Copper is a vital cofactor in various enzymes, plays a pivotal role in maintaining cell homeostasis. When copper metabolism is disordered and mitochondrial dysfunction is impaired, programmed cell death such as apoptosis, paraptosis, pyroptosis, ferroptosis, cuproptosis, autophagy and necroptosis can be induced. In this review, we focus on the metabolic mechanisms of copper. In addition, we discuss the mechanism by which copper induces various programmed cell deaths. Finally, this review examines copper's involvement in prevalent kidney diseases such as acute kidney injury and chronic kidney disease. The findings indicate that the use of copper chelators or plant extracts can mitigate kidney damage by reducing copper accumulation, offering novel insights into the pathogenesis and treatment strategies for kidney diseases.

This study analyzed human, goat, sheep, and pig milks using metabolomics, lipidomics, and proteomics, specifically untargeted LC-MS/MS metabolomics, untargeted LC-MS/MS lipidomics, and 4D-label-free proteomics. The aim was to determine differences among these milks and identify components with similar functions to human milk, providing a reference for the research and development of infant formulae. In goat milk, expression of lactoperoxidase, inosine, and allantoin were relatively high, while in sheep milk, concentrations of ceruloplasmin and alpha-ketoglutarate were higher. The content of linoleic acid (LA) was relatively high in both goat and sheep milks. A relatively high content of milk fat globule EGF factor 8 protein was found in pig milk.

Some studies have demonstrated the involvement of high concentrations of copper in the manifestation of insulin resistance in individuals with obesity. The objective of this study was to evaluate the copper nutritional status and its relationship with parameters of glycemic control in women with obesity. An observational case-control clinical study involving 203 women aged between 20 and 50 years, divided into two groups: obese (n = 84) and eutrophic (n = 119). Body weight, height and waist, hip and neck circumferences, dietary copper intake, copper biomarkers, determine ceruloplasmin activity and glycemic control parameters were measured. It was observed that women with obesity had higher copper concentrations in plasma and lower concentrations in erythrocytes when compared to the control group. Analysis of glycemic control parameters revealed a statistically significant difference in fasting blood glucose (p < 0.05) between groups. The study identified a significant positive correlation between plasma copper and fasting insulin values and the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) index (p < 0.05). The results of this study demonstrate that obese women have high copper concentrations in plasma and lower concentrations in erythrocytes. Furthermore, the significant positive correlation between plasma copper and fasting insulin and HOMA-IR index suggests the influence of this mineral on glycemic control parameters in obese women.

Undernutrition remains a global struggle and is associated with almost 45% of deaths in children younger than 5 years. Despite advances in management of severe wasting (though less so for nutritional edema), full and sustained recovery remains elusive. Children with severe wasting and/or nutritional edema (also commonly referred to as severe acute malnutrition and part of the umbrella term "severe malnutrition") continue to have a high mortality rate. This suggests a likely multifactorial etiology that may include micronutrient deficiency. Micronutrients are currently provided in therapeutic foods at levels based on expert opinion, with few supportive studies of high quality having been conducted. This narrative review looks at the knowledge base on micronutrient deficiencies in children aged 6-59 months who have severe wasting and/or nutritional edema, in addition to highlighting areas where further research is warranted (See "Future Directions" section).

In the past decade, evidence for the numerous roles of copper (Cu) in mammalian physiology has grown exponentially. The discoveries of Cu involvement in cell signaling, autophagy, cell motility, differentiation, and regulated cell death (cuproptosis) have markedly extended the list of already known functions of Cu, such as a cofactor of essential metabolic enzymes, a protein structural component, and a regulator of protein trafficking. Novel and unexpected functions of Cu transporting proteins and enzymes have been identified, and new disorders of Cu homeostasis have been described. Significant progress has been made in the mechanistic studies of two classic disorders of Cu metabolism, Menkes disease and Wilson's disease, which paved the way for novel approaches to their treatment. The discovery of cuproptosis and the role of Cu in cell metastatic growth have markedly increased interest in targeting Cu homeostatic pathways to treat cancer. In this review, we summarize the established concepts in the field of mammalian Cu physiology and discuss how new discoveries of the past decade expand and modify these concepts. The roles of Cu in brain metabolism and in cell functional speciation and a recently discovered regulated cell death have attracted significant attention and are highlighted in this review.

Copper is an essential trace element crucial for enzyme synthesis and metabolism. Adequate copper levels are beneficial for maintaining the normal immune function of the spleen. Copper deficiency disrupts the metabolic processes within the spleen and impairs its immune function. This research examines the impact of copper deficiency on the spleen and the potential recovery following copper supplementation.

Weaned mice underwent a 4-week copper-deficient diet, succeeded by 1-week of copper repletion via intraperitoneal copper sulfate injection. Histological examination was used to assess pathological changes in the spleen. Biochemical assays were performed to measure oxidative stress levels in the spleen. ELISA, qPCR, and Western blot were employed to examine alterations in inflammatory markers, immune indicators, and oxidative regulatory factors across various levels.

Copper deficiency caused histological damage to the spleen, altered the expression of oxidative stress regulatory pathways (Nrf2, Keap1, and HO-1), and affected the expression of key inflammatory enzymes (iNOS, COX2) and transcription factor NF-κB, leading to oxidative damage. This was reflected by decreased levels of SOD, GSH, and T-AOC, along with increased levels of CAT and MDA. The levels of inflammatory cytokines IL-1β, TNF-α, IL-6, and IL-8 were notably increased. Copper supplementation significantly improved these changes.

Copper deficiency leads to spleen tissue damage in mice, affecting the Nrf2 regulatory pathway and inducing oxidative damage. Subsequent copper supplementation with copper sulfate effectively ameliorates the damage caused by copper deficiency.

