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Zhai Y, Li P, Tang S, Zhang P, Kang H, Li S. Trace elements concentration, tissue distribution, and associated health risks in wild and captive pantropical spotted dolphins (Stenella attenuata). JOURNAL OF HAZARDOUS MATERIALS 2025; 493:138413. [PMID: 40300520 DOI: 10.1016/j.jhazmat.2025.138413] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/31/2024] [Revised: 04/03/2025] [Accepted: 04/24/2025] [Indexed: 05/01/2025]
Abstract
Trace element (TEs) concentrations are key indicators for evaluating the health status of cetaceans. However, there is currently no research on TEs levels and tissue distributions in captive dolphins. Investigating TEs in wild and captive dolphins could provide critical insights into the effects of diets and habitats on TEs accumulation and improve healthcare protocols for captive dolphins. This study investigated concentrations of six TEs (Hg, Cd, Cr, Se, Cu, and Zn) in seven tissues (skin, muscle, liver, spleen, lung, kidney, and intestine) of wild (n = 8) and captive (n = 6) Stenella attenuata. The findings indicated that most studied wild and captive individuals exhibited medium levels of Hg, Cd, and Cr globally, with low health risks. However, alarming concentrations, such as 306 μg/g Hg in captive individuals and 178 μg/g Cd in wild individuals, suggested localized contamination persists. Tissue distributions of TEs indicated that ingestion and inhalation were the predominant exposure routes for wild and captive dolphins. Additionally, positive correlations between Hg levels in skin and liver and Cd levels in skin and kidney indicated that skin could serve as a healthy indicator for captive dolphins. Consuming odontocete tissue, even from healthy individuals, poses potential health risks to humans.
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Affiliation(s)
- Yuhuan Zhai
- Marine Mammal and Marine Bioacoustics Laboratory, Institute of Deep-sea Science and Engineering, Chinese Academy of Sciences, Sanya 572000, China; University of Chinese Academy of Sciences, Beijing 100049, China; Analytical Instrumentation Center, Institute of Deep-sea Science and Engineering, Chinese Academy of Sciences, Sanya 572000, China
| | - Pingjing Li
- Analytical Instrumentation Center, Institute of Deep-sea Science and Engineering, Chinese Academy of Sciences, Sanya 572000, China.
| | - Shuai Tang
- Analytical Instrumentation Center, Institute of Deep-sea Science and Engineering, Chinese Academy of Sciences, Sanya 572000, China
| | - Peijun Zhang
- Marine Mammal and Marine Bioacoustics Laboratory, Institute of Deep-sea Science and Engineering, Chinese Academy of Sciences, Sanya 572000, China
| | - Hui Kang
- Marine Mammal and Marine Bioacoustics Laboratory, Institute of Deep-sea Science and Engineering, Chinese Academy of Sciences, Sanya 572000, China; The Innovation Research Center for Aquatic Mammals, and Key Laboratory of Aquatic Biodiversity and Conservation of the Chinese Academy of Sciences, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China
| | - Songhai Li
- Marine Mammal and Marine Bioacoustics Laboratory, Institute of Deep-sea Science and Engineering, Chinese Academy of Sciences, Sanya 572000, China; The Innovation Research Center for Aquatic Mammals, and Key Laboratory of Aquatic Biodiversity and Conservation of the Chinese Academy of Sciences, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China.
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Su J, Chen K, Zhou P, Li N. A Novel SERS Silent-Region Signal Amplification Strategy for Ultrasensitive Detection of Cu 2. Molecules 2025; 30:2188. [PMID: 40430360 PMCID: PMC12114283 DOI: 10.3390/molecules30102188] [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: 04/19/2025] [Revised: 05/14/2025] [Accepted: 05/14/2025] [Indexed: 05/29/2025] Open
Abstract
Due to its unique molecular fingerprinting capability and multiplex detection advantages, surface-enhanced Raman scattering (SERS) has shown great application potential in the field of biological analysis. However, the weak signal intensity and large background interference significantly limited the application of SERS in biosensing and bioimaging. Loading a large amount of Raman molecules with signal in the silent region on the hotspots of the electromagnetic field of the SERS substrate can effectively avoid severe background noise signals and significantly improve the signal intensity, making the sensitivity and specificity of SERS detection remarkably improved. To achieve this goal, a new SERS signal-amplification strategy is herein reported for background-free detection of Cu2+ by using Raman-silent probes loaded on cabbage-like gold microparticles (AuMPs) with high enhancement capabilities and single-particle detection feasibility. In this work, carboxyl-modified AuMPs were used to enable Cu2+ adsorption via electrostatic interactions, followed by ferricyanide coordination with Cu2+ to introduce cyano groups, therefore generating a stable SERS signal with nearly zero background signals owing to the Raman-silent fingerprint of cyano at 2137 cm-1. Based on the signal intensity of cyano groups correlated with Cu2+ concentration resulting from the specific coordination between Cu2+ and cyanide, a novel SERS method for Cu2+ detection with high sensitivity and selectivity is proposed. It is noted that benefiting from per ferricyanide possessing six cyano groups, the established method with the advantage of signal amplification can significantly enhance the sensing sensitivity beyond conventional approaches. Experimental results demonstrated this SERS sensor possesses significant merits towards the determination of Cu2+ in terms of high selectivity, broad linear range from 1 nM to 1 mM, and low limit of detection (0.1 nM) superior to other reported colorimetric, fluorescence, and electrochemical methods. Moreover, algorithm data processing for optimization of SERS original data was further used to improve the SERS signal reliability. As the proof-of-concept demonstrations, this work paves the way for improving SERS sensing capability through the silent-range fingerprint and signal amplification strategy, and reveals SERS as an effective tool for trace detection in complex biological and environmental matrices.
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Affiliation(s)
| | | | | | - Nan Li
- Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Department of Biomedical Engineering, Jinan University, Guangzhou 510632, China; (J.S.); (K.C.); (P.Z.)
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Zhu R, Zeng YY, Liu LM, Yin L, Xu KP, Chen WF, Li SC, Zhou XF. Pollution status and assessment of seven heavy metals in the seawater and sediments of Hangzhou Bay, China. MARINE POLLUTION BULLETIN 2024; 209:117261. [PMID: 39551022 DOI: 10.1016/j.marpolbul.2024.117261] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/12/2024] [Revised: 10/31/2024] [Accepted: 11/03/2024] [Indexed: 11/19/2024]
Abstract
Hangzhou Bay, one of the fastest economy and population growth region in China, was heavily polluted by a large amounts of industrial waste water and domestic sewage containing harmful heavy metal pollutants. To investigate the status of heavy metals pollution and assess the ecological risks in Hangzhou Bay, seven heavy metals (Cu, Zn, Pb, Cd, Cr, Hg and As) concentrations of water and sediments were analyzed. Heavy metals concentrations in sediments close to the estuarine coast and nearshore area were higher than that in other areas. Cu, Zn, Pb, Cd, Cr and As in sediments might have extensive homologies and originate from the petroleum industry. The pollutions of Cu, Zn, Pb, Cd, Cr and As in seawater and sediment were very light or no pollution. Both in seawater and sediments, the Hg contamination was the most serious among the measured seven heavy metals and should be paid more attention.
