Keshan Disease Research Articles

Erythrocyte Selenium as a Potential Key Indicator for Selenium Supplementation in Low-Selenium Populations: A Selenium Supplementation Study Based on Wistar Rats

Background: Selenium (Se) is an essential trace element for maintaining human health, with significant antioxidant and immunoregulatory functions. Inadequate Se intake may be associated with Keshan disease, Kashin–Beck disease, and hypothyroidism. However, effective indicators for scientifically guiding Se supplementation in Se-deficient populations are still lacking. Objectives: This study aims to explore the dynamic distribution of Se across various nutritional biomarkers and major organs in rats through a Se supplementation experiment, as well as the pairwise correlations between them, in order to identify reliable nutritional indicators for evaluating Se levels in the body. Methods: Se levels in hair, blood, and major tissues and organs were determined by atomic fluorescence spectrometry, and glutathione peroxidase (GSH-Px) levels were measured using an ELISA. Results: Se supplementation significantly increased Se levels in rat blood, hair, and major organs, as well as GSH-Px levels in blood. Se primarily accumulated in the liver and kidneys, followed by myocardium, spleen, and muscles. Serum and plasma Se were found to be the best indicators of short-term Se intake, while erythrocyte Se levels showed a stronger correlation with Se levels in tissues and organs, making it a better marker for assessing long-term Se nutritional status compared to hair Se. Conclusions: This study demonstrates the potential of erythrocyte Se levels as an indicator for evaluating long-term Se nutritional status, providing scientific evidence for Se nutritional assessments.

Selenium, selenoprotein P and autoantibodies to selenium transport proteins in Swedish heart failure patients - a pilot study in preparation for a randomized supplementation trial

Abstract Background Severe selenium (Se) deficiency, as in Keshan disease, is associated with a fatal form of heart failure (HF), preventable and reversible with Se supplementation. Recent studies have identified Se deficiency as highly prevalent, up to 70%, among patients with HF, and associated with a poorer prognosis. Observational data suggest that Se concentrations <100 μg/L in HF patients and selenoprotein P (SELENOP) concentrations <4.1 mg/L are associated with increased mortality and hospital readmissions. Further, in recent studies, natural autoantibodies (aAb) towards SELENOP have been detected with the potential to disrupt transportation mechanisms. While the evidence does not yet support Se supplementation for HF patients in clinical practice, it does justify the initiation of large, well-designed randomized controlled trials (RCTs). Purpose To assess and confirm the previously reported high prevalence of Se deficiency, measured by both Se and SELENOP concentrations in HF patients and exploring the prevalence of aAb to SELENOP. This will provide a rationale for further, adequately powered and designed, studies of Se supplementation in HF patients. Methods A total of 527 blood samples were obtained from a nationwide Swedish HF biobank, sourced from various hospitals. In those samples; serum Se concentrations in 455 samples using mass spectrometry, SELENOP concentrations in 520 samples using an immunoassay, and prevalence of aAb to SELENOP in 513 samples using an immunoluminometric assay were analyzed. In addition, SELENOP concentrations in 320 HF patients from a Swedish single-center study were analysed. Results The study population had a mean age of 70.3 (±11.8) years (30.5% women). Prevalence of Se deficiency was higher than previously reported. In the national HF registry, the median Se concentration was 75 µg/L and Se concentrations below 100 μg/L were found in 426 (93%) samples. SELENOP concentrations had a median of 3.5 mg/L, corresponding to ~80 μg/L Se, with 80.5% of subjects below SELENOP-concentration of 4.3 mg/L (corresponding to ~100 μg/L Se). In the confirmatory single-center study, the SELENOP median concentration was 3.1 mg/L, corresponding to Se concentrations of ~70 µg/L and SELENOP -concentrations below 4.3 mg/L (corresponding to approximately 100 μg/L Se) were observed in 89.4% of the study population. Further, aAb to SELENOP were prevalent in 9.7% of the population, compared to approximately 1% in healthy subjects. Conclusion This pilot study demonstrates a high prevalence of suboptimal Selenium status in Swedish HF patients which further underscores the need for suitably designed intervention studies to address the efficacy and safety of Se supplementation which can possibly constitute an inexpensive, safe and readily available treatment option for HF patients.

