Selenium (Se) is an essential trace element required by the human body, existing in selenium proteins as selenocysteine (Sec) and selenomethionine (SeMet). Through these proteins, Se exerts its biological effects such as free radical metabolism, antioxidant functions, immune response, reproductive functions, apoptosis, and endocrine hormone regulation. Both selenium deficiency and excess are can cause adverse effects on human health. A growing number of evidence highlights the involvement of selenium and its proteins in the development and progression of cardiovascular diseases (CVD). During hypoxia, the body undergoes a series of changes across all organ systems. Among these, the heart, lungs, and brain—due to their high oxygen demand and metabolic activity—demonstrate particularly prominent manifestations of injury. This review summarizes the effects of selenium/selenoproteins on the cardiovascular system, emphasizing new findings on their roles in hypoxic cardiorespiratory injury. This is to provide a scientific basis for preventing and treating high-altitude illnesses from both environmental and nutritional perspectives.
{"title":"Cardiopulmonary injury in hypoxia and selenium: A review","authors":"Lekang Han , Ting Huang , Zhongzhi Zhao , Zhancui Dang","doi":"10.1016/j.jtemb.2025.127767","DOIUrl":"10.1016/j.jtemb.2025.127767","url":null,"abstract":"<div><div>Selenium (Se) is an essential trace element required by the human body, existing in selenium proteins as selenocysteine (Sec) and selenomethionine (SeMet). Through these proteins, Se exerts its biological effects such as free radical metabolism, antioxidant functions, immune response, reproductive functions, apoptosis, and endocrine hormone regulation. Both selenium deficiency and excess are can cause adverse effects on human health. A growing number of evidence highlights the involvement of selenium and its proteins in the development and progression of cardiovascular diseases (CVD). During hypoxia, the body undergoes a series of changes across all organ systems. Among these, the heart, lungs, and brain—due to their high oxygen demand and metabolic activity—demonstrate particularly prominent manifestations of injury. This review summarizes the effects of selenium/selenoproteins on the cardiovascular system, emphasizing new findings on their roles in hypoxic cardiorespiratory injury. This is to provide a scientific basis for preventing and treating high-altitude illnesses from both environmental and nutritional perspectives.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"92 ","pages":"Article 127767"},"PeriodicalIF":3.6,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145159393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-24DOI: 10.1016/j.jtemb.2025.127765
Teresa Urbano , Tommaso Filippini , Barbara R. Cardoso , Lauren A. Wise , Giovanna Zamboni , Annalisa Chiari , Giulia Vinceti , Manuela Tondelli , Alessandro Marti , Marcella Malavolti , Marco Vinceti , Bernhard Michalke
Background
The validity of biomarkers to estimate exposure to selenium (Se) species and selenoproteins in the central nervous system (CNS) is not well studied.
Methods
Among 83 Italian participants with mild cognitive impairment, we estimated total Se and single Se species concentrations in paired serum and cerebrospinal fluid (CSF) samples using anion exchange chromatography-inductively coupled plasma-dynamic reaction cell-mass spectrometry. In each matrix (serum and CSF), we assessed associations between: 1) paired Se species and 2) total Se and Se species.
Results
The distribution of Se exposure was comparable to that generally found in European populations. We found few consistent patterns for most biomarkers, including total Se and some Se species. An exception was a positive association between the two matrices for selenoprotein-P-bound Se and the inorganic Se form selenate, and an unexpected inverse association for glutathione-peroxidase-bound Se. Total Se was positively associated with some Se species but inversely associated with other Se species in serum, while in CSF the positive association was stronger and more consistent across various Se species.
Conclusions
Concentrations of total Se and single Se species in serum were not strongly correlated with their respective concentrations in CSF, the gold standard to estimate CNS exposure. Furthermore, total Se and selected Se species showed consistent positive correlations within CSF but not serum. Our results suggest that relying on serum Se concentrations to assess CNS exposure can introduce error in human studies.
{"title":"Biomarkers of total selenium and selenium species in paired serum and cerebrospinal fluid samples","authors":"Teresa Urbano , Tommaso Filippini , Barbara R. Cardoso , Lauren A. Wise , Giovanna Zamboni , Annalisa Chiari , Giulia Vinceti , Manuela Tondelli , Alessandro Marti , Marcella Malavolti , Marco Vinceti , Bernhard Michalke","doi":"10.1016/j.jtemb.2025.127765","DOIUrl":"10.1016/j.jtemb.2025.127765","url":null,"abstract":"<div><h3>Background</h3><div>The validity of biomarkers to estimate exposure to selenium (Se) species and selenoproteins in the central nervous system (CNS) is not well studied.</div></div><div><h3>Methods</h3><div>Among 83 Italian participants with mild cognitive impairment, we estimated total Se and single Se species concentrations in paired serum and cerebrospinal fluid (CSF) samples using anion exchange chromatography-inductively coupled plasma-dynamic reaction cell-mass spectrometry. In each matrix (serum and CSF), we assessed associations between: 1) paired Se species and 2) total Se and Se species.</div></div><div><h3>Results</h3><div>The distribution of Se exposure was comparable to that generally found in European populations. We found few consistent patterns for most biomarkers, including total Se and some Se species. An exception was a positive association between the two matrices for selenoprotein-P-bound Se and the inorganic Se form selenate, and an unexpected inverse association for glutathione-peroxidase-bound Se. Total Se was positively associated with some Se species but inversely associated with other Se species in serum, while in CSF the positive association was stronger and more consistent across various Se species.</div></div><div><h3>Conclusions</h3><div>Concentrations of total Se and single Se species in serum were not strongly correlated with their respective concentrations in CSF, the gold standard to estimate CNS exposure. Furthermore, total Se and selected Se species showed consistent positive correlations within CSF but not serum. Our results suggest that relying on serum Se concentrations to assess CNS exposure can introduce error in human studies.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"92 ","pages":"Article 127765"},"PeriodicalIF":3.6,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145159460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-23DOI: 10.1016/j.jtemb.2025.127763
Hesham M. Hassan , Aqsa Bibi , Muhammad Faisal Hayat , Khalid J. Alzahrani , Fuad M. Alzahrani , Meshari A. Alsuwat , Maha A. Al-Aream
Background
Sodium arsenite (SA) is a potent carcinogenic compound which is evident to prompt multiple organs damage including the heart. Azaleatin (AZA) is a novel therapeutic agent with excellent biological properties.
