role of chance Colitis was found to impair male fertility in DSS-induced colitic mice, causing testis and epididymis tissue damage along with inflammatory cell infiltration. Colitis altered the immune cell phenotypes in the testis and epididymis. The proportion and absolute cell count of CD4+ T cells and CD19+ B cells increased after colon inflammation. Testicular sertoli cells in colitic mice exhibited ferroptosis, characterized by increased levels of iron deposition, malondialdehyde, and ROS. We assessed sperm parameters from the cauda epididymis of mice. Compared to the control group, there were significant reduction in sperm concentration, motility, viability and DNA integrity in the group with murine colitis induction. Consistently, we observed lower numbers of active pups from the fathers of the colitis group compared to control mice. CD4+ T cells with interferon-γ producing capabilities accumulated in the testes of colitis mice. Leukocyte flow cytometric analysis and parabiotic mouse model further demonstrated that colitis promoted pathogenic CD4+ T cells migration to the testis through circulation. The treatment of anti-CD4 antibody, anti-interferon-γ antibody or ferroptosis inhibitor can attenuate the colitis-associated testis pathologies. Limitations, reasons for caution Our study was conducted exclusively in mice. The pathogenic effect and the corresponding mechanism of colitis on male fertility in humans still needs to be confirmed. Wider implications of the findings Our team identified the mechanism linking dysregulated gut immune cell activity to testicular dysfunction. By identifying specific molecules on colitic immune cells, which allow their infiltration into the testis, may pave the way for a new therapeutic approach potentially improving the prognosis of colitis and related fertility impairments. Trial registration number not applicable

Cord Blood Hemoglobin Levels in Full Term Neonates of Mothers with Iron Deficiency Anemia

Abstract Background Iron is a critical micronutrient for tissue oxygenation, cellular metabolism, energy generation, and the metabolism of toxins. Iron transfer from mother to fetus is a regulated process involving iron status in the maternal circulation, its transport across the placenta and subsequent transfer into the fetal circulation. Objective To evaluate cord blood Hemoglobin (Hb) levels in neonates of mothers with iron deficiency anemia (IDA). Patients and Methods This prospective case-control study was conducted at Ain Shams University Hospitals. It included 60 full terms newborn who were born at Obstetrics and Gynecology Hospital. The study population included full term neonates delivered at ≥ completed 37 weeks of gestation which was divided into two groups according to maternal risk factor: Case: full term neonates with maternal risk factor. Control: full term neonates without maternal risk factor. Thorough clinical examination and investigations were performed including cord blood samples collected for measurement of the level of complete blood count (CBC; (Hb, MCV and MCH). For the mothers, venous blood samples were withdrawn with standard precautions and strict sterile conditions for CBC, transferrin saturation and serum ferritin. Results In comparison between cases and controls as regard RBCS parameter, there was no significant difference between cases and controls regarding neonatal hemoglobin( 14.93±1.14 vs 15.44 ±1.35(g/dL), p = 0.12) and MCH (32.51±2.9 vs33.57 ±1.9 (pg), p = 0.10), but there was significantly lower MCV in cases compared to controls (104.07± 7.36 vs 109.60±4.93 (fL), p = 0.001). There was no significant difference between cases and controls as regard maternal clinical characteristics including (age, weight, height, maternal diseases, gravidity, consanguinity and mode of delivery, p > 0.05 for all). Also, there was no significant difference between cases and controls regarding neonatal weight, Z score for weight, length (cm), head circumference (cm) and gestational age by Ballord Score and Apgar Score in 1-minute and 5-minute score p > 0.05 for all). Conclusion There was no relation between the maternal Hb deficient levels and neonatal Hb. The first sign of iron deficiency in neonates reflected in lower MCV in cases, but not reached to decrease Hb levels in neonates.

