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Background: Impaired cognitive function following exposure to heavy metals has emerged as a significant global health concern. Nevertheless, the impact of combined exposure to multiple heavy metals on cognitive impairment remains unclear., Objective: This study aimed to explore the association between multiple heavy metals exposure and cognitive function to provide theoretical evidence to guide prevention strategies., Methods: The blood levels of lead (Pb), cadmium (Cd), mercury (Hg), selenium (Se), copper (Cu) and zinc (Zn) and the results of the cognitive function tests were extracted from 811 elderly Americans who completed the NHANES between 2011 and 2014. Quantile regression (QR), restricted cubic splines (RCS), and Bayesian kernel machine regression (BKMR) were used to explore the individual and joint association between heavy metals exposure and performance in 4 standardized cognitive tests; Item Response Theory (IRT), Delayed Recall Test (DRT), Animal Fluency Test (AFT) and Digit Symbol Substitution Test (DSST)., Results: A negative association was noted between Cd levels and IRT (p = 0.048, 95%CI: -2.7, -0.1). Se concentrations ranging between 2.197 µg/L (95%CI: 0.004, 0.15) to 2.29 µg/L (95%CI: 2.56, 7.64) (log 10 Se) was postively associated with DSST (p = 0.001 ). Cu was negatively associated with DSST (p = 0.049, 95%CI: -37.75, -0.09), while Zn was positively associated with IRT (p = 0.022, 95%CI: 0.55, 11.73). Exposure to the 6 heavy metals combined showed a positive linear association with IRT, DRT, and a negative linear association with DSST. An interaction between Cd and the other heavy metals (excepted for Pb)., Conclusion: Exposure to Pb, Cd, Hg, Se, Cu, and Zn was associated with cognitive function. Joint exposure to the 6 heavy metals showed a positive linear association with IRT, DRT, contrarily, a negative linear association with DSST., Competing Interests: Declarations Ethics approval and consent to participate The NHANES database is publicly available and has been approved by the Institutional Review Board of the National Center for Health Statistics (NCHS). All participants provided written informed consent during their participation in the national survey conducted in the United States. Ethical review and approval were waived for this study as it involved secondary analysis and did not necessitate additional institutional review board approval. Consent for publication Not applicable. Competing interests The authors declare no competing interests. Highlight Pb, Cd, Hg, Se, Cu, and Zn were significantly associated with cognitive function.An interaction between Cd and the other heavy metals (excepted for Pb).Exposure to the 6 heavy metals combined showed a positive linear association with IRT, DRT and a negative linear association with DSST., (© 2024. The Author(s).)

Objectives: While some metals have been reported as carcinogens or potential carcinogens, only few modern-standard datasets including a large number of elements are available. The present analysis established a first trace elements spectrum by relating the concentration of metals and trace elements in the serum of sarcoma patients with survival data., Methods: Patients with sarcoma and controls were retrospectively selected from the International Sarcoma Kindred Study database (ISKS). As part of the ISKS study, blood samples were prospectively collected at the Leon Bérard Cancer Center from February 2012 to July 2019. Stable specimens and copper isotopes ( 65 Cu/ 63 Cu) were analyzed using Triple Quadrupole Inductively Coupled Plasma Mass Spectrometer (ICP-MS) and the Multicollector MC-ICP-MS Nu Plasma HR 500. Wilcoxon rank sum test, log-rank test, and multivariate Cox regression models were used for statistics., Results: In total, 151 patients and 59 healthy controls were included. At the time of blood sample collection, 62% of patients had locally advanced or metastatic disease. Copper (Cu), copper/zinc (Cu/Zn) and potassium/rubidium (K/Rb) ratio were significantly higher in patients compared to controls and were also significantly higher in patients with advanced compared to early-stage sarcoma. Whereas S and Se were significantly correlated in patients, no correlation was observed in controls. Importantly, levels of K, Rb, Se, Fe, P, Si, S, δ 65 Cu, Cu, S/Se and Cu/Zn ratio were independently associated with overall survival., Conclusions: These results depict the metallomic spectrum in sarcoma and highlight substantial variation associated with survival, enhancing our understanding of sarcoma's biology., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: A dual filtration-based method for determination of serum labile bound copper (LBC) and LBC fraction (LBC/total copper) was developed. Reduced total copper, elevated LBC, and elevated LBC fraction have been reported in Wilson disease (WD)., Methods: To evaluate the diagnostic performance of these markers, samples were obtained from 21 WD treatment-naïve (WD-TN, no WD treatment or <28 days of treatment) patients, 46 WD standard-of-care-treated (WD-SOC) patients, along with 246 patients representing other potential disorders of copper status. These were then compared to 213 reference interval population patients., Results: Receiver operating characteristic curves for the reference population vs WD-TN yielded areas under the curve for total copper, LBC, and LBC fraction, of 0.99, 0.81, and 0.98, respectively. Using Youden cutoffs, sensitivity/specificity for WD-TN was 95%/97% for total copper, 71%/85% for LBC, and 95%/94% for LBC fraction. LBC values, but not total copper and LBC fraction, differed substantially between WD-TN and WD-SOC cohorts.We propose a dual model wherein total copper and LBC fraction results must agree to be classified as a "positive" or "negative" result for WD. This correctly classified 19/21 WD-TN patients as positive, and 194/213 reference interval patients as negative. The remaining "indeterminate" patients (representing approximately 9% of the reference and the WD-TN populations) exhibited conflicting total copper and LBC fraction results. When indeterminate results are excluded, this model exhibited apparent 100% sensitivity/specificity., Conclusions: Agreement of total serum copper and LBC fraction classification may constitute an effective "rule-in" and "rule-out" assessment for WD-TN patients., (© Association for Diagnostics & Laboratory Medicine 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