Objectives
The current investigation was executed to evaluate the mitigative efficacy of AZA against SA induced sub-chronic cardiotoxicity in rats through the evaluation of biochemical and histological parameters.
Methodology
Thirty-two rats were apportioned into control, SA (10 mg kg−1), SA (10 mg kg−1) + AZA (25 mg kg−1), and AZA (25 mg kg−1) exposed group. Biochemical parameters were evaluated through different techniques including qRT-PCR, ELISA and already reported standard assays. Histological analysis was performed to validate the tissue damage. The curative potential of AZA was re-validated through in-silico approaches.
Findings
SA intoxication upregulated the expression of nuclear factor-kappa B (NF-κB), myeloid differentiation primary response 88 (MyD88), janus kinase 1 (JAK1), toll-like receptor 4 (TLR4), tumor necrosis factor-α (TNF-α), signal transducer and activator of transcription 3 (STAT3), interleukin-1β (IL-1β), interleukin-6 (IL-6), & cyclooxygenase-2 (COX-2) while increasing the levels of reactive oxygen species (ROS) and malondialdehyde (MDA). Moreover, the enzymatic activities glutathione peroxidase (GPx), glutathione reductase (GSR), glutathione S-transferase (GST), superoxide dismutase (SOD), catalase (CAT), heme-oxygenase-1 (HO-1) and glutathione (GSH) were lowered whereas the levels of Troponin I, ProBNP, C-reactive protein, LDH, troponin-T, BNP and CPK were exacerbated following the SA exposure. Furthermore, SA intoxication promoted the levels of Bax, Caspase-9, and Caspase-3 while lowering the levels of Bcl-2. Cardiac tissues showed impaired histology after SA administration. Nonetheless, AZA therapy excellently ameliorated cardiac toxicity owing to its anti-inflammatory, antioxidative and anti-apoptotic potential.
Conclusion
SA intoxication induced severe cardiac toxicity via disrupting biochemical and histological parameters while AZA excellently restored cardiac health profile. Collectively, AZA may serve as a cardioprotective agent in counteracting SA induced sub-chronic cardiotoxicity.
{"title":"Cardioprotective potential of azaleatin against sodium arsenite instigated sub-chronic cardiotoxicity via targeting TLR4/MyD88, JAK1/STAT3, and NF-κB in Sprague Dawley rats","authors":"Hesham M. Hassan , Aqsa Bibi , Muhammad Faisal Hayat , Khalid J. Alzahrani , Fuad M. Alzahrani , Meshari A. Alsuwat , Maha A. Al-Aream","doi":"10.1016/j.jtemb.2025.127763","DOIUrl":"10.1016/j.jtemb.2025.127763","url":null,"abstract":"<div><h3>Background</h3><div>Sodium arsenite (SA) is a potent carcinogenic compound which is evident to prompt multiple organs damage including the heart. Azaleatin (AZA) is a novel therapeutic agent with excellent biological properties.</div></div><div><h3>Objectives</h3><div>The current investigation was executed to evaluate the mitigative efficacy of AZA against SA induced sub-chronic cardiotoxicity in rats through the evaluation of biochemical and histological parameters.</div></div><div><h3>Methodology</h3><div>Thirty-two rats were apportioned into control, SA (10 mg kg<sup>−1</sup>), SA (10 mg kg<sup>−1</sup>) + AZA (25 mg kg<sup>−1</sup>), and AZA (25 mg kg<sup>−1</sup>) exposed group. Biochemical parameters were evaluated through different techniques including qRT-PCR, ELISA and already reported standard assays. Histological analysis was performed to validate the tissue damage. The curative potential of AZA was re-validated through in-silico approaches.</div></div><div><h3>Findings</h3><div>SA intoxication upregulated the expression of nuclear factor-kappa B (NF-κB), myeloid differentiation primary response 88 (MyD88), janus kinase 1 (JAK1), toll-like receptor 4 (TLR4), tumor necrosis factor-α (TNF-α), signal transducer and activator of transcription 3 (STAT3), interleukin-1β (IL-1β), interleukin-6 (IL-6), & cyclooxygenase-2 (COX-2) while increasing the levels of reactive oxygen species (ROS) and malondialdehyde (MDA). Moreover, the enzymatic activities glutathione peroxidase (GPx), glutathione reductase (GSR), glutathione S-transferase (GST), superoxide dismutase (SOD), catalase (CAT), heme-oxygenase-1 (HO-1) and glutathione (GSH) were lowered whereas the levels of Troponin I, ProBNP, C-reactive protein, LDH, troponin-T, BNP and CPK were exacerbated following the SA exposure. Furthermore, SA intoxication promoted the levels of Bax, Caspase-9, and Caspase-3 while lowering the levels of Bcl-2. Cardiac tissues showed impaired histology after SA administration. Nonetheless, AZA therapy excellently ameliorated cardiac toxicity owing to its anti-inflammatory, antioxidative and anti-apoptotic potential.</div></div><div><h3>Conclusion</h3><div>SA intoxication induced severe cardiac toxicity via disrupting biochemical and histological parameters while AZA excellently restored cardiac health profile. Collectively, AZA may serve as a cardioprotective agent in counteracting SA induced sub-chronic cardiotoxicity.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"92 ","pages":"Article 127763"},"PeriodicalIF":3.6,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145159458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-22DOI: 10.1016/j.jtemb.2025.127760
Ljubinko Đenić , Jovana Jagodić , Katarina Kozlica , Aleksandar Lukač , Aleksandar Ristanović , Janez Ščančar , Aleksandar Stojsavljević
