Iron loading is regarded as the primary cause of endocrine abnormalities in thalassemia major patients. Thus, the purpose of the current research was to explore the impact of thalassemia genotypes, hepcidin antimicrobial peptide (HAMP) and hereditary hemochromatosis (HFE) gene variants, and hepcidin expression on serum ferritin and endocrinal complications in thalassemia patients. The study comprised fifty beta-thalassemia cases and fifty age- and sex-matched controls. Genotyping of the Beta-globin gene (HBB), HAMP, and exon 2 of the HFE gene was performed using Sanger sequencing. C282Y (c.845G > A) variant of the HFE gene was determined by PCR-RFLP. Hepcidin mRNA expression was assessed by qRT-PCR. Biochemical and hormonal studies were done for all patients. Hypogonadism and short stature were found in 56% and 20% of the investigated cases, respectively. Molecular studies reported a statistically higher frequency of the HAMP variant c.-582A > G in thalassemic patients than controls. Significant downregulation of hepcidin expression was found in cases compared to healthy subjects that was significantly associated with short stature. Considering the thalassemia alleles, the IVSI.1G > A (β0) allele was statistically related to hypogonadism. Our results proposed that thalassemia genotypes and downregulated hepcidin expression were the potential risk factors for endocrinopathies in our cases. We also demonstrated an increased incidence of the HAMP promoter variant c.- 582A > G that might have a role in the pathogenesis of iron overload in thalassemic cases. Significant downregulation of hepcidin expression, that contributes to increased iron burden, could be used as a future therapeutic target in these patients.

BACKGROUND: Hepcidin is a peptide associated with controlling the distribution of iron in tissues. Growing interest is linked with its impact on neurodegenerative diseases, as disruption of the iron regulation may be considered an initiatory element of pathological protein accumulation. The possible impact of hepcidin was not previously sufficiently explored in progressive supranuclear palsy (PSP).
METHODS: Twelve patients with PSP-Richardson\'s syndrome (PSP-RS), 12 with PSP-Parkinsonism Predominant (PSP-P), and 12 controls were examined using Unified Parkinson\'s Disease Rating Scale-III part (UPDRS-III) in OFF stage and analyzed in the context of hepcidin levels in the serum.
RESULTS: The work revealed increased levels of hepcidin in PSP-RS when compared to PSP-P and controls. Moreover, hepcidin was found to be negatively correlated with UPDRS-III results in PSP-RS, whereas positively in PSP-P.
CONCLUSIONS: The work may suggest a possible impact of hepcidin in PSP, possibly differing depending on its subtype.

UNASSIGNED: Numerous clinical trials affirm the efficacy and safety of IV iron to treat cancer-related anemia (CRA). Nonetheless, evaluation and treatment of CRA remains suboptimal.
UNASSIGNED: This review summarizes CRA therapy with a focus on iron deficiency and its treatment. The literature search was conducted using the National Library of Medicine (PubMed) database from 2004 to 2024. Topics reviewed include CRA pathophysiology, laboratory diagnosis of iron deficiency, a summary of clinical trial results using IV iron to treat CRA, and safety aspects.
UNASSIGNED: Despite overwhelming positive efficacy and safety data, IV iron remains underutilized to treat CRA. This is likely due to persistent (unfounded) concerns about IV iron safety and lack of physician awareness of newer clinical trial data. This leads to poor patient quality of life and patient exposure to anemia treatments that have greater safety risks than IV iron. Solutions to this problem include increased educational efforts and considering alternative treatment models in which other providers separately manage CRA. The recent availability of new oral iron therapy products that are effective in treating anemia of inflammation has the potential to dramatically simplify the treatment of CRA.

Background/Objectives: This study aimed to explore the influence of hypoxia, inflammation, and erythropoiesis on hepcidin and other iron status parameters in non-anaemic COVID-19 patients admitted to the emergency unit before the introduction of therapeutic interventions. Methods: Ninety-six COVID-19 patients and 47 healthy subjects were recruited. Patients were subdivided into hypoxic or normoxic groups and, after follow-up, into mild and moderate, severe or critical disease severity groups. Iron, unsaturated iron-binding capacity (UIBC), ferritin, C-reactive protein (CRP), and interleukin 6 (IL-6) were measured on automatic analysers. ELISA kits were used for hepcidin and erythropoietin (EPO) determination. We calculated total iron-binding capacity (TIBC) and ratios of hepcidin with parameters of iron metabolism (ferritin/hepcidin, hepcidin/iron), inflammation (hepcidin/CRP, hepcidin/IL-6), and erythropoietic activity (hepcidin/EPO). Results: Hepcidin, ferritin, EPO, CRP, IL-6, ferritin/hepcidin, and hepcidin/iron were increased, while UIBC, TIBC, hepcidin/CRP, and hepcidin/IL-6 were decreased in hypoxic compared to normoxic patients as well as in patients with severe or critical disease compared to those with mild and moderate COVID-19. Regarding predictive parameters of critical COVID-19 occurrence, in multivariable logistic regression analysis, a combination of EPO and ferritin/hepcidin showed very good diagnostic performances and correctly classified 88% of cases, with an AUC of 0.838 (0.749-0.906). Conclusions: The hypoxic signal in our group of patients was not strong enough to overcome the stimulating effect of inflammation on hepcidin expression. EPO and ferritin/hepcidin might help to identify on-admission COVID-19 patients at risk of developing a critical form of the disease.

