Hepcidin Concentrations Research Articles

The Effect of Vitamin D3 Supplementation on Hepcidin, Iron, and IL-6 Responses after a 100 km Ultra-Marathon.

Deficiencies in iron and vitamin D are frequently observed in athletes. Therefore, we examined whether different baseline vitamin D3 levels have any impact on post-exercise serum hepcidin, IL-6 and iron responses in ultra-marathon runners. In this randomized control trial, the subjects (20 male, amateur runners, mean age 40.75 ± 7.15 years) were divided into two groups: experimental (VD) and control (CON). The VD group received vitamin D3 (10,000 UI/day) and the CON group received a placebo for two weeks before the run. Venous blood samples were collected on three occasions—before the run, after the 100 km ultra-marathon and 12 h after the run—to measure iron metabolism indicators, hepcidin, and IL-6 concentration. After two weeks of supplementation, the intervention group demonstrated a higher level of serum 25(OH)D than the CON group (27.82 ± 5.8 ng/mL vs. 20.41 ± 4.67 ng/mL; p < 0.05). There were no differences between the groups before and after the run in the circulating hepcidin and IL-6 levels. The decrease in iron concentration immediately after the 100-km ultra-marathon was smaller in the VD group than CON (p < 0.05). These data show that various vitamin D3 status can affect the post-exercise metabolism of serum iron.

Dapagliflozin Suppresses Hepcidin And Increases Erythropoiesis.

Dapagliflozin and other SGLT2 inhibitors are known to increase hematocrit, possibly due to its diuretic effects and hemoconcentration. Since type 2 diabetes is a proinflammatory state and since hepcidin, a known suppressor of erythropoiesis, is increased in proinflammatory states, we investigated the possibility that dapagliflozin suppresses hepcidin concentrations and thus increases erythropoiesis. Prospective, randomized, and placebo-controlled study. Single endocrinology center. Fifty-two obese type 2 diabetes patients. Patients were randomized (1:1) to either dapagliflozin (10 mg daily) or placebo for 12 weeks. Blood samples were collected before and after treatments and serum, plasma, and mononuclear cells (MNC) were prepared. Hepcidin and other hematopoietic factors. Following dapagliflozin treatment, there was a significant fall in HbA1c and a significant increase in hemoglobin concentration and hematocrit. Dapagliflozin treatment significantly reduced circulating hepcidin and ferritin concentrations while causing a significant increase in levels of the hepcidin inhibitor, erythroferrone, and a transient increase in erythropoietin. Additionally, dapagliflozin increased plasma transferrin levels and expression of transferrin receptors 1 and 2 in MNC, while there was no change in the expression of the iron cellular transporter, ferroportin. Dapagliflozin treatment also caused a decrease in hypoxia-induced factor-1α expression in MNC while it increased the expression of its inhibitor, prolyl hydroxylase-2. There were no significant changes in any of these indices in the placebo group. We conclude that dapagliflozin increases erythropoiesis and hematocrit through mechanisms that involve the suppression of hepcidin and the modulation of other iron regulatory proteins.

H2 O2 induces oxidative stress damage through the BMP-6/SMAD/hepcidin axis.

Age-related macular degeneration (AMD) is one of the leading causes of blindness in elderly individuals worldwide. Oxidative stress injury to retinal pigment epithelial (RPE) cells plays a major role in the pathogenesis of AMD. The purpose of this study was to observe the correlation between Hepcidin and neovascular age-related macular degeneration (nAMD) and to further observe whether oxidative stress can inhibit Hepcidin expression through relevant signaling pathways to produce oxidative damage. We compared the concentrations of Hepcidin in the aqueous humor of nAMD patients and a control group and found that the concentration of Hepcidin was lower in nAMD patients. Through PCR and western blotting, we observed that H2 O2 can significantly inhibit the expression of Bone morphogenetic protein-6 (BMP-6) and Hepcidin and increase the intracellular iron concentration in RPE cells, while BMP-6 can reverse the inhibition of Hepcidin and the increase in iron concentration caused by H2 O2 . In addition, alterations in smad1 and smad5 expression were examined, and pretreatment with BMP-6 was demonstrated to reduce H2 O2 -induced activation of smad1 and smad5. The effects of BMP-6 were attenuated by smad1 and smad5 siRNA, further verifying that oxidative stress inhibits the expression of Hepcidin by inhibiting activation of the BMP/SMAD signaling pathway. To some extent, this study verified that oxidative stress injury plays a role in nAMD by affecting the level of hepcidin, which lays a foundation for exploring new methods to treat nAMD.

