Copper Levels Research Articles

Evaluation of Oxidative Stress, Anti-Oxidant, Vitamins and Co-Factor Elements in The Sera of Gastric Cancer in Iraqi Patients.

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. 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. 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. 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.

Associations between multi-metal joint exposure and decreased estimated glomerular filtration rate (eGFR) in solar greenhouse workers: A study of a unique farmer group

BackgroundSolar greenhouse workers, a unique farmer group, have been reported to have a higher risk of chronic kidney disease (CKD) compared to the general population, possible due to exposure to multiple metals. ObjectiveThis study aimed to investigate the associations between exposure to multiple metals and the estimated glomerular filtration rate (eGFR). MethodsA cross-sectional study was conducted in the Northwest China. Urine samples were tested for concentration of 14 metals, including chromium, manganese, iron et al. Blood creatinine was measured to calculate eGFR, which was to evaluate the kidney function. Linear model and the Bayesian Kernel Machine Regression (BKMR) models were used to evaluate the associations between metals exposure and eGFR. ResultThe study included 281 solar greenhouse workers, with 128 (45.6%) males and 153 (54.4%) females. The highest median concentrations of metals were zinc (418.55 μg/L), strontium (368.77 μg/L), and iron (55.73 μg/L), respectively. The linear model analysis showed that urinary levels of copper and zinc were negatively associated with eGFR [β = −0.021, 95% CI (−0.048, −0.007); β = −0.018, 95% CI (−0.068, −0.005)] considering a false discovery rate. BKMR results indicated a significant overall negative effect of 14 metals exposure on the eGFR when all metal levels were above the 50th percentile compared to the median value. ConclusionsThe decrease in eGFR among solar greenhouse workers was related to mixed metal exposure. Reducing exposure to the metals of copper, zinc, and lead could effectively protects kidney function. Further prospective studies are needed to resolve concerns about reverse causality.

Comparative Analysis of Vitamin D, Folic Acid, and Trace Minerals Levels in Various Stages of Invasive Ductal Breast Cancer.

Invasive ductal carcinoma (IDC) is one of the most commonly diagnosed subtypes of breast cancer, representing the majority of breast cancer cases. This study investigates the levels of vitamin D, folic acid, and antioxidant minerals (zinc (Zn), copper (Cu), and magnesium (Mg)) in IDC patients across different disease stages to explore their potential roles in disease progression. We analyzed a cohort of 150 female patients with IDC, aged between 30 and 67 years (51 ± 15.5 years). Blood samples were collected to measure levels of vitamin D, folic acid, Cu, Mg, and Zn. Patients were categorized into Stage1 to Stage 4 of cancer. Variations in nutrient levels across these stages were statistically assessed using ANOVA and post-hoc tests. The study results revealed varying levels of key nutrients across different stages of the disease. Vitamin D levels averaged 17.7 ng/mL, with higher concentrations in early-stage patients, indicating a possible correlation with disease severity. Folic acid levels had a mean of 12.2 ng/mL, showing a decline in later stages, potentially linking it to cancer progression. Copper levels averaged 161.3μg/dL, peaking at 170μg/dL in Stage 3, suggesting a connection with cancer aggressiveness. Magnesium levels, with an average of 1.4 mg/dL, dropped notably to 0.6 mg/dL by Stage 4, highlighting its possible involvement in disease progression. Zinc levels averaged 69.4 μg/dL, with a significant decrease in advanced stages, emphasizing its importance for immune function and cellular health. The study demonstrates significant variations in the levels of vitamin D, folic acid, and antioxidant minerals across different stages of IDC. These nutrients may influence cancer progression, underscoring the potential benefits of nutritional assessments and interventions in managing IDC.

