A genome-wide association study provides insights into the genetic etiology of 57 essential and non-essential trace elements in humans.

Trace elements are important for human health but may exert toxic or adverse effects. Mechanisms of uptake, distribution, metabolism, and excretion are partly under genetic control but have not yet been extensively mapped. Here we report a comprehensive multi-element genome-wide association study of 57 essential and non-essential trace elements. We perform genome-wide association meta-analyses of 14 trace elements in up to 6564 Scandinavian whole blood samples, and genome-wide association studies of 43 trace elements in up to 2819 samples measured only in the Trøndelag Health Study (HUNT). We identify 11 novel genetic loci associated with blood concentrations of arsenic, cadmium, manganese, selenium, and zinc in genome-wide association meta-analyses. In HUNT, several genome-wide significant loci are also indicated for other trace elements. Using two-sample Mendelian randomization, we find several indications of weak to moderate effects on health outcomes, the most precise being a weak harmful effect of increased zinc on prostate cancer. However, independent validation is needed. Our current understanding of trace element-associated genetic variants may help establish consequences of trace elements on human health.

Ocean acidification impact on the uptake of trace elements by mussels and their biochemical effects.

This study delves into the intricate interplay between ocean acidification (OA), metal bioaccumulation, and cellular responses using mussels (Mytilus galloprovincialis) as bioindicators. For this purpose, environmentally realistic concentrations of isotopically labelled metals (Cd, Cu, Ag, Ce) were added to investigate whether the OA increase would modify metal bioaccumulation and induce adverse effects at the cellular level. The study reveals that while certain elements like Cd and Ag might remain unaffected by OA, the bioavailability of Cu and Ce could potentially escalate, leading to amplified accumulation in marine organisms. The present findings highlight a significant rise in Ce concentrations within different mussel organs under elevated pCO2 conditions, accompanied by an increased isotopic fractionation of Ce (140/142Ce), suggesting a heightened potential for metal accumulation under OA. The results suggested that OA influenced metal accumulation in the gills of mussels. Conversely, metal accumulation in the digestive gland was unaffected by OA. The exposure to both trace metals and OA affects the biochemical responses of M. galloprovincialis, leading to increased metabolic capacity, changes in energy reserves, and alterations in oxidative stress markers, but the specific effects on other biomarkers (e.g., lipid peroxidation, some enzymatic responses or acetylcholinesterase activity) were not uniform, suggesting complex interactions between the stressors and the biochemical pathways in the mussels.

The influence of steroidal implants and manganese sulfate supplementation on growth performance, trace mineral status, hepatic gene expression, hepatic enzyme activity, and circulating metabolites in feedlot steers.

Angus-cross steers (n = 144; 359 kg ±â€…13.4) were used to assess the effect of dietary Mn and steroidal implants on performance, trace minerals (TM) status, hepatic enzyme activity, hepatic gene expression, and serum metabolites. Steers (n = 6/pen) were stratified by BW in a 3 × 2 factorial. GrowSafe bunks recorded individual feed intake (experimental unit = steer; n = 24/treatment). Dietary treatments included (MANG; 8 pens/treatment; Mn as MnSO4): (1) no supplemental Mn (analyzed 14 mg Mn/kg DM; Mn0); (2) 20 mg supplemental Mn/kg DM (Mn20); (3) 50 mg supplemental Mn/kg DM (Mn50). Within MANG, steers received a steroidal implant treatment (IMP) on day 0: (1) no implant; NO; or (2) combination implant (Revalor-200; REV). Liver biopsies for TM analysis and qPCR, and blood for serum glucose, insulin, non-esterified fatty acids, and urea-N (SUN) analysis were collected on days 0, 20, 40, and 77. Data were analyzed as a randomized complete block with a factorial arrangement of treatments including fixed effects of Mn treatment (MANG) and implant (IMP) using PROC MIXED of SAS 9.4 using initial BW as a covariate. Liver TM, serum metabolite, enzyme activity, and gene expression data were analyzed as repeated measures. No MANG × IMP effects were noted (P ≥ 0.12) for growth performance or carcass characteristic measures. Dietary Mn did not influence final body weight, overall ADG, or overall G:F (P ≥ 0.14). Liver Mn concentration increased with supplemental Mn concentration (MANG; P = 0.01). An IMP × DAY effect was noted for liver Mn (P = 0.01) where NO and REV were similar on day 0 but NO cattle increased liver Mn from days 0 to 20 while REV liver Mn decreased. Relative expression of MnSOD in the liver was greater in REV (P = 0.02) compared to NO and within a MANG × IMP effect (P = 0.01) REV increased liver MnSOD activity. These data indicate current NASEM Mn recommendations are adequate to meet the demands of finishing beef cattle given a steroidal implant. Despite the roles of Mn in metabolic pathways and antioxidant defense, a basal diet containing 14 mg Mn/kg DM was sufficient for the normal growth of finishing steers. This study also provided novel insight into how implants and supplemental Mn influence genes related to arginine metabolism, urea synthesis, antioxidant capacity, and TM homeostasis as well as arginase and MnSOD activity in hepatic tissue of beef steers.

