Association of serum five heavy metals level with all-cause and cause-specific mortality: a large population-based cohort study.

The study aimed to explore the association between five heavy metals exposure (Cadmium, Lead, Mercury, Manganese, and Selenium) and mortality [all-cause, cardiovascular disease (CVD), and cancer-related]. We integrated the data into the National Health and Nutrition Examination Survey from 2011 to 2018 years. A total of 16,092 participants were recruited. The link between heavy metals exposure and mortality was analyzed by constructing a restricted cubic spline (RCS) curve, Cox proportional hazard regression model, and subgroup analysis. The RCS curve was used to show a positive linear relationship between Cadmium, Lead, and all-cause mortality. In contrast, there was a negative linear correlation between Mercury and all-cause mortality. Additionally, Manganese and Selenium also had a J-shaped and L-shaped link with all-cause mortality. The positive linear, positive linear, negative liner, J-shaped, and L-shaped relationships were observed for Cadmium, Lead, Mercury, Manganese, and Selenium and CVD mortality, respectively. Cadmium, Lead, Mercury, and Selenium were observed to exhibit positive linear, U-shaped, negative linear, and L-shaped relationships with cancer-related mortality, respectively. There was an increase and then a decrease in the link between Manganese and cancer-related morality. This study revealed the correlation between the content of different elements and different types of mortality in the U.S. general population.

The Influence of Copper and Zinc on Photosynthesis and Phenolic Levels in Basil (Ocimum basilicum L.), Borage (Borago officinalis L.), Common Nettle (Urtica dioica L.) and Peppermint (Mentha piperita L.).

This work is aimed at relationships which govern zinc and copper uptake by four popular medicinal herbs: basil (Ocimum basilicum L.), borage (Borago officinalis L.), common nettle (Urtica dioica L.) and peppermint (Mentha piperita L.). They are often grown in soils with significant copper or zinc levels. Herbs were cultivated by a pot method in controlled conditions. Manganese, iron, copper and zinc concentrations were determined by High-Resolution Continuum Source Flame Atomic Absorption Spectrometry. The efficiency of photosynthesis was estimated by measuring the chlorophyll content, water use efficiency, net photosynthesis, intercellular CO2, stomatal conductance, and transpiration rate. Phenolic compounds were determined by the Folin-Ciocalteu method. Analysis of variance showed that herbs grown in soil treated with copper exhibited a lower iron content in roots, while manganese behaved in the opposite way. The only exception was borage, where a decrease in the manganese content in roots was observed. Both copper and zinc supplementations increased the total content of phenolics, while the highest increases were observed for common nettle and basil. Peppermint and borage responded less to supplementation. In the majority of samples, zinc and copper did not significantly affect the photosynthesis. Herbal extracts from common nettle and basil had unique antioxidant properties and may be good free radical scavengers.

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.

Association between Multiple Trace Elements, Executive Function, and Cognitive Impairment with No Dementia in Older Adults.

Many studies suggest a significant association between individual essential trace elements (ETEs) and cognitive impairment in older adults, but evidence of the synchronized effect of multiple ETEs on cognitive function is lacking. We investigated the association between multiple ETEs, cognitive impairment with no dementia (CIND), and executive function in older Korean adults, using the Bayesian kernel machine regression (BKMR) model. Three hundred and thirty-six older adults were included as the study population and classified as the CIND and control groups. Blood manganese (Mn), copper (Cu), zinc (Zn), selenium (Se), and molybdenum (Mo) were measured as relevant ETEs. The frontal/executive tests included digit symbol coding (DSC), the Korean color word Stroop test (K-CWST), a controlled oral word association test (COWAT), and a trial-making test (TMT). Overall, the BKMR showed a negative association between multiple ETEs and the odds of CIND. Mn was designated as the most dominant element associated with the CIND (PIP = 0.6184), with a U-shaped relationship. Cu and Se levels were positively associated with the K-CWST percentiles (ß = 31.78; 95% CI: 13.51, 50.06) and DSC percentiles (ß = 25.10; 95% CI: 7.66, 42.53), respectively. Our results suggest that exposure to multiple ETEs may be linked to a protective mechanism against cognitive impairment in older adults.