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Affiliation(s)
- Rong Zhu
- Zhejiang Institute of Hydraulics & Estuary, Zhejiang Institute of Marine Planning & Design, Hangzhou 310020, China
| | - Yan-Yan Zeng
- Zhejiang Institute of Hydraulics & Estuary, Zhejiang Institute of Marine Planning & Design, Hangzhou 310020, China
| | - Li-Min Liu
- Zhejiang Institute of Hydraulics & Estuary, Zhejiang Institute of Marine Planning & Design, Hangzhou 310020, China
| | - Lu Yin
- Zhoushan Ecological and Environmental Emergency Management and Monitoring Center, Zhoushan 316000, China
| | - Kai-Ping Xu
- Zhejiang Institute of Hydraulics & Estuary, Zhejiang Institute of Marine Planning & Design, Hangzhou 310020, China
| | - Wei-Feng Chen
- Zhejiang Institute of Hydraulics & Estuary, Zhejiang Institute of Marine Planning & Design, Hangzhou 310020, China
| | - Shang-Chun Li
- Environmental Health Effects and Risk Assessment Key Laboratory of Luzhou, School of Public Health, Southwest Medical University, Luzhou 646000, China.
| | - Xiao-Feng Zhou
- Zhejiang Institute of Hydraulics & Estuary, Zhejiang Institute of Marine Planning & Design, Hangzhou 310020, China.
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Charkiewicz AE. Is Copper Still Safe for Us? What Do We Know and What Are the Latest Literature Statements? Curr Issues Mol Biol 2024; 46:8441-8463. [PMID: 39194715 DOI: 10.3390/cimb46080498] [Citation(s) in RCA: 10] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2024] [Revised: 07/29/2024] [Accepted: 07/31/2024] [Indexed: 08/29/2024] Open
Abstract
Copper (Cu) is a precious metal and one of the three most abundant trace elements in the body (50-120 mg). It is involved in a large number of cellular mechanisms and pathways and is an essential cofactor in the function of cellular enzymes. Both its excess and deficiency may be harmful for many diseases. Even small changes in Cu concentration may be associated with significant toxicity. Consequently, it can be damaging to any organ or tissue in our body, beginning with harmful effects already at the molecular level and then affecting the degradation of individual tissues/organs and the slow development of many diseases, such as those of the immunological system, skeletal system, circulatory system, nervous system, digestive system, respiratory system, reproductive system, and skin. The main purpose of this article is to review the literature with regard to both the healthiness and toxicity of copper to the human body. A secondary objective is to show its widespread use and sources, including in food and common materials in contact with humans. Its biological half-life from diet is estimated to range from 13 to 33 days. The retention or bioavailability of copper from the diet is influenced by several factors, such as age, amount and form of copper in the diet, lifestyle, and genetic background. The upper limit of normal in serum in healthy adults is approximately 1.5 mg Cu/L, while the safe upper limit of average intake is set at 10-12 mg/day, the reference limit at 0.9 mg/day, and the minimum limit at 0.6-0.7 mg/day. Cu is essential, and in the optimal dose, it provides antioxidant defense, while its deficiency reduces the body's ability to cope with oxidative stress. The development of civilization and the constant, widespread use of Cu in all electrical devices will not be stopped, but the health of people directly related to its extraction, production, or distribution can be controlled, and the inhabitants of nearby towns can be protected. It is extremely difficult to assess the effects of copper on the human body because of its ubiquity and the increasing reports in the literature about its effects, including copper nanoparticles.
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Yang DS, Wu Y, Kanatzidis EE, Avila R, Zhou M, Bai Y, Chen S, Sekine Y, Kim J, Deng Y, Guo H, Zhang Y, Ghaffari R, Huang Y, Rogers JA. 3D-printed epidermal sweat microfluidic systems with integrated microcuvettes for precise spectroscopic and fluorometric biochemical assays. MATERIALS HORIZONS 2023; 10:4992-5003. [PMID: 37641877 DOI: 10.1039/d3mh00876b] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/31/2023]
Abstract
Systems for capture, storage and analysis of eccrine sweat can provide insights into physiological health status, quantify losses of water, electrolytes, amino acids and/or other essential species, and identify exposures to adverse environmental species or illicit drugs. Recent advances in materials and device designs serve as the basis for skin-compatible classes of microfluidic platforms and in situ colorimetric assays for precise assessments of sweat rate, sweat loss and concentrations of wide-ranging types of biomarkers in sweat. This paper presents a set of findings that enhances the performance of these systems through the use of microfluidic networks, integrated valves and microscale optical cuvettes formed by three dimensional printing in hard/soft hybrid materials systems, for accurate spectroscopic and fluorometric assays. Field studies demonstrate the capability of these microcuvette systems to evaluate the concentrations of copper, chloride, and glucose in sweat, along with the pH of sweat, with laboratory-grade accuracy and sensitivity.
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Affiliation(s)
- Da Som Yang
- Querrey Simpson Institute for Bioelectronics, Northwestern University, Evanston, IL 60208, USA.
- Precision Biology Research Center (PBRC), Sungkyunkwan University, Suwon, 16419, South Korea
| | - Yixin Wu
- Querrey Simpson Institute for Bioelectronics, Northwestern University, Evanston, IL 60208, USA.
- Department of Materials Science and Engineering, Northwestern University, Evanston, IL 60208, USA
| | - Evangelos E Kanatzidis
- Querrey Simpson Institute for Bioelectronics, Northwestern University, Evanston, IL 60208, USA.
- Department of Molecular Biosciences, Northwestern University, Evanston, IL, USA
| | - Raudel Avila
- Department of Mechanical Engineering, Northwestern University, Evanston, IL 60208, USA
- Department of Mechanical Engineering, Rice University, Houston, TX, 77005, USA
| | - Mingyu Zhou
- Querrey Simpson Institute for Bioelectronics, Northwestern University, Evanston, IL 60208, USA.
- Department of Biomedical Engineering, Northwestern University, Evanston, IL 60208, USA
| | - Yun Bai
- Querrey Simpson Institute for Bioelectronics, Northwestern University, Evanston, IL 60208, USA.
- Department of Materials Science and Engineering, Northwestern University, Evanston, IL 60208, USA
| | - Shulin Chen
- Querrey Simpson Institute for Bioelectronics, Northwestern University, Evanston, IL 60208, USA.
- Department of Biomedical Engineering, Northwestern University, Evanston, IL 60208, USA
| | - Yurina Sekine
- Materials Sciences Research Center, Japan Atomic Energy Agency, Tokai, Ibaraki 319-1195, Japan
| | - Joohee Kim
- Querrey Simpson Institute for Bioelectronics, Northwestern University, Evanston, IL 60208, USA.
- Center for Bionics of Biomedical Research Institute, Korea Institute of Science and Technology, Seoul, 02792, Republic of Korea
| | - Yujun Deng
- Department of Mechanical Engineering, Northwestern University, Evanston, IL 60208, USA
- State Key Laboratory of Mechanical System and Vibration, Shanghai Jiao Tong University, Shanghai, China
| | - Hexia Guo
- Querrey Simpson Institute for Bioelectronics, Northwestern University, Evanston, IL 60208, USA.
- Department of Materials Science and Engineering, Northwestern University, Evanston, IL 60208, USA
| | - Yi Zhang
- Polymer Program, Institute of Materials Science, University of Connecticut, Storrs, Connecticut 06269, USA
- Department of Biomedical Engineering, University of Connecticut, Storrs, Connecticut 06269, USA
| | - Roozbeh Ghaffari
- Querrey Simpson Institute for Bioelectronics, Northwestern University, Evanston, IL 60208, USA.
- Department of Biomedical Engineering, Northwestern University, Evanston, IL 60208, USA
- Epicore Biosystems Inc., Cambridge, MA, USA
| | - Yonggang Huang
- Querrey Simpson Institute for Bioelectronics, Northwestern University, Evanston, IL 60208, USA.
