Search

Abstract: In view of the significant role of H2S in brain functioning, it is proposed that H2S may also possess protective effects against adverse effects of neurotoxicants. Therefore, the objective of the present review is to discuss the neuroprotective effects of H2S against toxicity of a wide spectrum of endogenous and exogenous agents involved in the pathogenesis of neurological diseases as etiological factors or key players in disease pathogenesis. Generally, the existing data demonstrate that H2S possesses neuroprotective effects upon exposure to endogenous (amyloid β, glucose, and advanced-glycation end-products, homocysteine, lipopolysaccharide, and ammonia) and exogenous (alcohol, formaldehyde, acrylonitrile, metals, 6-hydroxydopamine, as well as 1-methyl-4-phenyl- 1,2,3,6- tetrahydropyridine (MPTP) and its metabolite 1-methyl-4-phenyl pyridine ion (MPP)) neurotoxicants. On the one hand, neuroprotective effects are mediated by S-sulfhydration of key regulators of antioxidant (Sirt1, Nrf2) and inflammatory response (NF-κB), resulting in the modulation of the downstream signaling, such as SIRT1/TORC1/CREB/BDNF-TrkB, Nrf2/ARE/HO-1, or other pathways. On the other hand, H2S appears to possess a direct detoxicative effect by binding endogenous (ROS, AGEs, Aβ) and exogenous (MeHg) neurotoxicants, thus reducing their toxicity. Moreover, the alteration of H2S metabolism through the inhibition of H2S-synthetizing enzymes in the brain (CBS, 3-MST) may be considered a significant mechanism of neurotoxicity. Taken together, the existing data indicate that the modulation of cerebral H2S metabolism may be used as a neuroprotective strategy to counteract neurotoxicity of a wide spectrum of endogenous and exogenous neurotoxicants associated with neurodegeneration (Alzheimer’s and Parkinson’s disease), fetal alcohol syndrome, hepatic encephalopathy, environmental neurotoxicant exposure, etc. In this particular case, modulation of H2S-synthetizing enzymes or the use of H2S-releasing drugs should be considered as the potential tools, although the particular efficiency and safety of such interventions are to be addressed in further studies.

Introduction. Due to the many physiological functions of Selenium (Se), its deficiency is associated with a broad spectrum of adverse health effects. This review aims to analyze epidemiological data on the relation of selenium status to public health and the possibility of selenium-containing drugs usage. Material and methods. Based on the literature search in Pubmed, The Cochrane Library, and Google Scholar, epidemiological data on the association between Se status and population health and effects of Se supplementation were analyzed. Results. Meta-analyses indexed in the Cochrane Library demonstrated a significant association between Se status and many pathologies. Specifically, it has been shown that subjects with physiologically high Se body burden are characterized by a 24-31% lower risk of cancer and 36% lower risk of cancer-related mortality. It is also notable that Se supplementation in human immunodeficiency virus-infected women reduced the risk of maternal diarrhoea and low birth mass in offspring. Moreover, Se supplementation in premature newborns and critically low mass newborns significantly decreased the risk of sepsis. Many extensive epidemiological studies also demonstrated the efficiency of improvement in the Se status concerning coronary heart disease and sepsis mortality risk. At the same time, constant monitoring of Se body burden is essential for assessing Se supplementation efficiency and prevention of adverse health effects of Se overload. It is also noted that Se status is considered as the determinant of the efficiency of prevention of cardiovascular diseases and cancer under Se supplementation. Conclusion. Given the high incidence of Se deficiency in Russia (24-45% depending on the region), assessment and improvement of Se status may be considered a valuable tool for population health management.

