Intestinal mucin is a chaperone of multivalent copper.

Mucus protects the epithelial cells of the digestive and respiratory tracts from pathogens and other hazards. Progress in determining the molecular mechanisms of mucus barrier function has been limited by the lack of high-resolution structural information on mucins, the giant, secreted, gel-forming glycoproteins that are the major constituents of mucus. Here, we report how mucin structures we determined enabled the discovery of an unanticipated protective role of mucus: managing the toxic transition metal copper. Using two juxtaposed copper binding sites, one for Cu2+ and the other for Cu1+, the intestinal mucin, MUC2, prevents copper toxicity by blocking futile redox cycling and the squandering of dietary antioxidants, while nevertheless permitting uptake of this important trace metal into cells. These findings emphasize the value of molecular structure in advancing mucosal biology, while introducing mucins, produced in massive quantities to guard extensive mucosal surfaces, as extracellular copper chaperones.

Association between whole blood essential trace elements and cognitive function in older adults.

BACKGROUND: Essential trace elements (ETEs) are essential nutrients for keeping the nervous system functioning. Associations between ETEs and cognitive function are still inconclusive and limited. OBJECTIVES: We aimed to investigate the individual and joint associations between ETEs and cognitive function among older adults. METHODS: A population (N = 2181) at an average age≥ 65 from Yiwu cohort in China was available for this study. Whole blood chromium (Cr), selenium (Se), manganese (Mn), and copper (Cu) concentrations were measured by inductively coupled plasma mass spectrometry (ICP-MS). Cognitive function was assessed using the Mini-Mental State Examination (MMSE), consisting of five specific cognitive domains: orientation, registry, attention and calculation, recall, and language and praxis. Linear regression, restricted cubic spline (RCS) analysis, and Bayesian kernel machine regression (BKMR) were used to analyze the individual and joint associations between ETEs and cognitive function. RESULTS: The association between Cr and MMSE score presented an inverted-U shape (Q3 versus Q1: ß = 0.774, 95 % CI: 0.297, 1.250; Q4 versus Q1: ß = 0.481, 95 % CI: 0.006, 0.956); and Cr was especially associated with the registry, recall, and language and praxis. Per IQR (36.32 µg/L) increase of Se was positively associated with the MMSE score (ß = 0.497, 95 % CI: 0.277, 0.717) and all five cognitive domains. The BKMR showed that the dose-response association between Se and cognitive function increased initially and then decreased with increasing Se concentration when fixed the other ETEs in median. ETEs mixture was positively associated with cognitive function, and Se (posterior inclusion probabilities, PIPs = 0.915) was the most important contributor within the ETEs mixture. CONCLUSIONS: The nonlinear association between Cr and cognitive function suggested further exploration of an appropriate concentration range for ETEs. A positive association between mixed ETEs and cognitive function is a reminder that their joint association should be considered. Further prospective studies or intervention studies are warranted to validate our findings in the future.

The association between essential trace element mixture and cognitive function in Chinese community-dwelling older adults.

BACKGROUND: The evidence about the effect of essential trace element (ETE) mixture on cognitive function amongst older adults is limited. This study aims to evaluate the associations of single ETEs and ETE mixture with cognitive function using a representative sample of community-dwelling older adults in China. METHODS: A total of 3814 older adults were included in the study. Urinary concentrations of selenium (Se), vanadium (V), cobalt (Co), strontium (Sr), and molybdenum (Mo) were detected by inductively coupled plasma mass spectrometry. Cognitive function in older adults was assessed using the Chinese version of the Mini-Mental State Examination (MMSE). Linear regression and Bayesian kernel machine regression (BKMR) were performed to explore the associations of single ETEs and ETE mixture with cognitive function, respectively. RESULTS: Linear regression showed that urinary levels of Se and V were positively associated with MMSE scores in the adjusted single-element models. BKMR also showed marginally positive associations of Se and V with MMSE scores. Moreover, higher urinary levels of ETE mixture were significantly associated with increased MMSE scores in a dose-response pattern, and Se was the most important contributor within the mixture. Both Se and V demonstrated positive additive effects on the associations of other ETEs with MMSE scores, whereas Co had a negative additive effect. CONCLUSIONS: V and Se are positively associated with cognitive function, individually and as a mixture. ETE mixture exhibits a linear dose-response association with improved cognitive function, with Se being the most important component within the mixture. Mixture analyses rather than single ETE analyses may provide a real-world perspective on the relationship between ETE mixture and cognitive function. Further cohort studies are needed to clarify the association of multiple ETEs with cognitive function.