Prescribed fire increases forage mineral content in grazed rangeland

Background Sustainable rangeland management balances production and conservation. While a broad literature describesthe conservation benefits of prescribed fire, benefits for livestock production have emerged more slowly. Mineral nutrition is important for livestock health and performance, but the impact of prescribed fire on mineral concentration of forages, especially in the northern US Great Plains, remains unknown. Aims We investigated how burning affects the mineral concentration of forage early and late in the growing season. Methods Data were collected on mixed-grass prairie in south-central North Dakota, USA. Vegetation was clipped from recently burned, 1 year post-fire, 2 years post-fire, and not-yet-burned patches at the same sampling points in spring and late summer. Samples were analysed for calcium, phosphorus, magnesium, potassium, copper, iron, manganese, and zinc concentration. Key results Burning increased forage mineral concentration across most minerals. Phosphorous, potassium, copper and zinc were higher in burned areas in late spring and summer; calcium, magnesium and manganese were only higher during the late summer; Late-season iron levels increased with time since fire. Conclusions Prescribed fire has a positive effect on forage mineral content. Implications Prescribed fire has the potential to reduce mineral supplementation costs and improve cow performance.

Quantitative susceptibility mapping in amyotrophic lateral sclerosis: automatic quantification of the magnetic susceptibility in the subcortical nuclei

Objective: Previous studies have suggested a link between dysregulation of cortical iron levels and neuronal loss in amyotrophic lateral sclerosis (ALS) patients. However, few studies have reported differences in quantitative susceptibility mapping (QSM) values in subcortical nuclei between patients with ALS and healthy controls (HCs). Methods: MRI was performed using a 3 Tesla Prisma scanner (64-channel head coil), including 3D T1-MPRAGE and multi-echo 3D GRE for QSM reconstruction. Automated QSM segmentation was used to measure susceptibility values in the subcortical nuclei, which were compared between the groups. Correlations with clinical scales were analyzed. Group comparisons were performed using independent t-tests, with p < 0.05 considered significant. Correlations were assessed using Pearson’s correlation, with p < 0.05 considered significant. Cohen’s d was reported to compare the standardized mean difference (SMD) of QSM. Results: Twelve patients with limb-onset ALS (mean age 48.7 years, 75% male) and 13 age-, sex-, and handedness-matched HCs (mean age 44.6 years, 69% male) were included. Compared to HCs, ALS patients demonstrated significantly lower susceptibility in the left caudate nucleus (CN) (SMD = −0.845), right CN (SMD = −0.851), whole CN (SMD = −1.016), and left subthalamic nucleus (STN) (SMD = −1.000). Susceptibility in the left putamen (SMD = −0.857), left thalamus (SMD = −1.081), and whole thalamus (SMD = −0.968) was significantly higher in the patients. The susceptibility of the substantia nigra (SN), CN, and pulvinar was positively correlated with disease duration. Conclusions: QSM detects abnormal iron accumulation patterns in the subcortical gray matter of ALS patients, which correlates with disease characteristics, supporting its potential as a neuroimaging biomarker.

Changes in blood serum parameters in farmed rainbow trout (Oncorhynchus mykiss) during a piscine lactococcosis outbreak.

The aquaculture sector plays a vital role in global food security, yet it grapples with significant challenges posed by infectious diseases. Piscine lactococcosis is one of the significant threats in rainbow trout aquaculture due to its potential to cause severe economic losses through mortalities, reduced growth rates, and increased susceptibility to other pathogens. It poses challenges in disease management strategies, impacting the sustainability and profitability of rainbow trout farming. The current study focuses on the variations in serum blood parameters of farmed rainbow trout Oncorhynchus mykiss during a lactococcosis outbreak caused by Lactococcus garvieae. Blood samples were collected for biochemical analysis, fish were examined for parasites and bacteria, and DNA from bacterial colonies was PCR-amplified and sequenced for identification. Overall, 13 biochemical parameters, including proteins, enzymes, lipids, chemicals, and minerals, were measured in serum blood samples from both diseased and healthy fish. The results indicate significant alterations in the levels of these parameters during the outbreak, highlighting the impact of infections on the blood profile of farmed rainbow trout. Urea levels were significantly higher in diseased fish compared to controls, and creatinine, phosphorus, and magnesium also showed similar trends. Alanine aminotransferase and total protein levels were higher in control fish. Chloride levels differed significantly between groups. Iron levels were higher in controls and lower in diseased fish. No significant differences were found in other parameters. This study reveals significant changes in serum blood parameters of rainbow trout during a lactococcosis outbreak caused by L. garvieae. These changes highlight the potential of these parameters as tools for monitoring health status, stress, and aquaculture management. Continuous monitoring can provide valuable insights into disease severity and overall fish health, aiding in the development of improved management practices. The presented data contribute to understanding the pathophysiology of piscine lactococcosis and developing effective mitigation strategies for farmed rainbow trout.

