DNA methylation in human diseases.

Aberrant epigenetic modifications, particularly DNA methylation, play a critical role in the pathogenesis and progression of human diseases. The current review aims to reveal the role of aberrant DNA methylation in the pathogenesis and progression of diseases and to discuss the original data obtained from international research laboratories on this topic. In the review, we mainly summarize the studies exploring the role of aberrant DNA methylation as diagnostic and prognostic biomarkers in a broad range of human diseases, including monogenic epigenetics, autoimmunity, metabolic disorders, hematologic neoplasms, and solid tumors. The last section provides a general overview of the possibility of the DNA methylation machinery from the perspective of pharmaceutic approaches. In conclusion, the study of DNA methylation machinery is a phenomenal intersection that each of its ways can reveal the mysteries of various diseases, introduce new diagnostic and prognostic biomarkers, and propose a new patient-tailored therapeutic approach for diseases.

The effects of high doses of selenium supplementation on mRNA and protein levels of cMLCK levels and total antioxidant capacity in rat heart tissue.

BACKGROUND: High doses of selenium are associated with heart disease prevalence in high-risk areas. Cardiac myosin light chain kinase (cMLCK) is an essential enzyme for normal function of heart tissue. Therefore, we studied the effect of high doses of selenium on the expression of cMLCK gene and its protein in normal heart tissue in rats. MATERIALS AND METHODS: Twenty male rats were randomly divided into four groups: control, Se 0.3mg/kg, Se 1.5mg/kg, and Se 3mg/kg. Sodium-selenite was administered orally into drinking water for 20 weeks. Se levels of heart tissue were measured by atomic absorption. Serum creatine phosphokinase (CPK) and total serum antioxidant capacity were measured. Moreover, the concentration of MLCK protein and the gene expression level of cMLCK in normal heart tissue were analyzed. RESULTS: Excess Se in dietary can significantly increase CPK. Se concentration of heart tissue in the Se 3mg/kg group was significantly higher than the control. cMLCK mRNA levels were decreased by 0.3mg/kg and 3mg/kg sodium selenite intake. There was no significant difference between the three groups for total antioxidant capacity and MLCK protein. CONCLUSION: High concentrations of selenium can probably effect on normal function of the heart tissue by changing the expression levels of cMLCK.

Long-Term Excessive Selenium Supplementation Affects Gene Expression in Esophageal Tissue of Rats.

Esophageal cancer is one of the leading causes of cancer death and the seventh most prevalent cancer worldwide. Considering the positive association of high selenium with the prevalence of esophageal cancer, we have investigated the effect of high doses of selenium on gene expression in the normal esophageal tissue of rats. Twenty male rats were randomly divided into four groups: control group, group 2 mg Se/L, 10 mg Se/L, and 20 mg Se/L rats fed with a basal basic diet and 2, 10, and 20 mg Se/L as sodium selenite in drinking water, respectively, for 20 weeks. Serum malondialdehyde and glutathione peroxidase activity were measured. Moreover, the expression and concentration of the cyclin D1, cyclin E, KRAS, p53, NF-kB, TGF-ß, and MGMT in the esophageal tissue were analyzed and compared between the four groups. In normal esophageal tissue, selenium supplementations (2, 10, and 20 mg Se/L) increased the mRNA levels of cyclin D1, P53, KRAS, NF-κB p65, and MGMT and decreased the mRNA level of TGFß1. The concentrations of cyclin D1 and MGMT were also significantly increased by selenium supplementations. Selenium supplementations had no significant effect on serum MDA but significantly increased GPX activity. The present study suggests that selenium supplementation (2, 10, and 20 mg Se/L) affects gene expression related to inflammation, Cell proliferation, and apoptosis in the normal esophageal tissue. However, there were no observed abnormalities other than reduced growth with supplementation of 20 mg/L as Na2SeO3 in rats.

Serum Selenium, Vitamin A, and Vitamin E Levels of Healthy Individuals in High- and Low-Risk Areas of Esophageal Cancer.

Background: Esophageal cancer is one of the main causes of cancer mortality in the world. Golestan province, in the northern part of Iran, has the highest esophageal cancer rate in the world. The north and south districts of Golestan province can be classified as low and high-risk areas for esophageal cancer. One of the potential risk factors for esophageal cancer in this population is a nutrient-deficient diet. Dietary antioxidant compounds such as selenium, vitamin E, vitamin A, and ß-carotene are reactive oxygen species (ROC) scavengers that play a key role in cellular responses to oxidative stress and preventing DNA damage. This study aims to compare the serum levels of selenium, vitamin E, and vitamin A in healthy individuals in high and low-risk areas of esophageal cancer. Methods: This study is a population of 242 healthy individuals. Serum selenium levels were assessed by atomic absorption spectroscopy. Vitamin E and A were assessed by reversed-phase high-performance liquid chromatography. Results: Vitamin E levels of healthy individuals in high-risk areas were significantly lower than in low-risk areas, while there was no significant difference between the selenium and vitamin A levels of healthy individuals in high-risk areas and low-risk areas. Also, there was no significant difference between selenium, vitamin E, and vitamin A levels in urban and rural areas and men and women in Golestan province. Conclusion: High levels of selenium with lower levels of vitamin E, along with other risk factors, may be associated with esophageal squamous cell carcinoma in high-risk areas of Golestan province.

Decreased Serum Selenium Levels of COVID-19 Patients in Comparison with Healthy Individuals.

BACKGROUND: Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the cause of the COVID-19 pandemic and is the cause of increased mortality, especially among elderly patients and those who have severe complications, such as chronic pulmonary obstruction, hypertension, diabetes, and cancer. Nutrition, especially micronutrients, plays an important role in reducing mortality and complications from COVID-19 because micronutrients strengthen our immune system and nutritional status is an important factor that affects the outcome of patients with COVID-19. Among micronutrients, selenium has an important effect on both intrinsic and acquired immunity. Host selenium deficiency affects the viral genome and increases the virulence of viruses. We have investigated the serum selenium levels in COVID-19 patients and healthy control individuals. METHODS: A total of 50 patients with COVID-19 infection were included in this study. During hospitalization, 13 patients died (non-survivor group) and 37 patients recovered (survivor group). We assessed the serum selenium levels in 50 COVID-19 patients and 50 healthy individuals by Agilent SpectrAA-240 Z atomic absorption spectrometer. RESULTS: The serum selenium level was significantly lower in COVID-19 patients (77. 8 ± 13.9 µg/L) as compared to healthy control individuals (91.7 ± 16.7 µg/L), but there was no significant difference between the survivor and non-survivor groups. Also, there was no significant relationship between serum selenium levels and laboratory findings of COVID-19 patients. CONCLUSIONS: These results suggest that decreased serum selenium levels may be a risk factor for the COVID-19 infection, but there was no significant relationship between selenium and severity and mortality of COVID-19 disease.