Biometals最新文献

Agaricus crocodilinus (Agaricaceae), an edible saprotrophic mushroom, accumulates high concentrations of cadmium (Cd) in unpolluted environments. This study investigates whether this species has evolved mechanisms to store Cd complexed with metallothioneins (MTs), proteins that bind heavy metal ions via cysteinyl (Cys)–thiolate bonds, how these MTs originated, and how similar mechanisms are present in other fungal species. Size exclusion chromatography revealed that a substantial fraction of Cd in A. crocodilinus sporocarps was sequestered in a 3.4 kDa complex containing Cys-rich peptides. Screening a sporocarp cDNA expression library in a Cd-sensitive Saccharomyces cerevisiae strain identified two MT transcripts, AcMT1 and AcMT2, encoding 49-amino acid (AA) AcMT1 with 10 Cys and 32-AA AcMT2 with 7 Cys. The presence of AcMT2 in the 3.4 kDa Cd–peptide complex isolated from sporocarp was confirmed by mass spectrometry. In mycelial isolates exposed to heavy metals, AcMT1 was more strongly upregulated, while AcMT2 was more expressed under normal conditions. Sequence comparisons revealed that AcMT2 is closer to the ancestral gene, whereas AcMT1 is a more recent duplicate. Combined bioinformatic and functional evidence supports AcMT2 as a constitutively expressed MT involved in Cd binding in the sporocarp, while AcMT1, though more inducible in mycelia and more protective in yeast, appears to serve a transient detoxification role. Moreover, the gene duplication and domain rearrangement mechanism underlying this MT diversification was also identified in other Agaricales and Boletales species.

Pollution caused by heavy metals is one of the most prominent environmental challenges, and these pollutants induce various detrimental effects on plants. Copper (Cu) is an essential micronutrient for the normal growth and development of plants in trace amounts, while lead (Pb) causes deleterious effects even at low levels. Although pumpkin is used extensively worldwide for its nutritional and medicinal value, little is known about this plant in the context of heavy metal stress. Therefore, this study investigated the effects of different concentrations of lead (25 mM and 50 mM) and copper (50 mM and 100 mM) on pumpkin at the ecophysiological and molecular levels, focusing on the mechanisms involved in heavy metal tolerance. As a result, both lead and copper stress generally favored stem growth while limiting root growth. Pumpkin accumulated lead and copper mostly in the roots to reduce the hazardous effects of Pb and Cu, as evidenced by higher Pb and Cu content in the roots than in the leaves. Additionally, Pb-treated plants had noticeably higher chlorophyll amounts, whereas Cu-treated plants showed a concentration-dependent response. Pb and Cu stress increased malondialdehyde (MDA) content at higher concentrations, accompanied by a general decline in total protein amounts. Furthermore, Pb and Cu stress increased superoxide dismutase (SOD), catalase (CAT), and ascorbate peroxidase (APX) activities, as well as the gene expression of these enzymes. Overall, this study revealed that pumpkin is highly tolerant to lead and copper and achieves this tolerance by enhancing the activities and gene expressions of antioxidant enzymes.

