Review
Biochemistry & Molecular Biology
Simon Grootendorst, Jonathan de Wilde, Birgit van Dooijeweert, Annelies van Vuren, Wouter van Solinge, Roger Schutgens, Richard van Wijk, Marije Bartels
Summary: Rare hereditary anemias (RHA) are characterized by impaired red blood cell production or decreased survival, often leading to disturbances in iron metabolism and erythropoiesis, resulting in iron overload or exacerbation of chronic anemia. Iron overload is a significant issue in both transfusion-dependent and non-transfusion-dependent patients with RHA, suggesting common defects in erythroid development linked to intrinsic iron metabolism defects. Key regulators involved in the interaction between iron and erythropoiesis are discussed in the context of RHA.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Infectious Diseases
Lara Valente de Souza, Alexander Hoffmann, Guenter Weiss
Summary: This review highlights the complex interplay between iron, immunity, erythropoiesis, and infection control at the molecular and clinical level. It presents diagnostic algorithms for correct interpretation and diagnosis of iron status in the context of infection, as well as discusses therapeutic concepts for anemia correction.
EXPERT REVIEW OF ANTI-INFECTIVE THERAPY
(2021)
Review
Biochemistry & Molecular Biology
Margherita Correnti, Elena Gammella, Gaetano Cairo, Stefania Recalcati
Summary: Iron is essential for cellular processes, especially in erythropoiesis. The hormone hepcidin, produced by the liver, regulates iron homeostasis by interacting with ferroportin. During enhanced erythropoiesis, hepcidin expression is inhibited, allowing increased iron export and facilitating erythropoiesis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Yuhan Zhang, Mengying Chen, Caiyong Chen
Summary: Vertebrates generate mature red blood cells through a highly regulated, multistep process called erythropoiesis. Defects in erythropoiesis can lead to various blood disorders, and the molecular mechanisms are conserved between fish and mammals. Zebrafish has served as a powerful genetic model for studying erythropoiesis, providing important insights into RBC development and establishing models for human blood diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Environmental Sciences
Chun Pan, Minghao Yan, Haibo Jin, Hongqian Guo, Xiaodong Han
Summary: The study found that microcystins play an important role in human hematological parameters, potentially leading to microcytic anemia, and identified the related signaling pathway for the first time.
ENVIRONMENTAL POLLUTION
(2021)
Article
Immunology
Vanesa Garrido-Rodriguez, Ana Isabel Alvarez-Rios, Israel Olivas-Martinez, Maria del Mar Pozo-Balado, Angel Bulnes-Ramos, Manuel Leal, Yolanda Maria Pacheco
Summary: Virologically suppressed chronic HIV-infected patients under successful antiretroviral treatment exhibit altered levels of iron metabolism modulators, suggesting a complex functional iron deficiency.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Urology & Nephrology
Hirokazu Honda, Kenji Tanaka, Tetsuo Michihata, Keigo Shibagaki, Toshitaka Yuza, Keiichi Hirao, Naohisa Tomosugi, Tomas Ganz, Yuichiro Higashimoto
Summary: This study found that in hemodialysis patients, the long-acting ESA CERA may influence levels of intact FGF23 by suppressing hepcidin-25 levels for an extended period.
CLINICAL KIDNEY JOURNAL
(2021)
Article
Biology
Edouard Charlebois, Carine Fillebeen, Angeliki Katsarou, Aleksandr Rabinovich, Kazimierz Wisniewski, Vivek Venkataramani, Bernhard Michalke, Anastasia Velentza, Kostas Pantopoulos
Summary: This study investigates how iron affects inflammatory hepcidin levels and the subsequent hypoferremic response, revealing the antagonistic effect of iron on hepcidin induction and the critical role of de novo ferroportin synthesis in serum iron levels.
