Association study of selenium-related gene polymorphisms with geriatric depression in China.

Depression is a common mental health problem in older adults, but its cause remains unclear. Selenium is an essential micronutrient and a powerful antioxidant in the brain and nervous system. Several recent studies have reported a relationship between selenium levels and depression. This study aimed to investigate the relationship between 4 genes co-associated with selenium and geriatric depression. 1486 participants were included in this study from 5 communities in Ningxia Hui Autonomous Region during 2013 to 2016 in a health examination program for urban and rural residents. Polymorphisms of 4 selenium-related genes were analyzed in 1266 healthy volunteers and 220 patients with depression. The genotyping of rs2830072, rs2030324, rs6265, rs11136000, rs7982, rs10510412, rs1801282, rs1151999, rs17793951, rs709149, rs709154, and rs4135263 were performed by Matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF-MS) technology. The analysis of selenium-related genes showed that there were significant differences between depression and controls for allele and genotype frequencies of peroxisome proliferator activated receptor gamma (PPARG) rs10510412, rs709149, and rs709154 (all P < .05). In this study, when adjusting for age, sex, marital status, education, and alcohol consumption, results showed that rs709149 and rs709154 were still significantly correlated with geriatric depression in the codominant, dominant, overdominant, and log-additive models. Logistic regression analysis showed that rs709149 AG or GG gene carriers were 1.630 and 1.746 times more susceptible to depression than AA gene carriers (95% CI = 1.042-2.549; 1.207-2.526). The results of this study suggest that the rs709149 polymorphism of the selenium-related gene PPARG is a genetic risk factor for depression in older adults.

Effects of common plastic products heat exposure on cognition: Mediated by gut microbiota.

Considering plastic exposure patterns in modern society, the effects of exposure to leachate from boiled-water treated plastic products on cognitive function was probed in mice through changes in gut microbiota diversity. In this study, Institute for Cancer Research (ICR) mice were used to establish drinking water exposure models of three popular kinds of plastic products, including non-woven tea bags, food-grade plastic bags and disposable paper cups. 16S rRNA was used to detect changes in the gut microbiota of mice. Behavioral, histopathology, biochemistry, and molecular biology experiments were used to evaluate cognitive function in mice. Our results showed that the diversity and composition of gut microbiota changed at genus level compared to control group. Nonwoven tea bags-treated mice were proved an increase in Lachnospiraceae and a decreased in Muribaculaceae in gut. Alistipes was increased under the intervention of food grade plastic bags. Muribaculaceae decreased and Clostridium increased in disposable paper cups group. The new object recognition index of mice in the non-woven tea bag and disposable paper cup groups decreased, and amyloid ß-protein (Aß) and tau phosphorylation (P-tau) protein deposition. Cell damage and neuroinflammation were observed in the three intervention groups. Totally speaking, oral exposure to leachate from boiled-water treated plastic results in cognitive decline and neuroinflammation in mammals, which is likely related to MGBA and changes in gut microbiota.

Effects of oral exposure to leachate from boiled-water treated plastic products on gut microbiome and metabolomics.

By simulating plastic exposure patterns in modern society, the impact of daily exposure to plastic products on mammals was explored. In this study, Institute for Cancer Research (ICR) mice were used to establish drinking water exposure models of three popular kinds of plastic products, including non-woven tea bags, food-grade plastic bags and disposable paper cups. Feces and urine of mice were collected for gut microbiome and metabolomics analysis. Our results showed that the diversity and composition of gut microbiota changed at genus level compared to control group. Lactobacillus, Parabacteroides, Escherichia-shigella and Staphylococcus decreased while Lachnospiraceae increased treated with non-woven tea bags. Escherichia-shigella and Alistipes increased while Parabacteroides decreased treated with food grade plastic bags. Muribaculaceae decreased in the gut microbiota of mice treated with disposable paper cups. Metabolomics has seen changes in the number of metabolites and enrichment of metabolic pathways related to inflammatory responses and immune function. Inflammatory responses were found in histological and biochemical examination. In summary, this study demonstrated that long-term oral exposure to leachate form boiled-water treated plastic products might have effects on gut microbiome and metabolome, which further provided new insights about potential adverse effects for human beings.

Expression Profile Analysis of Selenium-Related Genes in Peripheral Blood Mononuclear Cells of Patients with Keshan Disease.

