Iron Status Research Articles

The hepcidin-ferroportin axis modulates liver endothelial cell BMP expression to influence iron homeostasis in mice

The liver hormone hepcidin regulates systemic iron homeostasis to provide enough iron for vital processes while limiting toxicity. Hepcidin acts by degrading its receptor ferroportin (encoded by Slc40a1) to decrease iron export to plasma. Iron controls hepcidin production in part by inducing liver endothelial cells (LECs) to produce bone morphogenetic proteins (BMPs), which activate hepcidin transcription in hepatocytes. Here, we used in vitro and in vivo models to investigate whether ferroportin contributes to LEC intracellular iron content to modulate BMP expression and thereby hepcidin. Quantitative proteomics of LECs from mice fed different iron diets demonstrated an inverse relationship between dietary iron and endothelial ferroportin expression. Slc40a1 knockdown primary mouse LECs and endothelial Slc40a1 knockout mice exhibited increased LEC iron and BMP ligand expression. Endothelial Slc40a1 knockout mice also exhibited altered systemic iron homeostasis with decreased serum and total liver iron but preserved erythropoiesis. Although endothelial Slc40a1 knockout mice had similar hepcidin expression as control mice, hepcidin levels were inappropriately high relative to iron levels. Moreover, when iron levels were equalized with iron treatment, hepcidin levels were higher in endothelial Slc40a1 knockout mice than controls. Finally, LEC ferroportin levels were inversely correlated with hepcidin levels in multiple mouse models, and treatment of hepcidin-deficient mice with mini-hepcidin decreased LEC ferroportin expression. Overall, these data show that LEC ferroportin modulates LEC iron and consequently BMP expression to influence hepcidin production. Furthermore, LEC ferroportin expression is regulated by hepcidin, demonstrating bidirectional communication between LECs and hepatocytes to orchestrate systemic iron homeostasis.

Iron deficiency and obesity in children: is there a relationship?

A close relationship between obesity and iron metabolism has been proven. Aim. To study the features of iron metabolism in obese children by evaluating dietary iron intake and the level of laboratory markers of iron status, with the goal of improving prevention and correction of identified disorders in this cohort of children. Materials and methods. The actual dietary iron intake was assessed in 75 obese children aged 7-17 years using the Optimal Nutrition 5.0 software. A set of clinical and laboratory research methods was performed in 30 children to identify iron deficiency, as well as a questionnaire on the symptoms of iron deficiency. Results. One third of children have insufficient iron intake with food. Most of the examined children complained and had clinical symptoms characteristic of iron deficiency in the body. 86.7% of obese children had one or more signs of iron deficiency. Laboratory diagnostics using only a general clinical blood test showed insufficient detection of iron deficiency: only in 13.3% of children this analysis showed the presence of abnormalities characteristic of iron deficiency. In the other children, it was detected after a biochemical blood test. Conclusions. The majority of obese children show both clinical and laboratory evidence of iron deficiency, which may contribute to the pathogenesis of obesity-related conditions. Biochemical blood tests are essential for accurate diagnosis of iron deficiency, as standard clinical blood test may not always show the presence of iron deficiency. The high prevalence of iron deficiency indicates the need for targeted nutritional iron support for obesity in children.

Iron load in the normal aging brain measured with QSM and at 7T: findings of the SENIOR cohort.

Iron accumulates in the brain during aging and is the focus of intensive research as an abnormal load, particularly in Deep Gray Matter (DGM), is related to neurodegeneration. Magnetic Resonance Imaging (MRI) metrics such as Quantitative Susceptibility Mapping (QSM) and apparent transverse relaxation rate can be used to follow up iron in vivo. While the influence of age and sex on iron levels has already been reported, a careful consideration of neuronal risk factors, as well as for an enhanced sensitivity, is needed to define the normal evolution. QSM and at ultra-high field MRI are used to study iron in DGM using a carefully-characterized cohort of the healthy aging brain (SENIOR). Seventy-seven cognitively healthy elders (from 54 to 78 y/o) with clinical, biology, genetics, and cardiovascular risk factors careful evaluation. Differences linked with age, sex, cardiovascular risk factors and weight are studied. Age and sex have an influence on the brain iron deposition measured by QSM and in a context of normal aging, without appearance of a pathological neurodegenerative process. Iron deposition shows higher values in the caudate and the putamen in older participants. Female participants present a higher level of iron in the amygdala, and males in the thalamus. Female participants also present differences in the accumbens, caudate and hippocampus when evaluating the joint age and sex effect. Participants with higher cardiovascular risk factors showed higher values of the iron, even without any impairment in their cognitive capability. An overweight is related with a higher iron load in the putamen for QSM and in female participants. We controlled that these modifications of iron deposition are not related to a specific profile in the genotype of ApoE loci. Establishing baseline values of QSM and as iron probes in the context of aging is essential to determine differences in the process of neurodegeneration. Age and sex of participants are important factors that affect brain iron normal values. On the other hand, the presence of cardiovascular risk factors, which can be associated with age related diseases, can also potentially be linked with the iron deposition in the brain.