Steroidal implants improve cattle growth and efficiency partially through increased net protein synthesis resulting in increased skeletal muscle hypertrophy. Necessary to support this increased growth are trace minerals (TM). Manganese (Mn) is essential, serving as a cofactor and activator of various enzymes. Manganese plays a crucial role in ruminant animals by supporting nitrogen recycling while also being essential for mitochondrial antioxidant defense. Consulting nutritionists routinely supplement Mn, amongst other TM, at concentrations greater than current recommendations. However, there is limited research on the impact of supplemental Mn in implanted finishing cattle. Our prior work suggests steroidal implants decrease liver Mn concentration. This is of interest as liver Mn concentration is tightly regulated. Therefore, this study evaluated the effects of steroidal implants and manganese sulfate supplementation on cattle growth performance, trace mineral status, expression of relevant hepatic genes, hepatic enzyme activity, and circulating metabolites in feedlot steers. In this study, supplementing Mn at the recommended concentration did not influence the growth of both implanted and non-implanted cattle.

Influence of copper source and dietary inclusion level on growth performance of weaned pigs and expression of trace element related genes in the small intestine.

Copper is routinely supplemented to weanling pig diets at concentrations above nutritional requirements to enhance growth performance. We hypothesised that this effect depends on the source of Cu and its dietary concentration. We tested this in weaned pigs (26 d of age) over a 35-d period using a 2 × 3 factorial arrangement with two Cu-sources (CuSO4 and Cu2O, monovalent copper oxide, CoRouge®) and three supplementary dietary Cu-levels (15, 80 and 160 mg Cu/kg) as respective factors. Increasing Cu level linearly increased (P < 0.001) final BW and daily gain. These effects tended (P = 0.09) to be greater with Cu2O than CuSO4. Feed conversion ratio decreased linearly (P < 0.001) with increasing dietary Cu content, independent of Cu source. Plasma Cu, Zn and Fe levels were unaffected, whereas liver Cu content increased quadratically (P < 0.001) with increasing dietary Cu content, with a larger increase (P < 0.001) with CuSO4 than Cu2O. Bile Cu content increased quadratically (P = 0.025) with increasing Cu content, irrespective of Cu source. RT-qPCR analysis revealed that increasing Cu content quadratically (P = 0.009) increased duodenal but not ileal metallothionein 1A (MT1A) mRNA, with greater effect (P = 0.010) of CuSO4. Regardless of the Cu source, increasing Cu dose linearly increased (P = 0.006) duodenal DMT1/SLC11A2 mRNA but decreased ZIP4/SLC39A4 mRNA in duodenum (P < 0.001) and ileum (P < 0.005). ZnT10/SLC30A10 mRNA was significantly (P = 0.021) and numerically (P = 0.061) greater with Cu2O compared to CuSO4, in duodenum and ileum, respectively. Copper content quadratically modulated duodenal but not ileal transferrin receptor (P = 0.029) and ferric reductase CYBRD1 mRNA (P = 0.022). In hypothalamus, high Cu dose (P = 0.024) and Cu2O as source (P = 0.028) reduced corticotropin-releasing hormone (CRH) mRNA. Low versus high CuSO4 increased corticotropin-releasing hormone receptor (CRHR2) mRNA, while low Cu2O had the opposite effect (P = 0.009). In conclusion, incremental Cu intake enhanced growth performance, with a tendency for a greater effect of Cu2O. The lower increase in duodenal MT1A mRNA and liver Cu content indicates that less Cu from Cu2O was absorbed by gut and sequestered in liver. Thus, high Cu absorption is not essential for its growth-promoting effect and dietary Cu may affect intestinal Fe and Zn absorption via the active, transcellular route. The effects on hypothalamic CRH and CRHR2 expression indicate a role for the hypothalamus in mediating the effects of Cu on growth performance.