It is unclear whether blood concentrations of copper (Cu), magnesium (Mg), and calcium (Ca) influence skeletal muscle mass and strength in children. We aimed to explore the associations between plasma Cu, Mg, and Ca and skeletal muscle indicators in Chinese children. A total of 452 children aged 6 to 9 years old were recruited for this cross-sectional study. Whole body lean soft tissue mass (WLSTM), trunk lean soft tissue mass (TLSTM), and appendicular skeletal muscle mass (ASMM) were measured using dual-energy X-ray absorptiometry. Parameters of these indicators divided by Height 2 (Ht 2 ) and Weight (Wt) at the corresponding sites were calculated. Handgrip strength was also measured. Parameters of skeletal muscle indicators and handgrip strength that were below the sex-specific 20th percentile were considered low levels. Plasma concentrations of Cu, Mg, and Ca were measured using ICP-MS. After adjusting for several potential covariates, among the total subjects, for every one standard deviation increase in Cu concentrations, there was a 0.939% decrease in WLSTM/Wt, a 0.415% decrease in TLSTM/Wt, and a 0.47% decrease in ASMM/Wt. For every one standard deviation increase in Cu concentrations, there was a higher odd (OR: 1.36, 95%CI 1.06, 1.75) of low WLSTM/Wt, TLSTM/Wt (OR: 1.33, 95%CI 1.03, 1.71), ASMM/Ht 2 (OR: 1.32, 95%CI 1.02, 1.69), as well as ASMM/Wt (OR: 1.56, 95%CI 1.23, 1.99). No significant associations were found between Mg, Ca, and most skeletal muscle indicators. Higher plasma Cu concentrations were adversely associated with skeletal muscle indicators at multiple sites in Chinese children., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Context: Copper deficiency myelopathy (CDM) is a rare disease that can present with spastic quadriparesis and sensory ataxia. As a result, it can precisely mimic cervical spondylitic myelopathy (CSM). Copper deficiency may be seen following gastric bypass surgery, malabsorption syndromes such as celiac disease, and with excessive exogenous zinc intake. We present a systematic review of the literature for CDM and an illustrative case., Purpose: Provide a systematic review of CDM to highlight the importance of recognizing the consideration of CDM in patients presenting to a spine surgeon with myelopathy that progress despite adequate surgical decompression, or myelopathy concomitant with cytopenia, thus requiring further workup., Study Design/setting: Retrospective medical record review and systematic review of the literature., Patient Sample: PubMed and Ovid-Embase database search was conducted in July 2022., Outcome Measures: Self-reported measures include PRISMA flow diagram for retrospective review; Physiological measures include retrospective review of MRI imaging of cervical spine; alternate demographic and laboratory value data extracted via literature review., Methods: A PubMed and Ovid-Embase database search was conducted in July 2022 searching for "copper deficiency myelopathy (MeSH)" from 2000 to 2022 via PRISMA guidelines. Following title and abstract review, the following data was extracted from full text: age, sex, etiology, hematological values upon presentation (mean corpuscular volume, white blood count, platelet count, and hemoglobin level), metal serum studies (serum copper, ceruloplasmin, and zinc), 24-hour collection of copper and zinc, and distinct radiographic findings on MRI., Results: A total of 116 studies were included in this review which contained 198 cases of copper deficiency myelopathy. The mean age was 53.57±14.14 years, with the majority being females (63.8%). The most common etiology was prior gastric surgery (n=55, 36.2 %) followed by excessive zinc consumption from the use of zinc denture cream (n=39, 19.9%). The mean serum copper was 15.67±17.84 (normal=80.0-155.0) mcg/dL and mean ceruloplasmin was 6.43±5.25 (normal=16-45) mg/dL. In spite of appropriate treatment with copper supplementation, only 47 cases (24%) reported improvement in neurological status, and only 10 (5.1%) recovered to baseline. A hyperintense T2 signal abnormality resembling an inverted "v" in the dorsal columns was the most common radiographic abnormality., Conclusion: Pertinent risk factors for copper deficiency myelopathy include prior upper gastrointestinal surgery, zinc excess, and malabsorption. Characteristic laboratory and imaging findings include cytopenia, low serum copper and ceruloplasmin, and distinct inverted "v" T2 signal hyperintensity in the dorsal columns. The neurologic deterioration with copper deficiency will progress in spite of decompressive surgery, and can be devastating and irreversible even with copper supplementation, reinforcing the importance of early detection. We thus recommend patients with myelopathy presenting with a history of gastric bypass, malabsorption syndromes, excessive zinc exposure, cytopenia, or imaging resembling an inverted "v" shaped hyperintense T2 MRI signal in the dorsal columns, should first undergo blood tests for copper, ceruloplasmin, and B12 levels prior to surgical consideration., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Illicit drug use has become a global issue, posing significant health, socioeconomic, and cultural risks. The study examined essential trace metals: selenium, zinc, and copper in blood concentrations, as well as in serum and scalp hair samples, from 240 male drug-abuse subjects/patients aged 18-45, categorized into three age groups. The study compared 45 healthy subjects of the same age group using an acid digestion method supported by a microwave oven during sample preparation. The technique of atomic absorption spectrometry was employed to identify essential and toxic elements, utilizing certified reference materials for accuracy. According to a recent study, plasma zinc and selenium concentrations in drug abusers are lower than those in referent subjects, potentially increasing vulnerability to infection due to poor nutritional status or other contaminants., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: This phase 1/2 study aimed to evaluate the safety and preliminary efficacy of combining disulfiram and copper (DSF/Cu) with radiation therapy (RT) and temozolomide (TMZ) in patients with newly diagnosed glioblastoma (GBM)., Methods and Materials: Patients received standard RT and TMZ with DSF (250-375 mg/d) and Cu, followed by adjuvant TMZ plus DSF (500 mg/d) and Cu. Pharmacokinetic analyses determined drug concentrations in plasma and tumors using high-performance liquid chromatography-mass spectrometry., Results: Thirty-three patients, with a median follow-up of 26.0 months, were treated, including 12 IDH-mutant, 9 NF1-mutant, 3 BRAF-mutant, and 9 other IDH-wild-type cases. In the phase 1 arm, 18 patients were treated; dose-limiting toxicity probabilities were 10% (95% CI, 3%-29%) at 250 mg/d and 21% (95% CI, 7%-42%) at 375 mg/d. The phase 2 arm treated 15 additional patients at 250 mg/d. No significant difference in overall survival or progression-free survival was noted between IDH- and NF1-mutant cohorts compared with institutional counterparts treated without DSF/Cu. However, extended remission occurred in 3 BRAF-mutant patients. Diethyl-dithiocarbamate-copper, the proposed active metabolite of DSF/Cu, was detected in plasma but not in tumors., Conclusions: The maximum tolerated dose of DSF with RT and TMZ is 375 mg/d. DSF/Cu showed limited clinical efficacy for most patients. However, promising efficacy was observed in BRAF-mutant GBM, warranting further investigation., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Copper is an essential trace element obtained from food. There is a paucity of observational or prospective studies that have investigated the relationship between copper and melanoma risk. Copper serves as a cofactor for pivotal enzymes involved in mitochondrial respiration, antioxidant defense, and neurotransmitter synthesis. Undoubtedly, copper plays an indispensable role in the initiation and progression of tumors, particularly melanoma; however, further investigations are warranted to elucidate the underlying mechanisms linking copper and melanoma risk. Given the availability of dietary copper and serum copper data in the NHANES database, we conducted an investigation into the association between dietary copper intake and serum copper levels with melanoma risk. We enrolled 26,401 individuals with dietary copper data in the 2007-2018 NHANES database. To mitigate confounding variables, a propensity score matching (PSM) was performed. To assess the association between dietary copper intake and melanoma risk, we employed a multivariate logistic regression analysis before and after PSM. The restricted cubic spline analysis was utilized to determine whether there is a non-linear relationship between dietary copper intake and melanoma risk, with subgroup analysis conducted to determine beneficiaries. Then, those with blood copper data from the enrolled population with dietary copper intake were screened out, and subsequently, multivariate logistic regression models were subsequently constructed to investigate the association between serum copper levels and melanoma risk after PSM. Mendelian analysis was further utilized to validate the results of the NHANES database using serum copper as the exposure factor and melanoma as the outcome variable. The study found that melanoma risk was associated with dietary copper intake before and after PSM, demonstrated by multiple logistic regression. The relationship between dietary copper intake and melanoma risk was non-linear, with a reduced risk observed above approximately 2.5 mg/day, as shown by the RCS. The evidence suggests that an increased intake of copper is linked to a decreased risk of melanoma. To clarify the mechanism behind the increased risk of melanoma due to higher dietary copper intake, we analyzed the population data from the NHANES database on serum copper and dietary copper intake. Our results indicated that there is no causal relationship between serum copper and melanoma risk. Mendelian randomization analysis of multi-database data sources confirmed the conclusion of the NHANES database analysis. Dietary copper is a protective factor against melanoma, and serum copper or blood copper is not associated with melanoma risk. This suggests that serum or blood copper is not responsible for the protective effect of dietary copper intake on melanoma risk, and the mechanisms need to be further investigated., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The role of copper in the etiology of metabolic syndrome (MetS) is uncertain. We evaluated associations of plasma copper concentrations with MetS and its components in a cross-sectional study of 198 children ages 7-12 years and 378 adult parents from eight Mesoamerican countries. In children, the outcome was a metabolic risk score based on waist circumference, insulin resistance, mean arterial pressure (MAP), and blood lipids. In adults, we defined MetS per Adult Treatment Panel III criteria. Plasma copper was not significantly related to MetS in children or adults; however, children with copper above the median had a MAP score 0.04 (95% CI, 0.002, 0.08; P = 0.04) adjusted units higher and a HDL-cholesterol score 0.07 (95% CI, - 0.13, - 0.003; P = 0.04) adjusted units lower than those with lower copper concentrations. In adults, copper was positively related to abdominal obesity. Longitudinal studies to confirm the deleterious role of copper on MetS components are warranted., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Various vitamins and minerals have been implicated in the aetiology of depression., Objective: To estimate the effects of micronutrient exposures on major depressive disorder (MDD) and recurrent depression (rMDD) using Mendelian randomisation (MR), a method using genetic data to estimate causal effects given certain assumptions., Methods: We undertook a comprehensive bidirectional MR study of multiple micronutrient exposures on MDD and rMDD. Summary statistics were obtained from the Psychiatric Genomics Consortium (PGC) genome-wide association studies (GWASs) of MDD (cases = 116,209; controls = 314,566) and rMDD (cases = 17,451; controls = 62,482)., Results: None of the micronutrients with available genetic instruments were strongly associated with MDD or rMDD using traditional MR methods. However, using methods to increase analytical power by accounting for genetically correlated variants (e.g., cIVW) highlighted five micronutrients with possible causal effects. Point estimates for rMDD were the largest magnitude, with three micronutrients suggestive of a protective effect: serum iron (OR cIVW 0.90 per SD increase; 95% CI 0.85-0.95; p = 0.0003); erythrocyte copper (OR cIVW 0.97; 95% CI 0.95-0.99; p = 0.0004); and 25(OH) vitamin D (OR cIVW 0.81; 0.66-0.99; p = 0.04). Apparent adverse effects of increased selenium on the risk of MDD (OR cIVW 1.03; 95% CI 1.02-1.05; p = 0.0003) and rMDD (OR cIVW 1.08; 95% CI 1.00-1.08; p = 0.06), and serum magnesium on rMDD (OR cIVW 1.21; 1.01-1.44; p = 0.04); were less consistent between methods and may be driven by pleiotropy., Conclusions: Our results suggest weak evidence for a protective effect of iron, copper and 25(OH)D on major depressive outcomes, with mixed evidence for selenium and magnesium. There was no evidence to support a causal effect of any other micronutrients on MDD or rMDD, although genetic instruments were lacking, with insufficient power to detect small but important effects. Future micronutrient supplementation trials should ensure ample statistical power given modest causal effect estimates and consider potential risks of supplementation, as some micronutrient effect estimates suggested potential harm in excess.