Upregulation of PRRX2 by silencing Marveld3 as a protective mechanism against radiation-induced ferroptosis in skin cells.

Radiation-induced skin injury (RISI) represents a significant complication in patients receiving radiotherapy and individuals exposed to nuclear accidents, characterized by a protracted wound-healing process relative to injuries from other etiologies. Current preventive and management approaches remain inadequate. Consequently, investigating efficacious intervention strategies that target the disease's progression characteristics holds significant practical importance. Small interfering RNA (siRNA) and overexpression plasmid were used to modulate the expression of Marvel domain containing 3 (Marveld3) and paired related homeobox 2 (PRRX2). Protein and mRNA levels were estimated by Western Blot and real-time PCR, respectively. Intracellular levels of Malondialdehyde (MDA), a terminal product of lipid peroxidation, were measured following the manufacturer's protocol for MDA assay kit. Similarly, intracellular levels of ferrous iron (Fe2+) and reactive oxygen species (ROS) were determined using their respective assay kits. Lipid peroxidation status within the cells was evaluated via BODIPY staining. Immunohistochemistry was conducted to ascertain the expression of PRRX2 in skin tissues collected at various time points following irradiation of rats. The H-score method was used to evaluate the percentage of positively stained cells and staining intensity. RNA sequencing, Gene Ontology (GO) analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were conducted by OE Biotech Company. In this study, our findings indicated that Marveld3 suppression could effectively inhibit lipid peroxidation levels in irradiated skin cells, concomitantly reducing intracellular Fe2+ content. Additionally, the silencing of Marveld3 effectively abrogated the impact of a ferroptosis agonist on cellular viability, resulting in the upregulation of 66 and 178 genes, as well as the downregulation of 188 and 31 genes in irradiated HaCaT and WS1 cells, respectively. Among the differentially expressed genes, the PRRX2 which was found to be involved in the process of ferroptosis, exhibited statistically significant upregulation. And the upregulation of PRRX2 expression may attenuate radiation-induced lipid peroxidation in skin cells, thereby functioning as a potential stress-responsive mechanism to counteract radiation effects. This study elucidates the role of Marveld3 in radiation-induced ferroptosis in skin cells. Inhibition of Marveld3 led to the upregulation of PRRX2, which subsequently resulted in a reduction of Fe2+ and ROS levels, as well as the suppression of lipid peroxidation. These effects collectively mitigated the occurrence of ferroptosis.

Intracellular Magnetic Hyperthermia Sensitizes Sorafenib to Orthotopic Hepatocellular Carcinoma Via Amplified Ferroptosis.

