Biometals最新文献

Wilson’s disease (WD) is a rare autosomal recessive disorder caused by mutations in ATP7B, which is marked by defective copper metabolism that leads to toxic copper buildup in organs such as the liver and brain, ultimately causing hepatocellular injury and liver fibrosis. This review systematically examined the multifaceted mechanisms through which copper overload drives liver fibrosis. In short, copper ions generate reactive oxygen species via the Fenton reaction, thereby directly impairing the mitochondrial structure and function and inducing hepatocyte apoptosis, necrosis, and cuproptosis. Copper ions also activate signaling pathways such as the TGF-β1/Smad and NF-κB pathways, which stimulate hepatic stellate cells and promote their transdifferentiation into collagen-secreting myofibroblasts, which then accelerate extracellular matrix deposition. Moreover, abnormal lipoylation of the copper-dependent proteins metal-binding domain of ferredoxin 1 and dihydrolipoamide transacetylase causes mitochondrial protein oligomer buildup and tricarboxylic acid cycle dysfunction, reinforcing an “oxidative damage–inflammation–fibrosis” vicious cycle. The disruption of copper chaperones and lysosomal copper accumulation further intensifies oxidative stress and dysregulates the immune microenvironment. Current therapies focus mainly on copper chelation but exhibit limited ability to reverse established fibrosis. Meanwhile, emerging gene therapies face the challenges of delivery efficiency and immunogenicity. Future research should therefore elucidate the dynamic interplay between copper metabolism and the liver microenvironment, identify key regulatory nodes across different disease stages, and shift treatment paradigms from narrow “symptomatic copper chelation” to integrated strategies aimed at restoring copper homeostasis. Such advances could yield novel approaches toward the prevention and treatment of WD liver fibrosis.

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The aim of this study was to evaluate biomarkers of zinc and copper status in patients with thyroid nodules. A cross-sectional study of 122 participants with thyroid nodules, diagnosed with cytological examinations (Nodule group) and 72 healthy subjects (Control group) were performed. Anthropometric data were collected; plasma concentrations of zinc and copper were analyzed by flame atomic absorption spectrophotometry and erythrocyte superoxide dismutase (SOD) activity was determined in an automatic biochemical analyzer using spectrophotometry to quantify the enzyme activity. The content of Zn in plasma was lower in the Nodule group than in the Control group, but plasma copper, copper/zinc ratio and erythrocyte SOD activity were higher in the Nodule group (p < 0.001). The levels of Cu and Zn are in the normal range, but the ratio Cu/Zn is altered in nodules group. Thyroid nodule patients exhibited changes in zinc and copper biomarker status compared to healthy individuals. The Cu/Zn ratio is a much more sensitive parameter for evaluating mineral metabolism in thyroid diseases.

Citrulline (CITRN) is a potent radical scavenger and osmolyte that plays a crucial role in plant drought stress tolerance. However, its role in mitigating chromium (Cr) phytotoxicity has not been studied yet. This study was conducted to appraise the potential of CITRN seed priming (1, 2, and 3 mM) for alleviating Cr toxicity (20 mg kg^‒1 soil) in sunflower plants. Chromium toxicity resulted in higher oxidative stress and membrane injury in plants, as evident by higher levels of superoxide radicals (O₂^·‾), hydroxyl radicals (·OH), hydrogen peroxide (H₂O₂), malondialdehyde (MDA), and electrolyte leakage (EL). Plants under Cr toxicity displayed higher cytotoxic methylglyoxal (MG) levels and lipoxygenase (LOX) activity, which exacerbated cellular damage. Consequently, plants suffered a significant reduction in growth attributes, photosynthetic pigments, total soluble proteins, leaf relative water content, and nutrient uptake. Chromium toxicity compromised photosystem II (PSII) health as reflected by diminished maximum efficiency of PSII (Fv/Fm), quenching coefficient (qP), and quantum efficiency of PSII (ΦPSII). However, CITRN significantly enhanced plant growth, chlorophyll concentration, PSII health, and nutrient acquisition by regulating reactive oxygen species scavenging, secondary metabolic pathways, and ionic equilibrium under Cr toxicity. Citrulline upregulated antioxidant defense and methylglyoxal detoxification in Cr-stressed plants. Furthermore, CITRN conferred protection against Cr-induced toxicity by elevating hydrogen sulfide, nitric oxide, glutathione, phenolic, and flavonoid compounds that boosted antioxidant defense and mitigated oxidative damage. The present study elucidates CITRN-priming as a potential strategy to mitigate Cr toxicity in Helianthus annuus plants.

