|
1
|
Wang C, Melgar‐Bermudez E, Welch D, Dagbay KB, Bhattacharya S, Lema E, Daman T, Sierra O, Todorova R, Drame PM, Grenha R, Fisher FM, Grayson D, Lerner L, Cadena SM, Seehra J, Lachey J. A Recombinant Antibody Against ALK2 Promotes Tissue Iron Redistribution and Contributes to Anemia Resolution in a Mouse Model of Anemia of Inflammation. Am J Hematol 2025; 100:797-812. [PMID: 39791515 PMCID: PMC11966360 DOI: 10.1002/ajh.27578] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2024] [Revised: 11/06/2024] [Accepted: 12/23/2024] [Indexed: 01/12/2025]
Abstract
Patients with chronic inflammation are burdened with anemia of inflammation (AI), where inflammatory cytokines inhibit erythropoiesis, impede erythropoietin production, and limit iron availability by inducing the iron regulator hepcidin. High hepcidin hinders iron absorption and recycling, thereby worsening the impaired erythropoiesis by restricting iron availability. AI management is important as anemia impacts quality of life and potentially affects morbidity and mortality. The bone morphogenetic protein (BMP)-SMAD pathway is crucial for hepcidin regulation. Here, we characterized a research antibody against BMP receptor ALK2, RKER-216, and investigated its mechanism in suppressing hepcidin and improving anemia in acute/chronic inflammation. Additive effects of RKER-216 and recombinant human erythropoietin (rhEPO) on erythropoiesis and iron utilization were also explored. We showed that RKER-216 neutralized ALK2 activity by competing with the binding of BMP6. RKER-216 reduced hepcidin transcription in Hep3B cells, and a subcutaneous dose of RKER-216 at 3 mg/kg suppressed serum hepcidin and increased circulating iron for 3-4 days in wildtype mice. Moreover, RKER-216 decreased hepcidin by inhibiting SMAD1/5/9 signaling in lipopolysaccharide-mediated inflammation and liberated iron from the recycling pathway to alleviate anemia in mice with adenine-induced chronic kidney disease (CKD), a mouse model of AI. Finally, RKER-216 reversed iron-restricted erythropoiesis in CKD mice and supplied the iron requirement for complete resolution of anemia when coupled with rhEPO in addressing AI. Our data support that ALK2 is a key hepcidin regulator and that a neutralizing ALK2 antibody has the potential to restore iron homeostasis as monotherapy or in combination with rhEPO to ameliorate AI.
Collapse
Affiliation(s)
| | | | | | | | | | - Evan Lema
- Keros TherapeuticsLexingtonMassachusettsUSA
| | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
2
|
Tefferi A, Gangat N. Therapeutic Targeting of the Activin Receptor Signaling Pathway: Proof of Concept in Myeloid Neoplasms. Am J Hematol 2025; 100:755-757. [PMID: 39932030 DOI: 10.1002/ajh.27638] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2025] [Accepted: 01/17/2025] [Indexed: 04/04/2025]
Affiliation(s)
- Ayalew Tefferi
- Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Naseema Gangat
- Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA
| |
Collapse
|
|
3
|
Han Y, Sun Y, Shu C, Yue Z, Chang X, Lin C, Zhang J, Liu K, Hou J. Hepcidin-regulated iron metabolism disorders in patients with stage III/IV periodontitis. J Dent Sci 2025; 20:995-1001. [PMID: 40224112 PMCID: PMC11993015 DOI: 10.1016/j.jds.2024.10.028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2024] [Revised: 10/26/2024] [Indexed: 04/15/2025] Open
Abstract
Background /purposeThe disorders of iron metabolism in periodontal diseases have been reported, however, there is still lack of comprehensive and thorough analyses about the association between periodontitis and iron metabolism disorders. This study aimed to examine the association between periodontitis and iron metabolism disorders, and to analyze the characteristic changes of iron metabolism in periodontitis patients. Materials and methods 79 Stage III/IV periodontitis patients and 79 healthy controls were enrolled in this study. Periodontal clinical parameters, system inflammation markers, iron metabolism parameters and hematological parameters were collected and compared at baseline and 3 months after non-surgical periodontal therapy. Results Stage III/IV periodontitis patients exhibited higher levels of systemic inflammatory markers including white blood cell (WBC) counts and high-sensitivity C-reactive protein (hs- CRP). Serum hepcidin and ferritin were significantly increased in the periodontitis group, meanwhile serum iron and transferrin were significantly decreased. Periodontal therapy attenuated the higher levels of hepcidin and ferritin, and the lower levels of Fe and transferrin in periodontitis patients at 3 months after therapy. Probing depth (PD), bleeding index (BI) and clinical attachment loss (CAL) were positively correlated with hepcidin and ferritin, and negatively correlated with Fe and transferrin respectively. Hepcidin was significantly negatively correlated with Fe and positively correlated with ferritin in periodontitis patients. Conclusion Our findings suggest the association between periodontitis and iron metabolism disorders and indicate that periodontitis-activated host responses may increase the risk of iron metabolism disorders, while meaningfully provide new insights into the systemic effects of periodontitis.
Collapse
Affiliation(s)
| | | | - Chang Shu
- Department of Periodontology, National Center of Stomatology & National Clinical Research Center for Oral Diseases, National Engineering Laboratory for Digital and Material Technology of Stomatology, Peking University School and Hospital of Stomatology, Beijing, China
| | - Zhaoguo Yue
- Department of Periodontology, National Center of Stomatology & National Clinical Research Center for Oral Diseases, National Engineering Laboratory for Digital and Material Technology of Stomatology, Peking University School and Hospital of Stomatology, Beijing, China
| | - Xiaochi Chang
- Department of Periodontology, National Center of Stomatology & National Clinical Research Center for Oral Diseases, National Engineering Laboratory for Digital and Material Technology of Stomatology, Peking University School and Hospital of Stomatology, Beijing, China
| | - Cheng Lin
- Department of Periodontology, National Center of Stomatology & National Clinical Research Center for Oral Diseases, National Engineering Laboratory for Digital and Material Technology of Stomatology, Peking University School and Hospital of Stomatology, Beijing, China
| | - Jie Zhang
- Department of Periodontology, National Center of Stomatology & National Clinical Research Center for Oral Diseases, National Engineering Laboratory for Digital and Material Technology of Stomatology, Peking University School and Hospital of Stomatology, Beijing, China
| | - Kaining Liu
- Department of Periodontology, National Center of Stomatology & National Clinical Research Center for Oral Diseases, National Engineering Laboratory for Digital and Material Technology of Stomatology, Peking University School and Hospital of Stomatology, Beijing, China
| | - Jianxia Hou
- Department of Periodontology, National Center of Stomatology & National Clinical Research Center for Oral Diseases, National Engineering Laboratory for Digital and Material Technology of Stomatology, Peking University School and Hospital of Stomatology, Beijing, China
| |
Collapse
|
|
4
|
Brock L, Ben-Atya H, Tiwari A, Saab D, Haj N, Folle L, Saar G, Maier A, Freiman M, Vandoorne K. Improved MRI detection of inflammation-induced changes in bone marrow microstructure in mice: a machine learning-enhanced T2 distribution analysis. Eur Radiol Exp 2025; 9:39. [PMID: 40140174 PMCID: PMC11947359 DOI: 10.1186/s41747-025-00574-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2024] [Accepted: 02/25/2025] [Indexed: 03/28/2025] Open
Abstract
BACKGROUND We investigated inflammation-induced changes in femoral hematopoietic bone marrow using advanced magnetic resonance imaging (MRI) techniques, including T2-weighted imaging, scalar T2 mapping, and machine learning-enhanced T2 distribution analysis to improve the detection of bone marrow microstructural alterations. Findings were correlated with histological markers and systemic inflammation. METHODS Using a 9.4-T magnet, T2-weighted and multislice multiecho sequences were applied to evaluate bone marrow in female C57BL/6J mice divided into three groups: (1) controls; (2) lipopolysaccharide-induced acute inflammation (LPS); and (3) streptozotocin (STZ)- and LPS-induced diabetic inflammation (STZ + LPS). T2 relaxation times and their distributions with scalar mapping and model-informed machine learning (MIML) were analyzed. Correlations with histological iron levels and blood neutrophil counts were assessed. RESULTS T2-weighted imaging showed a reduced signal-to-noise ratio in inflamed bone marrow (p = 0.034). Scalar T2 mapping identified decreased T2 relaxation times (p = 0.042), moderately correlating with neutrophil counts (ρ = 0.027) and iron levels (ρ = 0.016). MIML-enhanced T2 distribution analysis exhibited superior sensitivity than scalar T2 mapping, revealing significant reductions in the first T2 distribution peak (p = 0.0025), which strongly correlated with neutrophil counts (ρ = 0.0016) and iron sequestration (ρ = 0.0002). Histology confirmed elevated iron deposits in inflamed marrow, aligning with systemic inflammation. CONCLUSION Combining T2-weighted imaging, scalar T2 mapping, and MIML-enhanced T2 distribution analysis offers complementary insights into inflammation-induced bone marrow remodeling. T2 distribution analysis emerged as a more sensitive tool for detecting microstructural changes, such as iron sequestration, supporting its potential as a noninvasive biomarker for diagnosing and monitoring inflammatory diseases. RELEVANCE STATEMENT This study highlights the potential of advanced MRI T2 analysis and machine learning methods for noninvasive detection of inflammation-induced microstructural changes in bone marrow, offering promising diagnostic tools for inflammatory diseases. KEY POINTS This study investigated inflammation-induced changes in bone marrow with T2 MRI and MIML. MIML outperformed quantitative scalar T2 analysis, increasingly detecting inflammation and iron sequestration in the hematopoietic bone marrow. T2 MRI with MIML analysis could aid in the early diagnosis and management of inflammatory diseases.
Collapse
Affiliation(s)
- Luise Brock
- Faculty of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa, Israel
- Department Informatik, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
| | - Hadas Ben-Atya
- Faculty of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa, Israel
| | - Ashish Tiwari
- Faculty of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa, Israel
| | - Dareen Saab
- Faculty of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa, Israel
| | - Narmeen Haj
- Faculty of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa, Israel
| | - Lukas Folle
- Department Informatik, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
| | - Galit Saar
- Biomedical Core Facility, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
| | - Andreas Maier
- Department Informatik, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
| | - Moti Freiman
- Faculty of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa, Israel
| | - Katrien Vandoorne
- Faculty of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa, Israel.
| |
Collapse
|
|
5
|
Hu Q, Wang L, Chen Q, Wang Z. The global, regional, and national burdens of maternal sepsis and other maternal infections and trends from 1990 to 2021 and future trend predictions: results from the Global Burden of Disease study 2021. BMC Pregnancy Childbirth 2025; 25:285. [PMID: 40087648 PMCID: PMC11907898 DOI: 10.1186/s12884-025-07409-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2025] [Accepted: 03/03/2025] [Indexed: 03/17/2025] Open
Abstract
BACKGROUND Maternal sepsis and other maternal infections (MSMIs) significantly contribute to maternal morbidity and mortality worldwide, posing critical challenges due to their rapid progression and severe outcomes. METHODS Data from the Global Burden of Disease (GBD) 2021 study, covering 204 countries and territories, were used to evaluate the incidence, death, and disability-adjusted life years (DALYs) of MSMI. Statistical methods included joinpoint regression, age-period-cohort analysis, decomposition analysis, frontier analysis, and ARIMA model forecasting. RESULTS From 1990 to 2021, global MSMI incidence decreased from 22.45 million to 19.05 million, with the age-standardized rate (ASR) dropping from 764.03 (95% UI: 573.01-970.54) to 494.19 (95% UI: 377.34-623.90) per 100,000 people. High-SDI regions saw significant reductions, while low-SDI regions experienced increases. Women aged 20-24 consistently had the highest incidence, death, and DALYs. Iron deficiency was a significant risk factor, especially in lower SDI regions. Decomposition analysis showed that epidemiological changes and population growth were major drivers, particularly in low-SDI regions. Age-period-cohort analysis revealed women aged 20-29 as the most vulnerable, with notable improvements after 2000 and progressively decreasing risks in younger cohorts. Frontier analysis revealed that higher-SDI countries had greater improvement potential. ARIMA forecasting suggests continued declines in MSMI cases and ASR through 2040. CONCLUSIONS While significant progress has been made globally, challenges persist, including rising incidence in low-SDI regions, vulnerability of women aged 20-29, and the impact of iron deficiency. Efforts to address these and improve healthcare infrastructure are critical to further reduce MSMI and enhance maternal health outcomes.
Collapse
Affiliation(s)
- Qilin Hu
- Xuzhou Medical University, Xuzhou, 221000, China
- Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou, 221000, China
| | - Lvming Wang
- Xuzhou Medical University, Xuzhou, 221000, China
- Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou, 221000, China
| | - Qianmin Chen
- Department of Anesthesiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221000, China
| | - Zhiping Wang
- Xuzhou Medical University, Xuzhou, 221000, China.
- Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou, 221000, China.
- Department of Anesthesiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221000, China.
| |
Collapse
|
|
6
|
Herpich C, Walter S, Ott C, Haß U, Grune T, Müller-Werdan U, Norman K. Pro-inflammatory diet affects markers of iron metabolism in healthy older adults. J Trace Elem Med Biol 2025; 87:127583. [PMID: 39708661 DOI: 10.1016/j.jtemb.2024.127583] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2024] [Revised: 12/02/2024] [Accepted: 12/16/2024] [Indexed: 12/23/2024]
Abstract
BACKGROUND Inflammation and inadequate nutrition are common in older age and known to affect iron homeostasis. However, it is not known whether a pro-inflammatory diet affects iron status in older adults. We investigated the diet quality of healthy older adults considering markers of iron homeostasis and inflammation compared to a younger control. METHODS Serum markers of iron metabolism (iron, transferrin, ferritin, hepcidin, soluble transferrin receptor [sTfR]) and inflammation (interleukin-6 [IL-6], IL-10 high-sensitive C- reactive protein [hsCRP]) were quantified using immunosorbent assays. Insulin resistance was determined by calculating the homeostasis model assessment index (HOMA-IR). The Dietary Inflammatory Index® (DII) was computed based on dietary intake and inflammatory (ID) or less inflammatory diet (LID) groups were created by using median DII score specific to age group and sex. RESULTS DII did not differ by age (p = 0.668, n = 80, F: 75 %, >65 years, n = 60, F: 72 %, ≤35 years). Iron and inflammation status were different between age groups in terms of higher transferrin saturation, sTfR, ferritin and IL-6 concentrations in the old (all p ≤ 0.001). Only in older adults, BMI, HOMA-IR, hsCRP, ferritin and hepcidin concentrations were significantly higher in ID compared to LID (all p < 0.01). In addition, a risk-factor adjusted regression analysis showed that ID was independently associated with higher ferritin and hepcidin concentrations in older adults. CONCLUSION In older age, a pro-inflammatory diet is associated with systemic inflammation and disturbed iron homeostasis.