Manganese-based nanomaterials promote synergistic photo-immunotherapy: green synthesis, underlying mechanisms, and multiple applications.

Single phototherapy and immunotherapy have individually made great achievements in tumor treatment. However, monotherapy has difficulty in balancing accuracy and efficiency. Combining phototherapy with immunotherapy can realize the growth inhibition of distal metastatic tumors and enable the remote monitoring of tumor treatment. The development of nanomaterials with photo-responsiveness and anti-tumor immunity activation ability is crucial for achieving photo-immunotherapy. As immune adjuvants, photosensitizers and photothermal agents, manganese-based nanoparticles (Mn-based NPs) have become a research hotspot owing to their multiple ways of anti-tumor immunity regulation, photothermal conversion and multimodal imaging. However, systematic studies on the synergistic photo-immunotherapy applications of Mn-based NPs are still limited; especially, the green synthesis and mechanism of Mn-based NPs applied in immunotherapy are rarely comprehensively discussed. In this review, the synthesis strategies and function of Mn-based NPs in immunotherapy are first introduced. Next, the different mechanisms and leading applications of Mn-based NPs in immunotherapy are reviewed. In addition, the advantages of Mn-based NPs in synergistic photo-immunotherapy are highlighted. Finally, the challenges and research focus of Mn-based NPs in combination therapy are discussed, which might provide guidance for future personalized cancer therapy.

Zinc and manganese homeostasis closely interact in mammalian cells.

Understanding the homeostatic interactions among essential trace metals is important for explaining their roles in cellular systems. Recent studies in vertebrates suggest that cellular Mn metabolism is related to Zn metabolism in multifarious cellular processes. However, the underlying mechanism remains unclear. In this study, we examined the changes in the expression of proteins involved in cellular Zn and/or Mn homeostatic control and measured the Mn as well as Zn contents and Zn enzyme activities to elucidate the effects of Mn and Zn homeostasis on each other. Mn treatment decreased the expression of the Zn homeostatic proteins metallothionein (MT) and ZNT1 and reduced Zn enzyme activities, which were attributed to the decreased Zn content. Moreover, loss of Mn efflux transport protein decreased MT and ZNT1 expression and Zn enzyme activity without changing extracellular Mn content. This reduction was not observed when supplementing with the same Cu concentrations and in cells lacking Cu efflux proteins. Furthermore, cellular Zn homeostasis was oppositely regulated in cells expressing Zn and Mn importer ZIP8, depending on whether Zn or Mn concentration was elevated in the extracellular milieu. Our results provide novel insights into the intricate interactions between Mn and Zn homeostasis in mammalian cells and facilitate our understanding of the physiopathology of Mn, which may lead to the development of treatment strategies for Mn-related diseases in the future.

A cross-sectional analysis of the PURE study on minerals intake among Malaysian adult population with hypertension.

Hypertension (HPT) is the leading modifiable risk factor for cardiovascular diseases and premature death worldwide. Currently, attention is given to various dietary approaches with a special focus on the role of micronutrient intake in the regulation of blood pressure. This study aims to measure the dietary intake of selected minerals among Malaysian adults and its association with HPT. This cross-sectional study involved 10,031 participants from the Prospective Urban and Rural Epidemiological study conducted in Malaysia. Participants were grouped into HPT if they reported having been diagnosed with high blood pressure [average systolic blood pressure (SBP)/average diastolic blood pressure (DBP) ≥ 140/90 mm Hg]. A validated food frequency questionnaire (FFQ) was used to measure participants' habitual dietary intake. The dietary mineral intake of calcium, copper, iron, magnesium, manganese, phosphorus, potassium, sodium, and zinc was measured. The chi-square test was used to assess differences in socio-demographic factors between HPT and non-HPT groups, while the Mann-Whitney U test was used to assess differences in dietary mineral intake between the groups. The participants' average dietary intake of calcium, copper, iron, magnesium, manganese, phosphorus, potassium, selenium, sodium, and zinc was 591.0 mg/day, 3.8 mg/day, 27.1 mg/day, 32.4 mg/day, 0.4 mg/day, 1431.1 mg/day, 2.3 g/day, 27.1 µg/day, 4526.7 mg/day and 1.5 mg/day, respectively. The intake was significantly lower among those with HPT than those without HPT except for calcium and manganese. Continuous education and intervention should be focused on decreasing sodium intake and increasing potassium, magnesium, manganese, zinc, and calcium intake for the general Malaysian population, particularly for the HPT patients.