Objective: Lung adenocarcinoma (LA), the most prevalent type of lung cancer, is associated with a high mortality rate, especially among patients with cancer previously infected with coronavirus disease (COVID-19). Therefore, this study aimed to explore the mechanisms by which COVID-19 exacerbates LA progression in a clinical setting., Methods: The experiment involved collecting serum samples from three groups: a healthy control group (Con, n = 20), a lung adenocarcinoma group (LA, n = 30), and a group of lung adenocarcinoma patients with first-time COVID-19 infection (C-LA, n = 58). Metabolites were analyzed using liquid chromatography-mass spectrometry, and differentially expressed metabolites were identified through bioinformatics analysis. The concentrations of glutathione (GSH), reactive oxygen species (ROS), and copper ions (Cu 2+ ) in the serum of patients in the Con and C-LA groups were measured. Mitochondrial morphological changes in monocytes and lymphocytes were observed using electron microscopy., Results: Metabolomic analysis revealed 142 distinct metabolites, among which glutamine (Gln) expression was significantly decreased in the C-LA group. Compared to the Con group, the C-LA group showed a significant decrease in GSH and a notable increase in ROS and Cu 2+ . Further research revealed that the mitochondria of monocytes and lymphocytes in the C-LA group exhibited corresponding alterations indicative of cuproptosis., Conclusions: SARS-CoV-2 infection may reduce Gln levels, leading to reduced GSH levels, copper overload, and increased death of immune cells, which may further exacerbate rapid tumor development. Thus, glutamine regulation plays an important role in LA progression in patients with COVID-19 and represents a potential therapeutic target., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Vitamin D deficiency is prevalent worldwide and associated with worse outcomes in various lung diseases. This study examines the association between vitamin D deficiency and pulmonary function in healthy young adults., Methods: This prospective cohort study (2017-2019) explored the impact of vitamin D deficiency on pulmonary function in a community-based young adult population. Pulmonary function was assessed via spirometry, with serum 25-hydroxyvitamin D [25(OH)D] and urinary copper levels quantified. Multivariate regression was used to estimate the relationship between vitamin D levels and lung function, with mediation analysis evaluating copper's role., Results: The study included 1034 participants, average age 33.45 years, 41.93 % male. The median 25(OH)D level was 19.20 ng/mL (Interquartile Range: 13.48-24.90 ng/mL). Over half (54.74 %) had 25(OH)D levels below 20 ng/mL. Higher 25(OH)D levels were associated with better forced vital capacity (FVC) and forced expiratory volume in one second (FEV₁). Trends suggested subgroup differences, but these were not statistically significant, indicating a consistent effect of 25(OH)D on pulmonary function across groups. SEM analysis suggested urinary copper as a mediator between 25(OH)D levels and FVC., Conclusion: Vitamin D deficiency is significantly associated with reduced pulmonary function in young adults in Taiwan., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Vitiligo is a dermatological disease characterized by loss of melanocytes, causing non-scaly white macules on the skin. Zinc, copper, and selenium are important micronutrients that play a role in the normal functioning of the body and have been found to potentially aid in vitiligo treatment, although the relationship between their serum levels and vitiligo is not yet fully understood. This is a systematic review aimed at assessing the levels of serum zinc, copper, and selenium and their association with vitiligo. This review was performed following the Preferred Reporting Items of the systematic Review and Meta-Analysis (PRISMA) checklist and Cochrane guidelines. A comprehensive literature search was conducted on PubMed, Google Scholar and 41 studies published between 1970 and 2022 including 3353 vitiligo cases and 10,638 controls were included in the meta-analysis conducted from August 2022 till September 2023. The quality of the studies was assessed using the National Heart Lung and Blood Institute Study Quality Assessment tool, and the risk of bias was represented using the RobVis tool. The statistical analysis was performed using Review Manager (RevMan) Version 5.4. This meta-analysis indicate a significant decline in serum zinc levels (Z = 4.97; P < 0.0001; SMD = - 0.86; 95% CI - 1.19 to - 0.52) in vitiligo group with high statistical heterogeneity (Tau2 = 0.74; Chi2 = 513.95, d.f. = 26 [P < 0.00001]; I2 = 95%). Similarly for serum copper levels there was decline (Z = 2.43; P < 0.0001; SMD = - 0.50; 95% confidence interval [CI] - 0.91 to - 0.10) in vitiligo group and high statistical heterogeneity (Tau2 = 0.92; Chi2 = 475.10, d.f. = 22 [P < 0.00001]; I2 = 95%). On the other hand, there was a increase of serum selenium levels in the vitiligo group (Z = 0.56; P < 0.0001; SMD = 0.23; 95% confidence interval [CI], 0.58 to 1.04) and the results reveals high statistical heterogeneity among studies (Tau2 = 1.93; Chi2 = 406.44, d.f. = 11 [P < 0.00001]; I2 = 97%) in vitiligo patients compared to healthy controls. Publication bias was not found for the studies analysed. This study analyses the association of serum micronutrient levels and vitiligo among patients and controls from published research along with sub-group analysis specific to Asian populations using a meta-analysis. Low serum levels of Zinc and copper and high selenium levels are associated with Vitiligo., (© 2024. The Author(s).)

Objective: The objective of this study is to analyze oxidative stress markers Total Oxidant Status (TOS) and total Antioxidant Status (TAS), assess antioxidant levels (vitamin C, E), and evaluate co-factor element profiles zinc (Zn), copper (Cu), iron (Fe) in the serum of Iraqi gastric cancer patients. By elucidating these relationships, the research aims to enhance knowledge on oxidative stress, dietary factors, and potential therapeutic approaches for managing nutritional imbalances in this cohort., Methods: The study included 60 gastric cancer patients and 60 matched controls. Blood samples were collected and serum was extracted for analysis of TOS, TAS, Vitamin C, Vitamin E, copper, zinc, and iron levels. Measurements were conducted using spectrophotometry and ELISA kits from various companies. Statistical analysis was performed with IBM SPSS 25.0, presenting results as means ± SD, and differences between groups were assessed via independent samples t-test at p < 0.05 and p ≤ 0.01., Results: The study results indicated statistically significant differences between gastric cancer patients and controls in various biomarkers, with all comparisons showing p-values less than 0.001. This suggests strong evidence for the observed differences between the two groups in (TOS), (TAS), vitamins C and E, Cu, Zn, and  Fe levels. These relationships underscore the intricate connections among biomarkers in gastric cancer pathophysiology., Conclusion: The study underscores the intricate relationship between oxidative stress, antioxidant depletion, and micronutrient imbalances in gastric cancer. These findings offer valuable insights into the disease's pathophysiology, indicating potential diagnostic biomarkers. Further research is warranted to unravel underlying mechanisms and explore clinical applications for early gastric cancer diagnosis.

Objective: To investigate the value of relative exchangeable copper (REC) in diagnosing Wilson's disease (WD) and to determine its significance in the differentiation of Traditional Chinese Medicine (TCM) syndrome., Methods: A total of 78 patients with WD were recruited on the same day of the medical visit, and among them, 32 were suffering from non-WD (N-WD) and 37 were heterozygous ATP7B carriers (HC) enrolled as controls. Molecular genetic testing was performed for diagnosing WD and HC. Additionally, REC levels in different TCM syndromes were investigated. The correlation between REC and serum ceruloplasmin (Cp), serum copper oxidase (CO), and 24-h urinary copper was analyzed using the Global Assessment Scale and Unified Wilson's Disease Rating Scale and the significance of REC in WD diagnosis was investigated. Resting-state functional magnetic resonance imaging was used to assess the clinical symptoms of WD and analyze its severity in different TCM syndromes., Results: REC determination helped in significantly distinguishing patients with N-WD or HC from those with WD with a cut-off of 21.15%. Furthermore, the comparative analysis of REC ratios among different TCM syndromes showed markedly high REC levels in the dampness-heat internal accumulation syndrome group. Additionally, the seed-based functional connectivity value from the putamen to the cerebellum was significantly correlated with TCM syndromes., Conclusion: REC level is a high-quality biomarker for diagnosing WD that effectively reflects disease severity and plays an essential role in deciding on treatment strategies and prognosis. Furthermore, REC levels are closely related to TCM syndromes in WD; thus, it is a potential objective quantitative indicator for distinguishing TCM syndromes in WD.

