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38 pages, 536 KB  
Review
Toward Smart Salivary Diagnostics: A Comprehensive Review of Heavy Metal Biomarkers and Digital Risk Modeling
by Claudia Florina Bogdan-Andreescu, Lucia Bubulac, Cristina-Crenguţa Albu, Dan Alexandru Slăvescu, Andreea Mariana Bănăţeanu, Oana Botoacă, Gabriela-Cornelia Muşat, Viorica Tudor, Emin Cadar and Mariana Păcurar
Diagnostics 2026, 16(4), 635; https://doi.org/10.3390/diagnostics16040635 - 22 Feb 2026
Cited by 1 | Viewed by 1165
Abstract
Background: Saliva has been identified as a valuable diagnostic biofluid due to its non-invasive collection and its capacity to reflect oral and systemic biological processes. Advances in analytical chemistry, biosensing technologies, and artificial intelligence (AI)-assisted data integration have broadened the applications of [...] Read more.
Background: Saliva has been identified as a valuable diagnostic biofluid due to its non-invasive collection and its capacity to reflect oral and systemic biological processes. Advances in analytical chemistry, biosensing technologies, and artificial intelligence (AI)-assisted data integration have broadened the applications of salivary diagnostics. Among salivary exposome components, heavy metals such as lead, cadmium, mercury, nickel, chromium, arsenic, and aluminum serve as biologically and clinically relevant indicators of environmental exposure, toxic burden, and disease-associated molecular disorders. Methods: This structured review integrates clinical, experimental, and translational studies published between January 2020 and January 2026 that examined salivary heavy metal profiling in relation to oral health. Evidence was identified using systematic searches of PubMed/MEDLINE and supplementary sources. Studies were qualitatively assessed regarding analytical methodologies, reported concentration ranges, biological mechanisms, disease associations, and the development of digital and AI-assisted diagnostic applications. Results: Thirteen human clinical studies and six animal or in vivo investigations met the inclusion criteria. Across these studies, altered salivary metal profiles were linked to oxidative stress, inflammatory signaling, immune dysregulation, microbiome disturbances, and genotoxic markers relevant to periodontal disease, oral mucosal pathology, and the risk of oral squamous cell carcinoma. Inductively coupled plasma mass spectrometry was the predominant analytical platform, while emerging biosensor technologies showed potential for rapid detection and monitoring. Digital and AI-based approaches were identified as promising tools for integrating metallomic data with clinical and molecular biomarkers to support exposure-informed risk stratification. Conclusions: Salivary heavy metal profiling represents a biologically informative, non-invasive method for exposure-aware risk assessment in oral health. Although current clinical translation is limited by methodological variability, small cohort sizes, and the lack of standardized reference ranges, integration with digital biosensing platforms and explainable AI frameworks might facilitate scalable, precision-oriented salivary diagnostics. Full article
24 pages, 3292 KB  
Review
Redox Network Dysfunction: Integrating Ferroptosis and Cuproptosis Across Human Diseases
by Federica Li Pomi, Guglielmo Di Leo, Sara Genovese, Francesco Borgia and Sebastiano Gangemi
Antioxidants 2026, 15(1), 24; https://doi.org/10.3390/antiox15010024 - 23 Dec 2025
Cited by 6 | Viewed by 1811
Abstract
Oxidative stress (OS) is increasingly recognized as a dynamic disturbance of cellular redox networks rather than a simple imbalance between oxidants and antioxidants. In this context, ferroptosis and cuproptosis—two regulated and metal-dependent forms of cell death—emerge as key mechanisms linking OS to metabolic [...] Read more.