Collapse
Affiliation(s)
- Catrin Herpich
- Department of Nutrition and Gerontology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany; Institute of Nutritional Science, University of Potsdam, Nuthetal, Germany; Department of Geriatrics and Medical Gerontology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
| | - Sophia Walter
- Department of Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany; German Center for Cardiovascular Research (DZHK), Partner Site Berlin, Berlin, Germany; TraceAge-DFG Research Unit on Interactions of Essential Trace Elements in Healthy and Diseased Elderly, Potsdam-Berlin-Jena-Wuppertal, Germany
| | - Christiane Ott
- Department of Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany; German Center for Cardiovascular Research (DZHK), Partner Site Berlin, Berlin, Germany; TraceAge-DFG Research Unit on Interactions of Essential Trace Elements in Healthy and Diseased Elderly, Potsdam-Berlin-Jena-Wuppertal, Germany
| | - Ulrike Haß
- Department of Rehabilitation Medicine, Faculty of Health Sciences, University of Potsdam, Potsdam, Germany
| | - Tilman Grune
- Institute of Nutritional Science, University of Potsdam, Nuthetal, Germany; Department of Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany; German Center for Cardiovascular Research (DZHK), Partner Site Berlin, Berlin, Germany; TraceAge-DFG Research Unit on Interactions of Essential Trace Elements in Healthy and Diseased Elderly, Potsdam-Berlin-Jena-Wuppertal, Germany
| | - Ursula Müller-Werdan
- Department of Geriatrics and Medical Gerontology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; Evangelisches Geriatriezentrum Berlin gGmbH, Berlin, Germany
| | - Kristina Norman
- Department of Nutrition and Gerontology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany; Institute of Nutritional Science, University of Potsdam, Nuthetal, Germany; Department of Geriatrics and Medical Gerontology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; German Center for Cardiovascular Research (DZHK), Partner Site Berlin, Berlin, Germany; TraceAge-DFG Research Unit on Interactions of Essential Trace Elements in Healthy and Diseased Elderly, Potsdam-Berlin-Jena-Wuppertal, Germany
| |
Collapse
|
|
7
|
Chen SZQ, Pan RJ, Sun MY, He LP, Li CP. The relationship between whole blood iron and fasting blood glucose in community-dwelling elderly people: a cross-sectional study. JOURNAL OF HEALTH, POPULATION, AND NUTRITION 2025; 44:5. [PMID: 39773371 PMCID: PMC11706085 DOI: 10.1186/s41043-024-00720-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/29/2024] [Accepted: 12/14/2024] [Indexed: 01/11/2025]
Abstract
Iron overload increases fasting blood glucose level in mice, leading to insulin insensitivity. However, no such relationship has been shown in the population. The relationship between whole blood iron levels and fasting blood glucose levels remained unclear. This study aimed to determine whether whole blood iron levels were associated with fasting blood glucose levels in community-dwelling older adults. This cross-sectional study was based on a community population and analyzed the distribution of whole blood iron and fasting blood glucose in a community population. A sample of 1560 community residents had their fasting blood glucose, gender, and age measured during the study. Covariates were assessed using correlation analysis, partial correlation analysis, and Student's t-test. To further investigate the impact of confounding factors in this study, we compared variations in whole blood iron levels between genders. Pearson correlation analysis showed no correlation between whole blood iron and fasting blood glucose. After adjusting for age and gender, no correlation was found between whole blood iron and fasting blood glucose as well. However, Pearson correlation analysis showed a correlation between whole blood iron and age(P<0.05, r=-0.181). whole blood iron concentrations gradually decreased with age. At the same time, mean whole blood iron concentrations were lower 420 mg/l among women and men in the community. And the mean levels of whole blood iron were higher in men(504.08 mg/l ± 45.98 mg/l) than in women(453.80 mg/l ± 38.13 mg/l). Our study indicated no association between whole blood iron. Age was a covariate, but fasting blood glucose was not, and fasting blood glucose was independently associated with whole blood iron concentrations, suggesting that older women in this community need adequate iron supplementation.
Collapse
Affiliation(s)
- Shu-Zi-Qi Chen
- School of Medicine, Taizhou University, No.1139, Shifu Avenue, Jiaojiang, 318000, Zhejiang, China
| | - Rou-Jun Pan
- School of Medicine, Taizhou University, No.1139, Shifu Avenue, Jiaojiang, 318000, Zhejiang, China
| | - Meng-Yan Sun
- School of Medicine, Taizhou University, No.1139, Shifu Avenue, Jiaojiang, 318000, Zhejiang, China
| | - Lian-Ping He
- School of Medicine, Taizhou University, No.1139, Shifu Avenue, Jiaojiang, 318000, Zhejiang, China.
| | - Cui-Ping Li
- School of Medicine, Taizhou University, No.1139, Shifu Avenue, Jiaojiang, 318000, Zhejiang, China.
| |
Collapse
|
|
8
|
Herpich C, Göger L, Faust L, Kalymon M, Ott C, Walter S, Lehmkuhl E, Grune T, Moskiou V, Müller-Werdan U, Norman K. Disentangling Anemia in Frailty: Exploring the Role of Inflammation. J Gerontol A Biol Sci Med Sci 2024; 79:glae243. [PMID: 39360829 DOI: 10.1093/gerona/glae243] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2024] [Indexed: 11/21/2024] Open
Abstract
BACKGROUND In older patients, frailty and anemia frequently coexist. However, only few studies have been conducted in older patients with multimorbidity and several overlapping causes of anemia, such as inflammation, inadequate nutrition, or certain pathologies. This analysis aims to decipher potential factors associated with anemia in older hospital patients with frailty. METHODS Patients (n = 208, age: 62-98 years) were categorized as prefrail (n = 68) and frail (n = 140) using the Fried frailty phenotype. We quantified serum concentrations of markers of iron metabolism (iron, ferritin, transferrin, soluble transferrin receptor, and hepcidin), inflammation (interleukin [IL]-6 and IL-10 C-reactive protein), and hematology (hemoglobin). Principal component analysis was conducted to evaluate biomarker patterns and associations with frailty were assessed with logistic regression analysis. RESULTS Anemia prevalence was higher in patients with frailty (84.3% vs 70.6%, p = .021). Three principal components (PC1-3) were identified. PC1 was characterized by high factor loadings representing inflammation and factor scores differed between patients with prefrailty and frailty (-0.04 (interquartile range [IQR]: 1.45) vs -0.51 (IQR: 0.87), p < .001]. PC2 represents macrocytic anemia and thus vitamin B12 or folate deficiency, whereas PC3 indicates hematological pathologies. Only PC1 was associated with frailty status when controlled for age, sex, number of drugs, and comorbidities (OR: 2.018, 95% CI: 1.316; 3.094, p = .001). PC2 and PC3 were not associated with frailty. CONCLUSIONS Our results suggest that anemia in patients with frailty is driven by inflammation rather than being disease-related or solely the result of micronutrient deficiencies.
Collapse
Affiliation(s)
- Catrin Herpich
- Institute of Nutritional Science, University of Potsdam, Nuthetal, Germany
- TraceAge-DFG Research Unit on Interactions of Essential Trace Elements in Healthy and Diseased Elderly, Potsdam-Berlin-Jena-Wuppertal, Germany
| | - Lea Göger
- Department of Nutrition and Gerontology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany
| | - Lea Faust
- Department of Geriatrics and Medical Gerontology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Magdalena Kalymon
- Department of Geriatrics and Medical Gerontology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Christiane Ott
- Department of Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany
- German Center for Cardiovascular Research (DZHK), Partner Site Berlin, Berlin, Germany
| | - Sophia Walter
- Department of Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany
- German Center for Cardiovascular Research (DZHK), Partner Site Berlin, Berlin, Germany
| | - Elke Lehmkuhl
- Evangelisches Geriatriezentrum Berlin gGmbH, Berlin, Germany
| | - Tilman Grune
- TraceAge-DFG Research Unit on Interactions of Essential Trace Elements in Healthy and Diseased Elderly, Potsdam-Berlin-Jena-Wuppertal, Germany
- Department of Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany
| | - Varvara Moskiou
- Department of Geriatrics and Medical Gerontology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Ursula Müller-Werdan
- Department of Geriatrics and Medical Gerontology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
- Evangelisches Geriatriezentrum Berlin gGmbH, Berlin, Germany
| | - Kristina Norman
- TraceAge-DFG Research Unit on Interactions of Essential Trace Elements in Healthy and Diseased Elderly, Potsdam-Berlin-Jena-Wuppertal, Germany
- Department of Nutrition and Gerontology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany
| |
Collapse
|
|
9
|
Öztop H, Hunutlu FÇ. Neutrophil-to-ferritin ratio can predict hematological causes of fever of unknown origin. Sci Rep 2024; 14:22983. [PMID: 39362941 PMCID: PMC11449920 DOI: 10.1038/s41598-024-74569-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2024] [Accepted: 09/26/2024] [Indexed: 10/05/2024] Open
Abstract
Despite advancements in diagnostic modalities, delineating the etiology of fever of unknown origin (FUO) remains a significant challenge for clinicians. Notably, cases with hematological malignancies often have a poor prognosis due to delayed diagnosis. This study investigated the potential of readily obtainable laboratory markers to differentiate hematological causes from other etiologies during the early stages of FUO. A retrospective analysis was conducted on the medical records of 100 patients who fulfilled the modified FUO criteria between January 2010 and April 2023. Hematological etiologies were identified in 26 of the 100 patients. Peripheral blood neutrophil, lymphocyte, platelet counts, and the systemic immune inflammation (SII) index, were significantly lower in the hematological group compared to the non-hematological group. Conversely, serum ferritin levels were demonstrably higher in the hematological group. ROC analysis identified a neutrophil-to-ferritin ratio (NFR) cutoff value of < 8.53 as optimal for predicting hematological etiology. Subsequent multivariate analysis demonstrated that the NFR was the sole independent predictor of hematological etiology (p = 0.013).This study proposes a novel approach for early diagnosis of a potentially life-threatening subset of FUO patients. The NFR presents as an inexpensive and readily available marker for predicting hematological etiology in FUO cases.
Collapse
Affiliation(s)
- Hikmet Öztop
- Department of Internal Medicine, Faculty of Medicine, Bursa Uludag University, Gorukle Campus, Bursa, Turkey.
| | - Fazıl Çağrı Hunutlu
- Division of Hematology, Department of Internal Medicine, Faculty of Medicine, Bursa Uludag University, Bursa, Turkey
| |
Collapse
|
|
10
|
Reid BM. Early life stress and iron metabolism in developmental psychoneuroimmunology. Brain Behav Immun Health 2024; 40:100824. [PMID: 39161875 PMCID: PMC11331713 DOI: 10.1016/j.bbih.2024.100824] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2023] [Revised: 06/03/2024] [Accepted: 07/15/2024] [Indexed: 08/21/2024] Open
Abstract
An estimated 250 million children face adverse health outcomes from early life exposure to severe or chronic social, economic, and nutritional adversity, highlighting/emphasizing the pressing concern about the link between ELS and long-term implications on mental and physical health. There is significant overlap between populations experiencing high levels of chronic stress and those experiencing iron deficiency, spotlighting the potential role of iron as a key mediator in this association. Iron, an essential micronutrient for brain development and immune function, is often depleted in stress conditions. Iron deficiency among the most common nutrient deficiencies in the world. Fetal and infant iron status may thus serve as a crucial intermediary between early chronic psychological stress and subsequent immune system changes to impact neurodevelopment. The review presents a hypothesized pathway between early life stress (ELS), iron deficiency, and neurodevelopment through the hypothalamic-pituitary-adrenocortical (HPA) axis and the IL-6-hepcidin axis. This hypothesis is derived from (1) evidence that stress impacts iron status (2) long-term neurodevelopmental outcomes that are shared by ELS and iron deficiency exposure, and (3) possible mechanisms for how iron may mediate the relation between ELS and iron deficiency through alterations in the developing immune system. The article concludes by proposing future research directions, emphasizing the need for rigorous studies to elucidate how stress and iron metabolism interact to modify the developing immune system. Understanding these mechanisms could open new avenues for improving human health and neurodevelopment for women and children globally, making it a timely and vital area of study in psychoneuroimmunology research.
Collapse
Affiliation(s)
- Brie M. Reid
- Department of Psychiatry and Human Behavior, Warren Alpert Medical School, Brown University, USA
- Center for Behavioral and Preventive Medicine, The Miriam Hospital, USA
- Department of Psychology, Department of Health Sciences, Northeastern University, USA
| |
Collapse
|
|
11
|
Kakumani J, Koduri A, Lankapothu PBR, Kumar S M. Xanthogranulomatous Pyelonephritis and Plummer-Vinson Syndrome: A Case Report Exploring Potential Connections in a Single Patient. Cureus 2024; 16:e69097. [PMID: 39391408 PMCID: PMC11466314 DOI: 10.7759/cureus.69097] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/10/2024] [Indexed: 10/12/2024] Open
Abstract
Xanthogranulomatous pyelonephritis (XGP) and Plummer-Vinson Syndrome (PVS) are two rare disorders that pose considerable diagnostic difficulties mainly because their signs overlap and are multifaceted. XGP is a severe form of pyelonephritis imitating cancer, whereas PVS is defined by dysphagia, iron deficiency anemia, and esophageal webs. This article presents the case of a 53-year-old female with a previous history of renal calculi and multiple transfusions who presented with dysphagia, flank pain, and hematuria. Findings from investigations showed severe anemia, a renal lesion suggesting malignancy, and GI findings pointing to the presence of PVS. The coexistence of XGP and PVS in this patient highlights the need for careful differential diagnosis and the importance of a multidisciplinary approach in managing patients with rare overlapping syndromes. Furthermore, this example shows how chronic infection, malnutrition, and their potential for leading to neoplasms connect. In summary, one should recognize that the possibility these two conditions can coincide is paramount for accurate diagnosis and effective management. Lastly, this case demonstrates that comprehensive assessment can only be achieved through coordinated care addressing both direct effects as well as secondary complications due to such uncommon diseases.
Collapse
Affiliation(s)
- Jagadeswar Kakumani
- Internal Medicine, Saveetha Medical College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, IND
| | - Amukthamalyada Koduri
- General Medicine, Saveetha Medical College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, IND
| | - Prem Balaji Reddy Lankapothu
- General Medicine, Saveetha Medical College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, IND
| | - Magesh Kumar S
- General Medicine, Saveetha Medical College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, IND
| |
Collapse
|
|
12
|
Kohara C, Yamada S, Tanaka S, Hiyamuta H, Kitamura H, Arase H, Shimamoto S, Taniguchi M, Tsuruya K, Kitazono T, Nakano T. Blood Hemoglobin Concentrations and the Incidence of Lower Extremity Peripheral Arterial Disease in Patients Undergoing Hemodialysis: 10-Year Outcomes of the Q-Cohort Study. J Am Heart Assoc 2024; 13:e033853. [PMID: 39101503 PMCID: PMC11964019 DOI: 10.1161/jaha.123.033853] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2023] [Accepted: 06/20/2024] [Indexed: 08/06/2024]
Abstract
BACKGROUND Lower extremity peripheral arterial disease is a potentially lethal cardiovascular complication in patients undergoing hemodialysis. Anemia is a risk factor for cardiovascular disease among the hemodialysis population. However, whether blood hemoglobin concentration is associated with the risk of peripheral arterial disease progression in this population remains undetermined. METHODS AND RESULTS This is an extension of a 4-year multicenter, prospective, observational cohort study to 10 years. A total of 3504 Japanese patients undergoing maintenance hemodialysis were recruited between 2006 and 2007. The primary exposure was blood hemoglobin concentration at baseline. The main outcome was the first-ever incidence of major adverse limb events (MALE), composed of endovascular treatment, bypass surgery, and amputation. Multivariable-adjusted Cox proportional hazards model, Fine-Gray subdistribution hazards model, restricted cubic spline analysis, and restricted mean survival time analysis were used to determine the association of blood hemoglobin concentration with the incidence of MALE. During a median follow-up of 8.0 years, 257 patients experienced MALE. A Cox proportional hazards model showed that the risk of MALE in patients with blood hemoglobin concentrations <10.0 g/dL was significantly higher than in patients with concentrations of 11.0 to 11.9 g/dL, even after adjusting for confounding factors. In contrast, elevated hemoglobin concentration (≥12.0 g/dL) was not significantly associated with increased risk of MALE. Similar associations were observed when the Fine-Gray subdistribution regression model was used by setting all-cause mortality as the competing risk. CONCLUSIONS A low blood hemoglobin concentration is an independent risk factor for peripheral arterial disease progression in patients undergoing maintenance hemodialysis.