Metabolic response to dietary supplementation with iron and folic acid in the rat

AbstractFolic acid (FA) and iron absorption is performed by transporters encoded by the Slc46a1 and Slc11a2 genes, respectively. The aim of this study was to determine how FA and iron deficiency in rats, and subsequent supplementation of the animals’ diet with these nutrients, affects Slc11a2 and Slc46a1 gene expression and the metabolic biomarkers of FA and iron status.150 female Wistar rats were assigned to a group fed a diet deficient in iron and FA (D, n = 120) or to a group fed a control diet (C, n = 30, AIN-93M) for 28 days. After this period, the rats were randomized to a group fed for 2, 10, or 21 days with a diet deficient in FA and supplemented with iron (DFE), a diet deficient in iron and supplemented with FA (DFOL), a diet supplemented with iron and FA (FEFOL), or a diet deficient in iron and folic (D).Transcript and protein levels were determined in the duodenum using the real-time PCR and western blot methods, respectively. FA concentrations in serum were assessed using the electrochemiluminescence method, and homocysteine concentrations were determined with an enzymatic assay. Iron metabolism was evaluated by measuring the total and unsaturated iron-binding capacity (TIBC and UIBC) in serum, and iron concentrations were determined using a photometric method. Hepcidin concentrations were measured in plasma with an immunoenzymatic method. Morphological parameters of the blood were determined with a Sysmex XT-4000 analyzer.The D group had higher Slc11a2 transcript levels than the DFE group at every time-point (p &lt; 0.01). There were higher Slc46a1 mRNA levels in the DFE group than in the FEFOL group at the third time-point (p &lt; 0.05). We did not observe any differences in PCFT or DMT1 protein abundance. The DFOL, FEFOL, and C groups had higher serum FA concentrations at the second and third time-points (p &lt; 0.001), as well as the lowest homocysteine concentrations (p &lt; 0.001). TIBC concentrations were lowest in the DFE and the FEFOL groups at the final time-point (p &lt; 0.001). We did not observe any differences in hepcidin concentrations. Simultaneous supplementation with FA and iron resulted in significantly higher hemoglobin concentrations at the third time-point (p &lt; 0.01).This study shows that dietary FA and iron deficiency, and subsequent supplementation with moderate amounts of these nutrients, may affect the transcription but not the protein abundance of FA and iron transporters in the rat duodenum.

Controversial Impact of Hepcidin Metabolism in the Pathogenesis of Anemia in Myelofibrosis

Anemia in myelofibrosis (MF) is a result of a multifactorial process, which is incompletely understood. The central pathogenetic mechanism is a replacement of normal hemopoietic tissue by fibrotic stroma. However, ineffective erythropoiesis, inflammation and iron overload have an additional impact on anemia development, suggesting the role of dysregulated iron homeostasis and hepcidin. The aim of the study was to analyze parameters of iron metabolism and inflammation in patients with different forms and stages of myelofibrosis. Thirty-six patients with primary MF, post-polycythemia vera and post-essential thrombocythemia MF and fourteen healthy controls were included in the study. In the patient group, serum ferritin, Fe, TIBC and parameters of CBC were measured as a part of routine clinical assessment. Plasma total hepcidin levels and concentrations of Interleukin-6 (IL6) and Interleukin-8 (IL8) were measured in duplicate by ELISA (My BioSource, San Diego, USA) in patients and healthy controls. The hepcidin level in the patient group was found statistically lower compared to healthy controls (27,64±41,56 ng/ml; 111,13±49,56 ng/ml; F=2,81, p<0,001). Patients with newly diagnosed MF had significantly higher levels of hepcidin compared to those with prolonged evolution: between 1 and 5 years (p=0,005) and >5 years (p=0,038). Transfusion dependent patients presented with lower hepcidin compared to transfusions independent (10,10±6,67 ng/ml; 31,15±44,37 ng/ml; p=0,026). In patients receiving cytoreductive or target treatment hepcidin level was significantly lower compared to patients on best supportive care (17,74±21,99 ng/ml; 43,05±58,46 ng/ml; p=0,037). No difference was found in hepcidin level within the risk groups according to DIPSS, neither between the subtypes of disease (primary MF and secondary MF). Higher hepcidin positively correlated with leukocytosis (R=0,665, p=0,009) and age (R=0,392, p=0,0081). By multivariate analysis, a significant highly positive correlation was found between hepcidin and IL-6 (R=0,535, p=0,002) and weaker between hepcidin and IL-8 (R=0,413, p=0,21) A significant straight correlation was demonstrated between IL-6 and IL-8 (R=0,464, p=0,009) and a negative between serum iron and IL-6 (R=-0,367, p=0,42) and IL-8 (R=-0,438, p=0,14), respectively. The hepcidin regulation is complex and multifactorial. Its role in pathogenesis of anemia in myelofibrosis is controversary. Probably it has a higher impact in early stages of the disease and depends on treatment and transfusions.

