Iron Stores Research Articles

Renal damage-induced hepcidin accumulation contributes to anemia in angiotensinogen-deficient mice.

Angiotensin II (Ang II) is the most active peptide hormone produced by the renin-angiotensin system (RAS). Genetic deletion of genes that ultimately restrict Ang II formation has been shown to result in marked anemia in mice. In this study, adult mice with a genetic deletion of the RAS precursor protein angiotensinogen (Agt-KO) were used. Experimental analyses included capillary hematocrit, hemogram, plasma and tissue iron quantifications, expression analyses of genes encoding relevant proteins for body iron homeostasis in different organs as well as plasma and urine hepcidin quantifications. As previously reported Agt-KO were anemic with reduced red blood cell counts. Interestingly, we found that they presented microcytic anemia based on the reduced red blood cell volume. In agreement, plasma quantification of iron revealed lower levels of circulating iron in Agt-KO. The major body iron stores namely in liver and spleen were also depleted in the RAS-deficient line. Hepatic hepcidin expression was reduced as well as the one of its major regulator, BMP6, as a result of the iron deficiency. However, plasma hepcidin levels were unexpectedly increased in Agt-KO. We confirm the typical morphological alterations and impaired renal function of Agt-KO and conclude that hepcidin accumulates in the circulation due to the reduced glomerular filtration in Agt-KO, and therefore identified the culprit of iron deficiency in Agt-KO. Collectively, the data demonstrated that the severe anemia developed in RAS-deficient mice is exacerbated by iron deficiency which is secondary to the renal damage-induced hepcidin accumulation in the circulation.

Maternal Ferrous Sucrose Supplementation Improves Reproductive Performance of Sows and Hepatic Iron Stores of Neonatal Piglets

As one of the most important trace elements required by sows, especially in the late gestation period, iron plays a crucial role in the growth and development of a fetus. To explore the effects of dietary supplementation with ferrous sucrose on the reproductive performance of sows and the hepatic iron stores in offspring, sixty primiparous Landrace × Yorkshire sows on day 95 of gestation with an average body weight of 174.1 ± 7.7 kg were randomly assigned to two groups of a basic diet (control) and a basic diet supplemented with 109 mg/kg ferrous sucrose (FS) in a fully randomized block design. The trial lasted for 20 days. The results showed that maternal supplementation with ferrous sucrose significantly increased litter weight (p = 0.002) in neonatal piglets. Compared with the control group, the serum iron and serum transferrin saturation of farrowing sows increased by 45.67% (p = 0.002) and 37.01% (p = 0.033), respectively, and umbilical cord serum iron (p = 0.012) also increased in the FS group. Finally, the serum iron (p < 0.001) and hepatic iron stores (p = 0.071) of neonatal piglets were both increased to varying degrees. Taken together, supplementation of pregnant sows with ferrous sucrose has positive effects on the growth and hepatic iron stores of their offspring.

Antarctic Krill Protein Amyloid Fibrils as a Novel Iron Carrier for the Improvement of Iron Deficiency.

Iron fortification with food supplements remains the primary dietary strategy for improving iron deficiency anemia (IDA). This study used Antarctic krill protein for fibrillar design to form an Antarctic krill protein amyloid fibril (AKAF). The results indicated that peptides generated by proteolysis were a prerequisite for fibril assembly, forming elongated fibril structures and cross-linking upon heating. During this process, hydrogen bonds were rearranged, forming ordered β-sheet conformations (49.36 ± 0.21%); π-π stacking interactions among aromatic residues contributed to fibril formation. Further studies showed that AKAF effectively maintained iron in a bioavailable state and exhibited a high binding capacity (60.67 ± 0.69%). Moreover, the AKAF-iron complex markedly ameliorated hematological abnormalities in IDA mice, enhanced iron storage in the liver and spleen, and positively influenced the expression of iron homeostasis genes. This complex was also effective in alleviating gastric inflammatory responses induced by IDA. Overall, AKAF holds promise as an efficient iron delivery carrier.