Root-exuded specialized metabolites reduce arsenic toxicity in maize.

By releasing specialized metabolites, plants modify their environment. Whether and how specialized metabolites protect plants against toxic levels of trace elements is not well understood. We evaluated whether benzoxazinoids, which are released into the soil by major cereals, can confer protection against arsenic toxicity. Benzoxazinoid-producing maize plants performed better in arsenic-contaminated soils than benzoxazinoid-deficient mutants in the greenhouse and the field. Adding benzoxazinoids to the soil restored the protective effect, and the effect persisted to the next crop generation via positive plant-soil feedback. Arsenate levels in the soil and total arsenic levels in the roots were lower in the presence of benzoxazinoids. Thus, the protective effect of benzoxazinoids is likely soil-mediated and includes changes in soil arsenic speciation and root accumulation. We conclude that exuded specialized metabolites can enhance protection against toxic trace elements via soil-mediated processes and may thereby stabilize crop productivity in polluted agroecosystems.

Cu transport and complexation by the marine diatom Phaeodactylum tricornutum: Implications for trace metal complexation kinetics in the surface ocean.

Elucidating whether dissolved Cu uptake is kinetically or thermodynamically controlled, and the effects of speciation on Cu transport by phytoplankton will allow better modeling of the fate and impact of dissolved Cu in the ocean. To address these questions, we performed Cu physiological and physicochemical experiments using the model diatom, Phaeodactylum tricornutum, grown in natural North Atlantic seawater (0.44 nM Cu). Using competitive ligand equilibration-cathodic stripping voltammetry (CLE-CSV), we measured two organic ligand types released by P. tricornutum to bind Cu (L1 and L2) at concentrations of ~0.35 nM L1 and 1.3 nM L2. We also established the presence of two putative Cu-binding sites at the cell surface of P. tricornutum (S1 and S2) with log K differing by ~5 orders of magnitude (i.e., 12.9 vs. 8.1) and cell surface densities by 9-fold. Only the high-affinity binding sites, S1, exhibit reductase activity. Using voltammetric kinetic measurements and a theoretical kinetic model, we calculated the forward and dissociation rate constants of L1 and S1. Complementary 67Cu uptake experiments identified a high- and a low-affinity Cu uptake system in P. tricornutum, with half-saturation constant (Km) of 154 nM and 2.63 µM dissolved Cu, respectively. In the P. tricornutum genome, we identified a putative high-affinity Cu transporter (PtCTR49224) and a putative ZIP-like, low-affinity Cu transporter (PtZIP49400). PtCTR49224 has high homology to Homo sapiens hCTR1, which depending on the accessibility to extracellular reducing agents, the hCTR1 itself is involved in the reduction of Cu2+ to Cu+ before internalization. We combined these physiological and physicochemical data to calculate the rate constants for the internalization of Cu, and established that while the high-affinity Cu uptake system (S1) is borderline between a kinetically or thermodynamically controlled system, the low-affinity Cu transporters, S2, is thermodynamically-controlled. We revised the inverse relationship between the concentrations of inorganic complexes of essential metals (i.e., Ni, Fe, Co, Zn, Cd, Mn and Cu) in the mixed layer and the formation rate constant of metal transporters in phytoplankton, highlighting the link between the chemical properties of phytoplankton metal transporters and the availability and speciation of trace metals in the surface ocean.

Long-term suboptimal dietary trace element supply does not affect trace element homeostasis in murine cerebellum.

