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Hepcidin has a crucial role in iron homeostasis upon inflammatory conditions such as inflammatory bowel disease (IBD). Thus, we conducted a systematic review and meta‐analysis to determine the overall association between serum hepcidin concentrations and IBD. Based on the preferred reporting items for systematic review and meta‐analysis (PRISMA) protocols, an electronic literature search was conducted on PubMed/MEDLINE, Scopus, and Web of Science until June 2020. Studies were deemed eligible for inclusion if they met the following criteria: (1) diagnosis of IBD, (2) observational design, and (3) measured serum hepcidin and prohepcidin concentrations in IBD patients and control group. Overall, 10 studies including 1184 participants were evaluated. Random‐effects meta‐analysis revealed that subjects with IBD had 7.22 ng/mL (95% CI: 2.10, 12.34; p =.006) higher serum hepcidin concentrations compared to control groups. A nonsignificantly lower serum prohepcidin concentration (0.522 ng/mL, 95% CI: −1.983 to 0.939; p =.484) was found for IBD patients compared to healthy subjects. However, there was significant heterogeneity among the studies regarding both hepcidin (I2 = 98%, p <.001) and prohepcidin levels (I2 = 96%, p <.001), respectively. In an age‐based subgroup analysis, patients aged ≥18 years with IBD displayed higher serum hepcidin levels when compared to healthy individuals (22.36 ng/mL, 95% CI, 2.12–42.61; p =.030). Hepcidin concentrations are elevated in subjects with IBD; however, the clinical relevance of this finding requires further evaluation in future investigations as the increase is relatively small compared to the wide range of normal hepcidin values. [ABSTRACT FROM AUTHOR]

Aim:To study changes in hepcidin, a key protein synthesized in the liver, following chronic viral hepatitis, cirrhosis and/or liver transplant, as well as the effect of hepcidin level variation on liver function tests and iron levels.Materials and Methods:The patient population was distributed as follows: Group 1: inactive chronic hepatitis B (n=31); Group 2: chronic hepatitis C (n=30); Group 3: decompensated cirrhosis linked to hepatitis C virus (HCV) or hepatitis B virus (HBV) (n=29); Group 4: decompensated HCV- or HBV-related cirrhosis treated by liver transplantation (n=31).Results:The following characteristics were unequally distributed among the groups: age, Hb, AST, ALP, LDH, T. bil, albumin, total cholesterol, HDL, serum total iron binding capacity, and transferrin saturation (TS). In the two-group comparison of Groups 1 and 2, significant differences in Hb, AST, AP, albumin, and prohepcidin were observed; the latter was more elevated in HCV patients (Group 2) (p

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Hepcidin (DTHFPICIFCCGCCHRSKCGMCCKT), an iron-regulatory hormone, is a 25-amino-acid peptide with four intramolecular disulfide bonds circulating in blood. Its hormonal activity is indirect and consists of marking ferroportin-1 (an iron exporter) for degradation. Hepcidin biosynthesis involves the N-terminally extended precursors prepro-hepcidin and pro-hepcidin, processed by peptidases to the final 25-peptide form. A sequence-specific formation of disulfide bonds and export of the oxidized peptide to the bloodstream follows. In this study we considered the fact that prior to export, reduced hepcidin may function as an octathiol ligand bearing some resemblance to the N-terminal part of the α-domain of metallothioneins. Consequently, we studied its ability to bind Zn(II) and Cd(II) ions using the original peptide and a model for prohepcidin extended N-terminally with a stretch of five arginine residues (5R-hepcidin). We found that both form equivalent mononuclear complexes with two Zn(II) or Cd(II) ions saturating all eight Cys residues. The average affinity at pH 7.4, determined from pH-metric spectroscopic titrations, is 1010.1 M−1 for Zn(II) ions; Cd(II) ions bind with affinities of 1015.2 M−1 and 1014.1 M−1. Using mass spectrometry and 5R-hepcidin we demonstrated that hepcidin can compete for Cd(II) ions with metallothionein-2, a cellular cadmium target. This study enabled us to conclude that hepcidin binds Zn(II) and Cd(II) sufficiently strongly to participate in zinc physiology and cadmium toxicity under intracellular conditions. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate serum prohepcidin concentrations in preeclamptic pregnant women related to iron status markers and compared to healthy pregnant women. A total of 80 pregnant women admitted to a tertiary care obstetric clinic were included in this cross-sectional study. Pregnant women were divided into two groups based on preeclampsia screening results, including those with preeclampsia (n=40) and healthy pregnant women (n=40). Data on the gestational week at the time of blood sampling, and blood analysis findings including complete blood count (CBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), iron homeostasis parameters (serum iron, ferritin, and total iron-binding capacity [TIBC]), and plasma prohepcidin levels were recorded in each woman. The presence of preeclampsia was associated with significantly higher WBC count (13.5±4.4 vs. 10.9±2.9 x103/µL, p=0.001) and serum iron (102.7±65.0 vs. 74.8±54.0 µmol/L, p=0.04) and ferritin (40.9±41.2 vs. 18.6±29.1 µg/L, p=0.007) and plasma prohepcidin (38.2±39.3 vs. 17.91±14.71, p=0.004) levels compared to the healthy pregnant woman. Our findings indicate an increase in serum iron and ferritin levels coupled with elevated prohepcidin levels in pregnancies complicated by preeclampsia. Further longitudinal researches are needed to clarify the role of prohepcidin and active hepcidin in preeclampsia and the potential mechanisms underlying the unregulated hepcidin-iron homeostasis. [ABSTRACT FROM AUTHOR]