- Department of Materials Science and Engineering, Northwestern University, Evanston, IL 60208, USA
- Department of Mechanical Engineering, Northwestern University, Evanston, IL 60208, USA
- Department of Civil and Environmental Engineering, Northwestern University, Evanston, IL 60208, USA
| | - John A Rogers
- Querrey Simpson Institute for Bioelectronics, Northwestern University, Evanston, IL 60208, USA.
- Department of Materials Science and Engineering, Northwestern University, Evanston, IL 60208, USA
- Department of Mechanical Engineering, Northwestern University, Evanston, IL 60208, USA
- Department of Biomedical Engineering, Northwestern University, Evanston, IL 60208, USA
- Epicore Biosystems Inc., Cambridge, MA, USA
- Department of Neurological Surgery, Northwestern University, Evanston, IL 60208, USA
- Department of Electrical and Computer Engineering, Northwestern University, Evanston, IL 60208, USA
- Department of Chemistry, Northwestern University, Evanston, IL 60208, USA
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6
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Dias FCR, Cupertino MC, Silva PG, Oliveira EL, Ladeira LCM, Matta SLP, Otoni WC, Gomes MLM. Exposure to Pfaffia glomerata causes oxidative stress and triggers hepatic changes. BRAZ J BIOL 2023; 83:e271425. [PMID: 37341252 DOI: 10.1590/1519-6984.271425] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2023] [Accepted: 05/16/2023] [Indexed: 06/22/2023] Open
Abstract
Medicinal plant species are genetically engineered to obtain higher production of biomass and specific secondary metabolites, which can be used in the pharmaceutical industry. The aim of the present study was to evaluate the effect of Pfaffia glomerata (Spreng.) Pedersen tetraploid hydroalcoholic extract on the liver of adult Swiss mice. The extract was prepared from the plant roots and given to the animals by gavage, for 42 days. The experimental groups were treated with water (control), Pfaffia glomerata tetraploid hydroalcoholic extract (100, 200 and 400 mg/kg) and Pfaffia glomerata tetraploid hydroalcoholic extract discontinuously (200 mg/kg). The last group received the extract every 3 days, for 42 days. The oxidative status, mineral dynamics, and cell viability were analysed. The liver weight and the number of viable hepatocytes were reduced, despite the increased cell's number. Increased levels of malondialdehyde and nitric oxide, and changes in iron, copper, zinc, potassium, manganese and sodium levels were observed. aspartate aminotransferase levels were increased while alanine aminotransferase levels were decreased due to BGEt intake. Our results showed that BGEt induced alterations of oxidative stress biomarkers leading to liver injury, which was associated with a reduction in the number of hepatocytes.
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Affiliation(s)
- F C R Dias
- Universidade Federal do Triângulo Mineiro - UFTM, Departamento de Biologia Estrutural, Uberaba, MG, Brasil
- Universidade Federal Rural de Pernambuco - UFRPE, Departamento de Veterinária, Recife, PE, Brasil
| | - M C Cupertino
- Universidade Federal de Viçosa - UFV, Departamento de Medicina e Nutrição, Laboratório de Métodos Epidemiológicos e Computacionais em Saúde, Viçosa, MG, Brasil
- Universidade Federal de Viçosa - UFV, Departamento de Biologia Geral, Viçosa, MG, Brasil
| | - P G Silva
- Universidade Federal de Viçosa - UFV, Departamento de Biologia Animal, Viçosa, MG, Brasil
| | - E L Oliveira
- Universidade Federal de Viçosa - UFV, Departamento de Biologia Geral, Viçosa, MG, Brasil
| | - L C M Ladeira
- Universidade Federal de Viçosa - UFV, Departamento de Biologia Geral, Viçosa, MG, Brasil
| | - S L P Matta
- Universidade Federal de Viçosa - UFV, Departamento de Biologia Geral, Viçosa, MG, Brasil
| | - W C Otoni
- Universidade Federal de Viçosa - UFV, Departamento de Biologia Vegetal, Viçosa, MG, Brasil
| | - M L M Gomes
- Universidade Federal do Triângulo Mineiro - UFTM, Departamento de Biologia Estrutural, Uberaba, MG, Brasil
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Ortega-Romero M, Jiménez-Córdova MI, Barrera-Hernández Á, Sepúlveda-González ME, Narvaez-Morales J, Aguilar-Madrid G, Juárez-Pérez CA, Del Razo LM, Cruz-Angulo MDC, Mendez-Hernández P, Medeiros M, Barbier OC. Relationship between urinary biomarkers of early kidney damage and exposure to inorganic toxins in a pediatric population of Apizaco, Tlaxcala, Mexico. J Nephrol 2023; 36:1383-1393. [PMID: 37253904 DOI: 10.1007/s40620-023-01598-9] [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: 10/19/2022] [Accepted: 02/12/2023] [Indexed: 06/01/2023]
Abstract
BACKGROUND In recent years, chronic kidney disease has increased in the pediatric population and has been related to environmental factors. In the diagnosis of kidney damage, in addition to the traditional parameters, early kidney damage biomarkers, such as kidney injury molecule 1, cystatin C, and osteopontin, among others, have been implemented as predictors of early pathological processes. OBJECTIVE This study aimed to evaluate the relationship between exposure to environmental pollutants and early kidney damage biomarkers. METHODS A cross-sectional pilot study was conducted in February 2016 and involved 115 apparently healthy children aged 6-15 residing in Apizaco, Tlaxcala. Participant selection was carried out randomly from among 16,472 children from the municipality of Apizaco. A socio-demographic questionnaire included age, sex, education, duration of residence in the area, occupation, water consumption and dietary habits, pathological history, and some non-specific symptoms. Physical examination included blood pressure, weight, and height. The urine concentrations of urinary aluminum, total arsenic, boron, calcium, chromium, copper, mercury, potassium, sodium, magnesium, manganese, molybdenum, lead, selenium, silicon, thallium, vanadium, uranium, and zinc, were measured. Four of the 115 participants selected for the study were excluded due to an incomplete questionnaire or lack of a medical examination, leaving a final sample population of 111 participants. RESULTS The results showed a mean estimated glomerular filtration rate of 89.1 ± 9.98 mL/min/1.73m2 and a mean albumin/creatinine ratio of 12.9 ± 16.7 mg/g urinary creatinine. We observed a positive and significant correlation between estimated glomerular filtration rate with fluoride, total arsenic and lead, and a correlation of albumin/creatinine ratio with fluoride, vanadium, and total arsenic. There was also a significant correlation between the early kidney damage biomarkers and fluoride, vanadium, and total arsenic, except for cystatin C. CONCLUSION In conclusion, our results show that four urinary biomarkers: α1-microglobulin, cystatin C, kidney injury molecule 1, and neutrophil gelatinase-associated lipocalin are related to environmental exposure to urinary fluoride, vanadium, and total arsenic in our pediatric population.