The ageing process is associated with alterations of systemic trace element (TE) homeostasis increasing the risk, e.g. neurodegenerative diseases. Here, the impact of long-term modulation of dietary intake of copper, iron, selenium, and zinc was investigated in murine cerebellum. Four- and 40-wk-old mice of both sexes were supplied with different amounts of those TEs for 26 wk. In an adequate supply group, TE concentrations were in accordance with recommendations for laboratory mice while suboptimally supplied animals received only limited amounts of copper, iron, selenium, and zinc. An additional age-adjusted group was fed selenium and zinc in amounts exceeding recommendations. Cerebellar TE concentrations were measured by inductively coupled plasma-tandem mass spectrometry. Furthermore, the expression of genes involved in TE transport, DNA damage response, and DNA repair as well as selected markers of genomic stability [8-oxoguanine, incision efficiency toward 8-oxoguanine, 5-hydroxyuracil, and apurinic/apyrimidinic sites and global DNA (hydroxy)methylation] were analysed. Ageing resulted in a mild increase of iron and copper concentrations in the cerebellum, which was most pronounced in the suboptimally supplied groups. Thus, TE changes in the cerebellum were predominantly driven by age and less by nutritional intervention. Interestingly, deviation from adequate TE supply resulted in higher manganese concentrations of female mice even though the manganese supply itself was not modulated. Parameters of genomic stability were neither affected by age, sex, nor diet. Overall, this study revealed that suboptimal dietary TE supply does not substantially affect TE homeostasis in the murine cerebellum.

Trace and essential elements as vital components to improve the performance of the male reproductive system: Implications in cell signaling pathways.

Successful male fertilization requires the main processes such as normal spermatogenesis, sperm capacitation, hyperactivation, and acrosome reaction. The progress of these processes depends on some endogenous and exogenous factors. So, the optimal level of ions and essential and rare elements such as selenium, zinc, copper, iron, manganese, calcium, and so on in various types of cells of the reproductive system could affect conception and male fertility rates. The function of trace elements in the male reproductive system could be exerted through some cellular and molecular processes, such as the management of active oxygen species, involvement in the action of membrane channels, regulation of enzyme activity, regulation of gene expression and hormone levels, and modulation of signaling cascades. In this review, we aim to summarize the available evidence on the role of trace elements in improving male reproductive performance. Also, special attention is paid to the cellular aspects and the involved molecular signaling cascades.

Current Trends on the Involvement of Zinc, Copper, and Selenium in the Process of Hepatocarcinogenesis.

Numerous nutritional factors increase the risk of hepatocellular carcinoma (HCC) development. The dysregulation of zinc, copper, and selenium homeostasis is associated with the occurrence of HCC. The impairment of the homeostasis of these essential trace elements results in oxidative stress, DNA damage, cell cycle progression, and angiogenesis, finally leading to hepatocarcinogenesis. These essential trace elements can affect the microenvironment in HCC. The carrier proteins for zinc and copper and selenium-containing enzymes play important roles in the prevention or progression of HCC. These trace elements enhance or alleviate the chemosensitivity of anticancer agents in patients with HCC. The zinc, copper, or selenium may affect the homeostasis of other trace elements with each other. Novel types of cell death including ferropotosis and cupropotosis are also associated with hepatocarcinogenesis. Therapeutic strategies for HCC that target these carrier proteins for zinc and copper or selenium-containing enzymes have been developed in in vitro and in vivo studies. The use of zinc-, copper- or selenium-nanoparticles has been considered as novel therapeutic agents for HCC. These results indicate that zinc, copper, and selenium may become promising therapeutic targets in patients with HCC. The clinical application of these agents is an urgent unmet requirement. This review article highlights the correlation between the dysregulation of the homeostasis of these essential trace elements and the development of HCC and summarizes the current trends on the roles of these essential trace elements in the pathogenesis of hepatocarcinogenesis.

Parental obesity predisposes to exacerbated metabolic and inflammatory disturbances in childhood obesity within the framework of an altered profile of trace elements.

BACKGROUND: Family history of obesity is known to increase the odds of developing childhood obesity in the offspring, but its influence in underlying molecular complications remains unexplored. SUBJECTS/METHODS: Here, we investigated a population-based cohort comprising children with obesity, with and without parental obesity (PO+, N = 20; PO-, N = 29), and lean healthy children as controls (N = 30), from whom plasma and erythrocyte samples were collected to characterize their multi-elemental profile, inflammatory status, as well as carbohydrate and lipid metabolisms. RESULTS: We found parental obesity to be associated with unhealthier outcomes in children, as reflected in increased blood insulin levels and reduced insulin sensitivity, unfavorable lipid profile, and pro-inflammatory milieu. This was accompanied by moderate alterations in the content of trace elements, including increased copper-to-zinc ratios and iron deficiency in circulation, as well as metal accumulation within erythrocytes. CONCLUSIONS: Therefore, we hypothesize that family history of obesity could be an important risk factor in modulating the characteristic multi-elemental alterations behind childhood obesity, which in turn could predispose to boost related comorbidities and metabolic complications.