Hepcidin (DTHFPICIFCCGCCHRSKCGMCCKT), an iron-regulatory hormone, is a 25-amino-acid peptide with four intramolecular disulfide bonds circulating in blood. Its hormonal activity is indirect and consists of marking ferroportin-1 (an iron exporter) for degradation. Hepcidin biosynthesis involves the N-terminally extended precursors prepro-hepcidin and pro-hepcidin, processed by peptidases to the final 25-peptide form. A sequence-specific formation of disulfide bonds and export of the oxidized peptide to the bloodstream follows. In this study we considered the fact that prior to export, reduced hepcidin may function as an octathiol ligand bearing some resemblance to the N-terminal part of the α-domain of metallothioneins. Consequently, we studied its ability to bind Zn(II) and Cd(II) ions using the original peptide and a model for prohepcidin extended N-terminally with a stretch of five arginine residues (5R-hepcidin). We found that both form equivalent mononuclear complexes with two Zn(II) or Cd(II) ions saturating all eight Cys residues. The average affinity at pH 7.4, determined from pH-metric spectroscopic titrations, is 1010.1 M−1 for Zn(II) ions; Cd(II) ions bind with affinities of 1015.2 M−1 and 1014.1 M−1. Using mass spectrometry and 5R-hepcidin we demonstrated that hepcidin can compete for Cd(II) ions with metallothionein-2, a cellular cadmium target. This study enabled us to conclude that hepcidin binds Zn(II) and Cd(II) sufficiently strongly to participate in zinc physiology and cadmium toxicity under intracellular conditions.

Present studies on serum hepcidin levels in patients with rheumatoid arthritis (RA) are inconsistent. We aimed to synthetically evaluate the relationship between hepcidin and RA, and the correlation of serum hepcidin levels and RA disease activity as well as anemia associated with RA. Multiple electronic databases were searched. Pooled standard mean difference (SMD) with 95% confidence interval (CI) and correlation coefficients between hepcidin levels and rheumatoid factor (RF), disease activity for 28 joints (DAS28), and erythrocyte sedimentation rate (ESR) were calculated. Totally, 13 articles were available for this meta-analysis. The results revealed that serum levels of hepcidin were higher in RA patients compared to healthy controls (SMD = 0.573, 95% CI = 0.317 to 0.829, p <.001); RA patients with anemia had higher serum hepcidin levels than RA patients without anemia (SMD = 0.400, 95% CI = 0.080 to 0.720, p =.014); RA patients with pure ACD had higher serum hepcidin levels than RA patients with ACD and IDA (SMD = 0.658, 95% CI = 0.018 to 1.299, p =.044). Moreover, the result of correlation coefficients identified a significant positive correlation between hepcidin levels and RF, DAS28 as well as ESR. Serum hepcidin levels may be closely associated with the development of RA. [ABSTRACT FROM AUTHOR]

Aim: To find the correlations between the parameters of iron homeostasis, inflammatory activity and autoimmune disorders in rheumatoid arthritis (RA).