Effects of manganese glycine on eggshell quality, eggshell ultrastructure, and elemental deposition in aged laying hens.

Poor eggshell quality of eggs laid by aged laying hens is the major problem affecting the length of the rearing period in the laying hen industry. Trace elements are required and play vital roles in the eggshell quality of laying hens. Appropriate dose of organic microelements is environmentally friendly and sufficient to satisfy the needs of hens because of their greater bioavailability and lower excretion than inorganic forms. The aim of this experiment was to investigate the effects of manganese (Mn) glycine (MG) on eggshell quality, elemental deposition, and eggshell ultrastructure in aged laying hens. A total of 720 Hy-Line Brown hens 70 weeks old were assigned equally to four groups with six replicates of 30 birds each. The hens were fed basal diets (without Mn supplementation) supplemented with 120 mg/kg of Mn from manganese sulfate monohydrate (MSM), or 40, 80, or 120 mg/kg Mn from MG for 12 weeks. Dietary supplementation with 80 mg/kg Mn from MG resulted in the greatest eggshell strength after 6 weeks of treatment (P = 0.047), and in greater eggshell strength than observed in the MSM control after 12 weeks of treatment (P = 0.025). After 12 weeks of treatment, the eggs of hens in the MG groups showed lower mammillary layer thickness in the blunt end, equator, and acute end than observed in the MSM control group (P < 0.001). With the exception of the blunt ends of eggs from hens in the 120 mg/kg MG group, the eggs of hens in the MG groups, compared with the MSM control group, exhibited a lower mammillary layer ratio, and greater palisade layer ratio and effective layer ratio in the blunt end, equator, and acute end (P < 0.001). Dietary supplementation with 80 mg/kg Mn from MG, compared with the MSM control and 40 and 120 mg/kg MG, resulted in the greatest palisade layer thickness and effective layer thickness, and the lowest mammillary layer thickness in the equator (P < 0.001, P = 0.001, P < 0.001, respectively). Furthermore, supplementation with 80 mg/kg Mn from MG exhibited the greatest ratio of the palisade layer and effective layer, and the lowest mammillary layer ratio in the blunt end and equator (all P < 0.001). The Mn content of eggshells in hens-fed diets supplemented with 80 and 120 mg/kg Mn from MG was greater than that in the MSM control and 40 mg/kg MG groups (P = 0.035). Dietary supplementation with 80 or 120 mg/kg Mn from MG resulted in greater tibia Mn content than observed in the 40 mg/kg MG group (P = 0.019), and greater yolk Mn content than observed in the 40 mg/kg MG and MSM control groups (P = 0.018). In conclusion, dietary supplementation with 80 mg/kg Mn from MG, compared with the MSM control (120 mg/kg Mn), may increase the deposition efficiency of Mn, alter eggshell elemental composition, improve eggshell ultrastructure, and enhance eggshell strength in aged laying hens.

Assessing the health risks of heavy metals and seasonal minerals fluctuations in Camellia sinensis cultivars during their growth seasons.