Association between preoperative serum zinc level and prognosis in patients with advanced esophageal cancer in the neoadjuvant treatment era.

Background: Zinc (Zn), an essential trace element, has an adverse influence on the prognosis of several cancers. However, the association between the preoperative serum Zn level and outcomes in patients with advanced esophageal cancer in the current neoadjuvant treatment era remains unclear. Methods: This study involved 185 patients with esophageal cancer who underwent R0 surgery after neoadjuvant chemotherapy from August 2017 to February 2021. We retrospectively investigated the relationship between the preoperative serum Zn level and the patients' outcomes. Results: The patients were divided into a low Zn group (<64 µg/dL) and a high Zn group (≤64 µg/dL) according to the mean preoperative serum Zn level. Low Zn had significantly worse overall survival (OS) (2-year OS rate: 76.2% vs. 83.3% in low vs. high Zn; p = 0.044). A low Zn in pathological non-responders (Grade ≤ 1a) was significantly associated with a shorter 2-year recurrence-free survival (RFS) rate (39.6% vs. 64.1% in low vs. high Zn; p = 0.032). The multivariate analysis identified low BMI and Zn level among preoperative nutritional status indices as an independent risk factor for worse RFS in non-responders. Compared with responders, pathological non-responders comprised significantly more males and a performance status of ≥1, and there was no difference in Zn level according to pathological response. Conclusion: A preoperative low Zn level had a negative impact on early recurrence in esophageal cancer patients who underwent neoadjuvant chemotherapy. This suggests the need to administer Zn supplementation to patients with esophageal cancer who have preoperative Zn deficiency.

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.

Assessment on Solubility and Solid Phase Chemical Fractionation of Manganese in Hot Infusions of Green and Roasted Mate.

A solid phase chemical fractionation (SPCF) of the Mn in hot infusions prepared from commercial samples of roasted (RM) and green mate (GM) using a chelating resin Chelex 100 (NH4+ form) was performed to assess the relative lability of this essential trace element (ETE). In addition, total Mn contents in the RM and GM samples and their infusions were determined by flame atomic absorption spectrometry. Total polyphenol (TP) contents and the presence of soluble melanoidins (SM) were correlated with the Mn solubility in the RM and GM infusions. From the SPCF study, it was possible to observe that the soluble Mn forms in the mate infusions were essentially associated with relatively noninert chemical species (98.4-99.7%), suggesting that they may be potentially bioavailable. In addition, the soluble Mn contents in the GM infusions were 20.5% higher than those found in the RM. Mn solubility in the (RM) infusions was highly and directly correlated (r = 0.99) with the soluble TP, while in the GM infusions, it was high and inversely correlated with soluble TP (r = -0.87). On the other hand, Mn solubility in the RM and GM infusions was weakly correlated with the SM. It should be stressed that GM infusions can contribute with 57 and 44% more than the RM infusions to the recommended adequate intake of Mn established for females and males, respectively. Moreover, this work is the first to evaluate and compare the relative lability of Mn and its solubility in the RM and GM infusions.

Serum Cu, Zn and IL-1ß Levels May Predict Fetal Miscarriage Risk After IVF Cycles: A Nested Case-Control Study.

