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JOURNAL ARTICLE
Heng-Chih Pan, Thomas Tao-Min Huang, Chun-Te Huang, Chiao-Yin Sun, Yung-Ming Chen, Vin-Cent Wu
CONTEXT.—: Critically ill patients with acute kidney injury (AKI) requiring renal replacement therapy (RRT) have a poor prognosis. Several urinary AKI biomarkers have been proposed to predict renal recovery, but with limited discriminatory ability. OBJECTIVE.—: To validate the predictive performances of novel biomarkers to identify which critical patients with AKI may successfully wean from RRT. DESIGN.—: We prospectively recorded and analyzed clinical variables at several time points: (1) before starting RRT, (2) at the time of weaning off RRT, and (3) 24 hours after stopping RRT...
March 21, 2022: Archives of Pathology & Laboratory Medicine
#22
JOURNAL ARTICLE
Niteesh Bharadwaj, Srinivasan Peyam, Prateek Bhatia, Anmol Bhatia, Reena Das, Minu Singh, Deepak Bansal, Amita Trehan, Richa Jain
Patients with non-transfusion dependent thalassemia (NTDT) develop variable degrees of iron overload. Possible genes which may be implicated in causing iron overload are hepcidin ( HAMP ) and hemojuvelin ( HFE ). There is variable data assessing the role of c.-582Y A > G HAMP gene and H63D hotspot in HFE-1 gene in causing iron overload, while role of HFE-2 gene is undetermined. Twenty-five patients with NTDT (≥ 10 years) were assessed for iron overload. Genetic analysis for β-globin, α-globin, HAMP, HFE-2 and C282Y and H63D hotspots in HFE-1 genes was performed...
January 2022: Indian Journal of Hematology & Blood Transfusion
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JOURNAL ARTICLE
Inga Dziembowska, Małgorzata Wójcik, Ewa Żekanowska
BACKGROUND & AIMS: There is clear evidence that lifestyle factors affect iron bioavailability. However, information regarding the effect of alcohol and caffeine consumption on iron metabolism is limited. The aim of the current study was to evaluate the effect of caffeine and alcohol consumption on iron metabolism in healthy men, regarding their everyday physical activity level. METHODS: The study enrolled 83 men (59 physically active and 24 sedentary men) aged 18-32 years...
January 4, 2022: Journal of Trace Elements in Medicine and Biology
#24
JOURNAL ARTICLE
Giulia Ravasi, Sara Pelucchi, Francesca Bertola, Martina Maria Capelletti, Raffaella Mariani, Alberto Piperno
BACKGROUND: Several inherited diseases cause hyperferritinemia with or without iron overload. Differential diagnosis is complex and requires an extensive work-up. Currently, a clinical-guided approach to genetic tests is performed based on gene-by-gene sequencing. Although reasonable, this approach is expensive and time-consuming and Next Generation Sequencing (NGS) technology may provide cheaper and quicker large-scale DNA sequencing. METHODS: We analysed 36 patients with non- HFE -related hyperferritinemia...
November 9, 2021: Genes
#25
REVIEW
Pierre Brissot, Eolia Brissot
Major advances in the understanding of genetic iron overload have led to a clarification of the nosology and terminology of the related diseases. The term hemochromatosis should be reserved to the entities where iron overload is related to hepcidin deficiency or hepcidin resistance. The diagnosis of hemochromatosis is non-invasive, based on clinical examination, blood investigations and, whenever possible, magnetic resonance imaging. Phlebotomies remain the mainstay of the treatment, but new therapeutic approaches should, in the future, constitute a valuable advance, hopefully both as an adjunct to bleeding in the induction phase and as its replacement in the maintenance phase...
December 2020: Clinical hematology international
#26
JOURNAL ARTICLE
Lili Huang, Emma Fung, Sahana Bose, Andreas Popp, Preethne Böser, John Memmott, Yuliya A Kutskova, Renee Miller, Edit Tarcsa, Corinna Klein, Geertruida M Veldman, Bernhard K Mueller, Yi-Fang Cui
Repulsive guidance molecule A (RGMa) is a potent inhibitor of axonal growth and a regulator of neuronal cell death. It is up-regulated following neuronal injury and accumulates in chronic neurodegenerative diseases. Neutralizing RGMa has the potential to promote neuroregeneration and neuroprotection. Previously we reported that a rat anti-N terminal RGMa (N-RGMa) antibody r5F9 and its humanized version h5F9 (ABT-207) promote neuroprotection and neuroregeneration in preclinical neurodegenerative disease models...