Токсичные и биогенные элементы в органах и тканях белой куропатки (Lagopus lagopus L., 1758) на севере Красноярского края (обзор)

Studying the concentration of biogenic and toxic microelements in the body tissues of wild animals is relevant for organizing regional environmental monitoring, assessing the state of populations and ensuring the safety of meat and wild products. The studies were carried out to determine the content of biogenic and toxic elements in the organs and tissues of the willow ptarmigan in the north of the Krasnoyarsk Region, Russia, where different levels of technogenic pollution are expected. The iron, copper, nickel, lead, and cadmium content in the pectoral muscles and liver of willow ptarmigan (Lagopus lagopus L.) (n=162), bagged during five hunting seasons in 2005–2019, were determined using atomic absorption spectrometry. The levels of lead, cadmium and iron in the tissues were significantly higher in contaminated areas, while the copper levels did not differ. Element concentrations in liver and skeletal muscle in impact areas were highly correlated with each other. This may be related to common sources of pollutant emissions. Sex differences in micronutrient content can be determined by spatial differentiation of the sexes during migration, seasonal feeding patterns, and the specific birds’ metabolism in reproductive period. Cadmium and lead content in liver and muscle tissue samples from impact areas exceeded current food hygiene standards, which may pose a threat to consumers. Probably, high levels of lead and cadmium reflect the increased content of metals in food items primarily willow sprouts and buds, which are the most important winter food for ptarmigan.

The Relationship of Trace Element Levels with Obesity and Cardiovascular Health

Objective: One of the most important factors affecting cardiovascular health is obesity. Trace elements, which play a role in every stage of metabolism, are also related to our cardiovascular health. The aim of this study was to determine serum trace element levels in individuals and to examine the relationship between trace elements and cardiovascular risk. Methods: This cross-sectional study was conducted with individuals who applied to the outpatient clinic between 01.03.2022-31.04.2022. Sociodemographic characteristics, BMI, and Framingham risk score values were recorded. Serum iron, zinc, copper and selenium levels were analyzed in the laboratory. Results: A total of 180 individuals were included in the study. Of the individuals, 33.3% were overweight and 32.8% were obese. The mean Framingham Risk Score (FRS) was 9.31±7.99 (1-37). FRS values of normal weight individuals (7.84±3.05) were lower than the mean FRS values of overweight (8.80±3.39) and obese (13.39 ± 6.24) groups (p

The Added Value of Copper and Silver Metal from Printed Circuit Boards Waste Using Davis Tube with Variations of Size and Magnetic Intensity

The widespread use of electronic devices has led to a significant increase in electronic waste, including PCB (printed circuit board) waste. PCBs contain valuable metals like copper and silver, which can be reclaimed and reused. Recently, there has been a growing demand for urban mining processes to extract electronic waste PCB Flame Retardant-2 (FR-2) from laptops and computers. During the urban mining process, PCB FR-2 waste undergoes various physical treatments such as dismantling, crushing, and concentration processes. One of the concentration processes involves magnetic separation using a Davis tube. This study aims to investigate the effects of size and magnetic intensity variations on the recovery of copper and silver levels in FR-2 PCB waste. The magnetic concentration process was carried out using different size ranges (-63+100#, -100+150#, -150#) and magnetic intensities (1000 G, 2000 G, 3000 G). The results indicated that the most effective size for separating copper and silver is -63+100# and the optimal magnetic intensity is 1000 G. This resulted in copper and silver content of 45.66% and 0.162%, with recoveries of 80.135% and 62.505% respectively.

Unlocking vitiligo’s metal code: an analytical cross-sectional study of serum levels of trace elements in vitiligo patients

Background: Vitiligo is an acquired depigmenting skin disorder often associated with social stigma and having a significant psychological impact on patients. The study aimed to determine the correlation between serum levels of copper (Cu), zinc (Zn), selenium (Se), lead (Pb), mercury (Hg), cadmium (Cd), and Cu/Pb, Cu/Hg, Cu/Cd, Se/Hg, Se/Pb, Se/Cd, Zn/Hg, Zn/Pb, and Zn/Cd ratios in vitiligo patients. Materials and methods: In this analytical cross-sectional study, we enrolled 110 vitiligo patients as cases and 110 normal adults as controls. VIDA (Vitiligo Disease Activity Score) and VASI (Vitiligo Area Severity Index) were used to assess the activity and severity of vitiligo in patients. Venous blood samples of all study participants (aged &gt;12 years) were examined for serum levels of Zn, Cu, Se, Pb, Hg, and Cd using inductively coupled plasma mass spectrometry. SPSS.21 version software was used for the analysis of the data. Results: We noted a statistically significant (p-value &lt; 0.05, student’s t-test) difference in mean serum levels of Cu, Zn, and Se (microgram/liter) between cases and controls, denoted as 1370.67 ± 484.36 versus 2887.30 ± 3744.15, 1324.50 ± 555.02 versus 1603.81 ± 551.03, 248.95 ± 120.06 versus 287.15 ± 117.37, respectively. A significantly low serum level of Se was observed in female vitiligo patients, unlike controls. Vegetarian patients had low levels of Pb (p-value &lt;0.05) in comparison to non-vegetarian patients. Significantly low Zn/Hg and Cu/Hg ratios were observed in cases compared to controls. Limitations: Our study was limited by a small sample size. Being an observational study done from a single center, chances of inclusion of patients from a limited geographical area cannot be ruled out. Conclusion: Low levels of Zn, Cu, and Se could play a crucial role in the etiopathogenesis of vitiligo, which can vary based on the gender and diet pattern of the patient.