Lung cancer remains one of the leading causes of morbidity and mortality worldwide, yet the baseline status of trace elements in healthy/control lung tissues is largely unresolved, with no comprehensive elemental profile established for lung cancer. This study aimed to characterize baseline concentrations of 44 elements in healthy lung tissues (n = 92) and investigate changes in elemental composition in cancerous lung tissues (n = 92). The second aim was to observe possible differences in elemental concentrations in healthy and cancerous lung tissues based on age and sex. Additionally, this study aimed to identify trace elements potentially involved in lung cancer pathophysiology. Through detailed elemental analysis, this study revealed significant differences between healthy and cancerous lung tissues. Specifically, concentrations of Mn, Co, Ni, Cd, and U were significantly higher in healthy lung tissues, while Cu, Tl, Pb, Rh, Pd, and Bi were significantly higher in cancerous lung tissues. Age-related analysis of the control tissue group showed that healthy lung tissue from older individuals (above 64 years) had lower concentrations of elements Mn, Zn, Be, Al, Sb, Ba, Tl, Ga, Rb, Y, Re, Eu, Tb, Dy, Ho, Er, Yb, La, and Bi than healthy tissues from younger individuals (below 64 years). In cancerous lung tissues, those from females (n = 40) exhibited significantly lower concentrations of Cr, Cu, As, and Pb but higher Pt concentrations than cancerous lung tissues from males (n = 52). Furthermore, in cancerous lung tissues, those from younger patients displayed lower concentrations of As, Sb, and Au compared to equivalent tissues from older individuals. These findings offer valuable insights into the elemental composition of lung cancer tissue, enhancing the understanding of how trace elements could influence lung cancer pathophysiology.
{"title":"Comprehensive analysis of 44 elements in the lung cancer tissues of smokers: A comparative study with control lung tissues","authors":"Ljubinko Đenić , Jovana Jagodić , Katarina Kozlica , Aleksandar Lukač , Aleksandar Ristanović , Janez Ščančar , Aleksandar Stojsavljević","doi":"10.1016/j.jtemb.2025.127760","DOIUrl":"10.1016/j.jtemb.2025.127760","url":null,"abstract":"<div><div>Lung cancer remains one of the leading causes of morbidity and mortality worldwide, yet the baseline status of trace elements in healthy/control lung tissues is largely unresolved, with no comprehensive elemental profile established for lung cancer. This study aimed to characterize baseline concentrations of 44 elements in healthy lung tissues (n = 92) and investigate changes in elemental composition in cancerous lung tissues (n = 92). The second aim was to observe possible differences in elemental concentrations in healthy and cancerous lung tissues based on age and sex. Additionally, this study aimed to identify trace elements potentially involved in lung cancer pathophysiology. Through detailed elemental analysis, this study revealed significant differences between healthy and cancerous lung tissues. Specifically, concentrations of Mn, Co, Ni, Cd, and U were significantly higher in healthy lung tissues, while Cu, Tl, Pb, Rh, Pd, and Bi were significantly higher in cancerous lung tissues. Age-related analysis of the control tissue group showed that healthy lung tissue from older individuals (above 64 years) had lower concentrations of elements Mn, Zn, Be, Al, Sb, Ba, Tl, Ga, Rb, Y, Re, Eu, Tb, Dy, Ho, Er, Yb, La, and Bi than healthy tissues from younger individuals (below 64 years). In cancerous lung tissues, those from females (n = 40) exhibited significantly lower concentrations of Cr, Cu, As, and Pb but higher Pt concentrations than cancerous lung tissues from males (n = 52). Furthermore, in cancerous lung tissues, those from younger patients displayed lower concentrations of As, Sb, and Au compared to equivalent tissues from older individuals. These findings offer valuable insights into the elemental composition of lung cancer tissue, enhancing the understanding of how trace elements could influence lung cancer pathophysiology.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"92 ","pages":"Article 127760"},"PeriodicalIF":3.6,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145159459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Exposure to lead (Pb) poses significant risks to human brain development. This study investigates the molecular mechanisms underlying Pb acetate-induced neurotoxicity in LUHMES cells, which represent a human fetal-derived dopaminergic neuronal precursor model particularly suited for studies of neurotoxicity and Parkinson’s disease. Morphological analyses revealed that Pb acetate exposure at concentrations exceeding 10 µM induced cytotoxicity and disrupted neurite outgrowth. Distinct gene expression changes associated with Pb exposure were determined through RNA-sequencing. Principal component analysis highlighted significant alterations in gene expression at higher Pb concentrations (10 µM) compared with lower Pb concentrations (1 µM) and controls. Notably, Pb acetate exposure impaired ribosomal function, Spliceosome and protein processing in the endoplasmic reticulum (ER) pathways. Furthermore, these three pathways related that Pb acetate exposure resulted in the upregulation of genes related to ER-associated degradation and apoptosis, whereas the ubiquitin ligase complex was disrupted, suggesting compromised protein homeostasis. These findings underscore the potential of ribosomal processes and ER stress pathways as biomarkers of Pb acetate exposure. This study provides advanced mechanistic insights into the toxicological effects of lead (Pb) as a heavy metal, with a specific emphasis on its influence on cellular processes related to proteostasis and stress response pathways. Our findings further highlight the importance of LUHMES cells as a human-derived neuronal model for elucidating neurodevelopmental toxicity and identifying molecular biomarkers of Pb exposure, particularly those associated with dysregulation in ribosomal function and endoplasmic reticulum (ER) stress signaling.