Selective trace elements significantly enhanced methane production in coal bed methane systems by stimulating microbial activity.

Trace elements are associated with the microbial degradation of organic matter and methanogenesis, as enzymes in metabolic pathways often employ trace elements as essential cofactors. However, only a few studies investigated the effects of trace elements on the metabolic activity of microbial communities associated with biogenic coalbed methane production. We aimed to determine the effects of strategically selected trace elements on structure and function of active bacterial and methanogenic communities to stimulate methane production in subsurface coalbeds. Microcosms were established with produced water and coal from coalbed methane wells located in the Powder River Basin, Wyoming, USA. In initial pilot experiments with eight different trace elements, individual amendments of Co, Cu, and Mo lead to significantly higher methane production. Transcript levels of mcrA, the key marker gene for methanogenesis, positively correlated with increased methane production. Phylogenetic analysis of the mcrA cDNA library demonstrated compositional shifts of the active methanogenic community and increase of their diversity, particularly of hydrogenotrophic methanogens. High-throughput sequencing of cDNA obtained from 16S rRNA demonstrated active and abundant bacterial groups in response to trace element amendments. Active Acetobacterium members increased in response to Co, Cu, and Mo additions. The findings of this study yield new insights into the importance of essential trace elements on the metabolic activity of microbial communities involved in subsurface coalbed methane and provide a better understanding of how microbial community composition is shaped by trace elements.IMPORTANCEMicrobial life in the deep subsurface of coal beds is limited by nutrient replenishment. While coal bed microbial communities are surrounded by carbon sources, we hypothesized that other nutrients such as trace elements needed as cofactors for enzymes are missing. Amendment of selected trace elements resulted in compositional shifts of the active methanogenic and bacterial communities and correlated with higher transcript levels of mcrA. The findings of this study yield new insights to not only identify possible limitations of microbes by replenishment of trace elements within their specific hydrological placement but also into the importance of essential trace elements for the metabolic activity of microbial communities involved in subsurface coalbed methane production and provides a better understanding of how microbial community composition is shaped by trace elements. Furthermore, this finding might help to revive already spent coal bed methane well systems with the ultimate goal to stimulate methane production.

In vitro exposure to PM2.5 of olfactory Ensheathing cells and SH-SY5Y cells and possible association with neurodegenerative processes.

PM2.5 exposure represents a risk factor for the public health. PM2.5 is able to cross the blood-alveolar and blood-brain barriers and reach the brain through three routes: nasal olfactory pathway, nose-brain pathway, blood-brain barrier pathway. We evaluated the effect of PM2.5 to induce cytotoxicity and reduced viability on in vitro cultures of OECs (Olfactory Ensheathing Cells) and SH-SY5Y cells. PM2.5 samples were collected in the metropolitan area of Catania, and the gravimetric determination of PM2.5, characterization of 10 trace elements and 16 polycyclic aromatic hydrocarbons (PAHs) were carried out for each sample. PM2.5 extracts were exposed to cultures of OECs and SH-SY5Y cells for 24-48-72 h, and the cell viability assay (MTT) was evaluated. Assessment of mitochondrial and cytoskeleton damage, and the assessment of apoptotic process were performed in the samples that showed lower cell viability. We have found an annual average value of PM2.5 = 16.9 µg/m3 and a maximum value of PM2.5 = 27.6 µg/m3 during the winter season. PM2.5 samples collected during the winter season also showed higher concentrations of PAHs and trace elements. The MTT assay showed a reduction in cell viability for both OECs (44%, 62%, 64%) and SH-SY5Y cells (16%, 17%, 28%) after 24-48-72 h of PM2.5 exposure. Furthermore, samples with lower cell viability showed a decrease in mitochondrial membrane potential, increased cytotoxicity, and also impaired cellular integrity and induction of the apoptotic process after increased expression of vimentin and caspase-3 activity, respectively. These events are involved in neurodegenerative processes and could be triggered not only by the concentration and time of exposure to PM2.5, but also by the presence of trace elements and PAHs on the PM2.5 substrate. The identification of more sensitive cell lines could be the key to understanding how exposure to PM2.5 can contribute to the onset of neurodegenerative processes.