Methods established for the detection of mineral levels in whole blood by the dried blood spot technique

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.

Assessment of Essential Trace Elements Cu, Zn, Mn, and Ni in Mediterranean Mussels (Mytilus galloprovincialis) from the Algerian Coast.

The aim of this study was to determine the levels of essential trace elements copper, zinc, manganese, and nickel in two size groups of mussels, Mytilus galloprovincialis, sampled from three sites along the Algerian coast with different levels of pollution. The results of this work are very interesting for determining the effect of mussel size on the variation of contaminant levels in environmental monitoring studies. Thirty individuals from 2 size groups, less than 4-cm and more than 4-cm shell length, were collected over 4 seasons at each site studied. The samples were dissected, and copper, zinc, manganese, and nickel were measured in the whole soft tissues by inductively coupled plasma mass spectrometry (ICP-MS). The maximum concentrations of copper, zinc, manganese, and nickel expressed in mg/kg dry weight at the three sites were 54.01, 146.25, 20.69, and 8.85, respectively. A clear distribution pattern of the studied elements was observed in the two size classes. In fact, significantly higher concentrations (P < 0.05) were found in individuals with a shell length of less than 4 cm. Significantly, higher concentrations (P < 0.05) were found in individuals with a shell length of less than 4 cm due to their high filtration and low excretion activities compared to long individuals. In addition, metal pollution index (MPI) values were higher in small bivalve individuals. The trace element contents found in the mussel samples of the present study showed large spatial and temporal variations among the different sites studied, highlighting the typical exposure of marine sites to different marine pollutants. Notably, elevated concentrations of copper were observed in the port of Zemmouri, likely due to port activities. Conversely, the highest levels of manganese and nickel were recorded at Boudouaou El Bahri, potentially attributable to the use of fertilisers by agricultural activities. Some shellfish samples had exceeded the permissible concentration levels of copper and manganese, thereby posing a danger to bivalve consumers.

Relationship Between Serum Copper, Zinc Level and Tumour Aggressiveness in Invasive Cervical Cancer

&amp;lt;i&amp;gt;Background: &amp;lt;/i&amp;gt;Cervical cancer, a leading cause of cancer-related morbidity and mortality, exhibits considerable variability in aggressiveness. The role of trace elements such as copper and zinc in influencing tumor behavior and progression has garnered attention. This study investigates the relationship between serum copper and zinc levels and tumor aggressiveness in invasive cervical cancer.&amp;lt;i&amp;gt; Methods:&amp;lt;/i&amp;gt; A cross-sectional comparative study was conducted among 150 women with invasive cervical cancer attending the outpatient department and Colposcopy Clinic of the Department of Gynecological Oncology, BSMMU, Dhaka, from April 2022 to March 2023. Participants were divided into two groups based on tumor aggressiveness: Group 1 (less aggressive) and Group 2 (more aggressive), with 75 women in each group. Serum copper and zinc levels were measured and analyzed for differences between groups. &amp;lt;i&amp;gt;Result:&amp;lt;/i&amp;gt; Serum copper levels were significantly higher in Group 2 (152.31 ± 41.81 µg/dL) compared to Group 1 (139.31 ± 25.52 µg/dL) with a p-value of 0.023. Conversely, serum zinc levels were significantly lower in Group 2 (55.24 ± 28.13 µg/dL) compared to Group 1 (66.29 ± 31.58 µg/dL) with a p-value of 0.025. The copper/zinc ratio was significantly higher in Group 2 (2.76 ± 1.20) compared to Group 1 (2.10 ± 1.00) with a p-value of &amp;lt;0.001. &amp;lt;i&amp;gt;Conclusion:&amp;lt;/i&amp;gt; Elevated serum copper levels and copper/zinc ratio, along with decreased zinc levels, are associated with more aggressive cervical cancer. These findings suggest that trace element imbalances may serve as biomarkers for assessing tumor aggressiveness and could inform future therapeutic strategies.