High selenium diet attenuates pressure overload-induced cardiopulmonary oxidative stress, inflammation, and heart failure

Selenium (Se) deficiency is associated with the development of Keshan disease, a cardiomyopathy associated with massive cardiac immune cell infiltration that can lead to heart failure (HF). The purpose of this study was to determine whether high Se diet can attenuate systolic overload-induced cardiopulmonary inflammation and HF. Briefly, transverse aortic constriction (TAC)-induced cardiopulmonary oxidative stress, inflammation, left ventricular (LV) dysfunction, and pulmonary remodeling were determined in male mice fed with either high Se diet or normal Se diet. High Se diet had no detectable effect on LV structure and function in mice under control conditions, but high Se diet significantly protected mice from TAC-induced LV hypertrophy, dysfunction, increase of lung weight, and right ventricular hypertrophy. As compared with mice treated with normal Se diet, high Se diet also reduced TAC-induced LV cardiomyocyte hypertrophy, fibrosis, leukocyte infiltration, pulmonary inflammation, pulmonary fibrosis, and pulmonary micro-vessel muscularization. In addition, high Se diet significantly ameliorated TAC-induced accumulation and activation of pulmonary F4/80+ macrophages, and activation of dendritic cells. Interestingly, high Se diet also significantly attenuated TAC-induced activation of pulmonary CD4+ and CD8+ T cells. Moreover, we found that TAC caused a significant increase in cardiac and pulmonary ROS production, increases of 4-hydroxynonenal (4-HNE) and 3-nitrotyrosine (3-NT), as well as a compensatory increases of LV glutathione peroxidase 1 (GPX1) and 4 (GPX4) in mice fed with normal Se diet. Above changes were diminished in mice fed with high Se diet. Collectively, these data demonstrated that high Se diet significantly attenuated systolic pressure overload-induced cardiac oxidative stress, inflammation, HF development, and consequent pulmonary inflammation and remodeling.

A Comparative Study on Soil-Crop Selenium Characteristics in High-Incidence Areas of Keshan Disease in Chinese Loess and Black Soil

With the gradual emphasis on health by people, the research on the pathogenesis of endemic diseases has become increasingly in-depth. Through analyzing the environmental selenium characteristics and conducting a comparative study in typical areas of Chinese loess and black soil in this paper, it is concluded that the environmental selenium in the two regions has different characteristics. The soil in the loess area has the characteristics of high alkalinity, low selenium, and relatively high selenium availability, and the crops are selenium-deficient, while the soil in the black soil area has the characteristics of high organic matter, low selenium availability, and relatively high selenium in crops. The research concluded that the environmental occurrence mechanism of Keshan disease in the loess area and the black soil area is different. Keshan disease can be induced in both low-selenium and sufficient-selenium environments, and environmental selenium should be one of the inducing factors of Keshan disease. This research provides a reference for predicting the areas where Keshan disease occurs and for disease prevention, and it can also serve in the prevention and control of endemic diseases.

Selenium as a Modulator of Redox Reactions in the Prevention and Treatment of Cardiovascular Diseases.

Cardiovascular diseases stand as the predominant global cause of mortality, exerting a profound impact on both life expectancy and its quality. Given their immense public health burden, extensive efforts have been dedicated to comprehending the underlying mechanisms and developing strategies for prevention and treatment. Selenium, a crucial participant in redox reactions, emerges as a notable factor in maintaining myocardial cell homeostasis and influencing the progression of cardiovascular disorders. Some disorders, such as Keshan disease, are directly linked with its environmental deficiency. Nevertheless, the precise extent of its impact on the cardiovascular system remains unclear, marked by contradictory findings in the existing literature. High selenium levels have been associated with an increased risk of developing hypertension, while lower concentrations have been linked to heart failure and atrial fibrillation. Although some trials have shown its potential effectiveness in specific groups of patients, large cohort supplementation attempts have generally yielded unsatisfactory outcomes. Consequently, there persists a significant need for further research aimed at delineating specific patient cohorts and groups of diseases that would benefit from selenium supplementation.