In pregnant women with multiple infections, nutrient deficiencies, and inflammation (MINDI), the study of anemia and iron status is limited. For this cross-sectional study (n = 213 Panamanian indigenous women), we investigated if hemoglobin, anemia (Hb < 110 g/L), ferritin, serum iron, serum transferrin receptor, and hepcidin were associated with (1) maternal nutritional status and supplementation practices, (2) biomarkers of inflammation, and (3) presence/absence of infections. Hierarchical generalized linear and logistic regression models and dominance analyses identified the relative importance of these predictors. Anemia (38%), which was likely underestimated due to low plasma volume (95%), was associated with lower ferritin, vitamin A, and weight-for-height, suggesting anemia of undernutrition. Inflammation was not associated with Hb or anemia; nevertheless, higher CRP was associated with increased odds of low serum iron and higher ferritin and hepcidin, indicating iron restriction due to inflammation. The length of iron supplementation did not enter models for anemia or iron indicators, but a multiple nutrient supplement was associated with higher ferritin and hepcidin. Moreover, iron supplementation was associated with higher odds of vaginal trichomoniasis but lower odds of caries and bacterial vaginosis. The complex pathogenesis of anemia and iron deficiency in MINDI settings may require other interventions beyond iron supplementation.

Background Anemia is common in older adults and, together with heart failure and chronic kidney disease, forms a vicious cycle, whereas diseases such as chronic inflammation and cancer are associated with the anemia of chronic disease (ACD). Researchers have linked growth differentiation factor-15 (GDF-15) to a variety of conditions such as cardiovascular disease, inflammation, cancer, and kidney disease, and have reported hepcidin as a biomarker for iron regulation in ACD. Therefore, anemia, GDF-15, and hepcidin have significance in aging physiology. Hypothesis GDF-15 and hepcidin play important physiological roles in community-dwelling older adults. This study sought to explore the relationship between these biomarkers and anemia, inflammation, or other health outcomes. Methods This was a prospective study of 73 community-dwelling older adults (six men and 67 women, mean age of 76.3 years). Their serum iron level, percentage transferrin saturation (TSAT), high-sensitivity C-reactive protein (hs-CRP), and estimated glomerular filtration rate (eGFR) were measured. Enzyme-linked immunosorbent assays were used to assess their serum GDF-15, ferritin, and hepcidin levels. The participants\' grip strength and walking speed were measured. The skeletal muscle mass index (SMI) of each participant was determined by bioelectrical impedance analysis. Results The GDF-15 level was significantly inversely correlated with serum iron, ferritin, and hepcidin levels; percentage TSAT; the eGFR; and gait speed. Serum hepcidin was positively correlated with levels of ferritin, albumin, and hemoglobin. Handgrip strength, SMI, and hs-CRP were not correlated with either GDF-15 or hepcidin levels. After adjusting for age, sex, and body mass index (BMI), multivariate analysis identified the log GDF-15 and serum iron level (log GDF-15: β=-0.248, iron: β=0.296) as significant factors determining hemoglobin levels, whose findings have significance due to novel results. Multivariate analysis identified eGFR and levels of hemoglobin and hepcidin as significant factors associated with log GDF-15 (eGFR: β=-0.406, hemoglobin: β=-0.269, hepcidin: β=-0.235). Similarly, ferritin and albumin levels were identified as significant factors associated with hepcidin levels (ferritin: β=0.590, Alb: β=0.277). Conclusions Anemia in community-dwelling older adults was determined not only by increasing serum iron levels but also by decreasing GDF-15 levels. Also, the increasing GDF-15 level was determined by a decreasing hepcidin level as well as the presence of anemia and renal dysfunction, and the decreasing hepcidin level was determined by decreasing stored iron and decreasing albumin levels. Serum GDF-15 and hepcidin could potentially inform diagnostic or treatment strategies for anemia or age-related health conditions.

BACKGROUND: The interaction between iron status and malaria is incompletely understood. We evaluated longitudinal changes in iron homeostasis in volunteers enrolled in malaria volunteer infection studies (VIS) and in Malaysian patients with falciparum and vivax malaria.
METHODS: We retrieved data and samples from 55 participants (19 female) enrolled in malaria VIS, and 171 patients (45 female) with malaria and 30 healthy controls (13 female) enrolled in clinical studies in Malaysia. Ferritin, hepcidin, erythropoietin, and soluble transferrin receptor (sTfR) were measured by ELISA.
RESULTS: In the VIS, participants\' parasitaemia was correlated with baseline mean corpuscular volume (MCV), but not iron status (ferritin, hepcidin or sTfR). Ferritin, hepcidin and sTfR all increased during the VIS. Ferritin and hepcidin normalised by day 28, while sTfR remained elevated. In VIS participants, baseline ferritin was associated with post-treatment increases in liver transaminase levels. In Malaysian patients with malaria, hepcidin and ferritin were elevated on admission compared to healthy controls, while sTfR increased following admission. By day 28, hepcidin had normalised; however, ferritin and sTfR both remained elevated.
CONCLUSIONS: Our findings demonstrate that parasitaemia is associated with an individual\'s MCV rather than iron status. The persistent elevation in sTfR 4 weeks post-infection in both malaria VIS and clinical malaria may reflect a causal link between malaria and iron deficiency.
BACKGROUND: National Health and Medical Research Council (Program Grant 1037304, Project Grants 1045156 and 1156809; Investigator Grants 2016792 to BEB, 2016396 to JCM, 2017436 to MJG); US National Institute of Health (R01-AI116472-03); Malaysian Ministry of Health (BP00500420).