Purpose: Some studies showed the possible role of copper intake on bone mineral density (BMD) in adults or the elderly, but the association remained uncertain in children and adolescents. Our research explored the association between copper intake and BMD in individuals aged 8-19 years from the National Health and Nutrition Examination Survey (NHANES) 2011-2016., Methods: In the present study, 6,965 individuals aged 8-19 (mean age 13.18 ± 3.38 years) were enrolled from the NHANES 2011-2016. Copper intake was evaluated by averaging two 24-hour copper dietary intake recalls. Multivariate linear regression analyses were used to explore the association between copper intake and total BMD, subtotal BMD, and total spine BMD in children and adolescents. Stratified analyses and interaction tests were performed by age, gender, and race., Results: Participants of the higher quartile of copper intake were more likely to be older, men, Non-Hispanic White, and Other Hispanic. They have higher values of poverty income ratio (PIR), serum phosphorus, blood urea nitrogen, serum vitamin D, and BMD and lower values of body mass index (BMI), cholesterol, total protein, and serum cotinine. In the fully adjusted model, we found positive associations between copper intake and total BMD (β = 0.013, 95CI: 0.006, 0.019)), subtotal BMD (β = 0.020, 95CI: 0.015, 0.024), and total spine BMD (β = 0.014, 95CI: 0.009, 0.019). Stratified analyses showed that the association was stronger in men, individuals aged 14-19, Non-Hispanic White, and Other Hispanic., Conclusions: Our study suggests that copper intake is positively associated with BMD in U.S. children and adolescents. The study emphasizes the role of copper intake on bone health in the early stages of life. However, more investigations are needed to verify our findings and their underlying mechanisms., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Cui et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Quantitative susceptibility mapping (QSM) is a post-processing technique that creates brain susceptibility maps reflecting metal burden through tissue magnetic susceptibility. We assessed topographic differences in magnetic susceptibility between participants with and without Wilson's disease (WD), correlating these findings with clinical severity, brain volume, and biofluid copper and iron indices., Methods: A total of 43 patients with WD and 20 unaffected controls, were recruited. QSM images were derived from a 3T MRI scanner. Clinical severity was defined using the minimal Unified Wilson's Disease Rating Scale (M-UWDRS) and Montreal Cognitive Assessment scoring. Differences in magnetic susceptibilities between groups were evaluated using general linear regression models, adjusting for age and sex. Correlations between the susceptibilities and clinical scores were analyzed using Spearman's method., Results: In age- and sex-adjusted analyses, magnetic susceptibility values were increased in WD patients compared with controls, including caudate nucleus, putamen, globus pallidus, and substantia nigra (all p < 0.01). Putaminal susceptibility was greater with an initial neuropsychiatric presentation (n = 25) than with initial hepatic dysfunction (n = 18; p = 0.04). Susceptibility changes correlated negatively with regional brain volume in almost all topographic regions. Serum ferritin, but not serum copper or ceruloplasmin, correlated positively with magnetic susceptibility level in the caudate nucleus (p = 0.04), putamen (p = 0.04) and the hippocampus (p = 0.03). The dominance of magnetic susceptibility in cortical over subcortical regions correlated with M-UWDRS scores (p < 0.01)., Conclusion: The magnetic susceptibility changes could serve as a surrogate marker for patients with WD., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Micronutrient deficiencies associated with malnutrition in patients with inflammatory bowel disease (IBD) can lead to complications including anemia, coagulopathy, poor wound healing, and colorectal cancer. This study aimed to investigate micronutrient deficiencies (copper, vitamins A, B 9 , E, and K) in IBD patients and highlight associated symptoms to aid in the recognition of micronutrient deficiencies., Methods: A retrospective electronic chart review was performed on adults diagnosed with Crohn's disease or ulcerative colitis hospitalized at a tertiary care center for IBD flare between January 2013 and June 2017. Patients with serum or whole blood micronutrient levels were included. Pregnant and incarcerated patients were excluded., Results: A total of 611 IBD patients (440 Crohn's disease, 171 ulcerative colitis) met the inclusion criteria. Micronutrients were assessed in a subset of IBD patients (copper: 12.3%, A: 10.1%, B 9  : 95.9%, E: 10.3%, and K: 4.6%). Overall, 10.1% of patients had micronutrient deficiencies. The proportion of patients with copper, A, B 9 , E, and K deficiencies were 25.4, 53.3, 1.9, 23.7, and 29.4% for Crohn's disease and 50, 52.9, 1.2, 43.8, and 18.2% for ulcerative colitis, respectively. The most common symptoms or historical features associated with micronutrient deficiency were anemia (copper, B 9 ), muscle weakness (copper, E) thrombocytopenia, fatigue (copper, B 9 ), diarrhea (B 9 ), dry skin, hyperkeratosis, pruritus, significant weight loss, elevated C-reactive protein (A), bleeding, and osteoporosis (K)., Conclusion: Micronutrient deficiencies are common in IBD patients, yet they are not routinely assessed. Copper, vitamins A, E, and K deficiencies are particularly underrecognized. Associated historical features should raise suspicion and prompt assessment and treatment., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Objectives: Wilson's disease (WD) in children and adolescents is predominantly asymptomatic or oligo-symptomatic. The symptoms are nonspecific and difficult to distinguish from other hepatic or neuropsychiatric disorders. In this study, we present the experience of a pediatric referral center for WD diagnosis and treatment., Patients and Methods: We retrospectively analyzed clinical and laboratory data from 99 patients with WD of Sardinian origin, including physical examination, laboratory biochemical testing, liver biopsy, and genetic analysis., Results: Patients were prevalently oligo-symptomatic or asymptomatic. The median age of diagnosis was 8.78 years. Ceruloplasmin values were lower than normal values in all analyzed patients. Twenty-four-hour urinary copper levels were higher than 40 μg/24-h in 92/96 patients. In all analyzed patients with the exception of one, liver copper was higher than 250 μg/g of dry weight but all had >75 μg/g of dry weight. Statistical analysis showed correlation between the age at diagnosis, serum copper, and 24-h urinary copper. Correlation was also found between serum copper and 24-h urinary copper. Molecular analysis of ATP7B gene allowed complete characterization in all the analyzed patients., Conclusion: A high index of clinical suspicion and biochemical tests including liver tests, serum ceruloplasmin, and basal 24-h urinary copper excretion and genotype determination are key to WD diagnosis. The long experience that a referral center for WD possesses is an important factor in making WD diagnosis a more accurate process. Studies in animal models on WD could be used as a guide to further investigate the molecular mechanisms that regulate copper metabolism and influence the natural history of WD., (© 2024 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Aims: Previous studies have investigated the relationship between heart failure (HF) and levels of zinc and copper, but conflicting results have been reported. This meta-analysis aims to clarify the role of zinc and copper in HF progression by examining the associations between HF and concentrations of these minerals., Methods and Results: We utilized STATA 12.0 software to calculate the standard mean difference (SMD) and 95% confidence interval (CI) for serum zinc and copper levels in patients with HF compared with healthy controls (HCs). The meta-analysis indicated a lower serum zinc level in patients with HF compared with HCs, using a random effects model (SMD = -0.77; 95% CI: -1.01, -0.54; I 2  = 61.9%, the P-value for Q test = 0.002). Additionally, the meta-analysis showed an increased serum copper level in patients with HF compared with HCs, using a random effects model (SMD = 0.66; 95% CI: 0.09, 1.23; I 2  = 93.8%, the P-value for Q test < 0.001). Meta-regression analysis indicated that publication year, age, and gender were not responsible for heterogeneity across studies., Conclusions: This meta-analysis demonstrates that patients with HF have lower serum zinc and higher copper concentrations compared with healthy subjects. However, the potential of zinc supplementation as a therapy for HF should be approached with caution. The heterogeneity among the included studies was found to be high. It is recommended that further well-designed large sample studies be conducted to validate these findings., (© 2024 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

The association between the serum essential metal elements (magnesium, iron, copper, zinc, and calcium) and thyroid nodules is still inconsistent. The current study aims to investigate the relationship of metal elements with thyroid nodules and their malignant tendency. A total of 6480 Chinese euthyroid adults were included in our study. We collect basic information through questionnaires and medical checkups. We diagnose thyroid nodules by ultrasound and detect serum trace metal concentrations by using an automatic biochemical analyzer. Binary and multinomial logistic regressions were used to investigate the associations. As a result, we found that serum copper concentrations were positively associated with thyroid nodules in the second, third, and fourth quartiles, compared to the first quartile (P = 0.024, P = 0.016, P = 0.032) in women and P for trend is 0.038. There is a significant sex-specific association between copper concentrations and thyroid nodules (P for interaction = 0.009). The results of the multinomial logistic regression analyses indicate high serum calcium and magnesium concentrations emerged as consistent risk factors for thyroid nodules in both genders, whereas low zinc was a sex-specific factor. We also observed significant sex interactions in the relationships of magnesium (P for interaction = 0.043) with thyroid nodules with malignant tendency among participants with thyroid nodules. In conclusion, our study suggests that gender is an important factor when studying the association between serum metals and thyroid nodules. The imbalance of selected metal elements (calcium, copper, zinc, and magnesium) may relate to thyroid nodules and their malignant tendency, and future prospective studies are needed to further confirm the associations., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Copper functions as an essential micronutrient influencing diverse metabolic processes in mammals, encompassing oxidative stress responses, lipid metabolism, and participation in enzymatic reactions. However, the impact of serum copper on non-alcoholic fatty liver disease (NAFLD) remains controversial. Our aim was to explore the precise correlation between serum copper and NAFLD in a large-scale population-based study. A total of 1377 participants from the National Health and Nutrition Examination Survey (NHANES) 2011-2016 were included in our study. The diagnosis of NAFLD and its progress to advanced liver fibrosis were based on serological indexes. One-way ANOVA, Kruskal-Wallis H test, and Chi-square test were used to access variations between quartiles groups of serum copper. We conducted multivariate-adjusted logistic regression models and subgroup analyses to investigate the association between serum copper and NAFLD, along with several metabolic diseases. Among the 1377 participants, 661 were diagnosed with NAFLD, and 141 of whom were classified into advanced liver fibrosis. Higher serum copper levels (≥ 21.00 μmol/L) were associated with an increased incidence of NAFLD (odds ratio (OR) = 2.07 (1.38-3.10), p < 0.001), as well as advanced liver fibrosis (OR = 2.40 (1.17-5.19), p = 0.025). Moreover, serum copper exhibited a positive correlation with hypertension, overweight, and abdominal obesity, all of which have been identified as risk factors of NAFLD. Additionally, female participants, under the age of 60, and with a higher body mass index (BMI) (> 24.9 kg/m 2 ) emerged as the most vulnerable subgroup concerning the relationship between serum copper and NAFLD. In the U.S. population, a notable association has been identified, linking elevated serum copper to an increased susceptibility for both the onset and progression of NAFLD, along with several metabolic disorders associated with NAFLD. The adverse effects of excess copper warrant attention in the context of public health considerations., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Trace elements (TEs) play a crucial role in metabolism through their biochemical and catalytic effects, and alterations in their levels have been observed in various malignancies. Given that chemotherapy is a common treatment for cancer, it is important to understand how it may affect the levels of TEs in the body. By investigating changes in TEs levels before and after chemotherapy, this study aims to provide insights into the potential impact of chemotherapy on TEs levels in cancer patients. In the present study, analyses were performed on the serum level of some elements including Zn, Cu, Cd, and Se in 69 patients with leukemia, lymphoma, prostate and breast cancers before and after three courses of chemotherapy. The serum TEs were measured by atomic absorption spectroscopy. The serum Zn levels in patients with leukemia, lymphoma, and breast cancer significantly decreased after chemotherapy (P < 0.05). Significant reductions were also observed in the post-chemotherapy serum level of Cd in patients with prostate (P = 0.020) and breast cancer (P = 0.013). Moreover, the Se serum level significantly decreased after chemotherapy compared to before it in the breast cancer patients (P < 0.001). In contrast, the serum level of Cu was higher before than after chemotherapy in all the patients, but no significant difference was found (P > 0.05). The results show that chemotherapy can alter the level of TEs. The assessment of TEs in cancer patients may provide information about the side effects of chemotherapy as well as the use of appropriate strategies to better manage the clinical conditions of patients., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This study was to assess the individual effects of serum copper levels and environmental tobacco exposure and their joint effects on the risk of overweight and obesity among children and adolescents of 6 to 19 year olds. We analyzed cross-sectional data from 1849 children and adolescents participating in the National Health and Nutrition Examination Survey (NHANES) collected between 2011 and 2016. Environmental tobacco exposure was determined by cotinine levels. The serum copper level was divided into < median group and ≥ median groups according to the median of 109.81 µg/dL. The outcome was overweight/obese in children and adolescents. Weighted multinomial multivariate logistic regression models were used to assess the association of serum copper and cotinine levels, with the risk of overweight/obesity, and the joint effects on the risk of overweight and obesity among children and adolescents. The subgroup analyses based on age, gender, and household smoking status were conducted. Among 1849 children and adolescents, 332 children and adolescents had overweight BMI, and 450 children and adolescents had obese BMI. Higher serum copper levels were associated with the risk of obesity in children and adolescents (odds ratio (OR) 2.96, 95% confidence interval (CI) 1.39-6.31, P = 0.006). A positive association between increasing levels of cotinine levels and the risk of overweight (OR 1.83, 95% CI 1.16-2.87, P = 0.010) and obesity (OR 2.56, 95% CI 1.03-6.40, P = 0.044) in children and adolescents was observed. A remarkable association was found between higher serum copper in combination with higher cotinine levels and the risk of overweight (OR 3.23, 95% CI 1.19-8.83, P = 0.023) and obesity (OR 8.76, 95% CI 2.14-35.87, P = 0.003) in children and adolescents. The subgroup analyses revealed positive associations between high serum copper levels in combination with high cotinine levels and overweight and obesity in children and adolescents aged ≥ 12 years, of female sex, and without smoking family members. There may exist a joint effect of serum copper levels and environmental tobacco exposure on overweight/obesity among children and adolescents. These findings offer an insight that early weight control and reduction of tobacco exposure and the detection of serum copper levels may be important in reducing the risk of obesity in children., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Neutral bis(amino acidato)copper(II) [Cu(aa) 2 ] coordination compounds are the physiological species of copper(II) amino acid compounds in blood plasma taking the form of bis(l-histidinato)copper(II) and mixed ternary copper(II)-l-histidine complexes, preferably with l-glutamine, l-threonine, l-asparagine, and l-cysteine. These amino acids have three functional groups that can bind metal ions: the common α-amino and carboxylate groups and a side-chain polar group. In Cu(aa) 2 , two coordinating groups per amino acid bind to copper(II) in-plane, while the third group can bind apically, which yields many possibilities for axial and planar bonds, that is, for bidentate and tridentate binding. So far, the experimental studies of physiological Cu(aa) 2 compounds in solutions have not specified their complete geometries. This paper provides a brief review of my group's research on structural properties of physiological Cu(aa) 2 calculated using the density functional theory (DFT) to locate low-energy conformers that can coexist in aqueous solutions. These DFT investigations have revealed high conformational flexibility of ternary Cu(aa) 2 compounds for tridentate or bidentate chelation, which may explain copper(II) exchange reactions in the plasma and inform the development of small multifunctional copper(II)-binding drugs with several possible copper(II)-binding groups. Furthermore, our prediction of metal ion affinities for Cu 2+ binding with amino-acid ligands in low-energy conformers with different coordination modes of five physiological Cu(aa) 2 in aqueous solution supports the findings of their abundance in human plasma obtained with chemical speciation modelling., (© 2024 Jasmina Sabolović, published by Sciendo.)