INTRODUCTION: Trace elements are required for biological and metabolic processes. Several diseases and clinical conditions can affect enteral nutrition and adequate gastrointestinal uptake of these trace elements. In this respect, parenteral nutrition (PN) is necessary for the provision of deficient trace elements. However, some essential elements, such as manganese (Mn) may be toxic to children and adults when parenterally administered in excess, leading to toxic, especially neurotoxic, effects. AREAS COVERED: Here, we briefly provide an overview on Mn, addressing its sources of exposure, the role of Mn in the etiology of neurodegenerative diseases, and focusing on potential mechanisms associated with Mn-induced neurotoxicity. In addition, we discuss the potential consequences of over exposure to Mn inherent to parenteral nutrition in neonates/children and adults. EXPERT OPINION: In this critical review we suggest that additional research is required to safely set Mn levels in parenteral nutrition, and that eliminating Mn as an additive should be considered by physicians and nutritionists on a case by case basis in the meantime to avoid the greater risk of neurotoxicty by its presence. There is need to better define clinical biomarkers for Mn toxicity by PN, as well as identify new effective agents to treat Mn-neurotoxicity. Moreover, we highlight the importance of the development of new guidelines and practice safeguards to protect children and adults from excessive Mn exposure and neurotoxicity upon PN administration.

Iron (Fe) is an essential trace element required for several physiological processes. It plays important roles in mitochondrial function, synthesis, and metabolism of the neurotransmitter, as well as oxygen transport. However, excess Fe can cause toxicity. Particularly, Fe overload may result in neurotoxicity, contributing to the development and progression of neurodegenerative diseases, although the molecular mechanisms underlying Fe-induced neurodegeneration have yet to be entirely understood. Alternative (non-rodent) experimental models have been pointed as important approaches to elucidate molecular and physiological events mediating Fe-induced pathology. Among such alternative strategies, an advantageous experimental worm-model system

Summary Background The present study has the objective to assess the zinc (Zn), copper (Cu), and oxysterols plasma levels in type 1 (DM1) (n = 26) and type 2 (DM2) (n = 80) diabetes patients, as compared to healthy controls (n = 71), in order to testify whether metal levels may have a significant impact on the association between oxysterols and diabetes. Methods Plasma trace elements and plasma oxysterols were assessed using atomic absorption spectrometry and LC-MS/MS, respectively. Lifestyle, smoking status, alcohol intake, and drug usage, as well as microvascular complications, were also monitored and reported. Results The obtained data demonstrated that both DM1 and DM2 patients were characterized by significantly elevated HbA1c, FBG, TC, LDL-C, VLDL-C, and TG levels as compared to controls. Plasma Zn levels and Zn/Cu ratio in DM1 and DM2 patients were about 3- and 2-fold lower than controls. No significant differences in plasma Cu levels were reported. The 7-ketocholesterol (7-kchol) levels in DM1 and DM2 patients exceeded these values in healthy individuals by 2.5 and 5-fold, respectively. Similarly, cholestan-3β, 5α, 6β-triol (chol-triol) levels were more than 3- and 6-fold higher when compared to the respective values in non-diabetic controls. In regression models decreased plasma Zn and elevated oxysterol levels were significantly associated with HbA1c and fasting plasma glucose levels, after adjustment for anthropometric and clinical variables, as well as routine biochemical markers. Conclusions Plasma Zn concentration is inversely associated with both 7-kchol and chol-triol levels. Assessment of Zn and oxysterol levels may be used both for risk assessment and as targets for the treatment of diabetes mellitus.

The wide use of cobalt (Co) in food, industry, and medical devices requires full elucidation of its biological effects on tissues and organs. The aim was to assess serum metabolic alterations in immature mice after subchronic exposure to CoCl2. Pregnant ICR mice were subjected to a daily dose of 75 mg cobalt chloride/kg body weight (CoCl2x6H2O) 2-3 days before they gave birth, and treatment continued until days 25 and 30 after delivery. The compound was dissolved in and obtained with regular tap water. ICP-DRC-MS analysis showed significantly elevated serum Co2+ and diverse alterations in metabolic parameters of 25- and 30-day-old pups after exposure to CoCl2. Cholesterol and urea levels were significantly elevated in day 25 mice while HDL-C and LDL-C were reduced. In day 30, Co-exposed mice LDL-C and triglycerides were significantly increased while the total cholesterol level remained unchanged. Alkaline phosphatase was significantly reduced in day 25 Co-exposed mice. Blood glucose level of Co-exposed mice remained close to the untreated controls. Total protein content was slightly increased in day 30 mice. Co-exposure reduced albumin content and albumin/globulin ratio but increased significantly globulin content. Co administration showed strong correlation with cholesterol, urea, and HDL-C in both day 25 and 30 mice. Inverse correlation was found with alkaline phosphatase and albumin for day 25 and with triglycerides, globulin, and total protein content in day 30 Co-exposed mice. Subchronic CoCl2 exposure of immature mice induced significant changes in key metabolic parameters suggesting possible further disturbances in energy metabolism, osteogenesis, and reproduction.

