Dosage-effect of selenium supplementation on blood glucose and oxidative stress in type 2 diabetes mellitus and normal mice.

BACKGROUND: The effectiveness of selenium (Se) supplementation on glycemic control is disparate. OBJECTIVE: This study aims to evaluate the effects of different dosages of Se diets on the blood glucose in type 2 diabetes mellitus (T2DM, db/db) and normal (db/m) mice. METHODS: The db/db and db/m mice were fed with different dosages of Se supplemented diets (0, 0.1, 0.3, 0.9, 2.7 mg/kg) for 12 weeks, respectively. Se concentrations of tissues, physical and biochemical characteristics, oxidative stress indexes and gene expression related to glucose, lipid metabolism and Se transporters of liver were detected. RESULTS: The Se concentrations in tissues were related to the dosages of Se supplementation in db/db (blood: slope=11.69, r = 0.924; skeletal muscle: slope=0.36, r = 0.505; liver: slope=22.12, r = 0.828; kidney: slope=11.81, r = 0.736) and db/m mice (blood: slope=19.89, r = 0.876; skeletal muscle: slope=2.80, r = 0.883; liver: slope=44.75, r = 0.717; kidney: slope=60.15, r = 0.960). Compared with Se2.7 group, the fasting blood glucose (FBG) levels of Se0.1 and Se0.3 group were decreased at week3 in db/db mice. Compared with control (Se0) group, the FBG levels of Se2.7 group were increased from week6 to week12 in db/m mice. The oral glucose tolerance test (OGTT) showed that the area under the curve (AUC) of Se0.3 group was lower than that of Se0.9 and Se2.7 group in db/m mice. Furthermore, compared with control group, the malondialdehyde (MDA) level in skeletal muscle of Se0.1 group was decreased, while that of Se2.7 group was increased in db/db mice; the glutathione peroxidase (GPx) activity in skeletal muscle of Se0.3, Se0.9 and Se2.7 group was increased both in db/db and db/m mice. For db/db mice, glucose-6-phosphatase catalytic (G6pc) expression of other groups were lower and fatty acid synthase (Fasn) expression of Se0.9 group were lower compared with Se0.3 group. For db/m mice, compared with Se0.3 group, (peroxisome proliferative activated receptor gamma coactivator 1 alpha) Pgc-1α expression of control and Se0.9 group were higher; (phosphoenolpyruvate carboxykinase 1) Pck1 expression of Se0.1, Se0.9, and Se2.7 group were higher. CONCLUSION: Low dosages (0.1 and 0.3 mg/kg) of Se supplementation exerted beneficial effects on FBG levels and glucose tolerance through regulating hepatic glycolysis and gluconeogenesis and inhibit the oxidative stress while high dosages of Se (0.9 and 2.7 mg/kg) supplementation enhanced FBG levels, impaired glucose tolerance and aggravate oxidative stress.

Oat ß-glucan supplementation pre- and during pregnancy alleviates fetal intestinal immunity development damaged by gestational diabetes in rats.

Oat ß-glucan (OG) has been shown to improve intestinal microecology in gestational diabetes mellitus (GDM), but the effect on fetal intestine health is unknown. Herein, we aimed to investigate the effects of OG supplementation during gestation in GDM dams on fetal intestinal immune development. OG was supplemented one week before mating until the end of the experiment. GDM rats were made with a high-fat diet (HFD) with a minimal streptozotocin (STZ) dose. The fetal intestines were sampled at gestation day (GD) 19.5, and the intestinal morphology, chemical barrier molecules, intraepithelial immune cell makers, and levels of inflammatory cytokines were investigated. The results showed that OG supplementation alleviated the decrease of the depth of fetal intestinal villi and crypts, the number of goblet cells (GCs), protein expression of mucin-1 (Muc1) and Muc2, the mRNA levels of Gpr41, Gpr43, and T cell markers, and increased the number of paneth cells (PCs), the mRNA levels of defensin-6 (defa6), and macrophage (Mø) marker and the expression of cytokines induced by GDM. In addition, OG supplementation alleviated the function of immune cell self-proliferation, chemotaxis and assembly capabilities, protein, fat, folic acid, and zinc absorption damaged by GDM. As indicated by these findings, OG supplementation before and during pregnancy improved the fetal intestinal chemical barriers, immune cells, cytokines, and the metabolism of nutrients to protect the fetal intestinal immunity.

Dietary selenium excess affected spermatogenesis via DNA damage and telomere-related cell senescence and apoptosis in mice.

Selenium (Se) is a vital microelement for spermatogenesis and male fertility. The aim of this study was to investigate the effects of Se on the male reproductive function and possible mechanisms. Fourty male mice were randomly divided into 0, 0.1, 0.3 and 0.9 mg/kg Se supplementation groups and given with Se dietary intervention for 12 weeks. Our data showed that excessive Se intake damaged the tissue structure of testes and epididymides of the mice, resulting in decreased sperm quality and quantity. Moreover, excessive Se induced oxidative stress, causing DNA damage and activated DNA damage repair factors (Mre11/Rad50/Nbs1), and also disrupted telomere function by shortening telomere length and decreasing TERT expression. Se excess activated the senescence pathway p53/p21/p16, leading to germ cell senescence, and inhibited cell proliferation by suppressing the Sirt1/Foxo1/c-Myc pathway. All of this led to spermatogenic cell apoptosis, thereby causing a decrease of sperm quantity and quality. In conclusion, excessive Se caused reproductive toxicity via inducing telomere dysfunction due to DNA damage, leading to germ cellular senescence and apoptosis in the testes of male mice. Our research provide new proof to explain the underlying mechanism of male reproductive toxicity triggered by excessive Se intake.