Serum levels of hepcidin and interleukin 6 in Parkinson’s disease

Neurodegeneration in Parkinson's disease (PD) includes processes of chronic inflammation and oxidative stress which are related to dysregulation in the homeostasis of iron metabolism. Hepcidin is a peptide hormone responsible for systemic iron homeostasis and simultaneously the inflammatory response protein, induced in response to interleukin 6 (IL‑6). We assessed the serum concentration of hepcidin and IL‑6 in the groups of patients with PD treated only pharmacologically with optimal individualized therapy (MT) and treated additionally with deep brain stimulation (DBS), compared to the control group. The serum concentrations of hepcidin and IL‑6 in the group of all PD patients were significantly higher than in the control group. In the group of PD patients treated with DBS hepcidin and IL‑6 concentrations were significantly higher compared to the control group. Additionally, the positive correlations between serum hepcidin and IL‑6 were found in the PD (MT and DBS) and PD‑DBS group. The obtained results may indicate the influence of immunological mechanisms on iron metabolism and oxidative stress, in particular when the inflammatory process is more active in the DBS‑treated group. This effect can be protective as well as neurodegenerative.

Controversial Impact of Hepcidin Metabolism in the Pathogenesis of Anemia in Myelofibrosis

Anemia in myelofibrosis (MF) is a result of a multifactorial process, which is incompletely understood. The central pathogenetic mechanism is a replacement of normal hemopoietic tissue by fibrotic stroma. However, ineffective erythropoiesis, inflammation and iron overload have an additional impact on anemia development, suggesting the role of dysregulated iron homeostasis and hepcidin. The aim of the study was to analyze parameters of iron metabolism and inflammation in patients with different forms and stages of myelofibrosis. Thirty-six patients with primary MF, post-polycythemia vera and post-essential thrombocythemia MF and fourteen healthy controls were included in the study. In the patient group, serum ferritin, Fe, TIBC and parameters of CBC were measured as a part of routine clinical assessment. Plasma total hepcidin levels and concentrations of Interleukin-6 (IL6) and Interleukin-8 (IL8) were measured in duplicate by ELISA (My BioSource, San Diego, USA) in patients and healthy controls. The hepcidin level in the patient group was found statistically lower compared to healthy controls (27,64±41,56 ng/ml; 111,13±49,56 ng/ml; F=2,81, p&lt;0,001). Patients with newly diagnosed MF had significantly higher levels of hepcidin compared to those with prolonged evolution: between 1 and 5 years (p=0,005) and &gt;5 years (p=0,038). Transfusion dependent patients presented with lower hepcidin compared to transfusions independent (10,10±6,67 ng/ml; 31,15±44,37 ng/ml; p=0,026). In patients receiving cytoreductive or target treatment hepcidin level was significantly lower compared to patients on best supportive care (17,74±21,99 ng/ml; 43,05±58,46 ng/ml; p=0,037). No difference was found in hepcidin level within the risk groups according to DIPSS, neither between the subtypes of disease (primary MF and secondary MF). Higher hepcidin positively correlated with leukocytosis (R=0,665, p=0,009) and age (R=0,392, p=0,0081). By multivariate analysis, a significant highly positive correlation was found between hepcidin and IL-6 (R=0,535, p=0,002) and weaker between hepcidin and IL-8 (R=0,413, p=0,21) A significant straight correlation was demonstrated between IL-6 and IL-8 (R=0,464, p=0,009) and a negative between serum iron and IL-6 (R=-0,367, p=0,42) and IL-8 (R=-0,438, p=0,14), respectively. The hepcidin regulation is complex and multifactorial. Its role in pathogenesis of anemia in myelofibrosis is controversary. Probably it has a higher impact in early stages of the disease and depends on treatment and transfusions.