Overproduction of reactive oxygen species (ROS) causes oxidative stress, which is a significant risk factor for the onset and advancement of atherosclerosis. However, in current study, rats with experimentally generated atherosclerosis (EA) are used to examine the effects of prolonged cobalt nitrate exposure on oxidative stress and hematological markers. An atherogenic diet, methylprednisolone, alcohol, and mercazolil were all used in a polyetiological method to imitate atherosclerosis. In the following 60 days, rats were given drinking water containing 2 mg/kg of cobalt nitrate. The following oxidative stress markers were examined: hematological indices, diene conjugates (DC), catalase (CA), and malondialdehyde (MDA) at baseline, after EA induction, and during cobalt exposure. However, Significant oxidative imbalance was caused on by EA alone, which increased MDA (18%) and DC (20%) while decreasing CA activity (22%). By day 60, cobalt exposure amplified these effects, leading to a decrease in CA (27%) and increasing increases in MDA (64%) and DC (35%). Hematologically, EA first increased granulocytes (1.2 ×), leukocytes (1.8 ×), and lymphocytes (1.3 ×), which were indicative of systemic inflammation. Cobalt, however, overcomes these patterns, gradually causing hemoglobin depletion, erythrocytopenia, and leukopenia. Hemoglobin and mean corpuscular hemoglobin (MCH) dropped by 24% and 25%, respectively, by day 60, suggesting that erythropoiesis and iron metabolism were compromised. The investigation emphasizes that cobalt complicates oxidative stress and blood abnormalities associated with atherosclerosis. Chronic exposure contributes to vascular damage through oxidative and inflammatory mechanisms, even at subtoxic concentrations, exposing people with cardiovascular diseases at risk. In addition to offering treatment options for oxidative stress and hematopoietic support, it emphasizes the necessity of tracking cobalt exposure in at-risk populations. It is advised to conduct additional research and reevaluate the cobalt safety limits.

Given the need of more effective and safe treatments for diseases such as cancer, metal complexes can be highlighted. Among these, two copper(II) complexes linked to phenanthroline and two different sulfonamides identified as [Cu(smtr⁻)₂(phen)] (1) and [Cu(sdmx⁻)₂(phen)] (2) presented promising antibacterial and anti-proliferative activities. Continuing the in vitro preclinical studies, this study aimed to evaluate the cytotoxic effect on human colorectal tumor cells (HCT-15) and the genotoxic effect on immortalized Chinese hamster’s ovarian cells (CHO-K1) of complexes 1 and 2. Both complexes significantly reduced HCT-15 viability in monolayer and spheroid models, along with increased frequency of micronuclei after short-term treatment without metabolic activation in CHO-K1 cells. Furthermore, both in the presence of the metabolic enzyme mixture and with increasing exposure time, the genotoxic effect was not observed. In CHO-K1 cells, complexes 1 and 2 induced S-phase cycle arrest. Complex 2 was more active than complex 1 in increasing the production of reactive oxygen species in both cell lines evaluated. The cytotoxic and genotoxic effects observed for complexes 1 and 2 appear to be mediated by oxidative stress. Additional studies will be needed to further investigate the mechanisms of action, as well as to confirm the mutagenic potential of these complexes.

Alzheimer’s disease (AD) is a neurodegenerative disorder that causes cognitive impairment and loss of neurons. According to the Alzheimer’s Association’s 2022 US report, the USA saw a 145% increase in AD-related fatalities from 2000 to 2020, with an estimated financial burden of these disorders surpassing $1 trillion annually. Its pathological features include neurofibrillary tangles and amyloid-beta (Aβ) plaques. Although there is presently no treatment that may stop the growth of AD, new clinical trials have suggested that anti-amyloid disease-modifying drugs may reduce the progression of the illness. According to a recent study, Copper (Cu) dysregulation plays a crucial role in AD pathogenesis by causing oxidative stress and encouraging the aggregation of Aβ. Meanwhile, melatonin, a neurohormone with strong neuroprotective, antioxidant, and Cu chelation qualities, has drawn an interest due to its possible use for AD treatment. This review thoroughly summarizes the most recent research, including in vivo, in vitro, and human studies, and also examines the complex relationships among AD, melatonin, and Cu toxicity. We observe how an excess of Cu aggravates AD pathogenesis and how the special qualities of melatonin can counteract these effects. Melatonin is a promising molecule having a dual approach to address pathogenesis of AD by chelating excess Cu and lowering oxidative stress. Comprehending the interplay between Cu dysregulation and the protective mechanisms of melatonin may result in innovative therapies, providing promises for enhanced management of AD.

