Biometals最新文献

The individual functions of most iron-containing species in Saccharomyces cerevisiae are fairly-well understood, but less is known regarding how they function collectively as a unified system. Here, an ODE-based kinetic cell model was developed to reveal system's-level behavior of iron metabolism. The dimensionally-accurate in silico cell was divided into 5 compartments. It contained 80 components that engaged in 169 reactions. The cell grew on nutrients IRON, CARBON and OXYGEN. All major iron-related processes were represented including the biosynthesis and metallation of iron-containing proteins, trafficking of labile iron pools, homeostatic regulation, respiration, the TCA cycle, iron-sulfur-cluster and heme biosynthesis, the synthesis of DNA, phospholipids, amino acids, and nucleotide triphosphates, and reactions involving oxygen and reactive-oxygen-species. Iron and carbon were conserved in reaction stoichiometries. The time-dependent model was solved using the Basic Pathways approach, despite limited kinetic information. Once regulated appropriately, the system could withstand perturbations in component concentrations by returning to its original steady-state. It responded to changes in nutrient iron and oxygen concentrations and to changes in rate-constants, yielding altered sets of steady-state component concentrations. The latter type of perturbation is tantamount to altering the expression level of a gene. This ability offers the potential to explain phenotypic changes of genetic mutations on the mechanistic molecular level. The model included all established iron-related cellular processes (albeit in combined forms), and a highly interrelated reaction network reflecting a mutually autocatalytic system. Steady-state iron concentrations in the cell, organelles, and components were reasonably near to those observed/estimated experimentally.

Disturbances in zinc (Zn) and copper (Cu) homeostasis have emerged as reproducible biochemical features of autism spectrum disorder (ASD). This study presents an integrative reanalysis of six investigations (2014-2025) encompassing serum, whole-blood, and plasma measurements in ASD cases and controls, and one supplementation trial. Three case-control studies reporting mean ± SD values in circulating matrices were meta-analyzed. Circulating Zn levels were significantly lower in ASD (fixed-effect Hedges' g = -0.95; 95% CI -1.22 to -0.68; Q = 1.72, p = 0.42; I² = 0%; Egger intercept = 4.86, one-sided p = 0.044). The Zn/Cu ratio showed greater dispersion (random-effects g = -1.28; 95% CI -2.59 to 0.03; Q = 39.5, p < 0.001; I² = 95%), driven primarily by one cohort (leave-one-out g = -0.63; 95% CI -0.99 to -0.26). In Brazilian subjects, plasma Zn and Cu fell within reference ranges, consistent with short-term plasma buffering of marginal deficits. In an Egyptian 12-week oral elemental Zn intervention in children with ASD, serum Cu fell by ~8%, circulating metallothionein (MT) protein increased, and CARS and TGMD-2 motor scores improved. MT-1A gene expression changed with Zn. Taken together, the evidence indicates that Zn insufficiency and altered Cu homeostasis are recurring features of ASD and that oral elemental Zn lowers serum Cu and increases MT.

The relationship between serum electrolyte levels and nutrient intake in environmentally exposed populations has received little attention in the international literature. This study aimed to investigate serum potassium and sodium levels and nutrient intake in populations exposed to radiation from the former Semipalatinsk Nuclear Test Site compared with non-exposed populations. A cross-sectional study was conducted in four settlements of East Kazakhstan and Pavlodar provinces, with three classified as exposed and one as non-exposed. A total of 907 adults with lifelong residency were enrolled, and exposure status was verified using official residency documents and the state automated medical registry. Dietary intake was assessed using the validated EPIC-Norfolk Food Frequency Questionnaire, and fasting blood samples were collected to measure serum potassium and sodium using ion-selective electrodes. Compared with the non-exposed group, exposed individuals reported significantly lower consumption of nearly all macro- and micronutrients, except for vitamin A. Serum potassium levels did not differ significantly between groups (median 4.3 mmol/l, p = 0.337), whereas median serum sodium levels were significantly higher in the non-exposed group (141 vs. 140 mmol/l, p = 0.02). The sodium-to-potassium ratio was not significantly different between groups (32.56 in exposed vs. 32.79 in non-exposed, p = 0.156). Correlation analysis showed a moderate positive association between serum sodium levels and sodium intake (rho = 0.495, p < 0.001), and a strong positive association between sodium and potassium intake (rho = 0.642, p < 0.001). These findings underscore the need for further investigation into dietary patterns and possible physiological adaptations in environmentally exposed populations.