Effect of dietary iron levels on growth, iron concentration in tissues, and blood concentration levels of transferrin and hepcidin in bighead carp (Aristichthys nobilis)

A 60‐day feeding trial was conducted to estimate the effects of dietary iron (Fe) levels on growth, Fe concentration in the liver, spleen, and blood, and transferrin and hepcidin concentrations in the blood of bighead carp (Aristichthys nobilis). The six experimental diets were formulated to contain different Fe levels (0, 43.1, 84.2, 123.3, 162.2 and 203.1 mg/kg of dry diet) using ferrous sulphate (FeSO₄) as the source. The weight gain (WG) and the specific growth ratio (SGR) of A. nobilis fed with a dietary Fe level of 123.3 mg/kg were significantly higher than that of the 0 mg/kg Fe group (p liver > whole body. When the Fe dietary content increases to 162.2 mg/kg, the blood concentrations of Fe significantly decreased and thereafter increased, hepcidin significantly decreased and thereafter decreased, and transferrin significantly increased and thereafter decreased. The results indicate that the transferrin blood content significantly increased with decreasing hepcidin of up to 264.63 μg/ml content and thereafter decreased. It could be concluded that after transferrin saturation, hepcidin functions to maintain iron balance in the blood of A. nobilis by decreasing transferrin content.

Menstrual blood losses and body mass index are associated with serum ferritin concentrations among female varsity athletes.

Preventing and treating iron deficiency are important components in the nutritional care of female varsity athletes, as these interventions may improve aerobic endurance and athletic performance. We examined the factors associated with ferritin concentration in 30 female varsity athletes (18-30 years) at the University of British Columbia in Vancouver, Canada. Biochemical indicators of iron and inflammation status, dietary intake, supplementation practices, weight, height, and menstrual blood losses were assessed. Iron deficiency prevalence was 20% (n = 6/30; inflammation-adjusted ferritin <15 μg/L). Multiple linear regression was used to assess the associations of a number of independent explanatory variables with log-transformed serum ferritin (μg/L) as the continuous outcome variable. A 1-unit increase in body mass index (BMI; kg/m2) was associated with 22% (95% CI: 9%-37%) higher mean ferritin concentrations, and a 1-point increase in menstrual loss score was associated with 1% (95% CI: 1%-2%) lower ferritin concentrations. Hemoglobin and hepcidin concentrations, inflammation biomarkers, consumption of iron supplements in any form or dose for ≥3 days/week, and age were not significantly associated with ferritin concentrations in the final adjusted model. Novelty Estimated monthly menstrual losses and BMI were associated with serum ferritin concentrations in female athletes in our study. These are easy-to-measure, noninvasive measurements that should be considered in the assessment of risk of iron deficiency in female athletes.

Hypoxia-inducible factor-1α, hepcidin and interleukin-6 levels in pregnancies with preterm labour

The aim of the study was to investigate whether serum hypoxia-inducible factor-1alpha (HIF-1α), hepcidin and interleukin-6 (IL-6) concentrations differed between threatened preterm labour (TPL) and uncomplicated pregnancies. This study was conducted on 54 women with TDL pregnancies and 26 healthy pregnant women. The TPL group was further divided into two subgroups according to the gestational age at delivery. Patients who gave birth within 48–72 h after the hospitalisation were referred to as preterm delivery (PD) and who gave birth at ≥37 weeks were referred to as term delivery (TD). Maternal levels of serum HIF-1α, hepcidin and IL-6 were measured with the use of enzyme-linked immunosorbent assay kits. The mean maternal serum HIF-1α, hepcidin and IL-6 levels of PD were significantly higher than TD (p < .001*) and control group (p < .001*). The mean maternal serum HIF-1α and hepcidin levels of TD were no significantly higher than the control group (p=.058, p = .064). The mean maternal serum IL-6 level of TD was significantly higher than the control group (p < .001*). A negative correlation was found between serum concentration of HIF1α, hepcidin, IL-6 with the gestational week of delivery (r = –0.421, p < .01* for HIF-1α; r = –0.578, p < .01* for hepcidin and r = –0.435, p < .01* for IL-6). High levels of HIF-1α, hepcidin and IL-6 may have potential to be used as biomarkers for the differentiation of PD and TD.Impact statementWhat is already known on this subject? It is known that hypoxia-inducible factor-1alpha (HIF-1α) is a hypoxia marker and hepcidin and interleukin-6 (IL-6) increase in inflammation. Our study is the comparison of maternal serum HIF-1α, hepcidin and IL-6 levels between the TPL group (TD and PD) and healthy control group.What the results of this study add? The present study demonstrates that serum HIF-1α, hepcidin and IL-6 levels were significantly higher in TPD group than uncomplicated group. The mean maternal serum HIF-1α and hepcidin levels of TD were no significantly higher than the control group.What the implications are of these findings for clinical practice and/or further research? High levels of HIF-1α, hepcidin and IL-6 may be biomarkers in the determination of true preterm labour within the TPL group.