Collapse
Affiliation(s)
- Chiaki Kohara
- Department of Medicine and Clinical Science, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan
| | - Shunsuke Yamada
- Department of Medicine and Clinical Science, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan
| | - Shigeru Tanaka
- Department of Medicine and Clinical Science, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan
| | - Hiroto Hiyamuta
- Department of Medicine and Clinical Science, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan
| | - Hiromasa Kitamura
- Department of Medicine and Clinical Science, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan
| | - Hokuto Arase
- Department of Medicine and Clinical Science, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan
| | - Sho Shimamoto
- Department of Medicine and Clinical Science, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan
| | | | | | - Takanari Kitazono
- Department of Medicine and Clinical Science, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan
| | - Toshiaki Nakano
- Department of Medicine and Clinical Science, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan
- Kidney Care UnitKyushu University HospitalFukuokaJapan
| |
Collapse
|
|
13
|
Sussman-Dabach EJ, Joshi S, Dupuis L, White JA, Siavoshi M, Slukhinsky S, Singh B, Kalantar-Zadeh K. Preventing potential pitfalls of a liberalized potassium diet in the hemodialysis population. Semin Dial 2024; 37:317-325. [PMID: 34378234 DOI: 10.1111/sdi.13006] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2021] [Accepted: 07/08/2021] [Indexed: 12/23/2022]
Abstract
Emerging research suggests that a more liberalized diet, specifically a more plant-based diet resulting in liberalization of potassium intake, for people receiving hemodialysis is necessary and the benefits outweigh previously thought risks. If the prescribed hemodialysis diet is to be liberalized, the need to illuminate and prevent potential pitfalls of a liberalized potassium diet is warranted. This paper explores such topics as partial to full adherence to a liberalized diet and its consequences if any, the advantages of a high-fiber intake, the theoretical risk of anemia when consuming a more plant-dominant diet, the potential benefits against renal acid load and effect on metabolic acidosis with increased fruit and vegetable intake, the putative change in serum potassium levels, carbohydrate quality, and the healthfulness of meat substitutes. The benefits of a more plant-based diet for the hemodialysis population are multifold; however, the possible pitfalls of this type of diet must be reviewed and addressed upon meal planning in order to be avoided.
Collapse
Affiliation(s)
- Elizabeth J Sussman-Dabach
- Department of Family and Consumer Sciences, California State University, Northridge, Northridge, California, USA
| | - Shivam Joshi
- Department of Medicine, New York University Grossman School of Medicine, New York, New York, USA
- Department of Medicine, NYC Health + Hospitals/Bellevue, New York, New York, USA
| | - Léonie Dupuis
- College of Medicine, University of Central Florida College of Medicine, Orlando, Florida, USA
| | - Jennifer A White
- Department of Family and Consumer Sciences, California State University, Northridge, Northridge, California, USA
| | - Mehrnaz Siavoshi
- Department of Family and Consumer Sciences, California State University, Northridge, Northridge, California, USA
| | | | - Bhupinder Singh
- University of California, Irvine, School of Medicine, Irvine, California, USA
| | | |
Collapse
|
|
14
|
Nam HS, Ho JPY, Park SY, Cho JH, Kim YB, Lee YS. Postoperative Intravenous Iron Supplementation Increases Hemoglobin Level in Total Knee Arthroplasty. J Knee Surg 2024; 37:416-425. [PMID: 37625454 DOI: 10.1055/a-2160-2931] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 08/27/2023]
Abstract
Iron supplementation provides iron storage and facilitates effective production of hemoglobin. The purpose of this study was to investigate the effect of early postoperative intravenous (IV) iron supplementation in different types of total knee arthroplasty (TKA) surgery. We retrospectively analyzed 863 patients who underwent TKA between September 2017 and September 2021. The IV iron (I) and non-IV iron (NI) groups were compared. Hemoglobin responders, defined as patients who showed a change in hemoglobin level of ≥2 g/dL at 6 weeks of surgery compared to the baseline immediate postoperative hemoglobin level, were identified and they were compared with the nonresponders. After logistic regression analysis, the patients were classified according to the type of surgery (unilateral TKA, staged bilateral TKA, and simultaneous bilateral TKA). A subgroup analysis was performed according to the comorbidity as Charlson Comorbidity Index (CCI). The type of surgery and the rate of hemoglobin responders differed between the I and NI groups. The surgery type and iron supplementation significantly affected the hemoglobin responder in the logistic regression model. In each surgery type, hemoglobin drop in the I group was generally lower in the second and sixth weeks than that in the NI group. It was also effective in reducing hemoglobin drop on the first day of the second surgery in staged bilateral TKA. In addition, the number of hospital days was lower in the IV iron supplementation group who underwent a staged bilateral TKA. CCI did not affect hemoglobin responder, hemoglobin drop, and transfusion rate in both the I and NI groups. Postoperative IV iron supplementation affected the outcome of hemoglobin responders. In addition, it reduced early postoperative hemoglobin drop. However, iron supplementation did not affect the transfusion rate, complications, and clinical outcome, regardless of the type of surgery. LEVEL OF EVIDENCE: Level III, case-control study.
Collapse
Affiliation(s)
- Hee Seung Nam
- Department of Orthopedic Surgery, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
| | - Jade Pei Yuik Ho
- Department of Orthopedic Surgery, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
| | - Seung Yun Park
- Department of Orthopedic Surgery, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
| | - Joon Hee Cho
- Department of Orthopedic Surgery, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
| | - Yong Beom Kim
- Department of Orthopedic Surgery, Soonchunhyang University College of Medicine, Soonchunhyang University Hospital, South Korea
| | - Yong Seuk Lee
- Department of Orthopedic Surgery, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
| |
Collapse
|
|
15
|
de Brito EDCA, França ADO, Siqueira IV, Félix VLT, Rezende AA, Amorim BC, da Silva SER, Mendes RP, Weber SS, Paniago AMM. Analysis and Interpretation of Automated Blood Count in the Treatment of Chronic Paracoccidioidomycosis. J Fungi (Basel) 2024; 10:317. [PMID: 38786672 PMCID: PMC11122400 DOI: 10.3390/jof10050317] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2024] [Revised: 04/22/2024] [Accepted: 04/25/2024] [Indexed: 05/25/2024] Open
Abstract
Blood count is crucial for assessing bone marrow's cell production and differentiation during infections, gaging disease severity, and monitoring therapeutic responses. The profile of blood count in chronic forms of paracoccidioidomycosis (PCM) has been insufficiently explored. To better understand the changes in hematological cells in different stages of the PCM chronic form, we evaluated the blood count, including immature blood cells in automated equipment, before and during the treatment follow-up of 62 chronic PCM patients. Predominantly male (96.8%) with an average age of 54.3 (standard deviation SD 6.9) years, participants exhibited pre-treatment conditions such as anemia (45.2%), monocytosis (38.7%), and leukocytosis (17.7%), which became less frequent after clinical cure. Anemia was more prevalent in severe cases. Notably, hemoglobin and reticulocyte hemoglobin content increased, while leukocytes, monocytes, neutrophils, immature granulocytes, and platelets decreased. Chronic PCM induced manageable hematological abnormalities, mainly in the red blood series. Monocytosis, indicating monocytes' role in PCM's immune response, was frequent. Post-treatment, especially after achieving clinical cure, significant improvements were observed in various hematological indices, including immature granulocytes and reticulocyte hemoglobin content, underscoring the impact of infection on these parameters.
Collapse
Affiliation(s)
- Eliana da Costa Alvarenga de Brito
- Graduate Program in Infectious and Parasitic Diseases, Faculty of Medicine, Federal University of Mato Grosso do Sul, Campo Grande 79070-900, MS, Brazil; (E.d.C.A.d.B.); (A.d.O.F.); (B.C.A.)
| | - Adriana de Oliveira França
- Graduate Program in Infectious and Parasitic Diseases, Faculty of Medicine, Federal University of Mato Grosso do Sul, Campo Grande 79070-900, MS, Brazil; (E.d.C.A.d.B.); (A.d.O.F.); (B.C.A.)
| | - Igor Valadares Siqueira
- Scientific Initiation CNPq, Faculty of Medicine, Federal University of Mato Grosso do Sul, Campo Grande 79070-900, MS, Brazil; (I.V.S.); (V.L.T.F.); (A.A.R.); (S.E.R.d.S.)
| | - Vinícius Lopes Teodoro Félix
- Scientific Initiation CNPq, Faculty of Medicine, Federal University of Mato Grosso do Sul, Campo Grande 79070-900, MS, Brazil; (I.V.S.); (V.L.T.F.); (A.A.R.); (S.E.R.d.S.)
| | - Amanda Alves Rezende
- Scientific Initiation CNPq, Faculty of Medicine, Federal University of Mato Grosso do Sul, Campo Grande 79070-900, MS, Brazil; (I.V.S.); (V.L.T.F.); (A.A.R.); (S.E.R.d.S.)
| | - Bárbara Casella Amorim
- Graduate Program in Infectious and Parasitic Diseases, Faculty of Medicine, Federal University of Mato Grosso do Sul, Campo Grande 79070-900, MS, Brazil; (E.d.C.A.d.B.); (A.d.O.F.); (B.C.A.)
| | - Suzane Eberhart Ribeiro da Silva
- Scientific Initiation CNPq, Faculty of Medicine, Federal University of Mato Grosso do Sul, Campo Grande 79070-900, MS, Brazil; (I.V.S.); (V.L.T.F.); (A.A.R.); (S.E.R.d.S.)
| | - Rinaldo Poncio Mendes
- Department of Tropical Diseases, Botucatu Medical School, São Paulo State University, Botucatu 18618-687, SP, Brazil;
| | - Simone Schneider Weber
- Faculty of Pharmaceutical Sciences, Food and Nutrition, Federal University of Mato Grosso do Sul, Campo Grande 79070-900, MS, Brazil;
| | - Anamaria Mello Miranda Paniago
- Graduate Program in Infectious and Parasitic Diseases, Faculty of Medicine, Federal University of Mato Grosso do Sul, Campo Grande 79070-900, MS, Brazil; (E.d.C.A.d.B.); (A.d.O.F.); (B.C.A.)
| |
Collapse
|
|
16
|
Bolscher M, Koster SCE, Koopmans M, Haitsma Mulier JLG, Derde LPG, Juffermans NP. Anti-inflammatory therapies are associated with delayed onset of anemia and reduction in transfusion requirements in critically ill patients: results from two studies. Crit Care 2024; 28:114. [PMID: 38594746 PMCID: PMC11003051 DOI: 10.1186/s13054-024-04898-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2024] [Accepted: 04/02/2024] [Indexed: 04/11/2024] Open
Abstract
BACKGROUND Anemia is a hallmark of critical illness, which is largely inflammatory driven. We hypothesized that the use of anti-inflammatory agents limits the development of anemia and reduces the need for red blood cell (RBC) transfusions in patients with a hyper-inflammatory condition due to COVID-19. METHODS An observational cohort (n = 772) and a validation cohort (a subset of REMAP-CAP, n = 119) of critically ill patients with hypoxemic respiratory failure due to COVID-19 were analyzed, who either received no treatment, received steroids or received steroids plus IL-6 blocking agents. The trajectory of hemoglobin (Hb) decline and the need for RBC transfusions were compared using descriptive statistics as well as multivariate modeling. RESULTS In both cohorts, Hb level was higher in the treated groups compared to the untreated group at all time points. In the observational cohort, incidence and number of transfused patients were lower in the group receiving the combination treatment compared to the untreated groups. In a multivariate analysis controlling for baseline Hb imbalance and mechanical ventilation, receipt of steroids remained associated with a slower decline in Hb level and the combination treatment remained associated with a slower decline of Hb and with less transfusions. Results remained the same in the validation cohort. CONCLUSION Immunomodulatory treatment was associated with a slower decline in Hb level in critically ill patients with COVID-19 and with less transfusion. Findings point toward inflammation as an important cause for the occurrence of anemia in the critically ill.
Collapse
Affiliation(s)
- Madelief Bolscher
- Department of Intensive Care, OLVG Hospital, Oosterpark 9, Amsterdam, The Netherlands
| | | | - Matty Koopmans
- Department of Intensive Care, OLVG Hospital, Oosterpark 9, Amsterdam, The Netherlands
| | | | - Lennie P G Derde
- Department of Intensive Care, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Nicole P Juffermans
- Department of Intensive Care, Erasmus Medical Center, Molewaterplein 40, Rotterdam, The Netherlands.
- Laboratory of Translational Intensive Care, Erasmus Medical Center, Molewaterplein 40, Rotterdam, The Netherlands.
| |
Collapse
|
|
17
|
Adi G, Shaath MR, Adi K, Obaid Z, Aldosari E, AlKateb FA. Generalized pustular psoriasis in a toddler with IL36RN mutation: a case report. Front Immunol 2024; 15:1337799. [PMID: 38571950 PMCID: PMC10987684 DOI: 10.3389/fimmu.2024.1337799] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Accepted: 02/29/2024] [Indexed: 04/05/2024] Open
Abstract
Generalized Pustular Psoriasis (GPP) is a dermatological autoinflammatory disease that rarely occurs in children and is associated with complex genetic factors. GPP pathogenesis has been associated with mutations in IL36RN gene, which encodes an interleukin-36 receptor antagonist. GPP usually occurs without a history of psoriasis in the patients or their family members. This case report describes the clinical course of a 3-year-old toddler with GPP. The diagnosis of GPP was confirmed through a comprehensive series of examinations, and genetic testing revealed an IL36RN mutation, providing further insight into the genetic basis of the condition. This case highlights the importance of a genetic perspective for diagnosing GPP, particularly in children.
Collapse
Affiliation(s)
- Ghaith Adi
- College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
| | | | - Kareem Adi
- College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
| | - Zaki Obaid
- College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
| | - Egab Aldosari
- Children’s Specialised Hospital, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Faten Ahmed AlKateb
- Children’s Specialised Hospital, King Fahad Medical City, Riyadh, Saudi Arabia
| |
Collapse
|
|
18
|
Kisali EP, Iversen PO, Makani J. Low vitamin B 12 blood levels in sickle cell disease: Data from a large cohort study in Tanzania. Br J Haematol 2024; 204:1047-1053. [PMID: 38087805 DOI: 10.1111/bjh.19265] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2023] [Revised: 11/17/2023] [Accepted: 12/06/2023] [Indexed: 03/14/2024]
Abstract
Sickle cell disease (SCD) is associated with high rates of undernutrition and stunting. Undernutrition in combination with chronic haemolysis may lead to deficiencies in micronutrients necessary for erythropoiesis. Here we examined selected levels of ferritin, vitamins B2 , B6 , B9 and B12 , and vitamin C that were measured in blood samples from 820 SCD patients from Tanzania with no history of hospital admission, infections or painful episodes in the previous 30 days. We studied children (0-8 years), early adolescents (9-14 years), late adolescents (15-17 years) and adults (≥18 years). Severely low levels of vitamin B12 were observed across the four age groups. Despite the lowered vitamin B12 concentrations, total homocysteine concentrations were normal across both genders in all age groups. We found no significant gender-related differences between the other measured micronutrients. In this large SCD population, spanning the whole life cycle, a low level of vitamin B12 was consistently found across both genders and all age groups. Given the pivotal role of vitamin B12 in cellular metabolism, particularly in erythropoiesis, more studies are required to unravel how to better detect clinically relevant vitamin B12 deficiency among SCD patients, and thus to identify more precisely those who need supplementation of vitamin B12 .