Oxidative stress (OS) is increasingly recognized as a dynamic disturbance of cellular redox networks rather than a simple imbalance between oxidants and antioxidants. In this context, ferroptosis and cuproptosis—two regulated and metal-dependent forms of cell death—emerge as key mechanisms linking OS to metabolic dysfunction, inflammation, and tissue injury. This review integrates findings from biochemical, lipidomic and metallomic studies to describe how lipid peroxidation (LPO), glutathione (GSH)–Glutathione Peroxidase 4 (GPX4) activity, ferritinophagy, copper-induced mitochondrial protein lipoylation, and altered communication between organelles generate distinct redox signatures across diseases. By examining cutaneous, metabolic, cardiovascular, infectious, neurodegenerative, and oncologic conditions, we outline the shared redox pathways that connect iron- and copper-dependent cell death to systemic inflammation, immune dysregulation, and chronic tissue damage. Common oxidative markers—such as oxidized phospholipids, lipid aldehydes including 4-Hydroxynonenal (4-HNE) and malondialdehyde (MDA), and systemic metal imbalance—are highlighted as potential indicators of disease severity and as emerging therapeutic targets. We also discuss innovative analytical tools, including redox lipidomics, metallomic profiling and artificial-intelligence (AI)-based classification approaches, which improve the characterization of redox vulnerability and may guide the development of precision redox therapies. Overall, ferroptosis and cuproptosis represent unifying mechanisms that connect OS to multisystem disease and provide new opportunities for diagnostic refinement and targeted antioxidant-based interventions. Full article
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13 pages, 1261 KB  
Article
Metallomic Profile of Placental Tissue and Its Association with Maternal and Neonatal Parameters: A Cross-Sectional ICP-OES Study in Lower Silesia
by Aleksandra Kuzan, Emilia Królewicz, Marta Kardach, Justyna Rewak-Soroczyńska, Małgorzata Kowalska, Aldona Molęda and Rafal J. Wiglusz
Int. J. Mol. Sci. 2025, 26(24), 11985; https://doi.org/10.3390/ijms262411985 - 12 Dec 2025
Viewed by 587
Abstract
The placenta, a temporary organ that connects mother and child for nutrient and metabolite exchange, becomes medical waste after birth but can provide valuable metabolic insights. Thirty-three placenta samples were analyzed using ICP-OES to determine concentrations of ten elements, including macro-, micro-, trace, [...] Read more.
The placenta, a temporary organ that connects mother and child for nutrient and metabolite exchange, becomes medical waste after birth but can provide valuable metabolic insights. Thirty-three placenta samples were analyzed using ICP-OES to determine concentrations of ten elements, including macro-, micro-, trace, and heavy metals. Results were compared with maternal and neonatal data, including Apgar scores, maternal age, and blood parameters. Correlations were found between elements (e.g., Ca–Mg, Fe–Zn, and Mn–Cu) and between mineral levels and maternal or infant parameters (e.g., Ca–RBC, Mn–Hb, Cu–PLT, and Cu–UA Pi). No quantifiable heavy metals were detected, nor associations with smoking, gestational diabetes, preterm birth, birth weight, or Apgar scores. Findings suggest that maintaining proper blood morphology and preventing anemia in pregnancy requires attention not only to iron but also to Ca2+, Mg2+, and Mn2+ levels. Manganese and copper assessment may be beneficial for diagnostic purposes in pregnant women. Further large-scale tissue studies are recommended, including comprehensive maternal–fetal health data such as Doppler velocimetry of placental vessels. Full article
(This article belongs to the Special Issue Metals and Metal Ions in Human Health, Diseases, and Environment)
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15 pages, 867 KB  
Article
Diagnostic Stratification of Pancreatic Ductal Adenocarcinoma via Metallomics and Blood-Based Biomarkers
by Donatella Coradduzza, Teresa Perra, Leonardo Sibono, Andrea Sanna, Maurizio Cossu, Emanuela G. Azara, Francesco Petracca, Roberto Beniamino Madeddu, Maria Rosaria De Miglio, Ciriaco Carru, Massimiliano Grosso, Maria Laura Cossu and Serenella Medici
Diagnostics 2025, 15(21), 2818; https://doi.org/10.3390/diagnostics15212818 - 6 Nov 2025
Cited by 1 | Viewed by 1081
Abstract
Background: Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest cancers, largely due to late diagnosis and the lack of reliable non-invasive biomarkers. Altered trace element homeostasis has been implicated in tumor biology and systemic inflammation, but comprehensive metallomic profiling in PDAC is [...] Read more.
