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Mass Spectrometry Reviews 2024Glycans, carbohydrates, and glycoconjugates are involved in many crucial biological processes, such as disease development, immune responses, and cell-cell recognition.... (Review)
Review
Glycans, carbohydrates, and glycoconjugates are involved in many crucial biological processes, such as disease development, immune responses, and cell-cell recognition. Glycans and carbohydrates are known for the large number of isomeric features associated with their structures, making analysis challenging compared with other biomolecules. Mass spectrometry has become the primary method of structural characterization for carbohydrates, glycans, and glycoconjugates. Metal adduction is especially important for the mass spectrometric analysis of carbohydrates and glycans. Metal-ion adduction to carbohydrates and glycoconjugates affects ion formation and the three-dimensional, gas-phase structures. Herein, we discuss how metal-ion adduction impacts ionization, ion mobility, ion activation and dissociation, and hydrogen/deuterium exchange for carbohydrates and glycoconjugates. We also compare the use of different metals for these various techniques and highlight the value in using metals as charge carriers for these analyses. Finally, we provide recommendations for selecting a metal for analysis of carbohydrate adducts and describe areas for continued research.
Topics: Glycoconjugates; Metals; Mass Spectrometry; Carbohydrates; Humans; Polysaccharides; Ions; Deuterium Exchange Measurement; Animals
PubMed: 36005212
DOI: 10.1002/mas.21801 -
Ecotoxicology and Environmental Safety Dec 2023Exposure to metal mixtures may affect children's health but the conclusions are controversial. We aimed to investigate the associations of metal mixture exposure with...
Exposure to metal mixtures may affect children's health but the conclusions are controversial. We aimed to investigate the associations of metal mixture exposure with children's physical and behavioral development. 15 metals were detected in the urine samples of 278 preschoolers aged 3-6 years from eastern China. Multiple linear models and restricted cubic splines were used to evaluate dose-response relationships between single metal and children's physical and behavioral development. The Bayesian Kernel Machine Regression (BKMR) models, the weighted quantile sum (WQS) models and Quantile G-Computation were applied to evaluate the joint effects of metal mixtures. The results showed that arsenic (As) was negatively associated with z score of height for age (HAZ) in individual-metal models [β (95%CI): - 0.22 (-0.38, -0.06), P = 0.006]. Concerning children's behavioral development, multiple-metal models demonstrated a negative association with strontium (Sr) [β (95%CI): - 0.82 (-1.38, -0.26), P = 0.004], and a positive association with tin (Sn) [β (95%CI): 0.69 (0.16, 1.21), P = 0.010]. Notably, these associations remained significant or suggestive even after adjustments for multiple tests, sensitivity analyses, and application of different statistical models, including BKMR, WQS, and Quantile G-Computation. Furthermore, the study identified a negative joint effect of the metal mixture on HAZ, as demonstrated by BKMR and Quantile G-Computation models, with As playing an irreplaceable role in this observed impact. In summary, exposure to As appears to have adverse effects on HAZ, while exposure to Sn may hinder children's behavioral development. Conversely, exposure to Sr may have a protective effect on children's behavioral development. Additionally, the combined impact of metal mixtures is implicated in potentially impairing children's physical development, particularly in terms of HAZ.
Topics: Humans; Child; Child, Preschool; Environmental Exposure; Biological Monitoring; Bayes Theorem; Metals; Arsenic; Strontium; China
PubMed: 37992646
DOI: 10.1016/j.ecoenv.2023.115726 -
Journal of Inorganic Biochemistry Dec 2023The flexibility of mammalian metallothioneins (MTs) has contributed to the difficulty in obtaining structural information for this family of metalloproteins that bind...
The flexibility of mammalian metallothioneins (MTs) has contributed to the difficulty in obtaining structural information for this family of metalloproteins that bind divalent metals with its twenty cysteines. While the two-domain structure for CdMT is well-established as a CdS and CdS, a third structure has been reported when 8 Cd(II) ions bind to MT1. Isoform 3 of the MT family, MT3, has been of interest to the research community since its isolation as a growth inhibitory factor isolated in brain tissue, and has since been noted as a prominent participant in the mediation of neurodegenerative diseases and regular brain development. The differences between MT3 and the other isoforms of MT include an additional hexapeptide insertion of acidic residues in the α domain as well as the introduction of two prolines in the β domain. It is unclear whether these changes impact the metalation properties of MT3. We report the formation of a CdMT3 species is characterized by electrospray ionization mass spectrometry and UV-visible absorption spectroscopy. We report that the spectroscopic properties of this supermetalated CdMT3 are similar to those of the supermetalated CdMT1, with a clear indication of changes in structure from "fully-metalated" CdMT3 to supermetalated CdMT3 from circular dichroism spectra and both 1D Cd and 2D H-Cd HSQC NMR spectra. We conclude that the metalation properties are not impacted significantly due to the amino acid changes in MT3, and that the cysteinyl thiols are the key players in determining the capacity of metal-binding and the structure of metal-thiolate clusters.