Sorafenib (SRF) is recognized as the primary treatment for hepatocellular carcinoma (HCC), yet the emergence of SRF resistance in many HCC patients results in unfavorable outcomes. Enhancing the efficacy of SRF in HCC remains a significant challenge. SRF works in inducing ferroptosis, a form of cell death, in cancer cells through the inhibition of glutathione peroxidase 4 (GPX4). The effectiveness of this process is limited by the low levels of cellular iron and reactive oxygen species (ROS). A promising approach to circumvent this limitation is the use of intracellular magnetic hyperthermia (MH) mediated by magnetic iron oxide nanomaterials (MIONs). When MIONs are subjected to an alternating magnetic field (AMF), they heat up, enhancing the Fenton reaction, which in turn significantly increases the production of ROS within cells. In this study, we explore the capability of MH facilitated by high-performance ferrimagnetic vortex-domain iron oxide nanoring (FVIO) to enhance the effectiveness of SRF treatment in HCC. The increased iron uptake facilitated by FVIO significantly enhances the sensitivity of HCC cells to SRF-induced ferroptosis. Moreover, the nanoheat generated by FVIO in response to an AMF further elevates ROS levels and stimulates lipid hydroperoxide (LPO) production and GPX4 inactivation, thereby intensifying ferroptosis. Both in vitro and in vivo animal studies demonstrate that combining FVIO-mediated MH with SRF significantly reduces cell viability and inhibits tumor growth, primarily through enhanced ferroptosis, with minimal side effects. The effectiveness of this combination therapy is affected by the ferroptosis inhibitor ferrostatin-1 (Fer-1) and the iron chelator deferoxamine (DFO). The combination treatment of FVIO-mediated MH and SRF offers a strategy for HCC treatment by promoting accelerated ferroptosis, presenting a different perspective for the development of ferroptosis-based anticancer therapies.

Impact of Boiling on Composition of Oven-Dried Curcuma Longa Linn Rhizomes

The effect of boiling Curcuma longa Linn rhizomes prior to oven drying on its proximate, mineral and phytochemical composition was studied. Fresh turmeric rhizomes were sliced to 5 mm thickness and then divided into two parts. The first part was oven dried directly while the second part was boiled prior to oven drying. Both products were then pulverised and subjected to laboratory analysis following standard procedures of AOAC and spectrometry. Boiling had an impact on the proximate composition as there were significant (P<0.05) reductions in ether extract, crude fibre and crude protein. Sodium, calcium, potassium and phosphorus contents were significantly reduced with a significant increase in levels of magnesium, zinc and iron (P<0.05). Significant reductions in phytochemicals due to boiling prior to oven drying were also recorded (P<0.05). This experiment therefore shows that boiling Curcuma longa Linn rhizomes prior to oven drying could be of pharmacological importance.

SAT1/ALOX15 Signaling Pathway Is Involved in Ferroptosis After Skeletal Muscle Contusion

Skeletal muscle contusion (SMC) is common in daily life and clinical practice, but the molecular mechanisms underlying SMC healing are unclear. Ferroptosis, a regulated cell death type, has gained attention recently. We observed iron overload in skeletal muscle following contusion through HE and Perls staining. Abnormal iron levels are highly likely to induce ferroptosis. Therefore, we aimed to explore whether iron overload after contusion leads to ferroptosis in skeletal muscle and the underlying mechanisms, which will help us understand the effects of iron abnormalities on skeletal muscle repair. Initially, we searched SMC gene expression profiles from the GEO database and used bioinformatics analysis to reveal ferroptosis occurrence. Then, we identified the gene sat1 plays an important role in this process. We further established a rat SMC model and treated rats with ferroptosis inhibitors (Ferrostatin-1, Deferoxamine). Our findings confirmed iron overload from SMC can lead to ferroptosis in rats. We also demonstrated that SAT1 can regulate ferroptosis by affecting ALOX15. Moreover, we constructed a ferroptosis L6 cell model and found that SAT1 knockdown significantly inhibited ALOX15 expression and reduced cellular lipid peroxidation. In conclusion, these results indicated ferroptosis can occur following SMC, and SAT1, as a key regulator, affects skeletal muscle injury healing by mediating high ALOX15 expression, which in turn regulates lipid peroxidation.

Zinc oxide nanoparticle biofortification of lentil seedlings enhances plant growth and zinc bioavailability in rats

