Biometals最新文献

Metallothioneins (MTs) are low molecular weight, intracellular, metal sequestering proteins that are unusually rich in cysteine content. Although physiologically comparable to well defined eukaryotic MTs, studies on the roles of prokaryotic MTs are limited. We had previously characterized unannotated prokaryotic MT, namely nmtA in the diazotrophic filamentous cyanobacterium, Anabaena PCC 7120. In the present study, by modulation of the in vivo levels of NmtA, we identified its role in metal homeostasis and detoxification and antioxidant protection in Anabaena 7120. While overexpression of NmtA in Anabaena (AnnmtA⁺) resulted in enhanced accumulation of Zn²⁺ and resistance to Cd²⁺, downregulation of NmtA (AnASnmtA) caused increased Cd²⁺ sensitivity and lesser accumulation of Zn²⁺. Probing into metal dependent expression of nmtA, we identified metal sensing motifs in α5 helix of AzuR, the negative regulator of NmtA by site directed mutagenesis. Transcriptome analysis of recombinant Anabaena overexpressing AzuR (AnazuR⁺) recognized differential gene expression that regulated Zn²⁺ metabolism. The protective role under oxidative stress of NmtA was affirmed by free radical scavenging ability via oxidative stress-induced Zn²⁺ mobilization by NmtA and enhanced sensitivity of AnASnmtA to H₂O₂ stress. The metal binding potential of NmtA prompted us to immobilize NmtA onto citrate functionalized magnetic nanoparticles (CMNP-NmtA) that demonstrated ~ 51% Cd²⁺ removal from industrial wastewater supplemented with 10 µg/mL Cd in presence of other heavy metals. Overall, this study established the multifaceted functions of metallothionein from diazotrophic, filamentous cyanobacterium advancing information on the otherwise less explored prokaryotic MT diversity.

Attention-deficit/hyperactivity disorder (ADHD) is the most common neurodevelopmental disorder in childhood. Its clinical diagnosis primarily relies on behavioral assessments, lacking objective and non-invasive biological indicators. Trace elements are involved in neurotransmitter synthesis, myelin development, and prefrontal cortex function regulation, and their imbalance may be associated with the pathogenesis of ADHD. However, previous studies have mostly focused on single elements, lacking systematic evidence at the omics level. To analyze the differences in 30 skin element levels between children with ADHD and healthy controls, and to explore the associations of elemental imbalances with core symptoms, anxiety, and executive function, thereby providing a basis for non-invasive screening of childhood ADHD. A total of 549 children with ADHD and 963 healthy controls were enrolled. Skin element levels were measured using a non-invasive high-throughput technique. Behavioral assessments were performed using the CONNERS, SNAP‑IV, SCARED, and WEISS scales. Analysis of covariance (ANCOVA) with age as a covariate was used to compare intergroup differences in element levels. Partial correlation analysis was applied to control for age as a confounding factor. The Benjamini‑Hochberg method was used to control the false discovery rate (FDR) for multiple comparison correction, with a significance threshold of q < 0.05. After adjusting for age and FDR correction, 28 elements showed significant differences between the ADHD group and the control group. In the ADHD group, essential/potentially beneficial elements such as Mg, Zn, I, Cr, Li and Ge were decreased, whereas B and harmful elements including Pb, Hg, Cd, As, Al, Be, and Ba were increased. Multiple elements exhibited stable associations with inattention, hyperactivity-impulsivity, anxiety, and risk-taking behavior. Children with ADHD displayed a complex network pattern of synergistic and antagonistic inter-element relationships. Children with ADHD exhibit a characteristic skin trace elementomic imbalance, characterized by decreased beneficial elements and increased harmful elements, which is closely associated with behavioral symptoms. Non-invasive skin elementomics may serve as a reference indicator for population-based risk screening of childhood ADHD and holds promise for population-based screening.