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Affiliation(s)
- Manolo Ortega-Romero
- Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Mexico City, México
- Unidad de Investigación en Nefrología y Metabolismo Mineral Óseo, Hospital Infantil de México Federico Gómez, Mexico City, México
| | - Mónica I Jiménez-Córdova
- Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Mexico City, México
- Secretaría de Investigación y Posgrado, Instituto Politécnico Nacional (SIP-IPN), Mexico City, México
| | - Ángel Barrera-Hernández
- Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Mexico City, México
| | - María Eugenia Sepúlveda-González
- Unidad de Investigación en Nefrología y Metabolismo Mineral Óseo, Hospital Infantil de México Federico Gómez, Mexico City, México
| | - Juana Narvaez-Morales
- Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Mexico City, México
| | - Guadalupe Aguilar-Madrid
- Claustro Universitario de Chihuahua, Dirección de Investigación y de Posgrado, Chihuahua, México
| | - Cuauhtémoc Arturo Juárez-Pérez
- Unidad de Investigación de Salud en El Trabajo, Centro Médico Nacional SXXI Instituto Mexicano del Seguro Social, Mexico City, México
| | - Luz María Del Razo
- Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Mexico City, México
| | | | - Pablo Mendez-Hernández
- Departamento de Calidad y Educación en Salud, Secretaría de Salud de Tlaxcala, Tlaxcala, México
- Facultad de Ciencias de La Salud, Universidad Autónoma de Tlaxcala, Tlaxcala, México
| | - Mara Medeiros
- Unidad de Investigación en Nefrología y Metabolismo Mineral Óseo, Hospital Infantil de México Federico Gómez, Mexico City, México
- Departamento de Farmacología, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, México
| | - Olivier Christophe Barbier
- Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Mexico City, México.
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8
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Dias FCR, Matta SLP, Lima GDA, Souza ACF, Menezes TP, Melo FCSA, Otoni WC, Neves MM, Gomes MLM. Pfaffia glomerata polyploid accession compromises male fertility and fetal development. JOURNAL OF ETHNOPHARMACOLOGY 2023; 314:116680. [PMID: 37230282 DOI: 10.1016/j.jep.2023.116680] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/07/2023] [Revised: 05/19/2023] [Accepted: 05/22/2023] [Indexed: 05/27/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Pfaffia glomerata (Spreng.) Pedersen has traditionally been used as a tonic and a stimulant by the Brazilian population. It shows higher biomass accumulation and production of secondary compounds, such as the phytosterol 20-hydroxyecdysone. AIMS The present study aimed to evaluate the effects of the hydroalcoholic extract of the root of tetraploid P. glomerata (BGEt) on testicular parenchyma, and its implications on fertility. MATERIAL AND METHODS Adult Swiss mice were divided as: control (water) and sildenafil citrate (7 mg/kg), BGEt at 100, 200, and 400 mg/kg, and BGEtD 200 mg/kg (treated with BGE every three days). Males (n = 4/group) were mated with normal untreated adult females to assess fertility rates, while other animals (n = 6/group) were euthanized for testis, epididymis, and oxidative stress analyses. RESULTS Increase in tubule diameter and epithelium height in the discontinuous group, in addition to an increase in the proportion of tubules with moderate pathologies was observed. The pre-implantation loss was lower in all treated groups. The post-implantation loss was significantly increased in all treated groups, except for the lowest BGEt dose. BGEt intake caused a decrease in daily sperm production, along with the number and quality of sperm in the epididymis. Changes were observed in protein carbonylation and hydrogen peroxide and nitric oxide levels, characterizing oxidative stress. CONCLUSIONS The hydroalcoholic extract of P. glomerata tetraploid altered sperm and testicular parameters, compromising embryonic development after implantation.
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Affiliation(s)
- Fernanda C R Dias
- Department of Structural Biology, Federal University of Triângulo Mineiro, Uberaba, MG, Brazil.
| | - Sérgio L P Matta
- Department of General Biology, Federal University of Viçosa, Viçosa, MG, Brazil.
| | - Graziela D A Lima
- Department of General Biology, Federal University of Viçosa, Viçosa, MG, Brazil.
| | - Ana Cláudia F Souza
- Department of Animal Biology, Federal Rural University of Rio de Janeiro, Seropédica, RJ, Brazil.
| | - Tatiana P Menezes
- Department of General Biology, Federal University of Viçosa, Viçosa, MG, Brazil.
| | - Fabiana C S A Melo
- Department of Animal Biology, Federal University of Viçosa, Viçosa, MG, Brazil.
| | - Wagner C Otoni
- Department of Plant Biology, Federal University of Viçosa, Viçosa, MG, Brazil.
| | | | - Marcos L M Gomes
- Department of Structural Biology, Federal University of Triângulo Mineiro, Uberaba, MG, Brazil.
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9
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Lu Y, Wei X, Chen M, Wang J. Non-ceruloplasmin-bound copper and copper speciation in serum with extraction using functionalized dendritic silica spheres followed by ICP-MS detection. Anal Chim Acta 2023; 1251:340993. [PMID: 36925285 DOI: 10.1016/j.aca.2023.340993] [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: 01/22/2023] [Revised: 02/15/2023] [Accepted: 02/16/2023] [Indexed: 02/19/2023]
Abstract
The quantification of non-ceruloplasmin-bound copper (NCBC) and total copper in biological fluids is highly required for understanding the correlation of copper with various physiological processes and diseases. In the present work, we developed dendritic spherical silica particles functionalized with EDTA, shortly as DMSPs-EDTA, from the hydrolysis of tetraethyl orthosilicate with the aid of structure-directing agents and subsequent modification of EDTA. DMSPs-EDTA serves as adsorbent with abundant binding sites to facilitate efficient extraction of NCBC. The retained NCBC on DMSPs-EDTA may be readily recovered by stripping with HNO3 (2 mol L-1). By hyphenating with ICP-MS detection, it provides a limit of detection of 1.3 pmol for NCBC. The degradation of ceruloplasmin with 200 mmol L-1 H2O2 releases the bound copper as NCBC to distribute among other ligands, which may be efficiently retained by the adsorbent and facilitate the detection of total copper. The linear ranges of 0.21-10 μmol L-1 and 0.42-30 μmol L-1 were derived for the detection of NCBC and total copper. The recovery rates for spiked NCBC or total copper in serum were derived to be 97-108% and 94-102%, respectively. The analysis of serum for a healthy subject resulted in 1.8 μmol L-1 NCBC and 9.5 μmol L-1 total copper. In addition, the proportions of 8.5-12% for NCBC were derived from the serum of healthy adults, while those for the patients with lung, hepatocellular and esophageal carcinoma were found to be 10-12%, illustrating no obvious difference against the normal group.
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Affiliation(s)
- Yi Lu
- Department of Chemistry, College of Sciences, Northeastern University, Shenyang, 110819, PR China
| | - Xing Wei
- Department of Chemistry, College of Sciences, Northeastern University, Shenyang, 110819, PR China
| | - Mingli Chen
- Department of Chemistry, College of Sciences, Northeastern University, Shenyang, 110819, PR China.
| | - Jianhua Wang
- Department of Chemistry, College of Sciences, Northeastern University, Shenyang, 110819, PR China.
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10
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Yu L, Yousuf S, Yousuf S, Yeh J, Biggins SW, Morishima C, Shyu I, O’Shea-Stone G, Eilers B, Waldum A, Copié V, Burkhead J. Copper deficiency is an independent risk factor for mortality in patients with advanced liver disease. Hepatol Commun 2023; 7:e0076. [PMID: 36809345 PMCID: PMC9949837 DOI: 10.1097/hc9.0000000000000076] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2022] [Accepted: 11/17/2022] [Indexed: 02/23/2023] Open
Abstract
BACKGROUND AND AIM Copper is an essential trace metal serving as a cofactor in innate immunity, metabolism, and iron transport. We hypothesize that copper deficiency may influence survival in patients with cirrhosis through these pathways. METHODS We performed a retrospective cohort study involving 183 consecutive patients with cirrhosis or portal hypertension. Copper from blood and liver tissues was measured using inductively coupled plasma mass spectrometry. Polar metabolites were measured using nuclear magnetic resonance spectroscopy. Copper deficiency was defined by serum or plasma copper below 80 µg/dL for women or 70 µg/dL for men. RESULTS The prevalence of copper deficiency was 17% (N=31). Copper deficiency was associated with younger age, race, zinc and selenium deficiency, and higher infection rates (42% vs. 20%, p=0.01). Serum copper correlated positively with albumin, ceruloplasmin, hepatic copper, and negatively with IL-1β. Levels of polar metabolites involved in amino acids catabolism, mitochondrial transport of fatty acids, and gut microbial metabolism differed significantly according to copper deficiency status. During a median follow-up of 396 days, mortality was 22.6% in patients with copper deficiency compared with 10.5% in patients without. Liver transplantation rates were similar (32% vs. 30%). Cause-specific competing risk analysis showed that copper deficiency was associated with a significantly higher risk of death before transplantation after adjusting for age, sex, MELD-Na, and Karnofsky score (HR: 3.40, 95% CI, 1.18-9.82, p=0.023). CONCLUSIONS In advanced cirrhosis, copper deficiency is relatively common and is associated with an increased infection risk, a distinctive metabolic profile, and an increased risk of death before transplantation.