Aim: To find the correlations between the parameters of iron homeostasis, inflammatory activity and autoimmune disorders in rheumatoid arthritis (RA).

Background: The Anaemia of chronic disease (ACD) is a prevalent, poorly understood condition that afflicts patients with a wide variety of diseases, including infections, malignancies and rheumatologic disorders. Materials and Method: 40 patients 20-65 years of age with chronic periodontitis were assessed before and after periodontal therapy for Hb, ESR, Erythrocyte count, MCV, MCH, MCHC and PROHEPCIDIN (ELISA). Results: A significant (p<.000) increase in RBC (4.581) and Hb (12.77) values were estimated after SRP compared to baseline. Prohepcidin levels decreased insignificantly after SRP. Tailed t test results shows significant correlation at the 0.01 level between RBC parameters but no significance between probing depth or prohepcidin values with RBC parameters. Conclusion: The results conclude that reduction in periodontal inflammation by scaling and root planning improves RBC count and hemoglobin level significantly Prohepcidin levels decreases with periodontal treatment but rather insignificantly. [ABSTRACT FROM AUTHOR]

Introduction The aim of this study was to determine whether there is a relation between serum prohepcidin level and disease activity of rheumatoid arthritis (RA) and systemic lupus erythematous (SLE), and to discover whether it has a role in the anaemia of chronic disease occurring in RA and SLE patients. Patients and methods This study was carried out on 30 patients suffering from RA and 30 patients suffering from SLE. In addition, 20 healthy volunteers were recruited as controls. All patients and controls were subjected to full history taking, thorough clinical examination, locomotor system examination, assessment of the disease activity in RA patients using the Disease Activity Score-28, assessment of the disease activity in SLE patients using Systemic Lupus Erythematous Disease Activity Index, laboratory investigations, including complete blood count, erythrocyte sedimentation rate (ESR), rheumatoid factor and C-reactive protein (CRP), and measurement of serum prohepcidin levels by the enzyme-linked immunosorbant assay. Results The mean serum prohepcidin concentration was 395.2 ± 551.4 ng/ml in RA patients, whereas it was 381.5 ± 88.07 in SLE patients and 121.4 ± 11.1 ng/ml in healthy volunteers. The prohepcidin concentration correlated with the rheumatoid factor, C-reactive protein, ESR, disease duration, morning stiffness, tender joint count, swollen joint count, Larsen score, haemoglobin level and Disease Activity Score-28 in RA patients .There were positive significant correlations between the mean serum prohepcidin concentration and platelets number, haemoglobin level and ESR in SLE patients and insignificant correlations between the mean serum prohepcidin concentration and Systemic Lupus Erythematous Disease Activity Index. Conclusion Prohepcidin could be considered as a useful marker for RA, but not for SLE. Prohepcidin may have a role in anaemia of chronic disease occurring in RA and SLE.

"nBackground: Prohepcidin, a liver-derived peptide with antimicrobial properties, is regulated by factors such as iron load and inflammation. Hepcidin is a central player in iron homeostasis. It downregulates the iron exporter ferroportin, thereby inhibiting iron absorption, release and recycling. Thus, prohepcidin increases the possibility of iron-limited erythropoiesis and development of anemia. In end-stage renal disease (ESRD), plasma hepcidin levels are elevated, which may contribute to iron deficiency in these patients. This study was undertaken to investigate the relationship between prohepcidin and serum biochemical parameters related to anemia and inflammation in the aforesaid patients."n "nMethods: Fifty-four stable patients with uremia who were on chronic hemodialysis were enrolled in the study. The patients were withheld from intravenous iron two weeks prior to laboratory measurements. Later, (total) prohepcidin was measured by ELISA method as were other parameters including serum iron, TIBC, TSAT, Hct, ferritin, albumin, CRP, ESR, cholesterol and triglyceride."n "nResults: Serum prohepcidin levels were higher than normal values in the patients, but they were not correlated to the serum iron, TIBC, TSAT, Hct, ferritin, albumin, cholesterol and triglyceride (p>0.05). No significant association were also found with ESR (p=0.97, r= -0.005) or CRP (p=0.053, r =0.26)."n "nConclusion: Serum prohepcidin level was higher in chronic hemodialysis patients but it was not predictive of iron status or inflammatory conditions in these patients. Confirmation of these results may necessitate studies with larger sample sizes or measurement of the biologically active form of hepcidin.