To explore the association between serum-related indicators (levels of inflammatory cytokines and essential trace elements) and miscarriage risk among infertile women undergoing assisted reproductive techniques (ART) on the 14th day after embryo transfer, and to develop and establish a multivariable algorithm model that might predict pregnancy outcome. According to a nested case-control study design, a total of 100 miscarriage cases and 100 live birth controls were included in this study, and women in both groups were infertile and have underwent in vitro fertilization (IVF). Pregnancy tests were performed and serum levels of five essential trace elements (vanadium (V), copper (Cu), zinc (Zn), selenium (Se) and molybdenum (Mo)) and five inflammatory cytokines (interleukin-1ß (IL-1ß), IL-6, IL-8, IL-10 and tumor necrosis factor-α (TNF-α)) of the participants were measured on the 14th day after embryo transfer. The serum levels of five inflammatory cytokines were determined by multiple magnetic bead enzyme immunity analyzer; and the serum concentrations of five elements were determined simultaneously by inductively coupled plasma‒mass spectrometry (ICP ‒ MS). The logistic regression was used to evaluate the relationship between these serum indices and miscarriage risk among women undergoing ART, and a predictive model of pregnancy outcome based on these indices was established. The levels of IL-10, IL-1ß and TNF-α of infertile women in the live birth group were significantly higher than those in the miscarriage group (p = 0.009, p < 0.001, p = 0.006), and the levels of V, Cu, Zn and Se of infertile women in the live birth group were also significantly higher than those in the miscarriage group (all p < 0.001). Through logistic regression analyses, we found that serum levels of IL-1ß, TNF-α, V, Cu, Zn and Se were significantly and negatively associated with miscarriage risk. Different combination prediction models were generated according to the results of logistic regression analyses, and the combination of IL-1ß, Cu and Zn had the best prediction performance. The area under the curve (AUC) was 0.776, the sensitivity of the model was 60% and the specificity was 84%. In conclusion, the serum-related indicators of women undergoing ART on the 14th day after embryo transfer, including the inflammatory cytokines such as IL-1ß and TNF-α and the essential trace metal elements such as V, Cu, Zn and Se, were negatively correlated with miscarriage risk. A multivariate algorithm model to predict pregnancy outcome among women undergoing ART was established, which showed that IL-1ß, Cu and Zn might synergistically predict pregnancy outcome.

[Development and Assessment of a New Oral Selenium Fast-disintegrating Tablets].

Selenium is an essential trace element and its deficiency causes myositis, myocardial damage, and other symptoms. Patients receiving long-term intravenous nutrition or tube-feeding in particular are deficient in essential trace elements, including selenium, and require regular supplementation. In Japan, injectable selenium-containing products are listed on the National Health Insurance drug price list, and oral solutions are prepared and used in hospitals. However, these formulations have problems related to preservation and require complicated administration procedures. In this study, we developed a new fast-disintegrating tablet formulation of selenium, using SmartEx® (D-mannitol·low substituted hydroxypropylcellulose (L-HPC)·fully hydrolyzed polyvinyl alcohol (PVA) mixture) as a coprocessing additive, that can be administered orally or by feeding tube. The tablet formulation had excellent disintegrable capability, sufficient hardness, and did not cause tube blockage when administered in the simple suspension method. In addition, the tablet formulation showed no changes in properties in an accelerated test without packaging for 42 d, indicating that it could be stored for a long period. Fast-disintegrating tablets prepared with SmartEx® are expected to improve the adherence and quality of life of patients who require selenium supplementation.

The Effect of Flake Production and In Vitro Digestion on Releasing Minerals and Trace Elements from Wheat Flakes: The Extended Study of Dietary Intakes for Individual Life Stage Groups.