Background: Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest cancers, largely due to late diagnosis and the lack of reliable non-invasive biomarkers. Altered trace element homeostasis has been implicated in tumor biology and systemic inflammation, but comprehensive metallomic profiling in PDAC is still limited. Methods: Using inductively coupled plasma mass spectrometry (ICP-MS), we quantified 20 serum and 15 urinary metals in 71 PDAC patients and 69 matched controls. Statistical analyses included univariate Wilcoxon testing, correlation with systemic inflammatory indices (NLR, MLR, SIRI, AISI, HGB/RDW, PCT), and multivariate chemometric modeling (PCA-LDA). K-means clustering was applied to identify patient subgroups with distinct biochemical signatures. Results: PDAC patients showed significantly elevated urinary antimony, chromium, cadmium, and vanadium, whereas controls exhibited higher serum selenium, zinc, barium, vanadium, and cobalt (all p < 10−5). The PCA-LDA model achieved 99% classification accuracy (Monte Carlo cross-validation, 1000 iterations), highlighting complementary diagnostic contributions of serum and urinary profiles. Serum selenium was inversely associated with SIRI and NLR, while urinary cobalt correlated positively with NLR. Clustering revealed three PDAC subgroups with different inflammatory and metallomic patterns, suggesting underlying biological heterogeneity. Conclusions: PDAC is characterized by opposite serum-urine metal signatures, indicating altered absorption-excretion dynamics. Selenium depletion may represent a protective biomarker, whereas urinary cobalt excretion reflects systemic inflammation. This integrative ICP-MS–chemometric approach provides a promising diagnostic tool for improving early detection and patient stratification in clinical practice. Full article
(This article belongs to the Special Issue Biochemical Testing Applications in Clinical Diagnosis)
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14 pages, 1065 KB  
Article
An Innovative Multi-Omics Approach Reveals the Interactions Between Honeybees and Their Environment
by Cecilia Rudelli, Elisa Bellei, Giulia Andreani and Gloria Isani
Animals 2025, 15(18), 2660; https://doi.org/10.3390/ani15182660 - 11 Sep 2025
Cited by 3 | Viewed by 957
Abstract
Although traditional methods of evaluating colony health provide a general overview, they are often subjective and imprecise. Therefore, a more integrative approach is needed. The aim of this study is to use a multi-omics strategy—combining proteomic and metallomic approaches—to evaluate the interactions between [...] Read more.
Although traditional methods of evaluating colony health provide a general overview, they are often subjective and imprecise. Therefore, a more integrative approach is needed. The aim of this study is to use a multi-omics strategy—combining proteomic and metallomic approaches—to evaluate the interactions between honeybees and their environment. Two apiaries were selected for the study: apiary A, which is located in an extensive agricultural landscape, and apiary M, which is located in a less anthropized environment. The distribution of honeybee soluble proteins and small biomolecules was analyzed using size-exclusion chromatography. These profiles varied significantly between sampling times and apiaries. During spring, a reduced high molecular mass protein peak and an elevated very low molecular mass molecules peak were observed in honeybees from apiary A. Hemolymph analysis corroborated these findings, showing a depletion of key nutritional proteins, such as vitellogenin and apolipophorin in this apiary during the same season. In addition to protein distribution, we studied also the speciation of zinc and copper using chromatographic and atomic absorption techniques. Our results indicate site and season-dependent variation in metal binding profiles, with evidence for the presence of metallothionein-like proteins capable of binding both copper and zinc. This study highlights the urgent need for integrated, multi-method research to understand the complex dynamics of honeybee health and emphasizes the fundamental role of agricultural practices in ensuring the health of honeybees. Full article
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25 pages, 623 KB  
Review
Metallomic Profiling of the Human Eye and Its Relevance to Ophthalmic Diseases
by Alicja Forma, Andrzej Torbicz, Grzegorz Teresiński, Ryszard Maciejewski and Jacek Baj
Appl. Sci. 2025, 15(16), 8934; https://doi.org/10.3390/app15168934 - 13 Aug 2025
Cited by 2 | Viewed by 1650
Abstract
Levels of micro- and macroelements in the human organism change dynamically and undoubtedly remain critical for human health. Currently, much research is focused on searching for the concentrations of various metals (including toxic ones) in the tissues obtained from patients suffering from various [...] Read more.