OBJECTIVE: To determine the impact of periodontal treatment on serum levels of prohepcidin (the prohormone of hepcidin) and systemic inflammation markers, as well as correlations among these markers, in patients with chronic periodontitis and chronic kidney disease who were not undergoing dialysis. METHODS: We included 56 chronic periodontitis patients, 36 with chronic kidney disease and 20 without systemic diseases and with normal renal function (control group). Chronic kidney disease was defined as suggested by the clinical practice guidelines in the National Kidney Foundation. Chronic periodontitis was defined through clinical attachment level and by probing pocket depth, according to the American Association of Periodontology. The inflammatory markers ultrasensitive C-reactive protein, interleukin-6, and prohepcidin were evaluated before and 3 months after periodontal treatment. RESULTS: The efficacy of periodontal treatment was confirmed by the improvement in clinical parameters of chronic periodontitis in the control and chronic kidney disease groups. Periodontal treatment resulted in significant reductions in ultrasensitive C-reactive protein, interleukin-6 and serum prohepcidin levels in both groups. Moreover, in multivariate linear regression, the reduction in prohepcidin after periodontal treatment was significantly and independently associated with interleukin-6 levels in the control group. CONCLUSIONS: By inducing a decline in the systemic inflammatory response and a decrease in serum prohepcidin, successful periodontal treatment may represent an important means of ameliorating the inflammatory burden seen in patients with chronic kidney disease.

La hepcidina, péptido antimicrobiano, cuya síntesis se encuentra regulada por el estado del hierro e inflamación, juega un importante papel en la homeostasis del hierro en pacientes hemodializados (HD). Es medida a través de la prohepcidina sérica. Objetivo: Determinar los niveles séricos de prohepcidina y su relación con ferritina sérica, proteína C reactiva (PCR) y albúmina en pacientes HD tratados o no con eritropoyetina recombinante (EPO), que asistieron a un Centro de Salud del Estado Carabobo-Venezuela. Metodología: Esta investigación es de tipo descriptiva, correlacional y de campo, cuya muestra estuvo conformada por 71 pacientes HD; 57 de éstos tratados con EPO. Se determinó prohepcidina sérica, ferritina, hemoglobina, hematocrito, PCR y albúmina. Se definió anemia (hemoglobina < 10 g/dL) y deficiencia de hierro (ferritina < 100 ng/mL) de acuerdo al criterio recomendado por grupo K/DOQUI. Valores de referencia: Albúmina 3,5 a 4,8 g/dL, para procesos inflamatorios agudos (PCR > 10 mg/L). Resultados: El promedio para la prohepcidina fue de 397,5 ng/mL. Se observó un alto porcentaje de anemia (87,3%) y un 22,5% de pacientes con ferritina sérica baja. No se observaron diferencias estadísticamente significativas para ferritina, albúmina, PCR y prohepcidina, entre pacientes con y sin tratamiento con EPO. Solo la variable PCR se correlaciona significativamente (rho = 0,276; p =0,020), con prohepcidina. Conclusión: Pacientes HD presentan niveles elevados de prohepcidina, esto pudiera deberse al proceso inflamatorio frecuentemente observado en estos pacientes y no al estado de hierro medido a través de los niveles de ferritina sérica.Hepcidin, an antimicrobial peptide which synthesis is regulated by iron status and inflammation, plays an important role in iron homeostasis in hemodialysed (HD) patients. It is measured by measuring serum prohepcidin. Objective: To determine serum prohepcidin levels and their relationship with serum ferritin, C reactive protein (CRP), and albumin in HD patients treated or not with recombinant erythropoietin (EPO) that attended the Health Centre of the Carabobo State in Venezuela. Methodology: This is a descriptive, correlational, and field investigation with a sample comprised by 71 HD patients of whom 57 were treated with EPO. Serum prohepcidin, ferritin, haemoglobin, hematocrit, CRP, and albumin were determined. Anaemia (haemoglobin < 10 g/dL) and iron deficiency (ferritin < 100 ng/mL) were defined according to the criteria recommended by the K/DOQUI group. Reference values: Albumin 3.5-4.8 g/dL, and for acute inflammatory conditions (CRP > 10 mg/L.). Results: The mean value for prohepcidin was 397.5 ng/mL. A high percentage of anaemia was observed (87.3%) and 22.5% of the patients had low levels of serum ferritin. There were no statistically significant differences for ferritin, albumin, CRP, or prohepcidin, between patients with and without EPO therapy. Only the CRP value was significantly correlated (rho = 0.276; p = 0.020) with prohepcidin. Conclusion: HD patients present high levels of prohepcidin, and this may be due to the common ongoing inflammatory process in these patients and not to the iron status measured through serum ferritin levels.