Comparison of test performance of two commonly used multiplex assays to measure micronutrient and inflammatory markers in serum: results from a survey among pregnant women in South Africa.

The combined sandwich-ELISA (s-ELISA; VitMin Lab, Germany) and the Quansys Q-Plex™ Human Micronutrient Array (7-Plex) are multiplex serum assays that are used to assess population micronutrient status in low-income countries. We aimed to compare the agreement of five analytes, α-1-acid glycoprotein (AGP), C-reactive protein (CRP), ferritin, retinol-binding protein 4 (RBP4) and soluble transferrin receptor (sTfR) as measured by the 7-Plex and the s-ELISA. Serum samples were collected between March 2016 and December 2017. Pregnant women (n 249) were recruited at primary healthcare clinics in Johannesburg, and serum samples were collected between March 2016 and December 2017. Agreement between continuous measurements was assessed by Bland-Altman plots and concordance measures. Agreement in classifications of deficiency or inflammation was assessed by Cohen's kappa. Strong correlations (r > 0·80) were observed between the 7-Plex and s-ELISA for CRP and ferritin. Except for CRP, the 7-Plex assay gave consistently higher measurements than the s-ELISA. With the exception of CRP (Lin's ρ = 0·92), there was poor agreement between the two assays, with Lin's ρ < 0·90. Discrepancies of test results difference between methods increased as the serum concentrations rose. Cohen's kappa for all the five analytes was < 0·81 and ranged from slight agreement (vitamin A deficiency) to substantial (inflammation and Fe deficiency) agreement. The 7-Plex 1.0 is a research and or surveillance tool with potential for use in low-resource laboratories but cannot be used interchangeably with the s-ELISA. Further optimising and validation is required to establish its interchangeability with other validated methods.

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker on oxidative stress and metabolism of elements in kidney of STZ-induced diabetic rats.

In diabetes, increased oxidative stress and impaired trace element metabolism play an important role in the pathogenesis of diabetic nephropathy. The objective of this research was to examine the outcomes of blocking the renin-angiotensin system, using either the angiotensin-converting enzyme inhibitor (ACEI), perindopril, or the angiotensin II type 1 (AT1) receptor blocker, irbesartan, on oxidative stress and trace element levels such as Zn, Mg, Cu, and Fe in the kidneys of diabetic rats that had been induced with streptozotocin. Thirty-two Wistar albino male rats were equally divided into four groups. The first group was used as a control. The second group of rats developed diabetes after receiving a single intraperitoneal dose of STZ. The third and fourth groups of rats had STZ-induced diabetes and received daily dosages of irbesartan (15 mg/kg b.w/day) and perindopril (6 mg/kg b.w/day) treatment, respectively. Biochemical analysis of the kidneys showed a distinct increase in oxidative stress, indicated by heightened levels of malondialdehyde (MDA) and decreased superoxide dismutase (SOD) activities, as well as reduced glutathione (GSH) levels in the kidneys of diabetic rats. In the kidneys of diabetic rats, the mean levels of Fe and Cu were found to be significantly higher than those of the control group. Additionally, the mean levels of Zn and Mg were significantly lower in the diabetic rats compared to the control rats. Both perindopril and irbesartan decreased significantly MDA content and increased SOD activities and GSH levels in the kidneys of rats with diabetes. The Zn and Mg concentrations in the kidneys of diabetic rats treated with perindopril and irbesartan were markedly higher than in untreated STZ-diabetic rats, while the Cu and Fe concentrations were significantly lower. The urinary excretion of rats treated with perindopril and irbesartan showed a pronounced increase in Cu levels, along with a significant reduction in Zn and Mg levels. Although diabetic rats demonstrated degenerative morphological alterations in their kidneys, both therapies also improved diabetes-induced histopathological modifications in the kidneys. Finally, the present results suggest that manipulating the levels of Zn, Mg, Cu, and Fe - either through ACE inhibition or by blocking AT1 receptors - could be advantageous in reducing lipid peroxidation and increasing antioxidant concentration in the kidneys of diabetic rats.