Colorectal cancer has emerged as one of the predominant malignant tumors globally. Immunotherapy, as a novel therapeutic methodology, has opened up new possibilities for colorectal cancer patients. However, its actual clinical efficacy requires further enhancement. Copper, as an exceptionally crucial trace element, can influence various signaling pathways, gene expression, and biological metabolic processes in cells, thus playing a critical role in the pathogenesis of colorectal cancer. Recent studies have revealed that cuproptosis, a novel mode of cell death, holds promise to become a potential target to overcome resistance to colorectal cancer immunotherapy. This shows substantial potential in the combination treatment of colorectal cancer. Conveying copper into tumor cells via a nano-drug delivery system to induce cuproptosis of colorectal cancer cells could offer a potential strategy for eliminating drug-resistant colorectal cancer cells and vastly improving the efficacy of immunotherapy while ultimately destroy colorectal tumors. Moreover, combining the cuproptosis induction strategy with other anti-tumor approaches such as photothermal therapy, photodynamic therapy, and chemodynamic therapy could further enhance its therapeutic effect. This review aims to illuminate the practical significance of cuproptosis and cuproptosis-inducing nano-drugs in colorectal cancer immunotherapy, and scrutinize the current challenges and limitations of this methodology, thereby providing innovative thoughts and references for the advancement of cuproptosis-based colorectal cancer immunotherapy strategies.

Copper, a malleable and ductile transition metal, possesses two stable isotopes. These copper isotopic composition data have recently found diverse applications in various fields and disciplines. In geology, copper isotopes serve as tracers that aid in investigating ore formation processes and the mechanisms of copper deposits Likewise, it has emerged as a valuable tracer in polluted environments. In plant biology, copper acts as an essential micronutrient crucial for photosynthesis, respiration, and growth. Copper isotopes contribute to understanding how plants uptake and dispense copper from the soil within their tissues. Similarly, in animals, copper serves as an essential trace element, playing a vital role in growth, white blood cell function, and enzyme activity. In humans, copper acts as an antioxidant, neutralising harmful free radicals within the body. It also helps in maintaining the nervous and immune system. Furthermore, copper isotopes find medical applications, particularly in cancer diagnostics, neurodegenerative diseases, and targeted radiotherapy. However, excessive copper can have detrimental effects in humans such as it can cause liver damage, nausea, and abdominal pain, whilst in plants it can affect the growth of plants, photosynthesis, and membrane permeability. This review emphasises the significance of copper and its isotopes in geology, the environment, and human health.

Zinc deficiency causes dysgeusia and dermatitis as well as anemia. As approximately half of dialysis patients have zinc deficiency, zinc supplementation should be considered in case of erythropoiesis-stimulating agent (ESA)-hyporesponsive anemia. We report a case of a chronic dialysis patient with copper deficiency anemia caused by standard-dose zinc supplementation. The patient was a 70-year-old woman who had received maintenance hemodialysis for 8 years due to diabetic nephropathy. She had been treated with weekly administration of darbepoetin 30 μg for renal anemia, which resulted in Hb 12 to 14 g/dL. She had no dysgeusia. When zinc deficiency (44 μg/dL) had been identified 4 months earlier, 50 mg daily zinc acetate hydrate (Nobelzin®), which is the standard dose, was started. Unexpectedly, her anemia progressed slowly with macrocytosis together with granulocytopenia. Her platelet count did not decrease at that time. Laboratory tests revealed a marked decrease of serum copper (< 4 μg/dL) and ceruloplasmin (< 2 mg/dL), although serum zinc was within the normal limit (125 μg/dL). We discontinued zinc acetate and started copper supplementation including cocoa for 1 month. Her anemia and granulocytopenia were dramatically restored coincident with the increase in both serum copper and ceruloplasmin. Copper supplementation also improved her iron status as assessed by transferrin saturation and ferritin. Clinicians should monitor both zinc and copper status in anemic dialysis patients during zinc supplementation, as both are important to drive normal hematopoiesis.

Zinc supplementation induces metallothionein, leading to reduced serum copper levels. Conversely, serum copper concentrations tend to rise with the use of HIF-PH inhibitors.

To establish a safe level of zinc supplementation that avoids copper deficiency, serum copper and zinc concentrations measured every three months were retrospectively analyzed over five years in 50 patients undergoing hemodialysis.

At the initiation of the study, the median (IQR) concentrations were 100 (84.25-109) µg/dL for serum copper and 60.5 (50.5-70) µg/dL for serum zinc. All participants without zinc supplementation exhibited zinc deficiency (<80 µg/dL). After three months, copper deficiency (<71 µg/dL) was observed when serum copper concentrations were <98.6 µg/dL for patients with HIF-PH inhibitors and <90.3 µg/dL for patients without them. Reduced zinc supplementation may be necessary when serum copper falls below 90 µg/dL. Zinc levels remained deficient because supplementation was limited due to concerns about copper deficiency. Lowering the target zinc level to around 80 µg/dL instead of the conventional 80-120 µg/dL may be safer.

Regular monitoring of both copper and zinc levels, taking place at least every three months, is recommended to adjust zinc supplementation, especially in patients on HIF-PH inhibitors. Copper supplementation should also be considered alongside zinc supplementation to effectively treat hypozincemia.

Peri-operative anemia is a common condition encountered in adult surgical patients. It is increasingly recognized as a predictor of post-operative morbidity and mortality. Evaluation and treatment of anemia pre-operatively can reduce transfusion needs and potentially improve outcomes in surgical patients. This article discusses anemia optimization strategies in peri-operative setting with special focus on use of intravenous iron therapy. Additionally, the authors describe the role of transfusion medicine and best practices around red blood cell, platelet, and plasma transfusions.

Laboratory measurements of trace elements such as magnesium (Mg), copper (Cu), and zinc (Zn) in red blood cells (RBCs) are essential for assessing nutritional status and diagnosing metal toxicity. The purpose of this study was to develop and validate an ICP-MS method for quantifying these elements in RBCs.

Packed RBCs were aliquoted and diluted in an alkaline diluent solution containing internal standards, 0.1 % Triton X-100, 0.1 % EDTA, and 1 % ammonium hydroxide. The resulting diluted specimen was analyzed using inductively coupled plasma mass spectrometry (ICP-MS) to quantitatively determine the levels of Mg, Cu, and Zn. The method underwent validation for accuracy, precision, method comparison, linearity, analytical sensitivity, and carryover. Additionally, retrospective data were analyzed, and non-parametric reference intervals were calculated.

Accuracy and linearity fell within the expected range of ≤±15 % for all analytes. Within-run, between-run, and total imprecision were ≤15 % coefficient of variation. All other validation experiments met the established acceptance criteria. Retrospective data analysis was conducted on patient samples using the method. The application of Tukey's HSD test for multiple comparisons revealed statistically significant mean differences (p < 0.05) in Mg, Cu, and Zn concentrations between all pairwise groups of age and sex, except for the mean Cu concentration in adult males versus females and the mean Mg concentrations in adult versus minor males.