Ferritin Outperforms Other Biomarkers in Predicting Bone Marrow Iron Stores in Hematological Patients.

Although iron deficiency anemia is common, interpreting iron laboratory test results can be challenging in patients with comorbidities. We aimed to study the accuracy of common iron biomarkers compared with bone marrow iron staining in a large retrospective dataset of hematological patients. We collected from 6610 patients (median age 66 years) results of iron staining, with their concurrent ferritin, transferrin saturation, soluble transferrin receptor, transferrin, hemoglobin, and mean red blood cell volume results from Helsinki University Hospital electronic health records. In receiver operating characteristics (ROC) analysis, ferritin had the highest area under curve (AUC) with 88% (95% CI 86-90%) for females and 89% (87-91%) for males in predicting reduced bone marrow iron. Using a ferritin cut-off of 30 µg/L resulted in high specificity rates of 97% in females and 99% in males. However, sensitivity rates were only 54% and 35%, respectively. Other studied biomarkers had inferior AUCs. Multivariate logistic regression models did not significantly perform better in prediction compared to ferritin alone. With 50% pre-probability for reduced iron stores, a ferritin of 30 µg/L (females) and 51 µg/L (males) had 95% positive predictive value for reduced iron stores. A 95% negative predictive value was achieved at 1750 µg/L (females) and 4967 µg/L (males). In our large population study, ferritin was the best single biomarker for iron deficiency in secondary care. Adding other blood tests in a multivariate model did not improve performance. However, in these hematological patients, even a high ferritin did not rule out iron deficiency with 95% certainty.

P0574 Correlations Between Inflammatory Biomarkers and Hematological Parameters in Assessing Disease Activity in IBD

Abstract Background Monitoring ulcerative colitis (UC) and Crohn's disease (CD) involves assessing inflammatory and hematological biomarkers to evaluate disease activity, treatment response, and the impact of inflammation on overall health. The aim of this study was to assess if hematological and inflammatory biomarkers along with clinical parameters correlate with IBD inflammatory activity and severity. Methods The study retrospectively analyzed 100 IBD patients, of which 72 patients with UC and 38 patients with CD. Age, hematological parameters (hemoglobin, iron and ferritin), inflammatory biomarkers (CRP, fibrinogen and fecal calprotectin) and clinical scores such as Truelove and Witts for UC and UCDAI for CD were analyzed. Pearson's correlation coefficient demonstrated relationships between hematological and inflammatory biomarkers, while the Kruskal-Wallis test evaluated associations between these biomarkers and clinical scores. Results The mean age was 44.02 years, with UC patients averaging 43.03 years and CD patients 49.3 years, reflecting a slightly older demographic for CD. Age was negatively correlated with iron (-0.93) and positively with ferritin (0.88), indicating that older individuals have less iron deposits. Hemoglobin levels (mean 11.81 g/dL) were reduced across both diseases and exhibited significant negative correlations with CRP (-0.93) and fecal calprotectin (-0.91). Systemic (CRP) and intestinal (fecal calprotectin) inflammation can diminish hemoglobin levels in IBD patients, causing inflammatory anemia. Iron levels were lowest in CD (61.78 µg/dL) and correlated negatively with CRP (-0.93) and ferritin (-0.99) during active systemic inflammation, while ferritin levels (107.89 ng/mL) were elevated, particularly in active inflammation in CD group. Intestinal inflammation impacts iron status (-0.40), while ferritin and CRP are positively correlated (0.96), showing that systemic inflammation enhances iron storage. Fecal calprotectin emerged as a particularly sensitive marker of intestinal inflammation, showing the highest levels in UC patients (517.18 µg/g) and significant correlations with clinical activity scores (p = 0.02) for both Truelove-Witts and UCDAI. Hemoglobin was the only parameter that showed a weak trend of correlation with clinical scores (p=0.06), without statistical significance. Conclusion Hematological and inflammatory biomarkers along with clinical parameters correlate with IBD inflammatory activity and severity of the inflammatory process. The results highlight the effectiveness of biomarker evaluation in the personalized management of patients, enabling the adaptation, configuration, or establishment of monitoring schedules and therapeutic optimization based on the inflammatory profile.