Modulation of fecal microbiota and reductions in fecal antibiotic resistance genes (ARGs) driven by Weissella-fermented feed in growing pigs

Probiotics-induced feed fermentation can improve the composition of microbiota, leading to benefits in pig production. However, the influence of probiotics-driven feed fermentation on pollution reduction is limited. This study aimed to analyze the impact of Weissella-based feed fermentation on the chemical characteristics, changes in microbial abundance, and antibiotic resistance genes (ARGs). Moreover, the possible mechanism and the association among them was also analyzed. First, pigs reared on fermented feed exhibited improved growth performance. The fermentation group showed a significant reduction in emissions of total phosphorus (TP), total carbon (TC), organic matter (OM), copper (Cu), and zinc (Zn) levels in feces compared to the control group. The fermentation group also showed a significant decrease in the ARGs, especially for the tetX, tetW, tetQ, tetL, tetO, tet32, tet44, ermG, ermF, CfxA2, CfxA3, aph3-III, aadA, and ant9-I, compared to the control group. The primary functional microbiota, characterized by increased levels of Bifidobacterium, Megasphaera, and Mitsuokella, and decreased levels of Methanosphaera, and Ruminiclostridium, displayed both negative and positive correlations with ARGs, TC, TP, OM, Cu, and Zn. Furthermore, a significant association was observed between the alterations in microbiota and ARGs and the lactic acid concentration in the fermented feed. The molecular docking results showed a good fit between lactate dehydrogenase and three antibiotics, particularly tetracycline. In conclusion, these results offer novel targets and strategies to address environmental pollutants associated with pig farming.

Effect of Dietary Copper on Growth Performance, Antioxidant Capacity, and Immunity in Juvenile Largemouth Bass (Micropterus salmoides)

This study evaluated the optimal dietary copper (Cu) levels and their effects on growth performance, body composition, and antioxidant capacity in juvenile largemouth bass (Micropterus salmoides). A total of 360 fish (initial average weight (1.67 ± 0.01 g) and initial average length (2.5 ± 0.2 cm)) were randomly assigned to 18 tanks, each containing 20 fish and six dietary Cu concentrations: 2.13 (control), 3.00, 3.66, 4.58, 4.64, and 5.72 mg/kg. The results indicated that fish receiving 3.00 mg/kg of Cu exhibited the best final body weight (FBW), weight gain rate (WGR), and specific growth rate (SGR), with a significantly reduced feed conversion ratio (FCR). While body composition (moisture, protein, lipid, and ash) remained consistent across groups, plasma total protein (TP) levels increased with Cu supplementation. Elevated triglycerides (TG) and albumin (ALB) were noted at 4.64 and 5.72 mg/kg, respectively, while glucose (GLU) levels decreased with an increase in dietary Cu. Antioxidant capacity, assessed via hepatic glutathione (GSH) and the activities of catalase (CAT), and showed significant improvements at 3.00 and 3.66 mg/kg Cu, while superoxide dismutase (SOD) showed the highest activity at a dietary Cu level of 5.72 mg/kg. Additionally, the expressions of tgf-β and tnf-α genes were significantly upregulated at a dietary Cu level of 5.72 mg/kg, while il-8 and il-10 genes were upregulated at dietary 3.66 mg/kg. The expression of nrf2 was significantly upregulated in response to a dietary Cu level of 3.66 mg/kg compared to the control group, and the expression of the keap1 gene was significantly upregulated in the fish fed with 5.72 mg/kg of dietary Cu. The results indicated that appropriate dietary supplementation could promote the growth performance and improve the antioxidant status the immunity of largemouth bass, and the optimal Cu requirement for FCR and SGR were approximately 3.10 mg/kg and 3.00 mg/kg, respectively.