Gene expression and trace elements in Greenlandic ringed seals (Pusa hispida).

Marine top predators such as ringed seals biomagnify environmental contaminants; and with the increasing human activities in the Arctic, ringed seals are exposed to biologically significant concentrations of trace elements resulting in reproductive impairment, immunosuppression, and neurological damages. Little is known about the molecular effects of heavy metals on these vulnerable apex predators suffering from a rapidly changing Arctic with significant loss of sea-ice. In the present study, concentrations of cadmium (Cd), mercury (Hg) and selenium (Se) were measured in liver of sixteen Greenlandic ringed seals (nine adults and seven subadults) together with molecular biomarkers involved in bio-transformation, oxidative stress, endocrine disruption and immune activity in blood and blubber. The concentrations of trace elements increased in the following order: Hg > Se > Cd with levels of mercury and selenium being highest in adults. Aryl hydrocarbon receptor nuclear translocator (ARNT), peroxisome proliferator activated receptor alpha (PPARα, estrogen receptor alpha (ESR1), thyroid hormone receptor alpha (TRα) and interleukin - 2 (IL-2) mRNA transcript levels were highest in blubber, while heat shock protein 70 (HSP70) and interleukin - 10 (IL-10) were significantly higher in blood. There were no significant correlations between the concentrations of trace elements and mRNA transcript levels suggesting that stressors other than the trace elements investigated are responsible for the changes in gene expression levels. Since Hg seems to increase in Greenlandic ringed seals, there is a need to re-enforce health monitoring of this ringed seal population.

Enhancement of Growth and Secondary Metabolites by the Combined Treatment of Trace Elements and Hydrogen Water in Wheat Sprouts.

This study aimed to evaluate the response of Triticum aestivum to hydrogen water (HW) and trace elements treated with HW. A pot experiment was conducted to assess the growth indices, secondary metabolites, and antioxidant levels. The response surface methodology (RSM) approach was used to ascertain the concentrations and significant interaction between treatments. The outcomes demonstrated that the combined treatment of Se acid and Mo oxide exhibited a notable positive effect on the growth and secondary metabolites, when treated with HW as compared to distilled water (DW). Notably, the interaction between these two treatments is significant, and the higher response was observed at the optimal concentration of 0.000005% for Se acid and 0.06% for Mo oxide. Additionally, an in vitro experiment revealed that the mixture treatment inhibits the accumulation of lipids in HepG2 hepatocytes cells. Moreover, metabolic analysis revealed that upregulated metabolites are linked to the inhibition of lipid accumulation. In addition, the analysis emphasizes that the continued benefits of higher plants as a renewable supply for chemicals compounds, especially therapeutic agents, are being expanded and amplified by these state-of-the-art technologies.

Interactions between enzyme preparations and trace element sources on growth performance and intestinal health of broiler chicks.

This experiment was conducted to explore the interactions between enzyme preparations and trace element sources on growth performance and intestinal health of broilers chicks. A total of 480 one-day-old healthy male yellow-feather broilers with similar weight were randomly arranged in a 2  ×  2 factorial design with 2 kinds of compound trace element sources (inorganic [I] and organic [O] trace element supplemented with 80, 8, 60, 40, 0.15 mg/kg of Fe, Cu, Mn, Zn, and Se, respectively) and 2 levels of enzyme preparations (0 and 200 mg/kg). The 4 groups named I, O, IE, and OE with 6 replicates and 20 birds per replicate. The trail lasted for 28 days. Results showed that the average weight (ABW), average daily gain (ADG) of broilers in IE and OE groups significantly increased while the F/G significantly decreased as compared with group I and O (P < 0.05). Enzyme preparation supplementation, regardless of the trace element sources, significantly increased the duodenal and jejunal endogenous enzyme (e.g., Try and AACT) activity, and improved the morphology and jejunal barrier function evidenced by the increased villus height and MUC-2 mRNA expression (P < 0.05). Sequencing data manifested that enzyme preparations favorably modulated the cecal microflora by increasing bacterial diversity and abundance of short-chain fatty acid (SCFA)-producing bacteria (e.g., Anaerostipes, Anaerofusis, and Pygmaioactor), while decreasing the abundance of harmful bacteria (e.g., Desulfovibrio). Factorial analysis indicated that there were no interactions between enzyme preparation and trace element sources on growth performance and intestinal health of broiler chicks. In conclusion, dietary supplementation with enzyme preparations, regardless of the trace element sources, could enhance endogenous enzyme activity, improve intestinal morphology and barrier functions, and favorably modulate the cecal microflora, thereby improving the intestinal health and growth performance of broiler chicks.