{"title":"Impact of lead (Pb)-induced neurotoxicity on protein synthesis and cellular stress responses in LUHMES cells","authors":"Tsunehiko Hongen , Tomohiro Ito , Xian-Yang Qin , Hideko Sone","doi":"10.1016/j.jtemb.2025.127759","DOIUrl":"10.1016/j.jtemb.2025.127759","url":null,"abstract":"<div><div>Exposure to lead (Pb) poses significant risks to human brain development. This study investigates the molecular mechanisms underlying Pb acetate-induced neurotoxicity in LUHMES cells, which represent a human fetal-derived dopaminergic neuronal precursor model particularly suited for studies of neurotoxicity and Parkinson’s disease. Morphological analyses revealed that Pb acetate exposure at concentrations exceeding 10 µM induced cytotoxicity and disrupted neurite outgrowth. Distinct gene expression changes associated with Pb exposure were determined through RNA-sequencing. Principal component analysis highlighted significant alterations in gene expression at higher Pb concentrations (10 µM) compared with lower Pb concentrations (1 µM) and controls. Notably, Pb acetate exposure impaired ribosomal function, Spliceosome and protein processing in the endoplasmic reticulum (ER) pathways. Furthermore, these three pathways related that Pb acetate exposure resulted in the upregulation of genes related to ER-associated degradation and apoptosis, whereas the ubiquitin ligase complex was disrupted, suggesting compromised protein homeostasis. These findings underscore the potential of ribosomal processes and ER stress pathways as biomarkers of Pb acetate exposure. This study provides advanced mechanistic insights into the toxicological effects of lead (Pb) as a heavy metal, with a specific emphasis on its influence on cellular processes related to proteostasis and stress response pathways. Our findings further highlight the importance of LUHMES cells as a human-derived neuronal model for elucidating neurodevelopmental toxicity and identifying molecular biomarkers of Pb exposure, particularly those associated with dysregulation in ribosomal function and endoplasmic reticulum (ER) stress signaling.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"92 ","pages":"Article 127759"},"PeriodicalIF":3.6,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145202523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-20DOI: 10.1016/j.jtemb.2025.127762
Xia Chai , Zhen Wang , Yujie Li , Jinlin Lei , Chong Guo , Weiwei Gu , Biyun Zhang , Huailan Guo
Background
Maintaining normal thyroid function during pregnancy is crucial for maternal health as well as fetal growth and development. Exposure to environmental trace elements may influence thyroid function in pregnant women, but the specific role of cobalt remains unclear. This study aimed to systematically assess the relationship between serum cobalt concentration and thyroid function in pregnant women. Additionally, it explored cobalt’s role within trace element mixtures to further elucidate its potential effects on thyroid function and provide theoretical and experimental foundations for future research.
Methods
This cross-sectional study included 293 pregnant women with valid trace element and thyroid function data from an initial 303 recruits. Measurements included serum cobalt, other trace elements (chromium, manganese, aluminum, vanadium, nickel), and thyroid indicators (Tg, TSH, FT3, FT4, TPOAb, TgAb).The relationships between serum cobalt and thyroid function, including potential non-linear effects, were analyzed using multiple linear regression, Bayesian kernel machine regression (BKMR), and restricted cubic spline (RCS) models. Additionally, interactions between cobalt and other trace elements were examined.
Results
Higher cobalt exposure was significantly negatively correlated with FT3 and FT4 levels. The linear trend test (P for trend < 0.001) further supported this exposure-response relationship. BKMR analysis indicated that cobalt had the most significant effect on thyroid function among all the trace metals studied, with no significant interactions observed between trace elements. RCS analysis further revealed a non-linear correlation between cobalt and FT4, as well as a linear negative correlation with FT3. Spearman correlation analysis showed a positive correlation between cobalt and chromium, manganese, aluminum, and vanadium.