Iron homeostasis is dysregulated, but the iron-hepcidin axis is functional, in chronic liver disease

BackgroundPerturbations in iron homeostasis have been reported to be associated with irreversible liver injury in chronic liver disease (CLD). However, it is not clear whether liver dysfunction per se underlies such dysregulation or whether other factors also contribute to it. This study attempted to examine the issues involved. MethodsPatients diagnosed to have chronic liver disease (n = 63), who underwent a medically-indicated upper gastrointestinal endoscopy, were the subjects of this study. Patients with dyspepsia, who underwent such a procedure, and were found to have no endoscopic abnormalities, were used as control subjects (n = 49). Duodenal mucosal samples were obtained to study mRNA and protein levels of duodenal proteins involved in iron absorption. A blood sample was also obtained for estimation of hematological, iron-related, inflammatory and liver function-related parameters. ResultsPatients with CLD had impaired liver function, anemia of inflammation and lower serum levels of hepcidin than control subjects. Gene (mRNA) expression levels of duodenal ferroportin and duodenal cytochrome b (proteins involved in iron absorption) were decreased, while that of divalent metal transporter–1 (DMT-1) was unchanged. Protein expression of DMT-1 was, however, decreased while that of ferroportin was unchanged. In the CLD group, serum hepcidin was predicted independently by serum ferritin and hemoglobin, but not by C-reactive protein (a marker of inflammation). CLD patients with serum ferritin greater than 300 μg/dL had significantly greater liver dysfunction (as indicated by significantly higher serum concentrations of bilirubin, AST and ALT, and MELD scores), higher serum concentrations of CRP and hepcidin, and higher ferroportin protein expression, than those with serum ferritin ≤ 300 μg/dL. ConclusionsIn patients with CLD, anemia of inflammation and low serum hepcidin levels were found to paradoxically co-exist. Expression of duodenal proteins involved in iron absorption were either decreased or unaltered in these patients. The hepcidin response to higher body iron levels and/or inflammation appeared to be functional in these patients, despite the presence of liver disease.

Testing an infection model to explain excess risk of preterm birth with long-term iron supplementation in a malaria endemic area

BackgroundIn view of recent evidence from a randomized trial in Burkina Faso that periconceptional iron supplementation substantially increases risk of spontaneous preterm birth (< 37 weeks) in first pregnancies (adjusted relative risk = 2.22; 95% CI 1.39–3.61), explanation is required to understand potential mechanisms, including progesterone mediated responses, linking long-term iron supplementation, malaria and gestational age.MethodsThe analysis developed a model based on a dual hit inflammatory mechanism arising from simultaneous malaria and gut infections, supported in part by published trial results. This model is developed to understand mechanisms linking iron supplementation, malaria and gestational age. Background literature substantiates synergistic inflammatory effects of these infections where trial data is unavailable. A path modelling exercise assessed direct and indirect paths influencing preterm birth and gestation length.ResultsA dual hit hypothesis incorporates two main pathways for pro-inflammatory mechanisms, which in this model, interact to increase hepcidin expression. Trial data showed preterm birth was positively associated with C-reactive protein (P = 0.0038) an inflammatory biomarker. The malaria pathway upregulates C-reactive protein and serum hepcidin, thereby reducing iron absorption. The enteric pathway results from unabsorbed gut iron, which induces microbiome changes and pathogenic gut infections, initiating pro-inflammatory events with lipopolysaccharide expression. Data from the trial suggest that raised hepcidin concentration is a mediating catalyst, being inversely associated with shorter gestational age at delivery (P = 0.002) and positively with preterm incidence (P = 0.007). A segmented regression model identified a change-point consisting of two segments before and after a sharp rise in hepcidin concentration. This showed a post change hepcidin elevation in women with increasing C-reactive protein values in late gestation (post-change slope 0.55. 95% CI 0.39–0.92, P < 0.001). Path modelling confirmed seasonal malaria effects on preterm birth, with mediation through C-reactive protein and (non-linear) hepcidin induction.ConclusionsFollowing long-term iron supplementation, dual inflammatory pathways that mediate hepcidin expression and culminate in progesterone withdrawal may account for the reduction in gestational age observed in first pregnancies in this area of high malaria exposure. If correct, this model strongly suggests that in such areas, effective infection control is required prior to iron supplementation to avoid increasing preterm births.Trial registration NCT01210040. Registered with Clinicaltrials.gov on 27th September 2010

Anti-TNF-α Monoclonal Antibody Therapy Improves Anemia through Downregulating Hepatocyte Hepcidin Expression in Inflammatory Bowel Disease.