Generation of selenium-rich wheat mutants and exploration of responsive genes for selenium accumulation.

Salt tolerance, selenium accumulation and expression of the responsive genes were analyzed in the wheat high selenium mutants. Selenium is an essential trace element for the human body, and its deficiency can lead to various diseases such as Keshan disease and large bone disease. Wheat, being a major staple crop, plays a crucial role in providing dietary selenium supplementation to combat this deficiency. Despite progress in understanding the molecular regulation of selenium accumulation in certain crops, the molecular mechanisms governing selenium accumulation-related gene expression in wheat plants remain poorly understood. In this study, three mutant wheat lines with elevated selenium content were identified. Under the treatment of Na2SeO3 or NaCl, the selenium-rich wheat mutants exhibited decreased sensitivity to both selenium and NaCl compared to the wild type. Additionally, there was an increase in the activities of SOD and POD, while the content of MDA decreased. Through qRT-PCR analysis, the expression of selenium-related genes was affected, revealing that some of these genes not only regulate the response of wheat to salt stress, but also play a role in the process of selenium accumulation. The transcriptome results revealed that the important genes encoding glutathione S-transferases, peroxidases, superoxide dismutases, and UDP-glucosyltransferases may function in the regulation of salt tolerance and selenium accumulation in wheat. These findings significantly contribute to the current understanding of the molecular regulation of selenium accumulation in wheat crops, while also offering novel germplasm resources for cultivating selenium-rich and salt-tolerant wheat lines.

Recent Advances on Selenium Nutrition and Keshan Disease.

Keshan disease (KD) is a type of endemic cardiomyopathy with an unknown cause. It is primarily found in areas in China with low selenium levels, from northeast to southwest. The nutritional biogeochemical etiology hypothesis suggests that selenium deficiency is a major factor in KD development. Selenium is important in removing free radicals and protecting cells and tissues from peroxide-induced damage. Thus, low environmental selenium may affect the selenium level within the human body, and selenium level differences are commonly observed between healthy people in KD and nonKD areas. From the 1970s to the 1990s, China successfully reduced KD incidence in endemic KD areas through a selenium supplementation program. After years of implementing prevention and control measures, the selenium level of the population in the KD areas has gradually increased, and the prevalence of KD in China has remained low and stable in recent years. Currently, the pathogenesis of KD remains vague, and the effect of selenium supplementation on the prognosis of KD still needs further study. This paper comprehensively reviews selenium deficiency and its connection to KD. Thus, this study aims to offer novel ideas and directions to effectively prevent and treat KD in light of the current situation.

The cardiomyopathy of cystic fibrosis: a modern form of Keshan disease.

We conducted a study to determine the prevalence of structural heart disease in patients with CF, the characteristics of a cardiomyopathy not previously described in this population, and its possible relationship with nutritional deficiencies in CF. We studied 3 CMP CF patients referred for heart-lung transplantation and a prospective series of 120 adult CF patients. All patients underwent a clinical examination, blood tests including levels of vitamins and trace elements, and echocardiography with evaluation of myocardial strain. Cardiac magnetic resonance imaging (CMR) was performed in patients with CMP and in a control group. Histopathological study was performed on hearts obtained in transplant or necropsy. We found a prevalence of 10% (CI 4.6%-15.4%) of left ventricular (LV) dysfunction in the prospective cohort. Myocardial strain parameters were already altered in CF patients with otherwise normal hearts. Histopathological examination of 4 hearts from CF CMP patients showed a unique histological pattern of multifocal myocardial fibrosis similar to Keshan disease. Four of the five CF CMP patients undergoing CMR showed late gadolinium uptake, with a characteristic patchy pattern in 3 cases (p < 0.001 vs. CF controls). Selenium deficiency (Se < 60 µg/L) was associated with more severe LV dysfunction, higher prevalence of CF CMP, higher NTproBNP levels, and more severe pulmonary and digestive involvement. 10% of adults with CF showed significant cardiac involvement, with histological and imaging features resembling Keshan disease. Selenium deficiency was associated with the presence and severity of LV dysfunction in these patients.