Review
Immunology
Yaoyao Xia, Yikun Li, Xiaoyan Wu, Qingzhuo Zhang, Siyuan Chen, Xianyong Ma, Miao Yu
Summary: The review highlights the crucial role of iron in dictating macrophage polarization by orchestrating various aspects such as cellular signaling, cellular metabolism, and epigenetic regulation. Iron modulation affects the development and progression of multiple macrophage-associated diseases, suggesting the potential application of iron supplementation in adjuvant therapy for different inflammatory disorders relative to macrophage polarization balance.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Jiajie Li, Lin Liu, Junmin Xing, Dianhui Chen, Chao Fang, Feng Mo, Yumei Gong, Zhengrong Tan, Guikuan Liang, Wei Xiao, Shanni Tang, Haixia Wei, Shan Zhao, Hongyan Xie, Xingfei Pan, Xiaomao Yin, Jun Huang
Summary: Splenomegaly is a common symptom of malaria, but its causes are not fully understood. In this study, the researchers found that TLR7 played a role in promoting extramedullary splenic erythropoiesis in mice infected with Plasmodium yoelii NSM. They also found that TLR7 enhanced the production of IFN-? which promoted phagocytosis of infected erythrocytes and the iron metabolism of macrophages. Furthermore, neutralizing IFN-? partially inhibited extramedullary splenic erythropoiesis and reduced iron accumulation in the spleen. Overall, this study highlights the importance of TLR7 in regulating splenic erythropoiesis in malaria.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Orthopedics
Huixin Chen, Jing Yu, Qing Wei, Yu Zhang, Xilin Ouyang, Shun Wang
Summary: The study aimed to assess the role of intravenous iron and erythropoietin therapy in rapid correction of postoperative anemia following orthopedic surgery. The results showed that the combined therapy did not significantly correct postoperative anemia compared to placebo. It is also suggested not to administer vitamin B-12 during the early postoperative period.
JOURNAL OF ORTHOPAEDIC SURGERY AND RESEARCH
(2023)
Article
Cardiac & Cardiovascular Systems
Milton Packer
Summary: In patients with heart failure, the use of SGLT2 inhibitors can lead to worsening absolute iron deficiency, but it is not caused by poor dietary intake or gastrointestinal bleeding. There are two possible explanations for the observed changes in iron homeostasis proteins. According to the cytosolic iron depletion hypothesis, SGLT2 inhibitors decrease hepcidin and ferritin and increase transferrin receptor due to drug-induced erythropoietin-related increase in iron use. According to the cytosolic iron repletion hypothesis, SGLT2 inhibitors decrease hepcidin and ferritin and increase transferrin receptor by reversing inflammation-related increases in hepcidin and ferritin and increasing sirtuin-1 signaling.
JACC-HEART FAILURE
(2023)
Review
Nutrition & Dietetics
Richard F. Hurrell
Summary: Iron fortification of foods is a challenging task due to variations in absorption, changes in color or flavor, and the presence of inhibitors. Progress has been made in designing efficacious iron-fortified foods, especially for infants. Fortification technologies for wheat, maize, and rice are well established. However, barriers including inflammation caused by infections and obesity hinder the effectiveness of iron fortification programs, especially in LMICs. Further research is required to better understand the impact of inflammation on iron-fortified foods.
Review
Endocrinology & Metabolism
Danielle M. A. Ratsma, M. Carola Zillikens, Bram C. J. van der Eerden
Summary: FGF23 is a key regulator of mineral homeostasis and plays a role in iron deficiency, inflammation, and erythropoiesis. It is essential for maintaining phosphate balance, but its regulation through transcriptional and post-translational mechanisms is complex.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Medicine, General & Internal
Keiji Hirai, Hiroaki Nonaka, Moeka Ueda, Junki Morino, Shohei Kaneko, Saori Minato, Yuko Mutsuyoshi, Katsunori Yanai, Hiroki Ishii, Momoko Matsuyama, Taisuke Kitano, Akinori Aomatsu, Haruhisa Miyazawa, Kiyonori Ito, Yuichiro Ueda, Susumu Ookawara, Yoshiyuki Morishita
Summary: The study showed that roxadustat may improve anemia and reduce serum ferritin and TSAT levels in peritoneal dialysis patients, with a correlation between serum potassium concentration and roxadustat dose.
