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G Fenna van Breda, Lennart G Bongartz, Wenqing Zhuang, Rachel P L van Swelm, Jeanne Pertijs, Branko Braam, Maarten-Jan Cramer, Dorine W Swinkels, Pieter A Doevendans, Marianne C Verhaar, Roos Masereeuw, Jaap A Joles, Carlo A J M Gaillard
BACKGROUND: Hepcidin regulates systemic iron homeostasis by downregulating the iron exporter ferroportin. Circulating hepcidin is mainly derived from the liver but hepcidin is also produced in the heart. We studied the differential and local regulation of hepcidin gene expression in response to myocardial infarction (MI) and/or chronic kidney disease (CKD). We hypothesized that cardiac hepcidin gene expression is induced by and regulated to severity of cardiac injury, either through direct (MI) or remote (CKD) stimuli, as well as through increased local iron content...
October 22, 2016: American Journal of Nephrology
Lanfang Tian, Siyuan Chen, Haiyan Liu, Mingzhang Guo, Wentao Xu, Xiaoyun He, Yunbo Luo, Xiaozhe Qi, Hongxia Luo, Kunlun Huang
Hepcidin, one kind of antimicrobial peptides, is one of the promising alternatives to antibiotics with broad spectrum of antimicrobial activity. Hepcidins cloned from different kinds of fishes have been produced using exogenous expression systems, and their in vitro antimicrobial effects have been verified. However their in vivo effects on gut microbiota and gut health of hosts remain unclear. Here we performed a safety study of hepcidin so that it can be used to reduce microbial contaminations in the food and feed...
2016: PloS One
Tomas Ganz
Macrophages exert multiple important roles in iron metabolism. As scavengers, splenic and hepatic macrophages phagocytize and degrade senescent and damaged erythrocytes to recycle iron, predominantly for the production of hemoglobin in new erythrocytes. Splenic red pulp macrophages are specialized for iron recycling, with increased expression of proteins for the uptake of hemoglobin, breakdown of heme, and export of iron. Iron release from macrophages is closely regulated by the interaction of hepcidin, a peptide hormone produced by hepatocytes, with the macrophage iron exporter ferroportin...
October 2016: Microbiology Spectrum
Nicolas Leuenberger, Emanuele Bulla, Olivier Salamin, Raul Nicoli, Neil Robinson, Norbert Baume, Martial Saugy
The concentration of hepcidin, a key regulator of iron metabolism, is suppressed during periods of increased erythropoietic activity. The present study obtained blood samples from 109 elite athletes and examined the correlations between hepcidin and markers of erythropoiesis and iron metabolism (i.e., hemoglobin, erythropoietin (EPO), ferritin, erythroferrone (ERFE), and iron concentration). Furthermore, an administration study was undertaken to examine the effect of recombinant human EPO (rhEPO) delta (Dynepo™) on hepcidin concentrations in healthy male volunteers...
October 18, 2016: Drug Testing and Analysis
IJsbrand T Klip, Adriaan A Voors, Dorine W Swinkels, Stephan J L Bakker, Jenny E Kootstra-Ros, Carolyn S Lam, Pim van der Harst, Dirk J van Veldhuisen, Peter van der Meer
AIMS: Heart failure (HF) is a common manifestation of patients with primary and secondary causes of iron overload, whereas in patients with established HF iron deficiency impairs outcome. Whether iron stores, either depleted or in overload, amplify the risk for new-onset HF among healthy individuals is unknown. The present study aimed to assess whether markers of iron status or the iron-regulatory hormone hepcidin are associated with new-onset HF or cardiovascular (CV) events in the general population...
October 19, 2016: European Journal of Heart Failure
Monika Kasztura, Magdalena Dzięgała, Kamil Kobak, Jacek Bania, Grzegorz Mazur, Waldemar Banasiak, Piotr Ponikowski, Ewa Anita Jankowska
: Background Iron is presumed to play an important role in functioning of cardiomyocytes and skeletal myocytes. There is scarcity of direct data characterizing the cells functioning when exposed to iron depletion or iron overload in cellular environment. There is some clinical evidence demonstrating that iron deficiency has serious negative prognostic consequence in heart failure (HF) patients and its correction brought clinical benefit. BACKGROUND: Iron is presumed to play an important role in functioning of cardiomyocytes and skeletal myocytes...
October 17, 2016: Kardiologia Polska
José María Moreno-Navarrete, María Moreno, Josep Puig, Gerard Blasco, Francisco Ortega, Gemma Xifra, Wifredo Ricart, José Manuel Fernández-Real
BACKGROUND & AIMS: Serum hepcidin concentration is known to increase in parallel to circulating markers of iron stores. We aimed to investigate whether this is reflected at the tissue level in subjects with obesity. METHODS: Serum hepcidin and ferritin levels (ELISA) and hepatic iron content (using magnetic resonance imaging) were analyzed longitudinally in 44 participants (19 without obesity and 25 with obesity). In a subgroup of 16 participants with obesity, a weight loss intervention was performed...