Frequency, Types, and Risk Factors of Anemia in Pediatric Inflammatory Bowel Disease

Objective: Inflammatory bowel disease patients are prone to be anemic at diagnosis and follow-up. As it is a common extra-intestinal manifestation, its early identification and treatment are essential. We aimed to evaluate the frequency, types, and predictors of anemia and its treatment in pediatric inflammatory bowel disease patients. Methods: The electronic records of pediatric IBD patients who attended our outpatient clinics between 1 April 2018 and 01 May 2019 were retrospectively evaluated. Patients who had the results of hemoglobin, hematocrit, mean corpuscular volume, iron indices, vitamin B12 level, folic acid level, reticulocyte count, C-reactive protein, and erythrocyte sedimentation rate at least once on a single day were included in the study. Laboratory results associated with anemia and disease activity index scores at three- and six-months follow-ups were recorded. Anemia was diagnosed according to WHO criteria in childhood. Anemia, risk factors, and management of anemia were determined. Results: Forty patients were included in the study. At first evaluation, anemia was observed in 38.1% of Crohn’s disease patients and 57.9% of ulcerative colitis patients. Iron deficiency anemia was the main type of anemia in both groups. The rate of anemia decreased at follow-up. Out of 40 patients, 21 had treatment at the initial evaluation. Active disease was the only predictor of iron deficiency anemia. Conclusion: Anemia was common in pediatric inflammatory bowel disease patients, ranging between 25-47.5% during the 6-month follow-up in our study. Iron deficiency anemia was the main type of anemia. Having active disease was the only risk factor for anemia. The treatment of anemia and iron deficiency without anemia should be kept in mind in parallel with anti-inflammatory treatment.

Sequential Fractionation of Heavy Metals from Flooded and Non-Flooded Soils in Obunagha Community, Bayelsa State, Nigeria

Soil samples from flooded and non-flooded areas of different farmlands in Obunagha community, Bayelsa State were collected for this study. The aim of the study was to investigate the chemical fractionation and bioavailability of Cr, Cd, Zn, Ni, &amp; Fe in flooded and non-flooded farmlands. The soil samples were fractionated into six chemical fractions, each containing different heavy metal concentrations and analyzed using flame atomic absorption spectrophotometer. The highest average concentration for Cadmium (Cd) is 1.50g/kg, Zinc (Zn) is 7.53g/kg, Nickel (Ni) is 10.54g/kg, Iron (Fe) is 9.52g/kg, and Chromium (Cr) is 12.62g/kg all from the flooded areas of the farmlands. Sequential extraction showed heavy metals distributed throughout all extraction steps, with the water-soluble fraction prevailing, potentially increasing the mobility and bioavailability of these metals. The %bioavailability ranged from 37.98% – 90.00%. The results indicated also that the average concentration of the metals in flood affected farmland were more than the non-flooded areas. The results indicated that floods affect farmland metal content by altering contaminant bioavailability, causing adverse environmental effects. Also, the results of the heavy metals analyses revealed that the levels of nickel, zinc, chromium, cadmium and iron in all the farmland soil samples are above the maximum allowable concentration for heavy metals in soil set by WHO Guidelines provided. Hence, the farmland soils are not safe for agricultural activities. We therefore, recommend regular monitoring of the soils to prevent excessive build-up of these toxic heavy metals.