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Affiliation(s)
- Lei Yu
- Department of Medicine, Division of Gastroenterology and Center for Liver Investigation Fostering Discovery, University of Washington, Seattle, Washington, USA
| | - Sarim Yousuf
- College of Medicine, Ziauddin University, Karachi, Pakistan
| | - Shahrukh Yousuf
- Department of Medicine, Division of Gastroenterology and Center for Liver Investigation Fostering Discovery, University of Washington, Seattle, Washington, USA
| | - Jeffrey Yeh
- Department of Medicine, Division of Gastroenterology and Center for Liver Investigation Fostering Discovery, University of Washington, Seattle, Washington, USA
| | - Scott W. Biggins
- Department of Medicine, Division of Gastroenterology and Center for Liver Investigation Fostering Discovery, University of Washington, Seattle, Washington, USA
| | - Chihiro Morishima
- Department of Lab Medicine and Pathology, University of Washington, Seattle, Washington, USA
| | - Irene Shyu
- Department of Lab Medicine and Pathology, University of Washington, Seattle, Washington, USA
| | - Galen O’Shea-Stone
- Department of Chemistry, Montana State University, Bozeman, Montana, USA
| | - Brian Eilers
- Department of Chemistry, Montana State University, Bozeman, Montana, USA
| | - Annie Waldum
- Department of Chemistry, Montana State University, Bozeman, Montana, USA
| | - Valérie Copié
- Department of Chemistry, Montana State University, Bozeman, Montana, USA
| | - Jason Burkhead
- Department of Biological Sciences, University of Alaska Anchorage, Anchorage, Alaska, USA
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11
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Ossoliński K, Ruman T, Copié V, Tripet BP, Nogueira LB, Nogueira KO, Kołodziej A, Płaza-Altamer A, Ossolińska A, Ossoliński T, Nizioł J. Metabolomic and elemental profiling of blood serum in bladder cancer. J Pharm Anal 2022; 12:889-900. [PMID: 36605581 PMCID: PMC9805945 DOI: 10.1016/j.jpha.2022.08.004] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2022] [Revised: 08/19/2022] [Accepted: 08/27/2022] [Indexed: 01/09/2023] Open
Abstract
Bladder cancer (BC) is one of the most frequently diagnosed types of urinary cancer. Despite advances in treatment methods, no specific biomarkers are currently in use. Targeted and untargeted profiling of metabolites and elements of human blood serum from 100 BC patients and the same number of normal controls (NCs), with external validation, was attempted using three analytical methods, i.e., nuclear magnetic resonance, gold and silver-109 nanoparticle-based laser desorption/ionization mass spectrometry (LDI-MS), and inductively coupled plasma optical emission spectrometry (ICP-OES). All results were subjected to multivariate statistical analysis. Four potential serum biomarkers of BC, namely, isobutyrate, pyroglutamate, choline, and acetate, were quantified with proton nuclear magnetic resonance, which had excellent predictive ability as judged by the area under the curve (AUC) value of 0.999. Two elements, Li and Fe, were also found to distinguish between cancer and control samples, as judged from ICP-OES data and AUC of 0.807 (in validation set). Twenty-five putatively identified compounds, mostly related to glycans and lipids, differentiated BC from NCs, as detected using LDI-MS. Five serum metabolites were found to discriminate between tumor grades and nine metabolites between tumor stages. The results from three different analytical platforms demonstrate that the identified distinct serum metabolites and metal elements have potential to be used for noninvasive detection, staging, and grading of BC.
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Affiliation(s)
| | - Tomasz Ruman
- Rzeszów University of Technology, Faculty of Chemistry, 35-959, Rzeszów, Poland
| | - Valérie Copié
- The Department of Chemistry and Biochemistry, Montana State University, Bozeman, MT, 59717, USA
| | - Brian P. Tripet
- The Department of Chemistry and Biochemistry, Montana State University, Bozeman, MT, 59717, USA
| | - Leonardo B. Nogueira
- Department of Geology, Federal University of Ouro Preto, 35400-000, Ouro Preto, Brazil
| | - Katiane O.P.C. Nogueira
- Department of Biological Sciences, Federal University of Ouro Preto, 35400-000, Ouro Preto, Brazil
| | - Artur Kołodziej
- Doctoral School of Engineering and Technical Sciences at the Rzeszów University of Technology, 35-959, Rzeszów, Poland
| | - Aneta Płaza-Altamer
- Doctoral School of Engineering and Technical Sciences at the Rzeszów University of Technology, 35-959, Rzeszów, Poland
| | - Anna Ossolińska
- Department of Urology, John Paul II Hospital, 36-100, Kolbuszowa, Poland
| | - Tadeusz Ossoliński
- Department of Urology, John Paul II Hospital, 36-100, Kolbuszowa, Poland
| | - Joanna Nizioł
- Rzeszów University of Technology, Faculty of Chemistry, 35-959, Rzeszów, Poland
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12
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Ma C, Han L, Zhu Z, Heng Pang C, Pan G. Mineral metabolism and ferroptosis in non-alcoholic fatty liver diseases. Biochem Pharmacol 2022; 205:115242. [PMID: 36084708 DOI: 10.1016/j.bcp.2022.115242] [Citation(s) in RCA: 36] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2022] [Revised: 08/28/2022] [Accepted: 08/30/2022] [Indexed: 11/02/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) has become the most prevalent chronic liver disease worldwide. Minerals including iron, copper, zinc, and selenium, fulfil an essential role in various biochemical processes. Moreover, the identification of ferroptosis and cuproptosis further underscores the importance of intracellular mineral homeostasis. However, perturbation of minerals has been frequently reported in patients with NAFLD and related diseases. Interestingly, studies have attempted to establish an association between mineral disorders and NAFLD pathological features, including oxidative stress, mitochondrial dysfunction, inflammatory response, and fibrogenesis. In this review, we aim to provide an overview of the current understanding of mineral metabolism (i.e., absorption, utilization, and transport) and mineral interactions in the pathogenesis of NAFLD. More importantly, this review highlights potential therapeutic strategies, challenges, future directions for targeting mineral metabolism in the treatment of NAFLD.
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Affiliation(s)
- Chenhui Ma
- Department of Chemical and Environmental Engineering, University of Nottingham Ningbo China, Ningbo 315100, China; Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; University of Chinese Academy of Sciences, Beijing 100049, China
| | - Li Han
- Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; University of Chinese Academy of Sciences, Beijing 100049, China
| | - Zheying Zhu
- Division of Molecular Therapeutics & Formulation, School of Pharmacy, The University of Nottingham, University Park Campus, Nottingham NG7 2RD, UK.
| | - Cheng Heng Pang
- Department of Chemical and Environmental Engineering, University of Nottingham Ningbo China, Ningbo 315100, China.
| | - Guoyu Pan
- Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; University of Chinese Academy of Sciences, Beijing 100049, China.