The presented method was successfully validated and met the criteria for clinical use. Retrospective data analysis of patient results demonstrated the method's suitability for assessing nutritional deficiency and toxicity.

Non-alcoholic fatty liver disease (NAFLD), a metabolic-associated fatty liver disease, has become the most common chronic liver disease worldwide. Recently, the discovery of cuproptosis, a newly identified mode of cell death, further highlighted the importance of copper in maintaining metabolic homeostasis. An increasing number of studies have confirmed that liver copper metabolism is closely related to the pathogenesis of NAFLD. However, the relationship between NAFLD and copper metabolism, especially cuproptosis, remains unclear. In this review, we aim to summarize the current understanding of copper metabolism and its dysregulation, particularly the role of copper metabolism dysregulation in the pathogenesis of NAFLD. More importantly, this review emphasizes potential gene-targeted therapeutic strategies, challenges and the future of cuproptosis-related genes in the treatment of NAFLD. This review aims to provide innovative therapeutic strategies for NAFLD.

Dietary copper intake is a promising predictor of peripheral neuropathy. There is no research exploring the potential link between dietary copper intake and peripheral neuropathy.

The information utilized in our research was collected from the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2004. The relationship between dietary copper intake and peripheral neuropathy was analyzed using a multivariate logistic regression model and restricted cubic spline (RCS).

The RCS analysis results showed a U-shaped nonlinear relationship between dietary copper intake and peripheral neuropathy (P for nonlinearity < 0.001). The threshold effect analysis results indicated that when dietary copper intake was less than 0.889 mg/d, the risk of peripheral neuropathy decreased with increasing copper intake (OR: 0.388, 95% CI: 0.200-0.753). When dietary copper intake was ≥ 0.889 mg/d, the risk of peripheral neuropathy increased with increasing copper intake (OR: 1.129, 95% CI: 1.006-1.266). And the incidence rate of peripheral neuropathy in the first quantile (OR: 1.421, 95% CI: 1.143-1.766), the third quantile (OR: 1.358, 95% CI: 1.057-1.744), and the fourth quantile (OR: 1.676, 95% CI: 1.250-2.248) of dietary copper intake were significantly higher than that in the second quantile (where the inflection point was located).

Our study suggests that both insufficient and excessive dietary copper intake may be associated with an increased incidence of peripheral neuropathy. However, further research is needed to provide definitive evidence and confirm these findings.

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/m2) 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.

Previous studies have linked single metal to hemoglobin levels in children and adolescents; however, studies with regards to metal mixtures are still limited.

We aimed to investigate the associations of single metal and metal mixtures with hemoglobin levels in children and adolescents.

We conducted a cross-sectional study of 2064 children and adolescents aged 6 to 19 years in Liuzhou, China in 2018. The concentrations of 15 metals in urine were determined by inductively coupled plasma mass spectrometry. Generalized linear regression and weighted quantile sum (WQS) regression were used to estimate the associations of single metal and metal mixtures with hemoglobin levels, respectively.

The multivariable-adjusted β-values for the highest versus the first quartiles of urinary metal concentrations were - 1.57 (95 % confidence interval [CI]: -3.01, -0.13) for chromium, -2.47 (95 % CI: -3.90, -1.05) for nickel and 1.88 (95 % CI: 0.49, 3.28) for copper. In addition, we found a significant negative association between the WQS index and hemoglobin levels (adjusted β = -0.93, 95 % CI: -1.69, -0.19), with nickel contributing the most to the WQS index at 59.0 %. Subgroup analyses showed that exposure to urinary nickel or metal mixtures were associated with decreased hemoglobin levels in adolescents, but not in children (all Pinteration < 0.001).

Among children and adolescents, urinary chromium and nickel concentrations were associated with decreased hemoglobin levels, while copper showed a positive relationship. Moreover, a negative association was observed between exposure to metal mixtures and hemoglobin levels. These findings need to be further validated in prospective studies.

Extracts of Salvia officinalis (S. officinalis) have been described to have many therapeutic properties. However, the effect of S. officinalis on copper sulfate toxicity has not been previously reported. The aim of this study was to investigate the toxicity of copper sulfate and the potential beneficial effects of S. officinalis aqueous infusion on proinflammatory response and antioxidant status. 56 male mice were used and equally divided into 6 groups: control group, copper sulfate treated group (40 mg/kg), S. officinalis aqueous infusion treated groups (200 mg/kg and 400 mg/kg) separately or in combination with copper. IL-6 (interleukine-6) and TNF-α (Tumor necrosis factor alpha) were assessed by Elisa. Catalase (CAT), superoxide dismutase (SOD) and acetylcholinesterase (AChE) activities, malondialdehyde (MDA) and oxygen peroxide levels were determined. Serum biochemical parameters were analyzed. Copper enhanced aspartate aminotransferase (AST), alanine aminotransferase (ALT) and Lactate dehydrogenase (LDH) (p < 0.05). Copper enhances significantly IL-6, TNF-α and MDA levels in liver and kidney and reduced CAT, SOD and AChE activities (p < 0.05). Aqueous infusion of S. officinalis at 400 mg/kg abolished copper-induced changes in AST and ALT activity. S. officinalis aqueous infusion at 200 mg/kg reversed copper-induced IL-6 in kidney and TNF-α in liver at both doses. S. officinalis aqueous infusion at 400 mg/kg restored SOD in kidney and CAT and AChE activities in both liver and kidney. S. officinalis aqueous infusion may be useful in partially ameliorating tissue disorders induced by copper exposure such as inflammatory response, oxidative stress imbalance and organ dysfunction through its phenolic compounds and higher antioxidant capacity.

Copper is an essential trace element for biological systems, as it plays a critical role in the activity of various enzymes and metabolic processes. However, the dysregulation of copper homeostasis is closely associated with the onset and progression of numerous diseases. In recent years, copper-induced cell death, a novel form of cellular demise, has garnered significant attention. This process is characterized by the abnormal accumulation of intracellular copper ions, leading to cellular dysfunction and eventual cell death. Copper toxicity occurs through the interaction of copper with acylated enzymes in the tricarboxylic acid (TCA) cycle. This interaction results in subsequent protein aggregation, causing proteotoxic stress and ultimately resulting in cell death. Despite the promise of these findings, the detailed mechanisms and broader implications of cuproptosis remain underexplored. Therefore, our study aimed to investigate the role of copper in cell death and autophagy, focusing on the molecular mechanisms of cuproptosis. We also aimed to discuss recent advancements in copper-related research across various diseases and tumors, providing insights for future studies and potential therapeutic applications.