Second-generation BRAF inhibitor Encorafenib resistance is regulated by NCOA4-mediated iron trafficking in the drug-resistant malignant melanoma cells

The current study established the first in vitro Encorafenib resistance protocol in BRAF-mutated malignant melanoma (MM) cells and investigated the resistance-related mechanisms. After establishing Encorafenib-resistant A375-MM cells, resistant-related mechanisms were investigated using WST-1, Annexin V, cell cycle, morphological analysis, live-cell, Western blot, RNA-Seq, transmission electron microscopy-(TEM), oxidative stress and iron colorimetric assay. The most resistant group, called A375-R, was determined in the cells treated with a constant dose of 10 nM over 3 months. The viability, apoptosis, and G0/G1 arrest reflected the acquired chemoresistance. Autophagic Beclin and LC3 proteins, and AKT signaling increased in the A375-R. RNA-Seq results also exhibited altered epigenetic regulation of resistance; particularly ferritin family members, ion transport pathways. Then, increased NCOA4, FTH1, and iron levels detected in A375-R suggest that the iron metabolism-related mechanism, such as ferritinophagy, might be triggered, which was supported by TEM and oxidative stress analysis. Iron storage, transport, and ferritinophagy have the promising potential to be targeted for combining with BRAF-targeted therapy to reverse Encorafenib resistance in MM. Moreover, this is the first study evaluating in vitro Encorafenib resistance mechanisms, and we suggest that our findings contribute to improving new drug combinations targeting BRAF and iron metabolism in different MM cells.

Association between iron deficiency and fertility.

This retrospective, observational cohort study investigated the association between treatment of iron deficiency with conception results and pregnancy outcomes in women with infertility and iron deficiency, before and after intravenous ferric carboxymaltose infusion. Data were collected from electronic health records from the Dextra Fertility Clinic (Helsinki, Finland) between 2015 and 2020. The cohort included 292 women (<43 years) with infertility and iron deficiency (s-ferritin ≤30 μg/L), treated with a ferric carboxymaltose infusion (Ferinject®, 500 mg i.v.). The main outcomes were live birth and miscarriage rates before and after treatment of iron deficiency. The main explanatory variable studied was the administered iron infusion. Mean s-ferritin levels increased from 16.2 ± 7.0 μg/L before to 81.5 ± 49.8 μg/L after iron infusion. The proportion of patients who conceived increased from 65% before to 77% after treatment of iron deficiency (p < 0.001). Of the study population, 28% of patients experienced miscarriages and 26% gave a live birth before iron infusion, and 13% and 51% after treatment of iron deficiency (p < 0.001). In the model adjusted for age, use of preimplantation genetic testing for aneuploidy, and repeated iron infusions, treatment of iron deficiency with iron infusion was associated with a higher live birth rate (OR = 3.19; 95% CI = 2.21-4.66; p < 0.001). In the model adjusted for age, reason for infertility, and total number of pregnancies, treatment of iron deficiency was associated with lower miscarriage rates (OR = 0.32; 95% Cl = 0.20-0.52; p < 0.001). Filling of depleted iron stores was positively associated with conception results (higher number of pregnancies) and pregnancy outcomes (higher live birth rates and lower miscarriage rates), regardless of the assisted reproductive technology method used. Screening of iron status seems to be important in patients seeking help for infertility problems.

Prolonged tamoxifen treatment induces iron deposition and ferroptosis in the liver.