Introduction. The purpose of this study was to study and assess the elemental status of residents of the Kirov region as a part of the Volga Region Federal District (VFD). Material and methods. The content of elements in the hair of 295 men and women (73 and 222, respectively, 25-50 years old) and 120 boys and girls (46 and 74, respectively, 3-15 years old) were studied using massspectrometry with inductively coupled plasma. This indicator serves an index in assessing the impact of environment on human organism. Methods of non-parametric statistics were used for the mathematical simulation of our data. Results. It was found that women, girls and boys compared with other regions of the VFD are characterized by a relative increase in the absolute content (median) in the hair of Mg, Fe, V. For people living in the territory of the Kirov region a relative increase in the Si level in the hair is characterized with exception of boys. The relatively reduced level of Cu (with the exception of women) and Se (with the exception of men) also make oneself conspicuous. Discussion of the results. The main problems associated with a decrease in the content of Cu and Se compounds, as well as an increase in the content of Si, Mg, Fe and V, most likely have a geochemical nature and, in particular, are associated with the chemical composition of drinking water. The hair of children in a greater degree than in adults is shown to be a biological substrate, the elemental composition of which indicates to ecological and social factors, the quality of products and the development of the health care system. Conclusions. The obtained data can be recommended for the use as reference values in assessing the level of chemical compounds in the hair of adults and children living in the territory of the Kirov region.

The neurotransmitter dopamine is a neuromodulator in the positive and negative regulation of brain circuits. Dopamine insufficiency or overload has been implicated in aberrant activities of neural circuits that play key roles in the pathogenesis of neurological and psychiatric diseases. Dopaminergic neurons are vulnerable to environmental insults. The neurotoxin methylmercury (MeHg) produces dopaminergic neuron damage in rodent as well as in Caenorhabditis elegans (C. elegans) models. Previous studies have demonstrated the utility of C. elegans as an alternative and complementary experimental model in dissecting out mechanism of MeHg-induced dopaminergic neurodegeneration. However, a sensitive pathological change that marks early events in neurodegeneration induced by environmental level of MeHg, is still lacking. By establishing a chronic exposure C. elegans model, for the first time, we have shown the propensity of MeHg (5 μM, 10 days) to induce bright puncta of dat-1::mCherry aggreagtes in the dendrites of cephalic (2 CEPs) dopaminergic neurons in a dose- and time-dependent manner, while these changes were not found in other dopaminergic neurons: anterior deirids (2 ADEs) and posterior deirids (2 PDEs), cholinergic neurons (2 AlYs) or glutamatergic neurons (2 PVDs). The bright puncta appear as an aggregation of mCherry proteins accumulating in dendrites. Further staining shows that the puncta were not inclusions in lysosome, or amyloid protein aggregates. In addition, features of the puncta including enlarged sphere shape (0.5 – 2 μm diameters), bright and accompanying with the shrinkage of the dendrite suggest that the puncta are likely composed of homologous mCherry molecules packaged at the dendritic site for exportation. Moreover, in the glutathione S-transferase 4 (gst-4) transcriptional reporter strain and RT-PCR assay, the expression levels of gst-4 and tubulins (tba-1 and tba-2) genes were not significantly modified under this chronic exposure paradigm, but gst-4 did show significant changes in an one day exposure paradigm. Collectively, these results suggest that CEP dopaminergic neurons are a sensitive target of MeHg, and the current exposure paradigm could be used as a model to investigate mechanism of dopaminergic neurotoxicity.