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13
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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.
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Affiliation(s)
- Khalid M Sumaily
- Clinical Biochemistry Unit, Department of Pathology, College of Medicine, King Saud University, Riyadh P.O. Box 145111, Saudi Arabia
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14
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Mitra S, Chakraborty AJ, Tareq AM, Emran TB, Nainu F, Khusro A, Idris AM, Khandaker MU, Osman H, Alhumaydhi FA, Simal-Gandara J. Impact of heavy metals on the environment and human health: Novel therapeutic insights to counter the toxicity. JOURNAL OF KING SAUD UNIVERSITY - SCIENCE 2022; 34:101865. [DOI: 10.1016/j.jksus.2022.101865] [Citation(s) in RCA: 407] [Impact Index Per Article: 135.7] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/01/2023]
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15
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Yang Q, Rosati G, Abarintos V, Aroca MA, Osma JF, Merkoçi A. Wearable and fully printed microfluidic nanosensor for sweat rate, conductivity, and copper detection with healthcare applications. Biosens Bioelectron 2022; 202:114005. [DOI: 10.1016/j.bios.2022.114005] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2021] [Revised: 01/12/2022] [Accepted: 01/13/2022] [Indexed: 02/06/2023]
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16
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Atazadegan MA, Heidari-Beni M, Riahi R, Kelishadi R. Association of selenium, zinc and copper concentrations during pregnancy with birth weight: A systematic review and meta-analysis. J Trace Elem Med Biol 2022; 69:126903. [PMID: 34823102 DOI: 10.1016/j.jtemb.2021.126903] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Revised: 10/02/2021] [Accepted: 11/15/2021] [Indexed: 10/19/2022]
Abstract
BACKGROUND Normal fetal growth is associated with maternal nutrition. Trace elements play important roles in fetus growth. This review aims to provide a summary of the literature evaluating the relation between selenium, zinc and copper levels during pregnancy with birth weight. METHOD A systematic literature search was conducted in Medline database (PubMed), Scopus, Web of science and Google scholar up to September 2020. Fifty observational studies were included in the final analyses. The desired pooled effect size was considered as standardized mean differences with 95 % CI or correlation. Cochran's Q statistic was used to test the heterogeneity between the included studies (I2). RESULT A significant differences were found between pooled standardized mean differences (SMD) of umbilical cord blood copper levels in small-for-gestational age birth weight (SGA) and appropriate-for-gestational age birth weight (AGA) (SMD: 0.34 μg/L, 95 % CI: 0.13 to 0.56). There was a significant pooled correlation between umbilical cord blood selenium concentrations and birth weight (r: 0.08, 95 % CI: 0.01 to 0.16). A significant pooled correlation was found between umbilical cord blood zinc concentrations and birth weight (r: 0.09, 95 % CI: 0.04 to 0.15), with significant heterogeneity (I2 % = 0.63). There was significant positive association between maternal blood zinc concentrations and birth weight. CONCLUSION Findings showed the association of trace elements including selenium, zinc and copper during pregnancy with birth weight. There was significant correlation between umbilical cord and maternal blood selenium and zinc levels with birth weight. The umbilical cord blood copper levels in SGA birth weight was higher than copper levels in AGA birth weight.
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Affiliation(s)
- Mohammad Amin Atazadegan
- Department of Clinical Nutrition, School of Nutrition and Food Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Motahar Heidari-Beni
- Department of Nutrition, Child Growth and Development Research Center, Research Institute for Primordial Prevention of Non-Communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran.
| | - Roya Riahi
- Department of Pediatrics, Child Growth and Development Research Center, Research Institute for Primordial Prevention of Non-Communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Roya Kelishadi
- Department of Pediatrics, Child Growth and Development Research Center, Research Institute for Primordial Prevention of Non-Communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran
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17
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Nutritional therapy to cirrhotic patients on transplantation waiting lists. JOURNAL OF LIVER TRANSPLANTATION 2022. [DOI: 10.1016/j.liver.2021.100060] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
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18
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Tarantino G, Citro V, Capone D, Gaudiano G, Sinatti G, Santini SJ, Balsano C. Copper concentrations are prevalently associated with antithrombin III, but also with prothrombin time and fibrinogen in patients with liver cirrhosis: A cross-sectional retrospective study. J Trace Elem Med Biol 2021; 68:126802. [PMID: 34091123 DOI: 10.1016/j.jtemb.2021.126802] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2021] [Revised: 04/21/2021] [Accepted: 05/27/2021] [Indexed: 11/25/2022]
Abstract
BACKGROUND Concerning the link between copper excess and the pathogenesis of chronic liver diseases, its retention is reckoned to develop as a complication of cholestasis. Recently, it has been found that cholestatic liver injury involves largely inflammatory cell-mediated liver cell necrosis, with consequent reduced hepatic mass, more than occurring through direct bile acid-induced apoptosis. On the other hand, interference with protein synthesis could be expected to result, ending in an altered ability of the liver to retain copper. Little is known about the association between serum copper and clotting factors in cirrhotics. We aimed at studying a possible relationship between increased levels of copper and an aspect of the haemostatic process in liver cirrhosis patients, assessing an index of protein synthesis (albumin) and parameters of protein synthesis/coagulation/fibrinolysis, such as prothrombin time (PT), antithrombin (AT) III and fibrinogen. METHODS Records from 85 patients suffering from liver cirrhosis of various aetiology and different severity were retrospectively examined. Serum concentrations of copper were determined by atomic absorption spectrophotometer. An index of protein synthesis, such as albumin and parameters of both synthesis and coagulation/hypercoagulation such as PT %, AT III%, levels of fibrinogen were taken into account to study possible correlations to serum copper. The severity of cirrhosis was evaluated by the Child-Pugh (C-P) classification. The relationship among variables were studied by linear regression. RESULTS Copper levels of patients suffering from liver cirrhosis were increased respect to those of controls, 102.7+/-28.7 versus 80.4+/-19.5 mcg/dL, (P = .0009), independently from disease severity, and were positively predicted by PT% (P = 0. 017), fibrinogen (P = 0.007) and AT III% (P = 0.000), at linear regression. Among the previous parameters, to which serum albumin was added, the unique predictor of copper levels was AT III%, at multiple regression (P = 0. 010); AT III% was negatively predicted by the C-P classification (P = 0.000); copper levels, adjusted for C-P classification, were predicted by AT III% (P = 0.020) and fibrinogen concentrations, but not by PT% (P = 0.09). CONCLUSION The copper concentration is reckoned as responsible for production of the hydroxyl radicals. On the basis that oxidants may enhance the activity of the extrinsic coagulation cascade, ultimately leading to thrombin formation, via their combined effects on stimulation of tissue factor activity and inhibition of fibrinolytic pathways, the positive relationship of copper to coagulation/hypercoagulation parameters (mainly AT III) in our research could find a plausible interpretation.