Tamoxifen is an inhibitor of estrogen receptors and was originally developed for breast cancer therapy. Besides, tamoxifen is widely used for Cre-estrogen receptor-mediated conditional knockout in transgenic mice. However, we found that the 3-month feeding of 0.5 g/kg tamoxifen diet dramatically lowered the body weight of mice. The liver fat content and the serum lipid indicators were all decreased. But the liver injuries were identified, as illustrated by liver/body ratio and serum ALT and AST levels. The Sirius red staining and α-SMA staining even showed fibrosis in the liver. The increased lipid peroxidation indicators MDA and LPO, and ferroptosis markers COX-2, GPX4, SLC7A11, and ACSL4 implied the tamoxifen-induced ferroptosis in the liver. We further found that tamoxifen induced hepatic iron deposition. The investigation of iron transporters found that tamoxifen upregulated ferric iron reductase STEAP3, ferrous iron transporter DMT1, and iron storage molecule ferritin, which were probably the reasons for tamoxifen-induced iron deposition. The downregulation of the transferrin receptor and upregulation of hepcidin were more likely the responses to iron deposition. In conclusion, we found that tamoxifen disturbed the iron metabolism and induced liver injuries and ferroptosis, warranting attention to the applications of tamoxifen in cancer therapy and conditional gene knockout.

Iron deficiency and infection risk in Danish blood donors.

We aimed to investigate if iron deficiency was associated with infection susceptibility in a large cohort of healthy individuals. The Danish Blood Donor Study is a national ongoing prospective study of blood donors. We included 94,628 donors with 338,290 ferritin measurements from March 2010 to October 2022. We performed sex-stratified multivariable Cox regression to estimate the risk of infection for iron-deficient donors compared with iron-replete donors. Infection was defined as either a filled prescription of antibiotics registered in the Danish National Prescription Registry (NPR), or a hospital contact with infection registered in the Danish National Patient Registry (DNPR). Iron deficiency was associated with an overall increased risk of infection (defined as prescriptions of antibiotics) for women (hazard ratio [HR] 1.08, 95% confidence interval [CI] 1.02-1.15). Subgroup analyses showed an increased risk of respiratory tract infections (HR 1.16, 95% CI 1.05-1.28) and urinary tract infections (HR 1.16, 95% CI 1.04-1.29). Iron deficiency was not associated with overall risk of infection for men (HR 1.02, 95% CI 0.82-1.28). For both men and women, no association was found between iron deficiency and hospital contacts for infections. Iron deficiency was associated with an increased risk of infection in female blood donors. However, effect sizes were small, and there was no association between iron deficiency and hospital contacts for infection. Consequently, risk of infection should not be considered an apprehension regarding blood donation. These findings support the role of iron in immune function and monitorization of iron stores in female blood donors.

Peripheral blood immune cells from individuals with Parkinson's disease or inflammatory bowel disease share deficits in iron storage and transport that are modulated by non-steroidal anti-inflammatory drugs.

Parkinson's Disease (PD) is a multisystem disorder in which dysregulated neuroimmune crosstalk and inflammatory relay via the gut-blood-brain axis have been implicated in PD pathogenesis. Although alterations in circulating inflammatory cytokines and reactive oxygen species (ROS) have been associated with PD, no biomarkers have been identified that predict clinical progression or disease outcome. Gastrointestinal (GI) dysfunction, which involves perturbation of the underlying immune system, is an early and often-overlooked symptom that affects up to 80 % of individuals living with PD. Interestingly, 50-70 % of individuals with inflammatory bowel disease (IBD), a GI condition that has been epidemiologically linked to PD, display chronic illness-induced anemia - which drives toxic accumulation of iron in the gut. Ferroptotic (or iron loaded) cells have small and dysmorphic mitochondria-suggesting that mitochondrial dysfunction is a consequence of iron accumulation. In pro-inflammatory environments, iron accumulates in immune cells, suggesting a possible connection and/or synergy between iron dysregulation and immune cell dysfunction. Peripheral blood mononuclear cells (PBMCs) recapitulate certain PD-associated neuropathological and inflammatory signatures and can act as communicating messengers in the gut-brain axis. Additionally, this communication can be modulated by several environmental factors; specifically, our data further support existing literature demonstrating a role for non-steroidal anti-inflammatory drugs (NSAIDs) in modulating immune transcriptional states in inflamed individuals. A mechanism linking chronic gut inflammation to iron dysregulation and mitochondrial function within peripheral immune cells has yet to be identified in conferring risk for PD. To that end, we isolated PBMCs and simultaneously evaluated their directed transcriptome and bioenergetic status, to investigate if iron dysregulation and mitochondrial sensitization are linked in individuals living with PD or IBD because of chronic underlying remittent immune activation. We have identified shared features of peripheral inflammation and immunometabolism in individuals living with IBD or PD that may contribute to the epidemiological association reported between IBD and risk for PD.