SARS-CoV-2 still poses as a threat to health systems despite the vaccination and the use of emergency repurposed drugs. Therefore, the development of novel anti-SARS-CoV-2 compounds is still needed. Organometallic copper(I)-N-heterocyclic carbenes [Cu(NHC)] are a class of metallodrugs that hold promise for drug development due to their variety of geometries, charges, and ligand design. Here we evaluated the activity of Cu(IPr)Cl, Cu(IMes)Cl, and [Cu(IMes)₂]BF₄ molecules against SARS-CoV-2 infection. Through a dose-response assay using A549-AT cells and the SARS-CoV-2-Wuhan infectious clone expressing mNeonGreen (SARS-CoV-2-mNeonGreen), Cu(IPr)Cl, Cu(IMes)Cl, and [Cu(IMes)₂]BF₄ inhibited SARS-CoV-2 replication with a selectivity index (SI) of 11.23, 10.84, and 5.94, respectively. The complexes Cu(IMes)Cl and [Cu(IMes)₂]BF₄ inhibited all stages of viral replication (pretreatment: 99.9% and 87.7%, entry: 99.6% and 74%, post-entry steps: 99.6% and 87.6%, respectively), while Cu(IPr)Cl impaired only entry (48%) and post-entry steps (95%). In addition, Cu(IMes)Cl and [Cu(IMes)₂]BF₄ complexes decreased the titres of both Delta and Omicron variants, while Cu(IPr)Cl only inhibited Omicron. In addition, [Cu(IMes)₂]BF₄ was able to decrease cell to cell spread of SARS-CoV-2; and for Cu(IMes)Cl a strong interaction with PL^pro was revealed. Based on this data further investigations of Cu(I) based organometallics are warranted and Cu(IPr)Cl and Cu(IMes)Cl may be considered for utilization in pre-clinical assays.

Copper (Cu) is a vital trace element essential for numerous neurological functions, such as neurotransmission and antioxidant defense mechanisms. Nevertheless, Cu dyshomeostasis has been increasingly associated with neurodegenerative diseases, particularly Alzheimer's disease (AD).This review provides an overview of the intricate mechanisms of Cu homeostasis in the brain, detailing the pathways through which Cu enters neural tissues and its subsequent metabolic roles. We also discuss the emerging concept of cuproptosis, a Cu-dependent regulated cell death mechanism, and highlight its relevance to AD pathophysiology. Furthermore, we examine the interplay between glutamate, a key excitatory neurotransmitter, and cuproptosis, illustrating how alterations in glutamate levels may exacerbate Cu toxicity and contribute to neuronal degeneration in AD. Additionally, we review several compounds with the potential to modulate Cu concentrations, emphasizing their therapeutic implications for restoring Cu balance and mitigating neurodegenerative processes.By integrating current findings on Cu metabolism, cuproptosis, and glutamate interactions, this review provides novel insights into potential therapeutic interventions that may help prevent or slow AD progression.

The macronutrient phosphorus is vital for sustaining cellular processes in all life forms. Due to its frequent adsorption on iron minerals, phosphorus bioavailability is low in many soils. While the abiotic adsorption of phosphate on iron minerals has been well studied, the direct effects of this process on bioavailability to plants and microbes has not been thoroughly investigated in a simplified laboratory system. We developed a hydroponic growth system that uses hydrous ferric oxide (HFO) to induce phosphorus limitation and can enable both plant and microbial cultivation as well as gnotobiotic co-culture. We demonstrate that this system can be used for phosphorus-limited growth of the model plant Arabidopsis thaliana as well as two root-associated bacterial isolates (from the genera Rhizobium and Pseudomonas). Elemental analysis of phosphorus and iron concentration in A. thaliana shoots reveals that the addition of increasing amounts of HFO leads to a progressive decrease in phosphorus concentration but does not affect iron quotas. We also report that phosphorus concentrations in both bacterial isolates decrease when cultivated in media supplemented with HFO. We further show that A. thaliana can be co-cultured with a Rhizobium isolate in our phosphorus-limited hydroponic system with bacteria relying on plant photosynthate as their sole carbon source. Our work provides a controlled demonstration of the effects of mineral adsorption on phosphorus bioavailability and a tool for further investigation of how plants and microbes access phosphorus in the environment.