Studying the relationship betweenSerum Copper levels and Vitamin D in Alopecia Areata patients with Controls in India

Studying the relationship betweenSerum Copper levels and Vitamin D in Alopecia Areata patients with Controls in India

Spectrofluorometric determination of copper and lead in human plasma using 6,7-dihydroxy-4-methylcoumarin: Investigating their role in chronic otitis media

Chronic otitis media is a recurrent middle ear infection that poses a common health risk globally, particularly in the developing countries. Association between heavy metals, specifically copper and lead and otitis media has been underexplored. Herein, a spectrofluorometric method was developed to determine copper and lead in human plasma samples investigating their association with chronic otitis media. The method utilizes feasible interaction of 6,7-dihydroxy-4-methylcoumarin, with copper and lead to yield different fluorescent compounds that provides measurable approaches for their levels in the plasma matrix. Copper is quantitatively analyzed based on its quenching ability for the fluorescence of 6,7-dihydroxy-4-methylcoumarin exhibiting concentration-dependent behavior. On the other hand, lead forms a fluorescent complex with 6,7-dihydroxy-4-methylcoumarin that has remarked fluorescence enhancement and bathochromic shift, enabling sensitive lead quantification. The method was briefly validated and introduced accepted linear relationship over a concentration range of 100–3000 ng/mL for copper and 200–4000 ng/mL for lead. The method was used to determine the levels of copper and lead in the human plasma samples of healthy volunteers and patients with chronic otitis media. The results revealed a decrease in copper levels and an increase in lead levels in otitis media patients compared to healthy controls. These findings suggest a potential association between copper and lead levels and chronic otitis media, warranting further investigation into their role in the condition.

Evaluation of Heavy Metal Concentration in Sediments of Rupingazi River, Kenya

Heavy metal concentration (Cu, Zn, Fe, Mn, Ni) was evaluated in sediment samples of Rupingazi river during the wet and dry seasons. In this study, the sediment samples were collected from twenty sampling points along the river. The heavy metal levels were evaluated using Atomic Absorption Spectrphotometer.The obtained data was analyzed using one-way analysis of variance. The range of the concentration of copper was found to be 4.68- 12.69 mg/kg for the wet season and 0.98-24.10mg/kg for the dry season. The mean values of the concentration of iron was found to be 1422-6145.33 mg/kg for the wet season and 1254-5866.67 mg/kg for the dry season. The range of the concentration of Nickel was found to be 0.72- 30.73 mg/kg for the wet season and 2.63-12.48 mg/kg for the dry season. Concentration of manganese was found to be 48.03-411.20 mg/kg for the wet season and 6.15-248.35 mg/kg for the dry season Zinc concentration was found to be 26.29-167.10 mg/kg for the wet season and 4.82-28.39 mg/kg for the dry season. The Zinc, Manganese, Nickel Iron and Copper levels were not beyond the USEPA recommended limits.

Role of copper during microglial inflammation.

Copper plays crucial roles in various physiological functions of the nervous and immune systems. Dysregulation of copper homeostasis is linked to several diseases, including neurodegenerative diseases. Since dysfunctional microglial immunity can contribute to such diseases, we investigated the role of copper in microglial immunity. We found that both increased and decreased copper levels induced by chemical treatments suppresses lipopolysaccharide (LPS)-mediated inflammation in microglial cells, as determined by RT-qPCR analysis. RNA sequencing (RNA-seq) analysis confirmed that increased copper level reduces the inflammatory response to LPS; however, it also showed that decreased copper level affects genes involved in cell proliferation, transcription, and autophagosome regulation. These findings suggest that copper is vital for maintaining normal immune function in microglia, and both copper excess and deficiency can disrupt microglial immunity.

Copper ions: The invisible killer of cardiovascular disease (Review).

Copper, a vital trace element, is indispensable for the maintenance of physiological functioning, particularly in the cardiac system. Unlike other forms of cell death such as iron death and apoptosis, copper‑induced cell death has gained increasing recognition as a significant process influencing the development of cardiovascular diseases. The present review highlights the significance of maintaining copper homeostasis in addressing cardiovascular diseases. This review delves into the crucial roles of copper in physiology, including the metabolic pathways and its absorption, transport and excretion. It provides detailed insights into the mechanisms underlying cardiovascular diseases resulting from both excess and deficient copper levels. Additionally, it summarizes strategies for treating copper imbalances through approaches such as copper chelators and ion carriers while discussing their limitations and future prospects.