This study aimed to evaluate the potential of zinc oxide nanoparticles (ZnO NPs) in the biofortification of lentil seedlings and subsequently improve the Zn status in rats. In the first phase of the study, the effects of various ZnO NPs concentrations (0, 10, 20, 40, 80, and 160 ppm) on the lentil growth, Zn accumulation, and other physiological parameters were investigated. Subsequently, the rats were fed ZnO NP-biofortified lentil seedlings (20 and 160 ppm) to assess their impact on animal health and Zn status. The results highlighted a concentration-dependent response of lentil seedlings to ZnO NPs, with optimal growth observed at 20 ppm, whereas higher concentrations inhibited lentil growth. Pigment and biochemical analyses revealed a complex interplay between chlorophyll, carotenoids, soluble sugars, and proteins with distinct responses to nanoparticle concentrations. Elevated levels of hydrogen peroxide and malondialdehyde of lentil seedlings at high concentrations of ZnO NPs suggest oxidative stress, countered by the upregulation of antioxidant enzymes and increased phenolic compounds. On the other hand. animal studies have showed that ZnO NP-biofortified lentil seedlings enhance serum zinc and magnesium levels in rats without affecting body weight. While serum triglyceride levels of rats decreased in both treatment groups, an elevation in creatinine and a marked increase in aspartate aminotransferase (AST) levels were observed at a higher ZnO NP concentration (160 ppm), indicative of potential kidney and liver stress. Paradoxically, serum iron levels were lower in all groups consuming lentil seedlings than in the control group, suggesting a potential interaction between lentil components and iron metabolism. These findings suggest that ZnO NP-biofortified lentils may be a promising approach to enhance Zn nutrition; however, further investigation is needed to optimize ZnO NPs concentration and assess long-term safety.

Cognitive performance, mental health, and quality of life in β-thalassemia individuals: a comprehensive analysis

IntroductionBeta-thalassemia is a prevalent autosomal recessive haemolytic disorder, particularly in the Middle East. Patients with beta-thalassemia major (βTM) require iron chelation therapy and regular blood transfusions, while those with beta-thalassemia intermedia (βTI) exhibit milder symptoms. This study aimed to evaluate cognitive function, behavioural problems, quality of life, and related aspects in individuals with βTM and βTI.MethodsThe cross-sectional study included 20 βTM participants, 20 βTI participants, and 19 healthy controls. Participants underwent psychiatric interviews, the Wechsler Adult Intelligence Scale (WAIS-III), Symptom Checklist-90 Revised (SCL-90R), and Short-Form Health Survey (SF-36). Clinical data and laboratory investigations were also collected.ResultsβTM participants exhibited lower vocabulary and picture completion scores on the WAIS-III compared to other groups. βTI participants had significantly higher scores on SCL-90R subscales for somatization, depression, anxiety, paranoid ideation, and psychoticism. Both patient groups reported poorer quality of life across all SF-36 domains compared with controls. Longer disease duration correlated with lower levels of somatization, interpersonal sensitivity, depression, anxiety, and paranoid ideation. Less frequent blood transfusions were associated with better physical and mental health summary scores but also higher somatization. Elevated serum iron levels corresponded with increased anxiety, hostility, and psychoticism symptoms, while higher serum ferritin related to more obsessive–compulsive behaviours but less somatization and psychoticism.ConclusionsIndividuals with thalassemia exhibit cognitive deficits, psychological disturbances, and diminished quality of life, with distinct patterns depending on disease severity. Regular monitoring and appropriate interventions are crucial for optimizing their overall well-being and functioning.

The role of genetically predicted serum iron levels on neurodegenerative and cardiovascular traits.

Iron is an essential mineral that supports numerous biological functions. Studies have reported associations between iron dysregulation and certain cardiovascular and neurodegenerative diseases, but the direction of influence is not clear. Our goal was to use computational approaches to better understand the role of genetically predicted iron levels on disease risk. We meta-analyzed genome-wide association study summary statistics for serum iron levels from two cohorts and two previous meta-analyses. We then obtained summary statistics from 11 neurodegenerative, cerebrovascular, cardiovascular or lipid traits to assess global and regional genetic correlation between iron levels and these traits. We used two-sample Mendelian randomization (MR) to estimate causal effects. Sex-stratified analyses were also carried out to identify effects potentially differing by sex. Overall, we identified three significant global correlations between iron levels and (i) coronary heart disease, (ii) triglycerides, and (iii) high-density lipoprotein (HDL) cholesterol levels. A total of 194 genomic regions had significant (after correction for multiple testing) local correlations between iron levels and the 11 tested traits. MR analysis revealed two potential causal relationships, between genetically predicted iron levels and (i) total cholesterol or (ii) non-HDL cholesterol. Sex-stratified analyses suggested a potential protective effect of iron levels on Parkinson's disease risk in females, but not in males. Our results will contribute to a better understanding of the genetic basis underlying iron in cardiovascular and neurological health in aging, and to the eventual identification of new preventive interventions or therapeutic avenues for diseases which affect women and men worldwide.