The objective of the study was to evaluate the association between smoking and essential metal (Co, Cr, Cu, Fe, Mn, V, Zn) and metalloid (Se) levels in hair and serum of adult women using inductively coupled plasma-mass spectrometry (ICP-MS). In this cross-sectional study, a total of 344 women 20-70 years old including 199 smokers and 145 non-smoking women were enrolled. Serum Cu, Fe, and Zn levels in smoking women were found to be 6%, 8%, and 3% lower of levels in non-smokers, respectively. In contrast, circulating Mn, V, and especially Cr concentrations in smoking women exceeded the respective values in non-smoking women by 5%, 14%, and 54%. Hair Fe and Se levels in smoking women were 17% and 23% lower as compared to non-smoking controls, respectively. In multiple regression models, smoking severity was inversely associated with serum and hair Se concentrations, whereas the relationship to serum and hair Cr was positive. In addition, serum Zn and hair Fe levels were found to be inversely associated with the number of cigarettes per day. These findings hypothesize that health hazards of smoking may be at least in part be mediated by alteration in essential metal and metalloid metabolism.

The availability of clean drinking water impacts the quality of life of Arctic populations and is affected by climate change. We provide perceptions based on: (1) a study of the accessibility of the natural surface water to the nomadic and settled Indigenous inhabitants living in rural areas (in settlements and remote camps) in the Arctic zone of Western Siberia during climate change and industrial development; (2) an assessment of the impact of consuming different surface water resources on human health. We include primary data sources from medical examinations and surveys collected in the regions between the rivers of Ob, Nadym, Taz, and Yenisey in 2012, 2014–2019, and 2022 whereas the chemical analysis of the surface waters in the region was based on previous research. A total of 552 local residents from the Arctic zone of Western Siberia participated in the study. We discuss how the availability of high-quality drinking water is limited for them due to climatic and anthropogenic risks, despite the abundant water resources. The consumption of river water is associated with high health risks since it contains heavy metals (Pb, Cd, Mn, Fe), whereas the consumption of lake ice melt water likely affects health because of the low concentrations of beneficial ions.

Neurotoxicology is a specialty that aims to understand and explain the impact of chemicals, xenobiotics and physical conditions on nervous system function throughout the life span. Herein, we point to the need for integration of novel translational bioinformatics and chemo-informatics approaches, such as machine learning (ML) and artificial intelligence (AI) to the discipline. Specifically, we advance the notion that AI and ML will be helpful in identifying neurotoxic signatures, provide reliable data in predicting neurotoxicity in the context of genetic variability, and improve the understanding of neurotoxic outcomes associated with exposures to mixtures, to name a few.

In view of the significant role of H

Hepcidin is a regulator of iron metabolism. Diet affects the body’s iron status, but how it influences hepcidin concentrations and the risk of gestational iron-deficiency anemia (IDA) remains unclear. We investigated relationships of food and nutrient intake with serum hepcidin levels in relation to the iron status at a population scale. A retrospective cross-sectional study was conducted based on data obtained from the Nationwide Nutrition and Health Survey in pregnant women, Taiwan (2017~2020). In total, 1430 pregnant women aged 20~45 years with a singleton pregnancy were included. Data from blood biochemistry, 24-h dietary recall, and a food frequency questionnaire were collected during a prenatal checkup. Adjusted multivariate linear and logistic regression analyses were employed to measure the beta coefficient (ß) and 95% confidence interval (CI) of serum hepcidin and the odds ratio (OR) of IDA. In IDA women, serum hepcidin levels were positively correlated with the intake frequency of Chinese dim sum and related foods (β = 0.037 (95% CI = 0.015~0.058), p = 0.001) and dark leafy vegetables (β = 0.013 (0.001~0.025), p = 0.040), but they were negatively correlated with noodles and related products (β = −0.022 (−0.043~−0.001), p = 0.038). An adjusted multivariate logistic regression analysis showed that dietary protein [OR: 0.990 (0.981~1.000), p = 0.041], total fiber [OR: 0.975 (0.953~0.998), p = 0.031], and rice/rice porridge [OR: 1.007 (1.00~1.014), p = 0.041] predicted gestational IDA. Total carbohydrates [OR: 1.003 (1.000~1.006), p = 0.036], proteins [OR: 0.992 (0.985~0.999), p = 0.028], gourds/shoots/root vegetables [OR: 1.007 (0.092~1.010), p = 0.005], and to a lesser extent, savory and sweet glutinous rice products [OR: 0.069 (0.937~1.002), p = 0.067] and dark leafy vegetables [OR: 1.005 (0.999~1.011), p = 0.088] predicted IDA. The risk of IDA due to vegetable consumption decreased with an increasing vitamin C intake (p for trend = 0.024). Carbohydrates and vegetables may affect the gestational iron status through influencing hepcidin levels. Vitamin C may lower the risk of gestational IDA due to high vegetable consumption.