Keshan disease (KD) is an endemic cardiomyopathy, which mainly occurs in China. Selenium deficiency is believed to play an important role in the pathogenesis of KD, but the molecular mechanism of selenium-induced damage remains unclear. To identify the key genes involved in selenium-induced damage, we compared the expression profiles of selenium-related genes between patients with KD and normal controls. Total RNA was isolated, amplified, labeled, and hybridized to Agilent human 4 × 44 K whole genome microarrays. Selenium-related genes were screened using the Comparative Toxicogenomics Database. The microarray data were subjected to single-gene and gene ontology (GO) expression analysis using R Studio and Gene Set Enrichment Analysis (GSEA) software. Quantitative real-time PCR was conducted to validate the microarray results. We identified 16 upregulated and 11 downregulated selenium-related genes in patients. These genes are involved in apoptosis, metabolism, transcription regulation, ion transport, and growth and development. Of the significantly enriched GO categories in KD patients, we identified four apoptosis-related, two metabolism-related, four growth and development-related, and four ion transport-related GOs. Based on our results, we suggest that selenium might contribute to the development of KD through dysfunction of selenium-related genes involved in apoptosis, metabolism, ion transport, and growth and development in the myocardium.

Comparison of Self-Rated Health among Characteristic Groups of Vegetable Greenhouse Farmers Based on Exposure to Pesticide Residuals: A Latent Profile Analysis.

OBJECTIVE: The current study was aimed at using a latent profile analysis (LPA) model to classify greenhouse farmers into a potential cluster according to their exposure to pesticide residuals. Further, the association between self-rated health (SRH) and the cluster exposed to pesticide residual was explored. METHODS: Four hundred sixty-four farmers from vegetable greenhouses were selected, their SRH information was gathered through questionnaires from the "Self-Rated Health Measurement Scale (SRHMS)" Version 1.0, and the corresponding pesticide residuals were detected in a laboratory. The linear mixed regression model was employed for association assessment. RESULTS: Two latent clusters were extracted as samples, and the results showed that a high amount of pesticide residual accounted for poor physical health, but did not show statistical significance. In addition, an inverse significant association was observed between psychosocial symptoms and negative emotion and pesticide residual level. Furthermore, a diversity of significant relationship was observed in social health and its corresponding dimensions with latent cluster. CONCLUSIONS: LPA offers a holistic and parsimonious method to identify high-risk health clusters of greenhouse workers in various health aspects and allows for a personality-targeted intervention by a local health department.

Cytotoxic Activities of Total Saponins from Plena Clematis on Human Tumor Cell Lines In Vitro.

OBJECTIVE: To investigate the anti-proliferative effects of saponins prepared from Plena Clematis (PC) cultured in Fujian Province, China on 4 human tumor cell lines and its possible anti-tumor mechanism. METHODS: The growth inhibition assays of saponins on human esophageal squamous carcinoma cell line (EC9706), human hepatoma cell line (HepG-2), human oral cancer cell line (KB) and human gastric cancer cell line (BGC-823) were evaluated in vitro by thiazolyl blue (MTT) method. The inhibitory effects on EC9706 treated with different concentrations of saponins (15.62, 31.25, 62.50, 125, 250 and 500 µg/mL) were performed in vitro by MTT method. The morphology and nuclear staining with acridine orange/ethidium bromide of EC9706 cells treated with saponins were illustrated under an inverted phase fluorescence microscope. The apoptotic effects of saponins were further evaluated by annexin-V/propidium iodide dual staining experiment to examine the occurrence of phosphatidylserine externalization onto the cell surface by a flflow cytometer. RESULTS: MTT assay showed that the saponins could inhibit the proliferation of 4 tumor cell lines. Among them, the maximum inhibition rate of 73.1% was detected in EC9706 cells at the saponins concentration of 250 µg/mL for 24 h. Further investigation indicated that the saponins induced EC9706 cells apoposis. The EC9706 cells presented apoptotic characteristics when treated with saponins, including that the morphologies of EC9706 cells were appeared round-shaped with higher refraction, and the cell nuclear stained orange with EB after 250 µg/mL saponins exposure. The flow cytometry analysis results showed that the induction of cell cycle arrest in apoptotic system may participate in the anti-proliferative activity of saponins on EC9706 cells. CONCLUSION: The saponins from PC exhibited significant cytotoxicity against human EC9706, KB, BGC-823, and HepG-2 cells and might be beneficial to development of ethnic pharmaceutical plant for potential anti-tumor drugs.