November 2021: Neurobiology of Disease
#27
JOURNAL ARTICLE
Sachelly Julián-Serrano, Fangcheng Yuan, William Wheeler, Beben Benyamin, Mitchell J Machiela, Alan A Arslan, Laura E Beane-Freeman, Paige M Bracci, Eric J Duell, Mengmeng Du, Steven Gallinger, Graham G Giles, Phyllis J Goodman, Charles Kooperberg, Loic Le Marchand, Rachel E Neale, Xiao-Ou Shu, Stephen K Van Den Eeden, Kala Visvanathan, Wei Zheng, Demetrius Albanes, Gabriella Andreotti, Eva Ardanaz, Ana Babic, Sonja I Berndt, Lauren K Brais, Paul Brennan, Bas Bueno-de-Mesquita, Julie E Buring, Stephen J Chanock, Erica J Childs, Charles C Chung, Eleonora Fabiánová, Lenka Foretová, Charles S Fuchs, J Michael Gaziano, Manuel Gentiluomo, Edward L Giovannucci, Michael G Goggins, Thilo Hackert, Patricia Hartge, Manal M Hassan, Ivana Holcátová, Elizabeth A Holly, Rayjean I Hung, Vladimir Janout, Robert C Kurtz, I-Min Lee, Núria Malats, David McKean, Roger L Milne, Christina C Newton, Ann L Oberg, Sandra Perdomo, Ulrike Peters, Miquel Porta, Nathaniel Rothman, Matthias B Schulze, Howard D Sesso, Debra T Silverman, Ian M Thompson, Jean Wactawski-Wende, Elisabete Weiderpass, Nicolas Wenstzensen, Emily White, Lynne R Wilkens, Herbert Yu, Anne Zeleniuch-Jacquotte, Jun Zhong, Peter Kraft, Dounghui Li, Peter T Campbell, Gloria M Petersen, Brian M Wolpin, Harvey A Risch, Laufey T Amundadottir, Alison P Klein, Kai Yu, Rachael Z Stolzenberg-Solomon
BACKGROUND: Epidemiological studies have suggested positive associations for iron and red meat intake with risk of pancreatic ductal adenocarcinoma (PDAC). Inherited pathogenic variants in genes involved in the hepcidin-regulating iron metabolism pathway are known to cause iron overload and hemochromatosis. OBJECTIVES: The objective of this study was to determine whether common genetic variation in the hepcidin-regulating iron metabolism pathway is associated with PDAC...
October 4, 2021: American Journal of Clinical Nutrition
#28
JOURNAL ARTICLE
Monika Łęcka, Artur Słomka, Katarzyna Albrecht, Ewa Żekanowska, Michał Romiszewski, Jan Styczyński
OBJECTIVE: The aim of this study was to evaluate non-transferrin-bound iron (NTBI) and labile plasma iron (LPI) levels and other parameters of iron metabolism in children undergoing therapy for acute leukemia or after hematopoietic cell transplantation (HCT), in the context of iron overload. PATIENTS: A total number of 85 children were prospectively included into four groups: controls, acute leukemia de novo, acute leukemia after intensive treatment, and after HCT...
June 17, 2021: Cancers
#29
JOURNAL ARTICLE
Caroline A Enns, Shall Jue, An-Sheng Zhang
Neogenin (NEO1) is a ubiquitously expressed multi-functional transmembrane protein. It interacts with hemojuvelin (HJV), a BMP co-receptor that plays a pivotal role in hepatic hepcidin expression. Earlier studies suggest that the function of HJV relies on its interaction with NEO1. However, the role of NEO1 in iron homeostasis remains controversial because of the lack of an appropriate animal model. Here, we generated a hepatocyte-specific Neo1 knockout (Neo1fl/fl;Alb-Cre+) mouse model that circumvented the developmental and lethality issues of the global Neo1 mutant...
April 6, 2021: Blood
#30
JOURNAL ARTICLE
Jan Krijt, Jana Frýdlová, Iuliia Gurieva, Petr Přikryl, Martin Báječný, Andrea U Steinbicker, Martin Vokurka, Jaroslav Truksa
Matriptase-2, a serine protease expressed in hepatocytes, is a negative regulator of hepcidin expression. The purpose of the study was to investigate the interaction of matriptase-2 with hemojuvelin protein in vivo. Mice lacking the matriptase-2 proteolytic activity ( mask mice) display decreased content of hemojuvelin protein. Vice versa, the absence of hemojuvelin results in decreased liver content of matriptase-2, indicating that the two proteins interact. To further characterize the role of matriptase-2, we investigated iron metabolism in mask mice fed experimental diets...