To study the conjugate dynamics of vascular endothelial growth factor (VEGF) and the components of metal-ligand homeostasis in the development of ischemic stroke.The main group included patients with ischemic stroke (A significant increase in the concentrations of VEGF and trace elements Mg, Mn, Cu, Zn, and Se in the blood serum of patients with ischemic stroke was revealed. A significant relationship between the concentration of VEGF and the concentrations of Cu and Mn in the blood serum of patients with ischemic stroke was shown.The dynamics of VEGF and the concentrations of trace elements in the development of the ischemic process contribute to the solution of therapeutic and prognostic problems in clinical conditions.Изучение сопряженной динамики фактора роста эндотелия сосудов (VEGF) и компонентов металло-лигандного гомеостаза в остром периоде ишемического инсульта (ИИ).В основную группу вошли пациенты с ИИ (По сравнению с группой здоровых пациентов с диагнозом ИИ выявлено статистически значимое увеличение концентрации VEGF и микроэлементов Mg, Mn, Cu, Zn, Se в сыворотке крови. Была показана достоверная взаимосвязь концентрации VEGF и концентрации Cu и Mn в сыворотке крови пациентов с ИИ. Выявленные факты динамики VEGF и концентрации микроэлементов при развитии ишемического процесса способствуют в клинических условиях решению терапевтических и прогностических задач.

According to the United States Centers for Disease Control and Prevention (CDC), as of July 11, 2016, the reported average incidence of children diagnosed with an autism spectrum disorder (ASD) was 1 in 68 (1.46%) among 8-year-old children born in 2004 and living within the 11 monitoring sites' surveillance areas in the United States of America (USA) in 2012. ASD is a multifaceted neurodevelopmental disorder that is also considered a hidden disability, as, for the most part; there are no apparent morphological differences between children with ASD and typically developing children. ASD is diagnosed based upon a triad of features including impairment in socialization, impairment in language, and repetitive and stereotypic behaviors. The increasing incidence of ASD in the pediatric population and the lack of successful curative therapies make ASD one of the most challenging disorders for medicine. ASD neurobiology is thought to be associated with oxidative stress, as shown by increased levels of reactive oxygen species and increased lipid peroxidation, as well as an increase in other indicators of oxidative stress. Children with ASD diagnosis are considered more vulnerable to oxidative stress because of their imbalance in intracellular and extracellular glutathione levels and decreased glutathione reserve capacity. Several studies have suggested that the redox imbalance and oxidative stress are integral parts of ASD pathophysiology. As such, early assessment and treatment of antioxidant status may result in a better prognosis as it could decrease the oxidative stress in the brain before it can induce more irreversible brain damage. In this review, many aspects of the role of oxidative stress in ASD are discussed, taking into account that the process of oxidative stress may be a target for therapeutic interventions.

N,N' bis-(2-mercaptoethyl) isophthalamide (NBMI) is a lipophilic thiol-containing agent that has high affinity for toxic metal ions, such as Hg2+, Pb2+, and Cd2+. Studies have shown that NBMI is a potent chelator of heavy metals, yet its potential toxicity in animals has yet to be determined. Using the model organism Caenorhabditis elegans (C. elegans), we show no significant change in worms' death rate or lifespan following NBMI treatment (10-1000 μM). However, NBMI treatment was associated with a significant developmental delay. To determine if the daf-2/age-1/daf-16 pathway is involved in NBMI toxicity, mRNA levels of these genes were assessed in worms treated with NBMI. Here, we found that while NBMI failed to significantly alter the expression of daf-16 or daf-2; age-1 was significantly downregulated by NBMI. Furthermore, NBMI significantly increased DAF-16 nuclear localization. Consistent with a role for this pathway in NBMI toxicity, the developmental arrest by NBMI was more prominent in the DAF-16 transgenic strain than in the wild type N2 strain. Moreover, in the mutant strains harboring null alleles of daf-16, NBMI had no effect on development. In addition, NBMI repressed the expression of detoxifying genes (skn-1, gst-4 and gcs-1). In summary, NBMI has a low developmental toxicity in the C. elegans model, and the nuclear translocation of DAF-16 is involved in the developmental effect of NBMI.