Water Quality Assessment in an Area Degraded by Urban Solid Waste in Southern Brazil

ABSTRACTIn most Brazilian municipalities, urban solid waste (USW) is disposed of in open dumps, with numerous sites now being closed, monitored, and rehabilitated. One location, the “old dump” area in the Portão municipality (southern Brazil), previously served as an irregular repository for USW and industrial solid waste (ISW). Its use continued until 1993 when it was closed for a natural remediation process. For this reason, this study aimed to assess groundwater quality in the Portão “old dump,” employing physicochemical, microbiological, and toxicity quality indicators. The study's scope was extended to encompass the Portão Stream as well. Notably, the second collection campaign revealed elevated dissolved aluminum (Al3+), iron (Fe2+), and nitrate levels in all groundwater samples (from PZi wells, i = 1–6), with the PZ3 monitoring well experiencing the most pronounced impact. Further quality indicators, such as total phosphorus, thermotolerant coliforms, BOD5, as well as Al3+ and copper (Cu2+) levels in the second water collection campaign from Portão Stream, were classified as Class 4, suggesting that the water is suitable only for navigation and aesthetic purposes. Conductivity analysis identified Portão Stream as another impacted area. Moreover, during the second collection campaign, the study uncovered an escalation in micronuclei (MN) frequency and chromosomal alterations in PZ5. Downstream water samples from Portão Stream exhibited similarly heightened MN levels. This study's investigation into water quality is a concrete example of the implications of improper USW management. These findings underscore the pressing need for effective waste management strategies to mitigate environmental degradation and protect public health.

Haematological Profile in Patients With Acute Falciparum Malaria: A Hospital-Based Study.

Introduction Malaria is the most common parasitic disease affecting humans. Haematological alterations in malaria are expected, and these changes play a significant role in fatal complications. The present study aims to assess the clinical and haematological profile in patients with acute falciparum malaria and the significance of various haematological and coagulation alterations with the clinical severity of malaria. Methods The prospective cross-sectional study included 68 acute falciparum malaria cases. Thick and thin blood film microscopy and a rapid diagnostic kit were used to diagnose malaria. The cases were subjected to various haematological and biochemical investigations. Bone marrow aspiration samples were also collected. Using appropriate statistical methods, the findings were compared between severe and uncomplicated malaria cases. A p-value below 0.05 was considered significant. Results The participants' ages ranged from 14 to 78. Most participants (n = 51, 75%) were male and belonged to the lower income group (33, 48.5%). Significant variations in mean parasite count between severe and uncomplicated malaria cases (p-value < 0.01) were observed. The severe and uncomplicated groups showed significant differences in haemoglobin (gm/dL), haematocrit, red blood cell count, reticulocyte, serum iron, and ESR levels (p-value < 0.05). The severe malaria group had considerably reduced mean platelet counts (p-value < 0.01). Only five instances (7.3%) had an appropriate erythropoietic response after day 28. Erythroid hyperplasia with dyserythropoietic alterations was most common in patients with severe anaemia and low-grade parasitaemia. Conclusion Acute falciparum malaria is often associated with haematological alterations. Anaemia and thrombocytopenia were the most expected alterations associated with disease prognosis and mortality.

Assessment of dietary supplementation of green iron oxide nanoparticles: impact on growth performance, ammonia emissions, carcass criteria, tissue iron content, and meat quality in broiler chickens under hot climate conditions.

The potential significance and importance of green iron nanoparticles (Nano-Fe) in poultry production lie in their capability to effectively tackle iron deficiency in poultry. Iron, an indispensable mineral for numerous physiological functions in birds, such as oxygen transport, energy metabolism, and immune response, underscores the critical need for adequate iron levels. Nevertheless, conventional iron supplementation methods frequently face hurdles like limited bioavailability rates in poultry. To enhance performance, and promote sustainable broiler productivity, Nano-Fe showed promise as an efficient feed supplement for broiler chickens. The objective of this study was to assess the impact of green Nano-Fe inclusions in diets on growth, ammonia excretion, carcass criteria, and meat quality in broiler chickens. A total of 192 one-day-old male Ross 308 broiler chicks, were assigned to three treatment diets including Nano-Fe oxide at 0, 20, or 40 mg/kg, respectively, for 42 days. Each treatment comprised eight replicates, each with eight broiler chicks. Two phases comprised the 42-day study (0 to 21 days for the starter and 21 to 42 days for the finisher). In comparison to the control group, the Nano-Fe oxide groups 20 mg/kg and 40 mg/kg linearly improved (p < 0.05) body weight (R 2 = 0.574) and body weight gain (R 2 = 0.367) under hot climatic conditions at 42 days of age. Furthermore, Nano-Fe oxide to broiler diets, improved (linear, p < 0.05) feed conversion ratio (R 2 = 0.424) throughout whole periods. The feed intake did not show any significant difference (p > 0.05) among groups during the experimental periods under hot climatic conditions. The ammonia content of excreta (R 2 = 0.454) was linearly decreased (p < 0.05) with increasing Nano-Fe oxide levels in broiler diets compared to control at 21 and 42 days of age under hot climatic conditions. Nano-Fe oxide positively influences cook loss, water-holding capacity, and iron content in various tissues. Moreover, it contributes to a healthier carcass yield and reduced abdominal fat. In conclusion, broiler chickens fed diets containing Nano-Fe oxide at 20 mg/kg and 40 mg/kg demonstrated enhanced growth performance, improved meat quality, increased iron content in tissues, higher dressing percentage, and reduced abdominal fat deposition. Future research should explore the impact of green Nano-Fe oxide on additional factors such as the microbiome and gene expression related to immunity and heat stress.