Deciphering the role of hepcidin in iron metabolism and anemia management.

One of the most common diseases worldwide is anemia, which is characterized by insufficient erythrocyte production. Numerous complex factors, such as chronic diseases, genetic mutations, and nutritional inadequacies, contribute to this widespread syndrome. This review focuses specifically on anemias caused by defective hepcidin production. Hepcidin, a peptide hormone produced primarily by liver cells, plays a crucial role in regulating iron levels by controlling its absorption. Hepcidin's mechanism of action involves binding to the ferroportin iron transporter, causing its internalization. Disturbances in iron metabolism can have far-reaching consequences, affecting not only the blood but also organs like the liver, kidneys, and brain. Iron homeostasis is crucial for maintaining optimal physiological function. Several blood-based markers are employed to assess iron stores. However, these markers have inherent limitations. Hepcidin, a key regulator of iron metabolism, plays a pivotal role in preventing iron release into the plasma from absorptive enterocytes and macrophages. Elucidating the structure and function of hepcidin is essential for understanding its role in iron homeostasis, which has significant implications for the diagnosis and management of various anemia subtypes. A well-established correlation exists between hepcidin dysregulation and iron deficiency. Despite its potential as a biomarker, the clinical application of hepcidin is hindered by the lack of a commercially available, clinically validated assay. This review aims to provide a comprehensive overview of hepcidin's role in regulating blood iron concentrations and elucidate its implications in the pathogenesis of various anemia subtypes, paving the way for its future applications in research and clinical practice.

Comparative genomics analysis of the reason for 12C6+ heavy-ion irradiation in improving Fe3O4 nanoparticle yield of Acidithiobacillus ferrooxidans.

The Fe3O4 nanoparticle synthesized by Acidithiobacillus ferrooxidans have a broad practical value, while the low yield limits their commercial application. Herein, we employed a 12C6+ heavy-ion beam to induce mutagenesis of A. ferrooxidans BYM and successfully screened a mutant BYMT-200 with a 1.36 mg/L Fe3O4 nanoparticle yield, which could stably inherit over many generations based on assessing cell magnetism and Fe3O4 nanoparticle synthesis. Comparative genome analysis detected 14 mutation sites, causing six synonymous mutations, one missense mutation, and one nonsense mutation. We further annotated the genes involved in the mutation, such as hcp, hsdM, yghU, K7B00_11365, and K7B00_11355, which are responsible for the substantial changes in the Fe3O4 nanoparticle yield of A. ferrooxidans. Additionally, we performed a pan-genome analysis to understand how these genes regulate Fe3O4 nanoparticle synthesis. The core genome of 2376 orthologous clusters was identified and visualized by progressive Mauve alignment and OrthoVenn. A total of 109 regulatory genes related to iron metabolism were identified, mainly involved in electron transport, iron acquisition, iron storage, and oxidative stress. The mutant genes are closely related to iron-sulfur clusters and oxidative stress. Accordingly, we proposed a hypothetical mechanism for increasing Fe3O4 nanoparticle production in A. ferrooxidans BYMT-200 to withstand high oxidative stress caused by heavy ion radiation. Our study offers significant theoretical guidance for further acquiring the high-yield Fe3O4 nanoparticle-producing bacteria and studying the mechanism of its synthesis.

Iron-associated lipid peroxidation in Alzheimer's disease is increased in lipid rafts with decreased ferroptosis suppressors, tested by chelation in mice.