Comparative Study of the Phytonutrients Contents of Three Plants Grown as Vegetables in Burkina Faso

Diets with a high proportion of plants are nutritionally challenging. These food and generally medicinal plants certainly contribute to reducing hunger and mortality from diet-related diseases worldwide. The aim of this study is to assess the nutritional potential of <i>Cleome gynandra</i>, <i>Hibiscus sabdariffa</i> and <i>Corchorus olitorius</i>, three food plants widely consumed in Burkina Faso. The phytonutrient content of these three plants was assessed on a comparative basis. The parameters investigated in this study were: total ash and mineral content, total protein and carbohydrate content, total lipid content, vitamin C and provitamin A content. The results show that <i>Cleome gynandra</i> had the highest protein content at 160.6 ± 0.32 mg EBSA/g. Lipid levels were relatively close for all three leafy vegetables. They ranged from 3.36% to 4.35%, with the highest content obtained with <i>Corchorus olitorius</i>. Carbohydrate content values ranged from 0.05 to 0.15 mg/mg Glucose equivalent. The highest value was found in <i>Hibiscus sabdariffa</i> (0.15 Glucose equivalent mg/mg). The vitamin C contents of these three plants are relatively close, with the highest vitamin C content obtained with <i>Corchorus olitorius</i> (1.91±1.9 ug/mg). Provitamin A levels varied from 0.196 to 0.312 betac equivalent mg/g ES. The highest content was obtained with <i>Cleome gynandra</i>. Zinc, Calcium, Potassium, Iron, Magnesium and Sodium are also present in all three plants, with varying levels. <i>Cleome gynandra</i> stands out with higher levels of Zinc (59.79 mg/kg), Calcium (9517.5 mg/kg), Potassium (5817.5 mg/kg) and Iron (212.1 mg/kg). These different values justify <i>cleome gylandra</i>'s highest total ash content. These edible plants are therefore rich in phytonutrients, and their consumption could help ensure good health and prevent various chronic diseases.

Preterm Piglets Born by Cesarean Section as a Suitable Animal Model for the Study of Iron Metabolism in Premature Infants.

Preterm infants are most at risk of iron deficiency. However, our knowledge of the regulation of iron homeostasis in preterm infants is poor. The main goal of our research was to develop and validate an animal model of human prematurity to assess iron status in preterm infants. We performed a cesarean section on sows on the 109th day of pregnancy, which corresponds to the last trimester of human pregnancy. Preterm piglets showed decreased body weight, red blood cell indices, plasma iron level and transferrin saturation. Interestingly, higher hepatic and splenic non-heme iron content and plasma and hepatic ferritin levels were found in premature piglets compared with term ones. In addition, premature piglets showed higher mRNA levels of iron-regulatory hormone hepcidin in the liver than term animals, which have not been reflected in higher plasma hepcidin-25 levels. We also showed changes in hepcidin regulators, including hepatic bone morphogenetic protein 6, plasma erythroferrone and growth differentiation factor 15 in preterm piglets. Consequently, no difference was observed in iron-exporter ferroportin levels in the spleen and liver. Overall, it seems that premature piglets show a pattern of iron metabolism characteristic of functional iron deficiency and iron accumulation in the tissue.

A novel synthetic compound, deferiprone–resveratrol hybrid (DFP-RVT), promotes hepatoprotective effects and ameliorates iron-induced oxidative stress in iron-overloaded β-thalassemic mice