Background: Previous studies have highlighted that copper supplementation at 200% of the recommended daily dietary allowance modified vascular contraction and relaxation through increased reactive oxygen species (ROS) and prostaglandin formation, which modified the antioxidant status of middle-aged Wistar rats., Methods: In this study, young (1 month old) male Wistar rats ( n /group = 10) received a diet supplemented with 6.45 mg copper/kg (100% of daily recommendation-Group A) for 8 weeks. The experimental group received 12.9 mg copper/kg of diet (200% of the daily recommendation-Group B)., Results: Experimental supplementation with 200% copper modified the copper concentration in the blood (1.21-fold, p = 0.04), liver (1.15-fold, p = 0.032), and kidneys (1.23-fold, p = 0.045), potentiated the ROS formation in the aortic rings, and enhanced the sensitivity of the aortic rings to the vasodilator acetylcholine. We observed an increased participation of nitric oxide (NO) derived from inducible NO synthase (iNOS) in vascular contraction and a decreased net effect of vasodilator prostanoids derived from cyclooxygenase-2 in vascular relaxation. In rat kidneys, the concentrations of potassium (1.08-fold, p = 0.001) and iron (1.13-fold, p = 0.046) were higher, while, calcium (0.88-fold, p = 0.001) and chromium (0.77-fold, p = 0.005) concentrations were lower. In the rat liver, magnesium (1.06-fold, p = 0.012) was higher. No differences were observed in the concentrations of sodium, zinc, manganese, selenium, cobalt, molybdenum, and vanadium. The antioxidant activity of water- and lipid-soluble compounds; total antioxidant status in the blood; and superoxide dismutase, catalase, and malondialdehyde levels in the heart did not change., Conclusions: In young rats, prolonged supplementation with 200% copper had a lesser effect than anticipated on oxidative stress and vascular reactivity. Detailed data on the status of trace elements and their interactions in patients of different age groups are strongly required for effective nutritional and therapeutic intervention.

Objective: To establish a method for the simultaneous determination of 22 elements, including beryllium, vanadium, chromium, manganese, iron, calcium, magnesium, barium, cobalt, cadmium, copper, zinc, arsenic, selenium, titanium, strontium, nickel, molybdenum, tin, antimony, thallium and lead, in whole blood by inductively coupled plasma mass spectrometry (ICP-MS) . Methods: In September 2023, the analysis conditions were determined by optimizing the detection mode of the instrument, the pretreatment mode and the dilution factor of the samples, etc. Whole blood samples were diluted with a mixture of 0.1% nitric acid and 0.05% triton X-100, and centrifuged at 2000 r/min by high-speed centrifuge for 2 min. The supernatant was taken into inductively coupled plasma mass spectrometer to determine the content of 22 elements, and the detection limit and precision of the method were analyzed. Results: The 22 elements had a good linear relationship in their respective measurement ranges ( r =0.9991-0.9999), the detection limit ranged from 0.003 μg/L to 0.012 mg/L. The intra-batch precision ranged from 0.5% to 7.2%, the inter-batch precision ranged from 0.4% to 9.4%, and the average recoveries ranged from 80.6% to 114.9%. Conclusion: ICP-MS method has a good effect on the determination of 22 elements in whole blood. The method is fast and simple, and can be used for clinical detection of multiple elements in whole blood.

Background: Wilson disease (WD) is an autosomal recessive inherited disease caused by ATP7B variants and characterized by copper metabolism defects. However, children with WD are often asymptomatic, making the clinical diagnosis difficult. Therefore, more accurate methods are required for clinical diagnosis. The objective of this study was to highlight the phenotypic and genetic characteristics of children with WD in northeast China., Methods: We retrospectively analyzed the clinical data and gene sequencing results of 65 children with WD from January 1, 2014, to December 31, 2022, at the Shengjing Hospital of China Medical University. All data refer to the time of diagnosis before treatment., Results: The median age at diagnosis was 5 years (range 1.2-15 years). In 50 cases (50/65, 76.9%) patients, routine physical examinations revealed only abnormal liver function. However, they had a significantly negative (p < 0.05) Kayser-Fleischer ring (KF). Children with acute liver failure had significantly increased 24 h urinary copper excretion (p < 0.05). We detected 46 genetic variants of ATP7B, including seven novel variants. The most frequent variant was p.R778L with an allele frequency of 38.7%. Phenotype-genotype correlation analysis suggested that p.R778L was significantly associated with lower serum ceruloplasmin levels and higher zinc levels (p < 0.05). The loss-of-function (LOF) variant was associated with significantly lower albumin levels (p < 0.05)., Conclusion: Most children with WD are asymptomatic, which makes early diagnosis of WD difficult. Therefore, clinical and laboratory characteristics as well as genetic testing are essential. p.R778L is the most frequent variant of ATP7B in China and may play an important role in lowering serum ceruloplasmin levels., (© 2024. The Author(s).)

Copper is an essential element in the diet of mammals, including humans. It plays an important role in the physiological regulation of various enzymes and is consequently involved in several biological processes such as angiogenesis, oxidative stress regulation, neuromodulation, and erythropoiesis. Copper is essential for facilitating the transfer of iron from cells to the bloodstream, which is necessary for proper absorption of dietary iron and the distribution of iron throughout the body. In particular, patients with end-stage renal failure who require renal replacement therapy are at increased risk for disorders of copper metabolism. Many studies on hemodialysis, peritoneal dialysis, and kidney transplant patients have focused on serum copper levels. Some reported mild deficiency, while others reported elevated levels or even toxicity. In some cases, it has been reported that alterations in copper metabolism lead to an increased risk of cardiovascular disease, malnutrition, anemia, or mielopathy. The aim of this review is to evaluate the role of copper in patients undergoing hemodialysis and its potential clinical implications.