Recent research evidence suggests a central role for hepcidin in iron homeostasis. Hepcidin is a hormone synthesized in the liver. Hepcidin is also thought to play a vital role in the pathogenic mechanism of anaemia in patients with inflammation or chronic disease. A 38-year-old female who presented with recurrent abdominal pain was found to have raised urinary porphyrins and a blood lead level of 779 µg/l. Her haemoglobin level was 8.3 g/dl. Her MCV was normal. Serum ferritin, B12 and folate were normal. Her serum prohepcidin level was 2,489 ng/ml (normal

A number of pathophysiological conditions are related to iron metabolism disturbances. Some of them are well known, others are newly discovered or special. Hepcidin is a newly identified iron metabolism regulating hormone, which could be a promising biomarker for many disorders. In this review, we provide background information about mammalian iron metabolism, cellular iron trafficking, and the regulation of expression of hepcidin. Beside these molecular biological processes, we summarize the methods that have been used to determine blood and urine hepcidin levels and present those pathological conditions (cancer, inflammation, neurological disorders) when hepcidin measurement may have clinical relevance. [ABSTRACT FROM AUTHOR]

Since the immune system is suppressed before bone marrow transplantation (BMT), severe infections might arise. This clinical article considers the role of prohepcidin, in addition to interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in infections occurring after BMT. Serum prohepcidin, IL-6, TNF-α, and C-reactive protein (CRP) levels were measured in 10 pediatric BMT patients by enzyme-linked immunosorbent assay before and after BMT. The results were evaluated statistically. As a result of the analysis, it was observed that there was a significant correlation between serum prohepcidin and IL-6, TNF-α, and CRP levels in the pretransplantation, posttransplantation, and discharge periods of the patients. The relationship between CRP levels and prohepcidin levels suggests that the serum prohepcidin level might be an important parameter for transplantation patients in consideration of infection. Verification of these results from future studies may confirm the clinical importance of hepcidin. [ABSTRACT FROM AUTHOR]

The link between Helicobacter pylori and iron deficiency (ID) or iron deficiency anemia (IDA) has been investigated recently. We suggested that IDA/ID associated with H. pylori infection might be mediated by inflammation-driven hepcidin production. Patients with complaints of recurrent abdominal pain and dyspepsia aged between 7-16 years were included in this study. Patients were divided into two groups according to H. pylori status in upper gastrointestinal endoscopy. Group I who had H. pylori gastritis ( n = 50) received triple antibiotic therapy. Group II ( n = 50) who had H. pylori-negative gastritis only received proton pump inhibitor. Thirty healthy children with the similar age and gender were included in the study as a control group. Complete blood count, serum iron levels, iron-binding capacity, ferritin levels, prohepcidin and interleukin-6 (IL-6) values were evaluated in all children at the first visit. Initial tests were repeated after H. pylori eradication. Initial levels of ferritin ( p = 0.002), prohepcidin ( p = 0.003), and IL-6 ( p = 0.004) were found significantly lower in group I compared to group II and the control group. The mean prohepcidin level was lower in the anemic H. pylori-positive group than in non-anemic H. pylori-positive group; however, the difference was not statistically significant. While significant increases in hematocrit and mean corpuscular volume were observed, no significant difference was found in serum ferritin, prohepcidin, or IL-6 level after eradication treatment in H. pylori-positive group. Conclusion: H. pylori-induced gastritis appears to cause an increase in prohepcidin levels and a decrease in ferritin levels, supporting our hypothesis; but this relationship has not been proven. [ABSTRACT FROM AUTHOR]