Conclusion
Elevated serum cobalt concentration was significantly associated with lower FT3 and FT4 levels in pregnant women. The findings suggest that cobalt may affect FT3 and FT4 through different mechanisms, with FT4 exhibiting a non-linear response, while FT3 declines in a stable linear manner. Cobalt was positively correlated with several trace elements; however, no significant interactions were observed among them. This suggests that cobalt’s effect on thyroid function in pregnant women may be independent.
{"title":"Association between serum cobalt concentration and thyroid function in pregnant women: A cross-sectional study","authors":"Xia Chai , Zhen Wang , Yujie Li , Jinlin Lei , Chong Guo , Weiwei Gu , Biyun Zhang , Huailan Guo","doi":"10.1016/j.jtemb.2025.127762","DOIUrl":"10.1016/j.jtemb.2025.127762","url":null,"abstract":"<div><h3>Background</h3><div>Maintaining normal thyroid function during pregnancy is crucial for maternal health as well as fetal growth and development. Exposure to environmental trace elements may influence thyroid function in pregnant women, but the specific role of cobalt remains unclear. This study aimed to systematically assess the relationship between serum cobalt concentration and thyroid function in pregnant women. Additionally, it explored cobalt’s role within trace element mixtures to further elucidate its potential effects on thyroid function and provide theoretical and experimental foundations for future research.</div></div><div><h3>Methods</h3><div>This cross-sectional study included 293 pregnant women with valid trace element and thyroid function data from an initial 303 recruits. Measurements included serum cobalt, other trace elements (chromium, manganese, aluminum, vanadium, nickel), and thyroid indicators (Tg, TSH, FT3, FT4, TPOAb, TgAb).The relationships between serum cobalt and thyroid function, including potential non-linear effects, were analyzed using multiple linear regression, Bayesian kernel machine regression (BKMR), and restricted cubic spline (RCS) models. Additionally, interactions between cobalt and other trace elements were examined.</div></div><div><h3>Results</h3><div>Higher cobalt exposure was significantly negatively correlated with FT3 and FT4 levels. The linear trend test (P for trend < 0.001) further supported this exposure-response relationship. BKMR analysis indicated that cobalt had the most significant effect on thyroid function among all the trace metals studied, with no significant interactions observed between trace elements. RCS analysis further revealed a non-linear correlation between cobalt and FT4, as well as a linear negative correlation with FT3. Spearman correlation analysis showed a positive correlation between cobalt and chromium, manganese, aluminum, and vanadium.</div></div><div><h3>Conclusion</h3><div>Elevated serum cobalt concentration was significantly associated with lower FT3 and FT4 levels in pregnant women. The findings suggest that cobalt may affect FT3 and FT4 through different mechanisms, with FT4 exhibiting a non-linear response, while FT3 declines in a stable linear manner. Cobalt was positively correlated with several trace elements; however, no significant interactions were observed among them. This suggests that cobalt’s effect on thyroid function in pregnant women may be independent.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"92 ","pages":"Article 127762"},"PeriodicalIF":3.6,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145119937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-18DOI: 10.1016/j.jtemb.2025.127754
Andrea Pisano , Angela Sabalic , Giovanni Forte , Grazia Fenu , Beatrice Bocca , Federica Etzi , Davide Tutedde , Claudia Trignano , Giovanni Fiorito , Peter Massányi , Roberto Madeddu
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers, characterized by poor prognosis due to the late diagnosis and chemotherapy resistance. Both genetic and environmental factors, including heavy metals exposure are involved in PDAC development. In this study, we evaluated the association between a panel of miRNAs and metals with PDAC, and subsequently assessed their correlation using Spearman’s test to investigate potential biological links. miRNA expression was analysed in the serum of PDAC patients (n = 37) compared to healthy controls (n = 20), as well as in tumour biopsies (n = 23) versus adjacent healthy tissue (n = 21). For metals, whole blood and tumour biopsies were examined and compared with their respective healthy counterparts. The metals considered were cadmium (Cd), chromium (Cr), cobalt (Co), copper (Cu), manganese (Mn), lead (Pb), nickel (Ni), iron (Fe), zinc (Zn), and selenium (Se); the analysed miRNAs included miR-361–3p, miR-320d, miR-20b–5p, miR-4486, miR-216a–5p, miR-216b–5p, miR-324–5p, miR-125a–5p. Our results showed that miR-320d, miR-20b–5p, miR-4486, miR-216a–5p and miR-216b–5p were significantly overexpressed in PDAC serum samples compared to controls as well as PDAC patients showed high concentration of Cr and Cu. On the other hand, no significant differences were reported between PDAC biopsies and healthy counterpart. However, higher concentration of Cu, Fe, Se, and Zn were observed in tumour samples. Spearman's Rank Correlation analysis revealed a positive correlation between miR-216a-5p and Mn, Cd and Zn and negative correlation with miR-320d and miR-361–3p in tissue samples. While in serum, miR-361–3p was positively correlated with Cu, suggesting a potential link between oxidative stress regulation and PDAC development. This study suggests that specific miRNAs correlate with metals in PDAC, such as miR-361–3p with Cu and miR-216a-5p with Mn, hinting at a potential role of metal homeostasis in tumour-related pathways. However, these findings warrant further validation and functional studies, and may provide novel insights for biomarker development and therapeutic strategies in PDAC.