Golgi protein ACBD3 downregulation sensitizes cells to ferroptosis.

Ferroptosis, a form of cell death driven by iron-dependent lipid peroxidation, is emerging as a promising target in cancer therapy. It is regulated by a network of molecules and pathways that modulate lipid metabolism, iron homeostasis and redox balance, and related processes. However, there are still numerous regulatory molecules intricately involved in ferroptosis that remain to be identified. Here, we indicated that suppression of Golgi protein acyl-coenzyme A binding domain A containing 3 (ACBD3) increased the sensitivity of Henrieta Lacks and PANC1 cells to ferroptosis. ACBD3 knockdown increases labile iron levels by promoting ferritinophagy. This increase in free iron, coupled with reduced levels of glutathione peroxidase 4 due to ACBD3 knockdown, leads to the accumulation of reactive oxygen species and lipid peroxides. Moreover, ACBD3 knockdown also results in elevated levels of polyunsaturated fatty acid-containing glycerophospholipids through mechanisms that remain to be elucidated. Furthermore, inhibition of ferrtinophagy in ACBD3 downregulated cells by knocking down the nuclear receptor co-activator 4 or Bafilomycin A1 treatment impeded ferroptosis. Collectively, our findings highlight the pivotal role of ACBD3 in governing cellular resistance to ferroptosis and suggest that pharmacological manipulation of ACBD3 levels is a promising strategy for cancer therapy.

Social defeat stress impairs systemic iron metabolism by activating the hepcidin-ferroportin axis.

Chronic psychological stress has been reported to decrease circulating iron concentrations and impair hematopoiesis. However, the underlying mechanisms remain unclear. This study aimed to investigate the effects of psychological stress on biological iron metabolism by using the social defeat stress (SDS) model, a widely used model of depression. Compared with control mice, mice subjected to SDS (SDS mice) had lower social interaction (SI) behavior. The SDS mice also showed impaired hematopoiesis, as evidenced by reduced circulating red blood cell counts, elevated reticulocyte counts, and decreased plasma iron levels. In the SDS mice, the iron contents in the bone marrow decreased, whereas those in the spleen increased, suggesting dysregulation in systemic iron metabolism. The concentrations of plasma hepcidin, an important regulator of systemic iron homeostasis, increased in the SDS mice. Meanwhile, the concentrations of ferroportin, an iron transport protein negatively regulated by hepcidin, were lower in the spleen and duodenum of the SDS mice than in those of the control mice. Treatment with dalteparin, a hepcidin inhibitor, prevented the decrease in plasma iron levels in the SDS mice. The gene expression and enzyme activity of furin, which converts the precursor hepcidin to active hepcidin, were high and positively correlated with plasma hepcidin concentration. Thus, furin activation might be responsible for the increased plasma hepcidin concentration. This study is the first to show that psychological stress disrupts systemic iron homeostasis by activating the hepcidin-ferroportin axis. Consideration of psychological stressors might be beneficial in the treatment of diseases with iron-refractory anemia.

Ferritin and Serum Iron in a Causal Relationship with Estrogen Receptor-Negative Breast Cancer: a Two-Sample Mendelian Randomization Study.