Low Selenium and Low Protein Exacerbate Myocardial Damage in Keshan Disease by Affecting the PINK1/Parkin-mediated Mitochondrial Autophagy Pathway.

Keshan disease (KD) is a myocardial mitochondrial disease closely related to insufficient selenium (Se) and protein intake. PTEN induced putative kinase 1 (PINK1)/Parkin mediated mitochondrial autophagy regulates various physiological and pathological processes in the body. This study aimed to elucidate the relationship between PINK1/Parkin-regulated mitochondrial autophagy and KD-related myocardial injury. A low Se and low protein animal model was established. One hundred Wistar rats were randomly divided into 5 groups (control group, low Se group, low protein group, low Se + low protein group, and corn from KD area group). The JC-1 method was used to detect the mitochondrial membrane potential (MMP). ELISA was used to detect serum creatine kinase MB (CK-MB), cardiac troponin I (cTnI), and mitochondrial-glutamicoxalacetic transaminase (M-GOT) levels. RT-PCR and Western blot analysis were used to detect the expression of PINK1, Parkin, sequestome 1 (P62), and microtubule-associated proteins1A/1B light chain 3B (MAP1LC3B). The MMP was significantly decreased and the activity of CK-MB, cTnI, and M-GOT significantly increased in each experimental group (low Se group, low protein group, low Se + low protein group and corn from KD area group) compared with the control group (P<0.05 for all). The mRNA and protein expression levels of PINK1, Parkin and MAP1LC3B were profoundly increased, and those of P62 markedly decreased in the experimental groups compared with the control group (P<0.05 for all). Low Se and low protein levels exacerbate myocardial damage in KD by affecting the PINK1/Parkin-mediated mitochondrial autophagy pathway.

A preliminary predictive model for selenium nutritional status in residents based on three selenium biomarkers

BackgroundSelenium (Se) is an essential nutrient and an important component of many selenoproteins that possess fundamental importance to human health. Selenium deficiency and excess will cause corresponding diseases in the human body. The nutritional health of Se in the human body mainly depends on the daily dietary Se intake of the human body, which in turn depends to a certain extent on the content of Se transmitted along the food chain. This study aims to research the transport of Se through the soil-crop-human chain in regions with different Se levels, and to establish the model between the residents' dietary Se intake and the three Se biomarkers (hair, nails, and plasma), to predict the nutritional health status of Se in residents through Se biomarkers. MethodCarry out field and cross-sectional surveys of populations in Loujiaba Village and Longshui Village. Samples were collected from soil, crops, drinking water, residents' hair, nails, plasma, and diet. The concentration of available Se fractions was extracted from soil samples using 0.1 mol/L K2HPO4. The concentration of total Se for all samples was determined by Inductively Coupled Plasma-Mass Spectrometry (ICP-MS), and the relative standard deviation was less than 5%. In this study, hair, nails, and blood samples were collected from volunteers according to the Declaration of Helsinki and the Ethics Committee of Soochow University. The dietary nutritional structure and dietary Se intake of the population were randomly selected by 12 volunteers using the duplicate portion method. Data were described using mean ± standard deviation. We performed saliency analysis and correlation analysis (with Pearson correlation coefficient), and fitted a regression to evaluate the associations between these variables. ResultsThe soil total Se (5201 ± 609.2 μg/kg) and available Se (307.7 ± 83.5 μg/kg) in Luojiaba Village (LJB) were significantly higher than the soil total Se (229.2 ± 32.5 μg/kg) and available Se (21.9 ± 4.0 μg/kg) in Longshui Village (LS). The residents' dietary Se intake of LJB (150.3 ± 2.2 μg/d) was within the World Health Organization (WHO) recommended intake range, while LS (16.0 ± 0.4 μg/d) was close to the range of Keshan disease occurrence, and there was a risk of insufficient Se intake. The correlation analysis found significant positive correlations between residents' dietary Se intake and the three Se biomarkers. According to the preliminary model established in this study, if the daily dietary Se intake of residents reaches the WHO recommended value of 55–400 μg, the hair, nails, and plasma of Se concentration will be 522.1–2850.5 μg/kg, 1069.0–6147.4 μg/kg, and 128.3–661.36 μg/L, respectively. ConclusionSelenium is transmitted through the soil-crop-human chain, and the Se concentration that enters the human body through the food chain in high-Se areas is significantly higher than that in low-Se areas. The nutritional health status of Se in the human body depends on the daily dietary intake of the human body, and there is a significant correlation between the daily dietary Se intake of the human body and the three biomarkers of Se levels in the human body, so the three biomarkers can be used to evaluate the Se nutritional health of the human.