The study of elemental status was carried out as a result of a multielement analysis of hair by ICP-MS within the framework of the Federal Program "National System of chemical and biological security of the Russian Federation, 2009-2014". This parameter is an index of the impact of the environment on the body. A total of 1,138 adult residents of the Republic of Bashkortostan (624 women and 514 men aged of25-50 years) were examined. The features of the element status of the adult population of the Republic were shown. The obtained data can be used as reference values of chemical elements in the hair of the adult population of the Republic of Bashkortostan.

Mercury (Hg) exposure remains a major public health concern due to its widespread distribution in the environment. Organic mercurials, such as MeHg, have been extensively investigated especially because of their congenital effects. In this context, studies on the molecular mechanism of MeHg-induced neurotoxicity are pivotal to the understanding of its toxic effects and the development of preventive measures. Post-translational modifications (PTMs) of proteins, such as phosphorylation, ubiquitination, and acetylation are essential for the proper function of proteins and play important roles in the regulation of cellular homeostasis. The rapid and transient nature of many PTMs allows efficient signal transduction in response to stress. This review summarizes the current knowledge of PTMs in MeHg-induced neurotoxicity, including the most commonly PTMs, as well as PTMs induced by oxidative stress and PTMs of antioxidant proteins. Though PTMs represent an important molecular mechanism for maintaining cellular homeostasis and are involved in the neurotoxic effects of MeHg, we are far from understanding the complete picture on their role, and further research is warranted to increase our knowledge of PTMs in MeHg-induced neurotoxicity.

From literary data it is known the investigation of contents and influence on an organism of chemical elements to be urgent, the carrying out such researches in the urbanized territories is especially important. The Orenburg region as production and processing of minerals (metal ore, hydrocarbons, etc.) undoubtedly treats such territories having been conducted since the 12th century. In this regard in the territory of the Orenburg region, the complex large-scale research of the trace element status of the territory is implemented. In 35 administrative regions of area samples of a surrounding environment and biosubstrate (hair) of constantly living population was taken. Research on the detection of chemical elements (Zn, Cu, Cd, Pb) in biosubstrate were carried out in the Autonomous non-profit organization “Center for Biotic Medicine”, and samples of a surrounding environment were examined in laboratories of the Exploring Center "All-Russian scientific research institute of meat cattle breeding" of the Russian Academy of Agrarian Sciences. Results of researches show factors of natural and technogenic character to have an impact on the maintenance of essential and toxic minerals in the environment. In underground waters, there was established the minimum content of zincum, copper, cadmium, and lead to be revealed in samples from areas of the Western and the Central Orenburg region. Moreover, the concentration of zincum, copper, cadmium, and lead in water of East zone, achieves the threshold limit value. The concentration in soils of zincum and copper was found to correspond to the maximum allowable concentration in samples from the East Orenburg region. The performed research of trace element structure of hair of the population of the Orenburg region showed both the content of the vital chemical elements (Zincum and copper) in an organism of the studied population to fail to correspond to reference values, the increased level of the studied elements (woman) in inhabitants of East zone, and the lower level zincum and copper in the examined population of the Central and Western area. The correlation and regression analysis allowed to establish the content of chemical elements in the soil to have the significant, reliable (p ≤ 0.05) influence on the element status of the examined residents of the Orenburg region.