Anemia is one of the most common complications in patients with inflammatory bowel disease (IBD). Hepcidin as a key regulator of iron metabolism is pivotal in mediating the occurrence of anemia of chronic disease. Herein, we analyzed the levels of hepcidin in sera from IBD patients by enzyme-linked immunosorbent assay and investigated its potential role in regulating the anemia in IBD. We observed that the levels of serum hepcidin were increased in active IBD patients compared with those in remitted IBD patients and healthy controls and that serum hepcidin was associated with disease activity, CRP, and ESR, respectively. Importantly, we found that the increased levels of serum hepcidin were positively correlated with the severity of anemia and the imbalance of iron metabolism in anemic UC and CD patients. Proinflammatory factors (e.g., IL-6, IL-17, and TNF-α) were positively correlated with the concentrations of serum hepcidin in IBD patients. Interestingly, hepcidin was found to be decreased in patients with Crohn's disease after successful therapy with anti-TNF-α mAb (i.e., infliximab), indicating the underlying association between TNF-α and hepcidin expression. To investigate the specific mechanisms involved, we cultured LO2 and HepG2 cell lines in vitro under stimulation with TNF-α and observed that the levels of hepcidin mRNA were markedly upregulated in caspase-3/8- and NF-κB-dependent manners. Therefore, our data suggest that TNF-α stimulates the expression of hepcidin in IBD patients, resulting in aggravated anemia and that blockage of TNF-α or the caspase-3/8 and NF-κB pathways could downregulate hepcidin expression. This study provides inspiration for the therapy and management of anemia in IBD.

Control of HIV-1 Infection By Ferroportin Q248H Mutation

BACKGROUND: We recently showed that patients with Sickle Cell Disease (SCD), a hereditary hemolytic disorder, have low incidence of HIV-1 infection [1] and reduced ex vivo HIV-1 infection [2]. PBMC from SCD patients exhibited increased expression of iron export protein, ferroportin and reduced cellular iron levels leading to CDK2 inhibition, reduced SAMHD1 phosphorylation and increased expression of IkBα. Ferroportin expression is regulated by liver-produced hepcidin that facilitates ferroportin internalization and degradation. Ferroportin Q248H mutation has an allele frequency of 2.2-13.4% in African populations. We previously reported reduced sensitivity of ferroportin Q248H mutant to physiologic hepcidin concentrations in patients with sickle cell disease [3]. OBJECTIVES: To analyze the effect of ferroportin Q248H mutation on HIV-1 infection in vitro and in disease progression among a cohort of HIV-1 infected African-American women. METHODS: HEK293 cells were used to express ferroportin Q248H mutant and test cellular ferritin and intracellular labile iron using calcein-AM. Confocal microscopy was used to visualize ferroportin expression. HIV-1 transcription was measured in 293T cells transfected with HIV-1 LTR-Luciferase vector and Tat expressing vector. Ex vivo infection was analyzed in monocyte-derived macrophages infected with VSVg-pseudotyped HIV-1 virus. Ferroportin Q248H mutation was genotyped using Thermo Fisher probe (C_25753769_10) and genotyping services at University of Utah. RESULTS: We observed reduced intracellular iron in ferroportin Q248H expressing cells compared to WT ferroportin even when the cells were treated with hepcidin. In the absence of hepcidin, both WT ferroportin and Q248H ferroportin efficiently inhibited HIV-1 transcription and replication. Hepcidin induced HIV-1 transcription and replication in the cells with WT ferroportin but not Q248H mutant ferroportin. HIV-1 replication was reduced in primary macrophages obtained from patients with ferroportin Q248H mutation. To test whether expression of ferroportin Q248H offered protection from HIV-1 infection, we analyzed a cohort of HIV-1 infected women (WIHS). We genotyped 970 African-American subjects of whom 628 were HIV-1 infected and 342 were non-infected. The prevalence of Q248H hetero or homozygote mutations was 7.0% in non-infected and 11.8% among HIV-1 infected individuals (Odds Ratio=1.77, p=0.02). Analysis of HIV viral load showed significant lower viral load in the subjects with ferroportin Q248H mutation compared to WT. CONCLUSIONS: Our findings point to the contribution of iron metabolism in HIV-1 restriction and the potential role of the ferroportin Q248H mutation in the regulation of HIV-1 infection in vivo. ACKNOWLEDGMENTS: This work was supported by NIH Research Grants (1P50HL118006, 1R01HL125005, 5G12MD007597 and P30AI087714). We thank Women's Interagency HIV-1 study (WIHS) for sharing DNA samples and providing access to the clinical data. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. REFERENCES: Nouraie M, Nekhai S, Gordeuk VR. Sickle cell disease is associated with decreased HIV but higher HBV and HCV comorbidities in U.S. hospital discharge records: a cross-sectional study. Sex Transm Infect. 2012;88(7):528-533. Kumari N, Ammosova T, Diaz S, et al. Increased iron export by ferroportin induces restriction of HIV-1 infection in sickle cell disease. Blood Adv. 2016;1(3):170-183. Nekhai S, Xu M, Foster A, et al. Reduced sensitivity of the ferroportin Q248H mutant to physiological concentrations of hepcidin. Haematologica. 2013;98(3):455-463. Disclosures Anastos: NINR: Research Funding; NHGRI: Research Funding; NICHD: Research Funding; NIMH: Research Funding; NHLBI: Research Funding; NCI: Research Funding; NIAID: Research Funding; NINDS: Research Funding; NIDCR: Research Funding; NIMHD: Research Funding; NLM: Research Funding; Fogarty: Research Funding; NIDDK: Research Funding; NIA: Research Funding; NIAAA: Research Funding; NIDA: Research Funding.