Research Progress of Selenium-Enriched Foods.

Selenium is an essential micronutrient that plays a crucial role in maintaining human health. Selenium deficiency is seriously associated with various diseases such as Keshan disease, Kashin-Beck disease, cataracts, and others. Conversely, selenium supplementation has been found to have multiple effects, including antioxidant, anti-inflammatory, and anticancer functions. Compared with inorganic selenium, organic selenium exhibits higher bioactivities and a wider range of safe concentrations. Consequently, there has been a significant development of selenium-enriched foods which contain large amounts of organic selenium in order to improve human health. This review summarizes the physiological role and metabolism of selenium, the development of selenium-enriched foods, the physiological functions of selenium-enriched foods, and provides an analysis of total selenium and its species in selenium-enriched foods, with a view to laying the foundation for selenium-enriched food development.

Selenium intake and multiple health-related outcomes: an umbrella review of meta-analyses.

Selenium is an essential trace metalloid element that is associated with fundamental importance to human health. Our umbrella review aimed to evaluate the quality of evidence, validity, and biases in the relationship between selenium intake and health-related outcomes according to published systematic reviews with pooled data and meta-analyses. Selenium intake is associated with a decreased risk of digestive system cancers, all-cause mortality, depression, and Keshan disease, when in children reduce the risk of Kashin-Beck disease. Additionally, selenium supplementation can improve sperm quality, polycystic ovary syndrome, autoimmune thyroid disease, cardiovascular disease, and infective outcomes. Selenium supplementation also has relationship with a decreased concentration of serum lipids including total cholesterol and very low-density lipoprotein cholesterol. However, no evidence has shown that selenium is associated with better outcomes among patients in intensive care units. Furthermore, selenium intake may be related with a higher risk of type 2 diabetes and non-melanoma skin cancers. Moreover, most of included studies are evaluated as low quality according to our evidence assessment. Based on our study findings and the limited advantages of selenium intake, it is not recommended to receive extra supplementary selenium for general populations, and selenium supplementation should not be continued in patients whose selenium-deficient status has been corrected.

The Role of Selenium in Atherosclerosis Development, Progression, Prevention and Treatment.

Selenium is an essential trace element that is essential for various metabolic processes, protection from oxidative stress and proper functioning of the cardiovascular system. Se deficiency has long been associated with multiple cardiovascular diseases, including endemic Keshan's disease, common heart failure, coronary heart disease, myocardial infarction and atherosclerosis. Through selenoenzymes and selenoproteins, Se is involved in numerous crucial processes, such as redox homeostasis regulation, oxidative stress, calcium flux and thyroid hormone metabolism; an unbalanced Se supply may disrupt these processes. In this review, we focus on the importance of Se in cardiovascular health and provide updated information on the role of Se in specific processes involved in the development and pathogenesis of atherosclerosis (oxidative stress, inflammation, endothelial dysfunction, vascular calcification and vascular cell apoptosis). We also discuss recent randomised trials investigating Se supplementation as a potential therapeutic and preventive agent for atherosclerosis treatment.