The unique properties of nanoparticles have sparked intense research interest, driving innovation in production methodologies. Biological synthesis of nanoparticles has emerged as a game-changer, offering an efficient, cost-effective, and eco-friendly alternative. A diverse array of organisms, including bacteria, fungi, yeast, algae, and plants, can biosynthesize metallic nanoparticles with varying sizes and shapes through reduction reactions. A comprehensive analysis of existing literature reveals the bio reduction capabilities of bacterial biomass and extracts under different experimental conditions, providing valuable insights into this promising field. The applications of biosynthesized nanoparticles are vast, with notable potential in antimicrobial and anticancer activities. By exploring the achievements and current status of bacterial-mediated biosynthesis, this study aims to shed light on the opportunities and challenges in this rapidly evolving field. The surge in nanoparticle research is largely driven by the unexpected variations in surface properties that occur when particle size is reduced to the nanoscale, resulting in enhanced features such as particle size distribution and shape. The reduction of particle size to the nanoscale displays unique and improved features, including particle size distribution and shape. This variation in specific surface area is responsible for its high value, which influences critical factors such as surface reactivity. Gold particles have been employed for medicinal and Ayurvedic purposes in India and China since ancient times. Metal nanoparticles are being used globally in biomedicine and related fields. Researchers are currently focused on metal nanoparticles, nanostructures, and nanomaterial production due to their unique features. This paper examines various metal oxide nanoparticle preparation processes, including their benefits, drawbacks, and potential applications.

Soil microorganisms respond vigorously to environmental changes. However, the impact of varying levels of rare earth elements (REEs) contamination on microorganisms and their interactions remains unclear, with a scarcity of research on biomarkers for different levels of rare earth enrichment. This study categorized REE concentrations into distinct accumulation tiers. Utilizing Illumina high-throughput sequencing, the researchers investigated how different REE levels affect biodiversity, ecosystem structure, and functional dynamics. The results indicated that while the accumulation of rare earth elements (REEs) reduced soil bacterial diversity, the impact on the diversity of bacterial populations was minimal. Proteobacteria, Actinobacteria, and Chloroflexi were identified as the dominant bacterial communities near the uncommon rare earth tailings pond. According to linear discriminant analysis effect size (LEfSe), certain genera-Halomonas, Aliifodinibius, and Truepera-emerged as potential indicators of soils with elevated REE concentrations. Sphingomonas was identified as the biomarker in medium-concentration (MC) samples, whereas norank_Subgroup6, norank_Actinobacteria, and RB41 were enriched in low-concentration (LC) samples. Tax4fun function prediction revealed that the metabolic capacity of bacterial communities was inhibited under REE stress. Statistical analyses, including redundancy analysis and the Mantel test, pinpointed soil moisture and rare earth element concentrations as the primary environmental drivers in mining-affected regions. These findings illustrate that rare earth accumulation significantly alters bacterial community diversity, taxonomic composition, and ecological functions in these areas. Researchers also identified distinct microbial biomarkers corresponding to various levels of rare earth enrichment. The study offers deeper insights into how rare earth mining operations affect the composition and function of soil microbial communities.

Bacterial pathogens must rapidly adapt to fluctuating metal availability within the host, where essential micronutrients are actively sequestered as part of nutritional immunity. Among these, zinc is a critical cofactor for a wide array of enzymes and regulatory proteins, and its availability is tightly linked to the expression of key virulence traits in Pseudomonas aeruginosa. This opportunistic pathogen employs different zinc acquisition systems transcriptionally regulated by the Zinc Uptake Regulator Zur, enabling its persistence within the host. Recently, Zur-controlled operons involved in the uptake/export of cobalt have been identified. Although cobalt is primarily associated with cobalamin-dependent reactions, its selective import under zinc-limiting conditions suggests a potential role for cobalt in bacterial adaptation to zinc scarcity. Yet, the functional relevance of this metal-based compensation remains poorly defined. This study shows that cobalt supplementation alleviates key effects of severe zinc deficiency in P. aeruginosa, including reduced pyocyanin production, impaired swarming motility, and enhanced sensitivity to oxidative stress. Furthermore, in vitro assays demonstrate that cobalt can functionally replace zinc in the proteases LasA and LasB and the transcriptional regulator Zur. Finally, we found that a P. aeruginosa strain deficient in the pyochelin-cobalt receptor PA2911 exhibits impaired colonization of Galleria mellonella larvae, supporting the hypothesis that cobalt compensatory function may be crucial during infection. Our results suggest that cobalt may play a broader biological role than previously recognized, highlighting its potential to support P. aeruginosa survival and pathogenicity in zinc-limiting environments.