The risk assessment of heavy metals in tea is extremely imperative for the health of tea consumers. However, the effects of varietal variations and seasonal fluctuations on heavy metals and minerals in tea plants remain unclear. Inductively coupled plasma optical emission spectrometry (ICP-OES) was used to evaluate the contents of aluminum (Al), manganese (Mn), magnesium (Mg), boron (B), calcium (Ca), copper (Cu), cobalt (Co), iron (Fe), sodium (Na), zinc (Zn), arsenic (As), cadmium (Cd), chromium (Cr), nickel (Ni), and antimony (Sb) in the two categories of young leaves (YL) and mature leaves (ML) of tea (Camellia sinensis) cultivars throughout the growing seasons. The results showed significant variations in the contents of the investigated nutrients both among the different cultivars and growing seasons as well. Furthermore, the average concentrations of Al, Mn, Mg, B, Ca, Cu, Co, Fe, Na, Zn, As, Cd, Cr, Ni, and Sb in YL ranged, from 671.58-2209.12, 1260.58-1902.21, 2290.56-2995.36, 91.18-164.68, 821.95-5708.20, 2.55-3.80, 3.96-25.22, 37.95-202.84, 81.79-205.05, 27.10-69.67, 0.028-0.053, 0.065-0.127, 2.40-3.73, 10.57-12.64, 0.11-0.14 mg kg-1, respectively. In ML, the concentrations were 2626.41-7834.60, 3980.82-6473.64, 3335.38-4537.48, 327.33-501.70, 9619.89-13153.68, 4.23-8.18, 17.23-34.20, 329.39-567.19, 145.36-248.69, 40.50-81.42, 0.089-0.169, 0.23-0.27, 5.24-7.89, 18.51-23.97, 0.15-0.19 mg kg-1, respectively. The contents of all analyzed nutrients were found to be higher in ML than in YL. Target hazard quotients (THQ) of As, Cd, Cr, Ni, and Sb, as well as the hazard index (HI), were all less than one, suggesting no risk to human health via tea consumption. This research might provide the groundwork for essential minerals recommendations, as well as a better understanding and management of heavy metal risks in tea.

The protective role of sesame oil against Parkinson's-like disease induced by manganese in rats.

Chronic exposure to manganese (Mn) results in motor dysfunction, biochemical and pathological alterations in the brain. Oxidative stress, inflammation, and dysfunction of dopaminergic and GABAergic systems stimulate activating transcription factor-6 (ATF-6) and protein kinase RNA-like ER kinase (PERK) leading to apoptosis. This study aimed to investigate the protective effect of sesame oil (SO) against Mn-induced neurotoxicity. Rats received 25 mg/kg MnCl2 and were concomitantly treated with 2.5, 5, or 8 ml/kg of SO for 5 weeks. Mn-induced motor dysfunction was indicated by significant decreases in the time taken by rats to fall during the rotarod test and in the number of movements observed during the open field test. Also, Mn resulted in neuronal degeneration as observed by histological staining. The striatal levels of lipid peroxides and reduced glutathione (oxidative stress markers), interleukin-6 and tumor necrosis factor-α (inflammatory markers) were significantly elevated. Mn significantly reduced the levels of dopamine and Bcl-2, while GABA, PERK, ATF-6, Bax, and caspase-3 were increased. Interestingly, all SO doses, especially at 8 ml/kg, significantly improved locomotor activity, biochemical deviations and reduced neuronal degeneration. In conclusion, SO may provide potential therapeutic benefits in enhancing motor performance and promoting neuronal survival in individuals highly exposed to Mn.

Monitoring plant responses in field-grown peanuts exposed to exogenously applied chitosan under full and limited irrigation levels.