The aim of this study was to explore the causal relationship between different serum iron statuses (ferritin, transferrin, transferrin saturation, and serum iron) and the occurrence of estrogen receptor (ER)-positive or ER-negative breast cancer. The summary data on serum iron status exposure were gathered from the IEU OpenGWAS Project, the UK Biobank, and other databases. Concurrently, the summary data for ER+ and ER- breast cancer are sourced from the Breast Cancer Association Consortium (BCAC). By examining the causal link between iron status and breast cancer, we deployed five distinct Mendelian randomization (MR) algorithms, namely MR-Egger, inverse variance weighted (IVW), weighted median, simple mode, and MR-PRESSO. To assess heterogeneity and horizontal pleiotropy, Cochran's Q and MR-Egger algorithms were applied, respectively. Elevated ferritin levels are associated with an increased risk of ER-negative breast cancer (OR(IVW) = 1.042, 95% CI (1.005, 1.081), p = 0.025; OR (weighted median) = 1.050, 95% CI (1.001, 1.102), p = 0.046; and OR (MR-PRESSO) = 1.042, 95% CI (1.005, 1.081), p = 0.039). Conversely, an increase in the serum iron level is linked to a reduced risk of ER-negative breast cancer (OR (IVW) = 0.791, 95% CI (0.649, 0.962), p = 0.019; and OR (MR-PRESSO) = 0.791, 95% CI (0.649, 0.962), p = 0.028). However, there is no evidence of a causal relationship between transferrin, transferrin saturation, and ER-negative breast cancer. For ER-positive breast cancer, none of the four different iron statuses demonstrated a causal relationship. Ferritin is positively correlated with ER-negative breast cancer, while serum iron is negatively associated with ER-negative breast cancer. However, there is no causal relationship between the four iron statuses and ER-positive breast cancer.

Anemia and Iron Profile in Hemodialysis and Nonhemodialysis Patients with Chronic Kidney Disease

Abstract BACKGROUND: Chronic kidney disease (CKD) is a global health concern, with anemia being a significant complication. Anemia in CKD patients is multifactorial and often leads to poorer outcomes. Assessing the iron profile, including serum ferritin, iron, and transferrin saturation, is crucial for identifying absolute or functional iron deficiency anemia (IDA). An objective evaluation of the iron profile is essential for effective and comprehensive management of anemia. MATERIALS AND METHODS: The study involved 100 adult patients with CKD and anemia, who were divided into two groups based on age and sex. The patients were divided into two groups: one received regular hemodialysis (HD) 2–3 times per week, whereas the other received no dialysis or dialysis infrequently. Exclusion criteria included infections, inflammation, renal injury, neoplasms, acute hemolysis, and thalassemia. RESULTS: Anemia is a common complication in patients with CKD, both those on HD and non-HD. Among the types of anemia observed, 50% of HD patients and 72% of non-HD CKD patients have normochromic anemia. In addition, 46% of HD patients and 24% of non-HD patients have IDA. Specifically, 24% of HD patients have absolute IDA and 22% have functional IDA, compared to 12% of both absolute and functional IDA in non-HD CKD patients, with a significant statistical difference between the two groups. Furthermore, serum iron and transferrin saturation levels show significant differences between HD and non-HD CKD patients. CONCLUSION: Anemia, especially IDA in CKD patients undergoing HD, requires accurate diagnosis through transferrin saturation and serum iron levels, and customized treatment based on dialysis status and anemia type is crucial.

Role of hypoxia-inducible-factor-1α (HIF-1α) in ferroptosis of adipose tissue during ketosis