Prevalence of hypertension in endemic and non-endemic areas of Keshan disease: A cross-sectional study in rural areas of China.

Hypertension is a major public health concern that strongly influences the quality of life of people worldwide. Keshan disease (KD) is an endemic cardiomyopathy related to low selenium, threatening residents in rural areas of 16 provinces in China. Furthermore, the prevalence of hypertension in the KD-endemic areas has been increasing annually. However, hypertension research associated with KD has only focused on endemic regions, and no studies have compared hypertension prevalence between endemic and non-endemic areas. Therefore, this study investigated the prevalence of hypertension to provide a basis for preventing and controlling hypertension in the KD-endemic areas, even in rural areas. We extracted blood pressure information from cardiomyopathy investigation data from a cross-sectional study of the KD-endemic and non-endemic areas. The hypertension prevalence between the two groups was compared using the Chi-square test or Fisher s exact test. Additionally, Pearson's correlation coefficient was employed to evaluate the relationship between the per capita gross domestic product (GDP) and hypertension prevalence. There was a statistically significant increase of hypertension prevalence in the KD-endemic areas (22.79%, 95% confidence interval [CI]: 22.30-23.27%) over the non-endemic areas (21.55%, 95% CI: 21.09-22.02%). In the KD-endemic areas, more men had hypertension than women (23.90% vs. 21.65%, P < 0.001). Furthermore, the hypertension prevalence was higher in the north than in the south in the KD-endemic areas (27.52% vs. 18.76%, P < 0.001), non-endemic areas (24.86% vs. 18.66%, P < 0.001), and overall (26.17% vs. 18.68%, P < 0.001). Finally, the prevalence of hypertension positively correlated with per capita GDP at province level. The increasing hypertension prevalence is a public health problem in the KD-endemic areas. Healthy diets, such as high consumption of vegetables and seafoods, and foods that are rich in selenium, might help prevent and control hypertension in the KD-endemic areas and other rural areas in China.

Effects of directional adaptation on selenium tolerance and accumulation of heterotrophic Chlorella pyrenoidosa

Selenium (Se) is an essential trace element for organisms. Se deficiency will cause diseases such as Keshan disease and Kashin-Beck in human being, and huge loss to animal husbandry. Currently available Se supplements have such problems as low Se content, poor bioavailability, and poor safety. Chlorella pyrenoidosa can produce bioavailable and safe organic Se under suitable conditions, which is thus a promising Se supplement. Therefore, in this study, we tried to improve the Se tolerance and accumulation of C. pyrenoidosa by directional adaptation. To be specific, we gradually increased the concentration of Na2SeO3 in medium to domesticate C. pyrenoidosa and optimized the adapting time and concentration gradient of Na2SeO3 during the adaptation. The results showed that the adapted C. pyrenoidosa was more tolerant to Se and had stronger Se enrichment ability. In 5 L fermenter, the adapted strains could tolerate 40 mg/L Na2SeO3 and the synthesis rate of organic Se was 175.6% higher. Then, Se addition method in the 5 L fermenter was optimized. The result demonstrated that addition of Na2SeO3 at 40 mg/L during heterotrophic culture achieved the final dry weight of C. pyrenoidosa cells at 106.4 g/L, content of organic Se at 1 227 mg/kg, and synthesis rate of organic Se at 1.36 mg/(L·h). Compared with the reported highest cell density of 75 g/L and the highest organic Se content of 560 mg/kg, the corresponding figures in this study were 41.9% and 119.1% higher, respectively. In conclusion, directional adaptation can remarkably improve the Se tolerance and enrichment of C. pyrenoidosa.