This review delves into the biological significance of copper metabolism and the molecular mechanisms underlying copper-induced cell death. Furthermore, we discuss the role of copper toxicity in the pathogenesis of various diseases, emphasizing recent advancements in the field of oncology. Additionally, we explore the therapeutic potential of targeting copper toxicity.

The study highlights the need for further research to explore alternative pathways of copper-induced cell death, detailed mechanisms of cuproptosis, and biomarkers for copper poisoning. Future research should focus on exploring the molecular mechanisms of cuproptosis, developing new therapeutic strategies, and verifying their safety and efficacy in clinical trials.

The population in Latin America and Caribbean (LAC) has experienced a major demographic transition with increased numbers of older adults (OA). This change brings opportunities in the public health sector to implement health prevention interventions and delay the onset of geriatric syndromes. Micronutrients play an important role in the maintenance of biological function which contributes to longevity. Micronutrient deficiencies (MD) in OA increase the risk for onset of chronic comorbidities and geriatric syndromes.

To review and summarize the existing data on micronutrient status in OA in the LAC region and discuss the gaps and challenges in public health approaches to address deficiencies.

Literature review in Medline for records describing nutritional biomarkers in older adults (≥ 60y) from community dwelling and population-based studies in LAC.

Few countries (including Chile, Ecuador, Costa Rica, Brazil, and Mexico) have documented one or more nutritional deficiencies for OA in national health surveys, however across the entire region, evidence of micronutrient levels is scarce. Some surveys have documented a high prevalence and large heterogeneity in the prevalence of vitamin D followed by B12 deficiency, being the 2 MDs most studied due their effects on cognition, frailty, and bone mineral density in the OA population. Other MD including C, E, A, copper, zinc, iron, and selenium have also been reported.

Information on the micronutrient status in OA from LAC is poorly documented. Research and capacity building initiatives in the region are crucial to develop tailored strategies that address the specific nutritional needs and challenges faced by the ageing population in Latin America.

Copper (Cu) is a precious metal and one of the three most abundant trace elements in the body (50-120 mg). It is involved in a large number of cellular mechanisms and pathways and is an essential cofactor in the function of cellular enzymes. Both its excess and deficiency may be harmful for many diseases. Even small changes in Cu concentration may be associated with significant toxicity. Consequently, it can be damaging to any organ or tissue in our body, beginning with harmful effects already at the molecular level and then affecting the degradation of individual tissues/organs and the slow development of many diseases, such as those of the immunological system, skeletal system, circulatory system, nervous system, digestive system, respiratory system, reproductive system, and skin. The main purpose of this article is to review the literature with regard to both the healthiness and toxicity of copper to the human body. A secondary objective is to show its widespread use and sources, including in food and common materials in contact with humans. Its biological half-life from diet is estimated to range from 13 to 33 days. The retention or bioavailability of copper from the diet is influenced by several factors, such as age, amount and form of copper in the diet, lifestyle, and genetic background. The upper limit of normal in serum in healthy adults is approximately 1.5 mg Cu/L, while the safe upper limit of average intake is set at 10-12 mg/day, the reference limit at 0.9 mg/day, and the minimum limit at 0.6-0.7 mg/day. Cu is essential, and in the optimal dose, it provides antioxidant defense, while its deficiency reduces the body's ability to cope with oxidative stress. The development of civilization and the constant, widespread use of Cu in all electrical devices will not be stopped, but the health of people directly related to its extraction, production, or distribution can be controlled, and the inhabitants of nearby towns can be protected. It is extremely difficult to assess the effects of copper on the human body because of its ubiquity and the increasing reports in the literature about its effects, including copper nanoparticles.

A 59-year-old man with pancytopenia underwent 18F-fluorodeoxyglucose positron emission tomography/computed tomography for suspected carcinomatosis. The scan revealed diffuse bone marrow uptake, prompting further investigation. Bone marrow analysis revealed no malignant cells; however, erythroblasts with cytoplasmic vacuolization were observed. Subsequent testing showed low serum copper and ceruloplasmin levels, indicating copper deficiency. Copper supplementation resulted in significant improvement in cytopenia. Notably, the bone marrow uptake on subsequent scans decreased significantly. This case highlights the importance of considering copper deficiency as a potential cause of diffuse bone marrow uptake of 18F-fluorodeoxyglucose on positron emission tomography/computed tomography.

The concentration of trace elements (chromium, lead, zinc, copper, manganese, and iron) was determined in water, sediment and tissues of two Cyprinidae fish species - Labeo rohita and Tor putitora - collected from the eight sampling stations of Indus River in 2022 for four successive seasons (autumn, winter, spring, summer), and also study the present condition of macroinvertebrates after the construction of hydraulic structure. The obtained results of trace element concentrations in the Indus River were higher than the acceptable drinking water standards by WHO. The nitrate concentration ranges from 5.2 to 59.6 mg l-1, turbidity ranges from 3.00 to 63.9 NTU, total suspended solids and ammonium ions are below the detection limit (<0.05). In the liver, highest dry wt trace elements (μg/g) such as Cr (4.32), Pb (7.07), Zn (58.26), Cu (8.38), Mn (50.27), and Fe (83.9) for the Labeo rohita; and Tor Putitora has significantly greater accumulated concentration (Cr, Pb, Zn, Cu, Mn, Fe) in muscle and liver than did Labeo rohita species. Additionally, lower number of macroinvertebrates were recorded during the monsoonal season than pre-monsoon and post-monsoon. Local communities surrounded by polluted environments are more probably to consume more fish and expose them to higher concentrations of toxic trace elements (lead and copper). The findings also provide a basis for broader ecological management of the Indus River, which significantly influenced human beings and socioeconomic disasters, particularly in the local community.