This study presents a comprehensive analytical assessment of macro- and micro-element content in Artemisia abrotanum L. harvested during two distinct growth periods—pre-blooming and blooming. Using a validated ICP-MS method, both microwave digestion and infusion extraction techniques were applied to evaluate the elemental composition of the plant. The concentrations of essential, beneficial, and potentially toxic elements—including Na, K, Mg, Ca, Fe, P, S, Al, V, Cr, Mn, Co, Ni, Cu, Zn, As, Se, Sr, Mo, Cd, Ba, Tl, Pb, and U—were determined and compared across harvest times and extraction methods. Chemometric analyses, including principal component and hierarchical cluster analysis, were employed to classify the results and elucidate patterns among the elements and sample types. The findings revealed that the elemental distribution in Artemisia abrotanum L. varies significantly with harvest period and preparation method. Notably, Na, Mn, Ni, Co, As, Se, Sr, and Ba were more abundant during the blooming period, while K, Mg, Ca, Zn, Mo, Cd, and Pb were higher in the pre-blooming period. Differences in P, Fe, Al, V, Cr, and Tl concentrations were primarily attributed to the extraction technique. The study further evaluated the measured element concentrations against updated dietary and toxicological reference values, providing a clearer perspective on the potential health implications of consuming Artemisia abrotanum L. infusions. These results underscore the importance of both harvest timing and preparation method in determining the nutritional and safety profile of medicinal plants.

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There is very limited epidemiological research available to verify how metal exposure impacts the prognosis of individuals with asthma. This study aimed to investigate the value of multiple urinary metals in assessing the prognosis of asthma patients by utilizing data from NHANES and constructing the predictive models. This study employed Cox regression models, survival 3D interaction plots, and survival curves to examine the associations between urinary metals and the outcomes among asthmatic patients. This study also employed LASSO regression to find key variables for the prediction model and then employed time-dependent receiver operating characteristic (ROC) curves and Shapley additive explanations (SHAP) models to evaluate how well the prediction model performed and its usefulness. The Cox regression models, survival 3D interaction plots, and survival curves all verified that, after controlling for confounders, the higher concentrations of urinary cadmium (HR: 1.76, 95% CI: 1.08–2.87) and cobalt (HR: 1.27, 95% CI: 1.06–1.52), the lower the survival rate and the higher the risk of death for asthma patients. However, no significant associations were observed between the other seven urinary metals (barium, cesium, molybdenum, manganese, lead, tin, and tungsten) and the prognosis of asthma patients. According to the LASSO regression and SHAP model, the most significant indicators predicting mortality in individuals with asthma were age, cadmium, cobalt, diabetes, cancer, other chronic airway diseases, and cardiovascular disease. The combination of these seven indicators exhibited superior performance when predicting the 1-year (AUC: 0.82), 5-year (AUC: 0.86), and 9-year (AUC: 0.82) death risk of asthma populations. This study revealed that when the urinary cadmium concentration of asthma patients exceeded 0.21 µg/L or the urinary cobalt concentration exceeded 0.98 µg/L, urinary cadmium and cobalt concentrations were positively associated with mortality among asthma patients. Urinary cadmium and cobalt, when combined with other markers, can serve as effective and practical instruments for predicting adverse outcomes in asthmatic populations.

Ferroptosis-mediated injury in diabetic kidney (DKD) is receiving increasing attention. Glutathione Peroxidase 4 (GPX4) has long been considered a key protein to prevent ferroptosis, but its exact role in the progression of DKD, where this protein down-regulated, remains unclear. Thus, to clarify GPX4 in DKD progression, we have used adeno-associated viruses (AAVs) to overexpress it in kidneys of DKD rats. Streptozotocin (STZ)-induced DKD rats were injected once with GPX4-AAVs via tail vein. Renal function and kidney pathology were measured. Before and after treatment with GPX4-AAV, variations in kidney of ferroptosis-related indicators, such as GPX4, dihydroorotate dehydrogenase (DHODH), iron content, glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), transferrin receptor 1 (TFR1), ferritin heavy chain (FTH), were monitored. The kidneys of STZ-treated rats showed reduced expression of GPX4, DHODH, GSH and SOD, increased expression of TFR1 and FTH, and higher levels of iron and MDA. Histopathology was consistent with renal fibrosis and thickened renal tubules. Changes were partly reversed after overexpression of GPX4, with decreased expression of FTH, together with reduced iron and MDA levels, although expression of TFR1, GSH and SOD showed no significant change. Renal function showed a lower urine protein–creatinine ratio, whereas the effect on renal fibrosis and thickened renal tubules was alleviated. Our study demonstrates that GPX4 is downregulated in DKD, and its AAV-mediated overexpression in kidney of DKD rats partly alleviates the diabetic kidney injury induced by ferroptosis.