FRONTIERS IN MEDICINE
(2021)
Letter
Hematology
Amy Zhou, Tim Kong, Jared S. Fowles, Chun-Ling Jung, Maggie J. Allen, Daniel A. C. Fisher, Mary Fulbright, Elizabeta Nemeth, Tomas Ganz, Stephen T. Oh
BRITISH JOURNAL OF HAEMATOLOGY
(2022)
Article
Urology & Nephrology
Mark R. Hanudel, Brian Czaya, Shirley Wong, Maxime Rappaport, Shweta Namjoshi, Kristine Chua, Grace Jung, Victoria Gabayan, Bo Qiao, Elizabeta Nemeth, Tomas Ganz
Summary: This study demonstrates the efficacy of ferric citrate in high hepcidin models and shows that enteral ferric citrate absorption is dependent on conventional enterocyte iron transport by ferroportin, with minimal paracellular absorption occurring in these models.
KIDNEY INTERNATIONAL
(2022)
Article
Chemistry, Multidisciplinary
Jianqiang Zhu, Qingfeng Fu, Shunhao Wang, Liting Ren, Wenya Feng, Shuting Wei, Zhihong Zhang, Yong Xu, Tomas Ganz, Sijin Liu
Summary: In this study, a smart nanosystem was developed to deliver tocilizumab to the liver for correcting anemia. By diminishing IL-6 signaling, the nanosystem successfully suppressed tumor progression.
Article
Sport Sciences
Andreas Breenfeldt Andersen, Jacob Bejder, Thomas C. Bonne, Henrik Sorensen, Helle Sorensen, Grace Jung, Tomas Ganz, Elizabeta Nemeth, Niels H. Secher, Par I. Johansson, Nikolai Baastrup Nordsborg
Summary: This study examined the use of hepcidin and erythroferrone (ERFE) as biomarkers for indirectly detecting autologous blood transfusion. The results showed that hepcidin and ERFE could complement the athlete biological passport (ABP) in detecting blood transfusion. Besides, the endurance performance of the participants improved after the transfusion.
MEDICINE & SCIENCE IN SPORTS & EXERCISE
(2022)
Article
Multidisciplinary Sciences
Gan Luo, Jue Zhang, HanBin Wang, YaQi Sun, BaoLi Cheng, ZhiPeng Xu, Yan Zhang, Hui Li, WuYuan Lu, Elizabeta Nemeth, Tomas Ganz, XiangMing Fang
Summary: A new class of peptidomimetic antibiotics designed based on the structure of human alpha-defensin 5 (HD5) showed promising activity against drug-resistant bacteria through multiple mechanisms of action.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Mark R. Hanudel, Brian Czaya, Shirley Wong, Grace Jung, Kristine Chua, Bo Qiao, Victoria Gabayan, Tomas Ganz
Summary: Ferric citrate has been found to effectively lower phosphate levels and increase iron levels in mice with chronic kidney disease. It also reduces inflammation, improves kidney function, and decreases kidney inflammation and fibrosis, indicating its potential renoprotective effects.
SCIENTIFIC REPORTS
(2022)
Article
Hematology
Veena Sangkhae, Vivian Yu, Richard Coffey, Kimberly O. O'Brien, Tomas Ganz, Elizabeta Nemeth
Summary: Under iron-deficient conditions, maternal and embryo ERFE facilitate iron mobilization for embryonic erythropoiesis.
AMERICAN JOURNAL OF HEMATOLOGY
(2022)
Article
Hematology
Mark J. Koury, Rajiv Agarwal, Glenn M. Chertow, Kai-Uwe Eckardt, Steven Fishbane, Tomas Ganz, Volker H. Haase, Mark R. Hanudel, Patrick S. Parfrey, Pablo E. Pergola, Prabir Roy-Chaudhury, James A. Tumlin, Robert Anders, Youssef M. K. Farag, Wenli Luo, Todd Minga, Christine Solinsky, Dennis L. Vargo, Wolfgang C. Winkelmayer
Summary: Vadadustat has beneficial effects on three aspects of erythropoiesis in patients with anemia associated with chronic kidney disease: increased endogenous EPO production, improved iron availability to erythroid cells, and increased reticulocytes in the circulation.
AMERICAN JOURNAL OF HEMATOLOGY
(2022)
Editorial Material
Medicine, General & Internal
Steven Fishbane, Tomas Ganz, Raymond D. Pratt
Summary: Anemia is a common complication in patients with hemodialysis-dependent chronic kidney disease (HDD-CKD), primarily caused by erythropoietin deficiency, inflammation, and iron deficiency. Ferric pyrophosphate citrate (FPC) is a safe and effective choice for iron replacement and maintenance of hemoglobin in the long-term management of HDD-CKD patients.