A high amount of iron in β-thalassemia patients can lead to oxidative stress and organ dysfunction, especially liver, the main iron accumulated organ. Iron catabolism causes the generation of reactive oxygen species (ROS), triggering liver inflammation, fibrosis, and cirrhosis. Deferiprone-resveratrol hybrid (DFP-RVT) is chemically synthesized by combining deferiprone (DFP) and resveratrol (RVT) which shows an iron-chelating property along with antioxidant activity. This study explored the hepatoprotective effect of DFP-RVT in iron overloaded β-knockout (BKO) thalassemic mice. The results revealed that DFP-RVT treatment improved liver function in iron-overloaded BKO mice by reducing liver enzymes and increasing hepcidin levels compared to iron overload control mice. Both DFP alone and DFP-RVT treatment groups demonstrated iron chelation effects by decreasing liver iron content (LIC), iron profiles, and iron deposition in the liver. Moreover, DFP-RVT powerfully showed antioxidant properties by decreasing liver and plasma thiobarbituric acid reactive substances (TBARs) and increasing reduced glutathione (GSH) and superoxide dismutase (SOD). Interestingly, transforming growth factor β1 (TGFβ1), which can contribute to chronic liver disease through liver injury, inflammation, fibrosis, and cirrhosis, is highly expressed in iron-overloaded mice. However, both DFP and DFP-RVT treatment significantly reduced TGFβ1 levels compared to the iron-overloaded group. Therefore, DFP-RVT could be a potent hepatoprotective compound through the mobilization of iron, reduction of ROS, improvement of liver enzymes, and alleviation of liver damage, potentially relieving liver dysfunction in iron-overloaded BKO mice.

Infant Food Flours Made from Local Products to Combat Acute Malnutrition in Children Under 5 Years Old in Côte D’ivoire

In Côte d'Ivoire, recurring stock shortages and difficulties in accessing specialized food products compromise nutritional treatment. This study proposes food formulas of flours composed of locally available products capable of meeting the protein-energy needs of children aged 6 to 59 months diagnosed with moderate acute malnutrition. The methodological approach consists of formulating and determining the physicochemical, nutrient, and functional characteristics of four new formulations (1F, 2F, 3F, 4F, and 5F). The results indicate that the formulated foods have high levels of calcium (215.60-252,29 mg/100g MS), potassium (555,70-789,29 mg/100 g MS), magnesium (261,26-200,63 mg/100g MS), iron (4,86-7,03 mg/100g MS) and phosphorus (392,36 -469,36 mg/100g MS). The fat content varies from 9.66% to 23.86%. The energy value determined for all flours corresponds well to the Codex. The food formulas developed would also be able to meet more than 100% of the daily requirement of vitamins E and B1. The phytate (180.26 - 227.05 mg/100 g) and oxalate (66.00 - 88.00 mg/100 g) contents are low. The presence of phenolic compounds, including flavonoids (7.78-15.44 mg/100 g) and antioxidant activity (31.09-32.84%) would be a significant asset. The levels of deoxynivalenol (62 μg/kg) recorded in flours are below 200 μg/kg recommended for infants and young children. The proposed formulations have high-water absorption capacity (136.15 -252.94%) and high solubility index (56.84 -59.2%). The wettability time ranges from 3.66 ± 0.16 s to 33.71 ± 0.23 s. Flours (1F, 2F, 3F, 5F) have a better absorption capacity for refined palm oil (132 %, 139 %, 121 %; 115 %). The proposed new formulations have nutritional characteristics close to standard data and could therefore be recommended for children aged 6 to 59 months for complementary feeding in the context of the fight against moderate acute malnutrition.

Delving into diversity: Exploring different risk factors of premature greying of hair.

Dear Madam, Hair is said to grey prematurely when a minimum of five grey hairs occur before the age of 20 in Caucasians, 25 in Asians and 30 in Africans1. Some authors propose using 25 years as a cut-off for people in the South Asian subcontinent. Also, there's no universal grading system for premature greying of hair (PGH). This letter addresses the various evolving risk factors for PGH in young adults worldwide. PGH may be familial or genetically influenced, traveling in an Autosomal Dominant pattern. A positive family history, in particular the paternal history is the most powerful risk factor2. PGH is also linked to nutritional deficiencies including vitamins (especially B12) and minerals. For example in one study, significantly lower levels of serum calcium, ferritin, vitamin B12, and high HDL were observed in patients3. T3 and T4 act on hair follicles to cause melanogenesis and their deficiency is therefore associated with PGH, alopecia, and changes in hair morphology. Another study found notably reduced levels of copper in cases (PGH) as compared to the control group. This study, however, did not observe lower levels of zinc or iron among the affected population. A separate case-control study concerning the association of epidemiological and biochemical factors with PGH reported that a significantly higher percentage of individuals with premature greying had atopic diathesis, led sedentary lifestyles, had family histories of the condition, smoked, and had reported higher levels of perceived stress compared to controls. Though, interestingly enough, regular application of hair oil seemed to confer a safeguarding effect against premature greying. Upon further review of the literature, it became apparent that both BMI and exposure to sunlight emerged as substantial predictors of PGH. Despite the prescription of various vitamins and minerals like biotin, calcium pantothenate, zinc, copper, and selenium (all of which have been recognized as risk factors), the outcomes have been disappointing. Calcium pantothenate is frequently recommended for premature greying of hair (PGH)4. This highlights an existing knowledge gap concerning the precise causative risk factors, necessitating further investigation for a comprehensive understanding and improved management of individuals experiencing premature greying of hair.

