1. Determination of copper and other trace elements in serum samples from patients with biliary tract cancers : prospective noninterventional nonrandomized clinical study protocolMartina Reberšek, Nežka Hribernik, Katarina Kozlica, Stefan Marković, Katja Uršič Valentinuzzi, Maja Čemažar, Tea Zuliani, Radmila Milačič Ščančar, Janez Ščančar, 2024, original scientific article Abstract: Background Biliary tract cancers (BTCs) are usually diagnosed at an advanced stage, when the disease is incurable. Currently used tumor biomarkers have limited diagnostic value for BTCs, so there is an urgent need for sensitive and specific biomarkers for their earlier diagnosis. Deregulation of the homeostasis of trace elements is involved in the carcinogenesis of different cancers, including BTCs. The objective of the study is to determine/compare the total concentrations of copper (Cu), zinc (Zn) and iron (Fe) and the proportions of free Cu and Cu bound to ceruloplasmin (Cp) and the isotopic ratio of 65Cu/63Cu in serum samples from healthy volunteers and cancer patients using inductively coupled plasma-mass spectrometry-based methods (ICP-MS).
Keywords: trace elements, copper, predictive biomarkers of response
Published in DiRROS: 26.06.2026; Views: 125; Downloads: 55
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2. Clinical impact of trace elements as potential biomarkers for diagnosis and prediction of response to systemic treatment in gastrointestinal cancersMartina Reberšek, Radmila Milačič Ščančar, Janez Ščančar, Nežka Hribernik, 2026, original scientific article Abstract: Gastrointestinal cancers are among the most common malignancies worldwide and, at advanced stages, remain incurable. Currently used biomarkers, such as tumour markers, have limited diagnostic value for early detection and relapse, highlighting the urgent need for more sensitive and specific markers. Trace elements are involved in numerous physiological and metabolic processes, and deregulation of their homeostasis is implicated in the carcinogenesis of various cancers, including gastrointestinal malignancies. Several basic and preclinical studies have identified the importance of trace elements in key biological processes. Recent clinical studies and retrospective analyses suggest that fluctuations in trace element levels may be associated with the development and progression of many cancers. Thus, quantitative and dynamic determination of serum trace element concentrations during treatment and follow-up represents a promising option for monitoring treatment efficacy and disease prognosis. Conclusions. Trace elements may serve as potential prognostic and predictive biomarkers for diagnosis and response to systemic treatment.
Keywords: gastrointestinal cancers, systemic therapy, prognostic and predictive biomarkers, trace elements
Published in DiRROS: 18.06.2026; Views: 148; Downloads: 63
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3. Association between autism spectrum disorder, trace elements, and intracranial fluid spacesMatej Mlinarič, Maja Jekovec-Vrhovšek, David Neubauer, Alenka France Štiglic, Joško Osredkar, 2024, original scientific article Abstract: Autism spectrum disorder (ASD) belongs to the group of complex developmental disorders. Novel studies have suggested that genetic and environmental factors equally affect the risk of ASD. Identification of environmental factors involved in the development of ASD is therefore crucial for a better understanding of its etiology. Whether there is a causal link between trace elements, brain magnetic resonance imaging (MRI), and ASD remains a matter of debate and requires further studies. (2) In the prospective part of the study, we included 194 children, including an age-matched control group; in the retrospective study, 28 children with available MRI imaging were included. All children had urine analysis of trace elements performed. In those with available brain MRI, linear indexes for the ventricular volumes were measured and calculated. (3) We found the highest vanadium, rubidium, thallium, and silver levels in children with ASD. These elements also correlated with the estimated ventricular volume based on MRI indexes in children with ASD in the subanalysis. However, the severity of the deficits did not correlate with brain MRI indexes of our elements, except negatively with magnesium. (4) Trace elements have an impact on children with ASD, but further multi-centric studies are needed to explain the pathophysiological mechanisms.