Copper (Cu) is an essential micronutrient in various enzymatic and physiological functions. However, excessive copper intake, mainly resulting from industrial emissions and improper agricultural practices, has raised growing concerns due to its toxicological effects, particularly on the male reproductive system. This review summarizes current research progress on copper-induced reproductive toxicity in males, emphasizing its impact on sperm quality, androgen production, and testicular structure and function. The underlying molecular mechanisms are discussed in detail, including oxidative stress, apoptosis, autophagy, ferroptosis, and cuproptosis. In addition, emerging therapeutic approaches, such as antioxidant treatments and copper chelators, are evaluated for their potential to mitigate these toxic effects. A comprehensive understanding of copper-induced male reproductive toxicity may offer new insights into the prevention and management of metal-related infertility.

Bioaccumulation of metals and metalloids in marine environments poses a significant risk to both human and aquatic health, with seasonal fluctuations substantially influencing its dynamics and magnitude. This study investigated the impact of metals and metalloids exposure on the health of Wallago attu (Wallago catfish) and Catla catla (Indian carp) inhabiting the Head Siphon, Mailsi, Pakistan. This study involved the seasonal (May 2022, October 2022, April 2023) assessment of physicochemical properties and the concentrations of several metals and metalloids—copper (Cu), chromium (Cr), arsenic (As), cadmium (Cd), nickel (Ni), zinc (Zn), and iron (Fe)—in water samples. Additionally, we evaluated hematological indices and antioxidant enzyme such as superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) in both fish species. Our analysis revealed seasonal variations in water quality and metal/metalloid concentrations. The results indicate summer exhibited the highest metal concentrations, following the trend: Cu > Zn > Fe > Cd > Cr > As > Ni. Specifically, Cu peaked in summer, Cr and Ni remained relatively stable, Cd decreased from summer to winter/spring, and Zn mirrored Cu trends, while Fe significantly reduced in winter. Several trace elements and water parameters (pH, nitrate) exceeded USEPA permissible limits, indicating water quality deterioration and potential ecological risks. Antioxidant enzyme profiling revealed species-specific oxidative stress responses. In W. attu, SOD varied distinctly across organs and seasons, with unique winter CAT trends suggesting complex antioxidant defense mechanisms. C. catla displayed elevated SOD, POD, and CAT levels, indicative of a robust stress response. Species-specific hematological variations, potentially indicative of metal/metalloid contamination, were observed. Notably, increased white blood cell counts in spring suggested pollutant-induced immune responses. This study reveals a complex interplay between environmental stressors and fish health, showing that exposure to metals and metalloids can cause adverse physiological effects in W. attu and C. catla. These findings are important because they suggest a potential risk to human health through the consumption of contaminated fish.

Describe the levels of arsenic, mercury, manganese, and lead in the hair of older Mexican adults and analyze their association with exposure and sociodemographic factors. This cross-sectional study used a random subsample of 2474 adults aged 50 and older from the 2018 Mexican Health and Aging Study. Metal levels in hair were quantified using inductively coupled plasma mass spectrometry and an optical emission spectrometer with a hydride generator. Linear regression models were used to assess the associations between metal/metalloid levels and sociodemographic factors. Median hair levels were arsenic 0.04 μg/g, mercury 0.14 μg/g, manganese 0.79 μg/g, and lead 0.65 μg/g. Arsenic levels increased with age, while manganese and lead levels decreased. Males exhibited higher concentrations of all metalloids/metals compared to females. BMI was associated with increased arsenic levels. The use of wood or charcoal for cooking was associated with increased hair manganese. Household pesticide use was associated with elevated levels of mercury, manganese, and lead. Cooking with glazed clay pots was associated with increased lead levels. Residing near exposure sites increased mercury, manganese, and lead levels in hair. Additionally, seven or more years of schooling was associated with increased mercury levels, while low/middle socioeconomic status was associated with increased hair manganese levels. The results reveal significant metal exposure in older Mexican adults, varying according to sociodemographic and exposure factors. These findings underscore the need to implement public policies to reduce metal exposure and protect the health of these vulnerable communities.

Selenium’s role in aging is supported by its involvement in antioxidant defense, immune function, and cellular maintenance. Adequate selenium levels can contribute to healthier aging. This cross-sectional study investigated the associations of selenium status markers with anthropometric parameters, glycemic profile, and inflammatory biomarkers in 72 older adults living in nursing homes (NH). Plasma selenium levels were measured using inductively coupled plasma mass spectrometry, and selenoprotein P (SELENOP) was determined using enzyme-linked immunosorbent assay. Dietary selenium intake data were obtained by directly weighing the food at two different times, with an interval of 30 to 45 days between them. The mean age was 83 (8.6) years. The median (IQR) of plasma selenium levels was 88.20 (76.0–106.0)µg/L, for SELENOP 32.30 (29.2–33.5)ng/mL, and the mean (SD) of dietary selenium intake was 72.7 (11.9)µg/day. Overall, 65.2% of participants exhibited elevated glycated hemoglobin (HbA1c) levels. Insufficient plasma selenium levels to optimize SELENOP (< 100 μg/L) showed a significant association with being underweight (p = 0.04). Participants with low SELENOP and low dietary selenium intake had HbA1c levels above 6.4% (p = 0.05). Plasma selenium levels and dietary selenium intake were positively correlated with body mass index (ρ = 0.408, p = 0.001 and r = 0.382, p = 0.004, respectively). Selenium status markers were not associated with the inflammatory biomarkers. However, half of the population had high levels of IL-6 and TNF-α, and 98.5% had high levels of hs-CRP. In conclusion, lower plasma selenium was associated with underweight status, while reduced SELENOP and dietary selenium intake correlated with elevated HbA1c in older adults in NH.