Advanced chelate technology-based trace minerals reduce inflammation and oxidative stress in Eimeria-infected broilers by modulating NF-kB and Nrf2 pathways

This study investigated the effects of substituting inorganic trace minerals (ITM) with advanced chelate technology-based TM (ACTM) in broiler chicken feed on productive performance, metabolic profile, humoral immunity, antioxidant status, and modulation of NF-kB and Nrf2 signaling pathways in mixed Eimeria species exposure. The study involved 480 newly hatched male broiler chickens, which were divided into 5 treatment groups, each with 6 replicate cages and 16 chickens per replicate. The experimental treatments included an uninfected negative control group fed a basal diet with recommended inorganic TM levels (NC), an infected positive control group fed the same diet (PC), a PC group supplemented with salinomycin (SAL), and two PC groups in which the basal diet was replaced with 50% and 100% ACTM instead of inorganic TM (ACTM50 and ACTM100, respectively). All groups, except for the NC group, were orally challenged with mixed Eimeria species oocysts on day 14. According to the results, the PC group showed lower feed intake, breast yield, low-density lipoprotein-cholesterol concentration, lactobacillus spp. counts, and serum IgG levels, but higher jejunal TGF-β expression versus the NC group. The broilers in the NC, SAL, and ACTM100 groups showed higher body weight gain, carcass yield, and TGF-β expression, but lower serum alkaline phosphatase activity, ileal E. coli count, and jejunal expression levels of IL-1β, IL-6, IFN-γ, Nrf2, and SOD1 compared to the PC group, with the NC group having the highest body weight gain and lowest IL-1β and Nrf2 expression levels. Furthermore, the administration of ACTM100 treatment improved feed efficiency, increased serum iron, zinc, manganese, and copper levels, enhanced total antioxidant capacity and different antioxidant enzyme activities, and reduced malondialdehyde concentration. In conclusion, complete replacement of ITM with ACTM effectively protects broilers from Eimeria infection, with similar positive effects to SAL treatment in terms of productive performance and anti-inflammatory responses and better antioxidant responses and mineral availability.

Targeting Ferroptosis with Small Molecule Atranorin (ATR) as a Novel Therapeutic Strategy and Providing New Insight into the Treatment of Breast Cancer

Background/Objectives: Ferroptosis results from the accumulation of iron-dependent lipid peroxides and reactive oxygen species (ROS). Previous research has determined the effect of atranorin (ATR) on other cell death mechanisms, but its potential for a ferroptotic effect depending on ROS levels is unclear. This study details the therapeutic role of small-molecule ATR through ferroptosis by suppressing MDA-MB-231, MCF-7, BT-474, and SK-BR-3 breast cancer cells. Methods: The anti-proliferative effect of ATR on cells was evaluated by xCELLigence analysis, and ferroptotic activity was evaluated by enzymatic assay kits. The changes in gene and protein expression levels of ATR were investigated by the qRT-PCR and western blot. In addition, mitochondrial changes were examined by transmission electron microscopy. Results: ATR was found to reduce cell viability in cancer cells in a dose- and time-dependent manner without showing cytotoxic effects on normal breast cells. In BT-474 and MDA-MB-231 cells, ATR, which had a higher anti-proliferative effect, increased iron, lipid peroxidation, and ROS levels in cells and decreased the T-GSH/GSSG ratio. The results revealed for the first time that small-molecule ATR exhibited anti-cancer activity by inducing the glutathione pathway and ferroptosis. Conclusions: This study highlights the potential of ATR as a drug candidate molecule that can be used in the development of new therapeutic strategies for the treatment of triple-negative and luminal-B breast cancer subtypes.