Electrophysiological Effect of Citreoviridin on Human InducedPluripotent Stem Cell-derived Cardiomyocytes

Citreoviridin (CTV) is a mycotoxin produced by various fungi, including Penicillium citreonigrum. One of the toxicities reportedly associated with CTV is neurotoxicity. CTV is also suspected to be associated with acute cardiac beriberi (also known as "Shoshin-kakke") and Keshan disease, which can have adverse effects on the heart, so the in vivo and in vitro toxicity of CTV on the heart or cardiomyocytes in experimental animal models have been reported. However, the toxicity of CTV for the human heart, especially its electrophysiological effect, remains poorly understood. Therefore, to investigate the electrophysiological effect of CTV on the human cardiomyocytes, we conducted a multi-electrode array (MEA) using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). The MEA revealed that 30 μmol/L of CTV stopped the beating of hiPSC-CMs, and the field potential duration and first peak amplitude were shortened at 10 μmol/L. Before the hiPSC-CMs stopped beating, the length of the inter-spike interval varied two- to four-fold. These results demonstrated that CTV induced an electrophysiological disturbance on human cardiomyocytes. This is first paper to elucidate the electrophysiological effect of CTV on human heart directly and may aid in analyzing the risk associated with CTV to ensure food safety.

A county-level spatial epidemiological study of hair selenium and Keshan disease.

No spatial analysis of hair selenium and Keshan disease (KD) on a nationwide county-level has been performed. Selenium deficiency is a recognized environmental risk factor for KD. Hair selenium is one of the recognized biomarkers of selenium nutrition. This study aimed to perform a geographically precise and visualized assessment of the achievement of KD prevention and control at the level of selenium nutrition in terms of etiology. A spatial ecological study was conducted. The hair selenium content of the residents was assayed using an atomic fluorescence spectrometer. The spatial analysis was performed using ArcGIS. The median of the hair selenium levels of the 3,028 participants in the 1,174 counties was 0.38 mg/kg, and the content of inhabitants in KD endemic counties was significantly lower than that in KD non-endemic counties (0.34 vs. 0.39 mg/kg, z = -10.03, P < 0.0001). The proportion of Se-deficient and Se-marginal counties in KD endemic counties was significantly higher than that in KD non-endemic counties (59.4 vs. 29.0%, z = -7.45, P < 0.0001). The global autocorrelation analysis was not statistically significant (Moran's I = 0.0005, P = 0.68). Local autocorrelation analysis identified 174 low-low clusters of hair selenium levels, 83 (47.7%) of which are KD endemic counties located in KD endemic provinces of Henan, Gansu, Shaanxi, Inner Mongolia, Jilin, and Heilongjiang. The hair selenium featured a positive correlation with per capita GDP (r s = 0.20, P < 0.0001). The median of the hair selenium levels of inhabitants living in KD endemic counties was significantly lower than that in KD non-endemic counties. All the 83 KD endemic counties with low-low clusters of hair selenium levels should be prioritized in KD precision prevention and control. These findings are geographically precise and visualized evidence of the assessment of the effectiveness of KD prevention and control at the level of selenium nutrition in terms of etiology.

Integrative analysis of multiomics data identifies selenium-related gene ALAD associating with keshan disease.