In recent decades, numerous studies have examined the effects of climate change on the responses of plants. These studies have primarily examined the effects of solitary stress on plants, neglecting the simultaneous effects of mixed stress, which are anticipated to transpire frequently as a result of the extreme climatic fluctuations. Therefore, this study investigated the impact of applied chitosan on boosting the resistance responses of peanuts to alkali and mixed drought-alkali stresses. Peanuts were grown in mid-alkaline soil and irrigated with full irrigation water requirements (100%IR), represented alkali condition (100% IR × alkali soil) and stress conditions (70% IR × alkali soil-represented mixed drought-alkali conditions). Additionally, the plants were either untreated or treated with foliar chitosan. The study evaluated various plant physio-chemical characteristics, including element contents (leaves and roots), seed yield, and irrigation water use efficiency (IWUE). Plants that experienced solitary alkali stress were found to be more vulnerable. However, chitosan applications were effective for reducing (soil pH and sodium absorption), alongside promoting examined physio-chemical measurements, yield traits, and IWUE. Importantly, when chitosan was applied under alkali conditions, the accumulations of (phosphorus, calcium, iron, manganese, zinc, and copper) in leaves and roots were maximized. Under mixed drought-alkali stresses, the results revealed a reduction in yield, reaching about 5.1 and 5.8% lower than under (100% IR × alkali), in the first and second seasons, respectively. Interestingly, treated plants under mixed drought-alkali stresses with chitosan recorded highest values of relative water content, proline, yield, IWUE, and nutrient uptake of (nitrogen, potassium, and magnesium) as well as the lowest sodium content in leaves and roots. Enhances the accumulation of (N, K, and Mg) instead of (phosphorus, calcium, iron, manganese, zinc, and copper) was the primary plant response to chitosan applications, which averted severe damage caused by mixed drought-alkali conditions, over time. These findings provide a framework of the nutrient homeostasis changes induced by chitosan under mixed stresses. Based on the findings, it is recommended under mixed drought-alkali conditions to treat plants with chitosan. This approach offers a promising perspective for achieving optimal yield with reduced water usage.

Risk assessment and strontium isotopic tracing of potentially toxic metals in creek sediments around a uranium mine, China.

The contamination of creek sediments near industrially nuclear dominated site presents significant environmental challenges, particularly in identifying and quantifying potentially toxic metal (loid)s (PTMs). This study aims to measure the extent of contamination and apportion related sources for nine PTMs in alpine creek sediments near a typical uranium tailing dam from China, including strontium (Sr), rubidium (Rb), manganese (Mn), lithium (Li), nickel (Ni), copper (Cu), vanadium (V), cadmium (Cd), zinc (Zn), using multivariate statistical approach and Sr isotopic compositions. The results show varying degrees of contamination in the sediments for some PTMs, i.e., Sr (16.1-39.6 mg/kg), Rb (171-675 mg/kg), Mn (224-2520 mg/kg), Li (11.6-78.8 mg/kg), Cd (0.31-1.38 mg/kg), and Zn (37.1-176 mg/kg). Multivariate statistical analyses indicate that Sr, Rb, Li, and Mn originated from the uranium tailing dam, while Cd and Zn were associated with abandoned agricultural activities, and Ni, Cu, and V were primarily linked to natural bedrock weathering. The Sr isotope fingerprint technique further suggests that 48.22-73.84% of Sr and associated PTMs in the sediments potentially derived from the uranium tailing dam. The combined use of multivariate statistical analysis and Sr isotopic fingerprint technique in alpine creek sediments enables more reliable insights into PTMs-induced pollution scenarios. The findings also offer unique perspectives for understanding and managing aqueous environments impacted by nuclear activities.

Melatonin mitigates manganese-induced neural damage via modulation of gut microbiota-metabolism in mice.