A Practical Study on the Relationship between Serum Iron Elevation and Liver Enzymes Plus Other Factors in Patients with Beta-Thalassemia

Thalassemia is a genetic condition characterized by faulty hemoglobin synthesis and low hemoglobin concentration. Overload of iron is an unavoidable condition experienced by severe thalassemia patients as a result of excessive blood transfusions. We looked at impaired liver function in thalassemia individuals with Iraq as a result of these issues. Our findings demonstrated serum activity in hepatocytes, as well as a large rise in GOT and AIP in patients with elevated iron levels and a substantial rise in TSB. All of these elements may work together or independently to create chronic liver disease by causing damage in cells via oxidative mechanisms.

Pre-operative CBC reflex testing prior to cardiac surgery identifies treatable causes of anemia

Abstract Blood transfusion during or after cardiac surgery has been linked to poor patient outcomes. It is therefore desirable to optimize hemoglobin status by identifying and treating anemia pre-operatively. In order to identify reversible causes of anemia efficiently in this patient cohort, we implemented a reflex order for our institution’s cardiothoracic surgery center, to be ordered for patients undergoing assessment for cardiac surgery. When ordered, complete blood count (CBC) results with a hemoglobin (Hgb) of less than 13 g/dL reflex automatically to the following laboratory tests: iron profile, ferritin, vitamin B12, and reticulocyte count. Methods The purpose of our study was to investigate the impact of this reflex order over the initial 6 months of implementation. Test results and patient notes were extracted from the electronic health record and analyzed. Results Over six months, the order was placed 99 times (median Hgb 13.4 g/dL), with 36 (36%) triggering the reflex (Hgb < 13 g/dL). Of these 36 patients, 19 were women and 17 were men, and the cohort had a median age of 69 years. The median Hgb was 11.9 g/dL, ranging from 7.1 to 12.9 g/dL, with a median mean corpuscular volume (MCV) of 89.6 fl. The median Hgb differed by sex: 11.6 g/dL for men, 12.2 g/dL for women. Of these 36 patients, 16 had signs of iron deficiency anemia (IDA) based on laboratory results (below reference interval for iron, transferrin saturation, or ferritin), and two patients were found with vitamin B12 below the reference interval. Chart review demonstrated that 13 of the 36 patients underwent follow-up after reflex laboratory tests resulted, defined as a new diagnosis, new treatment, and/or new consult addressing the patient’s anemia. Five of these patients were given a new diagnosis of IDA, all of which were started on iron therapy. Three patients were transfused packed red blood cells prior to surgery; one was started on vitamin B12 supplementation; two had consults placed to address anemia; and two were given a new diagnosis of unspecified anemia. Conclusion Pre-operative CBC reflex testing facilitates the efficient and timely identification of reversible causes of anemia in patients undergoing diagnostic workup prior to cardiac surgery, while avoiding unnecessary panel testing in non-anemic patients.

Fe and Mn Removal from Acid Mine Drainage by Utilizing Chlorella sorokiniana and Monoraphidium neglectum as Biosorbent

The mining industry generates acid mine drainage (AMD) characterized with a low pH value and high dissolved metal concentration that leads to the negative impacts on the environment and human health. The objectives of this research were to investigate the growth response of mixed culture of microalgae Chlorella sorokiniana and Monoraphidium neglectum in a liquid media contaminated with AMD; generate the optimum environmental conditions (pH value and contact time) to determine the efficiency biosorption of iron and manganese contained in the solution of AMD into the consortium of microalgae; and quantify the maximum removal amount of iron and manganese contained in the solution of AMD by utilizing microalgae consortium of Chlorella sorokiniana and Monoraphidium neglectum as biosorbent. AMD used in this research was characterized with a pH value of 1.65 with iron and manganese concentrations of 8.28 mg/L and 4.57 mg/L. The research of biosorption was conducted in 150 rpm with pH level variations of 4, 5, and 6, and contact time variations of 60, 120, and 180 min. The maximum value of iron and manganese removals occurred when pH level reached 5 at 180 min of contact time with removal efficiency of 89.73% for iron and 94.53% for manganese. The results proved that the mixed culture of microalgae namely Chlorella sorokiniana and Monoraphidium neglectum can be utilized to remove iron and manganese contained in acid mine drainage.