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Affiliation(s)
- Giovanni Tarantino
- Department of Clinical Medicine and Surgery, Federico II University Medical School of Naples, 80131, Naples, Italy.
| | - Vincenzo Citro
- Department of General Medicine, "Umberto I" Hospital, 84014, Nocera Inferiore (SA), Italy
| | | | - Giuseppe Gaudiano
- Clinical Pathology Unit,"Umberto I" Hospital, 84014, Nocera Inferiore (SA), Italy
| | - Gaia Sinatti
- Department of Clinical Medicine, Life, Health & Environmental Sciences-MESVA, University of L'Aquila, 67100 L, Aquila, Italy
| | - Silvano Junior Santini
- Department of Clinical Medicine, Life, Health & Environmental Sciences-MESVA, University of L'Aquila, 67100 L, Aquila, Italy
| | - Clara Balsano
- Department of Clinical Medicine, Life, Health & Environmental Sciences-MESVA, University of L'Aquila, 67100 L, Aquila, Italy
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Nosewicz J, Spaccarelli N, Roberts KM, Hart PA, Kaffenberger JA, Trinidad JC, Kaffenberger BH. The Epidemiology, Impact, and Diagnosis of Micronutrient Nutritional Dermatoses Part 1: Zinc, Selenium, Copper, Vitamin A, and Vitamin C. J Am Acad Dermatol 2021; 86:267-278. [PMID: 34748862 DOI: 10.1016/j.jaad.2021.07.079] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2021] [Revised: 07/16/2021] [Accepted: 07/23/2021] [Indexed: 11/27/2022]
Abstract
Dermatologists play a critical role in diagnosing and managing nutritional deficiencies as they often present with cutaneous findings. Traditionally, nutritional dermatoses are taught in the context of developing countries, famine, population displacement, and poor healthcare access; however, in the United States, common risk factors include chronic liver disease, alcoholism, psychiatric disease, bariatric surgery, inflammatory bowel disease, and hemodialysis. Additionally, nutritional dermatoses may be underdiagnosed in the United States and result in increased morbidity and utilization of hospital resources. There is a need for providers in developed nations to identify these deficiencies, and this review aims to meet that practice gap and provide relevant context to these diseases for dermatologists. This two-part review series will focus on the epidemiology, impact, appearance, and diagnostic modalities for micronutrient deficiencies, including zinc, selenium, copper, and vitamins A and C in part one. The companion review will focus on the B-complex vitamins.
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Affiliation(s)
- Jacob Nosewicz
- Division of Dermatology, The Ohio State University Wexner Medical Center, Columbus, Ohio
| | - Natalie Spaccarelli
- Division of Dermatology, The Ohio State University Wexner Medical Center, Columbus, Ohio
| | - Kristen M Roberts
- Division of Gastroenterology, Hepatology and Nutrition, The Ohio State University Wexner Medical Center, Columbus, Ohio
| | - Phil A Hart
- Division of Gastroenterology, Hepatology and Nutrition, The Ohio State University Wexner Medical Center, Columbus, Ohio
| | - Jessica A Kaffenberger
- Division of Dermatology, The Ohio State University Wexner Medical Center, Columbus, Ohio
| | - John C Trinidad
- Division of Dermatology, The Ohio State University Wexner Medical Center, Columbus, Ohio
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20
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Ristic-Medic D, Petrovic S, Arsic A, Vucic V. Liver disease and COVID-19: The link with oxidative stress, antioxidants and nutrition. World J Gastroenterol 2021; 27:5682-5699. [PMID: 34629794 PMCID: PMC8473601 DOI: 10.3748/wjg.v27.i34.5682] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Revised: 04/11/2021] [Accepted: 08/17/2021] [Indexed: 02/06/2023] Open
Abstract
Varying degrees of liver injuries have been reported in patients infected with the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). In general, oxidative stress is actively involved in initiation and progression of liver damage. The liver metabolizes various compounds that produce free radicals. Maintaining the oxidative/antioxidative balance is important in coronavirus disease 2019 (COVID-19) patients. Antioxidant vitamins, essential trace elements and food compounds, such as polyphenols, appear to be promising agents, with effects in oxidative burst. Deficiency of these nutrients suppresses immune function and increases susceptibility to COVID-19. Daily micronutrient intake is necessary to support anti-inflammatory and antioxidative effects but for immune function may be higher than current recommended dietary intake. Antioxidant supplements (β-carotene, vitamin A, vitamin C, vitamin E, and selenium) could have a potential role in patients with liver damage. Available evidence suggests that supplementing the diet with a combination of micronutrients may help to optimize immune function and reduce the risk of infection. Clinical trials based on the associations of diet and SARS-CoV-2 infection are lacking. Unfortunately, it is not possible to definitively determine the dose, route of administration and best timing to intervene with antioxidants in COVID-19 patients because clinical trials are still ongoing. Until then, hopefully, this review will enable clinicians to understand the impact of micronutrient dietary intake and liver status assessment in COVID-19 patients.
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Affiliation(s)
- Danijela Ristic-Medic
- Group for Nutritional Biochemistry and Dietology, Centre of Research Excellence in Nutrition and Metabolism, National Institute for Medical Research, University of Belgrade, Belgrade 11129, Serbia
| | - Snjezana Petrovic
- Group for Nutritional Biochemistry and Dietology, Centre of Research Excellence in Nutrition and Metabolism, National Institute for Medical Research, University of Belgrade, Belgrade 11129, Serbia
| | - Aleksandra Arsic
- Group for Nutritional Biochemistry and Dietology, Centre of Research Excellence in Nutrition and Metabolism, National Institute for Medical Research, University of Belgrade, Belgrade 11129, Serbia
| | - Vesna Vucic
- Group for Nutritional Biochemistry and Dietology, Centre of Research Excellence in Nutrition and Metabolism, National Institute for Medical Research, University of Belgrade, Belgrade 11129, Serbia
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21
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Copper Toxicity Is Not Just Oxidative Damage: Zinc Systems and Insight from Wilson Disease. Biomedicines 2021; 9:biomedicines9030316. [PMID: 33804693 PMCID: PMC8003939 DOI: 10.3390/biomedicines9030316] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Revised: 03/13/2021] [Accepted: 03/17/2021] [Indexed: 12/13/2022] Open
Abstract
Essential metals such as copper (Cu) and zinc (Zn) are important cofactors in diverse cellular processes, while metal imbalance may impact or be altered by disease state. Cu is essential for aerobic life with significant functions in oxidation-reduction catalysis. This redox reactivity requires precise intracellular handling and molecular-to-organismal levels of homeostatic control. As the central organ of Cu homeostasis in vertebrates, the liver has long been associated with Cu storage disorders including Wilson Disease (WD) (heritable human Cu toxicosis), Idiopathic Copper Toxicosis and Endemic Tyrolean Infantile Cirrhosis. Cu imbalance is also associated with chronic liver diseases that arise from hepatitis viral infection or other liver injury. The labile redox characteristic of Cu is often discussed as a primary mechanism of Cu toxicity. However, work emerging largely from the study of WD models suggests that Cu toxicity may have specific biochemical consequences that are not directly attributable to redox activity. This work reviews Cu toxicity with a focus on the liver and proposes that Cu accumulation specifically impacts Zn-dependent processes. The prospect that Cu toxicity has specific biochemical impacts that are not entirely attributable to redox may promote further inquiry into Cu toxicity in WD and other Cu-associated disorders.