Background and Aims: Few studies have focused on the outcomes of Wilson's disease (WD) diagnosed before age of 5 years. This study aimed to summarize the clinical features of early diagnosed WD and analyse treatment outcomes and the risk factors associated with treatment failure., Methods: A total of 139 children confirmed with WD before 5 years were enrolled in this study. Only patients with follow-up over 1 year were analysed with Kaplan-Meier survival analysis. The composite outcomes included death, progression to liver failure or acute hepatitis, development of renal or neurological symptoms and persistent elevation of alanine aminotransferase (ALT). The treatment failure was defined as occurrence of at least one of above outcomes., Results: Among 139 WD patients at diagnosis, two (1.4%) WD patients presented with symptomatic liver disease, whereas 137 (98.6%) were phenotypically asymptomatic, including 135 with elevated ALT and 2 with normal liver function. Median serum ceruloplasmin (Cp) was 3.1 mg/dL, and urinary copper excretion was 87.4 μg/24-h. There were 71 variants identified in the the copper-transporting ATPase beta gene, and 29 were loss of function (LOF). 51 patients with LOF variant were younger at diagnosis and had lower Cp than 88 patients without LOF. Among 93 patients with over 1 year of follow-up, 19 (20.4%) received zinc monotherapy, and 74 (79.6%) received a zinc/D-penicillamine combination therapy. 14 (15.1%) patients underwent treatment failure, and its occurrence was associated with poor compliance (p < .01)., Conclusions: Cp is a reliable biomarker for early diagnosis, and zinc monotherapy is an effective treatment for WD during early childhood. Good treatment compliance is critical to achieve a favourable outcome., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: It is widely known that sex differences have a significant impact on patients with major depressive disorder (MDD). This study aims to evaluate the sex-related connection between serum trace elements and changes in neurometabolism in the anterior cingulate cortex (ACC) of MDD patients., Methods: 109 untreated MDD patients and 59 healthy controls underwent proton magnetic resonance spectroscopy ( 1 H-MRS) under resting conditions. We measured metabolic ratios in the ACC from both sides. Additionally, venous blood samples were taken from all participants to detect calcium (Ca), phosphorus, magnesium (Mg), copper (Cu), ceruloplasmin (CER), zinc (Zn), and iron (Fe) levels. We performed association and interaction analyses to explore the connections between the disease and gender., Results: In individuals with MDD, the Cu/Zn ratio increased, while the levels of Mg, CER, Zn and Fe decreased. Male MDD patients had lower Cu levels, while female patients had an increased Cu/Zn ratio. We observed significant gender differences in Cu, CER and the Cu/Zn ratio in MDD. Male patients showed a reduced N-acetyl aspartate (NAA)/phosphocreatine + creatine (PCr + Cr) ratio in the left ACC. The NAA/PCr + Cr ratio decreased in the right ACC in patients with MDD. In the left ACC of male MDD patients, the Cu/Zn ratio was inversely related to the NAA/PCr + Cr ratio, and Fe levels were negatively associated with the GPC + PC/PCr + Cr ratio., Conclusions: Our findings highlight gender-specific changes in Cu homeostasis among male MDD patients. The Cu/Zn ratio and Fe levels in male MDD patients were significantly linked to neurometabolic alterations in the ACC., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Mineral are intimately related to human health and disease, and detection of mineral content in the body is of great significance for the diagnosis and prevention of diseases. In this study, we validated the method developed to detect magnesium (Mg), copper (Cu), iron (Fe), zinc (Zn), and selenium (Se) levels in dried blood spots (DBS). In accordance with the requirements of the guidelines for the Bioanalytical Method Validation Guidance for Industry, we evaluate the linearity, sensitivity, precision, accuracy and selectivity of the developed methods. In addition, Mg, Cu, Fe, Zn and Se were quantified in 195 older adults using DBS technique, and its accuracy was assessed by comparing the results to those detected by inductively coupled plasma-mass spectrometry (ICP-MS). The method has excellent sensitivity and linear range to cover the concentration range of mineral elements in the general population with the required precision, accuracy and selectivity. The correlation coefficients of Mg, Cu, Fe, Zn and Se levels in blood detected by the DBS technique and ICP-MS were 0.638, 0.823, 0.463, 0.728 and 0.751, respectively (all P < 0.05), which indicated that there was a strong correlation between the detection results of the two methods. More than 95 % of the sample results in the Bland-Altman consistency test were within the acceptable limits of agreement (LOA) range, indicating that they had good consistency. DBS technique has good accuracy and reliability in detecting blood mineral levels in the elderly, suggesting potential in the quantification of mineral level in blood., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Guowei Huang reports financial support was provided by Ministry of Science and Technology of the People's Republic of China. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Copper (Cu), an essential trace element in the metabolism of mammals, plays a central role in various metabolic processes. However, overdosing can lead to severe symptoms and even fatalities. Chronic Cu intoxication continues to be a problem in grazing and domestic animals, with sheep being particularly sensitive. There are few comparative studies on its impact on South American camelids (SACs). Therefore, this work presents the results of literature research combined with a case report on a 3-year-old female vicuña (Vicugna vicugna) presented to the clinic from a zoological garden in northern Germany. The animal showed reduced food intake, recumbency, bruxism, icteric mucous membranes and sclera. Auscultation revealed atony of the third compartment and the digestive tract. Similar to cases described in the literature, the animal showed rapid deterioration of its condition with unspecific symptoms of liver failure and rapid death. However, in contrast to descriptions in sheep, clinical icterus has not been previously reported in cases of other SACs. Laboratory findings from EDTA and serum samples revealed neutrophilia with a left shift, hypoproteinaemia, lymphopaenia, azotaemia, elevated levels of creatine kinase (CK), aspartate aminotransferase (AST) and glutamate dehydrogenase (GLDH) in the serum. Hyperbilirubinaemia and significantly elevated serum and liver Cu levels were observed. Subsequent blood samples from the remaining vicuñas and alpacas in the same enclosure showed no remarkable abnormalities. To the best of the authors' knowledge, this case report represents the first documented case of Cu intoxication specifically in vicuñas., (© 2024. The Author(s).)

Magnesium (Mg), iron (Fe), copper (Cu), and zinc (Zn) are indispensable elements in children's growth and development. However, epidemiological evidence regarding essential elements and their mixed exposure to behavior problems remains in its infancy. The objective of the present study was to evaluate the association between essential elements and the manifestation of behavior problems, with an additional focus on the implications of their mixture. An electronic medical records review was performed among 4122 subjects aged 6-18 years who underwent examinations at Children's Hospital, Zhejiang University School of Medicine, between January 2019 and July 2022. The concentrations of essential elements were measured by atomic absorption spectrometry, and behavior problems were assessed by using the Conners' Parent Rating Scale (CPRS). A total of 895 (21.7%) children and adolescents were identified as having behavior problems. For single exposure, inversely linear dose-response relationships were identified between continuous Mg and Zn levels and the prevalence of behavior problems, and the prevalence ratios (PRs) in the categorical lowest tertile were 1.28 (95% confidence interval, CI: 1.07-1.54) for Mg and 1.31 (95% CI: 1.05-1.63) for Zn compared to the highest tertile. For mixture exposure, an inverse association between essential elements and behavior problems was also found, mainly contributed by Mg (posterior inclusion probability, PIP = 0.854). Whole blood levels of Mg and Zn were significantly inversely associated with behavior problems. The findings highlight the pivotal role of essential elements in behavior problems and emphasize the importance of maintaining adequate levels of essential elements during children's maturation., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Given the importance of achieving optimal therapeutical concentration in patients treated with antidepressants, this study investigates a novel technique for the simultaneous determination of trazodone (TRZ) and doxepin (DOX) in human plasma and serum samples for the first time., Results: To achieve simultaneous determination of two antidepressants, TRZ and DOX, a novel detection system was designed: a non-enzymatic voltammetric biosensor based on boron-reduced graphene oxide/manganese oxide nanoparticles (GCE/B-rGO/MnO NPs). The detection was accomplished after pre-concentration and extraction trace amounts of the analytes using the thin film-solid phase microextraction (TF-SPME) technique, which employed polyvinyl alcohol/polyvinyl acetate/copper oxide nanoparticles (PVA/PVAc/CuO NPs) electrospun nanofibers. The successful preparation of composite nanofibers and modified electrodes was confirmed using the evaluation of field emission-scanning electron microscopy (FE-SEM) and energy-dispersive X-ray spectroscopy (EDX). Also, the composite nanofibers were characterized with attenuated total reflectance-Fourier transform-infrared (ATR-FT-IR) and X-ray diffraction (XRD). In the solution of TRZ and DOX, under optimum experimental conditions, the linear dynamic ranges (LDRs) were 0.1-20.0 μmol L -1 and 0.5-27.0 μmol L -1 , respectively. Also, the limit of detection (LOD) values of TRZ and DOX were 0.032 and 0.150 μmol L -1 ., Significance: PVAc acts as a cross-linking agent for PVA, and their mixture is effective for sample preparation and pre-concentration of analytes in complex matrices. Also, adding CuO NPs to this polymeric mixture enhanced the adsorption efficiency. Taking advantage of the high surface area of MnO NPs and the high electrical conductivity of B-rGO, and considering the superiority of their simultaneous utilization, the constructed electrochemical biosensor is both cost-effective and rapid. It demonstrates excellent stability, repeatability, and sensitivity for the simultaneous determination of TRZ and DOX under optimal conditions. This biosensor, the first of its kind, is specifically designed for the simultaneous determination of TRZ and DOX in human plasma and serum samples, representing a significant advancement in biosensing technology., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background and Aims: Neural tube defects (NTDs) occur when the neural tube fails to close within 28 days of human embryonic development. This results in central nervous system disorders like anencephaly, spina bifida, and encephalocele. Early diagnosis and treatment are crucial to minimize their impact on an individual's health and well-being. The present study aims to define the association between prenatal exposure to trace elements (Cu and Zn) and the single nucleotide polymorphism (SNP) of the MTHFR gene involved in folate metabolism pathways in neural tube defects in children and their mothers., Material and Methods: A cross-sectional study involving 331 participants (90 NTD cases, 88 healthy mothers, 85 NTD children, and 68 healthy children) from antenatal check-ups in Obstetrics and Gynaecology and Pediatric Surgery for Neural Tube Defects in the Outpatient Department (OPD) and Inpatient Department (IPD). Assessed Cu and Zn concentrations and their associations. Genomic DNA was extracted, and real-time PCR was used to determine genotypes. Atomic absorption spectrophotometry measured trace elements. Statistical analyses included Chi-Square tests, odds ratios, and Mann-Whitney U tests., Results: Significant associations were found between MTHFR C677T genotypes and NTD risk in mothers (p = 0.0491) and children (p = 0.0297). Allelic frequency analysis indicated a T allele association with NTD risk in children (p = 0.0107). Recessive models showed significant associations in mothers (p = 0.0169) and children (p = 0.1678). Cu levels differed significantly between NTD cases and controls (p < 0.0001), with MTHFR genotypes influencing Cu levels. Zinc levels also varied significantly (p < 0.0001)., Conclusion: This study reveals complex associations between MTHFR C677T genotypes, trace element concentrations, and NTD risk in mothers and children. This targeted approach allows healthcare providers to identify at-risk pregnancies early, enabling personalised interventions like folic acid supplementation and counselling to moderate neural tube defect (NTD) risk in a future pregnancy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Drug-resistant epilepsy is defined as failure of seizure control in spite of using 2 or 3 proper antiepileptic drugs in appropriate time. Mineral elements play important roles in neuronal function; it is believed that mineral deficiency may lead to complications through seizure management. In the present study, serum levels of zinc (Zn), copper (Cu), magnesium (Mg), calcium (Ca), and 25-hydroxy vitamin D (Vit D) in drug-resistant-epilepsy (DRE) patients were evaluated and compared with the controlled patients., Methods: In this cross-sectional study, epileptic patients were included and categorized into two groups of DRE and well-controlled patients. Patients' serum samples were analysed to evaluate Zn, Cu, Mg, Ca, and Vit D levels. The primary objective was comparison of serum levels of different trace elements between the groups., Results: Sixty-four epileptic children including 33 DRE and 31 well-controlled children entered the study. The DRE children showed a significantly earlier onset of disease compared to the other group (p = 0.014). Comparing the frequency of developmental delay between the groups, the results showed this complication was significantly more frequent in the DRE group (p < 0.001). Concerning serum elements, the results showed a significantly higher concentration of Zn in the well-controlled group than the DRE group (p = 0.007). On the other hand, no significant differences were observed between the groups regarding the means of Vit D, Ca, Cu, and Mg levels (p > 0.05)., Conclusion: The results of the present study delineated that drug-resistant epilepsy patients had earlier onset of disease and were at higher risk of neurodevelopmental delay compared with well-controlled-epilepsy patients. A significant lower serum levels of Zn were also observed in drug-resistant-epilepsy patients. This finding may suggest the role of zinc supplementation in help to better control of drug-resistant seizures, as well as, the importance of serum zinc monitoring in epileptic patients., (© 2024. The Author(s).)