Collapse
Affiliation(s)
- Eka Patricia Kisali
- Muhimbili Sickle Cell Programme, Department of Hematology and Blood Transfusion, Muhimbili University of Health and Allied Sciences, Dar-es-Salaam, Tanzania
- Department of Physiology, Muhimbili University of Health and Allied Sciences, Dar-es-Salaam, Tanzania
- Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Per Ole Iversen
- Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
- Department of Haematology, Oslo University Hospital, Oslo, Norway
- Division of Human Nutrition, Stellenbosch University, Tygerberg, South Africa
| | - Julie Makani
- Muhimbili Sickle Cell Programme, Department of Hematology and Blood Transfusion, Muhimbili University of Health and Allied Sciences, Dar-es-Salaam, Tanzania
- Department of Immunology and Inflammation, Center for Haematology, Imperial College of London, London, UK
| |
Collapse
|
|
19
|
Zhang Y, Ding R, Zhang Y, Qi J, Cao W, Deng L, Zhou L, Ye Y, Xue Y, Liu E. Dysfunction of DMT1 and miR-135b in the gut-testis axis in high-fat diet male mice. GENES & NUTRITION 2024; 19:1. [PMID: 38243197 PMCID: PMC10797958 DOI: 10.1186/s12263-024-00737-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/24/2023] [Accepted: 01/04/2024] [Indexed: 01/21/2024]
Abstract
BACKGROUND Obese patients have been found to be susceptible to iron deficiency, and malabsorption of dietary iron is the cause of obesity-related iron deficiency (ORID). Divalent metal transporter 1 (DMT1) and ferroportin (FPN), are two transmembrane transporter proteins expressed in the duodenum that are closely associated with iron absorption. However, there have been few studies on the association between these two proteins and the increased susceptibility to iron deficiency in obese patients. Chronic inflammation is also thought to be a cause of obesity-related iron deficiency, and both conditions can have an impact on spermatogenesis and impair male reproductive function. Based on previous studies, transgenerational epigenetic inheritance through gametes was observed in obesity. RESULTS Our results showed that obese mice had decreased blood iron levels (p < 0.01), lower protein and mRNA expression for duodenal DMT1 (p < 0.05), but no statistically significant variation in mRNA expression for duodenal FPN (p > 0.05); there was an increase in sperm miR-135b expression (p < 0.05). Bioinformatics revealed ninety overlapping genes and further analysis showed that they were primarily responsible for epithelial cilium movement, fatty acid beta-oxidation, protein dephosphorylation, fertilization, and glutamine transport, which are closely related to spermatogenesis, sperm development, and sperm viability in mice. CONCLUSIONS In obese mice, we observed downregulation of DMT1 in the duodenum and upregulation of miR-135b in the spermatozoa.
Collapse
Affiliation(s)
- Yanru Zhang
- Laboratory Animal Center, Xi'an Jiaotong University Health Science Centre, Xi'an, 710061, China
| | - Ruike Ding
- Laboratory Animal Center, Xi'an Jiaotong University Health Science Centre, Xi'an, 710061, China
| | - Yulin Zhang
- Laboratory Animal Center, Xi'an Jiaotong University Health Science Centre, Xi'an, 710061, China
| | - Jia Qi
- Laboratory Animal Center, Xi'an Jiaotong University Health Science Centre, Xi'an, 710061, China
| | - Wenbin Cao
- Laboratory Animal Center, Xi'an Jiaotong University Health Science Centre, Xi'an, 710061, China
| | - Lijun Deng
- Spring Biological Technology Development Co., Ltd, Fangchenggang, Guangxi, 538000, China
| | - Lin Zhou
- Laboratory Animal Center, Xi'an Jiaotong University Health Science Centre, Xi'an, 710061, China
| | - Yun Ye
- Central Laboratory, The First Affiliated Hospital of Xi'an Medical University, Xi'an, 710000, China
| | - Ying Xue
- Laboratory Animal Center, Xi'an Jiaotong University Health Science Centre, Xi'an, 710061, China.
| | - Enqi Liu
- Laboratory Animal Center, Xi'an Jiaotong University Health Science Centre, Xi'an, 710061, China.
- Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education of China, Xi'an, 710049, China.
| |
Collapse
|
|
20
|
Suarez-Ortegón MF, Ordoñez-Betancourth JE, Ortega-Ávila JG, Yibby Forero A, Fernández-Real JM. Excess adiposity and iron-deficient status in Colombian women of reproductive age. Obesity (Silver Spring) 2023; 31:3025-3042. [PMID: 37814827 DOI: 10.1002/oby.23871] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2023] [Accepted: 07/06/2023] [Indexed: 10/11/2023]
Abstract
OBJECTIVE Information about excess adiposity markers different from BMI and iron status is limited and more so about the shape of these associations. This study evaluated the relationship between three adiposity markers and iron-deficient status in reproductive-age women. METHODS Cross-sectional analysis in 6357 non-pregnant women from the Colombian nutritional health survey (ENSIN) 2010. Exposures were the following: waist circumference (WC), waist-to-height ratio (W-HtR), BMI, and WC > 80 cm, W-HtR > 0.5, and BMI ≥ 25 and ≥30. Outcomes were the following: iron deficiency (ID) as serum ferritin <15 μg/L, ID as ferritin <30 μg/L, anemia, and continuous values of ferritin and hemoglobin. Logistic and linear regressions adjusted for sociodemographic/inflammation covariates were conducted. RESULTS All the adiposity markers, continuous or categorical, were inversely and significantly associated with both ID thresholds in fully adjusted models (p < 0.05). W-HtR reported stronger effect estimates for ID (odds ratios < 0.5) and for prediction of log-ferritin levels (fully adjusted β-coefficient [95% CI] 0.61 [0.39-0.82], p < 0.01) and was also inversely associated with anemia (p < 0.05). In cubic splines analyses, W-HtR, WC, and BMI were linearly associated with ID from values closer to international thresholds of general or central obesity, and the patterns of WC and BMI tended toward flatness. A significant decline in the likelihood of anemia was steeper by increasing W-HtR than by increasing BMI. After exclusion of women with C reactive protein > 5 mg/L or adjustment for C reactive protein, adiposity markers remained significantly related to ferritin levels and W-HtR with anemia. CONCLUSIONS Women with higher adiposity were less likely to have an iron-deficient status. W-HtR was the strongest and most consistently associated marker. Inflammation would not be involved in the associations found.
Collapse
Affiliation(s)
- Milton Fabián Suarez-Ortegón
- Departamento de Alimentación y Nutrición, Facultad de Ciencias de la Salud, Pontificia Universidad Javeriana Seccional Cali, Cali, Colombia
| | | | - José Guillermo Ortega-Ávila
- Departamento de Ciencias Básicas, Facultad de Ciencias de la Salud, Pontificia Universidad Javeriana Seccional Cali, Cali, Colombia
| | | | - José Manuel Fernández-Real
- Department of Diabetes, Endocrinology and Nutrition, Institut d'Investigació Biomèdica de Girona (IdIBGi) and Hospital Trueta, Girona, Spain
- CIBERobn Fisiopatología de la Obesidad y Nutrición, Girona, Spain
- Department of Medical Sciences, School of Medicine, University of Girona, Girona, Girona, Spain
| |
Collapse
|
|
21
|
Reid B, East P, Blanco E, Doom J, Burrows R, Correa-Burrows P, Lozoff B, Gahagan S. Early-life adversity is associated with poor iron status in infancy. Dev Psychopathol 2023; 35:1856-1867. [PMID: 35678178 PMCID: PMC9732147 DOI: 10.1017/s0954579422000517] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Exposure to early-life adversity (ELA) and iron deficiency early in life are known risk factors for suboptimal brain and socioemotional development. Iron deficiency may arise from and co-occur with ELA, which could negatively affect development. In the present study, we investigated whether ELA is associated with iron deficiency in infants receiving no iron supplementation. This study is a secondary analysis of extant data collected in the 1990s; participants were healthy infants from working-class communities in Santiago, Chile (N = 534, 45.5% female). We measured stressful life events, maternal depression, and low home support for child development during infancy and assessed iron status when the infant was 12 months old. Slightly more than half of the infants were iron-deficient (51%), and 25.8% were iron-deficient anemic at 12 months. Results indicated that ELA was associated with lower iron levels and iron deficiency at 12 months. The findings are consistent with animal and human prenatal models of stress and iron status and provide evidence of the association between postnatal ELA and iron status in humans. The findings also highlight a nutritional pathway by which ELA may impact development and present a nutritionally-focused avenue for future research on ELA and psychopathology.
Collapse
Affiliation(s)
- B.M. Reid
- Department of Psychiatry and Human Behavior, Warren Alpert Medical School, Brown University, Providence, RI
- Center for Behavioral and Preventive Medicine, The Miriam Hospital, Providence, RI
| | - P. East
- Department of Pediatrics, University of California, San Diego
| | - E. Blanco
- Department of Public Health, School of Medicine, Pontificia Universidad Católica de Chile
| | - J.R. Doom
- Department of Psychology, University of Denver
| | - R.A. Burrows
- Institute of Nutrition and Food Technology, University of Chile, Santiago, Chile
| | - P. Correa-Burrows
- Institute of Nutrition and Food Technology, University of Chile, Santiago, Chile
| | - B. Lozoff
- Department of Pediatrics, University of Michigan, Ann Arbor
| | - S Gahagan
- Department of Pediatrics, University of California, San Diego
| |
Collapse
|
|
22
|
Reid BM, Georgieff MK. The Interaction between Psychological Stress and Iron Status on Early-Life Neurodevelopmental Outcomes. Nutrients 2023; 15:3798. [PMID: 37686831 PMCID: PMC10490173 DOI: 10.3390/nu15173798] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2023] [Revised: 08/18/2023] [Accepted: 08/22/2023] [Indexed: 09/10/2023] Open
Abstract
This review presents evidence from animal and human studies demonstrating the possible connection and significant impact of poor iron status and psychological distress on neurocognitive development during pregnancy and the neonatal period, with implications for long-term cognition. Stress and iron deficiency are independently prevalent and thus are frequently comorbid. While iron deficiency and early-life stress independently contribute to long-term neurodevelopmental alterations, their combined effects remain underexplored. Psychological stress responses may engage similar pathways as infectious stress, which alters fundamental iron metabolism processes and cause functional tissue-level iron deficiency. Psychological stress, analogous to but to a lesser degree than infectious stress, activates the hypothalamic-pituitary-adrenocortical (HPA) axis and increases proinflammatory cytokines. Chronic or severe stress is associated with dysregulated HPA axis functioning and a proinflammatory state. This dysregulation may disrupt iron absorption and utilization, likely mediated by the IL-6 activation of hepcidin, a molecule that impedes iron absorption and redistributes total body iron. This narrative review highlights suggestive studies investigating the relationship between psychological stress and iron status and outlines hypothesized mechanistic pathways connecting psychological stress exposure and iron metabolism. We examine findings regarding the overlapping impacts of early stress exposure to iron deficiency and children's neurocognitive development. We propose that studying the influence of psychological stress on iron metabolism is crucial for comprehending neurocognitive development in children exposed to prenatal and early postnatal stressors and for children at risk of early iron insufficiency. We recommend future directions for dual-exposure studies exploring iron as a potential mediating pathway between early stress and offspring neurodevelopment, offering opportunities for targeted interventions.
Collapse
Affiliation(s)
- Brie M. Reid
- Department of Psychiatry and Human Behavior, Warren Alpert Medical School, Brown University, Providence, RI 02912, USA
- Center for Behavioral and Preventive Medicine, The Miriam Hospital, Providence, RI 02906, USA
| | - Michael K. Georgieff
- Division of Neonatology, Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN 55455, USA;
| |
Collapse
|
|
23
|
Patel S, Yang K, Malik R, Sanchez-Melendez S, Nambudiri VE. Impact of deficiency anaemia comorbidity in generalized pustular psoriasis hospitalizations. Exp Dermatol 2023; 32:1314-1316. [PMID: 36808654 DOI: 10.1111/exd.14771] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Revised: 02/02/2023] [Accepted: 02/11/2023] [Indexed: 02/20/2023]
Affiliation(s)
- Shrey Patel
- Department of Dermatology, Brigham and Women's Hospital, Boston, Massachusetts, USA
| | - Kevin Yang
- Department of Dermatology, Brigham and Women's Hospital, Boston, Massachusetts, USA
| | - Rhea Malik
- Department of Dermatology, Brigham and Women's Hospital, Boston, Massachusetts, USA
| | | | - Vinod E Nambudiri
- Department of Dermatology, Brigham and Women's Hospital, Boston, Massachusetts, USA
| |
Collapse
|
|
24
|
Thompson KN, Bonham KS, Ilott NE, Britton GJ, Colmenero P, Bullers SJ, McIver LJ, Ma S, Nguyen LH, Filer A, Brough I, Pearson C, Moussa C, Kumar V, Lam LH, Jackson MA, Pawluk A, Kiriakidis S, Taylor PC, Wedderburn LR, Marsden B, Young SP, Littman DR, Faith JJ, Pratt AG, Bowness P, Raza K, Powrie F, Huttenhower C. Alterations in the gut microbiome implicate key taxa and metabolic pathways across inflammatory arthritis phenotypes. Sci Transl Med 2023; 15:eabn4722. [PMID: 37494472 DOI: 10.1126/scitranslmed.abn4722] [Citation(s) in RCA: 21] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Accepted: 06/22/2023] [Indexed: 07/28/2023]
Abstract
Musculoskeletal diseases affect up to 20% of adults worldwide. The gut microbiome has been implicated in inflammatory conditions, but large-scale metagenomic evaluations have not yet traced the routes by which immunity in the gut affects inflammatory arthritis. To characterize the community structure and associated functional processes driving gut microbial involvement in arthritis, the Inflammatory Arthritis Microbiome Consortium investigated 440 stool shotgun metagenomes comprising 221 adults diagnosed with rheumatoid arthritis, ankylosing spondylitis, or psoriatic arthritis and 219 healthy controls and individuals with joint pain without an underlying inflammatory cause. Diagnosis explained about 2% of gut taxonomic variability, which is comparable in magnitude to inflammatory bowel disease. We identified several candidate microbes with differential carriage patterns in patients with elevated blood markers for inflammation. Our results confirm and extend previous findings of increased carriage of typically oral and inflammatory taxa and decreased abundance and prevalence of typical gut clades, indicating that distal inflammatory conditions, as well as local conditions, correspond to alterations to the gut microbial composition. We identified several differentially encoded pathways in the gut microbiome of patients with inflammatory arthritis, including changes in vitamin B salvage and biosynthesis and enrichment of iron sequestration. Although several of these changes characteristic of inflammation could have causal roles, we hypothesize that they are mainly positive feedback responses to changes in host physiology and immune homeostasis. By connecting taxonomic alternations to functional alterations, this work expands our understanding of the shifts in the gut ecosystem that occur in response to systemic inflammation during arthritis.