CURRENT MEDICAL RESEARCH AND OPINION
(2022)
Article
Chemistry, Multidisciplinary
Wenya Feng, Yuanjing Xiao, Chuanfang Zhao, Zhanming Zhang, Wei Liu, Juan Ma, Tomas Ganz, Junliang Zhang, Sijin Liu
Summary: Excess iron accumulation can lead to genetic disorders or occur after repeated transfusions. Iron chelation therapy is crucial for preventing iron toxicity in these patients. However, current iron chelators have limitations, necessitating the search for new agents. A library of new deferric amine compounds (DFAs), synthesized based on the properties of conventional chelators, shows promising efficacy in binding iron and ameliorating iron overload in murine models. Additionally, the compound DFA1 suppresses iron-induced ferroptosis by modulating intracellular signaling. This study introduces a new approach for developing iron chelators to treat iron overload.
Article
Hematology
Vida Zhang, Supak Jenkitkasemwong, Qingli Liu, Tomas Ganz, Elizabeta Nemeth, Mitchell D. Knutson, Airie Kim
Summary: ZIP8 is a transmembrane protein that imports divalent metal ions and is highly expressed in the lung. It can transport iron and is inducible by inflammatory stimuli. This study found that ZIP8 plays a role in systemic iron homeostasis and transports iron from the airway into lung tissue, but it does not modulate the severity of inflammatory lung injury or the host defense against a common bacterial cause of pneumonia.
Review
Medicine, Research & Experimental
Tomas Ganz, Elizabeta Nemeth, Stefano Rivella, Paul Goldberg, Andrew R. Dibble, Michael L. McCaleb, Shuling Guo, Brett P. Monia, Terrance D. Barrett
Summary: TMPRSS6 is a serine protease that is highly expressed in the liver. Mutations in TMPRSS6 were found to be the cause of iron-refractory iron deficiency anemia (IRIDA) in humans and mice. TMPRSS6 negatively regulates the expression of hepcidin, a systemic iron-regulatory hormone. Understanding the biology and mechanism of action of TMPRSS6 has led to the development of new therapeutic approaches for erythropoiesis and iron homeostasis-related diseases.
ADVANCES IN THERAPY
(2023)
Article
Hematology
Jihyun Song, Krishna M. Sundar, Monika Horvathova, Radhika Gangaraju, Karel Indrak, Robert D. Christensen, Samuel Genzor, Carsten Lundby, Vladimir Divoky, Tomas Ganz, Josef T. Prchal
Summary: Obstructive sleep apnea (OSA) does not cause significant increase in red cell mass due to neocytolysis and inflammation-mediated suppression of erythropoiesis. Accelerated erythropoiesis in OSA patients is offset by the lysis of newly generated erythrocytes upon return to normoxia, resulting in a normal blood hemoglobin concentration.
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Article
Cell Biology
Corbin R. Azucenas, T. Alex Ruwe, John P. Bonamer, Bo Qiao, Tomas Ganz, Mika Jormakka, Elizabeta Nemeth, Bryan Mackenzie
Summary: Fpn is a protein expressed in the plasma membrane of macrophages, enterocytes, and hepatocytes, which mediates the transfer of cellular iron into the blood plasma. Research has shown that human Fpn does not transport manganese, but mouse Fpn may be involved in manganese metabolism. Comparative analysis of mouse and human Fpn revealed that they share identical properties in terms of substrate profile, calcium dependence, optimal pH, and hepcidin sensitivity.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2023)
Article
Hematology
Binal N. Shah, Xu Zhang, Adelina I. Sergueeva, Galina Y. Miasnikova, Tomas Ganz, Josef T. Prchal, Victor R. Gordeuk
Summary: Von Hippel-Lindau protein (VHL) is crucial for regulating cellular processes under hypoxic conditions. Mutations in VHLR200W lead to Chuvash erythrocytosis, a congenital disorder characterized by heightened hypoxia sensing. Increased levels of HIFs, which are regulated by VHL, result in elevated erythropoietin gene transcription and hematocrit levels.
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