This thorough study analyses the amounts of 43 minerals and trace elements in non-traditional wheat grains, flakes, and undigested flake portions using ICP-MS and establishes declines in their respective contents after the flake production. It also identifies appropriate dietary intakes, in vitro digestibility values, retention factors, and metal pollution indexes. The element contents in wheat flakes are lower than in wheat grains after the hydrothermal treatment process, and their declines are: Na (48-72%), Ce (47-72%), Sr (43-55%), Tl (33-43%), Ti (32-41%), U (31-44%), Ho (29-69%), Cr (26-64%), Zr (26-58%), Ag (25-52%), and Ca (25-46%). The flakes significantly contributed to the recommended dietary intake or adequate intake of particular elements for men of all categories as follows: Mn (143%) > Mo > Cu > Mg ≥ Cr > Fe (16%); for women: Mn (up to 183%) > Mo > Cu > Cr ≥ Mg > Fe (7-16%); for pregnant women aged 19-30: Mn (165%) > Mo > Cu > Mg > Cr (25%); and finally, for lactating women: Mn (127%) > Mo > Cu > Mg > Cr (17%). The contributions to the provisional tolerable weekly or monthly intakes of all toxic elements were established as being within the official limits. The daily intakes for non-essential elements were also calculated. The retention factors were calculated to assess the element concentrations in the undigested part using the digestibility values (87.4-90.5%). The highest retention factors were obtained for V (63-92%), Y (57-96%), Ce (43-76%), Pb (34-58%), Tl (32-70%), Ta (31-66%), and Ge (30-49%). K, Mg, P, Zn, Ba, Bi, Ga, Sb, Cu, Ni, and As appear to be released easily from flake matrices during digestion. The metal pollution index has been confirmed as being lower for non-traditional wheat flakes when compared with grains. Importantly, 15-25% of the metal pollution index assessed for native flakes remains in the undigested flake portion after in vitro digestion.

The association between essential trace element (copper, zinc, selenium, and cobalt) status and the risk of early embryonic arrest among women undergoing assisted reproductive techniques.

Background: Early embryonic arrest (EEA) leads to repeated cessation of fresh cycles among infertile women undergoing in vitro fertilization (IVF). Whether the levels of some essential trace elements [copper (Cu), zinc (Zn), selenium (Se) and cobalt (Co)] in the bodies of women are related to the risk of EEA warrants study. Objective: Our study aimed to investigate the associations of peripheral blood levels of Cu, Zn, Se, and Co and their mixtures with the risk of EEA. Methods: A total of 74 EEA cases (123 IVF cycles) and 157 controls (180 IVF cycles) from the reproductive center of the First Affiliated Hospital of Anhui Medical University in Hefei, China, between June 2017 and March 2020 were included in our study. Demographic and clinical data were collected from electronic medical records. Cu, Zn, Se, and Co levels were measured in blood samples collected on the day of oocyte retrieval when infertile women entered clinical treatment for the first time using an inductively coupled plasma mass spectrometer (ICP-MS). Generalized estimating equation (GEE) models were used to evaluate the associations of four essential trace element concentrations individually with the risk of EEA, and Bayesian kernel machine regression (BKMR) was used to explore the associations between four essential trace element mixtures and the risk of EEA. Results: Se concentrations of infertile women were significantly lower in the case group compared with the control group. Co levels were significantly higher in the case group compared with the control group. The differences in Cu and Zn concentrations between the two groups were not significant. Based on single-metal models, Co was positively associated with the risk of EEA before and after adjustment for all confounders (odd ratio (OR) = 1.72, 95% confidence interval (CI): 1.18-2.52; OR = 2.27, 95% CI: 1.37-3.77, respectively), and Se was negatively associated with the risk of EEA before adjustment for all confounders (OR = 0.18, 95% CI: 0.07-0.51). BKMR analyses showed that Se was significantly and negatively associated with the risk of EEA when all the other three metals (Cu, Zn, and Co) were fixed at the 25th, 50th, or 75th percentiles, whereas Zn displayed a significant and positive association with the risk of EEA when all the other three metals (Cu, Se and Co) were fixed at the 25th, 50th, or 75th percentiles. Co did not show any effect on the risk of EEA when all the other metals (Cu, Zn, and Se) were fixed at the 25th, 50th, or 75th percentiles. In addition, an increasing trend of the joint effect of four essential trace elements on the risk of EEA was found, although it was not statistically significant. Conclusion: The levels of essential trace elements (Cu, Zn, Se, and Co) might correlate with the risk of EEA to some extent. The present study might provide a real-world perspective on the relationship between essential trace elements and the risk of EEA when considering them as a single element or as mixtures.