The objective of the present study was investigation of the selenium (Se) levels in environmental samples, main consumed food products, as well as human hair in the areas of the Orenburg region. Se levels in the environmental objects (water, soil, wheat), frequently consumed food products (wheat bread, ryebread, beef, pork, chicken, milk, cottage cheese), as well as human hair samples in the western (n = 210), central (n = 195), and eastern (n = 120) areas were assessed using inductively-coupled plasma mass-spectrometry and atomic absorption spectrometry (soil). The obtained data demonstrate that water (87% and 89%), soil (41% and 48%), and wheat (11% and 11%) Se levels Central and Eastern areas were significantly higher than those in the Western area. The level of Se in foods was found to be the highest in the Eastern (wheat bread and beef), Central and Eastern (ryebread and pork), or Central (milk and cottage cheese) areas of the Orenburg region. Hair Se content (0.298 (0.233–0.591) μg/g) as well as dietary Se intake (84.3 (73.7–95.8) μg/day) did not differ significantly between the studied areas. At the same time, regression analysis demonstrated that Se intake with wheat bread (β = 0.634; p = 0.042) was the strongest predictor of hair Se. The revealed associations between environmental and food Se content and Se status of the population underline the necessity of continuous monitoring of Se intake and exposure in order to prevent potential health effects associated with both deficiency and overload.

The objective of the present study was to evaluate hair toxic metal levels in patients with obesity and/or coronary heart disease (CHD). Following a 2 × 2 factorial design, subjects without CHD were grouped into normal weight control (n = 123) and obese groups (n = 140). Patients suffering from CHD were divided into normal weight (n = 180) and obese CHD subjects (n = 240). Hair Al, As, Cd, Hg, Ni, and Pb levels were evaluated using inductively-coupled plasma mass-spectrometry. The data demonstrate that hair Al and Hg levels were higher in obese subjects as compared to normal weight controls. Normal weight CHD patients were characterized by significantly higher hair Al, As, Cd, and Pb levels when compared to healthy subjects. The highest hair Al, As, and Pb levels were observed in obese CHD patients, significantly exceeding the respective values in other groups. Factorial analysis revealed significant influence of factorial interaction (CHD*obesity) only for hair Pb content. Given the role of obesity as a risk factor for CHD, it is proposed that increased toxic metal accumulation in obesity may promote further development of cardiovascular diseases.

The aim of the present review is to discuss traditional hypotheses on the etiopathogenesis of Alzheimer's disease (AD), as well as the role of metabolic-syndrome-related mechanisms in AD development with a special focus on advanced glycation end-products (AGEs) and their role in metal-induced neurodegeneration in AD. Persistent hyperglycemia along with oxidative stress results in increased protein glycation and formation of AGEs. The latter were shown to possess a wide spectrum of neurotoxic effects including increased Aβ generation and aggregation. In addition, AGE binding to receptor for AGE (RAGE) induces a variety of pathways contributing to neuroinflammation. The existing data also demonstrate that AGE toxicity seems to mediate the involvement of copper (Cu) and potentially other metals in AD pathogenesis. Specifically, Cu promotes AGE formation, AGE-Aβ cross-linking and up-regulation of RAGE expression. Moreover, Aβ glycation was shown to increase prooxidant effects of Cu through Fenton chemistry. Given the role of AGE and RAGE, as well as metal toxicity in AD pathogenesis, it is proposed that metal chelation and/or incretins may slow down oxidative damage. In addition, selenium (Se) compounds seem to attenuate the intracellular toxicity of the deranged tau and Aβ, as well as inhibiting AGE accumulation and metal-induced neurotoxicity. Keywords: GLP-1 agonist; advanced glycation end-products; copper; glycemic dysregulation; iron; selenium. This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Summary Background & aims Coronavirus disease 2019 (COVID-19) patients are at high risk of malnutrition, and their doctors are part of a multidisciplinary team, including nutritionists. However, adherence to nutritional guidelines may be difficult in the context of capacity constraints during the COVID-19 pandemic. The aim of this study was to investigate barriers to doctors' adherence to nutritional guidelines and the impacts of guideline adherence on the outcomes of hospitalized COVID-19 patients. Methods A multinational electronic survey involving 51 doctors was conducted between November 2020 and January 2021 from 17 COVID-19-designated hospitals in countries with high (Indonesia) and low (Vietnam) numbers of confirmed COVID-19 cases. Results In general, doctors reported concerns related to nutritional practices in patients with Covid-19 which included feeling stress when performing medical nutritional therapy (65%), lacking self-efficacy or confidence in performing nutritional care (49%), lacking clear nutritional guidelines (45%), and experiencing budget limitations (33%). A regression analysis adjusted for age, country, and the number of hospitalized COVID-19 cases revealed that guideline knowledge (β: −1.01 (−1.78, −0.23); p = 0.012) and awareness of guidelines (β: −1.37 (−2.66, −0.09); p = 0.037) were negatively correlated with the length of stay of critically ill COVID-19 patients, but non-significant after adjusting for specialization of the doctor. When stratified according to country, a significant relationship between guideline adherence and length of stay of critically ill patients was only found in Vietnam [guideline adherence: β: −0.55 (−1.08, −0.03); p = 0.038; guideline knowledge: β: −1.01 (−1.9, −0.13); p = 0.027] after adjusting for age, specialty, and number of hospitalized COVID-19 cases. In Indonesia, the significant relationship between guideline adherence and mortality of COVID-19 patients remained strong (β: −14 (−27, −1); p = 0.033) after adjusting for age, specialty, and number of hospitalized COVID-19 cases Conclusions Inadequate nutritional knowledge is a key barrier to guideline adherence, and this was international and may be related to doctors' specialties and the COVID-19 pandemic. Adherence to nutritional guidelines may represent a prognostic factor for survival in COVID-19 patients.