Keywords: autism spectrum disorders, trace elements, ventricular indexes
Published in DiRROS: 11.06.2026; Views: 118; Downloads: 99
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4. Associations between APOE genotypes, urine 8-isoprostane and blood trace elements in middle-aged mothers (CROME study)Alenka France Štiglic, Anja Stajnko, Alenka Sešek-Briški, Janja Snoj Tratnik, Darja Mazej, Aleš Jerin, Milan Skitek, Milena Horvat, Janja Marc, Ingrid Falnoga, 2024, original scientific article Abstract: Background. There is almost no data on the combined associations between apolipoprotein E gene (APOE) genotypes, trace elements (TEs), and lipid peroxidation in vivo. The aim of our study was to evaluate the association between APOE genotypes and TE levels in blood (B-TEs) and erythrocytes (E-TEs), and 8-isoprostane in urine (U-8-isoprostane) in women with low exposure to potentially toxic TEs and with adequate supply of essential TEs. Methods. B-TEs, E-TEs and U-8-isoprostane were determined in 172 healthy women of childbearing age (30.1–51.4 years) using ICP-MS and ELISA competitive assay, respectively. All women were divided into three APOE genotype groups according to the presence of the ɛ4 allele, ɛ2 allele or ɛ3 homozygotic allele. The associations between B-TEs, E-TE, U-8-isoprostane, and the APOE genotype groups were estimated by multiple variable linear regression models with relevant explanatory variables (e.g., age, BMI, and seafood). Results. All TE and U-8-isoprostane levels were inside the reference ranges for the healthy population. In the multiple variable linear regression models, our results showed that urine 8-isoprostane levels increased by up to 43.3% in the APOE4 group compared to the APOE3 group and a negligible negative modifying effect for essential TEs. However, the APOE genotype groups were associated also with some TEs. A clear positive association was found between the APOE2 and APOE4 groups (vs. APOE3) with B-molybdenum. Conclusions. Our study suggests that the APOE4 genotype played an important role in 8-isoprostane variability in a population with an adequate supply of essential and with low exposure to potentially toxic TEs. Adequate copper, zinc and selenium status seemed to be protective against, while the levels of nonessential TEs were probably too low to play a decisive role in 8-isoprostane formation. The observed impact of the APOE2 and APOE4 groups on increased B-molybdenum opens a new research topic.
Keywords: apolipoprotein E, polymorphisms, trace elements, multiple variable linear regression models
Published in DiRROS: 05.06.2026; Views: 222; Downloads: 310
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5. Trace element dysregulation and detoxification dysfunction in autism spectrum disorder : a urinary biomarker study with element ratio analysisJoško Osredkar, Uroš Godnov, Maja Jekovec-Vrhovšek, Damjan Osredkar, Gorazd Avguštin, Alenka France Štiglic, Teja Fabjan, Kristina Kumer, 2026, original scientific article Abstract: Background: Autism spectrum disorder (ASD) arises from complex gene–environment interactions. While trace element abnormalities have been studied, associations with autism severity remain inconsistent. Ratios indicating detoxification balance, rather than single toxic elements, may better reflect severity. Objective: To examine the relationships between urinary trace element levels, detoxification-related element ratios, and autism severity measured by the Childhood Autism Rating Scale (CARS). Methods: In a crosssectional study of 168 participants (103 ASD, 65 controls), thirty urinary trace elements were quantified by ICP-MS. ASD patients were stratified by CARS into subthreshold ASD (n = 29), mild–moderate ASD (n = 36), and severe ASD (n = 38). Analyses included Mann–Whitney U, Kruskal–Wallis, and Spearman correlation tests, focusing on Li/Pb, Cu/Pb, and Cr/Pb ratios. Results: Individual elements showed weak associations with CARS; lead correlated positively (ρ = 0.209, p = 0.035) and lithium inversely (ρ = −0.194, p = 0.051). In contrast, element ratios showed stronger links: Li/Pb (ρ = −0.349, p = 0.0003), Cu/Pb (ρ = −0.320, p = 0.0011), and Cr/Pb (ρ = −0.209, p = 0.035). Severe ASD exhibited modest 90th-percentile elevations for toxic elements but high heterogeneity. Conclusions: Single-element levels showed limited associations with ASD severity. Element ratios, particularly Li/Pb, showed stronger statistical associations than individual elements in this cross-sectional dataset; however, these findings should be interpreted as candidate correlates rather than causal or clinically validated biomarkers.