The association between essential trace element mixture and atherosclerotic cardiovascular disease risk among Chinese community-dwelling older adults.

The evidence about the association of the essential trace element (ETE) mixture with atherosclerotic cardiovascular disease (ASCVD) amongst older adults is limited. This study aims to evaluate the associations of single ETEs and the ETE mixture with the 10-year ASCVD risks and its predicting factors in Chinese community-dwelling older adults. A total of 607 community-dwelling older adults were included in this study. Blood levels of vanadium (V), chromium (Cr), manganese (Mn), cobalt (Co), nickel (Ni), and selenium (Se) were assessed by inductively coupled plasma mass spectrometry. The predicted 10-year ASCVD risk was calculated using the Prediction for ASCVD Risk in China (China-PAR) equations. Traditional linear regressions and Bayesian kernel machine regression (BKMR) were used to assess the associations of single ETEs and the ETE mixture with the 10-year ASCVD risks and its predicting factors such as systolic blood pressure (SBP), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), diabetes, and waist circumference (WC). In linear regression models, blood Cr levels were negatively associated with the 10-year ASCVD risks after adjustment for covariates (ß = - 0.07, 95% CI = - 0.11 ~ - 0.03); The 3th quartile (Q3) of Se levels was also associated with a lower 10-year ASCVD risks when compared with the lowest quartile (Q1) of Se levels (ßQ3 vs. Q1: - 0.12, 95% CI = - 0.22 ~ - 0.02). In BKMR models, the negative associations of Cr and Se with the 10-year ASCVD risks were observed. Higher blood levels of ETE mixture were associated with decreased 10-year ASCVD risks in a dose-response pattern, with Cr having the highest value of the posterior inclusion probability (PIP) within the mixture. Furthermore, a positive association between Cr and HDL-C and a negative association between Se and SBP were found in both linear regression and BKMR models. Cr and Se were negatively associated with the 10-year ASCVD risks, individually and as a mixture. ETE mixture showed a linear dose-response association with decreased 10-year ASCVD risks, with Cr being the most important component within the mixture. The negative association of the ETE mixture with the 10-year ASCVD risks may be attributed to Cr and Se, mainly mediated by HDL-C and SBP, respectively. Further cohort studies are needed to clarify this association.

Analysis of essential and non-essential trace elements in the organs of a mother-fetus pair of spotted seals (Phoca largha) from the Sea of Japan.

Concentrations of 22 essential and non-essential trace elements (Be, Al, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Mo, Ag, Cd, Sb, Ba, Tl, Pb, Th, U, and Hg) were measured in the organs of a mother-fetus pair (at the last trimester of pregnancy) of spotted seals from the Sea of ​Japan. The concentrations of eleven elements are reported for the first time. Eight organs of the pair were examined: lungs, heart, liver, kidneys, intestines, spleen, muscles, and bones. All trace elements detected in the organs of the mother were found also in the organs of the fetus at various concentrations. Placenta is not an effective barrier to prevent non-essential elements from getting into the fetus, but can control entry of some of them, e.g., aluminum, cadmium, and mercury. In most organs of the fetus, the concentrations of toxic trace elements (beryllium, antimony, thorium, and uranium) were noticeably higher than in the same organs of the mother, which indicates that during pregnancy female removes excess of non-essential trace elements by transferring them to the fetal body through the placental barrier.

Selected essential trace elements in maternal serum and risk for fetal orofacial clefts.