Topics: Humans; Animals; Metallothionein 3; Cadmium; Metals; Metallothionein; Circular Dichroism; Mammals
PubMed: 37832463
DOI: 10.1016/j.jinorgbio.2023.112392 -
Environmental Science and Pollution... Nov 2023Pelvic inflammatory disease (PID) is a common medical condition in women. However, the correlation between exposure to heavy metals, including cadmium (Cd), lead (Pb),...
Association between heavy metal exposures and the prevalence of pelvic inflammatory disease: a cross-sectional study from the National Health and Nutrition Examination Survey 2013-2018.
Pelvic inflammatory disease (PID) is a common medical condition in women. However, the correlation between exposure to heavy metals, including cadmium (Cd), lead (Pb), manganese (Mn), mercury (Hg), and selenium (Se), and PID, is unclear. Using a large sample size from the National Health and Nutrition Examination Survey, these relationships were studied and verified. PID diagnosis was acquired through a self-reported questionnaire (2013-2018). Heavy metal exposure (Cd, Pb, Mn, Hg, and Se) was measured using mass spectrometry of blood samples. Covariate data were obtained through questionnaires and physical tests. Individuals with complete covariate data were included in the study. The relationship between heavy metal exposure (Cd, Pb, Mn, Hg, and Se) and PID was demonstrated using logistic regression analysis, weighted quantile sum (WQS) regression analysis, and restricted cubic splines (RCS). Overall, 2743 participants were included. Of these, 183 were diagnosed with PID. Through weighted univariate and multivariate regression analyses, the heavy metals of Cd and Pb were positively correlated with the prevalence of PID. However, no significant relationship was observed in the heavy metals of Mn, Hg, and Se. The joint effect of heavy metals further confirmed the important role of Cd and Pb in WQS analysis. After visualizing the RCS, significant curved and linear relationships were observed for Cd and Pb, respectively. Most subgroup analyses confirmed these results. In conclusion, exposure to Cd was nonlinearly correlated with the risk of PID, whereas exposure to Pb showed a linear relationship. Our findings increase the awareness of the environmental effects of exposure to heavy metals in PID. However, further studies are needed to elucidate the causality and underlying mechanisms between heavy metal exposure and the prevalence of PID.
Topics: Female; Humans; Cadmium; Cross-Sectional Studies; Nutrition Surveys; Pelvic Inflammatory Disease; Prevalence; Lead; Metals, Heavy; Mercury; Selenium; Manganese
PubMed: 37831240
DOI: 10.1007/s11356-023-30176-6 -
Biological Trace Element Research Apr 2024Heavy metals, including lead (Pb), cadmium (Cd), arsenic (As), cobalt (Co), copper (Cu), manganese (Mn), zinc (Zn), and others, have a significant impact on the... (Review)
Review
Heavy metals, including lead (Pb), cadmium (Cd), arsenic (As), cobalt (Co), copper (Cu), manganese (Mn), zinc (Zn), and others, have a significant impact on the development and progression of neurodegenerative diseases in the human brain. This comprehensive review aims to consolidate the recent research on the harmful effects of different metals on specific brain cells such as neurons, microglia, astrocytes, and oligodendrocytes. Understanding the potential influence of these metals in neurodegeneration is crucial for effectively combating the ongoing advancement of these diseases. Metal-induced neurodegeneration involves molecular mechanisms such as apoptosis induction, dysregulation of metabolic and signaling pathways, metal imbalance, oxidative stress, loss of synaptic transmission, pathogenic peptide aggregation, and neuroinflammation. This review provides valuable insights by compiling the supportive evidence from recent research findings. Additionally, we briefly discuss the modes of action of natural neuroprotective compounds. While this comprehensive review aims to consolidate the recent research on the harmful effects of various metals on specific brain cells, it may not cover all studies and findings related to metal-induced neurodegeneration. Studies that are done using bioinformatics tools, microRNAs, long non-coding RNAs, emerging disease models, and studies based on the modes of exposure to toxic metals are a future prospect to be explored.
Topics: Humans; Metals, Heavy; Manganese; Zinc; Copper; Cadmium; Brain; Environmental Monitoring
PubMed: 37462849
DOI: 10.1007/s12011-023-03778-x -
Cell Calcium Mar 2024Several trace metals, including iron, copper, manganese and zinc are essential for normal function of the nervous system. Both deficiency and excessive accumulation of... (Review)
Review
Several trace metals, including iron, copper, manganese and zinc are essential for normal function of the nervous system. Both deficiency and excessive accumulation of these metals trigger neuropathological developments. The central nervous system (CNS) is in possession of dedicated homeostatic system that removes, accumulates, stores and releases these metals to fulfil nervous tissue demand. This system is mainly associated with astrocytes that act as dynamic reservoirs for trace metals, these being a part of a global system of CNS ionostasis. Here we overview physiological and pathophysiological aspects of astrocyte-cantered trace metals regulation.