Copper is an essential trace element for all aerobic organisms because of its unique biological functions. In recent years, researchers have discovered that copper can induce cell death through various regulatory mechanisms, thereby inducing inflammation. Efforts have also been made to alter the chemical structure of copper to achieve either anticancer or anti-inflammatory effects. The copper ion can exhibit bactericidal effects by interfering with the integrity of the cell membrane and promoting oxidative stress. Sepsis is a systemic inflammatory response caused by infection. Some studies have revealed that copper is involved in the pathophysiological process of sepsis and is closely related to its prognosis. During the infection of sepsis, the body may enhance the antimicrobial effect by increasing the release of copper. However, to avoid copper poisoning, all organisms have evolved copper resistance genes. Therefore, further analysis of the complex relationship between copper and bacteria may provide new ideas and research directions for the treatment of sepsis.

This review examines the correlation between plant-based diets and athletic performance, with a specific emphasis on the vital aspect of optimizing micronutrients for athletes. In light of the increasing prevalence of plant-based nutrition among athletes due to its perceived advantages in terms of health, ethics, and the environment, this study investigates the ability of these diets to satisfy the demanding nutritional requirements essential for achieving optimal performance and facilitating recovery. The article emphasizes the significance of essential micronutrients such as iron, vitamin B12, calcium, vitamin D, zinc, and omega-3 fatty acids and also addressing the challenges with their absorption and bioavailability from plant sources. The review consolidates existing scientific knowledge to propose strategies for improving micronutrient consumption, comparing the effects of supplements against whole foods, and highlighting the significance of enhancing bioavailability. The proposal supports the implementation of personalized meal planning, with the assistance of sports nutritionists or dietitians, and is substantiated by case studies showcasing the success of plant-based athletes. Future research directions examine the long-term effects of plant-based diets on micronutrient status and athletic performance, as well as developing nutritional trends and technology. The review concludes that plant-based diets can meet athletes' nutritional demands and improve peak performance while aligning with personal and ethical values with strategic planning and professional guidance. This study intends to help athletes, coaches, and nutritionists understand plant-based nutrition for enhanced athletic performance.

Due to the degradation of pasture and strict restrictions on grazing ranges in recent years, copper (Cu) deficiency in Yudong black goats has been occurring, mainly manifested as emaciation, anemia, loss of appetite and lack of spirit. To explore the main causes of Cu deficiency in Yudong black goats, 40 black goats (1 year old, 25.11 ± 0.52 kg) were selected for this experiment; among them, 20 Yudong black goats with Cu deficiency from the experimental pasture were used as the experimental group, and 20 healthy Yudong black goats from the control pasture were used as the control group. In the pre-experiment, the mineral contents of the soil, forage, blood, and liver of black goats in both groups were determined, and in formal experiments, blood hematological, biochemical, antioxidant, and hemorheological parameters were analyzed. An experiment on the treatment of Cu deficiency in black goats was also conducted. This study showed that selenium (Se) levels in the soil, forage, blood, and liver from the experimental group were significantly lower than those from the control group (p < 0.01). The content of sulfur (S) in the forage was considerably higher than that of the control group (p < 0.01). The contents of Cu in the blood and liver from the experimental group were significantly lower than that from the control group (p < 0.01), and the content of S was considerably higher than that from the control group (p < 0.01). The blood hematology of the experimental group was affected, as evidenced by a decrease in hemoglobin, hematocrit value, mean corpuscular volume and mean corpuscular hemoglobin. The immunity and antioxidant capacity of black goats in the experiment group were impaired to varying degrees, with significant decreases in ceruloplasmin, immunoglobulin M, immunoglobulin G, glutathione peroxidase, and superoxide dismutase, and substantial increases in malondialdehyde. In addition, the experimental group showed a decrease in blood viscosity as evidenced by the rise in high shear viscosity, low shear viscosity, erythrocyte rigidity index, erythrocyte aggregation index, and erythrocyte deformation index, and a decrease in plasma viscosity. In the treatment experiment, oral administration of copper sulfate solution was carried out on 10 black goats with Cu deficiency. All the Cu deficiency goats were cured, and the Cu content in their bodies rebounded. In summary, low Se soil caused an increase in S content in the forage, and Yudong black goats feeding on high S forage resulted in a decrease in Cu absorption, which led to a secondary Cu deficiency.

Exploring the pathogenesis of osteoarthritis (OA) is important for its prevention, diagnosis, and treatment. Therefore, we aimed to construct novel signature genes (c-FRGs) combining cuproptosis-related genes (CRGs) with ferroptosis-related genes (FRGs) to explore the pathogenesis of OA and aid in its treatment.

Differentially expressed c-FRGs (c-FDEGs) were obtained using R software. Enrichment analysis was performed and a protein-protein interaction (PPI) network was constructed based on these c-FDEGs. Then, seven hub genes were screened. Three machine learning methods and verification experiments were used to identify four signature biomarkers from c-FDEGs, after which gene set enrichment analysis, gene set variation analysis, single-sample gene set enrichment analysis, immune function analysis, drug prediction, and ceRNA network analysis were performed based on these signature biomarkers. Subsequently, a disease model of OA was constructed using these biomarkers and validated on the GSE82107 dataset. Finally, we analyzed the distribution of the expression of these c-FDEGs in various cell populations.

A total of 63 FRGs were found to be closely associated with 11 CRGs, and 40 c-FDEGs were identified. Bioenrichment analysis showed that they were mainly associated with inflammation, external cellular stimulation, and autophagy. CDKN1A, FZD7, GABARAPL2, and SLC39A14 were identified as OA signature biomarkers, and their corresponding miRNAs and lncRNAs were predicted. Finally, scRNA-seq data analysis showed that the differentially expressed c-FRGs had significantly different expression distributions across the cell populations.

Four genes, namely CDKN1A, FZD7, GABARAPL2, and SLC39A14, are excellent biomarkers and prospective therapeutic targets for OA.

Nutrition management is fundamental for children with chronic kidney disease (CKD). Fluid balance and low-protein and low-sodium diets are the more stressed fields from a nutritional point of view. At the same time, the role of micronutrients is often underestimated. Starting from the causes that could lead to potential micronutrient deficiencies in these patients, this review considers all micronutrients that could be administered in CKD to improve the prognosis of this disease.