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Lactoferrin (LF) is a glycoprotein found in neutrophils, milk, and various mammalian secretions that plays a crucial role in host defense by modulating the immune response. Previous studies have shown that LF is taken up by human monocytes and can be present in their nucleus. However, it is unclear whether the iron saturation levels or the protease activity of LF are involved in this uptake and nuclear translocation. In addition, the activation of monocytes might influence these processes. The present study investigated the uptake and nuclear translocation of bovine LF (bLF) and porcine LF (pLF) in porcine blood-derived monocytes and how this affects monocyte function. Both bLF and pLF were internalized by porcine monocytes. Their uptake was not affected by increased iron saturation levels or by inactivation of the proteolytic activity of LF. Similarly, LPS-induced activation of monocytes did not affect LF internalization. We further investigated whether bLF could modulate LPS-induced cytokine responses by monocytes. Across all tested LPS serotypes and concentrations, bLF failed to decrease the LPS-induced TNF-α secretion by porcine monocytes. Besides internalization, we found that bLF and pLF translocated to the nucleus in a subset of porcine monocytes. This nuclear translocation was not affected by the iron saturation level and proteolytic activity of LF, nor by LPS-induced monocyte activation. Together, these findings further deepen our understanding of LF’s interaction with porcine innate immune cells and provide insights into its immunomodulatory properties.

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Medicinal plants are valuable sources of bioactive compounds. In this study, we analyzed the levels of essential metals (Fe, Cu, Zn, Mn) in the leaves of Punica granatum, Teucrium montanum, Chaerophyllum coloratum, Petteria ramentacea, and Menyanthes trifoliata using atomic absorption spectrophotometry. Ethanolic leaf extracts were assessed for anti-inflammatory activity via bovine serum albumin BSA and egg albumin (EgA) denaturation assays and for antioxidant potential by hydroxyl radical scavenging using EPR (Electron Paramagnetic Resonance) spectroscopy. Metal concentrations varied across species: Fe (33–93 mg/kg), Cu (4.29–11.61 mg/kg), Zn (12.39–105 mg/kg), and Mn (1.38–1005 mg/kg), with T. montanum showing the highest Fe and M. trifoliata with highest Cu, Zn and Mn levels. Total phenolic content (TPC) ranged from 32 to 117 mg/g_DW, with the highest in P. granatum, which also demonstrated the strongest hydroxyl radical scavenging. The highest BSA inhibition (~ 80%) was observed in Ch. coloratum, P. granatum, and T. montanum at 0.01 µg/mL TPC. Egg albumin inhibition ranged from 28–50%, with Ch. coloratum being the most active. Significant correlations were found between Cu, Mn, and anti-inflammatory activity, and between Zn, TPC, and both antioxidant and anti-inflammatory effects. These findings suggest a synergistic role of phenolics and trace elements and support the potential use of these plants as dietary supplements against inflammation and oxidative stress.

Zinc (Zn²⁺) is the second most abundant trace element after iron, with most of it is stored in skeletal muscles. Although a large part of Zn²⁺ is tightly bound to metalloproteins, the small portion of free Zn²⁺ can participate in nerve signaling. Here we examined the effects of Zn²⁺ at nanomolar concentrations on neuromuscular transmission in the diaphragm, the main respiratory muscle. Zn²⁺ reduced spontaneous neurotransmitter release at both lowered and physiological external Ca²⁺ levels. Additionally, Zn²⁺ effectively decreased the probability of neurotransmitter release upon single nerve stimulation under lowered external Ca²⁺, and inhibited Ca²⁺-independent sucrose-induced exocytosis. At physiological external Ca²⁺ concentration, Zn²⁺ decreased neurotransmitter release during low-frequency stimulation. The reduction became increased during short trains of moderate-to-high frequency stimuli. Furthermore, Zn²⁺ diminished both neurotransmitter release and the participation of dye-labeled synaptic vesicles in exocytosis during prolonged nerve firing at moderate frequency. Zn²⁺ aggravated muscle fatigue and impaired contraction recovery upon nerve stimulation. This was linked to a reduction in peak inspiratory flow in mice, an indicator of diaphragm function, after injection of low-dose Zn²⁺. Our data suggest that at nanomolar concentrations, Zn²⁺ is a negative modulator of neuromuscular function.