Objective: The objective of the study was to compare pro-hepcidin, hemoglobin (Hb) concentration, hematocrit (Hct), C-reactive protein (CRP), IL-6 and iron status parameters in preeclamptic (PE) and healthy pregnant women, and to examine the relationship between serum pro-hepcidin levels and iron parameters of preeclampsia (PE). Methods: In a prospective controlled study, we collected serum from women with normal pregnancy ( n = 37) and from women with PE ( n = 30) at the Department of Obstetrics and Gynecology at Turgut Ozal University between February 2010 and January 2013. Pro-hepcidin, hemoglobin (Hb) concentration, hematocrit (Hct), CRP, IL-6 and iron status parameters were measured in all patients and compared between groups. Results: Levels of serum prohepcidin in PE and control groups were similar and amount 69.4 ± 19.7 and 71.9 ± 22.1 ng/ml, respectively. The difference was not statistically significant ( p: 0.694). On the other hand, the study group had a statistically lower iron binding capacity (IBC), total iron binding capacity, transferin, total protein, albumin levels ( p < 0.05). No significant differences were found among prohepcidin, Hb concentration, Hct, iron, ferritin, IL-6, urea and creatine in both the groups. Conclusion: In pregnancies complicated by PE with normal values of hemoglobin and hematocrit, serum prohepcidin concentrations are similar to those observed in healthy pregnant women. The analysis revealed no significant correlations between prohepcidin level and serum iron, serum ferritin or transferrin in the PE. [ABSTRACT FROM AUTHOR]

Background/aim: To investigate whether spontaneous preterm labor (PTL) with intact membranes is associated with changes in maternal serum prohepcidin concentrations. Materials and methods: The study consisted of patients with spontaneous PTL with intact membranes (n = 25), a control group of healthy pregnant women between the 24th and 37th gestational weeks (n = 22), and uncomplicated term pregnancies in spontaneous labor (n = 19). Blood samples were collected from patients at the time of clinical diagnosis. Levels of prohepcidin, hemoglobin, serum ferritin, serum iron, unsaturated iron binding capacity, total iron binding capacity, transferrin and transferrin saturation, C reactive protein, and interleukin-6 were measured. Results: Patients with spontaneous PTL had significantly lower maternal serum prohepcidin concentrations than term delivery and control subjects. Conclusion: Maternal serum prohepcidin concentration is lower in patients with spontaneous PTL compared to term delivery and control subjects. This suggests that measuring maternal serum prohepcidin concentrations in PTL may be a feasible method for understanding etiologic causes of spontaneous preterm delivery, but, before suggesting this as a course of action, low levels of prohepcidin in patients with PTL need to be more fully investigated. [ABSTRACT FROM AUTHOR]

Introduction: Hepcidin, a small peptide hormone synthesized in the liver, plays central role in regulation of iron metabolism. Hepcidin generation in chronic kidney disease (CKD) is dependent on iron status, anemia, inflammation, and hypoxia and erythropoietin levels. In our study, the relationship between Prohepcidin levels and inflammation and iron indices in non-diabetic uremic patients was investigated. Methods: This study has a cross-sectional design which includes four groups: Non-diabetic 21 patients with stage 4 CKD (predialysis), 20 hemodialysis (HD) and 21 peritoneal dialysis (PD) patients and 17 healthy volunteers as the control group. Complete blood count, iron, total iron binding capacity (TIBC), ferritin, high-sensitive C-reactive protein (hsCRP), fibrinogen, parathyroid hormone, interleukin (IL)-6 and Prohepcidin levels were recorded. Results: Serum Prohepcidin levels in the predialysis, HD, PD and the control groups were 119.6 ± 45.1 ng/mL, 140.2 ± 41.8 ng/mL, 148.2 ± 35.0 ng/mL and 93.8 ± 21.9 ng/mL, respectively ( p < 0.001). Prohepcidin was positively correlated with urea ( r = 0.345, p = 0.002), creatinine ( r = 0.465, p < 0.001), phosphorus ( r = 0.253, p = 0.025), hsCRP ( r = 0.275, p = 0.019), duration of dialysis treatment ( r = 0.443, p < 0.001), fibrinogen ( r = 0.467, p < 0.001) and IL-6 ( r = 0.615, p < 0.001) levels. A negative correlation was detected between Prohepcidin levels and albumin ( r = −0.286, p < 0.001), TIBC ( r = −0.573, p < 0.001), GFR ( r = −0.473, p < 0.001), hemoglobin ( r = −0.351, p = 0.002) and hematocrit ( r = −0.342, p = 0.002) levels. Discussion: Prohepcidin levels increase with deepening anemia and show positive correlation with inflammatory markers. Therapeutic interventions regarding Prohepcidin action on inflammatory status may play a role in the treatment of anemia due to inflammation. Functional iron deficiency is frequent in uremic patients. It may be beneficial to measure Prohepcidin level together with ferritin among these patients. [ABSTRACT FROM AUTHOR]