Manganese (Mn), a common environmental and occupational risk factor for Parkinson's disease (PD), can cause central nervous system damage and gastrointestinal dysfunction. The melatonin has been shown to effectively improve neural damage and intestinal microbiota disturbances in animal models. This research investigated the mechanism by which exogenous melatonin prevented Mn-induced neurogenesis impairment and neural damage. Here, we established subchronic Mn-exposed mice model and melatonin supplement tests to evaluate the role of melatonin in alleviating Mn-induced neurogenesis impairment. Mn induced neurogenesis impairment and microglia overactivation, behavioral dysfunction, gut microbiota dysbiosis and serum metabolic disorder in mice. All these events were reversed with the melatonin supplement. The behavioral tests revealed that melatonin group showed approximately 30 % restoration of motor activity. According to quantitative real time polymerase chain reaction (qPCR) results, melatonin group showed remarkable restoration of the expression of dopamine neurons and neurogenesis markers, approximately 46.4 % (TH), 68.4 % (DCX in hippocampus) and 48 % (DCX in striatum), respectively. Interestingly, melatonin increased neurogenesis probably via the gut microbiota and metabolism modulation. The correlation analysis of differentially expressed genes associated with hippocampal neurogenesis indicated that Firmicutes-lipid metabolism might mediate the critical repair role of melatonin in neurogenesis in Mn-exposed mice. In conclusion, exogenous melatonin supplementation can promote neurogenesis, and restore neuron loss and neural function in Mn-exposed mice, and the multi-omics results provide new research ideas for future mechanistic studies.

Supplemental trace minerals as complexed or inorganic sources for beef cattle during the receiving period.

To investigate effects of inorganic or complexed trace mineral source (zinc, copper, manganese, and cobalt) on receiving period performance and morbidity, crossbred beef heifer calves (n = 287) arriving on three delivery dates were used in a 42-d receiving trial. Heifers were processed after arrival, stratified by day -1 body weights (BW) and allocated randomly to eight pens (11 to 13 heifers/pen, 24 pens total). Within truckload, pens were assigned randomly to dietary treatment (n = 12 pens/treatment). Heifers were housed on 0.42-ha grass paddocks, provided ad libitum bermudagrass hay and provided dietary treatments in grain supplements fed daily. Treatments consisted of supplemental zinc (360 mg/d), copper (125 mg/d), manganese (200 mg/d), and cobalt (12 mg/d) from complexed (Zinpro Availa 4, Zinpro Corp. Eden Prairie, MN) or inorganic sources (sulfates). Heifers were observed daily for clinical bovine respiratory disease (BRD). If presenting BRD symptoms and rectal temperature ≥ 40 °C, heifers were deemed morbid and treated with antibiotics. Six heifers/pen were bled to determine serum haptoglobin concentrations on days 0, 14, and 28. Liver biopsies were taken on day 5 ±â€…2 and 43 ±â€…1 from three calves selected randomly from each pen for mineral status comparisons. Statistical analyses were performed using the MIXED, GLIMMIX, and repeated measures procedures of SAS 9.4 with truckload as a random effect and pen within truckload specified as subject. There tended to be a treatment by day interaction for BW (P = 0.07). Heifer BW did not differ on day 0 (P = 0.82) and day 14 (P = 0.36), but heifers fed complexed trace minerals had greater BW on day 28 (P = 0.04) and day 42 (P = 0.05). Overall average daily gains were greater for heifers fed complexed trace minerals (P = 0.05; 0.78 vs. 0.70 kg, SE = 0.03). Heifers supplemented with inorganic trace minerals had greater BRD incidence (P = 0.03; 58 vs. 46%, SE = 3.6). Haptoglobin concentrations decreased throughout the trial (P < 0.001), and heifers fed complexed trace minerals tended to have a decrease in haptoglobin concentrations (P = 0.07). The source of trace mineral supplementation had no effect (P ≥ 0.20) on liver mineral concentrations and there were no treatment × day interactions (P ≥ 0.35). In conclusion, supplementing diets for the first 42 d after arrival with complexed trace mineral sources improved heifer performance as compared to heifers supplemented with inorganic trace minerals.

Issues associated with health and management of newly received cattle continue to pose significant animal welfare and economic challenges for the beef industry. Diagnosis of bovine respiratory disease, accompanied with poor growth performance, can be addressed by nutritional intervention in receiving cattle. Trace mineral inclusion in receiving rations is vital to calf performance. There are numerous sources of trace mineral supplements that exist commercially for cattle and their effects on immune function, growth, and performance measures were evaluated. Organic trace mineral supplements are being used in replacement of inorganic salts due to potentially greater bioavailability and functionality. An organic source that is commonly used are amino acid complexes. Replacing inorganic sources with complexed sources of trace minerals (zinc, copper, manganese, and cobalt) improved growth performance and decreased sickness during the 42-d receiving study.