Concentrations of heavy metal residues in the environment are increasing due to human activity and climate change. Iron is one of the most elements that increased in the environment, as a byproduct of industrial activities, fertilizers, and mining, leading to its deposition in the soil and subsequent transfer to plants and groundwater. In addition, iron is available as over the counter drug without prescriptions, and reported as the second common overdose drug during pregnancy. Iron poisoning affects the cells and tissues, and accumulated iron in lungs is risk and causes health problems, hematological diseases and aging processes. Iron overload chelation therapy is depending on the chelating agents such as deferoxamine. The antioxidant and anti-inflammatory therapeutic N-acetylcysteine (NAC) is also working as metal chelator, but it would be limited in some improper circumstances. This study hypothesized that the prepared acetylated whey protein (AWP) could be alternative to NAC. This study designed to investigate the impact of iron overload on the structure and function of the respiratory system in mammals, regardless of the mechanism behind the iron accumulation. The study aims to identify food supplemented compound that is at least as effective as N-acetyl cysteine (NAC) in mitigating or preventing the risks associated with high doses or prolonged exposure of NAC. Albino male rats were used as animal model. Forty-eight rats were randomized selected equally and divided into four groups. treated groups were intoxicated by iron dextran interperitoneally. Two groups were orally supplemented with N-Acetylcysteine and Acetylated whey protein individually. The pulmonary histopathological examinations and biochemical markers were done. Reduced glutathione, nitric oxide and malondialdehyde as oxidative stress markers. Lung tissue Ferritin and vascular endothelial growth factor (VEGF) were measured. All oxidative stress markers were significantly improved with both NAC and AWP groups especially AWP group. Tissue ferritin and VEGF exhibited significant improvement in the lung tissue. Acetylated whey protein can play crucial chelation therapeutic role of intoxicated individuals with iron as supplement in safe and no effects for short- or long-term treatment.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disorder primarily affecting the synovial joints, characterized by persistent synovitis, progressive joint destruction, and systemic complications that contribute to significant morbidity. Despite advances in disease-modifying anti-rheumatic drugs and biologic therapies, many patients fail to achieve sustained disease control or experience treatment-related adverse effects, highlighting the need for safe adjunctive strategies. Zinc, an essential trace element with critical roles in immune regulation, antioxidant defense, and inflammatory signaling, has gained increasing attention in the pathogenesis and management of RA. Clinical studies consistently report altered zinc homeostasis and reduced circulating zinc levels in RA, which are associated with increased disease activity, oxidative stress, and immune dysregulation. However, human interventional studies evaluating zinc supplementation remain limited, involve relatively small sample sizes, and report heterogeneous findings. In contrast, experimental studies in validated animal models have more consistently demonstrated anti-inflammatory and immunomodulatory effects of zinc, including modulation of macrophage and T-cell activation, cytokine production, synovial fibroblast behaviour, and bone remodelling. Importantly, the therapeutic effects of zinc appear to be formulation-dependent, as organic zinc salts, chelated forms, and emerging nano-based formulations have demonstrated superior bioavailability and anti-inflammatory efficacy compared with conventional inorganic salts. This review aims to explain the molecular and immunological mechanisms underlying the effect of zinc in RA, evaluates findings from clinical and preclinical studies of zinc supplementation, and highlights formulation-specific considerations relevant to clinical practice. While existing evidence supports the potential of zinc as a safe and beneficial adjunct to conventional RA therapy, further well-designed randomized clinical trials are required to establish optimal dosing strategies and identify patient populations most likely to benefit.

To assess temporal trends of urinary heavy metal(loid)s burden and lipid levels, and explore the single and joint associations of heavy metal(loid)s exposure with lipid profiles among children in Guiyu, a typical e-waste dismantling area in China. Based on 2016 and 2024 surveys in Guiyu, 197 children (aged 3-7) were enrolled. Urinary concentrations of 13 heavy metal(loid)s were determined using inductively coupled plasma mass spectrometry (ICP-MS). Serum lipid parameters including total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were measured, and non-high-density lipoprotein cholesterol (non-HDL-C) was calculated. To investigate the independent and combined associations between metals and blood lipid profiles, multiple linear regression and Bayesian kernel machine regression (BKMR) models were employed. Urinary concentrations of Chromium (Cr), Nickel (Ni), Copper (Cu), Cadmium (Cd), and Lead (Pb) in 2024 were significantly lower than those in 2016 (all P < 0.05). In adjusted models, Manganese (Mn), Cobalt (Co), Cd, and Pb were positively associated with TC and non-HDL-C, while Cd and Pb were negatively associated with HDL-C (all P < 0.05). BKMR confirmed a significant joint positive effect of a 12-metal mixture on TC and non-HDL-C, and a negative effect on HDL-C. Despite decreased individual metal levels over the eight-year interval, the biological risk from co‑exposure to these metals remains a critical concern These findings highlight the need for vigilance regarding the synergistic cardiovascular toxicity of heavy metals on pediatric lipid homeostasis.