Iron-mediated cell death (ferroptosis) is a proposed mechanism of Alzheimer's disease (AD) pathology. While iron is essential for basic biological functions, its reactivity generates oxidants which contribute to cell damage and death. To further resolve mechanisms of iron-mediated toxicity in AD, we analyzed post mortem human brain and ApoEFAD mice. AD brains had decreased antioxidant enzymes, including those mediated by glutathione (GSH). Subcellular analyses of AD brains showed greater oxidative damage and lower antioxidant enzymes in lipid rafts, the site of amyloid processing, than in the non-raft membrane fraction. Apolipoprotein E ε4 carriers had lower lipid raft yield with greater membrane oxidation. The hypothesized role of iron in AD pathology was tested in ApoEFAD mice by iron chelation with deferoxamine, which decreased fibrillar amyloid and lipid peroxidation, together with increased GSH-mediated antioxidants. These novel molecular pathways highlight iron-mediated damage to lipid rafts during AD. Alzheimer's disease (AD) brains have numerous markers for ferroptosis, including increased lipid peroxidation, reduced antioxidant levels, and increased iron storage. Lipid rafts in AD cases have increased oxidative damage and reduced antioxidant enzyme levels and activity which are most severe in apolipoprotein E ε4 carriers. Neuronal markers are correlated with lipid peroxidation, antioxidant defense, and iron signaling proteins suggesting that neuronal loss is linked to these events. Chelation of iron in the early-onset familial AD model reduces iron-mediated lipid peroxidation and fibrillar amyloid.

Comparative analysis of oral iron therapy regimens in premenopausal women with iron deficiency anemia

Iron deficiency anemia (IDA) is prevalent among women of reproductive age. Treatment aims to replenish iron stores and normalize hemoglobin levels, with oral iron therapy being the preferred route in most cases. This study aimed to compare the efficacy and side effects of three common oral treatment regimens in premenopausal women with IDA. An observational study was conducted on patients initiated on oral ferrous glycine sulfate therapy (100 mg elemental iron). Patients were divided into three groups based on treatment regimen: alternate-day (n = 40), daily single-dose (n = 41), and daily twice dose (n = 40). Hemoglobin, ferritin, and transferrin saturation levels were measured before and after one month of therapy. The primary outcome was to compare laboratory changes from baseline to post-treatment within and between groups. The secondary outcome was to compare the frequency of gastrointestinal side effects. The mean age was 41.2 ± 8 years, with a mean hemoglobin level of 10.4 ± 1.1 g/dl, and a mean ferritin level of 7 ± 3.2 ng/mL at the time of diagnosis. After one month of therapy, hemoglobin, ferritin, and transferrin saturation levels significantly increased in all groups (p < 0.001 for all). However, the increase in hemoglobin and ferritin levels was significantly lower in the alternate-day group compared to the other groups (p < 0.001). Gastrointestinal side effects were more prevalent in the daily twice group (66.1%) compared to the alternate-day (16.7%) and daily single-dose (23.4%) groups (p < 0.001). Daily single-dose oral ferrous glycine sulfate therapy emerged as an effective and well-tolerated treatment regimen for premenopausal women with IDA.

Salvianolic acid B influences the ferritin function in iron(II)/iron(III) transformation and iron chelation.

Ferritin is a cage-like iron storage protein and can regulate the iron balance of life. It can be developed as a new type of iron supplement, while its function may be influenced by certain food bioactive components. To evaluate the effects of the typical food biomolecules, such as phenolic acid, on the physicochemical property of ferritin are of great importance to clarify the ferritin function in maintaining iron balance. In this study, the interaction mechanism of ferritin with iron ions and salvianolic acid B (SalB) was investigated. The complex formed by SalB and iron ions can interact with the ferritin mainly through hydrogen bonding and van der Waals forces. Compared with ascorbic acid, SalB effectively promoted the initial iron oxidation of ferritin, but showed a lower iron release rate. In addition, SalB exhibited a stronger iron chelating ability and a higher free radical scavenging ability during iron release of ferritin than ascorbic acid. This study clarifies the structure and property of ferritin influenced by SalB, and reveals the interaction mechanism of ferritin-SalB-iron system. The finding helps elucidate the role of phenolic acid and benefits the non-heme iron-ferritin for potential food applications such as iron supplementation. © 2024 Society of Chemical Industry.