Collapse
Affiliation(s)
- Kelsey N Thompson
- Department of Biostatistics, T. H. Chan School of Public Health, Harvard University, Boston, MA 02115, USA
- Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
- Harvard Chan Microbiome in Public Health Center, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA
| | - Kevin S Bonham
- Department of Biostatistics, T. H. Chan School of Public Health, Harvard University, Boston, MA 02115, USA
- Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
| | - Nicholas E Ilott
- Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedic, Rheumatology and Musculoskeletal Sciences, Oxford University, Oxford OX3 7FY, UK
| | - Graham J Britton
- Marc and Jennifer Lipschultz Precision Immunology Institute and Department of Genetics and Genomic Science, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Paula Colmenero
- Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedic, Rheumatology and Musculoskeletal Sciences, Oxford University, Oxford OX3 7FY, UK
| | - Samuel J Bullers
- Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedic, Rheumatology and Musculoskeletal Sciences, Oxford University, Oxford OX3 7FY, UK
| | - Lauren J McIver
- Department of Biostatistics, T. H. Chan School of Public Health, Harvard University, Boston, MA 02115, USA
- Harvard Chan Microbiome in Public Health Center, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA
| | - Siyuan Ma
- Department of Biostatistics, T. H. Chan School of Public Health, Harvard University, Boston, MA 02115, USA
- Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
| | - Long H Nguyen
- Department of Biostatistics, T. H. Chan School of Public Health, Harvard University, Boston, MA 02115, USA
- Harvard Chan Microbiome in Public Health Center, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
| | - Andrew Filer
- Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Queen Elizabeth Hospital, Birmingham B15 2TT, UK
- MRC Versus Arthritis Centre for Musculoskeletal Ageing Research and Research Into Inflammatory Arthritis Centre Versus Arthritis, University of Birmingham, Chesterfield S41 7TD, UK
| | - India Brough
- Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedic, Rheumatology and Musculoskeletal Sciences, Oxford University, Oxford OX3 7FY, UK
- Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford OX3 7LD, UK
| | - Claire Pearson
- Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedic, Rheumatology and Musculoskeletal Sciences, Oxford University, Oxford OX3 7FY, UK
| | - Caroline Moussa
- Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedic, Rheumatology and Musculoskeletal Sciences, Oxford University, Oxford OX3 7FY, UK
| | - Vinod Kumar
- Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedic, Rheumatology and Musculoskeletal Sciences, Oxford University, Oxford OX3 7FY, UK
| | - Lilian H Lam
- Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedic, Rheumatology and Musculoskeletal Sciences, Oxford University, Oxford OX3 7FY, UK
| | - Matthew A Jackson
- Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedic, Rheumatology and Musculoskeletal Sciences, Oxford University, Oxford OX3 7FY, UK
| | - April Pawluk
- Department of Biostatistics, T. H. Chan School of Public Health, Harvard University, Boston, MA 02115, USA
- Harvard Chan Microbiome in Public Health Center, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA
| | - Serafim Kiriakidis
- Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford OX3 7LD, UK
| | - Peter C Taylor
- Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford OX3 7LD, UK
| | - Lucy R Wedderburn
- Centre for Adolescent Rheumatology Versus Arthritis, University College London, UCLH, and GOSH, Chesterfield S41 7TD, UK
- NIHR Great Ormond Street Biomedical Research Centre, University College London, London WC1N 1EH, UK
- UCL GOS Institute of Child Health, University College London, London WC1N 1EH, UK
| | - Brian Marsden
- Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedic, Rheumatology and Musculoskeletal Sciences, Oxford University, Oxford OX3 7FY, UK
| | - Stephen P Young
- Department of Rheumatology, Sandwell & West Birmingham NHS Trust, West Bromwich B71 4HJ, UK
| | - Dan R Littman
- Howard Hughes Medical Institute and the Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA
| | - Jeremiah J Faith
- Marc and Jennifer Lipschultz Precision Immunology Institute and Department of Genetics and Genomic Science, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Arthur G Pratt
- Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne NE2 4HH, UK
- Research into Inflammatory Arthritis Centre Versus Arthritis, Newcastle Birmingham, Glasgow, and Oxford, Chesterfield S41 7TD, UK
- Department of Rheumatology, Musculoskeletal Services Directorate, Newcastle upon Tyne Hospitals NHS Trust, Newcastle upon Tyne NE7 7DN, UK
| | - Paul Bowness
- Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford OX3 7LD, UK
| | - Karim Raza
- Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Queen Elizabeth Hospital, Birmingham B15 2TT, UK
- MRC Versus Arthritis Centre for Musculoskeletal Ageing Research and Research Into Inflammatory Arthritis Centre Versus Arthritis, University of Birmingham, Chesterfield S41 7TD, UK
- Department of Rheumatology, Sandwell & West Birmingham NHS Trust, West Bromwich B71 4HJ, UK
| | - Fiona Powrie
- Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedic, Rheumatology and Musculoskeletal Sciences, Oxford University, Oxford OX3 7FY, UK
| | - Curtis Huttenhower
- Department of Biostatistics, T. H. Chan School of Public Health, Harvard University, Boston, MA 02115, USA
- Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
- Harvard Chan Microbiome in Public Health Center, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA
- Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA
| |
Collapse
|
|
25
|
Park JY, Kang OJ, Lee YY, Kim YS. A prospective randomized controlled trial evaluating the safety and efficacy of patient blood management program in patients with gynecologic cancer (KGOG 4011/PBM). Int J Gynecol Cancer 2023; 33:1140-1144. [PMID: 37094968 PMCID: PMC10359505 DOI: 10.1136/ijgc-2023-004403] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/30/2023] [Indexed: 04/26/2023] Open
Abstract
BACKGROUND Gynecologic cancer has a high frequency of anemia, which is associated with increased morbidity and mortality. Blood transfusion is used to correct anemia, but carries its own side effects and problems in the blood supply have been emerging. As such, methods other than transfusion are needed to correct anemia in patients with cancer. PRIMARY OBJECTIVE To determine whether intravenous administration of high-dose iron supplements before and after surgery as a patient blood management program is helpful in correcting anemia and reducing the frequency of transfusion in patients with gynecologic cancer. STUDY HYPOTHESIS Patient blood management will reduce the transfusion rate by up to 25%. TRIAL DESIGN This prospective, multicenter, interventional, randomized controlled study will consist of three steps. In step 1, the safety and effectiveness of patient blood management for surgical patients before, during, and after surgery will be evaluated. In steps 2 and 3, the safety and effectiveness of patient blood management in patients before, during, and after adjuvant radiation therapy and chemotherapy will be evaluated. MAJOR INCLUSION/EXCLUSION CRITERIA Patients who are diagnosed with gynecologic cancer (ie, endometrial cancer, cervical cancer, ovarian cancer) and scheduled for surgery will be included and their iron deficiency status will be assessed. Only those with a pre-operative hemoglobin level of 7 g/dL or higher will be included. Patients who underwent neoadjuvant chemotherapy or pre-operative radiation therapy will be excluded. Also, patients with serum ferritin >800 ng/mL or transferrin saturation >50% on serum iron panel tests will be excluded. PRIMARY ENDPOINT Rate of transfusion within 3 weeks after surgery. SAMPLE SIZE Eligible participants will be randomly assigned in a 1:1 ratio (167 patients each) into the patient blood management group and the conventional management group. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS Patient recruitment will be completed by mid-2025, and management and follow-up will be completed by the end of 2025. TRIAL REGISTRATION NUMBER NCT05669872.
Collapse
Affiliation(s)
- Jeong-Yeol Park
- Department of Obstetrics and Gynecology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea (the Republic of)
| | - Ok Ju Kang
- Department of Obstetrics and Gynecology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea (the Republic of)
| | - Yoo-Young Lee
- Department of Obstetrics and Gyneoology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea (the Republic of)
| | - Young Seok Kim
- Department of Radiation Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea (the Republic of)
| |
Collapse
|
|
26
|
Hayashi I, Sakane N, Suganuma A, Nagai N. Association of a pro-inflammatory diet and gestational diabetes mellitus with maternal anemia and hemoglobin levels during pregnancy: a prospective observational case-control study. Nutr Res 2023; 115:38-46. [PMID: 37295325 DOI: 10.1016/j.nutres.2023.05.003] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2022] [Revised: 05/11/2023] [Accepted: 05/11/2023] [Indexed: 06/12/2023]
Abstract
Anemia is prevalent in pregnant women, and the causes include inadequate diet, increased demand for iron, and inflammation. We hypothesized that gestational diabetes mellitus (GDM) and hepcidin-related gene polymorphisms may contribute to maternal anemia and that an anti-inflammatory diet can alleviate this negative effect. The aim of this study was to investigate the association of an inflammatory diet, GDM, and single nucleotide polymorphisms (SNPs) in hepcidin-related genes, which are key regulators of iron, with maternal anemia. This was a secondary data analysis of a prospective prenatal diet and pregnancy outcome study in Japan. The Energy-Adjusted Dietary Inflammatory Index was calculated using a brief self-administered diet history questionnaire. We analyzed 121 SNPs in 4 genes: TMPRS6 (43 SNPs), TF (39 SNPs), HFE (15 SNPs), and MTHFR (24 SNPs). Multivariate regression analysis was conducted to determine the association between the first variable and maternal anemia. The prevalence of anemia in first, second, and third trimesters were 5.4%, 34.9%, and 45.8%, respectively. The pregnant women with GDM had a significantly higher incidence of moderate anemia than those without GDM (40.0% vs. 11.4%, P = .029). In multivariate regression analysis, Energy-adjusted Dietary Inflammatory Index (β = -0.057, P = .011) and GDM (β = -0.657, P = .037) were significantly associated with hemoglobin levels during the third trimester. Using Stata's qtlsnp command, TMPRSS6 rs2235321 was found to be associated with hemoglobin levels during the third trimester. These results indicate that inflammatory diets, GDM, and TMPRSS6 rs2235321 polymorphism are associated with maternal anemia. This result suggests that a pro-inflammatory diet and GDM are associated with maternal anemia.
Collapse
Affiliation(s)
- Ikuyo Hayashi
- Division of Preventive Medicine, Clinical Research Institute, National Hospital Organization Kyoto Medical Center, Kyoto, Japan; Department of Food and Nutrition Faculty of Contemporary Home Economics, Kyoto Kacho University, Kyoto, Japan.
| | - Naoki Sakane
- Division of Preventive Medicine, Clinical Research Institute, National Hospital Organization Kyoto Medical Center, Kyoto, Japan
| | - Akiko Suganuma
- Division of Preventive Medicine, Clinical Research Institute, National Hospital Organization Kyoto Medical Center, Kyoto, Japan
| | - Narumi Nagai
- Graduate School of Human Science and Environment, University of Hyogo, Himeji, Japan
| |
Collapse
|
|
27
|
Liu X, Liang Y, Shen Z, Wei L, Yang J, Piao Y, Sang W, Li P, Wang L. A novel prognostic model based on ferritin and nomogram-revised risk index could better stratify patients with extranodal natural killer/T-cell lymphoma. Cancer Med 2023; 12:10660-10671. [PMID: 36924334 PMCID: PMC10225229 DOI: 10.1002/cam4.5820] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2022] [Revised: 02/08/2023] [Accepted: 03/07/2023] [Indexed: 03/18/2023] Open
Abstract
BACKGROUND Extranodal natural killer (NK)/T-cell lymphoma (ENKTCL) is an aggressive lymphoma with marked heterogeneity, resulting in a distinct prognosis even in patients with the same disease stage. The nomogram-revised risk index (NRI) has been proposed to stratify patients with ENKTCL. Numerous reports have revealed the prognostic role of serum ferritin in various cancers. PURPOSE We aimed to evaluate the role of NRI in our single cohort of patients with ENKTCL treated uniformly, explore the prognostic value of ferritin, and establish a new prognostic model to better stratify patients with ENKTCL. METHODS We included 326 patients with ENKTCL with detailed data regarding clinical characteristics and survival outcomes. All patients were treated with asparaginase-based chemotherapy with or without radiotherapy. Multiple R packages were used to analyze the prognostic factors and derive a novel prognostic model. RESULTS In the training cohort comprising 236 patients with ENKTCL, NRI significantly correlated with progression-free survival (PFS) and overall survival (p < 0.0001). Using a ferritin level of 400 μg/L as the cutoff value, patients with high ferritin levels had significantly inferior PFS (p = 0.00028). Integrating the NRI score and four easily accessible clinical parameters, namely ferritin, hemoglobin, albumin, and D-dimer, a new prognostic model was constructed, stratifying patients with ENKTCL into three risk groups. This new prognostic model was independent of disease stage and NRI and performed better than NRI. Furthermore, this model helped to stratify patients within the same NRI risk groups. Finally, the role of this novel prognostic model was validated in the external validation cohort comprising 90 patients with ENKTCL. CONCLUSIONS Serum ferritin level could be a novel prognostic factor in patients with ENKTCL. The new prognostic model combining NRI and clinical parameters could better predict the prognosis of ENKTCL, thereby warranting further validation and potentially guiding individualized treatment in future prospective clinical trials.
Collapse
Affiliation(s)
- Xindi Liu
- Department of Hematology, Beijing TongRen HospitalCapital Medical UniversityBeijingChina
| | - Yuanzheng Liang
- Department of Hematology, Beijing TongRen HospitalCapital Medical UniversityBeijingChina
| | - Ziyuan Shen
- Department of Epidemiology and Biostatistics, School of Public HealthAnhui Medical UniversityHefeiChina
| | - Liqiang Wei
- Department of Hematology, Beijing TongRen HospitalCapital Medical UniversityBeijingChina
| | - Jing Yang
- Department of Hematology, Beijing TongRen HospitalCapital Medical UniversityBeijingChina
| | - Yingshi Piao
- Department of Pathology, Beijing TongRen HospitalCapital Medical UniversityBeijingChina
- Beijing Key Laboratory of Head and Neck Molecular Diagnostic Pathology, Beijing TongRen HospitalCapital Medical UniversityBeijingChina
| | - Wei Sang
- Department of HematologyAffiliated Hospital of Xuzhou Medical UniversityXuzhouChina
| | - Pengfei Li
- Department of Oncology, Cancer Center, Integrated Hospital of Traditional Chinese MedicineSouthern Medical UniversityGuangzhouChina
| | - Liang Wang
- Department of Hematology, Beijing TongRen HospitalCapital Medical UniversityBeijingChina
| |
Collapse
|
|
28
|
Lee J, Hyun DH. The Interplay between Intracellular Iron Homeostasis and Neuroinflammation in Neurodegenerative Diseases. Antioxidants (Basel) 2023; 12:antiox12040918. [PMID: 37107292 PMCID: PMC10135822 DOI: 10.3390/antiox12040918] [Citation(s) in RCA: 51] [Impact Index Per Article: 25.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Revised: 03/23/2023] [Accepted: 04/07/2023] [Indexed: 04/29/2023] Open
Abstract
Iron is essential for life. Many enzymes require iron for appropriate function. However, dysregulation of intracellular iron homeostasis produces excessive reactive oxygen species (ROS) via the Fenton reaction and causes devastating effects on cells, leading to ferroptosis, an iron-dependent cell death. In order to protect against harmful effects, the intracellular system regulates cellular iron levels through iron regulatory mechanisms, including hepcidin-ferroportin, divalent metal transporter 1 (DMT1)-transferrin, and ferritin-nuclear receptor coactivator 4 (NCOA4). During iron deficiency, DMT1-transferrin and ferritin-NCOA4 systems increase intracellular iron levels via endosomes and ferritinophagy, respectively. In contrast, repleting extracellular iron promotes cellular iron absorption through the hepcidin-ferroportin axis. These processes are regulated by the iron-regulatory protein (IRP)/iron-responsive element (IRE) system and nuclear factor erythroid 2-related factor 2 (Nrf2). Meanwhile, excessive ROS also promotes neuroinflammation by activating the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). NF-κB forms inflammasomes, inhibits silent information regulator 2-related enzyme 1 (SIRT1), and induces pro-inflammatory cytokines (IL-6, TNF-α, and IL-1β). Furthermore, 4-hydroxy-2,3-trans-nonenal (4-HNE), the end-product of ferroptosis, promotes the inflammatory response by producing amyloid-beta (Aβ) fibrils and neurofibrillary tangles in Alzheimer's disease, and alpha-synuclein aggregation in Parkinson's disease. This interplay shows that intracellular iron homeostasis is vital to maintain inflammatory homeostasis. Here, we review the role of iron homeostasis in inflammation based on recent findings.
Collapse
Affiliation(s)
- Jaewang Lee
- Department of Life Science, Ewha Womans University, Seoul 03760, Republic of Korea
| | - Dong-Hoon Hyun
- Department of Life Science, Ewha Womans University, Seoul 03760, Republic of Korea
| |
Collapse
|
|
29
|
Abioye AI, Hughes MD, Sudfeld CR, Premji Z, Aboud S, Hamer DH, Roberts DJ, Duggan CP, Fawzi WW. The effect of iron supplementation on maternal iron deficiency anemia does not differ by baseline anemia type among Tanzanian pregnant women without severe iron deficiency anemia. Eur J Nutr 2023; 62:987-1001. [PMID: 36344770 PMCID: PMC9987582 DOI: 10.1007/s00394-022-03029-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2022] [Accepted: 10/05/2022] [Indexed: 11/10/2022]
Abstract
PURPOSE Whether anemia type modifies the risk of pregnancy and newborn outcomes and the effectiveness of iron supplementation is unclear. We examined the association of iron deficiency anemia (IDA) and non-iron deficiency anemia (NIDA) on the risks of these outcomes and the extent to which anemia type modifies the impact of prenatal iron supplementation. METHODS This was a secondary analysis of a placebo-controlled trial of iron supplementation among 1450 HIV-negative women in Tanzania. Eligibility criteria included gestational age < 27 weeks, hemoglobin > 85 g/L, and ferritin > 12 µg/L. Individuals were categorized as non-anemia, IDA or NIDA using hemoglobin, ferritin and CRP. Analyses were conducted using regression models and likelihood ratio tests. RESULTS Compared to the non-anemia group, delivery hemoglobin was lower by 15 g/L (95% CI 10.9, 19.3) in the baseline IDA group, and 7.3 g/L (95% CI 3.1, 11.5) in the baseline NIDA group. The RRs of anemia severity, iron deficiency, placental malaria, stillbirths, perinatal mortality, birthweight, and preterm birth were not different among women in the baseline NIDA group (vs. non-anemia) compared to the baseline IDA group (vs. non-anemia). The difference in the mean delivery hemoglobin for iron supplementation and placebo arms was 8 g/L (95% CI 6, 11) in the non-anemia group, 7 g/L (95% CI 2, 13) in the NIDA group, and 16 g/L (95% CI 10, 22) in the IDA group. CONCLUSION Iron supplementation is effective even among pregnant women with NIDA. TRIAL REGISTRATION NCT01119612 (May 7, 2010).