Due to the fencing of the Przewalski's gazelle (Procapra przewalskii), the microcytic anemia incidence rate continues to increase. The primary pathological symptoms include emaciation, anemia, pica, inappetence, and dyskinesia. To investigate the cause of microcytic anemia ailment in the Przewalski's gazelle, the Upper Buha River Area with an excessive incidence was chosen as the experimental pasture, and the Bird Island Area without microcytic anemia disease was chosen as the control field. Then, the mineral contents in the soil, forage, blood, and liver, as well as the blood routine parameters and biochemical indexes were measured. The findings showed that the experimental pasture had much lower Se content in the soil and forage than the control field (p < 0.01), while the impacted pasture had significantly higher S content in the forage. The damaged gazelles had considerably lower Se and Cu contents and higher S content in the blood and liver than the healthy gazelles (p < 0.01). The presences of Hb, HCT, MCV, and MCH were significantly decreased compared to those in healthy gazelles (p < 0.01). The experimental group had a significantly lower level of GSH-Px activity in their serums compared to the control group (p < 0.01). In the treatment experiment, ten gazelles from the affected pasture were orally administered CuSO4, 6 g/animal once every 10 days for two consecutive times, and all gazelles were successfully cured. Therefore, it is possible that low Se content in the soil induced an increase in the absorption of S content by forage, leading to the deficiency of secondary Cu in the Przewalski's gazelles, resulting in microcytic anemia.

Trace elements are essential for maintaining the body's homeostasis, and their special role has been demonstrated in skin physiology. Among the most important trace elements are zinc, copper, and iron. A deficiency or excess of trace elements can be associated with an increased risk of skin diseases, so increasing their supplementation or limiting intake can be helpful in dermatological treatment. In addition, determinations of their levels in various types of biological material can be useful as additional tests in dermatological treatment. This paper describes the role of these elements in skin physiology and summarizes data on zinc, copper, and iron in the course of selected, following skin diseases: psoriasis, pemphigus vulgaris, atopic dermatitis, acne vulgaris and seborrheic dermatitis. In addition, this work identifies the potential of trace elements as auxiliary tests in dermatology. According to preliminary studies, abnormal levels of zinc, copper, and iron are observed in many skin diseases and their determinations in serum or hair can be used as auxiliary and prognostic tests in the course of various dermatoses. However, since data for some conditions are conflicting, clearly defining the potential of trace elements as auxiliary tests or elements requiring restriction/supplement requires further research.

Ischemia-reperfusion injury (IRI) is a critical pathological condition in which cell death plays a major contributory role, and negatively impacts post-transplant outcomes. At the cellular level, hypoxia due to ischemia disturbs cellular metabolism and decreases cellular bioenergetics through dysfunction of mitochondrial electron transport chain, causing a switch from cellular respiration to anaerobic metabolism, and subsequent cascades of events that lead to increased intracellular concentrations of Na+, H+ and Ca2+ and consequently cellular edema. Restoration of blood supply after ischemia provides oxygen to the ischemic tissue in excess of its requirement, resulting in over-production of reactive oxygen species (ROS), which overwhelms the cells' antioxidant defence system, and thereby causing oxidative damage in addition to activating pro-inflammatory pathways to cause cell death. Moderate ischemia and reperfusion may result in cell dysfunction, which may not lead to cell death due to activation of recovery systems to control ROS production and to ensure cell survival. However, prolonged and severe ischemia and reperfusion induce cell death by apoptosis, mitoptosis, necrosis, necroptosis, autophagy, mitophagy, mitochondrial permeability transition (MPT)-driven necrosis, ferroptosis, pyroptosis, cuproptosis and parthanoptosis. This review discusses cellular and molecular mechanisms of these various forms of cell death in the context of organ transplantation, and their inhibition, which holds clinical promise in the quest to prevent IRI and improve allograft quality and function for a long-term success of organ transplantation.

The accumulation of potentially toxic elements (PTEs) has raised public awareness due to harmful contamination to both human and marine creatures. This study was designed to determine the concentration of copper (Cu), zinc (Zn), cadmium (Cd), and nickel (Ni) in the intestine, kidney, muscle, gill, and liver tissues of local commercial edible fish, fourfinger threadfin (Eleutheronema tetradactylum), and black pomfret (Parastromateus niger) collected from Morib (M) and Kuala Selangor (KS). Among the studied PTEs, Cu and Zn were essential elements to regulate body metabolism with certain dosages required while Cd and Ni were considered as non-essential elements that posed chronic and carcinogenic risk. The concentration of PTEs in fish tissue samples was analyzed using flame atomic absorption spectrometry (F-AAS). By comparing the concentration of PTEs in fish tissues as a bioindicator, the environmental risk of Morib was more serious than Kuala Selangor because both fish species collected from Morib resulted in a higher PTEs concentration. For an average 62 kg adult with a fish ingestion rate (FIR) of 0.16 kg/person/day in Malaysia, the estimated weekly intake (EWI) of Cd from the consumption of E. tetradactylum (M: 0.0135 mg/kg; KS: 0.0134 mg/kg) and P. niger (M: 0.0140 mg/kg; KS: 0.0132 mg/kg) had exceeded the provisional tolerable weekly intake (Cd: 0.007 mg/kg) established by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) and oral reference dose (ORD) values of Cd (0.001 mg/kg/day) as provided by the United States Environmental Protection Agency (USEPA) regional screening level, thus it posed chronic risks for daily basis consumption. Besides, the value of the carcinogenic risk of Cd (0.7-3 to 0.8-3) and Ni (0.5-3 to 0.6-3) were in between the acceptable range (10-6 to 10-4) of the health index that indicates a relatively low possibility cancer occurrence to the consumers in both Morib and Kuala Selangor. This study recommended FIR to be 0.80 kg/person/day to reduce the possibility of posing chronic and carcinogenic risks while at the same time obtaining the essential nutrients from the fish.

Anemia during pregnancy is an important global health concern, affecting 40% of women worldwide, and iron deficiency shares a significant proportion of the burden. From conception to birth, pregnancy is a period when women undergo metabolic and physiological changes. The nutritional needs are higher during pregnancy; thus, adequate nutrition is essential to maintain fetal growth and development. However, adverse effects due to deficiency in nutrition during pregnancy can result in maternal, fetal and neonatal complications. Despite the multifactorial etiology of anemia, iron deficiency is assumed as the primary cause of anemia during pregnancy and hence, mitigation strategy pivots around it for anemia management. Therefore, excluding other contributors, a single-micronutrient approach with iron supplements remains a myopic approach and this can exacerbate iron deficiency anemia. Micronutrient deficiencies are of particular concern as they may pose a silent threat to the survival and well-being of reproductive-age women and their infants.