Myelodysplastic neoplasms (MDS) are a heterogenous group of clonal stem cell disorders characterized by dysplasia and cytopenia in one or more cell lineages. Anemia is a very common symptom that is often treated with blood transfusions and/or erythropoiesis stimulating factors. Iron overload results from a combination of these factors together with the disease-associated ineffective erythropoiesis, that is seen especially in MDS cases with SF3B1 mutations. A growing body of research has shown that erythroferrone is an important regulator of hepcidin, the master regulator of systemic iron homeostasis. Consequently, it is of interest to understand how this molecule contributes to regulating the iron balance in MDS patients. This short review evaluates our current understanding of erythroferrone in general, but more specifically in MDS and seeks to place in context how the current knowledge could be utilized for prognostication and therapy.

Hepcidin is a crucial regulator of iron homeostasis with protective effects on liver fibrosis. Additionally, gut microbiota can also affect liver fibrosis and iron metabolism. Although the hepatoprotective potential of Akkermansia muciniphila and Faecalibacterium duncaniae, formerly known as F. prausnitzii, has been reported, however, their effects on hepcidin expression remain unknown. We investigated the direct and macrophage stimulation-mediated effects of active, heat-inactivated, and cell-free supernatant (CFS) forms of A. muciniphila and F. duncaniae on hepcidin expression in HepG2 cells by RT-qPCR analysis. Following stimulation of phorbol-12-myristate-13-acetate (PMA) -differentiated THP-1 cells with A. muciniphila and F. duncaniae, IL-6 concentration was assessed via ELISA. Additionally, the resulting supernatant was treated with HepG2 cells to evaluate the effect of macrophage stimulation on hepcidin gene expression. The expression of genes mediating iron absorption and export was also examined in HepG2 and Caco-2 cells via RT-qPCR. All forms of F. duncaniae increased hepcidin expression while active and heat-inactivated/CFS forms of A. muciniphila upregulated and downregulated its expression, respectively. Active, heat-inactivated, and CFS forms of A. muciniphila and F. duncaniae upregulated hepcidin expression, consistent with the elevation of IL-6 released from THP-1-stimulated cells as a macrophage stimulation effect in HepG2 cells. A. muciniphila and F. duncaniae in active, inactive, and CFS forms altered the expression of hepatocyte and intestinal iron-mediated absorption /exporter genes, namely dcytb and dmt1, and fpn in HepG2 and Caco-2 cells, respectively. In conclusion, A. muciniphila and F. duncaniae affect not only directly but also through macrophage stimulation the expression of hepcidin gene in HepG2 cells. These findings underscore the potential of A. muciniphila and F. duncaniae as a potential therapeutic target for liver fibrosis by modulating hepcidin and intestinal and hepatocyte iron metabolism mediated gene expression.

OBJECTIVE: This study aimed to assess the associations of maternal iron status and placental iron transport proteins expression with the risk of pre-eclampsia (PE) in Chinese pregnant women.
METHODS: A total of 94 subjects with PE and 112 healthy pregnant women were enrolled. Fasting blood samples were collected to detect maternal iron status. The placenta samples were collected at delivery to detect the mRNA and protein expression of divalent metal transporter 1 (DMT1) and ferroportin-1 (FPN1). Logistic analysis was used to explore the associations of maternal iron status with PE risk. The associations of placental iron transport proteins with maternal iron status were explored.
RESULTS: After adjusting for covariates, dietary total iron, non-heme iron intake and serum hepcidin were negatively associated with PE, with adjusted ORs (95%CIs) were 0.40 (0.17, 0.91), 0.42 (0.18, 0.94) and 0.02 (0.002, 0.13) for the highest versus lowest tertile, respectively. For the highest tertile versus lowest tertile, serum iron (4.08 (1.58, 10.57)) and ferritin (5.61 (2.36, 13.31)) were positively associated with PE. The mRNA expressions and protein levels of DMT1 and FPN1 in placenta were up-regulated in the PE group (p < 0.05). The mRNA expressions of DMT1 and FPN1 in placenta showed a negative correlation with the serum hepcidin (r = -0.71, p < 0.001; r = -0.49, p < 0.05).
CONCLUSIONS: In conclusion, the maternal iron status were closely associated with PE risk, placental DMT1 and FPN1 were upregulated in PE which may be a promising target for the prevention of PE.