Collapse
Affiliation(s)
- Ajibola Ibraheem Abioye
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Harvard T.H. School of Public Health, 677 Huntington Ave, Boston, MA, 02115, USA.
| | - Michael D Hughes
- Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Christopher R Sudfeld
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Harvard T.H. School of Public Health, 677 Huntington Ave, Boston, MA, 02115, USA
- Department of Global Health and Population, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | | | - Said Aboud
- Department of Microbiology and Immunology, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania
| | - Davidson H Hamer
- Department of Global Health, School of Public Health, Boston University, Boston, MA, USA
- Section of Infectious Diseases, Department of Medicine, Boston University School of Medicine, Boston, MA, USA
- Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA, USA
| | - Drucilla J Roberts
- Department of Pathology, Massachusetts General Hospital, Boston, MA, USA
| | - Christopher P Duggan
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Harvard T.H. School of Public Health, 677 Huntington Ave, Boston, MA, 02115, USA
- Department of Global Health and Population, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, MA, USA
| | - Wafaie W Fawzi
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Harvard T.H. School of Public Health, 677 Huntington Ave, Boston, MA, 02115, USA
- Department of Global Health and Population, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| |
Collapse
|
|
30
|
Szczerba K, Stokowa-Soltys K. What Is the Correlation between Preeclampsia and Cancer? The Important Role of Tachykinins and Transition Metal Ions. Pharmaceuticals (Basel) 2023; 16:366. [PMID: 36986466 PMCID: PMC10058266 DOI: 10.3390/ph16030366] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2022] [Revised: 02/09/2023] [Accepted: 02/24/2023] [Indexed: 03/06/2023] Open
Abstract
Metal ions are irreplaceable in many biological processes. They are components of numerous metalloproteins and serve as cofactors or structural elements for enzymes. Interestingly, iron, copper and zinc play important roles in accelerating or preventing neoplastic cell transformation. Noteworthily, a lot of proliferative and invasive mechanisms are exploited by both malignant tumors and pregnancy. Cancer cells, as well as developing placenta cells, create a microenvironment supportive of immunologic privilege and angiogenesis. Therefore, pregnancy and cancer progression share many similarities. Moreover, during preeclampsia and cancer, significant changes in relevant trace element concentrations, tachykinin levels, expressions of neurokinin receptors, oxidative stress and angiogenic imbalance are observed. This sheds a new light on the role of metal ions and tachykinins in cancer progression and pregnancy, especially in preeclamptic women.
Collapse
Affiliation(s)
| | - Kamila Stokowa-Soltys
- Faculty of Chemistry, University of Wroclaw, F. Joliot-Curie 14, 50-383 Wroclaw, Poland
| |
Collapse
|
|
31
|
Doherty JL, Larvie DY, Shivappa N, Hebert JR, Armah SM. Inflammatory diets are associated with lower total iron binding capacity in sera of young adults. INT J VITAM NUTR RES 2023; 93:9-17. [PMID: 33593088 DOI: 10.1024/0300-9831/a000697] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
Chronic, systemic inflammation, which is associated with obesity and numerous other diseases, impairs iron status by increasing hepcidin concentration. Inflammation also decreases the concentration of transferrin, the main iron transport protein and a negative acute phase protein, which is indirectly assessed by measuring total iron binding capacity (TIBC). However, the contribution of diet-induced inflammation has not been studied. Data from two studies, namely Diet and Inflammation and Selenium and Inflammation Studies (total n=98) were used to assess the associations among Dietary Inflammatory Index (DII®) scores derived from three-day dietary records, body mass index (BMI=weight[kg]/height[m]2), inflammatory and hematological markers among young adults with normal-weight, overweight or obesity. Subjects' diets were also categorized as less inflammatory diets (LID) and inflammatory diets (ID) using cluster analysis. Independent t-test and regression analyses were used to assess associations in the data. Intakes of iron, proteins, fat, fiber, and calories were higher in the LID group compared to the ID group (p<0.05). Demographic characteristics and concentrations of C-reactive protein (CRP) and iron status biomarkers did not differ significantly between the two groups (p>0.05). Higher DII score was associated with increasing CRP (β+SE=0.23+0.07, p=0.002) and lower TIBC (β+SE=-8.46+3.44, p=0.02), independent of BMI category. The LID diet was associated with higher TIBC (β+SE=29.87+10.75, p=0.007) compared to the ID diet. In conclusion, inflammatory diets may impair iron status by reducing the iron binding capacity of transferrin.
Collapse
Affiliation(s)
- Jeanne L Doherty
- Department of Nutrition, University of North Carolina at Greensboro, Greensboro, USA
| | - Doreen Y Larvie
- Department of Nutrition, University of North Carolina at Greensboro, Greensboro, USA
| | - Nitin Shivappa
- Cancer Prevention and Control Program and the Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, USA.,Department of Nutrition, Connecting Health Innovations LLC, Columbia, USA
| | - James R Hebert
- Cancer Prevention and Control Program and the Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, USA.,Department of Nutrition, Connecting Health Innovations LLC, Columbia, USA
| | - Seth M Armah
- Department of Nutrition, University of North Carolina at Greensboro, Greensboro, USA
| |
Collapse
|
|
32
|
Tang Y, Ge S, Zheng X, Zheng J. High Hepcidin expression predicts poor prognosis in patients with clear cell renal cell carcinoma. Diagn Pathol 2022; 17:100. [PMID: 36585741 PMCID: PMC9805116 DOI: 10.1186/s13000-022-01274-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2022] [Accepted: 12/19/2022] [Indexed: 01/01/2023] Open
Abstract
Clear cell renal cell carcinoma (ccRCC) is a growing public health challenge worldwide. Hepcidin antimicrobial peptide (HAMP) is differentially expressed in various tumors. However, the roles and functions of HAMP in ccRCC remain unclear. In the present study, we integrated systematic bioinformatics approaches to investigate the roles and functions of HAMP and its association with immune cell infiltration in ccRCC. Compared with paracancerous tissue, HAMP expression was significantly upregulated in ccRCC patients. Meanwhile, we found good diagnostic performance of HAMP for ccRCC patients and its close associations with the clinicopathological features of ccRCC patients. In addition, we found that HAMP is closely related to multiple immune pathways and positively correlated with various immune cells. HAMP was a significant independent predictor for ccRCC. High expression of HAMP was associated with worse clinical prognosis and more immune cell infiltration in ccRCC patients. HAMP may offer potential as a biomarker to predict prognosis and the clinical treatment outcome of ccRCC patients.
Collapse
Affiliation(s)
- Yuting Tang
- grid.412540.60000 0001 2372 7462Department of Rehabilitation, Municipal Hospital of Traditional Chinese Medicine, Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 200071 People’s Republic of China
| | - Shengdong Ge
- grid.284723.80000 0000 8877 7471Department of Urology, The First School of Clinical Medicine, Nanfang Hospital, Southern Medical University, Southern Medical University, Guangzhou, China
| | - Xiao Zheng
- grid.412540.60000 0001 2372 7462Department of Rehabilitation, Municipal Hospital of Traditional Chinese Medicine, Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 200071 People’s Republic of China
| | - Jiejiao Zheng
- grid.413597.d0000 0004 1757 8802Department of Rehabilitation, HuaDong Hospital, FuDan University, Shanghai, 200040 People’s Republic of China
| |
Collapse
|
|
33
|
Patel S, Patel S, Shah S, Lio PA. Identifying prevalence and inpatient outcomes of anemia and hidradenitis suppurativa. Arch Dermatol Res 2022; 315:1287-1291. [DOI: 10.1007/s00403-022-02515-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2022] [Revised: 12/06/2022] [Accepted: 12/12/2022] [Indexed: 12/24/2022]
|
|
34
|
Yadav D, Pvsn KK, Tomo S, Sankanagoudar S, Charan J, Purohit A, Nag V, Bhatia P, Singh K, Dutt N, Garg MK, Sharma P, Misra S, Purohit P. Association of iron-related biomarkers with severity and mortality in COVID-19 patients. J Trace Elem Med Biol 2022; 74:127075. [PMID: 36174458 PMCID: PMC9472468 DOI: 10.1016/j.jtemb.2022.127075] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2022] [Revised: 09/02/2022] [Accepted: 09/12/2022] [Indexed: 01/08/2023]
Abstract
BACKGROUND Nutritional deficiency is associated with weaken immune system and increased susceptibility to infection. Among other nutrients, several trace elements have been shown to regulate immune responses. Iron is one of the most abundant trace elements present in our body, which is required in various biological processes. Iron has an immunomodulatory function and thus influence the susceptibility to the course and outcome of a variety of viral infections. So, this present study was aimed to study relations of different iron-related biomarkers in association to severity and mortality in SARS-CoV-2 patients. MATERIALS AND METHODS A total of 150 individuals infected with COVID-19 and 50 healthy individuals were recruited. Cases were divided based on severity (mild, moderate, and severe) and outcome (discharged or deceased). Serum iron, TIBC, ferritin, transferrin, transferrin saturation levels were analyzed by the direct colourimetric method. RESULTS In cases the median levels of serum iron, TIBC, transferrin, transferrin saturation and ferritin are 29 µg/dL, 132.53 µg/dL, 106.3 mg/dL, 17.74 % and 702.9 ng/dL respectively. Similarly, in controls the median levels of serum iron, TIBC, transferrin, transferrin saturation and ferritin are 53 µg/dL, 391.88 µg/dL, 313.51 mg/dL, 12.81 % and 13.52 ng/dL respectively. On comparing the cases with the controls, a significant lower level of iron, TIBC, and transferrin were found in the cases along with the significant higher levels of ferritin and transferrin saturation. On comparing the Receiver operating characteristic (ROC) curves of Iron, Ferritin, Transferrin, Transferrin sat % and TIBC in relation to survival in COVID-19 patients it was found that iron, followed by transferrin and ferritin has the highest area under the curve (AUC) with 74 %, 63 % and 61 % respectively. Further, in pairwise analysis of ROC curve, a significant difference was found between the Iron-transferrin (p < 0.01), iron-TIBC (p < 0.001) and transferrin-ferritin (P < 0.01). The multiple regression model based on Iron and transferrin outperformed any other combination of variables via stepwise AIC selection with an AUC of 98.2 %. The cutoff point according to Youden's J index is characterized with a sensitivity of 98 % and a specificity of 96.8 %, indicating that iron along with transferrin can be a useful marker that may contribute to a better assessment of survival chances in COVID-19. CONCLUSION Our study demonstrated a significantly decreased levels of iron, TIBC, & transferrin and a significantly increased levels of ferritin and transferrin saturation in COVID-19 patients when compared with controls. Further, Iron and transferrin were observed to be a good predictor of mortality in patients with COVID-19. From the above analysis we confirm that iron-related biomarkers play an important role in the development of oxidative stress and further lead to activation of the cytokine storm. So, continuous monitoring of these parameters could be helpful in the early detection of individuals developing the severe disease and can be used to decrease mortality in upcoming new waves of COVID-19.
Collapse
Affiliation(s)
- Dharamveer Yadav
- Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, India
| | - Kiran Kumar Pvsn
- Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, India
| | - Sojit Tomo
- Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, India
| | | | - Jayakaran Charan
- Department of Pharmacology, All India Institute of Medical Sciences, Jodhpur, India
| | - Abhishek Purohit
- Department of Pathology, All India Institute of Medical Sciences, Jodhpur, India
| | - Vijaylakshami Nag
- Department of Microbiology, All India Institute of Medical Sciences, Jodhpur, India
| | - Pradeep Bhatia
- Department of Anaesthesia, All India Institute of Medical Sciences, Jodhpur, India
| | - Kuldeep Singh
- Department of Paediatrics, All India Institute of Medical Sciences, Jodhpur, India
| | - Naveen Dutt
- Department of Pulmonary Medicine, All India Institute of Medical Sciences, Jodhpur, India
| | - Mahendra Kumar Garg
- Department of General Medicine, All India Institute of Medical Sciences, Jodhpur, India
| | - Praveen Sharma
- Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, India
| | - Sanjeev Misra
- Department of Surgical Oncology, Director and CEO, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
| | - Purvi Purohit
- Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, India.
| |
Collapse
|
|
35
|
Stoudenmire JL, Greenawalt AN, Cornelissen CN. Stealthy microbes: How Neisseria gonorrhoeae hijacks bulwarked iron during infection. Front Cell Infect Microbiol 2022; 12:1017348. [PMID: 36189345 PMCID: PMC9519893 DOI: 10.3389/fcimb.2022.1017348] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2022] [Accepted: 08/30/2022] [Indexed: 11/13/2022] Open
Abstract
Transition metals are essential for metalloprotein function among all domains of life. Humans utilize nutritional immunity to limit bacterial infections, employing metalloproteins such as hemoglobin, transferrin, and lactoferrin across a variety of physiological niches to sequester iron from invading bacteria. Consequently, some bacteria have evolved mechanisms to pirate the sequestered metals and thrive in these metal-restricted environments. Neisseria gonorrhoeae, the causative agent of the sexually transmitted infection gonorrhea, causes devastating disease worldwide and is an example of a bacterium capable of circumventing human nutritional immunity. Via production of specific outer-membrane metallotransporters, N. gonorrhoeae is capable of extracting iron directly from human innate immunity metalloproteins. This review focuses on the function and expression of each metalloprotein at gonococcal infection sites, as well as what is known about how the gonococcus accesses bound iron.
Collapse
Affiliation(s)
| | | | - Cynthia Nau Cornelissen
- Center for Translational Immunology, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, United States
| |
Collapse
|
|
36
|
Neglected Comorbidity of Chronic Heart Failure: Iron Deficiency. Nutrients 2022; 14:nu14153214. [PMID: 35956390 PMCID: PMC9370238 DOI: 10.3390/nu14153214] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2022] [Revised: 08/01/2022] [Accepted: 08/02/2022] [Indexed: 11/17/2022] Open
Abstract
Iron deficiency is a significant comorbidity of heart failure (HF), defined as the inability of the myocardium to provide sufficient blood flow. However, iron deficiency remains insufficiently detected. Iron-deficiency anemia, defined as a decrease in hemoglobin caused by iron deficiency, is a late consequence of iron deficiency, and the symptoms of iron deficiency, which are not specific, are often confused with those of HF or comorbidities. HF patients with iron deficiency are often rehospitalized and present reduced survival. The correction of iron deficiency in HF patients is associated with improved functional capacity, quality of life, and rehospitalization rates. Because of the inflammation associated with chronic HF, which complicates the picture of nutritional deficiency, only the parenteral route can bypass the tissue sequestration of iron and the inhibition of intestinal iron absorption. Given the negative impact of iron deficiency on HF progression, the frequency and financial implications of rehospitalizations due to decompensation episodes, and the efficacy of this supplementation, screening for this frequent comorbidity should be part of routine testing in all HF patients. Indeed, recent European guidelines recommend screening for iron deficiency (serum ferritin and transferrin saturation coefficient) in all patients with suspected HF, regular iron parameters assessment in all patients with HF, and intravenous iron supplementation in symptomatic patients with proven deficiency. We thus aim to summarize all currently available data regarding this common and easily improvable comorbidity.