March 6, 2021: International Journal of Molecular Sciences
#31
JOURNAL ARTICLE
Ling-Yan Wu, Zhen-Ya Song, Qing-Hai Li, Li-Jun Mou, Ying-Ying Yu, Si-Si Shen, Xiao-Xiao Song
RATIONALE: Hereditary hemochromatosis (HH) is a hereditary disorder of iron metabolism. It is classified into 4 main types depending on the underlying genetic mutation: human hemochromatosis protein (HFE) (type 1), hemojuvelin (HJV) (type 2A), HAMP (type 2B), transferrin receptor-2 (TFER2) (type 3), and ferroportin (type 4). Type 4 HH is divided into 2 subtypes according to different mutations: type 4A (classical ferroportin disease) and type 4B (non-classical ferroportin disease). Type 4B HH is a rare autosomal dominant disease that results from mutations in the Solute Carrier Family 40 member 1 (SLC40A1) gene, which encodes the iron transport protein ferroportin...
April 2, 2021: Medicine (Baltimore)
#32
JOURNAL ARTICLE
Chao Wang, Xing Wang, Guangyao Song, Hanying Xing, Linquan Yang, Kang Han, Yan-Zhong Chang
Nonalcoholic fatty liver disease (NAFLD) correlates with the high intake of fructose-rich soft drinks. Both inflammation and dysregulated iron metabolism are pathogenic factors in the development of NAFLD. The present investigation assessed the effects of a high-fructose diet (HF diet) on inflammation and iron metabolism. In this study, rats were fed a control or HF diet for 4, 8, or 12 weeks, after which insulin resistance, transaminases levels, serum and liver lipid profiles, inflammatory factors, and iron metabolism-related molecules were evaluated...
January 2021: Journal of Food Biochemistry
#33
JOURNAL ARTICLE
Paul J Schmidt, Kevin Fitzgerald, James S Butler, Mark D Fleming
β-thalassemias result from mutations in β-globin, causing ineffective erythropoiesis and secondary iron overload due to inappropriately low levels of the iron regulatory hormone hepcidin. Mutations in transferrin receptor 2 (TFR2) lead to hereditary hemochromatosis (HH) as a result of inappropriately increased iron uptake from the diet, also due to improperly regulated hepcidin. TFR2 is also thought to be required for efficient erythropoiesis through its interaction with the erythropoietin receptor in erythroid progenitors...
February 1, 2021: American Journal of Hematology
#34
JOURNAL ARTICLE
Torsak Tippairote, Geir Bjørklund, Massimiliano Peana, Sittiruk Roytrakul
The mutation of the homeostatic iron regulatory genes (HFE) impaired the hepatic hepcidin transcription leading to the chronic excess of the iron pool, with the adverse consequences of free radical oxidative damages. We herein reported the findings of Thai family members who had the compound of uncommon HFE rs2794719, together with transferrin (TF) rs1867504, transferrin receptor 2 (TfR2) rs7385804, and hemojuvelin (HJV) rs16827043 genetic variants involved in the hepcidin transcriptional pathway. These compounded genetic variants could produce the spectrum of clinical phenotypes that spanned from mild to moderate symptoms of chronic anemia to an established motor neuron disorder...
March 2021: Journal of Molecular Neuroscience: MN
#35
JOURNAL ARTICLE
Akiyoshi Takami, Yasuaki Tatsumi, Katsuhisa Sakai, Yasumichi Toki, Katsuya Ikuta, Yuka Oohigashi, Junko Takagi, Koichi Kato, Kazuhisa Takami
Juvenile hemochromatosis (JH), type 2A hemochromatosis, is a rare autosomal recessive disorder of systemic iron overload due to homozygous mutations of HJV ( HFE2 ), which encodes hemojuvelin, an essential regulator of the hepcidin expression, causing liver fibrosis, diabetes, and heart failure before 30 years of age, often with fatal outcomes. We report two Japanese sisters of 37 and 52 years of age, with JH, who showed the same homozygous HJV I281T mutation and hepcidin deficiency and who both responded well to phlebotomy on an outpatient basis...