Levels of micro- and macroelements in the human organism change dynamically and undoubtedly remain critical for human health. Currently, much research is focused on searching for the concentrations of various metals (including toxic ones) in the tissues obtained from patients suffering from various diseases including ophthalmic diseases. However, the knowledge in this matter is still scarce and highly limited. Previous studies related to the changes in the levels of micro- and macroelements within the morphological elements of the eye and visual tract were performed on animal models in most cases, and only for the chosen elements. In addition, the majority of the studies performed on human samples were mostly focused only on the group of patients with chosen ophthalmic diseases such as glaucoma or cataracts. Moreover, usually, the results of the studies are contradictory, and some hypotheses are still unexplained. The understanding of the physiology and pathophysiology of the processes that lead to the changes in the distribution of the levels of micro- and macroelements that are crucial in the etiology of ophthalmic diseases might provide more effective prevention and better therapeutic strategies, or even improvements in the treatment of chosen ophthalmic diseases. In this paper, we summarized the current knowledge regarding the metallomic analysis of the human organ of vision and its relationship with chosen ophthalmic diseases. Full article
(This article belongs to the Special Issue Exposure Pathways and Health Implications of Environmental Chemicals)
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14 pages, 3286 KB  
Article
The Impact of Hydroxytyrosol on the Metallomic-Profile in an Animal Model of Alzheimer’s Disease
by Miguel Tabanez, Ilma R. Santos, Juliane M. Ikebara, Mariana L. M. Camargo, Bianca A. Dos Santos, Bruna M. Freire, Bruno L. Batista, Silvia H. Takada, Rosanna Squitti, Alexandre H. Kihara and Giselle Cerchiaro
Int. J. Mol. Sci. 2023, 24(19), 14950; https://doi.org/10.3390/ijms241914950 - 6 Oct 2023
Cited by 15 | Viewed by 2841
Abstract
It is undeniable that as people get older, they become progressively more susceptible to neurodegenerative illnesses such as Alzheimer’s disease (AD). Memory loss is a prominent symptom of this condition and can be exacerbated by uneven levels of certain metals. This study used [...] Read more.
It is undeniable that as people get older, they become progressively more susceptible to neurodegenerative illnesses such as Alzheimer’s disease (AD). Memory loss is a prominent symptom of this condition and can be exacerbated by uneven levels of certain metals. This study used inductively coupled plasma mass spectrometry (ICP-MS) to examine the levels of metals in the blood plasma, frontal cortex, and hippocampus of Wistar rats with AD induced by streptozotocin (STZ). It also tested the effects of the antioxidant hydroxytyrosol (HT) on metal levels. The Barnes maze behavior test was used, and the STZ group showed less certainty and greater distance when exploring the Barnes maze than the control group. The results also indicated that the control group and the STZ + HT group exhibited enhanced learning curves during the Barnes maze training as compared to the STZ group. The ICP-MS analysis showed that the STZ group had lower levels of cobalt in their blood plasma than the control group, while the calcium levels in the frontal cortex of the STZ + HT group were higher than in the control group. The most important finding was that copper levels in the frontal cortex from STZ-treated animals were higher than in the control group, and that the STZ + HT group returned to equivalent levels to the control group. The antioxidant HT can restore copper levels to their basal physiological state. This finding may help explain HT’s potential beneficial effect in AD-patients. Full article
(This article belongs to the Special Issue Essential Metals in Neurological Diseases and Cancer)
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14 pages, 3493 KB  
Article
Metallomic Signatures of Lung Cancer and Chronic Obstructive Pulmonary Disease
by Belén Callejón-Leblic, Saida Sánchez Espirilla, Carolina Gotera-Rivera, Rafael Santana, Isabel Díaz-Olivares, José M. Marín, Ciro Casanova Macario, Borja García Cosio, Antonia Fuster, Ingrid Solanes García, Juan P. de-Torres, Nuria Feu Collado, Carlos Cabrera Lopez, Carlos Amado Diago, Amparo Romero Plaza, Luis Alejandro Padrón Fraysse, Eduardo Márquez Martín, Margarita Marín Royo, Eva Balcells Vilarnau, Antonia Llunell Casanovas, Cristina Martínez González, Juan Bautista Galdíz Iturri, Celia Lacárcel Bautista, José Luis Gómez-Ariza, Antonio Pereira-Vega, Luis Seijo, José Luis López-Campos, Germán Peces-Barba and Tamara García-Barreraadd Show full author list remove Hide full author list
Int. J. Mol. Sci. 2023, 24(18), 14250; https://doi.org/10.3390/ijms241814250 - 18 Sep 2023
Cited by 6 | Viewed by 2888
Abstract
Lung cancer (LC) is the leading cause of cancer deaths, and chronic obstructive pulmonary disease (COPD) can increase LC risk. Metallomics may provide insights into both of these tobacco-related diseases and their shared etiology. We conducted an observational study of 191 human serum [...] Read more.