Exchangeable manganese regulates carbon storage in the humus layer of the boreal forest.

The huge carbon stock in humus layers of the boreal forest plays a critical role in the global carbon cycle. However, there remains uncertainty about the factors that regulate below-ground carbon sequestration in this region. Notably, based on evidence from two independent but complementary methods, we identified that exchangeable manganese is a critical factor regulating carbon accumulation in boreal forests across both regional scales and the entire boreal latitudinal range. Moreover, in a novel fertilization experiment, manganese addition reduced soil carbon stocks, but only after 4 y of additions. Our results highlight an underappreciated mechanism influencing the humus carbon pool of boreal forests.

Evaluation of urinary trace element levels in patients with opioid use disorder undergoing methadone treatment in western Iran.

The monitoring of essential and toxic elements in patients with Opioid Use Disorder (OUD) undergoing methadone treatment (MT) is important, and there is limited previous research on the urinary levels of these elements in MT patients. Therefore, the present study aimed to analyze certain elements in the context of methadone treatment compared to a healthy group. In this study, patients with opioid use disorder undergoing MT (n = 67) were compared with a healthy group of companions (n = 62) in terms of urinary concentrations of some essential elements (selenium (Se), zinc (Zn), copper (Cu), iron (Fe), manganese (Mn), calcium (Ca)) and toxic elements (lead (Pb), cadmium (Cd), arsenic (As), and chromium (Cr)). Urine samples were prepared using the acid digestion method with a mixture of nitric acid and perchloric acid and assessed using the ICP-MS method. Our results showed that the two groups had no significant differences in terms of gender, education level, occupation, and smoking status. Urinary concentrations of Se, Cu, and Fe levels were significantly lower in the MT group compared to the healthy subjects. However, the concentrations of Pb, Cd, As, Mn, Cr, and Ca in the MT group were higher than in the healthy group (p < 0.05). No significant difference was established between the levels of Zn in the two groups (p = 0.232). The results of regression analysis revealed that the differences between the concentration levels of all metals (except Zn) between two groups were still remained significant after adjusting for all variables (p < 0.05). The data obtained in the current study showed lower urinary concentrations of some essential elements and higher levels of some toxic elements in the MT group compared to the healthy subjects. These findings should be incorporated into harm-reduction interventions.

Serum 25-hydroxyvitamin D mediates the association between heavy metal exposure and cardiovascular disease.

BACKGROUND: Mediation analysis aims to determine how intermediate variables affect exposure to disease. In this study, 25-hydroxyvitamin D (25(OH)D) was evaluated to assess its role in mediating heavy metal exposure and cardiovascular disease (CVD). METHODS: A total of 9,377 participants from the National Health and Nutrition Examination Survey (NHANES) for the years 2011-2018 were included. Firstly, restricted cubic spline (RCS), and multivariable logistic regression model were performed to estimate the association between heavy metal exposure (Cadmium, Lead, Mercury, Manganese, and Selenium), as well as serum 25(OH)D and CVD. Secondly, using generalized linear regression model and generalized additive models with smooth functions, we investigated the correlation between heavy metal exposure and serum 25(OH)D. Finally, the mediation effect of serum 25(OH)D in the associations between heavy metal exposure and CVD was explored. RESULTS: The RCS plots revealed that Cadmium, and Lead were positively and linearly associated with CVD, while Mercury, and Manganese were inversely and linearly associated with CVD. Additionally, a roughly L- and U-shaped relationship existed between Selenium, as well as 25(OH)D and CVD. When potential confounding factors were adjusted for, serum 25(OH)D had negative associations with Cadmium, Lead, and Manganese, while serum 25(OH)D had positive relationship with Selenium. There was a mediation effect between Manganese exposure and CVD, which was mediated by 25(OH)D. CONCLUSION: According to the mediation analysis, the negative association between Manganese exposure and incident CVD was increased by 25(OH)D. The increasing dietary intake of Vitamin D could increase the protective effect of manganese intake on CVD.