Collapse
|
|
37
|
A Nano Erythropoiesis Stimulating Agent (Nano-ESA) for the Treatment of Anemia and Associated Disorders. iScience 2022; 25:105021. [PMID: 36111254 PMCID: PMC9468392 DOI: 10.1016/j.isci.2022.105021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2022] [Revised: 06/20/2022] [Accepted: 08/19/2022] [Indexed: 11/24/2022] Open
|
|
38
|
Emerging Roles of the Iron Chelators in Inflammation. Int J Mol Sci 2022; 23:ijms23147977. [PMID: 35887336 PMCID: PMC9318075 DOI: 10.3390/ijms23147977] [Citation(s) in RCA: 44] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2022] [Revised: 07/13/2022] [Accepted: 07/14/2022] [Indexed: 02/06/2023] Open
Abstract
Iron is a crucial element for mammalian cells, considering its intervention in several physiologic processes. Its homeostasis is finely regulated, and its alteration could be responsible for the onset of several disorders. Iron is closely related to inflammation; indeed, during inflammation high levels of interleukin-6 cause an increased production of hepcidin which induces a degradation of ferroportin. Ferroportin degradation leads to decreased iron efflux that culminates in elevated intracellular iron concentration and consequently iron toxicity in cells and tissues. Therefore, iron chelation could be considered a novel and useful therapeutic strategy in order to counteract the inflammation in several autoimmune and inflammatory diseases. Several iron chelators are already known to have anti-inflammatory effects, among them deferiprone, deferoxamine, deferasirox, and Dp44mT are noteworthy. Recently, eltrombopag has been reported to have an important role in reducing inflammation, acting both directly by chelating iron, and indirectly by modulating iron efflux. This review offers an overview of the possible novel biological effects of the iron chelators in inflammation, suggesting them as novel anti-inflammatory molecules.
Collapse
|
|
39
|
Kumar SB, Arnipalli SR, Mehta P, Carrau S, Ziouzenkova O. Iron Deficiency Anemia: Efficacy and Limitations of Nutritional and Comprehensive Mitigation Strategies. Nutrients 2022; 14:nu14142976. [PMID: 35889932 PMCID: PMC9315959 DOI: 10.3390/nu14142976] [Citation(s) in RCA: 55] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2022] [Revised: 07/12/2022] [Accepted: 07/13/2022] [Indexed: 12/16/2022] Open
Abstract
Iron deficiency anemia (IDA) has reached epidemic proportions in developing countries and has become a major global public health problem, affecting mainly 0–5-year-old children and young women of childbearing age, especially during pregnancy. Iron deficiency can lead to life-threatening loss of red blood cells, muscle function, and energy production. Therefore, the pathogenic features associated with IDA are weakness and impaired growth, motor, and cognitive performance. IDA affects the well-being of the young generation and the economic advancement of developing countries, such as India. The imbalance between iron intake/absorption/storage and iron utilization/loss culminates into IDA. However, numerous strategic programs aimed to increase iron intake have shown that improvement of iron intake alone has not been sufficient to mitigate IDA. Emerging critical risk factors for IDA include a composition of cultural diets, infections, genetics, inflammatory conditions, metabolic diseases, dysbiosis, and socioeconomic parameters. In this review, we discuss numerous IDA mitigation programs in India and their limitations. The new multifactorial mechanism of IDA pathogenesis opens perspectives for the improvement of mitigation programs and relief of IDA in India and worldwide.
Collapse
|
|
40
|
Nowak R, Rój K, Ciechanowicz A, Lewandowska K, Kostrzewa-Nowak D. Capillary Blood Recovery Variables in Young Swimmers: An Observational Case Study. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:ijerph19148580. [PMID: 35886433 PMCID: PMC9318784 DOI: 10.3390/ijerph19148580] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/28/2022] [Revised: 07/09/2022] [Accepted: 07/12/2022] [Indexed: 11/24/2022]
Abstract
Sport diagnostics is still in pursuit of the optimal combination of biochemical and hematological markers to assess training loads and the effectiveness of recovery. The biochemical and hematological markers selected for a panel should be specific to the sport and training program. Therefore, the aim of this study was to evaluate the usefulness of selected biochemical and hematological variables in professional long-distance and sprint swimming. Twenty-seven participants aged 15–18 years took part in the study. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and alkaline phosphatase (ALP) activities and creatinine (Cr), C-reactive protein (CRP), ferritin, total bilirubin (TB), direct bilirubin (DB) and iron concentrations were measured for 10 weeks and compared with the traditional sport diagnostic markers of creatine kinase (CK) activity and urea (U) concentration. Additionally, capillary blood morphology was analyzed. An effective panel should consist of measurements of CK and AST activities and urea, TB, DB and ferritin concentrations. These markers provide a good overview of athletes’ post-training effort changes, can help assess the effectiveness of their recovery regardless of sex or competitive distance and are affordable. Moreover, changes in ferritin concentration can indicate inflammation status and, when combined with iron concentration and blood morphology, can help to avoid iron deficiencies, anemia and adverse inflammatory states in swimmers.
Collapse
Affiliation(s)
- Robert Nowak
- Institute of Physical Culture Sciences, University of Szczecin, 17C Narutowicza Str., 70-240 Szczecin, Poland;
- Correspondence:
| | - Konrad Rój
- Student of ”Sports Diagnostics”, Faculty of Physical Education and Health, University of Szczecin, 40b Piastów Al., 70-240 Szczecin, Poland;
| | - Andrzej Ciechanowicz
- Department of Clinical and Molecular Biochemistry, Pomeranian Medical University in Szczecin, 72 Powstańców Wlkp. Al., 70-111 Szczecin, Poland; (A.C.); (K.L.)
| | - Klaudyna Lewandowska
- Department of Clinical and Molecular Biochemistry, Pomeranian Medical University in Szczecin, 72 Powstańców Wlkp. Al., 70-111 Szczecin, Poland; (A.C.); (K.L.)
| | - Dorota Kostrzewa-Nowak
- Institute of Physical Culture Sciences, University of Szczecin, 17C Narutowicza Str., 70-240 Szczecin, Poland;
- Department of Clinical and Molecular Biochemistry, Pomeranian Medical University in Szczecin, 72 Powstańców Wlkp. Al., 70-111 Szczecin, Poland; (A.C.); (K.L.)
| |
Collapse
|
|
41
|
Sumaily KM. The Roles and Pathogenesis Mechanisms of a Number of Micronutrients in the Prevention and/or Treatment of Chronic Hepatitis, COVID-19 and Type-2 Diabetes Mellitus. Nutrients 2022; 14:2632. [PMID: 35807813 PMCID: PMC9268086 DOI: 10.3390/nu14132632] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2022] [Revised: 06/18/2022] [Accepted: 06/21/2022] [Indexed: 02/06/2023] Open
Abstract
A trace element is a chemical element with a concentration (or other measures of an amount) that is very low. The essential TEs, such as copper (Cu), selenium (Se), zinc (Zn), iron (Fe) and the electrolyte magnesium (Mg) are among the most commonly studied micronutrients. Each element has been shown to play a distinctive role in human health, and TEs, such as iron (Fe), zinc (Zn) and copper (Cu), are among the essential elements required for the organisms' well-being as they play crucial roles in several metabolic pathways where they act as enzyme co-factors, anti-inflammatory and antioxidant agents. Epidemics of infectious diseases are becoming more frequent and spread at a faster pace around the world, which has resulted in major impacts on the economy and health systems. Different trace elements have been reported to have substantial roles in the pathogenesis of viral infections. Micronutrients have been proposed in various studies as determinants of liver disorders, COVID-19 and T2DM risks. This review article sheds light on the roles and mechanisms of micronutrients in the pathogenesis and prevention of chronic hepatitis B, C and E, as well as Coronavirus-19 infection and type-2 diabetes mellitus. An update on the status of the aforementioned micronutrients in pre-clinical and clinical settings is also briefly summarized.
Collapse
Affiliation(s)
- Khalid M Sumaily
- Clinical Biochemistry Unit, Department of Pathology, College of Medicine, King Saud University, Riyadh P.O. Box 145111, Saudi Arabia
| |
Collapse
|
|
42
|
Ishibashi A, Maeda N, Kojima C, Goto K. Iron Metabolism following Twice a Day Endurance Exercise in Female Long-Distance Runners. Nutrients 2022; 14:nu14091907. [PMID: 35565873 PMCID: PMC9105615 DOI: 10.3390/nu14091907] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2022] [Revised: 04/21/2022] [Accepted: 04/27/2022] [Indexed: 12/04/2022] Open
Abstract
Iron deficiency anemia (IDA) and iron deficiency (ID) are frequently observed among endurance athletes. The iron regulatory hormone hepcidin may be involved in IDA and/or ID. Endurance athletes incorporate multiple training sessions, but the influence of repeated bouts of endurance exercise within the same day on iron metabolism remains unclear. Therefore, the purpose of the present study was to investigate the influence of twice a day endurance exercise on iron metabolism, including the hepcidin level, in female long-distance runners. Thirteen female long-distance runners participated in this study. They completed the twice-a-day endurance exercise in the morning and afternoon. Blood samples were collected four times in total: at 06:00 (P0), 14:00 (P8), 20:00 (P14), and 06:00 the next day (P24). In addition to the blood variables, nutritional intake was assessed throughout the exercise day. Serum hepcidin levels were significantly elevated (compared to P0) until the following morning (P24). Moreover, dietary analysis revealed that subjects consumed a low volume of carbohydrates (<6 g/kg body mass/day). In conclusion, twice a day endurance exercise resulted in significant elevation of serum hepcidin level 24 h after completion of the exercise in female long-distance runners. Therefore, athletes with a high risk of anemia should pay attention to training frequency and nutritional intake in order to maintain optimal iron metabolism.
Collapse
Affiliation(s)
- Aya Ishibashi
- Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, Tokyo 153-8902, Japan;
| | - Naho Maeda
- Graduate School of Sport and Health Science, Ritsumeikan University, Kusatsu 525-8577, Japan;
| | - Chihiro Kojima
- Department of Sports Science, Japan Institute of Sports Science, Tokyo 115-0056, Japan;
| | - Kazushige Goto
- Graduate School of Sport and Health Science, Ritsumeikan University, Kusatsu 525-8577, Japan;
- Correspondence: ; Tel./Fax: +81-77-599-4127
| |
Collapse
|
|
43
|
Evaluation of Serum Iron and Ferritin Levels as Inflammatory Markers in Calves with Bovine Respiratory Disease Complex. ACTA VET-BEOGRAD 2022. [DOI: 10.2478/acve-2022-0005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Abstract
Iron and ferritin have been used in human medicine for years to reveal the presence of inflammation. However, studies evaluating these parameters, especially in respiratory system diseases, are quite rare in veterinary medicine. We aimed to test the usability of serum Fe and Fe-related parameters [total iron-binding capacity (TIBC), unsaturated iron-binding capacity (UIBC) and transferrin saturation (TS) levels] as inflammatory and diagnostic biomarkers in calves with bovine respiratory disease complex (BRDC). To mark inflammation, some selected acute-phase proteins including serum ferritin and transferrin levels were measured because of their close relationship with iron metabolism. The material of this study consisted of 15 calves, aged 1-3 months with BRDC (Group I) and 10 healthy calves aged 1-3 months (Group II) based on the presence of respiratory clinical findings. Serum Fe, TIBC and TS levels were low and ferritin levels were high in Group I (P ≤ 0.001). The BRDC group was separated into two subgroups based on PCR results, namely Virus+ (n=9) and Virus- (n=6). The calves in the Virus+ group had significantly lower levels of Fe (P=0.001) and significantly higher values of ferritin (P=0.002), compared to the healthy group. On the basis of inter-group comparison and ROC analysis, we concluded that Fe (primarily), ferritin, TIBC and TS levels can be used as inflammatory biomarkers and possible diagnostic markers in the BRDC as useful, practical, inexpensive substitutes. As a suggestion, these parameters which are believed to play a role in the pathogenesis of the disease, can be used as potential prognostic biomarkers in studies involving treatment.
Collapse
|
|
44
|
Pandrangi SL, Chittineedi P, Chikati R, Lingareddy JR, Nagoor M, Ponnada SK. Role of dietary iron revisited: in metabolism, ferroptosis and pathophysiology of cancer. Am J Cancer Res 2022; 12:974-985. [PMID: 35411219 PMCID: PMC8984875] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2021] [Accepted: 02/10/2022] [Indexed: 06/14/2023] Open
Abstract
Iron is the most abundant metal in the human body. No independent life forms on earth can survive without iron. However, excess iron is closely associated with carcinogenesis by increasing oxidative stress via its catalytic activity to generate hydroxyl radicals. Therefore, it is speculated that iron might play a dual role in cells, by both stimulating cell growth and causing cell death. Dietary iron is absorbed by the intestinal enterocytes in the form of ferrous ion which forms cLIP. Excess iron stored in the form of Ferritin serves as a reservoir under iron depletion conditions. Ferroptosis, is an iron-dependent non-mutational form of cell death process and is suppressed by iron-binding compounds such as deferoxamine. Blocking transferrin-mediated iron import or recycling of iron-containing storage proteins (i.e., ferritin) also attenuates ferroptosis, consistent with the iron-dependent nature of this process. Unsurprisingly, ferroptosis also plays a role in the development of cancer and maybe a beneficial strategy for anticancer treatment. Different lines of evidence suggest that ferroptosis plays a crucial role in the suppression of tumorigenesis. In this review, we have discussed the pros and cons of iron accumulation, utilization and, its role in cell proliferation, ferroptosis and pathophysiology of cancer.
Collapse
Affiliation(s)
- Santhi Latha Pandrangi
- Onco-Stem Cell Research Laboratory, Department of Biochemistry and Bioinformatics, Institute of Science, GITAM (Deemed to be) UniversityVisakhapatnam 530045, India
| | - Prasanthi Chittineedi
- Onco-Stem Cell Research Laboratory, Department of Biochemistry and Bioinformatics, Institute of Science, GITAM (Deemed to be) UniversityVisakhapatnam 530045, India
| | | | - Joji Reddy Lingareddy
- Department of Biotechnology, Loyola AcademyOld Alwal, Secunderabad, Telangana 500010, India
| | | | - Suresh Kumar Ponnada
- Department of Biotechnology, Loyola AcademyOld Alwal, Secunderabad, Telangana 500010, India
| |
Collapse
|
|
45
|
Van Coillie S, Van San E, Goetschalckx I, Wiernicki B, Mukhopadhyay B, Tonnus W, Choi SM, Roelandt R, Dumitrascu C, Lamberts L, Dams G, Weyts W, Huysentruyt J, Hassannia B, Ingold I, Lele S, Meyer E, Berg M, Seurinck R, Saeys Y, Vermeulen A, van Nuijs ALN, Conrad M, Linkermann A, Rajapurkar M, Vandenabeele P, Hoste E, Augustyns K, Vanden Berghe T. Targeting ferroptosis protects against experimental (multi)organ dysfunction and death. Nat Commun 2022; 13:1046. [PMID: 35210435 PMCID: PMC8873468 DOI: 10.1038/s41467-022-28718-6] [Citation(s) in RCA: 107] [Impact Index Per Article: 35.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2021] [Accepted: 02/07/2022] [Indexed: 12/26/2022] Open
Abstract
The most common cause of death in the intensive care unit (ICU) is the development of multiorgan dysfunction syndrome (MODS). Besides life-supporting treatments, no cure exists, and its mechanisms are still poorly understood. Catalytic iron is associated with ICU mortality and is known to cause free radical-mediated cellular toxicity. It is thought to induce excessive lipid peroxidation, the main characteristic of an iron-dependent type of cell death conceptualized as ferroptosis. Here we show that the severity of multiorgan dysfunction and the probability of death are indeed associated with plasma catalytic iron and lipid peroxidation. Transgenic approaches underscore the role of ferroptosis in iron-induced multiorgan dysfunction. Blocking lipid peroxidation with our highly soluble ferrostatin-analogue protects mice from injury and death in experimental non-septic multiorgan dysfunction, but not in sepsis-induced multiorgan dysfunction. The limitations of the experimental mice models to mimic the complexity of clinical MODS warrant further preclinical testing. In conclusion, our data suggest ferroptosis targeting as possible treatment option for a stratifiable subset of MODS patients.