Colon cancer is among the most common colorectal malignancies and a leading cause of cancer-related mortality worldwide. Conventional therapies, including chemotherapy, often cause severe side effects and drug resistance, underscoring the need for safer and more effective alternatives. Green nanotechnology has emerged as a promising approach in cancer therapy, offering sustainable and biocompatible therapeutic options. In this study, Zinc oxide nanoparticles (ZnO NPs) were synthesized using Oxalis stricta leaf extract via an eco-friendly green synthesis approach and evaluated for their anticancer potential against colon cancer. Characterization by UV–VIS spectroscopy, Dynamic Light Scattering, Scanning Electron Microscopy, Fourier-transform Infrared spectroscopy, and X-ray Photoelectron Spectroscopy confirmed the nanoscale size, stability, and surface functionalization of the ZnO NPs. Cytotoxicity evaluation using the MTT assay revealed a dose-dependent anti-proliferative effect on colon cancer cells, with an IC₅₀ value of 30.27 µg/mL. Hemolysis assay indicated good biocompatibility with minimal red blood cell lysis. Apoptosis induction was evidenced by fluorescence staining techniques, including DAPI, AO/EB, DCF-DA, and Rhodamine 123, revealing nuclear condensation, oxidative stress, and mitochondrial membrane disruption. In silico molecular docking demonstrated strong binding interactions between phytoconstituents of Oxalis stricta and cancer-related targets MMP-9, GSK3β, and Bcr-Abl. Furthermore, ZnO NPs inhibited cell migration and matrix metalloproteinase activity, as evidenced by wound healing and gelatin zymography assays. These findings suggest that Oxalis stricta mediated ZnO NPs hold significant promise as a biocompatible, multi-targeted nanotherapeutic agent for colon cancer treatment.

Lead (Pb) and arsenic (As) are two of the most widespread environmental toxicants, posing significant immunological and systemic health risks worldwide. This review synthesizes current knowledge on the immunotoxicity of Pb and As, highlighting their shared and unique cellular mechanisms, with a focus on oxidative stress, mitochondrial dysfunction, immune dysregulation, and epigenetic modifications. Pb exposure has been shown to suppress CD4⁺ T cell populations, alter CD8⁺ and NK cell ratios, elevate Th2 cytokines like IL-4 and IL-6, and increase IgE levels, contributing to heightened allergy risk and systemic inflammation. Arsenic disrupts IL-6/STAT3 signaling, suppresses IFN-α/β-mediated antiviral responses, and promotes chronic inflammation through NF-κB and HIF-1α activation. Both metals generate reactive oxygen species (ROS), impair mitochondrial membrane potential, trigger apoptotic cascades, and induce genotoxic markers such as γH2AX and micronuclei. Co-exposure to Pb and As results in enhanced toxicity, with synergistic increases in lipid peroxidation (MDA), nitric oxide, cytokine release, and histopathological damage in liver and kidney tissues. However, most toxicological models overlook low-dose, chronic, and combined exposures. We emphasize the urgent need for chronic exposure studies, prospective human cohorts, multi-metal models, and omics-integrated approaches to identify early biomarkers of dysfunction. This review underscores the global public health urgency of addressing Pb and As co-exposure through multidisciplinary research, regulatory reform, and targeted interventions, particularly in vulnerable populations across high-risk regions.