Maternal choline supplementation lessens the behavioral dysfunction produced by developmental manganese exposure in a rodent model of ADHD.

Studies in children have reported associations between elevated manganese (Mn) exposure and ADHD-related symptoms of inattention, impulsivity/hyperactivity, and psychomotor impairment. Maternal choline supplementation (MCS) during pregnancy/lactation may hold promise as a protective strategy because it has been shown to lessen cognitive dysfunction caused by numerous early insults. Our objectives were to determine whether (1) developmental Mn exposure alters behavioral reactivity/emotion regulation, in addition to impairing learning, attention, impulse control, and sensorimotor function, and (2) MCS protects against these Mn-induced impairments. Pregnant Long-Evans rats were given standard diet, or a diet supplemented with additional choline throughout gestation and lactation (GD 3 - PND 21). Male offspring were exposed orally to 0 or 50 mg Mn/kg/day over PND 1-21. In adulthood, animals were tested in a series of learning, attention, impulse control, and sensorimotor tasks. Mn exposure caused lasting dysfunction in attention, reactivity to errors and reward omission, learning, and sensorimotor function, recapitulating the constellation of symptoms seen in ADHD children. MCS lessened Mn-induced attentional dysfunction and partially normalized reactivity to committing an error or not receiving an expected reward but provided no protection against Mn-induced learning or sensorimotor dysfunction. In the absence of Mn exposure, MCS produces lasting offspring benefits in learning, attention, and reactivity to errors. To conclude, developmental Mn exposure produces a constellation of deficits consistent with ADHD symptomology, and MCS offered some protection against the adverse Mn effects, adding to the evidence that maternal choline supplementation is neuroprotective for offspring and improves offspring cognitive functioning.

Association between maternal blood or cord blood metal concentrations and catch-up growth in children born small for gestational age: an analysis by the Japan environment and children's study.

BACKGROUND: Catch-up growth issues among children born small for gestational age (SGA) present a substantial public health challenge. Prenatal exposure to heavy metals can cause adverse effects on birth weight. However, comprehensive studies on the accurate assessment of individual blood concentrations of heavy metals and their effect on the failure to achieve catch-up growth remain unavailable. This study aimed to evaluate the effects of uterine exposure to toxic metals cadmium, lead, and mercury and essential trace metals manganese and selenium at low concentrations on the postnatal growth of children born SGA. METHODS: Data on newborn birth size and other factors were obtained from the medical record transcripts and self-administered questionnaires of participants in the Japan Environment and Children's Study. The blood concentrations of lead, cadmium, mercury, selenium, and manganese in pregnant women in their second or third trimester were determined by inductively coupled plasma mass spectrometry. These heavy metal concentrations were also assessed in pregnant women's cord blood. Furthermore, the relationship between each heavy metal and height measure/catch-up growth in SGA children aged 4 years was analyzed using linear and logistic regression methods. These models were adjusted for confounders. RESULTS: We studied 4683 mother-child pairings from 103,060 pregnancies included in the Japan Environment and Children's Study. Of these, 278 pairs were also analyzed using cord blood. At 3 and 4 years old, 10.7% and 9.0% of children who were born below the 10th percentile of body weight had height standard deviation scores (SDSs) below 2, respectively. Cord blood cadmium concentrations were associated with the inability to catch up in growth by 3 or 4 years old and the height SDS at 3 years old. In maternal blood, only manganese was positively associated with the height SDS of SGA children aged 2 years; however, it was not significantly associated with catch-up growth in these children. CONCLUSION: Cadmium exposure is associated with failed catch-up development in SGA children. These new findings could help identify children highly at risk of failing to catch up in growth, and could motivate the elimination of heavy metal (especially cadmium) pollution to improve SGA children's growth.

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.