{"title":"Relationship between heavy metals and miRNAs in pancreatic ductal adenocarcinoma","authors":"Andrea Pisano , Angela Sabalic , Giovanni Forte , Grazia Fenu , Beatrice Bocca , Federica Etzi , Davide Tutedde , Claudia Trignano , Giovanni Fiorito , Peter Massányi , Roberto Madeddu","doi":"10.1016/j.jtemb.2025.127754","DOIUrl":"10.1016/j.jtemb.2025.127754","url":null,"abstract":"<div><div>Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers, characterized by poor prognosis due to the late diagnosis and chemotherapy resistance. Both genetic and environmental factors, including heavy metals exposure are involved in PDAC development. In this study, we evaluated the association between a panel of miRNAs and metals with PDAC, and subsequently assessed their correlation using Spearman’s test to investigate potential biological links. miRNA expression was analysed in the serum of PDAC patients (n = 37) compared to healthy controls (n = 20), as well as in tumour biopsies (n = 23) versus adjacent healthy tissue (n = 21). For metals, whole blood and tumour biopsies were examined and compared with their respective healthy counterparts. The metals considered were cadmium (Cd), chromium (Cr), cobalt (Co), copper (Cu), manganese (Mn), lead (Pb), nickel (Ni), iron (Fe), zinc (Zn), and selenium (Se); the analysed miRNAs included miR-361–3p, miR-320d, miR-20b–5p, miR-4486, miR-216a–5p, miR-216b–5p, miR-324–5p, miR-125a–5p. Our results showed that miR-320d, miR-20b–5p, miR-4486, miR-216a–5p and miR-216b–5p were significantly overexpressed in PDAC serum samples compared to controls as well as PDAC patients showed high concentration of Cr and Cu. On the other hand, no significant differences were reported between PDAC biopsies and healthy counterpart. However, higher concentration of Cu, Fe, Se, and Zn were observed in tumour samples. Spearman's Rank Correlation analysis revealed a positive correlation between miR-216a-5p and Mn, Cd and Zn and negative correlation with miR-320d and miR-361–3p in tissue samples. While in serum, miR-361–3p was positively correlated with Cu, suggesting a potential link between oxidative stress regulation and PDAC development. This study suggests that specific miRNAs correlate with metals in PDAC, such as miR-361–3p with Cu and miR-216a-5p with Mn, hinting at a potential role of metal homeostasis in tumour-related pathways. However, these findings warrant further validation and functional studies, and may provide novel insights for biomarker development and therapeutic strategies in PDAC.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"92 ","pages":"Article 127754"},"PeriodicalIF":3.6,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145159457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-18DOI: 10.1016/j.jtemb.2025.127761
Yi Lin , Yimei Wu , Haihui Zhu , Laizan Zheng
Background
This study was to investigate the associations between Magnesium Depletion Score (MDS) and all-cause and cardiovascular disease (CVD) mortality in American adults with diabetes.
Materials and methods
Data was gathered from NHANES between 1999 and 2018 and utilized together with the National Death Index to track deaths. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95 % confidence intervals (CIs) of MDS for all-cause and CVD mortality. Kaplan–Meier survival analyses were performed using log-rank tests. Subgroup analyses were conducted while accounting for confounding variables.
Results
A total of 7078 adults with diabetes were included in this study. This study observed a total of 1904 all-cause deaths and 542 deaths due to CVD over a median follow-up period of 88 months. After adjusting for all relevant factors, HR of MDS ≥ 3 was 1.47 (95 % CI: 1.21–1.77) for all-cause mortality and 1.89 (95 % CI: 1.31–2.72) for CVD mortality compared to MDS = 0 (P for trend < 0.001). The HRs were 1.13 (95 % CI: 1.07–1.19) for all-cause mortality and 1.24 (95 % CI: 1.13–1.37) for CVD mortality. The strength of the correlation was significantly affected by age (p for interaction = 0.003) and hypertension (p for interaction = 0.001). The subgroup analysis findings demonstrated the constant association between MDS and CVD mortality across various subgroups (all p for interaction > 0.05).
Conclusion
The findings of this study suggest that individuals with diabetes who have a high MDS may have an increased risk of all-cause and CVD mortality. Timely interventions, particularly in those with an MDS of 3 or higher, could potentially mitigate this risk.