The structural and functional analysis of mycobacteria cysteine desulfurase-loaded encapsulin

Encapsulin nanocompartments loaded with dedicated cargo proteins via unique targeting peptides, play a key role in stress resistance, iron storage and natural product biosynthesis. Mmp1 and cysteine desulfurase (Enc-CD) have been identified as the most abundant representatives of family 2 encapsulin systems. However, the molecular assembly, catalytic mechanism, and physiological functions of the Mmp1 encapsulin system have not been studied in detail. Here we isolate and characterize an Enc-CD-loaded Mmp1 encapsulin system from Mycobacterium smegmatis mc2155. The cryo-EM structure of the Mmp1 encapsulin and the crystal structure of the naked cargo Enc-CD have been determined. The structure shows that the Mmp1 protomer assembles two conformation models, the icosahedron (T = 1) and homodecamer, with the resolution of 2.60 Å and 2.69 Å. The Enc-CD at 2.10 Å resolution is dimeric and loaded into the Mmp1 (T = 1) encapsulin through the N-terminal long disordered region. Mmp1 encapsulin protects Enc-CD against oxidation as well as to maintain structural stability. These studies provide new insights into the mechanism by which Enc-CD-loaded encapsulin stores sulfur and provides a framework for discovery of new anti-mycobacterial therapeutics.

The Interplay Between Vitamin D Deficiency, Iron Status, and Anemia Risk in Moroccan Women of Reproductive Age: A Cross-Sectional Analysis.

Background: Vitamin D and iron deficiencies are prevalent among Moroccan women of reproductive age (WRA). Research suggests that Vitamin D deficiency (VDD) may impair iron bioavailability, potentially leading to iron deficiency (ID) and anemia. Objectives: This study investigates associations between vitamin D status, iron levels, and anemia risk in WRA, aged 18-49, from Meknes, Morocco. Methods: A cross-sectional study was conducted among 463 participants, measuring serum 25(OH)D, blood count parameters, iron, ferritin, C-reactive protein, and creatinine. Lifestyle factors, including dietary intake, sun exposure, and physical activity, were assessed through validated questionnaires, and anthropometric data were collected. Linear and logistic regression models analyzed associations, while ROC analysis evaluated VDD's predictive accuracy for ID and anemia. Results: VDD (25(OH)D < 20 ng/mL) was significantly associated with reduced hemoglobin, hematocrit, red blood cells, and ferritin (all p < 0.01), indicating vitamin D's role in erythropoiesis and iron storage. Multivariate logistic regression showed that VDD increased the risk of anemia (OR: 7.17, 95% CI: 3.19-19.28, p < 0.001), ID (OR: 2.20, 95% CI: 1.32-3.77, p = 0.007), and IDA (OR: 4.10, 95% CI: 1.73-12.08, p = 0.004). Dietary iron intake was inadequate, showing minimal protective effects against anemia and ID (β(SE): -0.08(0.03), p = 0.030 and β(SE): -0.05(0.02), p = 0.037). Conclusions: VDD is a significant risk factor for impaired iron status and anemia in Moroccan WRA, highlighting the need for targeted nutritional interventions and further research.

A clinical study on single-dose intravenous iron therapy’s impact on hemoglobin and its outcomes in hospitalized chronic kidney disease patients