Lung cancer (LC) is the leading cause of cancer deaths, and chronic obstructive pulmonary disease (COPD) can increase LC risk. Metallomics may provide insights into both of these tobacco-related diseases and their shared etiology. We conducted an observational study of 191 human serum samples, including those of healthy controls, LC patients, COPD patients, and patients with both COPD and LC. We found 18 elements (V, Al, As, Mn, Co, Cu, Zn, Cd, Se, W, Mo, Sb, Pb, Tl, Cr, Mg, Ni, and U) in these samples. In addition, we evaluated the elemental profiles of COPD cases of varying severity. The ratios and associations between the elements were also studied as possible signatures of the diseases. COPD severity and LC have a significant impact on the elemental composition of human serum. The severity of COPD was found to reduce the serum concentrations of As, Cd, and Tl and increased the serum concentrations of Mn and Sb compared with healthy control samples, while LC was found to increase Al, As, Mn, and Pb concentrations. This study provides new insights into the effects of LC and COPD on the human serum elemental profile that will pave the way for the potential use of elements as biomarkers for diagnosis and prognosis. It also sheds light on the potential link between the two diseases, i.e., the evolution of COPD to LC. Full article
(This article belongs to the Special Issue Metals and Cancer)
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11 pages, 564 KB  
Article
Metal Homeostasis and Exposure in Distinct Phenotypic Subtypes of Insulin Resistance among Children with Obesity
by Álvaro González-Domínguez, María Millán-Martínez, Jesús Domínguez-Riscart, Alfonso María Lechuga-Sancho and Raúl González-Domínguez
Nutrients 2023, 15(10), 2347; https://doi.org/10.3390/nu15102347 - 17 May 2023
Cited by 16 | Viewed by 2740
Abstract
Background: Trace elements and heavy metals have proven pivotal roles in childhood obesity and insulin resistance. However, growing evidence suggests that insulin resistance could encompass distinct phenotypic subtypes. Methods: Herein, we performed a comprehensive metallomics characterization of plasma samples from children and adolescents [...] Read more.
Background: Trace elements and heavy metals have proven pivotal roles in childhood obesity and insulin resistance. However, growing evidence suggests that insulin resistance could encompass distinct phenotypic subtypes. Methods: Herein, we performed a comprehensive metallomics characterization of plasma samples from children and adolescents with obesity and concomitant insulin resistance, who were stratified as early (N = 17, 11.4 ± 2.4 years), middle (N = 16, 11.8 ± 1.9 years), and late (N = 33, 11.7 ± 2.0 years) responders according to the insulin secretion profile in response to an oral glucose tolerance test. To this end, we employed a high-throughput method aimed at determining the biodistribution of various essential and toxic elements by analyzing total metal contents, metal-containing proteins, and labile metal species. Results: Compared with the early responders, participants with delayed glucose-induced hyperinsulinemia showed a worsened insulin resistance (HOMA-IR, 4.5 vs. 3.8) and lipid profile (total cholesterol, 160 vs. 144 mg/dL; LDL-cholesterol, 99 vs. 82 mg/dL), which in turn was accompanied by sharpened disturbances in the levels of plasmatic proteins containing chromium (4.8 vs. 5.1 µg/L), cobalt (0.79 vs. 1.2 µg/L), lead (0.021 vs. 0.025 µg/L), and arsenic (0.077 vs. 0.17 µg/L). A correlation analysis demonstrated a close inter-relationship among these multielemental perturbations and the characteristic metabolic complications occurring in childhood obesity, namely impaired insulin-mediated metabolism of carbohydrates and lipids. Conclusions: These findings highlight the crucial involvement that altered metal homeostasis and exposure may have in regulating insulin signaling, glucose metabolism, and dyslipidemia in childhood obesity. Full article
(This article belongs to the Special Issue Bioactive Compounds and Metabolic Disease)
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14 pages, 1385 KB  
Article
Tear nanoDSF Denaturation Profile Is Predictive of Glaucoma
by Viktoriia E. Baksheeva, Veronika V. Tiulina, Elena N. Iomdina, Sergey Yu. Petrov, Olga M. Filippova, Nina Yu. Kushnarevich, Elena A. Suleiman, Rémi Eyraud, François Devred, Marina V. Serebryakova, Natalia G. Shebardina, Dmitry V. Chistyakov, Ivan I. Senin, Vladimir A. Mitkevich, Philipp O. Tsvetkov and Evgeni Yu. Zernii
Int. J. Mol. Sci. 2023, 24(8), 7132; https://doi.org/10.3390/ijms24087132 - 12 Apr 2023
Cited by 8 | Viewed by 4629
Abstract
Primary open-angle glaucoma (POAG) is a frequent blindness-causing neurodegenerative disorder characterized by optic nerve and retinal ganglion cell damage most commonly due to a chronic increase in intraocular pressure. The preservation of visual function in patients critically depends on the timeliness of detection [...] Read more.