Keywords: autism spectrum disorder, trace elements, lead, llithium, detoxification, biomarkers, CARS, element ratios, environmental toxins, metallothionein
Published in DiRROS: 01.06.2026; Views: 176; Downloads: 124
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6. Method development and production of an ambient-stable blood certified reference material for total mercury, methylmercury, and trace elementsKoichi Haraguchi, Mineshi Sakamoto, Hiromitsu Nagasaka, Milena Horvat, Ermira Begu, Polona Klemenčič, Adna Alilović Osolin, Masaaki Nakamura, 2026, original scientific article Abstract: Background. Certified reference materials (CRMs) for mercury speciation of biological fluids have hitherto been limited to frozen or cold-storage types, which impedes the participation of laboratories in tropical or remote regions. Existing CRMs often do not fully meet user needs, particularly regarding storage stability and concentration relevance. Results. Using pooled Japanese human blood, we developed a freeze-dried, ambient-stable blood CRM, with certified values of 6.16 μg L−1 for total mercury (THg) and 5.46 μg L−1 for methylmercury (MeHg, as Hg). These concentrations are congruent with median exposure levels in fish-consuming populations (e.g., small island states and riverine Amazonian communities) derived from global biomonitoring data. Homogeneity, stability, and traceability were validated through inter-laboratory comparisons and rigorous uncertainty assessment. Significance. This ambient-stable blood CRM broadens global access to high-quality QA/QC of mercury speciation, especially in regions lacking cold-chain infrastructure. It contributes to capacity building under the Minamata Convention and strengthens interlaboratory comparability. Registration in COMAR and international collaborative deployment are under active development, enhancing the global infrastructure for mercury biomonitoring.
Keywords: passive monitoring, methylmercury, blood samples, mercury detection, human biomonitoring, trace elements
Published in DiRROS: 04.05.2026; Views: 285; Downloads: 259
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7. Pesticides and trace element residues in honey from Northern CroatiaDamir Pavliček, Marija Sedak, Nina Bilandžić, Ivana Varenina, Ivana Tlak Gajger, Anton Gradišek, Mariša Ratajec, Maja Đokić, 2026, original scientific article Abstract: The rapid translocation of pesticide and metal residues in the environment and their entry into the food chain pose a significant risk to human health. Given the high global consumption of honey, quality control emphasizes the need for continuous monitoring and risk assessment. To evaluate contamination levels in honey from northern Croatia, a region with intensive agricultural land use, 38 comb honey and 22 extracted honey samples were collected by purposive one-time sampling in June 2023. These samples were analyzed for 190 pesticides using liquid chromatography–tandem mass spectrometry (LC-MS/MS) and gas chromatography–tandem mass spectrometry (GC-MS/MS), and for 17 trace metal(loid)s using inductively coupled plasma mass spectrometry (ICP-MS). The highest detection frequencies were observed for fipronil-sulfone, trifloxystrobin, and coumaphos in comb honey, and for N-(2,4-dimethylphenyl)-formamide (DMF) and N-(2,4-dimethylphenyl)-N′-methylformamidine (DPMF) in extracted honey. Glyphosate was the only pesticide to exceed the European Union (EU) maximum residue level (MRL) of 0.05 mg/kg in three honey samples. Elemental analysis quantified most target metals, with aluminum (Al), copper (Cu), iron (Fe), manganese (Mn), nickel (Ni) and zinc (Zn) being the most abundant, while silver (Ag), arsenic (As), and selenium (Se) were not detected in this study. None of the samples contained lead (Pb) above the regulatory limit for honey established in the EU (0.1 mg/kg). To ensure food safety, further efforts are required to assess the health risks associated with exposure to these contaminants through consumption of the evaluated food.
Keywords: trace elements, residues
Published in DiRROS: 30.04.2026; Views: 274; Downloads: 210
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8. Association of trace elements with polycystic ovary syndrome in women - a case-control studyTinkara Srnovršnik, Bojana Pinter, Milena Horvat, Janja Snoj Tratnik, Ingrid Falnoga, Darja Mazej, Ivan Verdenik, Irma Virant-Klun, 2025, original scientific article Abstract: Objectives: There are still limited or lacking data on the association of trace elements (TEs) with polycystic ovary syndrome (PCOS). This case–control study aimed to determine levels of essential TEs (manganese (Mn), copper (Cu), zinc (Zn), selenium (Se), molybdenum (Mo)) and non-essential TEs (arsenic (As), cadmium (Cd), mercury (Hg), lead (Pb)) in urine, whole blood, and serum to investigate a possible association with kidney and liver function, endocrine and metabolic parameters, and environmental and lifestyle sources of potential exposure and provide possible recommendations. Methods: In our case–control study, women with PCOS (n = 35) and healthy controls (n = 35) underwent clinical and ultrasonographic examination, filled in questionnaires targeting general, lifestyle, and environmental information, and provided fasting venous blood samples and first morning urine for biochemical, hormonal, and TE analysis. Multiple linear regression models were used to evaluate the association between TE levels and data obtained through questionnaires. Results: In women with PCOS, lower Mo levels in whole blood (p = 0.024) and serum (p = 0.011) and higher serum Cu levels (p = 0.026) were detected when compared to healthy controls. Results of this study show that amendments in Cu and Mo levels might be related to altered kidney and liver function and disrupted hormonal balance in PCOS women. Cu levels positively correlated with leukocyte count. There was a negative correlation of Mo levels with proteinuria and luteinizing hormone levels. Regarding liver function, Mo negatively correlated with urinary bilirubin levels, and there was a positive association with alanine and aspartate aminotransferase, respectively. Dietary supplement consumption and certain diet habits appeared to be important predictors of exposure to Cu (beef consumption) or Mo (cereal and boiled vegetable consumption) and modify Mo and Cu levels in women. Conclusions: Concentrations of the chemical elements Mo and Cu in biological samples of women appear to be related to PCOS and nutrition. To our knowledge, this is a novel finding for Mo. Additional research is needed to provide more insights into the causality of the PCOS relationship with Mo and Cu in humans.