Micronutrients, especially trace minerals, play a myriad of roles in pregnancy, and the lack of each one causes adverse complications to both the mother and the fetus. In this review paper, we attempt to piece together available information regarding the adverse effects of abnormal trace mineral levels along with iron deficiency on the mother and the fetus.

A non-systematic literature search in PubMed, Google Scholar, and the Cochrane databases, for publications on minerals and vitamins during pregnancy and the possible influence of supplements on pregnancy outcomes.

Micronutrient deficiency exacerbates the pregnancy-induced anemia and other adverse birth outcomes. Micronutrient supplementation during pregnancy can combat anemia as well as reduce a number of adverse pregnancy outcomes in a comprehensive manner.

Adding foreign ions to hydroxyapatite (HAp) is a popular approach for improving its properties. This study focuses on the effects of calcium substitution with copper in HAp. Instead of calcium, copper ions were doped into the structure of hydroxyapatite nanoparticles at 1%, 3%, and 5% concentrations. XRD analysis showed that the amount of substituted copper was less than needed to generate a distinct phase, yet its lattice parameters and crystallinity slightly decreased. Further, the results of degradation tests revealed that copper doping in hydroxyapatite doubled calcium ion release in water. The incorporation of copper into the apatite structure also boosted the HAp zeta potential and FBS protein adsorption onto powders. According to antibacterial investigations, a concentration of 200 mg/ml of hydroxyapatite containing 5% copper was sufficient to effectively eradicate E. coli and S. aureus bacteria. Furthermore, copper improved hydroxyapatite biocompatibility. Alkaline phosphatase activity and alizarin red tests showed that copper in hydroxyapatite did not inhibit stem cell differentiation into osteoblasts. Also, the scratch test demonstrated that copper-containing hydroxyapatite extract increased HUVEC cell migration. Overall, our findings demonstrated the utility of incorporating copper into the structure of hydroxyapatite from several perspectives, including the induction of antibacterial characteristics, biocompatibility, and angiogenesis.

This study aimed to develop and validate a cuproptosis-related gene signature for the prognosis of gastric cancer. The data in TCGA GC TPM format from UCSC were extracted for analysis, and GC samples were randomly divided into training and validation groups. Pearson correlation analysis was used to obtain cuproptosis-related genes co-expressed with 19 Cuproptosis genes. Univariate Cox and Lasso regression analyses were used to obtain cuproptosis-related prognostic genes. Multivariate Cox regression analysis was used to construct the final prognostic risk model. The risk score curve, Kaplan-Meier survival curves, and ROC curve were used to evaluate the predictive ability of Cox risk model. Finally, the functional annotation of the risk model was obtained through enrichment analysis. Then, a six-gene signature was identified in the training cohort and verified among all cohorts using Cox regression analyses and Kaplan-Meier plots, demonstrating its independent prognostic significance for gastric cancer. In addition, ROC analysis confirmed the significant predictive potential of this signature for the prognosis of gastric cancer. Functional enrichment analysis was mainly related to cell-matrix function. Therefore, a new cuproptosis-related six-gene signature (ACLY, FGD6, SERPINE1, SPATA13, RANGAP1, and ADGRE5) was constructed for the prognosis of gastric cancer, allowing for tailored prediction of outcome and the formulation of novel therapeutics for gastric cancer patients.

Intervertebral disc degeneration (IVDD) is a common illness of aging, and its pathophysiological process is mainly manifested by cell aging and apoptosis, an imbalance in the production and catabolism of extracellular matrix, and an inflammatory response. Oxidative stress (OS) is an imbalance that decreases the body's intrinsic antioxidant defense system and/or raises the formation of reactive oxygen species and performs multiple biological functions in the body. However, our current knowledge of the effect of OS on the progression and treatment of IVDD is still extremely limited. In this study, we obtained 35 DEGs by differential expression analysis of 437 OS-related genes (OSRGs) between IVDD patients and healthy individuals from GSE124272 and GSE150408. Then, we identified six hub OSRGs (ATP7A, MELK, NCF1, NOX1, RHOB, and SP1) from 35 DEGs, and the high accuracy of these hub genes was confirmed by constructing ROC curves. In addition, to forecast the risk of IVDD patients, we developed a nomogram. We obtained two OSRG clusters (clusters A and B) by consensus clustering based on the six hub genes. Then, 3147 DEGs were obtained by differential expression analysis in the two clusters, and all samples were further divided into two gene clusters (A and B). We investigated differences in immune cell infiltration levels between different clusters and found that most immune cells had higher infiltration levels in OSRG cluster B or gene cluster B. In conclusion, OS is important in the formation and progression of IVDD, and we believe that our work will help guide future research on OS in IVDD.

Anemia seriously affects the health and quality of life of the older adult population and may be influenced by various types of environmental metal exposure. Current studies on metals and anemia are mainly limited to single metals, and the association between polymetals and their mixtures and anemia remains unclear.

We determined 11 urinary metal concentrations and hemoglobin levels in 3781 participants. Binary logistic regression and restricted cubic spline (RCS) model were used to estimate the association of individual metals with anemia. We used Bayesian kernel machine regression (BKMR) and Quantile g-computation (Q-g) regression to assess the overall association between metal mixtures and anemia and identify the major contributing elements. Stratified analyses were used to explore the association of different metals with anemia in different populations.

In a single-metal model, nine urinary metals significantly associated with anemia. RCS analysis further showed that the association of arsenic (As) and copper (Cu) with anemia was linear, while cobalt, molybdenum, thallium, and zinc were non-linear. The BKMR model revealed a significant positive association between the concentration of metal mixtures and anemia. Combined Q-g regression analysis suggested that metals such as Cu, As, and tellurium (Te) were positively associated with anemia, with Te as the most significant contributor. Stratified analyses showed that the association of different metals with anemia varied among people of different sexes, obesity levels, lifestyle habits, and blood pressure levels.

Multiple metals are associated with anemia in the older adult population. A significant positive association was observed between metal mixture concentrations and anemia, with Te being the most important factor. The association between urinary metal concentrations and anemia is more sensitive in the non-hypertensive populations.