Primary open-angle glaucoma (POAG) is a frequent blindness-causing neurodegenerative disorder characterized by optic nerve and retinal ganglion cell damage most commonly due to a chronic increase in intraocular pressure. The preservation of visual function in patients critically depends on the timeliness of detection and treatment of the disease, which is challenging due to its asymptomatic course at early stages and lack of objective diagnostic approaches. Recent studies revealed that the pathophysiology of glaucoma includes complex metabolomic and proteomic alterations in the eye liquids, including tear fluid (TF). Although TF can be collected by a non-invasive procedure and may serve as a source of the appropriate biomarkers, its multi-omics analysis is technically sophisticated and unsuitable for clinical practice. In this study, we tested a novel concept of glaucoma diagnostics based on the rapid high-performance analysis of the TF proteome by differential scanning fluorimetry (nanoDSF). An examination of the thermal denaturation of TF proteins in a cohort of 311 ophthalmic patients revealed typical profiles, with two peaks exhibiting characteristic shifts in POAG. Clustering of the profiles according to peaks maxima allowed us to identify glaucoma in 70% of cases, while the employment of artificial intelligence (machine learning) algorithms reduced the amount of false-positive diagnoses to 13.5%. The POAG-associated alterations in the core TF proteins included an increase in the concentration of serum albumin, accompanied by a decrease in lysozyme C, lipocalin-1, and lactotransferrin contents. Unexpectedly, these changes were not the only factor affecting the observed denaturation profile shifts, which considerably depended on the presence of low-molecular-weight ligands of tear proteins, such as fatty acids and iron. Overall, we recognized the TF denaturation profile as a novel biomarker of glaucoma, which integrates proteomic, lipidomic, and metallomic alterations in tears, and monitoring of which could be adapted for rapid non-invasive screening of the disease in a clinical setting. Full article
(This article belongs to the Special Issue Molecular Research of Ocular Pathology)
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24 pages, 3287 KB  
Article
Multi-Omics Investigation into Acute Myocardial Infarction: An Integrative Method Revealing Interconnections amongst the Metabolome, Lipidome, Glycome, and Metallome
by Si Ying Lim, Felicia Li Shea Lim, Inmaculada Criado-Navarro, Xin Hao Yeo, Hiranya Dayal, Sri Dhruti Vemulapalli, Song Jie Seah, Anna Karen Carrasco Laserna, Xiaoxun Yang, Sock Hwee Tan, Mark Y. Chan and Sam Fong Yau Li
Metabolites 2022, 12(11), 1080; https://doi.org/10.3390/metabo12111080 - 8 Nov 2022
Cited by 14 | Viewed by 4077
Abstract
Acute myocardial infarction (AMI) is a leading cause of mortality and morbidity worldwide. This work aims to investigate the translational potential of a multi-omics study (comprising metabolomics, lipidomics, glycomics, and metallomics) in revealing biomechanistic insights into AMI. Following the N-glycomics and metallomics studies [...] Read more.
Acute myocardial infarction (AMI) is a leading cause of mortality and morbidity worldwide. This work aims to investigate the translational potential of a multi-omics study (comprising metabolomics, lipidomics, glycomics, and metallomics) in revealing biomechanistic insights into AMI. Following the N-glycomics and metallomics studies performed by our group previously, untargeted metabolomic and lipidomic profiles were generated and analysed in this work via the use of a simultaneous metabolite/lipid extraction and liquid chromatography–tandem mass spectrometry (LC–MS/MS) analysis workflow. The workflow was applied to blood plasma samples from AMI cases (n = 101) and age-matched healthy controls (n = 66). The annotated metabolomic (number of features, n = 27) and lipidomic (n = 48) profiles, along with the glycomic (n = 37) and metallomic (n = 30) profiles of the same set of AMI and healthy samples were integrated and analysed. The integration method used here works by identifying a linear combination of maximally correlated features across the four omics datasets, via utilising both block-partial least squares-discriminant analysis (block-PLS-DA) based on sparse generalised canonical correlation analysis. Based on the multi-omics mapping of biomolecular interconnections, several postulations were derived. These include the potential roles of glycerophospholipids in N-glycan-modulated immunoregulatory effects, as well as the augmentation of the importance of Ca–ATPases in cardiovascular conditions, while also suggesting contributions of phosphatidylethanolamine in their functions. Moreover, it was shown that combining the four omics datasets synergistically enhanced the classifier performance in discriminating between AMI and healthy subjects. Fresh and intriguing insights into AMI, otherwise undetected via single-omics analysis, were revealed in this multi-omics study. Taken together, we provide evidence that a multi-omics strategy may synergistically reinforce and enhance our understanding of diseases. Full article
(This article belongs to the Section Integrative Metabolomics)
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14 pages, 1173 KB  
Article
Quercetin and Egg Metallome
by Evangelos Zoidis, Athanasios C. Pappas, Michael Goliomytis, Panagiotis E. Simitzis, Kyriaki Sotirakoglou, Savvina Tavrizelou, George Danezis and Constantinos A. Georgiou
Antioxidants 2021, 10(1), 80; https://doi.org/10.3390/antiox10010080 - 9 Jan 2021
Cited by 14 | Viewed by 3692
Abstract
The objective of the present study was to investigate the effect of the natural flavonoid quercetin dietary supplementation on the alteration of egg metallome by applying the basic principles of elemental metabolomics. One hundred and ninety-two laying hens were allocated into 4 treatment [...] Read more.