Non-communicable diseases (NCDs) are a significant public health concern globally. Among the most prevalent NCDs the study aims to explore the association of some elements with the the likelihood of cardiovascular diseases (CVDs) and type 2 diabetes mellitus (T2D) development. In this cross-sectional case control study, 300 individuals with CVDs (n = 110), T2D (n = 70), and a control group (n = 120) from the Ravansar Non-Communicable Disease (RaNCD) cohort in western Iran were examined. The RaNCD cohort is part of the PERSIAN cohort study, consisting of 10,000 adults. Participants aged 35-65 were stratified into three clusters based on their health status. Various elements, including aluminum (Al), calcium (Ca), magnesium (Mg), phosphorus (P), manganese (Mn), potassium (K), cobalt (Co), lithium (Li), boron (B), molybdenum (Mo), and vanadium (V) in the blood serum was performed using the ICP-MS method, and data were analyzed using multivariable techniques, including logistic regression and clustering analysis. Our analysis revealed a notable association between most elements and the risks of CVD and T2D in the logistic regression model after adjusting for age and gender. Specifically, increased odds ratios of CVD and T2D were identified for higher Ca, Mn, Mg, Li, V, Al, P, and Mo levels. In the T2D group, four clusters were identified: Al-B, Mn-Co-Mo, K-P, and V-Li-Ca-Mg. In the CVD group, five clusters were observed: K, B-Co-Mo, Li-Mg, Ca-P, and Mn-Al-V. The study provides valuable insights into the role of some essential elements in the development of CVDs and T2D. The key elements that are most linked to the elevated risk of CVDs and T2D include calcium, manganese, molybdenum, vanadium, lithium, aluminum, phosphorus, and magnesium. Further exploration of the intricate relationships between elements and disease risk could enhance our understanding of preventive strategies and personalized interventions for individuals at risk of CVDs and T2D.

Metal pollution and emerging contaminants, such as metal nanoparticles, are increasingly found in estuarine and coastal environments. These pollutants pose significant risks to aquatic life and human health and may affect food security. This study evaluates host-associated microbiome engineering as a biological method to reduce cadmium toxicity in an aquatic invertebrate model. We designed a consortium of metal-resistant bacteria through systematic screening and exclusion of isolates from various marine ecosystems. This process resulted in a functionally compatible consortium comprising Bacillus altitudinis, Lacticaseibacillus rhamnosus, Bacillus cereus and Weissella cibaria. The consortium members tolerated up to 1 mM CdCl₂ independent of active efflux mechanisms, bile salts, and gastric juices, and formed stable biofilms. The strains did not display antagonistic behaviour towards each other and effectively inhibited pathogenic Vibrio spp. from both environmental and clinical sources. Scanning electron microscopy (SEM) and Inductively Coupled Plasma Optical Emission Spectroscopy (ICP-OES) analyses confirmed the maintenance of cell wall integrity under cadmium stress and the presence of bioaccumulation factors greater than one. Artemia nauplii pre-colonized with the bacterial consortium demonstrated a 33.6% increase in survival during acute (1.5 mM) cadmium exposure compared to untreated controls. These findings suggest that microbiome-based interventions can enhance host tolerance to metal pollution and represent a promising biological approach to mitigating the ecological impacts of metal contamination in aquatic environments.

The development of novel metal-based antifungals requires rigorous characterization of their toxicological mechanisms to ensure patient safety. This study investigated the toxicogenetic profile and cellular interactions of lawsone silver salt (LSS), a compound with established activity against Sporothrix spp. and emerging multidrug-resistant pathogens. Antifungal efficacy was confirmed against planktonic Aspergillus fumigatus, Candida albicans, and C. auris (MIC 1.45-23.2 µM), with significant anti-biofilm activity against C. albicans (185.9 µM) and A. fumigatus (92.9 µM). In silico ADMET modeling predicted high oral bioavailability and blood-brain barrier permeability, despite the genotoxicity alerts. Experimentally, LSS (0.005-50 µg/plate) was non-mutagenic in the Salmonella/microsome assay (TA1535, TA97a, TA98, TA100, and TA102), regardless of the metabolic activation. However, LSS (0.5-500 µM) induced significant genomic instability in HepG2 cells. The micronucleus assay revealed a dose-dependent increase in micronuclei, nucleoplasmic bridges, and nuclear buds, indicating clastogenic and aneugenic effects. Comparative cytotoxicity was evaluated in BALB/3T3 fibroblasts using 2D monolayers and scaffold-based 3D models (0.005-5000 µM). In 2D cultures, LSS exhibited potent cytotoxicity (CC₅₀: 2.7-19.9 µM). Crucially, the 3D microenvironment significantly attenuated these effects (CC₅₀: 1,797-1,919 µM), suggesting a markedly higher safety margin in physiologically relevant tissue architectures. These findings demonstrate that while LSS induces chromosomal damage in human cells, its toxicity is fundamentally modulated by cellular organization, providing essential data for risk assessment and therapeutic optimization of naphthoquinone derivatives.