Background: Selenoproteins regulate pathways controlling neurodevelopment, e.g., redox signaling and thyroid hormone metabolism. However, studies investigating maternal selenium in relation to child neurodevelopmental disorders are scarce., Methods: 719 mother-child pairs from the prospective population-based Odense Child Cohort study in Denmark were included. Three selenium biomarkers, i.e. concentrations of serum selenium, selenoprotein P (SELENOP), and activity of glutathione peroxidase 3 (GPX3), along with serum copper, zinc and iron were measured in early third trimester (at 28.9+/-0.8 weeks of pregnancy). ADHD and ASD traits in children were assessed systematically using the established Child Behaviour Checklist at 5 years of age, based on a Danish reference cohort with cut-off at 90th percentile. Multivariable regression models adjusted for biologically relevant confounders were applied., Results: 155 of 719 (21.6 %) children had ASD traits and 59 of 719 (8.2 %) children had traits of ADHD at 5 years of age. In crude and adjusted models, all three selenium biomarkers associated inversely with ADHD traits. For ADHD, fully adjusted OR for 10 μg/L increment in selenium was 0.76 (95 % CI 0.60, 0.94), for one mg/L increment in SELENOP was 0.73 (0.56, 0.95), and for 10 U/L increment in GPx3 was 0.93 (0.87,1.00). Maternal total selenium was inversely associated with child ASD traits, OR per 10 μg/L increment was 0.85 (0.74, 0,98). SELENOP and GPx3 were not associated with ASD traits. The associations were specific to selenium, as other trace elements such as copper, zinc, or iron were not associated with the outcomes., Conclusions: The results provide coherent evidence for selenium deficiency as a risk factor for ADHD and ASD traits in an environment with borderline supply, the causality of which should be elucidated in a randomized controlled trial., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Epidemiological studies examining the association between circulating micronutrients and the risk of hypertensive disorders during pregnancy (HDP) have produced inconsistent results. Therefore, we conducted a Mendelian randomization (MR) analysis to evaluate the potential causal relationship between micronutrients and HDP., Methods: Nine micronutrients (beta-carotene, vitamin B6, vitamin B12, calcium, zinc, selenium, copper, folate, and phosphorus) were selected as the exposure factors. Summary data for gestational hypertension (14,727 cases and 196,143 controls) and preeclampsia/eclampsia (7212 cases and 174,266 controls) were extracted from the FinnGen consortium. The MR analysis employed the inverse variance weighted method and conducted a range of sensitivity analyses., Results: The inverse variance weighted method indicated no significant causal relationship between nine genetically predicted micronutrient concentrations and gestational hypertension, as well as preeclampsia/eclampsia. Sensitivity analyses suggested the absence of pleiotropy., Conclusion: There is no strong evidence to support the causation between circulating micronutrients and hypertensive disorder during pregnancy., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Context.—: Clinical testing for Wilson disease (WD) is potentially challenging. Measuring the fraction of labile bound copper (LBC) to total copper may be a promising alternative diagnostic tool with better sensitivity and specificity than some current biomarker approaches. A dual filtration-based inductively coupled mass spectrometry (ICP-MS) assay to measure LBC in serum was developed., Objective.—: To establish a reference interval for LBC and LBC to total copper (LBC fraction) in a healthy adult population, and to examine associations between total copper, LBC, and LBC fraction with age, sex, menopausal status, hormone replacement therapy, and supplement use., Design.—: Serum samples were collected from healthy male (n = 110) and female (n = 104) patients between the ages of 19 and 80 years. Total copper and LBC were analyzed using ICP-MS. Results were used to calculate the LBC fraction. Reference intervals were calculated for the 2.5th and 97.5th percentiles for both LBC and LBC fraction., Results.—: The reference intervals for LBC were determined to be 13 to 105 ng/mL and 12 to 107 ng/mL for female and male patients, respectively. The reference intervals for the LBC fraction were 1.0% to 8.1% and 1.2% to 10.5% for female and male patients, respectively. No significant associations were found regarding age, menopausal status, hormone replacement therapy, or vitamin and supplement use., Conclusions.—: Sex-specific reference intervals have now been established for LBC and LBC fraction. These data in conjunction with further testing of WD populations can be used to assess the sensitivity and specificity of LBC fraction in screening, monitoring, and diagnosis., (© 2024 College of American Pathologists.)

Background: The essential trace element copper is relevant for many important physiological processes. Changes in copper homeostasis can result from disease and affect human health. A reliable assessment of copper status by suitable biomarkers may enable fast detection of subtle changes in copper metabolism. To this end, additional biomarkers besides serum copper and ceruloplasmin (CP) concentrations are required., Objectives: The aim of this study was to investigate the emerging copper biomarkers CP oxidase (CPO) activity, exchangeable copper (CuEXC) and labile copper in serum of healthy women and compare them with the conventional biomarkers total serum copper and CP., Method and Main Findings: This observational study determined CPO activity, the non CP-bound copper species CuEXC and labile copper, total serum copper and CP in sera of 110 healthy women. Samples were collected at four time points over a period of 24 weeks. The concentrations of total serum copper and CP were within the reference ranges. The comparison of all five biomarkers provided insight into their relationship, the intra- and inter-individual variability as well as the age dependence. The correlation and Principal Component Analyses (PCA) indicated that CP, CPO activity and total copper correlated well, followed by CuEXC, while the labile copper pool was unrelated to the other parameters., Conclusions: This study suggests that the non-CP-bound copper species represent copper pools that are differently regulated from total copper or CP-bound copper, making them interesting complementary biomarkers to enable a more complete assessment of body copper status with potential relevance for clinical application., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Since little is known about the comparison of the biotoxic effects of heavy metals exposure on biochemical and hematological parameters in miners and non-miners, the current study aimed to compare the effects of arsenic (As), lead (Pb), and copper (Cu) in both groups. Demographic information and blood samples were collected from all participants and measures of As, Pb and Cu were obtained using Atomic Absorption Spectrophotometry. As and Pb mean concentrations in miners and Cu concentration were greater in non-miners. Miners also showed significantly higher level of RBC, HBG and HCT. In the adjusted model, cholesterol showed a positively association with Pb and Cu levels. Triglycerides, GGT, ALP, WBC and PLT positively and HDL-cholesterol negatively were associated with Cu. Creatinine was negatively associated with group variable. In conclusion, miners' high blood heavy metals concentrations can impact biochemical and hematological indices. These observations make monitoring of heavy metals necessary in miners., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Trace elements are essential for several physiological processes. To date, various data have suggested that inadequate levels of trace elements may be involved in the pathogenesis of different chronic diseases, including immune-mediated ones, or may develop during their course. Systemic sclerosis (SSc) is a complex autoimmune multisystemic disease, primarily characterized by microvascular dysregulation, the widespread activation of the immune system and tissue fibrosis. According to the latest reports regarding the pathogenesis of SSc, the main pathophysiological processes-inflammation, vasculopathy and fibrosis-may include various trace element derangements. The present literature review aims to update the available data regarding iron, zinc, copper and selenium status in SSc as well as to underline the possible implications of these trace elements in the complexity of the pathogenic process of the disease. We observe that the status of trace elements in SSc plays a crucial role in numerous pathogenic processes, emphasizing the necessity for proper monitoring and supplementation. The reported data are heterogenous and scarce, and future studies are needed in order to draw clearer conclusions about their complete spectrum.