Abstract: It is well known that the iron content of the body is tightly regulated. Iron excess induces adaptive changes that are differentially regulated in each tissue. The pancreas is particularly susceptible to iron-related disorders. We studied the expression and regulation of key iron proteins in the pancreas, duodenum and liver, using an animal model of iron overload (female CF1 mice injected i.p. with iron saccharate, colloidal iron form). Divalent metal transporter 1, prohepcidin and ferritin (pancreas, duodenum, liver) were assessed by immunohistochemistry; divalent metal transporter 1 (pancreas, duodenum) by Western blot. In the iron overloaded mice, prohepcidin expression increased in islets of Langerhans and hepatocytes, and divalent metal transporter 1 expression decreased in cells of islets and in enterocytes. In the iron overloaded mice, ferritin expression decreased in islets of Langerhans and increased in acinar cells; hemosiderin was localized in connective tissue cells. The inverse relationship between divalent metal transporter 1 and prohepcidin may indicate a negative regulation by hepcidin, and hence reduction of iron stores in islets of Langerhans. Our data showed that in iron overloaded mice model, induced by colloidal iron form, a coordinated expression of key iron proteins in the pancreas, duodenum and liver may occur. Further research will be necessary to determine the adaptive responses induced by iron in the pancreas. [Copyright &y& Elsevier]

Background: Hepcidin, a key regulator of iron homeostasis, increases when inflammation and some infections occur. It plays a critical role in macrophage iron retention, which underlies inflammation/infection caused anemia. It is known that Helicobacter pylori (HP) may lead to iron deficiency (ID) due to occult blood loss or reduced iron absorption. This study investigates the role of prohepcidin, hepcidin's precursor, in ID and ID anemia (IDA) with a concurrent HP infection. Methods: In this prospectively designed study, 15 patients with IDA and a concurrent HP infection (group 1), 11 patients with an ID and a concurrent HP infection (group 2), and 18 patients with HP infection (group 3) were observed. All groups received only HP eradication therapy. Twenty-five age- and sex-matched children without ID/IDA and HP infection were included in the study as the control group. In all groups and control group, measurements were taken for pre- and posttreatment hemoglobin, serum prohepcidin, serum ferritin, serum iron (SI), transferrin saturation, erythrocyte sedimentation rate, fibrinogen, and C-reactive protein levels. Results: The pretreatment prohepcidin levels were significantly higher only in group 1 compared to the control group ( P < .05). In group 1, a significant increase in hemoglobin and SI levels and a significant reduction in prohepcidin levels were additionally observed following HP eradication treatment ( P < .05). However, in groups 2 and 3, significant differences in hemoglobin, iron, and prohepcidin levels between pre- and posttreatment were not observed. Conclusion: Elevated serum prohepcidin might indicate the role of inflammation in the etiology of anemia concurrent with HP. [ABSTRACT FROM AUTHOR]

To analyze the interconnection between erythropoiesis and iron metabolism, one of the issues raised in this study was to know iron bioavailability under physiopathological conditions. Our aim was to understand the functional axis response composed of erythropoietin (Epo)-hepcidin-ferroportin (FPN), when 2 dysfunctional states coexist, using an animal model of iron overload followed by hypoxia. FPN and prohepcidin were assessed by immunohistochemistry using rabbit anti-mouse FPN polyclonal and prohepcidin monoclonal antibodies. Goat-labeled polymer − horseradish peroxidase anti-rabbit EnVision + System (DAB) was used as the secondary antibody. Epo levels were measured by ELISA. Tissue iron was studied by Prussian blue iron staining. Erythropoietic response was assessed using conventional hematological tests. Iron overload increased prohepcidin that remained high in hypoxia, coexisting with high levels of Epo in hypoxia, with or without iron overload. In hypoxia, FPN was clearly evident in reticuloendothelial macrophages, more than in hypoxia with iron overload. Interestingly, duodenal FPN was clearly identified on the basolateral membrane in hypoxia, with or without iron overload. Our data indicate that 2 signals could induce the cell-specific response as follows: ( i) iron signal, induced prohepcidin, which reduced reticuloendothelial FPN and reduced iron availability; and ( ii) hypoxia signal, stimulated Epo, which affected iron absorption by stabilizing duodenal FPN and allowed iron supply to erythropoiesis independently of store size. [ABSTRACT FROM AUTHOR]