Associations of essential trace elements with epigenetic aging indicators and the potential mediating role of inflammation.

BACKGROUND: Essential trace elements (ETEs) play essential roles in vital functions, but their effects on epigenetic aging remain poorly understood. OBJECTIVES: This study aimed to investigate the associations of ETEs with four epigenetic aging indicators and assess the potential mediating role of inflammation. METHODS: We recruited 93 individuals from hospitals between October 2018 and August 2019. Plasma levels of cobalt, copper, iron, manganese, molybdenum, selenium, and zinc were measured by ICP-MS, and leukocyte DNA methylation levels were measured using Illumina MethylationEPIC beadchip. Linear regression was used to estimate the association between seven plasma ETEs and epigenetic aging indicators. Weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) models were used to evaluate the effect of ETEs mixtures. Inflammatory status was assessed using four systemic inflammation indices (neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and systemic immune-inflammation index (SII)) and three cytokines (IL-4, IL-6, and IL-13). Mediation analysis was performed to explore the role of inflammation in the above associations. RESULTS: Plasma Se levels were significantly negatively associated with DunedinPACE, whereas Cu levels were significantly positively associated with it. Both WQS regression and BKMR models suggested that Se and Cu dominate the effect of the ETEs mixture. MLR and interleukin 6 were significantly and positively associated with DunedinPACE. Further mediation analysis indicated that inflammation partially mediated the association between ETEs and DunedinPACE. DISCUSSION: Plasma Se and Cu levels are closely associated to epigenetic aging, and inflammation might be a potential mechanism underlying this relationship. These findings contribute to the prevention of health hazards associated with population aging.

Synchrotron X-rays reveal the modes of Fe binding and trace metal storage in the brown algae Laminaria digitata and Ectocarpus siliculosus.

Iron is accumulated symplastically in kelp in a non-ferritin core that seems to be a general feature of brown algae. Microprobe studies show that Fe binding depends on tissue type. The sea is generally an iron-poor environment and brown algae were recognized in recent years for having a unique, ferritin-free iron storage system. Kelp (Laminaria digitata) and the filamentous brown alga Ectocarpus siliculosus were investigated using X-ray microprobe imaging and nanoprobe X-ray fluorescence tomography to explore the localization of iron, arsenic, strontium, and zinc, and micro-X-ray absorption near-edge structure (µXANES) to study Fe binding. Fe distribution in frozen hydrated environmental samples of both algae shows higher accumulation in the cortex with symplastic subcellular localization. This should be seen in the context of recent ultrastructural insight by cryofixation-freeze substitution that found a new type of cisternae that may have a storage function but differs from the apoplastic Fe accumulation found by conventional chemical fixation. Zn distribution co-localizes with Fe in E. siliculosus, whereas it is chiefly located in the L. digitata medulla, which is similar to As and Sr. Both As and Sr are mostly found at the cell wall of both algae. XANES spectra indicate that Fe in L. digitata is stored in a mineral non-ferritin core, due to the lack of ferritin-encoding genes. We show that the L. digitata cortex contains mostly a ferritin-like mineral, while the meristoderm may include an additional component.

Trace Mineral Nutrition of Sheep.

Trace mineral nutrition of sheep often focuses on their greater susceptibility to copper toxicosis due to a lesser biliary excretion ability compared with other ruminants. Our understanding of sheep trace mineral requirements has improved for most elements allowing for a factorial approach to determining daily requirement instead of a dietary concentration. Forage trace mineral content is influenced by many factors making issues of trace mineral supplementation geographic-dependent. Oral delivery of trace elements is a preferred supplementation method, and this can be achieved through free choice trace mineralized salt or direct dietary incorporation.