Postpartum cows experience lipolysis in adipose tissue due to negative energy balance (NEB), and accumulation of free fatty acids (FFA) leads to metabolic stress in adipose tissue. Ferroptosis is a type of cell death triggered by excessive buildup of iron-dependent lipid peroxides, which is involved in the occurrence and development of various metabolic diseases in nonruminants. However, it is still unclear whether ferroptosis occurs in the adipose tissue of ketotic cows and the regulatory mechanisms behind ferroptosis. Despite multiple studies demonstrating the significant involvement of hypoxia-inducible-factor-1α (HIF-1α) in regulating cellular dysfunction, its specific function in adipose tissue of ketotic dairy cows remains uncertain, particularly its regulation of oxidative stress and ferroptosis. The study aimed to explore the impact of HIF-1α on oxidative stress and ferroptosis in bovine subcutaneous adipose tissue and isolated adipocytes. The adipose tissue of clinical ketosis cows (n = 15) with a serum BHB concentration of 3.13 mM (interquartile range = 0.14) and healthy cows (n = 15) with a serum BHB concentration of and 0.58 mM (interquartile range = 0.13) was collected. The results showed that the concentrations of lipid peroxidation malondialdehyde (MDA), reactive oxygen species (ROS), Fe2+ and total iron were increased in adipose tissue of cows with ketosis, while the contents of glutathione (GSH) were reduced. Furthermore, the protein levels of HIF-1α, heme oxygenase 1 (HMOX1), catalase (CAT), superoxide dismutase 1 (SOD1), acyl-CoA synthetase 4 (ACSL4), and nuclear factor erythroid-derived 2-like 2 (NFE2L2) exhibited higher abundance in adipose tissue obtained from cows with ketosis, whereas the protein abundance of solute carrier family 7 member 11 (SLC7A11), glutamate cysteine ligase catalytic subunit (GCLC), kelch-like ECH-associated protein 1 (KEAP1), glutamate cysteine ligase regulatory subunit (GCLM) and glutathione peroxidase 4 (GPX4) were lower. To simulate the ferroptosis state of adipose tissue in ketotic cows, primary bovine adipocytes were isolated from the adipose tissue of healthy cows and cultured with erastin to construct ferroptosis model. Adipocytes were cultured with either an adenovirus overexpressing HIF-1α or small interfering RNA targeting HIF-for 48 h, followed by exposure to erastin (1 μM) for 24 h. Treatment with erastin led to higher protein abundance of CAT, SOD1, NFE2L2 and HMOX1, while it inhibited the protein expression levels of GCLC, SLC7A11, GCLM, GPX4 and KEAP1. Furthermore, erastin treatment elevated the levels of ROS, MDA, Fe2+, total iron and reduced the content of GSH. The overexpression of HIF-1α reversed the erastin-induced decreases in the protein abundance of GPX4 and SLC7A11, as well as the levels of MDA, ROS, Fe2+ and total iron, while significantly increasing protein abundance and content of CAT, SOD1, NFE2L2, HMOX1, GCLC, GCLM, GPX4, SLC7A11 and GSH. Conversely, the silencing of HIF-1α further exacerbated the erastin-induced levels of MDA, ROS, Fe2+ and total iron, while inhibiting the upregulation of SOD1, CAT, NFE2L2 and HMOX1. Collectively, these findings suggest that activation of HIF-1α may function as an adaptive mechanism to mitigate ferroptosis and alleviate oxidative stress in adipose tissue.

Evaluation of the Role of Trace Elements in Malignant Transformation of Oral Submucous Fibrosis: A Study in the Population of Krishna District, Andhra Pradesh, India.

Oral submucous fibrosis (OSMF) is a chronic, potentially malignant disorder linked predominantly to areca nut chewing. This study investigates the role of serum trace elements (Cu, Fe, Zn, Se) in the progression and malignant transformation of OSMF. A community-based cross-sectional study involved 80 participants from the Government Dental College, Vijayawada, Krishna District, AP. Participants were divided into four groups: areca nut users without OSMF, areca nut users with OSMF, areca nut users with malignant-transformed OSMF, and healthy controls. Blood samples were analyzed for serum iron, copper, zinc, and selenium levels. Significant differences were found in serum copper(P=0.032) and zinc levels (P=0.006), with elevated levels observed in the malignant-transformed OSMF group compared to controls. No significant differences were observed in serum iron (P=0.542) and selenium levels(P=0.062) across the groups. Elevated serum copper levels can serve as a reliable diagnostic marker for malignant transformation in OSMF. Future research should explore the potential therapeutic benefits of copper chelation in OSMF management.

Iron Status, Blood Sugar and Dietary Habit Assessment of Pregnant Mothers Attending Antenatal Clinical in Urban and Rural Areas of Owerri, Imo State, Nigeria

Iron Status, Blood Sugar and Dietary Habit Assessment of Pregnant Mothers Attending Antenatal Clinical in Urban and Rural Areas of Owerri, Imo State, Nigeria