Copper deficiency can trigger various diseases such as Amyotrophic Lateral Sclerosis (ALS), Parkinson's disease (PD) and even compromise the development of living beings, as manifested in Menkes disease (MS). Thus, the regulated administration (controlled release) of copper represents an alternative to reduce neuronal deterioration and prevent disease progression. Therefore, we present, to the best of our knowledge, the first experimental in vitro investigation for the kinetics of copper release from MOF-74(Cu) and its distribution in vivo after oral administration in male Wistar rats. Taking advantage of the abundance and high periodicity of copper within the crystalline-nanostructured metal-organic framework material (MOF-74(Cu)), it was possible to control the release of copper due to the partial degradation of the material. Thus, we simultaneously corroborated a low accumulation of copper in the liver (the main detoxification organ) and a slight increase of copper in the brain (striatum and midbrain), demonstrating that MOF-74(Cu) is a promising pharmacological alternative (controlled copper source) to these diseases.

The discovery of regulated cell death (RCD) revolutionized chemotherapy. With caspase-dependent apoptosis initially being thought to be the only form of RCD, many drug development strategies aimed to synthesize compounds that turn on this kind of cell death. While yielding a variety of drugs, this approach is limited, given the acquired resistance of cancers to these drugs and the lack of specificity of the drugs for targeting cancer cells alone. The discovery of non-apoptotic forms of RCD is leading to new avenues for drug design. Evidence shows that ferroptosis, a relatively recently discovered iron-based cell death pathway, has therapeutic potential for anticancer application. Recent studies point to the interrelationship between iron and other essential metals, copper and zinc, and the disturbance of their respective homeostasis as critical to the onset of ferroptosis. Other studies reveal that several coordination complexes of non-iron metals have the capacity to induce ferroptosis. This collective knowledge will be assessed to determine how chelation approaches and coordination chemistry can be engineered to program ferroptosis in chemotherapy.

Serum micronutrient analysis can provide insight into diet and clinical assessment, despite the complicated interplay between micronutrients and species idiosyncrasies. Approach serum nutrient analytes with skepticism, before jumping to alter diets or offering supplementation. Utilize across species but know that some exotics have exceptions to typical ranges, such as calcium in rabbits or iron in reptiles. Make sure you trust that referenced ranges reflect normal and healthy for that species. Micronutrients are integral to every bodily process, so measurement of serum analytes can tell a story that aids in the clinical picture, when one can recognize what stands out.

As a transitional metal, copper plays a crucial role in maintaining the normal physiological activities of mammals. The intracellular copper concentration is meticulously regulated to maintain extremely low levels through homeostatic regulation. Excessive accumulation of free copper in cells can have deleterious effects, as observed in conditions such as Wilson's disease. Moreover, data accumulated over the past few decades have revealed a crucial role of copper imbalance in tumorigenesis, progression and metastasis. Recently, cuproptosis, also known as copper-induced cell death, has been proposed as a novel form of cell death. This discovery offers new prospects for treating copperrelated diseases and provides a promising avenue for developing copper-responsive therapies, particularly in cancer treatment. We present a comprehensive overview of the Yin- Yang equilibrium in copper metabolism, particularly emphasising its pathophysiological alterations and their relevance to copper-related diseases and malignancies.

The present study investigates the effect of conventional and organic farming systems on the nutritional profile of crops. Different crops, namely -millet, sorghum, sesame, mustard, fenugreek, berseem, pea, potato, and onion were cultivated through conventional agriculture in which chemical fertilizers like urea, DAP (Diammonium Phosphate) and pesticides were used and organic farming in which organic fertilizers like seaweed and vermicompost were used.

The experimental study was done on a field in north India from 2019 to 2021 in six different seasons, and the nutrient profile of the crops with respect to macroelements (S, K, Na, P, Ca, Mg) and microelements (B, Cu, Fe, Mn, Zn, Al) was compared.

Macro and microelements were analyzed by Element analyzer and ICP-OES in both types of farming systems. The content of macro, as well as microelements, was found to be significantly higher in all the organically produced crops as compared to the conventionally grown crops.

Significant differences were observed in the macroelement content of organic onion (P- 900 mg/kg, K-2000mg/kg) and organic pea (K 2250 mg/kg) as compared to the content of conventionally grown onion (P-756 mg/kg, K- 1550 mg/kg) and pea (K-2000 mg/kg). Similarly, microelement content in the organic sesame (Fe - 3.12 mg/kg), organic millet (Fe- 2.19 mg/kg), and organic potato (Zn-200 mg/kg) was higher as compared to conventionally grown sesame (Fe 2.05 mg/kg), millet (Fe- 1.56 mg/kg) and potato (Zn 167 mg/kg).

This investigation concludes that crops with optimum nutritional content can be produced through organic farming with minimum input and maximum production.

Copper (Cu) is an essential micronutrient for the correct development of eukaryotic organisms. This metal plays a key role in many cellular and physiological activities, including enzymatic activity, oxygen transport, and cell signaling. Although the redox activity of Cu is crucial for enzymatic reactions, this property also makes it potentially toxic when found at high levels. Due to this dual action of Cu, highly regulated mechanisms are necessary to prevent both the deficiency and the accumulation of this metal since its dyshomeostasis may favor the development of multiple diseases, such as Menkes' and Wilson's diseases, neurodegenerative diseases, diabetes mellitus, and cancer. As the relationship between Cu and cancer has been the most studied, we analyze how this metal can affect three fundamental processes for tumor progression: cell proliferation, angiogenesis, and metastasis. Gynecological diseases are characterized by high prevalence, morbidity, and mortality, depending on the case, and mainly include benign and malignant tumors. The cellular processes that promote their progression are affected by Cu, and the mechanisms that occur may be similar. We analyze the crosstalk between Cu deregulation and gynecological diseases, focusing on therapeutic strategies derived from this metal.

Mitochondria serve as sites for energy production and are essential for regulating various forms of cell death induced by metal metabolism, targeted anticancer drugs, radiotherapy and immunotherapy. Cuproptosis is an autonomous form of cell death that depends on copper (Cu) and mitochondrial metabolism. Although the recent discovery of cuproptosis highlights the significance of Cu and mitochondria, there is still a lack of biological evidence and experimental verification for the underlying mechanism. We provide an overview of how Cu and cuproptosis affect mitochondrial morphology and function. Through comparison with ferroptosis, similarities and differences in mitochondrial metabolism between cuproptosis and ferroptosis have been identified. These findings provide implications for further exploration of cuproptotic mechanisms. Furthermore, we explore the correlation between cuproptosis and immunotherapy or radiosensitivity. Ultimately, we emphasize the therapeutic potential of targeting cuproptosis as a novel approach for disease treatment.