Keshan disease is an endemic fatal dilated cardiomyopathy that can cause heart enlargement, heart failure, and cardiogenic death. Selenium deficiency is considered to be the main cause of Keshan disease. However, the molecular mechanism underlying Keshan disease remains unclear. Our whole-exome sequencing from 68 patients with Keshan disease and 100 controls found 199 candidate genes by gene-level burden tests. Interestingly, using multiomics data, the selenium-related gene ALAD (δ-aminolevulinic acid dehydratase) was the only candidate causative gene identified by three different analysis approaches. Based on single-cell transcriptome data, ALAD was highly expressed in cardiomyocytes and double mutations of human ALAD dramatically reduced its enzyme activity in vitro compared to negative control. Functional analysis of ALAD inhibition in mice resulted in a Keshan phenotype with left ventricular enlargement and cardiac dysfunction, whereas administration of sodium selenite markedly reversed the changes caused by ALAD inhibition. In addition, sodium selenite reversed Keshan phenotypes by affecting energy metabolism and mitochondrial function in mice as shown by the transcriptomic and proteomic data and the ultrastructure of cardiac myocytes. Our findings are the first to demonstrate that the selenium-related gene ALAD is essential for cardiac function by maintaining normal mitochondrial activity, providing strong molecular evidence supporting the hypothesis of selenium deficiency in Keshan disease. These results identified ALAD as a novel target for therapeutic intervention in Keshan disease and Keshan disease-related dilated cardiomyopathy.

The Dynamics of Selenium in Dairy Agroecosystems

Environmental selenium deficiency and toxicity can result in Keshan disease and selenosis, respectively. Due to dietary preferences, milk is considered a primary source of selenium, where, in controlled environments milk selenium concentration reflects the selenium provided in fodder to lactating cows. However, the movement of selenium through agroecosystems is not well understood. Therefore, the aim of this current study was to investigate variables that are responsible for transfer of selenium from soil to milk. Investigated parameters include spatial variability, soil selenium status, season, herd diet and husbandry of cattle. Farm-based sample collections were carried out, where soil, grass, silage and milk were collected over forty-eight geographically spaced locations over Northern Ireland during both summer and winter. Selenium concentrations were determined using ICP-MS. Median selenium concentrations for soil (0.46 mg/kg DM), grass (0.06 mg/kg DM) silage (0.03 mg/kg DM) and milk (0.23 mg/kg DM). Results showed that soil selenium concentrations were significantly affected by the pH and organic matter composition of soil. Additionally, a statistically significant relationships between soil and grass selenium concentrations were also found. Despite these strong environmental relationships with grass, these relationships were not reflected in the milk selenium concentrations, indicating a disconnect between the selenium concentration in the agricultural environment and the milk from which it is derived. Selenium was higher in milk in winter months as compared to summer, related to supplemental feed practices over the winter when cows are housed. This study highlighted that cattle feed supplementation of feed with selenium, an essential element, was an effective way of enhancing dietary exposure through a commonly consumed foodstuffs derived from dairy.

Hair Selenium of Residents in Keshan Disease Endemic and Non-endemic Regions in China.

Few nationwide investigations on hair selenium (Se) and Keshan disease (KD) have been conducted. KD is closely associated with Se deficiency. Hair Se is an important biomarker for selenium nutrition. This research aimed to provide evidence for assessment of KD prevention, control, and elimination at the molecular level from the etiological perspective of selenium nutrition. The hair Se of the residents living in the KD endemic and non-endemic areas were determined through atomic fluorescence spectrometer. The median of the hair Se levels of the inhabitants living in KD endemic counties was significantly lower than that in KD non-endemic counties (0.34 vs 0.39 mg/kg, U = -10.03, P < 0.0001). The proportion of Se-deficient or Se-marginal residents in KD endemic counties was significantly higher than that in KD non-endemic counties (56.9% vs 36.6%, U = -9.57, P < 0.0001). The medians of the hair Se levels in KD endemic provinces of Shannxi, Heilongjiang, and Gansu were the lowest (0.35mg/kg), and in the category of Se-marginal status. The hair Se level featured a positive Spearman correlation with per capita disposable income (rs = 0.20, P < 0.0001). In conclusion, the median of the hair Se contents of residents living in KD endemic counties was significantly lower than that in KD non-endemic counties. The hair Se contents of nearly 57% of inhabitants living in KD endemic regions were in Se-deficient or Se-marginal status. The KD endemic provinces of Shannxi, Heilongjiang, and Gansu should be given high priority in KD prevention and control.