August 15, 2020: Pharmaceuticals
#36
JOURNAL ARTICLE
Wasanthi Wickramasinghe, Chathurika Karunathilaka, Saroj Jayasinghe, Lallindra Gooneratne
INTRODUCTION: Hereditary hemochromatosis is an inherited disorder of iron metabolism, characterized by excessive iron deposition in major organs of the body, leading to multi-organ dysfunction. It is a genetically heterogeneous disease caused by mutations in one or more different genes, the most common being mutations in the HFE gene. HFE hereditary hemochromatosis is mostly found in Europeans and is almost always a result of two mutations: C282Y and H63D. The H63D mutation is not as penetrant as the C282Y mutation, but there are rare reported cases of hereditary hemochromatosis with homozygous H63D genotype...
July 9, 2020: Journal of Medical Case Reports
#37
REVIEW
Lingyan Duan, Xiangju Yin, Hong'en Meng, Xuexian Fang, Junxia Min, Fudi Wang
Iron homeostasis plays an important role for the maintenance of human health. It is known that iron metabolism is tightly regulated by several key genes, including divalent metal transport-1( DMT1 ), transferrin receptor 1( TFR1 ), transferrin receptor 2( TFR2 ), ferroportin( FPN ), hepcidin( HAMP ), hemojuvelin( HJV ) and Ferritin H . Recently, it is reported that DNA methylation, histone acetylation, and microRNA (miRNA) epigenetically regulated iron homeostasis. Among these epigenetic regulators, DNA hypermethylation of the promoter region of FPN, TFR2, HAMP , HJV and bone morphogenetic protein 6 ( BMP6 ) genes result in inhibitory effect on the expression of these iron-related gene...
May 25, 2020: Zhejiang da Xue Xue Bao. Yi Xue Ban, Journal of Zhejiang University. Medical Sciences
#38
REVIEW
Xia Xiao, Víctor M Alfaro-Magallanes, Jodie L Babitt
The bone morphogenetic protein (BMP)-SMAD signaling pathway plays a central role in regulating hepcidin, which is the master hormone governing systemic iron homeostasis. Hepcidin is produced by the liver and acts on the iron exporter ferroportin to control iron absorption from the diet and iron release from body stores, thereby providing adequate iron for red blood cell production, while limiting the toxic effects of excess iron. BMP6 and BMP2 ligands produced by liver endothelial cells bind to BMP receptors and the coreceptor hemojuvelin (HJV) on hepatocytes to activate SMAD1/5/8 signaling, which directly upregulates hepcidin transcription...
September 2020: Bone
#39
JOURNAL ARTICLE
Agnieszka Ścibior, Iwona Hus, Joanna Mańko, Dariusz Jawniak
BACKGROUND: The current knowledge about the effects of vanadium (V) on iron (Fe)-related proteins and Fe homeostasis (which is regulated at the systemic, organelle, and cellular levels) is still insufficient. OBJECTIVE: This fact and our earlier results prompted us to conduct studies with the aim to explain the mechanism of anemia accompanied by a rise in hepatic and splenic Fe deposition in rats receiving sodium metavanadate (SMV) separately and in combination with magnesium sulfate (MS)...
May 15, 2020: Journal of Trace Elements in Medicine and Biology
#40
JOURNAL ARTICLE
Matthew Nayor, Meghan I Short, Humaira Rasheed, Honghuang Lin, Christian Jonasson, Qiong Yang, Kristian Hveem, Janine F Felix, Alanna C Morrison, Philipp S Wild, Michael P Morley, Thomas P Cappola, Mark D Benson, Debby Ngo, Sumita Sinha, Michelle J Keyes, Dongxiao Shen, Thomas J Wang, Martin G Larson, Ben M Brumpton, Robert E Gerszten, Torbjørn Omland, Ramachandran S Vasan
BACKGROUND: We used a large-scale, high-throughput DNA aptamer-based discovery proteomic platform to identify circulating biomarkers of cardiac remodeling and incident heart failure (HF) in community-dwelling individuals. METHODS: We evaluated 1895 FHS (Framingham Heart Study) participants (age 55±10 years, 54% women) who underwent proteomic profiling and echocardiography. Plasma levels of 1305 proteins were related to echocardiographic traits and to incident HF using multivariable regression...
May 2020: Circulation. Heart Failure
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