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22
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Grzeszczak K, Kwiatkowski S, Kosik-Bogacka D. The Role of Fe, Zn, and Cu in Pregnancy. Biomolecules 2020; 10:E1176. [PMID: 32806787 PMCID: PMC7463674 DOI: 10.3390/biom10081176] [Citation(s) in RCA: 91] [Impact Index Per Article: 18.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2020] [Revised: 08/05/2020] [Accepted: 08/05/2020] [Indexed: 12/15/2022] Open
Abstract
Iron (Fe), copper (Cu), and zinc (Zn) are microelements essential for the proper functioning of living organisms. These elements participatein many processes, including cellular metabolism and antioxidant and anti-inflammatory defenses, and also influence enzyme activity, regulate gene expression, and take part in protein synthesis. Fe, Cu, and Zn have a significant impact on the health of pregnant women and in the development of the fetus, as well as on the health of the newborn. A proper concentration of these elements in the body of women during pregnancy reduces the risk of complications such as anemia, induced hypertension, low birth weight, preeclampsia, and postnatal complications. The interactions between Fe, Cu, and Zn influence their availability due to their similar physicochemical properties. This most often occurs during intestinal absorption, where metal ions compete for binding sites with transport compounds. Additionally, the relationships between these ions have a great influence on the course of reactions in the tissues, as well as on their excretion, which can be stimulated or delayed. This review aims to summarize reports on the influence of Fe, Cu, and Zn on the course of single and multiple pregnancies, and to discuss the interdependencies and mechanisms occurring between Fe, Cu, and Zn.
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Affiliation(s)
- Konrad Grzeszczak
- Department of Biology and Medical Parasitology, Pomeranian Medical University in Szczecin, Powstańców Wielkopolskich 72, 70-111 Szczecin, Poland;
| | - Sebastian Kwiatkowski
- Department of Obstetrics and Gynecology, Pomeranian Medical University in Szczecin, Powstańców Wielkopolskich 72, 70-111 Szczecin, Poland;
| | - Danuta Kosik-Bogacka
- Independent Laboratory of Pharmaceutical Botany, Pomeranian Medical University in Szczecin, Powstańców Wielkopolskich 72, 70-111 Szczecin, Poland
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Kang NL, Zhang JM, Lin MX, Chen XD, Huang ZX, Zhu YY, Liu YR, Zeng DW. Serum ceruloplasmin can predict liver fibrosis in hepatitis B virus-infected patients. World J Gastroenterol 2020; 26:3952-3962. [PMID: 32774069 PMCID: PMC7385565 DOI: 10.3748/wjg.v26.i27.3952] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2020] [Revised: 05/06/2020] [Accepted: 06/30/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The presence of significant liver fibrosis in hepatitis B virus (HBV)-infected individuals with persistently normal serum alanine aminotransferase (PNALT) levels is a strong indicator for initiating antiviral therapy. Serum ceruloplasmin (CP) is negatively correlated with liver fibrosis in HBV-infected individuals. AIM To examine the potential value of serum CP and develop a noninvasive index including CP to assess significant fibrosis among HBV-infected individuals with PNALT. METHODS Two hundred and seventy-five HBV-infected individuals with PNALT were retrospectively evaluated. The association between CP and fibrotic stages was statistically analyzed. A predictive index including CP [Ceruloplasmin hepatitis B virus (CPHBV)] was constructed to predict significant fibrosis and compared to previously reported models. RESULTS Serum CP had an inverse correlation with liver fibrosis (r = -0.600). Using CP, the areas under the curves (AUCs) to predict significant fibrosis, advanced fibrosis, and cirrhosis were 0.774, 0.812, and 0.853, respectively. The CPHBV model was developed using CP, platelets (PLT), and HBsAg levels to predict significant fibrosis. The AUCs of this model to predict significant fibrosis, advanced fibrosis, and cirrhosis were 0.842, 0.920, and 0.904, respectively. CPHBV was superior to previous models like the aspartate aminotransferase (AST)-to-PLT ratio index, Fibrosis-4 score, gamma-glutamyl transpeptidase-to-PLT ratio, Forn's score, and S-index in predicting significant fibrosis in HBV-infected individuals with PNALT. CONCLUSION CPHBV could accurately predict liver fibrosis in HBV-infected individuals with PNALT. Therefore, CPHBV can be a valuable tool for antiviral treatment decisions.
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Affiliation(s)
- Na-Ling Kang
- Liver Center, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian Province, China
| | - Jie-Min Zhang
- Department of Pharmacy, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian Province, China
| | - Meng-Xin Lin
- Department of Infectious Diseases, The First Hospital of Quanzhou Affiliated with Fujian Medical University, Quanzhou 362000, Fujian Province, China
| | - Xu-Dong Chen
- Department of Gastroenterology, the 910th Hospital of the People's Liberation Army, Quanzhou 362000, Fujian Province, China
| | - Zu-Xiong Huang
- Hepatology, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350005, Fujian Province, China
| | - Yue-Yong Zhu
- Liver Center, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian Province, China
| | - Yu-Rui Liu
- Liver Center, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian Province, China
| | - Da-Wu Zeng
- Liver Center, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian Province, China
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Soldath P, Lund A, Vissing J. Late-onset MADD: a rare cause of cirrhosis and acute liver failure? ACTA MYOLOGICA : MYOPATHIES AND CARDIOMYOPATHIES : OFFICIAL JOURNAL OF THE MEDITERRANEAN SOCIETY OF MYOLOGY 2020; 39:19-23. [PMID: 32607475 PMCID: PMC7315895 DOI: 10.36185/2532-1900-003] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/03/2020] [Accepted: 03/20/2020] [Indexed: 06/11/2023]
Abstract
Late-onset multiple acyl-CoA dehydrogenase deficiency (MADD) is a severe inborn error of fat metabolism. In late-onset MADD, hepatopathy in the form of steatosis is commonplace and considered a benign and stable condition that does not progress to more advanced stages of liver disease, however, progression to cirrhosis and acute liver failure (ALF) has been reported in two previous case reports. Here, we report a 22-year-old man, who suffered from late-onset MADD and died from cirrhosis and ALF. In the span of three months repeated clinical examinations, blood tests, and diagnostic imaging as well as liver biopsy revealed rapid progression of hepatopathy from steatosis to decompensated cirrhosis with portal hypertension. Routine studies for recognized etiologies found no evident cause besides MADD. This case report supports the findings of the two previous case reports and adds further evidence to the suggestion that late-onset MADD should be considered a rare cause of cirrhosis and ALF.
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Affiliation(s)
- Patrick Soldath
- Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Copenhagen Neuromuscular Center, Department of Neurology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - Allan Lund
- Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Centre for Inherited Metabolic Diseases, Departments of Paediatrics and Clinical Genetics, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - John Vissing
- Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Copenhagen Neuromuscular Center, Department of Neurology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
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Kozeniecki M, Ludke R, Kerner J, Patterson B. Micronutrients in Liver Disease: Roles, Risk Factors for Deficiency, and Recommendations for Supplementation. Nutr Clin Pract 2019; 35:50-62. [PMID: 31840874 DOI: 10.1002/ncp.10451] [Citation(s) in RCA: 36] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Micronutrients are essential components of the diet and are required to maintain fundamental bodily functions. Liver disease has a profound effect on nutrient intake, metabolism of nutrients, and nutrition status, often resulting in some degree of malnutrition, including micronutrient deficiency. Vitamin and mineral deficiencies can impair metabolic processes at the cellular and biochemical level even before clinical and physical alterations are seen. It is essential that micronutrient status is evaluated as part of a comprehensive nutrition assessment for all patients with chronic or advanced liver disease. Early intervention to correct suspected or confirmed deficiencies may minimize symptoms and improve clinical outcomes and quality of life. In this narrative review, different types of liver disease and associated micronutrient abnormalities are outlined, and methods of micronutrient assessment and supplementation are discussed.
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Affiliation(s)
- Michelle Kozeniecki
- Department of Nutrition Services, Froedtert Hospital, Milwaukee, Wisconsin, USA
| | - Rachel Ludke
- Department of Nutrition Services, Froedtert Hospital, Milwaukee, Wisconsin, USA
| | - Jennifer Kerner
- Transplant Institute, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA
| | - Brittney Patterson
- Clinical Nutrition Department, Stanford Health Care, Stanford, California, USA
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