The objective of the present study was to investigate the effect of the natural flavonoid quercetin dietary supplementation on the alteration of egg metallome by applying the basic principles of elemental metabolomics. One hundred and ninety-two laying hens were allocated into 4 treatment groups: the control (C) group that was fed with a commercial basal diet and the other experimental groups that were offered the same diet further supplemented with quercetin at 200, 400 and 800 mg per kg of feed (Q2, Q4 and Q8 group, respectively) for 28 days. The diets contained the same vitamin and mineral premix, thus all birds received the same amount of elements since no differences on feed intake existed. The egg elemental profile consisted of As, Ca, Cd, Co, Cr, Cu, Fe, Mg, Mn, Mo, Ni, Pb, Sb, Se, Sr, V, Zn and was determined using inductively coupled plasma mass spectrometry (ICP-MS). Quercetin supplementation altered the elemental profile. Most notably, quercetin altered the element concentrations predominantly in egg shell and albumen. It increased the concentration of Sb while reduced that of Cr and Se in both egg shell and albumen. Moreover, it increased As, Cd in albumen and V in yolk, while compared to the control, reduced As, Cd, Cr, Cu and V and also raised Ca, Fe, Mg and Ni in egg shell. The presence of quercetin led to differentiation of the deposition of certain trace minerals in egg compartments compared to that of hens fed a basal diet, possibly indicating that tailor made eggs for specific nutritional and health requirements could be created in the future. Full article
(This article belongs to the Special Issue The Potential of Dietary Antioxidants)
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18 pages, 5691 KB  
Article
Tracking of Glycans Structure and Metallomics Profiles in BRAF Mutated Melanoma Cells Treated with Vemurafenib
by Monika K. Nisiewicz, Agata Kowalczyk, Anna Sobiepanek, Agata Jagielska, Barbara Wagner, Julita Nowakowska, Marianna Gniadek, Ireneusz P. Grudzinski, Tomasz Kobiela and Anna M. Nowicka
Int. J. Mol. Sci. 2021, 22(1), 439; https://doi.org/10.3390/ijms22010439 - 4 Jan 2021
Cited by 2 | Viewed by 4113
Abstract
Nearly half of patients with advanced and metastatic melanomas harbor a BRAF mutation. Vemurafenib (VEM), a BRAF inhibitor, is used to treat such patients, however, responses to VEM are very short-lived due to intrinsic, adaptive and/or acquired resistance. In this context, we present [...] Read more.
Nearly half of patients with advanced and metastatic melanomas harbor a BRAF mutation. Vemurafenib (VEM), a BRAF inhibitor, is used to treat such patients, however, responses to VEM are very short-lived due to intrinsic, adaptive and/or acquired resistance. In this context, we present the action of the B-Raf serine-threonine protein kinase inhibitor (vemurafenib) on the glycans structure and metallomics profiles in melanoma cells without (MeWo) and with (G-361) BRAF mutations. The studies were performed using α1-acid glycoprotein (AGP), a well-known acute-phase protein, and concanavalin A (Con A), which served as the model receptor. The detection of changes in the structure of glycans can be successfully carried out based on the frequency shifts and the charge transfer resistance after interaction of AGP with Con A in different VEM treatments using QCM-D and EIS measurements. These changes were also proved based on the cell ultrastructure examined by TEM and SEM. The LA-ICP-MS studies provided details on the metallomics profile in melanoma cells treated with and without VEM. The studies evidence that vemurafenib modifies the glycans structures and metallomics profile in melanoma cells harboring BRAF mutation that can be further implied in the resistance phenomenon. Therefore, our data opens a new avenue for further studies in the short-term addressing novel targets that hopefully can be used to improve the therapeutic regiment in advanced melanoma patients. The innovating potential of this study is fully credible and has a real impact on the global patient society suffering from advanced and metastatic melanomas. Full article
(This article belongs to the Section Molecular Biology)
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15 pages, 1009 KB  
Article
Elemental Metabolomics: Modulation of Egg Metallome with Flavonoids, an Exploratory Study
by Athanasios C. Pappas, Evangelos Zoidis, Michael Goliomytis, Panagiotis E. Simitzis, Kyriaki Sotirakoglou, Maria A. Charismiadou, Christos Nikitas, George Danezis, Stelios G. Deligeorgis and Constantinos A. Georgiou
Antioxidants 2019, 8(9), 361; https://doi.org/10.3390/antiox8090361 - 1 Sep 2019
Cited by 8 | Viewed by 3904
Abstract
The basic principles of elemental metabolomics were applied to investigate whether alteration of egg metallome could be achieved after two flavonoids addition, namely hesperidin and naringin in diets of laying hens. A total of 72 hens were divided into six groups: Control (C) [...] Read more.