BACKGROUND: Disturbances in the homeostasis of essential trace elements (ETEs) may interfere with embryonic organogenesis. However, the effect of ETEs on the development of orofacial clefts (OFCs) remains unclear. OBJECTIVES: This study examined associations between concentrations of iron (Fe), zinc (Zn), selenium (Se), cuprum (Cu), cobalt (Co), and molybdenum (Mo) in maternal serum and risk for OFCs in offspring. METHODS: A total of 130 cases of OFCs and 260 nonmalformed controls were included in this study. Concentrations of Fe, Zn, Se, Cu, Co, and Mo in maternal serum were detected by inductively coupled plasma mass spectrometry. We examined associations between levels of the six ETEs in maternal serum and risk for OFCs for each element separately using multilevel mixed-effects logistic regression and for all elements collectively using Bayesian kernel machine regression (BKMR). RESULTS: Higher concentrations of Mo and Co in maternal serum were associated with a decreased risk for OFCs in a dose-dependent manner, with odds ratios and 95% confidence intervals of 0.37 (0.20-0.66) for the second tertile of Mo, 0.28 (0.15-0.54) for the third tertile of Mo, 0.54 (0.29-1.00) for the second tertile of Co, and 0.47 (0.25-0.87) for the third tertile of Co, with the lowest tertile as the referent. When all six ETEs were considered together, increased levels of ETEs were associated with a decreased risk for OFCs. In addition, Mo showed a protective effect against risk for OFCs when the other ETEs were fixed at their 25th, 50th, or 75th percentile, whereas the protective effect of Co turned to a null effect in the BKMR model. No association was observed between levels of Fe, Zn, Se, or Cu and risk for OFCs in either statistical model. CONCLUSION: Elevated concentrations of Mo in maternal serum were associated with a reduced risk for OFCs.

Essential trace elements in umbilical cord tissue and risk for neural tube defects.

Deficient or excessive quantities of essential trace elements (ETEs)1 in the fetal environment can compromise developmental processes. We investigated whether concentrations of zinc (Zn), manganese (Mn), selenium (Se), cobalt (Co), molybdenum (Mo), and nickel (Ni) in umbilical cord tissue are associated with risk for neural tube defects (NTDs). Umbilical cord tissues from 166 cases of NTD cases and 166 matched controls were collected and element concentrations were measured using inductively coupled plasma-mass spectrometry. Associations between ETE concentrations and the risk for NTDs were estimated using multivariate logistic regression while adjusting for potential confounders. Bayesian kernel machine regression (BKMR) was used to examine the joint effects of these ETEs. We found that median concentrations of Ni were higher but those of Mo and Co were lower in the NTD group than in the control group. Co was the only element that was associated with NTD risk after adjusting for confounders (OR 0.31, 95 % CI 0.12-0.79 for the second and OR 0.37, 95 % CI 0.15-0.91 for the top tertile relative to the lowest tertile). The association between Co and NTD risk was confirmed with the BKMR model. In addition, a joint effect of the six ETE mixture on NTD risk was observed: the risk decreased with the levels of the mixture from 25th percentile through 75th percentile. In conclusion, higher levels of Co were associated with lower risk for NTDs, and NTD risk decreased with the levels of the six ETEs as a co-exposure mixture, suggesting a protective effect.

Essential trace elements in placental tissue and risk for fetal neural tube defects.

This study examined the associations between concentrations of cobalt (Co), iron (Fe), manganese (Mn), molybdenum (Mo), selenium (Se), and zinc (Zn) in placental tissue and risks for NTDs with a case-control design consisting of 408 fetuses or newborns with neural tube defects (NTDs) and 593 non-malformed fetuses or newborns. The concentrations of Zn and Fe were determined by inductively coupled plasma-emission spectrometer and the other four elements by inductively coupled plasma-mass spectrometer. Element concentrations were presented in ng/g or µg/g dry weight of placental tissue. The associations between the levels of each of the six ETEs and risk for NTDs were evaluated using multivariable logistic regression, and the associations between overall levels of all six ETEs and risk for NTDs were examined using Bayesian kernel machine regression (BKMR). Concentrations above the median concentration of all participants for an individual element were associated with increased risk for NTDs: Mn, 3.17-fold (95% CI 2.35-4.28); Mo, 3.73-fold (95% CI 2.74-5.07); Se, 3.28-fold (95% CI 2.44-4.42); and Zn, 2.85-fold (95% CI 2.13-3.83), and a decreased risk for Co [OR, 0.18 (95% CI 0.14-0.25)]. The risk for NTDs increased with the increase in the concentrations of Mn, Mo, Se, and Zn, but decreased for Co, in the second, third, and fourth quartiles, respectively, compared to their lowest quartile (all Pstrend < 0.01). In BKMR model, the risk for NTDs increased constantly when the overall exposure levels were higher than the median of the six ETEs as a co-exposure mixture, and the associations between Co, Mn, Se, and Zn and NTD risk remained when the remaining five elements were taken into consideration simultaneously. Taken together, when evaluated individually, higher levels of Mn, Se, and Zn in placental tissue are associated with increased risk for NTDs, while higher levels of Co are associated with decreased risk for NTDs; when examined collectively, the risk of NTDs increases continuously when exposure levels are higher than the median of the six ETE mixture.