September 29, 2016: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
Mariia Lunova, Peggy Schwarz, Renwar Nuraldeen, Kateryna Levada, Deniz Kuscuoglu, Michael Stützle, Maja Vujic, Johannes Haybaeck, Piotr Ruchala, Milan Jirsa, Jean-Christophe Deschemin, Sophie Vaulont, Christian Trautwein, Pavel Strnad
Iron is both an essential and a potentially toxic element and its systemic homeostasis is controlled by the iron-hormone hepcidin. Hepcidin binds to the cellular iron exporter ferroportin, causes its degradation and thereby diminishes iron uptake from the intestine and the release of iron from macrophages. Given that hepcidin-resistant ferroportin mutant mice display exocrine pancreas dysfunction, we analysed pancreata of aging hepcidin knockout mice (KOs). Hepcidin and Hfe KOs were compared to wild type animals (WTs) kept on standard or iron-rich diets...
October 14, 2016: Journal of Pathology
Débora Villaño, Cristina Vilaplana, Sonia Medina, Francisco Algaba-Chueca, Roberto Cejuela-Anta, Jose Miguel Martínez-Sanz, Federico Ferreres, Angel Gil-Izquierdo
The effects of polyphenol-rich foods on the iron status of athletes, as well as the effect of physical training on the hormone hepcidin, implicated in iron metabolism, are not clear. We investigated the influence on iron metabolism of a long-term training intervention of 120 days, measuring the hepcidin concentration in the plasma of 16 elite triathletes, and the effect of the ingestion of 200 mL of either aronia-citrus juice or a placebo drink for 45 days, in a crossover design. The highest plasma hepcidin concentrations were observed at the beginning of the study (116 ± 63 nM) and levels steadily decreased until the end of the intervention (final value 10 ± 7...
October 8, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Sandra Azevedo Antunes, Maria Eugênia Fernandes Canziani
Anemia is a common complication and its impact on morbimortality in patients with chronic kidney disease (CKD) is well known. The discovery of hepcidin and its functions has contributed to a better understanding of iron metabolism disorders in CKD anemia. Hepcidin is a peptide mainly produced by hepatocytes and, through a connection with ferroportin, it regulates iron absorption in the duodenum and its release of stock cells. High hepcidin concentrations described in patients with CKD, especially in more advanced stages are attributed to decreased renal excretion and increased production...
July 2016: Jornal Brasileiro de Nefrologia: ʹorgão Oficial de Sociedades Brasileira e Latino-Americana de Nefrologia
Mark R Hanudel, Kristine Chua, Maxime Rappaport, Victoria Gabayan, Erika Valore, David Goltzman, Tomas Ganz, Elizabeta Nemeth, Isidro B Salusky
In the setting of normal kidney function, iron deficiency is associated with increased FGF23 production and cleavage, altering circulating FGF23 levels. Our objective was to determine how chronic kidney disease (CKD) and dietary iron intake affect FGF23 production and metabolism in wild type (WT) and hepcidin knockout (HKO) mice. For eight weeks, the mice were fed diets that contained adenine (to induce CKD) or no adenine (control group), with either low iron (4 ppm) or standard iron (335 ppm) concentrations...
October 12, 2016: American Journal of Physiology. Renal Physiology
Katarzyna Sikorska, Agnieszka Bernat, Anna Wroblewska
BACKGROUND: The liver, as the main iron storage compartment and the place of hepcidin synthesis, is the central organ involved in maintaining iron homeostasis in the body. Excessive accumulation of iron is an important risk factor in liver disease progression to cirrhosis and hepatocellular carcinoma. Here, we review the literature on the molecular pathogenesis of iron overload and its clinical consequences in chronic liver diseases. DATA SOURCES: PubMed was searched for English-language articles on molecular genesis of primary and secondary iron overload, as well as on their association with liver disease progression...
October 2016: Hepatobiliary & Pancreatic Diseases International: HBPD INT
Yuping Li, Ke Pan, Lin Chen, Jiao-Lin Ning, Xiaojun Li, Ting Yang, Niccolò Terrando, Jianteng Gu, Guocai Tao
BACKGROUND: Postoperative cognitive dysfunction (POCD) is a common complication after surgery, especially amongst elderly patients. Neuroinflammation and iron homeostasis are key hallmarks of several neurological disorders. In this study, we investigated the role of deferoxamine (DFO), a clinically used iron chelator, in a mouse model of surgery-induced cognitive dysfunction and assessed its neuroprotective effects on neuroinflammation, oxidative stress, and memory function. METHODS: A model of laparotomy under general anesthesia and analgesia was used to study POCD...