Hepcidin is the major regulatory peptide hormone of iron metabolism, encoded by the HAMP (hepcidin antimicrobial peptide) gene. Hepcidin is expressed mainly in hepatocytes, but is also found in the blood in both a mature and prohormone form. Although, the function of mature hepcidin and the regulation of the HAMP gene have been extensively studied, the intracellular localization and the fate of prohepcidin remains controversial. In the present study, we propose a novel role for prohepcidin in the regulation of its own transcription. Using indirect immunofluorescence and mCherry tagging, a portion of prohepcidin was detected in the nucleus of hepatocytes. Prohepcidin was found to specifically bind to the STAT3 (signal transducer and activator of transcription 3) site in the promoter of HAMP. Overexpression of prohepcidin in WRL68 cells decreased HAMP promoter activity, whereas decreasing the amount of prohepcidin caused increased promoter activity measured by a luciferase reporter-gene assay. Moreover, overexpression of the known prohepcidin-binding partner, α-1 antitrypsin caused increased HAMP promoter activity, suggesting that only the non-α-1 antitrypsin-bound prohepcidin affects the expression of its own gene. The results of the present study indicate that prohepcidin can bind to and transcriptionally regulate the expression of HAMP, suggesting a novel autoregulatory pathway of hepcidin gene expression in hepatocytes. [ABSTRACT FROM AUTHOR]

Abstract: The aim of this study was to evaluate biochemical parameters of iron metabolism in rats experimentally infected with Trypanosoma evansi. To this end, 20 rats (Wistar) were intraperitoneally inoculated with blood containing trypomastigotes 106 (Group T) and 12 animals were used as negative control (Group C) and received saline (0.2mL) through same route. Blood samples were collected by cardiac puncture on day 5 (C5, T5) and 30 (C30, T30) post-inoculation (pi) to perform complete blood count and determination of serum iron, transferrin, ferritin, total and latent iron fixation capacity, transferrin saturation and prohepcidin concentration. Also, bone marrow samples were collected, to perform Pearls staining reaction. Levels of iron, total and latent iron binding capacity and prohepcidin concentration were lower (P <0.05) in infected rats (T5 and T30 groups) compared to controls. On the other hand, levels of transferrin and ferritin were higher when compared to controls (P <0.05). The transferrin saturation increased on day 5pi, but decreased on day 30pi. The Pearls reaction showed a higher accumulation of iron in the bone marrow of infected animals in day 5pi (P <0.01). Infection with T. evansi in rats caused anemia and changes in iron metabolism associated to the peaks of parasitemia. These results suggest that changes in iron metabolism may be related to the host immune response to infection and anemic status of infected animals. [Copyright &y& Elsevier]

The aim of the study is to investigate the role of circulating prohepcidin and hepcidin, which are homeostatic regulators of iron metabolism and mediators of inflammation, in anemia associated with Behcet's disease (BD) and the differential diagnosis of healthy controls. Twenty patients with BD and twenty healthy controls were included in this prospective study. Laboratory tests including complete blood count, serum prohepcidin, hepcidin, iron, total iron binding capacity (TIBC), transferrin, ferritin, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were determined. Serum prohepcidin and hepcidin levels in patients with BD were significantly higher than healthy group. In the group with BD positive correlation was determined between the values of serum prohepcidin, hepcidin, hemoglobin, total binding capacity and ferritine. Serum prohepcidin and hepcidin levels are closely associated with disease activity in patients and might play a role in the pathobiology of chronic disease anemia associated with patients with BD. [ABSTRACT FROM AUTHOR]