Collapse
Affiliation(s)
- Samya Van Coillie
- VIB-UGent Center for Inflammation Research, Ghent, Belgium.,Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium
| | - Emily Van San
- VIB-UGent Center for Inflammation Research, Ghent, Belgium.,Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium
| | - Ines Goetschalckx
- Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium
| | - Bartosz Wiernicki
- VIB-UGent Center for Inflammation Research, Ghent, Belgium.,Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium
| | - Banibrata Mukhopadhyay
- Department of Nephrology, Muljibhai Patel Society for Research in Nephro-Urology, Nadiad, India
| | - Wulf Tonnus
- Department of Internal Medicine 3, University Hospital Carl Gustav Carus, the Technische Universität Dresden, Dresden, Germany
| | - Sze Men Choi
- VIB-UGent Center for Inflammation Research, Ghent, Belgium.,Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium
| | - Ria Roelandt
- VIB-UGent Center for Inflammation Research, Ghent, Belgium.,Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.,Department of Applied Mathematics, Computer Science and Statistics, Ghent University, Ghent, Belgium
| | - Catalina Dumitrascu
- Department of Pharmaceutical Sciences, Toxicological Centre, University of Antwerp, Antwerp, Belgium
| | - Ludwig Lamberts
- Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium
| | - Geert Dams
- Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium
| | - Wannes Weyts
- VIB-UGent Center for Medical Biotechnology, Ghent, Belgium
| | - Jelle Huysentruyt
- VIB-UGent Center for Inflammation Research, Ghent, Belgium.,Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium
| | - Behrouz Hassannia
- VIB-UGent Center for Inflammation Research, Ghent, Belgium.,Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium
| | - Irina Ingold
- Institute of Metabolism and Cell Death, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich, Germany.,Department of Medicine III, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
| | - Suhas Lele
- Department of Nephrology, Muljibhai Patel Society for Research in Nephro-Urology, Nadiad, India
| | - Evelyne Meyer
- Department of Pharmacology, Toxicology and Biochemistry, Ghent University, Merelbeke, Belgium
| | - Maya Berg
- Department of Pharmaceutical Sciences, Toxicological Centre, University of Antwerp, Antwerp, Belgium
| | - Ruth Seurinck
- VIB-UGent Center for Inflammation Research, Ghent, Belgium.,Department of Applied Mathematics, Computer Science and Statistics, Ghent University, Ghent, Belgium
| | - Yvan Saeys
- VIB-UGent Center for Inflammation Research, Ghent, Belgium.,Department of Applied Mathematics, Computer Science and Statistics, Ghent University, Ghent, Belgium
| | - An Vermeulen
- Department of Bioanalysis, Ghent University, Ghent, Belgium
| | - Alexander L N van Nuijs
- Department of Pharmaceutical Sciences, Toxicological Centre, University of Antwerp, Antwerp, Belgium
| | - Marcus Conrad
- Institute of Metabolism and Cell Death, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich, Germany.,National Research Medical University, Laboratory of Experimental Oncology, Moscow, Russia
| | - Andreas Linkermann
- Department of Internal Medicine 3, University Hospital Carl Gustav Carus, the Technische Universität Dresden, Dresden, Germany.,Biotechnology Center, Technische Universität Dresden, Dresden, Germany
| | - Mohan Rajapurkar
- Department of Nephrology, Muljibhai Patel Society for Research in Nephro-Urology, Nadiad, India
| | - Peter Vandenabeele
- VIB-UGent Center for Inflammation Research, Ghent, Belgium.,Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.,Methusalem program, Ghent University, Ghent, Belgium
| | - Eric Hoste
- Intensive Care Unit, Ghent University Hospital; Ghent University, Ghent, Belgium
| | - Koen Augustyns
- Department of Pharmaceutical Sciences, Toxicological Centre, University of Antwerp, Antwerp, Belgium
| | - Tom Vanden Berghe
- VIB-UGent Center for Inflammation Research, Ghent, Belgium. .,Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium. .,Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.
| |
Collapse
|
|
46
|
Kilercik M, Ucal Y, Serdar M, Serteser M, Ozpinar A, Schweigert FJ. Zinc protoporphyrin levels in COVID-19 are indicative of iron deficiency and potential predictor of disease severity. PLoS One 2022; 17:e0262487. [PMID: 35113876 PMCID: PMC8812978 DOI: 10.1371/journal.pone.0262487] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2021] [Accepted: 12/27/2021] [Indexed: 12/24/2022] Open
Abstract
Background Coronavirus disease (COVID-19) has a severe impact on all aspects of patient care. Among the numerous biomarkers of potential validity for diagnostic and clinical management of COVID-19 are biomarkers at the interface of iron metabolism and inflammation. Methods The follow-up study included 54 hospitalized patients with laboratory-confirmed COVID-19 with a moderate and severe/critical form of the disease. Iron deficiency specific biomarkers such as iron, ferritin, transferrin receptor, hepcidin, and zinc protoporphyrin (ZnPP) as well as relevant markers of inflammation were evaluated twice: in the first five days when the patient was admitted to the hospital and during five to 15 days; and their validity to diagnose iron deficiency was further assessed. The regression and Receiver Operating Characteristics (ROC) analyses were performed to evaluate the prognosis and determine the probability for predicting the severity of the disease in the first five days of COVID-19. Results Based on hemoglobin values, anemia was observed in 21 of 54 patients. Of all iron deficiency anemia-related markers, only ZnPP was significantly elevated (P<0.001) in the anemic group. When patients were grouped according to the severity of disease, slight differences in hemoglobin or other anemia-related parameters could be observed. However, the levels of ZnPP were significantly increased in the severely ill group of patients. The ratio of ZnPP to lymphocyte count (ZnPP/L) had a discrimination power stronger than the neutrophil to lymphocyte count ratio (N/L) to determine disease severity. Additionally, only two markers were independently associated with the severity of COVID-19 in logistic regression analysis; D-dimer (OR (5.606)(95% CI 1.019–30.867)) and ZnPP/L ratio (OR (74.313) (95% CI 1.081–5108.103)). Conclusions For the first time ZnPP in COVID-19 patients were reported in this study. Among all iron-related markers tested, ZnPP was the only one that was associated with anemia as based on hemoglobin. The increase in ZnPP might indicate that the underlying cause of anemia in COVID-19 patients is not only due to the inflammation but also of nutritional origin. Additionally, the ZnPP/L ratio might be a valid prognostic marker for the severity of COVID-19.
Collapse
Affiliation(s)
- Meltem Kilercik
- Department of Medical Biochemistry, School of Medicine, Acıbadem Mehmet Ali Aydınlar University, Istanbul, Turkey
- Department of Medical Biochemistry, Acibadem Labmed Clinical Laboratories, Istanbul, Turkey
| | - Yasemin Ucal
- Department of Medical Biochemistry, School of Medicine, Acıbadem Mehmet Ali Aydınlar University, Istanbul, Turkey
| | - Muhittin Serdar
- Department of Medical Biochemistry, School of Medicine, Acıbadem Mehmet Ali Aydınlar University, Istanbul, Turkey
| | - Mustafa Serteser
- Department of Medical Biochemistry, School of Medicine, Acıbadem Mehmet Ali Aydınlar University, Istanbul, Turkey
- Department of Medical Biochemistry, Acibadem Labmed Clinical Laboratories, Istanbul, Turkey
| | - Aysel Ozpinar
- Department of Medical Biochemistry, School of Medicine, Acıbadem Mehmet Ali Aydınlar University, Istanbul, Turkey
- * E-mail: (FJS); (AO)
| | - Florian J. Schweigert
- Department of Physiology and Pathophysiology, Institute of Nutritional Science, University of Potsdam, Potsdam, Germany
- * E-mail: (FJS); (AO)
| |
Collapse
|
|
47
|
Hamada Y, Hirano E, Sugimoto K, Hanada K, Kaku T, Manda N, Tsuchida K. A farewell to phlebotomy-use of placenta-derived drugs Laennec and Porcine for improving hereditary hemochromatosis without phlebotomy: a case report. J Med Case Rep 2022; 16:26. [PMID: 35065677 PMCID: PMC8784004 DOI: 10.1186/s13256-021-03230-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2021] [Accepted: 12/14/2021] [Indexed: 01/19/2023] Open
Abstract
BACKGROUND Human hepcidin, produced by hepatocytes, regulates intestinal iron absorption, iron recycling by macrophages, and iron release from hepatic storage. Recent studies indicate that hepcidin deficiency is the underlying cause of the most known form of hereditary hemochromatosis. CASE PRESENTATION A 44-year-old Asian man who developed type 2 diabetes mellitus had elevated serum ferritin levels (10,191 ng/mL). Liver biopsy revealed remarkable iron deposition in the hepatocytes and relatively advanced fibrosis (F3). Chromosomal analysis confirmed the presence of transferrin receptor type 2 mutations (c.1100T>G, c.2008_9delAC, hereditary hemochromatosis type 3 analyzed by Kawabata). The patient received intravenous infusions of Laennec (672 mg/day, three times/week) or oral administration with Porcine (3.87 g/day) for 84 months as an alternative to repeated phlebotomy. At the end of the treatment period, serum ferritin level decreased to 428.4 ng/mL (below the baseline level of 536.8 ng/mL). Hemoglobin A1c levels also improved after treatment with the same or lower dose of insulin (8.8% before versus 6.8% after). Plural liver biopsies revealed remarkable improvements in the grade of iron deposition and fibrosis (F3 before versus F1 after) of the liver tissue. CONCLUSION The discovery of hepcidin and its role in iron metabolism could lead to novel therapies for hereditary hemochromatosis. Laennec (parenteral) and Porcine (oral), which act as hepcidin inducers, actually improved iron overload in this hereditary hemochromatosis patient, without utilizing sequential phlebotomy. This suggests the possibility of not only improving the prognosis of hereditary hemochromatosis (types 1, 2, and 3) but also ameliorating complications, such as type 2 diabetes, liver fibrosis, and hypogonadism. Laennec and Porcine can completely replace continuous venesection in patients with venesection and may improve other iron-overloading disorders caused by hepcidin deficiency.
Collapse
Affiliation(s)
- Yuki Hamada
- Hamada Clinic for Gastroenterology and Hepatology, Sapporo, Japan
| | - Eiichi Hirano
- Research Institute, Japan Bio Products Co., Ltd., 1-1 Kurume Research Center bldg. 2F, Hyakunenkoen, Kurume, Fukuoka 839-0864 Japan
| | - Koji Sugimoto
- Research Institute, Japan Bio Products Co., Ltd., 1-1 Kurume Research Center bldg. 2F, Hyakunenkoen, Kurume, Fukuoka 839-0864 Japan
| | | | | | | | | |
Collapse
|
|
48
|
Zeidan RS, Han SM, Leeuwenburgh C, Xiao R. Iron homeostasis and organismal aging. Ageing Res Rev 2021; 72:101510. [PMID: 34767974 DOI: 10.1016/j.arr.2021.101510] [Citation(s) in RCA: 80] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2021] [Revised: 11/02/2021] [Accepted: 11/02/2021] [Indexed: 12/21/2022]
Abstract
Iron is indispensable for normal body functions across species because of its critical roles in red blood cell function and many essential proteins and enzymes required for numerous physiological processes. Regulation of iron homeostasis is an intricate process involving multiple modulators at the systemic, cellular, and molecular levels. Interestingly, emerging evidence has demonstrated that many modulators of iron homeostasis contribute to organismal aging and longevity. On the other hand, the age-related dysregulation of iron homeostasis is often associated with multiple age-related pathologies including bone resorption and neurodegenerative diseases such as Alzheimer's disease. Thus, a thorough understanding on the interconnections between systemic and cellular iron balance and organismal aging may help decipher the etiologies of multiple age-related diseases, which could ultimately lead to developing therapeutic strategies to delay aging and treat various age-related diseases. Here we present the current understanding on the mechanisms of iron homeostasis. We also discuss the impacts of aging on iron homeostatic processes and how dysregulated iron metabolism may affect aging and organismal longevity.
Collapse
|
|
49
|
Chaudhary S, Ashok A, Wise AS, Rana NA, McDonald D, Kritikos AE, Kong Q, Singh N. Upregulation of brain hepcidin in prion diseases. Prion 2021; 15:126-137. [PMID: 34224321 PMCID: PMC8259718 DOI: 10.1080/19336896.2021.1946377] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2021] [Revised: 06/04/2021] [Accepted: 06/17/2021] [Indexed: 12/14/2022] Open
Abstract
Accumulation of redox-active iron in human sporadic Creutzfeldt-Jakob disease (sCJD) brain tissue and scrapie-infected mouse brains has been demonstrated previously. Here, we explored whether upregulation of local hepcidin secreted within the brain is the underlying cause of iron accumulation and associated toxicity. Using scrapie-infected mouse brains, we demonstrate transcriptional upregulation of hepcidin relative to controls. As a result, ferroportin (Fpn), the downstream effector of hepcidin and the only known iron export protein was downregulated, and ferritin, an iron storage protein was upregulated, suggesting increased intracellular iron. A similar transcriptional and translational upregulation of hepcidin, and decreased expression of Fpn and an increase in ferritin expression was observed in sCJD brain tissue. Further evaluation in human neuroblastoma cells (M17) exposed to synthetic mini-hepcidin showed downregulation of Fpn, upregulation of ferritin, and an increase in reactive oxygen species (ROS), resulting in cytotoxicity in a dose-dependent manner. Similar effects were noted in primary neurons isolated from mouse brain. As in M17 cells, primary neurons accumulated ferritin and ROS, and showed toxicity at five times lower concentration of mini-hepcidin. These observations suggest that upregulation of brain hepcidin plays a significant role in iron accumulation and associated neurotoxicity in human and animal prion disorders.
Collapse
Affiliation(s)
- Suman Chaudhary
- Department of Pathology, School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA
| | - Ajay Ashok
- Department of Pathology, School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA
| | - Aaron S. Wise
- Department of Pathology, School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA
| | - Neil A. Rana
- Department of Pathology, School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA
| | - Dallas McDonald
- Department of Pathology, School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA
| | - Alexander E. Kritikos
- Department of Pathology, School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA
| | - Qingzhong Kong
- Department of Pathology, School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA
| | - Neena Singh
- Department of Pathology, School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA
| |
Collapse
|
|
50
|
Shah HE, Bhawnani N, Ethirajulu A, Alkasabera A, Onyali CB, Anim-Koranteng C, Mostafa JA. Iron Deficiency-Induced Changes in the Hippocampus, Corpus Striatum, and Monoamines Levels That Lead to Anxiety, Depression, Sleep Disorders, and Psychotic Disorders. Cureus 2021; 13:e18138. [PMID: 34692346 PMCID: PMC8525689 DOI: 10.7759/cureus.18138] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2021] [Accepted: 09/20/2021] [Indexed: 01/09/2023] Open
Abstract
Iron deficiency anemia caused by severe iron deficiency in infancy is associated with poor health and severe neurological impairment such as mental, motor, social, emotional, neurophysiological, and neurocognitive dysfunction. The behavioral effects of iron deficiency can present themselves in infancy, but they are also found in adulthood. Some behaviors can start in childhood but persist throughout adulthood. The behaviors that are particularly often seen in infants and children include wariness and hesitance, lack of positive affect, and diminished social engagement. The affected behaviors in adults include anxiety, depression, higher complex cogitative tasks, and other psychological disorders. The mechanisms of how iron deficiency affects behavior include affecting the hippocampus, the corpus striatum, and certain neurotransmitters. The hippocampus is a brain region that is essential for memory, learning, and other purposes. The hippocampus is very sensitive to lack of Iron during early development. The corpus striatum dispatches dopamine-rich projects to the prefrontal cortex, and it is involved in controlling executive activities such as planning, inhibitory control, sustained attention, working memory, regulation of emotion, memory storage and retrieval, motivation, and reward. Iron deficiency has been known to cause changes in behavioral and developmental aspects by affecting neurotransmitters such as serotonin, noradrenaline, and dopamine. Iron deficiency causes behavior changes that can present in infancy and, even if corrected postnatally, it can have long-lasting effects well into adulthood.
Collapse
Affiliation(s)
- Hira E Shah
- Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Nitin Bhawnani
- Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Aarthi Ethirajulu
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Almothana Alkasabera
- General Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Chike B Onyali
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | | | - Jihan A Mostafa
- Psychiatry, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| |
Collapse
|