Long-Term Selenium-Deficient Diet Induces Liver Damage by Altering Hepatocyte Ultrastructure and MMP1/3 and TIMP1/3 Expression in Growing Rats.

The effects of selenium (Se)-deficient diet on the liver were evaluated by using growing rats which were fed with normal and Se-deficient diets, respectively, for 109 days. The results showed that rats fed with Se-deficient diet led to a decrease in Se concentration in the liver, particularly among male rats from the low-Se group. This causes alterations to the ultrastructure of hepatocytes with condensed chromatin and swelling mitochondria observed after low Se intake. Meanwhile, pathological changes and increased fibrosis in hepatic periportal were detected by hematoxylin and eosin and Masson's trichrome staining in low-Se group. Furthermore, through immunohistochemistry (IHC) staining, higher expressions of metalloproteinases (MMP1/3) and their tissue inhibitors of metalloproteinases (TIMP1/3) were observed in the hepatic periportal of rats from the low-Se group. However, higher expressions of MMP1/3 and lower expressions of TIMP1/3 were detected in hepatic central vein and hepatic sinusoid. In addition, upregulated expressions of MMP1/3 and downregulated expressions of TIMP1/3 at the messenger RNA (mRNA) and protein levels also appeared to be relevant to low Se intake. In conclusion, Se-deficient diet could cause low Se concentration in the liver, alterations of hepatocyte ultrastructure, differential expressions of MMP1/3 and TIMP1/3 as well as fibrosis in the liver hepatic periportal.

Selenium deficiency induced damages and altered expressions of metalloproteinases and their inhibitors (MMP1/3, TIMP1/3) in the kidneys of growing rats.

Selenium is an essential trace element for the maintenance of structures and functions of kidney. To evaluate the effects of low selenium on the kidneys of growing rats, newborn rats were fed with selenium deficient and normal diets respectively for 109 days. As a result, rats fed with low selenium diets resulted in a decline in the body weight and the concentration of selenium in the kidney, especially the male rats from the low selenium groups. Moreover, the ultrastructure of glomerulus and tubules were damaged in low selenium group: the glomeruli were observed with hyperplasia of mesangial cells, fusion of podocyte foot processes and thickening of basement membrane; and the tubules were observed with vacuolar degenerated epithelial cells, increased edema fluid or protein solution between cells, microvilli edema, increased cell gaps and decreased cell links. Furthermore, the pathological changes in selenium deficient group included the increase of fibers around renal hilum aorta and in the renal collecting duct, and shed of cells in the proximal convoluted tubules. In addition, up-regulated expressions of matrix metalloproteinases (MMP1/3) and down-regulated expressions of their inhibitors (TIMP1/3) at the mRNA and protein levels were also appeared to be relevant to low selenium. The results suggested that low selenium in diet may cause low selenium concentration in the kidney of growing rat and lead to damages of the ultrastructure and extracellular matrix (ECM) of kidney.

Effect of Selenium Deficiency on Phosphorylation of the AMPK Pathway in Rats.

Selenium is an important trace element for human health. Previous studies have raised concern that dietary selenium intake may change energy metabolism. AMP-activated protein kinase (AMPK) is a sensor of energy status that controls cellular energy homeostasis. We aimed to determine the effect of selenium on the phosphorylation of AMPK pathway between Se-deficient and normal Sprague-Dawley rats. Twenty-four weaning rats were fed either a Se-deficient diet (0.02 mg Se/kg) or a standard diet (0.18 mg Se/kg). After 109 days, total serum levels of non-esterified fatty acid and total amino acids were significantly higher and the serum insulin concentration was significantly lower in Se-deficient rats than in healthy controls. Selenium concentration and the activity of glutathione peroxidase (GPx) in myocardial tissue were significantly lower in Se-deficient rats. Importantly, mRNA levels of acetyl-CoA carboxylase beta (ACACB), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), and protein levels of p-AMPKα were increased in the Se-deficient group compared to normal controls (p < 0.05). In conclusion, our results suggest that selenium deficiency induces changes in metabolic and molecular parameters involved in energy metabolism in the AMPK pathway.