Breast cancer remains a major malignancy, with triple-negative breast cancer (TNBC) representing an aggressive subtype with limited therapeutic options. This study investigated the synthesis, physicochemical properties, and biological activity of Dodonaea viscosa-derived gold nanoparticles (DV-AuNPs). Synthesis was optimised for reaction temperature, extract concentration, and extract-to-gold chloride ratio. DV-AuNPs were characterised using ultraviolet-visible spectroscopy, dynamic light scattering, X-ray diffraction, Fourier-transform infrared spectroscopy, and electron microscopy, and their colloidal stability was assessed in biologically relevant media over two weeks. The nanoparticles were predominantly spherical (19.6 ± 3.6 nm) and exhibited surface functionalisation with plant-derived compounds. Cellular metabolic activity/viability assessment revealed differential responses across breast-cell models: MDA-MB-231 cells demonstrated concentration-dependent sensitivity to DV-AuNP exposure, whereas MCF-7 and non-tumorigenic MCF-12A cells were comparatively less responsive under the tested conditions. In MDA-MB-231 cells, DV-AuNP treatment markedly suppressed clonogenic capacity, while functional assays revealed limited effects on migration and epithelial-to-mesenchymal transition (EMT)-associated proteins. Transmission electron microscopy demonstrated intracellular localisation of electron-dense particles consistent with DV-AuNPs. To the best of our knowledge, this study provides the first integrated evaluation of DV-AuNPs in a TNBC model encompassing physicochemical characterisation, colloidal stability, differential cellular responses, clonogenic capacity, migration, EMT-associated proteins, and intracellular localisation. Altogether, these findings demonstrate cell-line-dependent biological responses to DV-AuNPs and support their continued investigation as biologically functionalised gold nanoparticles for breast-cancer applications. Further studies are required to define the underlying mechanisms and evaluate activity across additional TNBC models.

Polycystic ovarian syndrome (PCOS) is a common endocrine disorder in women of reproductive age. Metal ions can disrupt antioxidant defenses, alter the endometrial environment, and contribute to its pathophysiology. To compare element levels in menstrual effluent (ME) between women with PCOS and healthy controls, and to assess their association with antioxidant defence mechanisms, a case-control study was conducted among women diagnosed with PCOS according to the Rotterdam criteria. ME was collected and analysed by Inductively Coupled Plasma Mass Spectrometry (ICP-MS) for elements. Antioxidant enzymes like catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), non-enzymatic antioxidants glutathione (GSH), hydrogen sulfide (H₂S), oxidative stress markers lipid peroxidase (LPO), nitric oxide (NO), and myeloperoxidase (MPO) were measured in the ME-derived erythrocytes. Significant differences were observed in Boron (B), Barium (Ba), Calcium (Ca), Copper (Cu), Iron (Fe), Magnesium (Mg), Manganese (Mn), Sodium (Na), Potassium (K), Nickel (Ni), Phosphorus (P), and Zinc (Zn) in the ME of PCOS women compared to healthy controls. Elevated CAT, SOD and GPx correlated with elements like Mn, Cu, and Zn. LPO, NO, and MPO were correlated with Fe, Cu, Zn, Cd, Ni, Pb, Cu and Mn. GSH and H₂S levels decreased in women with PCOS, correlating with elements such as B, Ba, Cu, Fe, Ni, and Zn. Common proteins were found between metal-interacting and PCOS-related genes, implicating the role of elements in oxidative pathways. ME-based metal profiling offers a non-invasive approach for the early detection of oxidative stress-related inflammation in PCOS, with implications for cancer risk monitoring.