Mycobacterium marinum MMAR_0267-regulated copper utilization facilitates bacterial escape from phagolysosome

The host limits Mycobacterium tuberculosis (Mtb) by enriching copper in high concentrations. This research investigates how Mtb escapes copper stress. The membrane protein encoded by Mtb Rv0102, when its homolog in M. smegmatis (MSMEG_4702) was knocked out, resulted in a fourfold decrease in intracellular copper levels and enhanced tolerance to elevated extracellular copper concentrations. Similarly, knockout mutants of its homolog in M. marinum (MMAR_0267) showed increased virulence in zebrafish and higher bacterial load within macrophages. In THP-1 cells infected with MMAR_0267 deletion mutants, the intracellular survival of these mutants increased, along with reduced THP-1 cell apoptosis. Deficiency in copper down-regulated the transcriptional level of the virulence factor CFP-10 in M. marinum, suppressed cytosolic signaling via the macrophage STING pathway, leading to decreased production of IFN-β and reduced cell apoptosis. In conclusion, these findings highlight the significant impact of copper on the survival and reproduction of mycobacteria, underscoring the importance of studying mycobacterial adaptation mechanisms in copper-rich environments.

Copper homeostasis and cuproptosis in health and disease.

Copper is a vital trace element in human physiology, essential for the synthesis of numerous crucial metabolic enzymes and facilitation of various biological processes. Regulation of copper levels within a narrow range is imperative for maintaining metabolic homeostasis. Numerous studies have demonstrated the significant roles of copper homeostasis and cuproptosis in health and disease pathogenesis. However, a comprehensive and up-to-date systematic review in this domain remains absent. This review aims to consolidate recent advancements in understanding the roles of cuproptosis and copper homeostasis in health and disease, focusing on the underlying mechanisms and potential therapeutic interventions. Dysregulation of copper homeostasis, manifesting as either copper excess or deficiency, is implicated in the etiology of various diseases. Cuproptosis, a recently identified form of cell death, is characterized by intracellular copper overload. This phenomenon mediates a diverse array of evolutionary processes in organisms, spanning from health to disease, and is implicated in genetic disorders, liver diseases, neurodegenerative disorders, and various cancers. This review provides a comprehensive summary of the pathogenic mechanisms underlying cuproptosis and copper homeostasis, along with associated targeted therapeutic agents. Furthermore, it explores future research directions with the potential to yield significant advancements in disease treatment, health management, and disease prevention.

Clinical experience on switching trientine tetrahydrochloride to trientine dihydrochloride in Wilson disease patients.

This study evaluates the effectiveness and safety of trientine dihydrochloride (TETA 2-HCl) in patients with Wilson disease (WD) following a switch from trientine tetrahydrochloride (TETA 4-HCl). A total of 30 WD patients with stable copper metabolism were identified for treatment with TETA 2-HCl (Cufence™) after prior use of TETA 4-HCl (Cuprior™). Biochemical markers including urinary copper, non-ceruloplasmin bound copper (NCC) and liver function were analyzed at baseline and followed up over 12 months. Safety was assessed based on reported adverse events (AEs). Urinary copper levels and NCC remained stable across all follow-ups, indicating adequate copper metabolism control. Reported AEs during TETA 2-HCl treatment were mostly gastrointestinal discomfort (n = 6). In two patients, progressive elevation of transaminases occurred (despite stable copper metabolism). AEs led to discontinuation of treatment in five cases. Median baseline dose per day was 10.2 mg TETA 4-HCl/kg bodyweight, whereas median baseline dose after therapeutic switch to TETA 2-HCl was 12.8 mg/kg bodyweight. Median daily dose at 12 months did not differ significantly from TETA 2-HCl dose at switching timepoint, with stable biochemical markers and markers of copper metabolism in most (25/30) of the patients. Transitioning from TETA 4-HCl to TETA 2-HCl maintained stable copper parameters and liver function in most of analyzed patients. TETA 2-HCl treatment was generally well tolerated, suggesting that switching medications is safe and effective. In our real-life cohort, adjustment factor of ~1.25× for the switch of TETA 4-HCl to TETA 2-HCl resulted in adequate copper metabolism control.