The hepcidin concentration decreases in hypothyroid patients with Hashimoto\u2019s thyroiditis following restoration of euthyroidism

The purpose of the study was to measure the hepcidin concentration and evaluate Fe homeostasis indices in a prospective study on patients with newly diagnosed hypothyroidism in the course of Hashimoto’s thyroiditis (HT) and following successful therapy. The prospective observational study consisted of 34 patients. The clinical evaluation and laboratory tests were performed at diagnosis (T0) and after restoration of euthyreosis 12 weeks later (T1). The median level of hepcidin was significantly lower (p = 0.002) after recovery (7.7 [6.2–13.0] ng/mL) than that before treatment (17.4 [7.6–20.4] ng/mL), while creatinine (p = 0.011) and GFR (p < 0.001) significantly improved after euthyroidism was achieved. A positive correlation was observed between hepcidin and fT3 (p = 0.033, r = 0.465) at T0. In the females, the level of hepcidin positively correlated with ferritin concentration before (p < 0.001, r = 0.928) and after treatment (p < 0.001, r = 0.835). A statistically significant difference was observed in RDW-CV (red blood cell distribution width - coefficient of variation) between the hypothyroid and euthyroid states. In conclusion, a decrease in hepcidin concentration during the transition from the hypothyroid state to euthyroidism in patients with HT is associated with the observed dynamics in iron homeostasis, mainly reflected by improvement in RDW-CV and significant correlations between ferritin and hepcidin as well as between hepcidin and fT3.

Relationship between Selenium and Hematological Markers in Young Adults with Normal Weight or Overweight/Obesity.

Selenium deficiency has been linked to anemia of inflammation, which is mediated by hepcidin. However, there are few studies providing evidence of the role of hepcidin in this relationship. In this study, we investigated the interrelationships among selenium biomarkers, hepcidin concentration, and iron status among individuals with overweight/obesity compared to their normal weight counterparts, since obesity is associated with chronic inflammation. A total of 59 college students were recruited for this study. Fasting blood samples were collected for the analysis of iron status, plasma selenoproteins (glutathione peroxidase (GPX) activity and selenoprotein P (SEPP1)), and plasma hepcidin. Subjects completed three-day dietary records to determine average daily nutrient intakes. SEPP1 concentration, GPX activity, and iron status biomarkers (serum iron, transferrin saturation, and hemoglobin concentration) were lower among individuals with overweight/obesity compared with individuals with normal weight, but these differences were not significant (p > 0.05). Regression analysis showed that GPX activity (β = −0.018, p = 0.008) and SEPP1 concentration (β = −1.24, p = 0.03) were inversely associated with hepcidin concentration. The inverse association between selenoproteins and hepcidin concentration supports a potential role of hepcidin as a mediator between selenium and iron status and warrants further studies to better understand this relationship.

Changes of cytokine profile in the blood of pregnant women with anemia.