Topics: Astrocytes; Copper; Iron; Trace Elements; Zinc
PubMed: 38199057
DOI: 10.1016/j.ceca.2024.102843 -
Internal Medicine Journal Feb 2024The first dedicated tracheobronchial silicone stent was designed by the French pulmonologist Jean-Paul Dumon. The most common indications for stenting are to minimise... (Review)
Review
The first dedicated tracheobronchial silicone stent was designed by the French pulmonologist Jean-Paul Dumon. The most common indications for stenting are to minimise extrinsic airway compression from mass effect, maintain airway patency due to intrinsic obstruction or treat significant nonmalignant airway narrowing or fistulae. Silicone stents require rigid bronchoscopy for insertion; however, they are more readily repositioned and removed compared with metallic stents. Metallic stents demonstrate luminal narrowing when loads are applied to their ends, therefore stents should either be reinforced at the ends or exceed the area of stenosis by a minimum of 5 mm. Nitinol, a nickel-titanium metal alloy, is currently the preferred material used for airway stents. Airway stenting provides effective palliation for patients with severe symptomatic obstruction. Drug-eluting and three-dimensional printing of airway stents present promising solutions to the challenges of the physical and anatomical constraints of the tracheobronchial tree. Biodegradable stents could also be a solution for the treatment of nonmalignant airway obstruction.
Topics: Humans; Bronchoscopy; Airway Obstruction; Silicones; Metals; Stents; Treatment Outcome; Nickel; Titanium
PubMed: 38140778
DOI: 10.1111/imj.16304 -
Emerging Topics in Life Sciences Feb 2024Metal ions such as zinc and copper play important roles in host-microbe interactions and their availability can drastically affect the survival of pathogenic bacteria in... (Review)
Review
Metal ions such as zinc and copper play important roles in host-microbe interactions and their availability can drastically affect the survival of pathogenic bacteria in a host niche. Mechanisms of metal homeostasis protect bacteria from starvation, or intoxication, defined as when metals are limiting, or in excess, respectively. In this mini-review, we summarise current knowledge on the mechanisms of resistance to metal stress in bacteria, focussing specifically on the homeostasis of cellular copper and zinc. This includes a summary of the factors that subvert metal stress in bacteria, which are independent of metal efflux systems, and commentary on the role of small molecules and metabolic systems as important mediators of metal resistance.
Topics: Copper; Metals; Homeostasis; Bacteria; Zinc
PubMed: 38362914
DOI: 10.1042/ETLS20230115 -
ACS Chemical Biology Sep 2023The natural product holomycin contains a unique cyclic ene-disulfide and exhibits broad-spectrum antimicrobial activities. Reduced holomycin chelates metal ions with a...
The natural product holomycin contains a unique cyclic ene-disulfide and exhibits broad-spectrum antimicrobial activities. Reduced holomycin chelates metal ions with a high affinity and disrupts metal homeostasis in the cell. To identify cellular metalloproteins inhibited by holomycin, reactive-cysteine profiling was performed using isotopic tandem orthogonal proteolysis-activity-based protein profiling (isoTOP-ABPP). This chemoproteomic analysis demonstrated that holomycin treatment increases the reactivity of metal-coordinating cysteine residues in several zinc-dependent and iron-sulfur cluster-dependent enzymes, including carbonic anhydrase II and fumarase A. We validated that holomycin inhibits fumarase A activity in bacterial cells and diminishes the presence of iron-sulfur clusters in fumarase A. Whole-proteome abundance analysis revealed that holomycin treatment induces zinc and iron starvation and cellular stress. This study suggests that holomycin inhibits bacterial growth by impairing the functions of multiple metalloenzymes and sets the stage for investigating the impact of metal-binding molecules on metalloproteomes by using chemoproteomics.
Topics: Anti-Bacterial Agents; Metalloproteins; Cysteine; Metals; Zinc; Iron; Homeostasis
PubMed: 37561838
DOI: 10.1021/acschembio.3c00360 -
Methods in Molecular Biology (Clifton,... 2024Metal-mediated ligand affinity chemistry (MLAC) enables site-specific protein modification and represents a powerful bioorthogonal strategy. Conventional bioorthogonal...
Metal-mediated ligand affinity chemistry (MLAC) enables site-specific protein modification and represents a powerful bioorthogonal strategy. Conventional bioorthogonal methods often involve two steps: (i) incorporation of the bioorthogonal handle (e.g., non-canonical amino acid, enzyme domain, peptide sequences) and (ii) the binding of functional molecules such as drugs, affinity tags, and fluorophores. This two-step protocol often involves genetic manipulation, which makes it impossible to chemically modify endogenous proteins in living systems. Thus, we propose the development of a transition metal-based chemical strategy that is ligand-directed to the endogenous protein of interest in a single step, which we refer to as metal-mediated ligand affinity chemistry (MLAC).
Topics: Ligands; Metals; Humans; Proteins; Protein Binding
PubMed: 37775659
DOI: 10.1007/978-1-0716-3469-1_6