Keywords: essential elements, non-essential elements, polycystic ovary syndrome, endocrine disruptors, hepatic damage, trace elements
Published in DiRROS: 16.04.2026; Views: 233; Downloads: 181
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9. Urinary porphyrin profiles and trace element imbalances in children with autism spectrum disorders : insights into environmental and metabolic biomarkersJoško Osredkar, Kristina Kumer, Maja Jekovec-Vrhovšek, Lidija Čuturič, Alenka France Štiglic, Teja Fabjan, 2025, original scientific article Abstract: Porphyrins are intermediates in heme biosynthesis and have been proposed as biomarkers of metabolic dysfunction and environmental exposure in autism spectrum disorder (ASD). This study aimed to evaluate urinary porphyrin fractions and trace element ratios in children with ASD compared to neurotypical controls. Urinary porphyrins were quantified using high-performance liquid chromatography (HPLC), and trace elements were measured via inductively coupled plasma mass spectrometry (ICP-MS) normalized to urinary creatinine. Trace element ratios (e.g., Zn/Cu, Se/Pb) were calculated. Statistical comparisons were made using the Mann–Whitney U-test. Children with ASD showed significantly elevated urinary levels of coproporphyrin (median: 1.94 µg/g creatinine vs. 1.32 in controls; p = 0.02) and pentacarboxyporphyrin (0.86 vs. 0.57; p = 0.01), and reduced hexacarboxyporphyrin (0.12 vs. 0.23; p = 0.03). Lead (Pb) levels were significantly higher in ASD (median: 1.96 µg/g creatinine vs. 0.82; p = 0.004), while mercury (Hg) was not significantly different. Several trace element ratios differed significantly: Zn/Cu (ASD 41.9 vs. controls 49.1; p = 0.021), Se/Pb (12.9 vs. 25.7; p = 0.002), Cu/Se (0.49 vs. 0.38; p = 0.008), and Zn/Pb (19.5 vs. 44.8; p = 0.002). The Hg/Se ratio did not differ significantly.: Children with ASD demonstrate altered porphyrin profiles and trace element imbalances, including increased Pb and disrupted Zn/Cu and Se/Pb ratios, indicating oxidative stress and impaired detoxification. Combined assessment of porphyrins and trace element ratios may provide valuable non-invasive biomarkers for environmental and metabolic disturbances in ASD.
Keywords: autism spectrum disorder, porphyrins, lead, heme biosynthesis, environmental toxicants, biomarkers, trace elements, ICP-MS
Published in DiRROS: 14.04.2026; Views: 236; Downloads: 179
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10. The Influence of Foliar Application of Selenium (VI) on the Concentration of Fe, Mn, Cd, Cu, Zn, S, and Mo in Common BuckwheatMaja Vogrinčič, Vekoslava Stibilj, 2025, original scientific article Abstract: Selenium in the form of selenate (Se VI) was foliarly applied to buckwheat plants to evaluate its influence on the uptake and accumulation of other selected elements, including copper (Cu), zinc (Zn), sulfur (S), molybdenum (Mo), iron (Fe), manganese (Mn), and cadmium (Cd). Among these, Cu, Zn, Mo, Fe, and Mn are essential elements while cadmium, on the other hand, is a toxic pollutant absorbed by plants from contaminated soils. Foliar selenium (VI) application resulted in modest changes in the concentrations of Cd, Mo, Fe, Mn, and S in the leaves; Cu in the husks; and Mo and Mn in inflorescences. However, selenium had no significant effect on Zn accumulation. These results suggest that foliar application of selenium (VI) may both enhance and inhibit the uptake of specific elements, with effects varying by plant tissue.
Keywords: common buckwheat, Tartary buckwheat, selenium, trace elements
Published in DiRROS: 08.01.2026; Views: 611; Downloads: 318
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