Anemia is a common complication in Chronic Kidney Disease (CKD) due to reduced erythropoietin production and iron deficiency, leading to poor patient outcomes. Intravenous (IV) iron therapy is preferred over oral supplements for its efficacy in rapidly improving hemoglobin levels and replenishing iron stores. Single-dose IV iron formulations like Ferric Carboxymaltose offer a convenient and effective option for anemia management in Chronic Kidney Disease (CKD) patients. Study on single-dose intravenous iron therapy’s impact on hemoglobin and its outcomes in hospitalized chronic kidney disease patients. A cross-sectional study was conducted on 200 hospitalized Chronic Kidney Disease (CKD) patients receiving single-dose IV iron therapy (Ferric Carboxymaltose, Iron Sucrose, or Monoferric). Outcomes including hemoglobin improvement, iron parameters, adverse events, and cost-effectiveness were analyzed pre- and post-treatment.The majority of patients (59%) were over 50 years old, with males accounting for 55% of the study group. The most prevalent comorbidities were Hypertension (91.5%) and type 2 diabetes (51%). The average Body Mass Index (BMI) reduced from 22.8 to 21.2 after the intervention. The most commonly provided iron formulation was Ferric Carboxymaltose (69.5%), followed by iron sucrose (16.5%) and Monoferric (14%). Hemoglobin levels rose by an average of 2.3 units in 51.5% of patients, with a mean time to target of 5.1 days. Ferritin levels increased by 41.4% after therapy, whereas TIBC and transferrin saturation remained stable. Hypertension was the most common side effect, with 74 cases documented (23 mild, 43 moderate, and 8 severe). The study found that Single-Dose Intravenous Iron therapy increases hemoglobin levels and Iron parameters in CKD patients, with Ferric Carboxymaltose being the most effective formulation. The medication also reduced post-hemodialysis BMI and was cost-effective for anemia management. The most common comorbidity was hypertension, and while there were some adverse events, they were largely controlled. Overall, Intravenous Iron therapy reduced anemia and its associated hazards, leading to better patient outcomes in Chronic Kidney Disease (CKD) care.

Structural Analysis of Variants of the Ferritin Light Chain Protein and Its Relationship with Neuroferritinopathy.

Ferritin is a highly conserved spherical protein that stores iron and possesses triple and quadruple symmetry input ports. Additionally, it is composed of light chains that can be affected by post-translational mutations, reducing the iron storage capacity in the brain and leading to neuroferritinopathy, which is a rare disease with limited bioinformatics data. In this study, we analyzed the biochemical mechanism of different ferritin mutations reported in the literature, through the characterization and determination of the in silico structural model by searching databases, implementing bioinformatics programs such as Jalview, NetNGlyc 1.0, NetOGlyc 3.1, and three-dimensional structure predictors with machine learning such as Alphafold, demonstrating the generation of hairpin and steric hindrances that hinder the aggregation of subunits and changes in the size and arrangement of quadruple and triple entry holes of the A96T mutation compared to the wild-type protein, since in the quadruple entry hole, a decrease in area is observed compared to the wild-type protein and the triple entry hole has a decrease in distance measurements of 6.504 Å. This possibly affects the functionality of the protein, thus releasing high concentrations of iron in the brain and causing neurodegeneration.

Clinical profile of female patients with chronic telogen effluvium and its association with serum ferritin level

Background: Diffuse hair loss persisting longer than 6 months without any cause is referred to as chronic telogen effluvium (CTE). The role of iron deficiency without anemia in causing chronic diffuse hair loss is unclear. Some studies have reported a critical threshold of 40 mcg/mL of serum ferritin, below which increased telogen shedding was observed. Screening all patients with CTE for iron deficiency will aid us in finding a possible cause and help in its management. Aims and Objectives: To study the clinico-epidemiological profile of female patients with CTE and its association with serum ferritin levels. Materials and Methods: Cross-sectional study on 263 female patients aged 13–60 years with CTE attending the Department of Dermatology at Government Medical College, Kottayam. Results: The mean age of patients with CTE was 28.92 years. Trichodynia was reported by 20% among which 70% reported associated mental stress which was statistically significant. Bitemporal thinning was noted in 57% and 68% had short growing hairs in the frontal/bitemporal region. The hair pull test was positive in 37.6%, high visual analog grade of hair loss in 92%. Only 32% had anemia (Hb &lt;12) but 86% had S. ferritin &lt;40 mcg/L with the mean S. ferritin being 23.93 ng/mL and the majority were in the age group of 20–29 years. Conclusion: The majority were found to have low serum ferritin levels without clinical anemia, which could indicate an association between low iron stores and CTE. Additional case–control studies are needed to establish the role of iron deficiency in causing hair loss.