The basic principles of elemental metabolomics were applied to investigate whether alteration of egg metallome could be achieved after two flavonoids addition, namely hesperidin and naringin in diets of laying hens. A total of 72 hens were divided into six groups: Control (C) (basal diet), E1 (750 mg hesperidin/kg diet), E2 (1500 mg hesperidin/kg diet), N1 (750 mg naringin/kg diet), N2 (1500 mg naringin/kg diet), and VE (200 mg vitamin E/kg diet). The same diet was provided to birds of all treatments, with the exception of added supplements. The diets had the same vitamin and mineral premix; thus, all birds received the same number of elements because no differences on feed intake existed. The egg elemental profile consisted of As, Ca, Cd, Co, Cr, Cu, Fe, Mg, Mn, Mo, Ni, Pb, Sb, Se, Sr, V, Zn, and was determined using ICP-MS. Flavonoid supplementation altered the elemental profile. Most notably, in both albumen and yolk, hesperidin increased Ni, Pb, and Sr concentration while it decreased that of Co and Sb. Naringin increased Cd, Cr, Cu, Ni, and V and lowered the concentration of Co and Sb in both yolk and albumen. Vitamin E supplementation, in comparison to the control, decreased Co in both albumen and yolk and also raised Sb in albumen. Flavonoid presence led to the differences in deposition of certain trace minerals in egg compared to that of hens fed a basal diet or a diet with vitamin E supplementation. Full article
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Review
The Metallome of Lung Cancer and its Potential Use as Biomarker
by Belén Callejón-Leblic, Ana Arias-Borrego, Antonio Pereira-Vega, José Luis Gómez-Ariza and Tamara García-Barrera
Int. J. Mol. Sci. 2019, 20(3), 778; https://doi.org/10.3390/ijms20030778 - 12 Feb 2019
Cited by 23 | Viewed by 5709
Abstract
Carcinogenesis is a very complex process in which metals have been found to be critically involved. In this sense, a disturbed redox status and metal dyshomeostasis take place during the onset and progression of cancer, and it is well-known that trace elements participate [...] Read more.
Carcinogenesis is a very complex process in which metals have been found to be critically involved. In this sense, a disturbed redox status and metal dyshomeostasis take place during the onset and progression of cancer, and it is well-known that trace elements participate in the activation or inhibition of enzymatic reactions and metalloproteins, in which they usually participate as cofactors. Until now, the role of metals in cancer have been studied as an effect, establishing that cancer onset and progression affects the disturbance of the natural chemical form of the essential elements in the metabolism. However, it has also been studied as a cause, giving insights related to the high exposure of metals giving a place to the carcinogenic process. On the other hand, the chemical species of the metal or metallobiomolecule is very important, since it finally affects the biological activity or the toxicological potential of the element and their mobility across different biological compartments. Moreover, the importance of metal homeostasis and metals interactions in biology has also been demonstrated, and the ratios between some elements were found to be different in cancer patients; however, the interplay of elements is rarely reported. This review focuses on the critical role of metals in lung cancer, which is one of the most insidious forms of cancer, with special attention to the analytical approaches and pitfalls to extract metals and their species from tissues and biofluids, determining the ratios of metals, obtaining classification profiles, and finally defining the metallome of lung cancer. Full article
(This article belongs to the Special Issue Metallomics: Integrated Biosciences for Elements)
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