{"title":"Association of Magnesium Depletion Score with all-cause and cardiovascular mortality in adults with diabetes","authors":"Yi Lin , Yimei Wu , Haihui Zhu , Laizan Zheng","doi":"10.1016/j.jtemb.2025.127761","DOIUrl":"10.1016/j.jtemb.2025.127761","url":null,"abstract":"<div><h3>Background</h3><div>This study was to investigate the associations between Magnesium Depletion Score (MDS) and all-cause and cardiovascular disease (CVD) mortality in American adults with diabetes.</div></div><div><h3>Materials and methods</h3><div>Data was gathered from NHANES between 1999 and 2018 and utilized together with the National Death Index to track deaths. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95 % confidence intervals (CIs) of MDS for all-cause and CVD mortality. Kaplan–Meier survival analyses were performed using log-rank tests. Subgroup analyses were conducted while accounting for confounding variables.</div></div><div><h3>Results</h3><div>A total of 7078 adults with diabetes were included in this study. This study observed a total of 1904 all-cause deaths and 542 deaths due to CVD over a median follow-up period of 88 months. After adjusting for all relevant factors, HR of MDS ≥ 3 was 1.47 (95 % CI: 1.21–1.77) for all-cause mortality and 1.89 (95 % CI: 1.31–2.72) for CVD mortality compared to MDS = 0 (P for trend < 0.001). The HRs were 1.13 (95 % CI: 1.07–1.19) for all-cause mortality and 1.24 (95 % CI: 1.13–1.37) for CVD mortality. The strength of the correlation was significantly affected by age (p for interaction = 0.003) and hypertension (p for interaction = 0.001). The subgroup analysis findings demonstrated the constant association between MDS and CVD mortality across various subgroups (all p for interaction > 0.05).</div></div><div><h3>Conclusion</h3><div>The findings of this study suggest that individuals with diabetes who have a high MDS may have an increased risk of all-cause and CVD mortality. Timely interventions, particularly in those with an MDS of 3 or higher, could potentially mitigate this risk.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"92 ","pages":"Article 127761"},"PeriodicalIF":3.6,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145119936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-17DOI: 10.1016/j.jtemb.2025.127757
Aqsa Bibi , Hong-xing Zhang , Muhammad Faisal Hayat , Khalid J. Alzahrani , Khalaf F. Alsharif , Fuad M. Alzahrani
Background
Cadmium (Cd) is a potent environmental toxicant that affect different body organs including the liver. Spinacetin (SPI) is a plant-derived polyphenolic compound with diverse biological activities.
Objective
The current investigation assessed the palliative potential of SPI against Cd-exacerbated hepatic ischemic/reperfusion (I/R) injury in rats.
Methodology
Forty male albino rats were apportioned into five groups including the sham, I/R induced, I/R + Cd (5 mg/kg), I/R + Cd (5 mg/kg) + SPI (50 mg/kg), and I/R + SPI (50 mg/kg) treated group. Gene expressions were quantified using qRT PCR. Biochemical assessments were performed using ELISA technique and standard assays. Results were cross validated through molecular simulation and molecular docking analysis.
Findings
It was revealed that Cd intoxication in I/R group downregulated the gene expression of silent information regulator sirtuin-1 (SIRT1), adenosine monophosphate-activated protein kinase (AMPK), mitochondrial transcription factor-A (TFAM), peroxisome proliferator-activated receptor-γ coactivator 1-α (PGC-1α), and Estrogen-Related Receptor Alpha (ERRα) while upregulating the mRNA expressions of COX-2, TNF-α, IL-6, IL-1β, and NF-κB. Enzymatic potential of glutathione reductase (GSR), superoxide dismutase (SOD), glutathione reductase (GSR), catalase (CAT), heme-oxygenase-1 (HO-1), glutathione peroxidase (GPx), and concentration of glutathione (GSH) were suppressed while the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) were upregulated following the Cd intoxication in I/R induced group. Cd intoxication in IR group escalated the levels of ALT, AST, ALP, and GGT while reducing the intensity of albumin and total protein. Moreover, I/R-induced and IR + Cd group showed upregulation in Bax, Caspase-3 and Caspase-9 while reducing the levels of Bcl-2. Severe histological impairments were observed in I/R as well as I/R + Cd treated group. Nonetheless, SPI therapy showed significant protection of hepatic tissues against I/R and I/R + Cd intoxication via regulating mitochondrial biogenesis, oxidative stress, inflammation, apoptosis and histological impairments.
Conclusion
Cd intoxication escalates the hepatic ischemic injury via upregulating oxidative injury, inflammation and other key regulatory pathways. Spinacetin reversed I/R-mediated hepatic damage, demonstrating its potential hepatoprotective efficacy.
{"title":"Therapeutic potential of spinacetin against cadmium-exacerbated hepatic ischemia/reperfusion injury via regulating AMPK/SIRT1/PGC-1α and NF-κB pathway","authors":"Aqsa Bibi , Hong-xing Zhang , Muhammad Faisal Hayat , Khalid J. Alzahrani , Khalaf F. Alsharif , Fuad M. Alzahrani","doi":"10.1016/j.jtemb.2025.127757","DOIUrl":"10.1016/j.jtemb.2025.127757","url":null,"abstract":"<div><h3>Background</h3><div>Cadmium (Cd) is a potent environmental toxicant that affect different body organs including the liver. Spinacetin (SPI) is a plant-derived polyphenolic compound with diverse biological activities.</div></div><div><h3>Objective</h3><div>The current investigation assessed the palliative potential of SPI against Cd-exacerbated hepatic ischemic/reperfusion (I/R) injury in rats.</div></div><div><h3>Methodology</h3><div>Forty male albino rats were apportioned into five groups including the sham, I/R induced, I/R + Cd (5 mg/kg), I/R + Cd (5 mg/kg) + SPI (50 mg/kg), and I/R + SPI (50 mg/kg) treated group. Gene expressions were quantified using qRT PCR. Biochemical assessments were performed using ELISA technique and standard assays. Results were cross validated through molecular simulation and molecular docking analysis.