Selenium and Selenoproteins in Immune Mediated Thyroid Disorders.

Selenium is an essential micronutrient that is required for the synthesis of selenocysteine-containing selenoproteins, processing a wide range of health effects. It is known that the thyroid is one of the tissues that contain more selenium. The "selenostasis" maintenance seems to contribute to the prevention of immune mediated thyroid disorders. Prospective, observational studies, randomized, controlled studies evaluating selenium supplementation, and review articles that are available in Medline and PubMed have undergone scrutiny. The differences concerning methodology and results variability have been analyzed. Several authors support the idea of a potential efficacy of selenium (mainly selenomethionine) supplementation in reducing antithyroperoxidase antibody levels and improve thyroid ultrasound features. In mild Graves' orbitopathy, selenium supplementation has been associated with a decrease of the activity, as well as with quality of life improvement. Future research is necessary to clearly understand the selenium supplementation biologic effects while considering the basal selenium levels/biomarkers, selenoprotein gene polymorphisms that may be involved, underlying comorbidities and the major clinical outcomes.

Dietary Selenium and Human Health.

Next year (2017), the micronutrient Selenium (Se) is celebrating its birthday-i.e., 200 years after first being identified by the Swedish chemist Jöns Jakob Berzelius. Despite its impressive age, research into the functions of this essential trace element is very alive and reaching out for new horizons. This special issue presents some recent fascinating, exciting, and promising developments in Se research in the form of eight original contributions and seven review articles. Collectively, aspects of Se supply, biochemical, physiological, and chemotherapeutic effects, and geobiological interactions are covered by leading scientists in the areas of nutritional, basic, and clinical research. It is obvious from the contributions that the bicentennial anniversary will celebrate a micronutrient still in its infancy with respect to being understood in terms of its biomedical importance.

The essential toxin: impact of zinc on human health.

Compared to several other metal ions with similar chemical properties, zinc is relatively harmless. Only exposure to high doses has toxic effects, making acute zinc intoxication a rare event. In addition to acute intoxication, long-term, high-dose zinc supplementation interferes with the uptake of copper. Hence, many of its toxic effects are in fact due to copper deficiency. While systemic homeostasis and efficient regulatory mechanisms on the cellular level generally prevent the uptake of cytotoxic doses of exogenous zinc, endogenous zinc plays a significant role in cytotoxic events in single cells. Here, zinc influences apoptosis by acting on several molecular regulators of programmed cell death, including caspases and proteins from the Bcl and Bax families. One organ where zinc is prominently involved in cell death is the brain, and cytotoxicity in consequence of ischemia or trauma involves the accumulation of free zinc. Rather than being a toxic metal ion, zinc is an essential trace element. Whereas intoxication by excessive exposure is rare, zinc deficiency is widespread and has a detrimental impact on growth, neuronal development, and immunity, and in severe cases its consequences are lethal. Zinc deficiency caused by malnutrition and foods with low bioavailability, aging, certain diseases, or deregulated homeostasis is a far more common risk to human health than intoxication.