This research paper presents the results of a study of some indicators of iron metabolism in anaemia in pregnant women. The venous blood of 39 pregnant women with anaemia was examined. Serum ferritin, ferroportin and hepcidin were investigated for this purpose. The comparison group consisted of 19 pregnant women without anaemia. The haemoglobin concentration was measured by using «Mythic-18» haematological autoanalyzer. The concentrations of hepcidin and ferroportin were determined by using «Cloud-Clone Corp.» (USA), and ferritin concentrations were determined by using «Pishtaz teb» (Iran) reagents through enzyme-linked immunosorbent assay (ELISA) method. The study revealed a significant decrease in the level of ferritin, hepcidin and a significant increase in ferroportin level. A comprehensive definition of various indicators of iron metabolism provides important information not only for understanding the pathogenesis of iron deficiency anaemia in pregnant women but also for early diagnosis of the disease and the appointment of the correct treatment.

Development of strategic approaches to modern diagnosis of anemic syndrome in patients with breast cancer.

A study of the clinical analysis of blood and major metabolites of ferrokinetics in 107 breast cancer patients before treatment was conducted. In 31 (28.9%) patients revealed anemic syndrome (AS). A feature of the AS is pronounced microcytosis, erythrocyte hypochromia and low hemoglobin content in reticulocytes. Most often (n = 22; 71%) there was iron deficiency (IDA), which was characterized by a low concentration of iron (F), ferritin (FR), hepcidin 25 (GP25), interleukin-6 (IL-6) and high - soluble transferrin receptors (rTFR), transferrin (TRF). In 9 (29%) patients with AS, on the basis of a high concentration of FR, GP25, IL-6, the anemia of chronic disease (AHZ) with functional iron deficiency (FDI) was established. In 23 (74.2%) patients with AS, the was a deficiency of erythropoietin (EPO), the lowest rates were found in the group of patients with a common tumor process and FDI, with less in patients with IDA.

Expression and influencing factors of hepcidin in classical paroxysmal nocturnal hemoglobinuria

目的研究铁调素在经典型阵发性睡眠性血红蛋白尿症（PNH）患者血清中的表达及其影响因素。方法以2016年3月至2017年3月36例经典型PNH患者为研究对象，采用ELISA方法检测血清铁调素水平，并结合患者铁稳态状况和临床资料，分析经典型PNH患者血清铁调素水平与血清铁蛋白（SF）、可溶性转铁蛋白受体、C反应蛋白、EPO、网织红细胞绝对值、网织红细胞血红蛋白等血液学参数的相关性。结果36例经典型PNH患者血清铁调素水平为32.03（23.11，118.48）µg/L，明显低于正常对照组的181.42（106.80，250.53）µg/L（z=−5.107，P<0.001）。其中，铁蛋白正常经典型PNH患者血清铁调素水平为56.41（44.60，95.06）µg/L，经典型PNH伴缺铁组血清铁调素水平为23.75（21.77，30.35）µg/L，均低于正常对照组；而经典型PNH伴铁蛋白升高组血清铁调素水平为336.19（304.19，375.08）µg/L，高于正常对照组、铁蛋白正常经典型PNH组及经典型PNH伴缺铁组。多重线性回归分析显示SF、转铁蛋白饱和度和血清白蛋白水平是经典型PNH患者血清铁调素水平的独立影响因素。结论经典型PNH患者血清铁调素水平减低，其表达主要受铁代谢因素影响。

Systemic hepcidin quantified with LC–MS/MS in dementia in association with disease pathology and severity and with structural changes in the brain

Hepcidin is a peptide hormone regulating iron metabolism, the dyshomeostasis of which has been implicated in dementia. Yet, data on hepcidin status in dementia are scanty, limited to Alzheimer’s disease (AD) and inconsistent due to methodological problems with its determination using immunoassays and/or lack of homogeneity of evaluated groups. Hepcidin association with vascular dementia (VaD) remains unknown. We proposed a mass spectrometry method of hepcidin quantification in sera and aimed at determining hepcidin systemic status in patients with dementia of AD, VaD, or mixed (MD) pathology, with reference to the degree of cognitive loss and structural changes in the brain as well as at evaluating the diagnostic potential of hepcidin as a biomarker. We found that hepcidin concentrations were significantly elevated in VaD and insignificantly so in AD or MD and that they positively correlated with the Clinical Dementia Rating and inversely with the Mini Mental State Examination. Hepcidin tended to be more pronouncedly elevated in patients with advanced cortical atrophy and white matter lesions. It displayed a biphasic relationship with the Hachinski Ischemic Scale and a good accuracy as dementia but not differential marker. Taken together, our results demonstrated that dementia of vascular and not neurodegenerative pathology is associated with significant elevation of systemic hepcidin. Hepcidin elevation reflects the degree of cognitive loss as well as the severity of structural changes in the brain. If confirmed in a prospective study, hepcidin quantification may hold promise as a diagnostic marker; its accuracy as a differential marker of VaD is insufficient.