</div></div><div><h3>Findings</h3><div>It was revealed that Cd intoxication in I/R group downregulated the gene expression of silent information regulator sirtuin-1 (SIRT1), adenosine monophosphate-activated protein kinase (AMPK), mitochondrial transcription factor-A (TFAM), peroxisome proliferator-activated receptor-γ coactivator 1-α (PGC-1α), and Estrogen-Related Receptor Alpha (ERRα) while upregulating the mRNA expressions of COX-2, TNF-α, IL-6, IL-1β, and NF-κB. Enzymatic potential of glutathione reductase (GSR), superoxide dismutase (SOD), glutathione reductase (GSR), catalase (CAT), heme-oxygenase-1 (HO-1), glutathione peroxidase (GPx), and concentration of glutathione (GSH) were suppressed while the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) were upregulated following the Cd intoxication in I/R induced group. Cd intoxication in IR group escalated the levels of ALT, AST, ALP, and GGT while reducing the intensity of albumin and total protein. Moreover, I/R-induced and IR + Cd group showed upregulation in Bax, Caspase-3 and Caspase-9 while reducing the levels of Bcl-2. Severe histological impairments were observed in I/R as well as I/R + Cd treated group. Nonetheless, SPI therapy showed significant protection of hepatic tissues against I/R and I/R + Cd intoxication via regulating mitochondrial biogenesis, oxidative stress, inflammation, apoptosis and histological impairments.</div></div><div><h3>Conclusion</h3><div>Cd intoxication escalates the hepatic ischemic injury via upregulating oxidative injury, inflammation and other key regulatory pathways. Spinacetin reversed I/R-mediated hepatic damage, demonstrating its potential hepatoprotective efficacy.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"92 ","pages":"Article 127757"},"PeriodicalIF":3.6,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145097809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-16DOI: 10.1016/j.jtemb.2025.127751
João Silva , Eva Marguí , Romain Guillemaut , Jasna Jablan , Alessandro Migliori , Paula Kasprzyk , Joaquim J. Ferreira , Sofia Pessanha
Background
The accurate detection and quantification of elemental content in skin appendages, such as, hair and nails are pivotal in biomedical research, including disease diagnostics, environmental exposure monitoring, and forensic investigations.
Methods
This study evaluates and compares the suitability of different sample treatments and four spectroscopic techniques—Energy Dispersive X-ray Fluorescence (EDXRF), Total Reflection X-ray Fluorescence (TXRF), Inductively Coupled Plasma Mass Spectrometry (ICP-MS), and Inductively Coupled Plasma Optical Emission Spectroscopy (ICP-OES) for multielemental analysis of these biological tissues. Making use of different Certified Reference Materials (CRMs), the performance of the developed methods was assessed based on their sensitivity, precision, range of detectable elements, and the extent of sample preparation required.
Results
EDXRF method is suited for rapid and non-destructive determination of light elements present at relatively high concentrations – Sulfur (S), Chlorine (Cl), Potassium (K) and Calcium (Ca) – in hair and nail samples. TXRF provides information of most of the elements present in the target samples, including Bromine (Br), but the determination of light element (i.e, Phosphorus (P), S, Cl) is not feasible. Finally, the proposed ICP-OES/ICP-MS method is useful for the determination of major, minor and trace elements, except chlorine.
Conclusion
This comparative study reveals the distinct strengths, range of elements and suitable applications of each technique, providing a valuable framework for selecting appropriate methods based on specific analytical needs.
{"title":"Evaluation of the quantitative performance of different spectroscopic techniques for multielemental analysis of nail and hair samples: A comparative study","authors":"João Silva , Eva Marguí , Romain Guillemaut , Jasna Jablan , Alessandro Migliori , Paula Kasprzyk , Joaquim J. Ferreira , Sofia Pessanha","doi":"10.1016/j.jtemb.2025.127751","DOIUrl":"10.1016/j.jtemb.2025.127751","url":null,"abstract":"<div><h3>Background</h3><div>The accurate detection and quantification of elemental content in skin appendages, such as, hair and nails are pivotal in biomedical research, including disease diagnostics, environmental exposure monitoring, and forensic investigations.</div></div><div><h3>Methods</h3><div>This study evaluates and compares the suitability of different sample treatments and four spectroscopic techniques—Energy Dispersive X-ray Fluorescence (EDXRF), Total Reflection X-ray Fluorescence (TXRF), Inductively Coupled Plasma Mass Spectrometry (ICP-MS), and Inductively Coupled Plasma Optical Emission Spectroscopy (ICP-OES) for multielemental analysis of these biological tissues. Making use of different Certified Reference Materials (CRMs), the performance of the developed methods was assessed based on their sensitivity, precision, range of detectable elements, and the extent of sample preparation required.</div></div><div><h3>Results</h3><div>EDXRF method is suited for rapid and non-destructive determination of light elements present at relatively high concentrations – Sulfur (S), Chlorine (Cl), Potassium (K) and Calcium (Ca) – in hair and nail samples. TXRF provides information of most of the elements present in the target samples, including Bromine (Br), but the determination of light element (i.e, Phosphorus (P), S, Cl) is not feasible. Finally, the proposed ICP-OES/ICP-MS method is useful for the determination of major, minor and trace elements, except chlorine.</div></div><div><h3>Conclusion</h3><div>This comparative study reveals the distinct strengths, range of elements and suitable applications of each technique, providing a valuable framework for selecting appropriate methods based on specific analytical needs.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"92 ","pages":"Article 127751"},"PeriodicalIF":3.6,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145097746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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