An increasing body of literature has demonstrated that armed conflicts and military activity may contribute to environmental pollution with metals, although the existing data are inconsistent. Therefore, in this paper, we discuss potential sources of military-related metal emissions, environmental metal contamination, as well as routes of metal exposure and their health hazards in relation to military activities. Emission of metals into the environment upon military activity occurs from weapon residues containing high levels of particles containing lead (Pb; leaded ammunition), copper (Cu; unleaded), and depleted uranium (DU). As a consequence, military activity results in soil contamination with Pb and Cu, as well as other metals including Cd, Sb, Cr, Ni, Zn, with subsequent metal translocation to water, thus increasing the risk of human exposure. Biomonitoring studies have demonstrated increased accumulation of metals in plants, invertebrates, and vertebrate species (fish, birds, mammals). Correspondingly, military activity is associated with human metal exposure that results from inhalation or ingestion of released particles, as well as injuries with subsequent metal release from embedded fragments. It is also notable that local metal accumulation following military injury may occur even without detectable fragments. Nonetheless, data on health effects of military-related metal exposures have yet to be systematized. The existing data demonstrate adverse neurological, cardiovascular, and reproductive outcomes in exposed military personnel. Moreover, military-related metal exposures also result in adverse neurodevelopmental outcome in children living within adulterated territories. Experimental in vivo and in vitro studies also demonstrated toxic effects of specific metals as well as widely used metal alloys, although laboratory data report much wider spectrum of adverse effects as compared to epidemiological studies. Therefore, further epidemiological, biomonitoring and laboratory studies are required to better characterize military-related metal exposures and their underlying mechanisms of their adverse toxic effects.

The objective of the present study was to evaluate of serum metal levels in COVID-19 patients with different disease severity, and to investigate the independent association between serum metal profile and markers of lung damage. The cohort of COVID-19 patients consisted of groups of subjects with mild, moderate, and severe illness, 50 examinees each. Forty-four healthy subjects of the respective age were involved in the current study as the control group. Serum metal levels were evaluated using inductively-coupled plasma mass-spectrometry. Examination of COVID-19 patients demonstrated that heart rate, respiratory rate, body temperature, C-reactive protein levels, as well as lung damage increased significantly with COVID-19 severity, whereas SpO2 decreased gradually. Increasing COVID-19 severity was also associated with a significant gradual decrease in serum Ca, Fe, Se, Zn levels as compared to controls, whereas serum Cu and especially Cu/Zn ratio were elevated. No significant group differences in serum Mg and Mn levels were observed. Serum Ca, Fe, Se, Zn correlated positively with SpO2, being inversely associated with fever, lung damage, and C-reactive protein concentrations. Opposite correlations were observed for Cu and Cu/Zn ratio. In regression models, serum Se levels were inversely associated with lung damage independently of other markers of disease severity, anthropometric, biochemical, and hemostatic parameters. Cu/Zn ratio was also considered as a significant predictor of lower SpO2 in adjusted regression models. Taken together, these findings demonstrated that metal metabolism significantly interferes with COVID-19 pathogenesis, although the causal relations as well as precise mechanisms are yet to be characterized.