October 12, 2016: Journal of Neuroinflammation
Gaetano Bergamaschi, Antonio Di Sabatino, Alessandra Pasini, Cristina Ubezio, Filippo Costanzo, Davide Grataroli, Michela Masotti, Costanza Alvisi, Gino R Corazza
BACKGROUND & AIMS: Through inhibition of iron absorption and iron mobilization from tissue stores, hepcidin exerts a negative control on iron homeostasis. Hepcidin, in fact, promotes the degradation of ferroportin (Fpn1), the iron exporter molecule expressed on the membrane of hepatocytes and macrophages, thus preventing iron release from cells to plasma. Hepcidin effects on enterocytes, however, are less clear. Aim of the present study was to further investigate the regulation of iron absorption by hepcidin...
September 30, 2016: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
Tomas Ganz
Hepcidin is an iron-regulating peptide hormone made in the liver. It controls the delivery of iron to blood plasma from intestinal cells absorbing iron, from erythrocyte-recycling macrophages, and from iron-storing hepatocytes. Hepcidin acts by binding to and inactivating the sole cellular iron exporter, ferroportin, which delivers iron to plasma from all iron-transporting cells. In a classical endocrine feedback system, hepcidin production is stimulated by plasma iron and iron stores. Reflecting a likely role of hepcidin in innate immunity, hepcidin is also induced by inflammation...
2016: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Claudio A Álvarez, Fernando A Gomez, Luis Mercado, Ramón Ramírez, Sergio H Marshall
Piscirickettsia salmonis is a facultative intracellular bacterium that causes the disease called "salmon rickettsial syndrome". Attempts to control this disease have been unsuccessful, because existing vaccines have not achieved the expected effectiveness and the antibiotics used fail to completely eradicate the pathogen. This is in part the product of lack of scientific information that still lacks on the mechanisms used by this bacterium to overcome infected-cell responses and survive to induce a productive infection in macrophages...
2016: PloS One
Eva Rombout-Sestrienkova, Marian G J van Kraaij, Ger H Koek
A number of disorders cause iron overload: some are of genetic origin, such as hereditary haemochromatosis, while others are acquired, for instance due to repeated transfusions. This article reviews the treatment options for hereditary haemochromatosis, with special attention to the use of erythrocytapheresis. In general, therapy is based on the removal of excess body iron, for which ferritin levels are used to monitor the effectiveness of treatment. For many decades phlebotomy has been widely accepted as the standard treatment...
October 10, 2016: British Journal of Haematology
Michela Asperti, Tanja Stuemler, Maura Poli, Magdalena Gryzik, Lena Lifshitz, Esther G Meyron-Holtz, Israel Vlodavsky, Paolo Arosio
Hepcidin is the key regulator of systemic iron availability that acts by controlling the degradation of the iron exporter ferroportin. It is expressed mainly in the liver and regulated by iron, inflammation, erythropoiesis and hypoxia. The various agents that control its expression act mainly via the BMP6/SMAD signaling pathway. Among them are exogenous heparins, which are strong hepcidin repressors with a mechanism of action not fully understood but that may involve the competition with the structurally similar endogenous Heparan Sulfates (HS)...
2016: PloS One
Michele F Eisenga, Robin P F Dullaart, Stefan P Berger, John H Sloan, Aiko P J de Vries, Stephan J L Bakker, Carlo A J M Gaillard
BACKGROUND: Hepcidin is considered the master regulator of iron homeostasis. Novel hepcidin antagonists have recently been introduced as potential treatment for iron-restricted anemia. Meanwhile, serum hepcidin has been shown to be positively associated with cardiovascular disease and inversely with acute kidney injury. These properties may lead to contrasting effects, especially in renal transplant recipients (RTR) which are prone to cardiovascular diseases and graft failure. To date, the role of serum hepcidin in RTR is unknown...
October 3, 2016: European Journal of Clinical Investigation
Jing Wang, Ailian Dong, Gang Liu, Gregory J Anderson, Tony Y Hu, Jian Shi, Yulin Hu, Guangjun Nie
Chronic hepatitis B virus (HBV) infection often develop into cirrhosis, and both are major risk factors of hepatocellular carcinoma. However, effective approaches for the monitoring of HBV-related disease progress are still in need. Increased iron storage has an important role in HBV-related diseases. Hepcidin is a key regulator of iron homeostasis whose expression changes are often indicative of abnormal iron metabolism. There are few reports of hepcidin levels in patients with HBV infections, and the available results are inconsistent...
October 3, 2016: Scientific Reports
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