Background: Copper (Cu) homeostasis are important processes in the cause of metabolic diseases, but the association between Cu and obesity remains unclear., Methods: Participants were drawn from the 2011-2016 National Health and Nutrition Examination Survey (NHANES). Weighted logistic regression assessed the associations of serum Cu concentrations (tertiles) with obesity and central obesity in individuals without comorbidities. Obesity was defined as a BMI ≥30.0 kg/m2, and central obesity was defined as a waist circumference ≥80 cm for women and ≥95 cm for men., Results: This cross-sectional study included 1,665 adults without comorbidities, representing 24,744,034 people (mean age 35.1 years, 48.5% female). High serum Cu levels (tertile 3: ≥19.19 μmol/L) were associated with higher odds of obesity (adjusted odds ratio [OR]: 4.48, 95% CI[confidence interval]: 2.44-8.32) and central obesity (OR: 2.36, 95% CI: 1.19-4.66) compared to low serum Cu levels (tertile 1: ≤15.64 μmol/L). The dose-response curve showed a nonlinear association between Cu levels and obesity (P-nonlinear = 0.02) and a linear association with central obesity (P-nonlinear = 0.21)., Conclusion: This study suggests that higher serum Cu levels are associated with increased odds of obesity in healthy American adults., Competing Interests: NHANES is a comprehensive cross-sectional study conducted in the United States. The survey employs a sophisticated, stratified, and multistage probability sampling design. The research protocol received approval from the Research Ethics Review Board of the National Center for Health Statistics, and NHANES ensures that written informed consent is obtained from all participants. It’s important to note that our analysis exclusively utilized publicly available data, ensuring the absence of personally identifiable information. All procedures strictly adhered to relevant guidelines and regulations. The interview questionnaires and examination response rates are accessible to the public. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Globally, metabolic dysfunction-associated steatotic liver disease (MASLD), previously termed nonalcoholic fatty liver disease (NAFLD), is one of the most common liver disorders and is strongly associated with copper deficiency. To explore the potential effects and mechanisms of Lactiplantibacillus plantarum LPJZ-658, copper deficiency combined with a high-sugar diet-induced MASLD mouse model was utilized in this study. We fed 40-week-old (middle-aged) male C57BL/6 mice a copper-deficient and high-sugar diet for 16 weeks (CuDS), with supplementary LPJZ-658 for the last 6 weeks (CuDS + LPJZ-658). In this study, we measured body weight, liver weight, and serum biochemical markers. Lipid accumulation, histology, lipidomics, and sphingolipid metabolism-related enzyme expression were investigated to analyze liver function. Untargeted metabolomics was used to analyze the serum and the composition and abundance of intestinal flora. In addition, the correlation between differential liver lipid profiles, serum metabolites, and gut flora at the genus level was measured. The results show that LPJZ-658 significantly improves abnormal liver function and hepatic steatosis. The lipidomics analyses and metabolic pathway analysis identified sphingolipid, retinol, and glycerophospholipid metabolism as the most relevant metabolic pathways that characterized liver lipid dysregulation in the CuDS group. Consistently, RT-qPCR analyses revealed that the enzymes catalyzing sphingolipid metabolism that were significantly upregulated in the CuDS group were downregulated by the LPJZ-658 treatment. In addition, the serum metabolomics results indicated that the linoleic acid, taurine and hypotaurine, and ascorbate and aldarate metabolism pathways were associated with CuDS-induced MASLD. Notably, we found that treatment with LPJZ-658 partially reversed the changes in the differential serum metabolites. Finally, LPJZ-658 effectively regulated intestinal flora abnormalities and was significantly correlated with differential hepatic lipid species and serum metabolites. In conclusion, we elucidated the function and potential mechanisms of LPJZ-658 in alleviating copper deficiency combined with sugar-induced middle-aged MASLD and hope this will provide possible treatment strategies for improving MASLD.

Excessive Cu 2+ intake can cause neurological disorders (e.g. Wilson's disease) and adversely affect the gastrointestinal, liver, and kidney organs. The presence of Cu 2+ is strongly linked to the emergence and progression of Wilson's disease (WD), and accurately measuring the amount of copper is a crucial step in diagnosing WD at an early stage in a clinical setting. In this work, CQDs were fabricated through a facile technique as a novel fluorescence-based sensing platform for detecting Cu(II) in aqueous solutions, and in the serum samples of healthy and affected individuals by WD. The CQDs interact with Cu(II) ions to produce Turn-on and Turn-off states at nano-molar and micro-molar levels, respectively, with LODs of 0.001 µM and 1 µM. In fact, the Cu 2+ ions can act like a bridge between two CQDs by which the charge and electron transfer between the CQDs may increase, possibly can have significant effects on the spectroscopic features of the CQDs. To the best of our knowledge, this is the first reported research that can detect Cu(II) at low levels using two different complexation states, with promising results in testing serum. The potential of the sensor to detect Cu(II) was tested on serum samples from healthy and affected individuals by WD, and compared to results obtained by ICP-OES. Astonishingly, the results showed an excellent correlation between the measured Cu(II) levels using the proposed technique and ICP-OES, indicating the high potential of the fluorimetric CQD-based probe for Cu(II) detection. The accuracy, sensitivity, selectivity, high precision, accuracy, and applicability of the probe toward Cu(II) ions make it a potential diagnostic tool for Wilson's disease in a clinical setting., (© 2024. The Author(s).)

Background & Aims: In this study, we assessed serum trace element concentrations in patients with pancreatic cancer and compared the results to those of healthy controls and patients with chronic pancreatitis. We evaluated the association between trace element concentrations during cancer treatment and the risk of cancer progression and mortality in pancreatic cancer patients., Methods: A retrospective cohort study was conducted at a tertiary center in Korea. Serum trace element concentrations of cobalt (Co), copper (Cu), selenium (Se), and zinc (Zn) were measured at diagnosis using an inductively coupled plasma-mass spectrometry in 124 patients with pancreatic cancer, 50 patients with chronic pancreatitis, and 120 healthy controls. Trace elements were measured after a median of 282.5 (95% confidence interval [CI], 224.0-326.5) days from treatment initiation to assess changes in trace element concentrations during treatment., Results: Serum Co concentrations were significantly higher in patients with chronic pancreatitis and pancreatic cancer compared to healthy controls, while serum Se concentrations were significantly lower. During treatment, serum concentrations of Cu, Se, and Zn significantly decreased in patients with pancreatic cancer. During the follow-up (median 152.5; 95% CI, 142.8-160.0 months), 85.5% of patients experienced progression or relapse, and 84.7% of patients died. Patients with decreased Se and Zn concentrations during treatment had a higher mortality (hazard ratio [HR], 2.10; 95% CI, 1.31-3.38; P = 0.0020 for Se; HR, 1.72; 95% CI, 1.06-2.79; P = 0.0269 for Zn) compared to those with unchanged or increased trace element concentrations during treatment. Patients with a greater reduction in Zn concentrations during treatment had a higher mortality than those with a smaller reduction (HR, 1.59; 95% CI, 1.01-2.52; P = 0.0483). Patients whose Zn status changed from normal to deficient during treatment had an increased mortality (HR, 1.76; 95% CI, 1.16-2.67, P = 0.0084). Patients with multiple (≥2) trace element deficiencies after treatment had poorer outcomes than those with no or single trace element deficiency., Conclusions: This study revealed that decreases in Se and Zn concentrations during cancer treatment were associated with adverse outcomes in terms of cancer progression and mortality in patients with pancreatic cancer. Further prospective investigations are recommended., Competing Interests: Conflict of interest The authors declare no potential conflicts of interest., (Copyright © 2024 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Objective: To describe the copper and selenium statuses of beef calves at weaning., Animal: Calves ( n = 1998) were sampled from 106 Canadian cow-calf herds in the fall of 2021., Procedure: Serum samples from calves were tested for copper, selenium, and molybdenum concentrations., Results: Although the percentages of calves classified as selenium deficient (< 0.025 ppm) were relatively low (0.5% western Canada, 3% eastern Canada), 53% of calves from western Canada and 77% of calves from eastern Canada were classified as having less than adequate selenium concentrations (< 0.08 ppm). Copper deficiency (< 0.5 ppm) was common in calves from both western (17%) and eastern (14%) Canada. High molybdenum concentrations (> 0.10 ppm) were identified in 6% of calves from western Canada and 7% of calves from eastern Canada., Conclusion: Selenium concentrations were higher in calves from western Canada than from those in eastern Canada ( P < 0.001). Copper and molybdenum concentrations were not significantly different between western and eastern Canada. Less-than-adequate serum copper was the most common deficiency identified in Canadian beef calves at weaning., Clinical Relevance: Trace minerals are important for immune system function in calves at weaning. Selenium concentrations in calves at weaning were lower than in cows from the same herds collected at pregnancy testing 2 y earlier. Copper deficiency was also identified, though less frequently than for mature cows. Supplementation programs for calves should be customized based on testing and recognize both regional and age differences in risk., (Copyright and/or publishing rights held by the Canadian Veterinary Medical Association.)

Cardiomyopathies (CMP) represent a significant health problem as they have a poor long-term prognosis and often require transplantation. Heavy metals are known to have cardiotoxic effects and some of them, such as cadmium (Cd), are found to be elevated in the urine and blood of individuals with heart diseases; nevertheless, direct measurement of metals (e.g. zinc (Zn) which is necessary for normal heart function), in the myocardium of individuals with CMP has not been performed. Here, we aimed to analyze the levels of a group of metals in the myocardium of the left ventricle in individuals with CMP. At the Institute of Pathology, we collected 52 samples of left ventricle post-mortem, out of which 19 subjects had been diagnosed with CMP (mean age: 72 y ± 10), and 33 subjects had not suffered from any heart disease (mean age: 67 y ± 15). We found out that individuals with CMP had a significantly higher concentrations of lead, nickel, manganese and copper than non-CMP subjects (p = 0.002, p < 0.001, p = 0.011, and p = 0.002). Interestingly, zinc was significantly lower in CMP subjects than in n-CMP individuals (p = 0.017). Our results indicated the involvement of an increased lead, nickel, copper and manganese heart load in individuals with CMP coupled with lower concentrations of zinc., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)