Biometals最新文献

The formation and maintenance of a biological seal between the peri-implant soft tissue and the titanium (Ti) abutment are critical for preventing peri-implant disease and ensuring implant longevity. However, this seal is fragile and prone to breakdown, particularly under inflammatory conditions. This study aimed to investigate the potential of a polyethylene glycol (PEG) coating associated to a bioactive flavonoid naringenin (NA) to enhance human gingival fibroblast (HGF) functions related to biological sealing on Ti surfaces. Initially, the effects of NA (10 µg/mL) on HGF proliferation, adhesion, and collagen synthesis were assessed under tumor necrosis factor alpha (TNF-α)-induced inflammatory challenge. Subsequently, Ti discs were coated with PEG or PEG incorporated with 10 µg/mL (v/v) of NA, and their surface morphology, chemical composition, and NA release profiles were evaluated. HGF responses, including viability, adhesion/spreading, matrix metalloproteinases (MMPs) and collagen production, were analyzed on the coated discs in the presence or absence of TNF-α-challenge. The results demonstrated that NA enhanced critical cellular processes underlying biological seal formation, including cell proliferation, adhesion, and collagen synthesis, while Ti discs were successfully coated with PEG-NA, which enabled rapid NA release. Moreover, the Ti/PEG-NA coating improved HGF viability and collagen synthesis while reducing TNF-α-induced MMP-2 and MMP-9 production. These in vitro findings underscore the potential of the PEG-NA coating to modulate HGF adhesion and metabolism, representing a promising strategy to enhance soft tissue integration and, consequently, long-term implant stability.

Manganese is an essential trace element for the human body, yet its role in heart function remains inadequately understood, this study aimed to reveal the influence of Mn deficiency on the heart, and uncover underlying mechanisms involved. A manganese-deficient diet was provided to weaned mice, to which manganese chloride (MnCl₂) was administered intraperitoneally to correct Mn deficiency. The pathological changes in the heart were evaluated through histological examination. Cardiac oxidative stress levels were assessed using flow cytometry and biochemical assay kits. The adenosine triphosphate (ATP) content and the levels of mitochondrial respiratory chain (MRC) complexes I-IV were measured with biochemical assay kits. Real-time PCR and Western blotting were performed to determine protein expression related to the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. Mn deficiency induced significant cardiac structural damage and elevated serum levels of cardiac injury markers. It also promoted oxidative stress and compromised antioxidant defenses. Mitochondrially, Mn deficiency impaired function, evidenced by reduced ATP levels and suppressed activities of MRC complexes I-IV. Crucially, Mn deficiency inhibited the Nrf2 pathway, demonstrated by decreased Nrf2, HO-1, and NQO1 expression and increased Keap1 expression. However, MnCl₂ supplementation significantly improved these alterations. Research results indicated the association of myocardial damage caused by Mn deficiency with mitochondrial dysfunction and oxidative damage, both of which show close correlations with the Nrf2 signaling pathway.

Breast cancer remains one of the most common and lethal malignancies among women worldwide. Although conventional treatment approaches—including surgery, radiotherapy, chemotherapy, and targeted therapy—have achieved substantial progress, clinical outcomes are still severely limited by issues such as drug resistance, recurrence, and metastasis. In this context, metal-based immunotherapy has emerged as a novel and highly promising strategy, gaining increasing attention for its unique advantages in enhancing anti-tumor immune responses and remodeling the tumor immune microenvironment. In recent years, mounting evidence has demonstrated that metal nanoparticles, metal–organic frameworks (MOFs), and metal complexes hold great potential in breast cancer immunotherapy. These agents exert immunotherapeutic effects through mechanisms such as immune activation, modulation of immunosuppressive cells, and synergistic enhancement of immune checkpoint blockade. Despite these encouraging developments, several critical challenges remain, including systemic toxicity, limited clinical translation, and insufficient understanding of their immunomodulatory mechanisms. This review provides a comprehensive summary of recent advances in metal-based immunotherapy for breast cancer, with a particular focus on the applications of metal nanoparticles, metal complexes, and metal-based nanocarriers. The mechanisms of action, therapeutic advantages, and existing limitations are thoroughly discussed, and future directions are proposed to facilitate further research and clinical translation in this emerging field.

Major depressive disorder (MDD) is a prevalent psychiatric condition associated with increased oxidative stress, which may contribute to its pathophysiology. Elevated malondialdehyde (MDA) levels and reduced total antioxidant capacity (TAC) and glutathione peroxidase (GPX) activity have been observed in individuals with MDD. Nano-selenium, a novel formulation with enhanced bioavailability and antioxidant potency compared to conventional selenium, may help modulate these oxidative stress biomarkers. In this randomized, triple-blind, placebo-controlled trial, 50 adults newly diagnosed with MDD received either nano-selenium (55 µg/day) or placebo, both alongside sertraline (50 mg/day), over a 12-week period. A total of 42 participants (21 per group) completed the study. Depressive symptoms were measured using the Hamilton Depression Rating Scale (HDRS), and serum levels of GPX, TAC, and MDA were assessed at baseline and post-intervention. Compared to placebo, nano-selenium significantly reduced depressive symptoms (mean change: −5.09 ± 4.94; P < 0.001) and increased TAC (mean change: 0.03 ± 0.04 mmol/L; P = 0.003) and GPX levels (median change: 9.56 U/L; IQR: −7.86 to 30.31; P = 0.044). While MDA levels decreased significantly in both groups, between-group differences were not statistically significant. These findings suggest that nano-selenium may serve as a safe and effective adjunctive therapy for reducing depressive symptoms and improving antioxidant status in MDD. However, the short duration and modest sample size of this study limit generalizability. Larger, multicenter trials with extended follow-up are recommended to confirm and expand upon these results. This study was approved by the Research Ethics Committee of Iran University of Medical Sciences (IR.IUMS.REC.1402.206; June 13, 2023) and registered with the Iranian Registry of Clinical Trials (IRCT20091114002709N62; July 29, 2023). Written informed consent was obtained from all participants.

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The chemotaxis response of E. coli to metal cations is less understood than their response to organic molecules. Using dark-field videomicroscopy, E. coli behavior was analyzed in a 17 mm-long microfluidic channel exposed to a Zn(NO₃)₂ chemorepellent gradient, generated by a 250 mM solution placed in a well at the channel extremity, with or without prior Zn²⁺ pre-exposure of the cultures (10 µM). The bacteria exhibited an escape wave away from the zinc source. Compared to unexposed cultures, zinc pre-exposure resulted in a constant and shorter passage time at a given position of the wave peak, despite unchanged growth and swimming speed. The time lag decreased with growth duration. Given the one-dimensional gradient setup, this decrease is associated to a reduced diffusion duration from the Zn²⁺ source. The content of Zn²⁺ in the extracellular medium at the peak of the wave is therefore lower, but allows bacteria to escape more rapidly. These findings suggested an increase in bacterial Zn²⁺ sensitivity. By analogy to Ni²⁺ binding to the cytoplasmic HAMP domain of the Tar receptor, Zn²⁺ likely triggers a chemorepellent response through a cytoplasmic receptor. The activation of this receptor relies on the available zinc pool, which is specifically buffered by substantial other intracellular zinc reservoirs. In this model, saturating the reservoirs in pre-exposed cultures would enable the fastest response time, and a gradual filling of the reservoirs in unexposed cells would reduce a delay in chemotactic escape.

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.