Assessment of evidence on reported non-genetic risk factors of congenital heart defects: the updated umbrella review.

BACKGROUND: Congenital heart defect (CHD) is the leading cause of birth defects globally, which results in a great disease burden. It is still imperative to detect the risk factors of CHD. This umbrella review aimed to comprehensively summarize the evidence and grade the evidence of the associations between non-genetic risk factors and CHD. METHODS: Databases including Medline, Embase, Web of Science, Cochrane Library, and four Chinese databases were searched from inception to 18 Jan 2022. The reference lists of systematic reviews (SR) and meta-analyses (MA) were screened, which aimed to explore the non-genetic risk factors of CHD. Subsequently, titles and abstracts of identified records and full texts of selected SR/MA were screened by two independent reviewers based on predefined eligibility criteria. A priori developed extraction form was used to abstract relative data following the PRISMA 2020 and MOOSE guidelines. The risk of bias was assessed with the AMSTAR2 instrument. Data were synthesized using fixed-effects and random-effects meta-analyses, respectively. Finally, the evidence on the association of non-genetic risk factors and CHD was graded using Ioannidis's five-class evidence grade. RESULTS: A total of 56 SRs, encompassing 369 MAs, were identified. The risk factors included relative factors on air pollution, reproductive-related factors, parental age and BMI, parental life habits, working and dwelling environment, maternal drug exposure, and maternal disease. Based on AMSTAR2 criteria, only 16% (9/56) of SRs were classified as "Moderate". One hundred and two traceable positive association MAs involving 949 component individual studies were included in further analysis and grading of evidence. Family genetic history, number of abortions, maternal obesity, especially moderate or severe obesity, decoration materials, harmful chemicals, noise during pregnancy, folic acid supplementation, SSRIs, SNRIs, any antidepressants in the first trimester, maternal DM (including both PGDM and GDM), and gestational hypertension were convincing and highly suggestive factors for CHD. After sensitivity analyses based on cohort studies, some grades of evidence changed. CONCLUSION: The present umbrella review will provide evidence-based information for women of childbearing age before or during pregnancy to prevent CHD. In addition, sensitivity analysis based on cohort studies showed the changed evidence levels. Therefore, future SR/MA should concern the sensitivity analysis based on prospective birth cohort studies and case-control studies.

Prenatal Choline Supplementation during High-Fat Feeding Improves Long-Term Blood Glucose Control in Male Mouse Offspring.

Maternal obesity increases the risk of metabolic dysregulation in rodent offspring, especially when offspring are exposed to a high-fat (HF), obesogenic diet later in life. We previously demonstrated that maternal choline supplementation (MCS) in HF-fed mouse dams during gestation prevents fetal overgrowth and excess adiposity. In this study, we examined the long-term metabolic influence of MCS. C57BL/6J mice were fed a HF diet with or without choline supplementation prior to and during gestation. After weaning, their pups were exposed to either a HF or control diet for 6 weeks before measurements. Prenatal and post-weaning dietary treatments led to sexually dimorphic responses. In male offspring, while post-weaning HF led to impaired fasting glucose and worse glucose tolerance (p < 0.05), MCS in HF dams (HFCS) attenuated these changes. HFCS (versus maternal normal fat control) appeared to improve metabolic functioning of visceral adipose tissue during post-weaning HF feeding, preventing the elevation in leptin and increasing (p < 0.05) mRNA expression of insulin receptor substrate 1 (Irs1) that promotes peripheral insulin signaling in male offspring. In contrast, MCS had minimal effects on metabolic outcomes of female offspring. In conclusion, MCS during HF feeding in mice improves long-term blood glucose homeostasis in male offspring when they are faced with a postnatal obesogenic environment.

Milk Powder Co-Supplemented with Inulin and Resistant Dextrin Improves Glycemic Control and Insulin Resistance in Elderly Type 2 Diabetes Mellitus: A 12-Week Randomized, Double-Blind, Placebo-Controlled Trial.

SCOPE: The objective of the present study is to evaluate the effects of milk powder co-supplemented with inulin and resistant dextrin (MPCIR) on elderly patients with type 2 diabetes mellitus (T2DM). METHODS AND RESULTS: A randomized, double-blind, placebo-controlled clinical trial is carried out among elderly T2DM patients. The subjects recruited from the community are randomly assigned to either the MPCIR group or placebo group for 12 weeks intervention. Each group receives 45 g milk powder with or without inulin and resistant dextrin. Anthropometric and metabolic variables are measured. For the MPCIR group, systolic blood pressure (BP) and diastolic BP are reduced significantly by 5.45 and 4.56 mm Hg (p < 0.001, vs placebo group), respectively. Compared with the placebo group, the fasting and 2-h postprandial plasma glucose levels, glycosylated serum protein, and insulin resistance index of the MPCIR group are significantly decreased by 0.96 mmol L-1 , 1.47 mmol L-1 , 16.33 µmol L-1 , and 0.65 respectively (p < 0.001). The MPCIR group shows an increase by 7.09 µIU mL-1 and 20.43 in 2-h postprandial insulin (p = 0.016) and ß-cell function index (p < 0.001), respectively. CONCLUSION: MPCIR supplementation helps to improve glycemic control, insulin resistance, and blood pressure.

Genistein alleviates ß-amyloid-induced inflammatory damage through regulating Toll-like receptor 4/nuclear factor κB.

Genistein (GEN), a major soybean isoflavone (SIF), might possess neuroprotective properties through its anti-inflammatory activity. We hypothesized that GEN could prevent the inflammatory damage detected in C6 cells induced by ß-amyloid peptides 25-35 (Aß25-35). Accordingly, we evaluated the inflammatory damage induced by Aß25-35 and the protective effect of GEN against Aß25-35 in C6 cells. In our study, the C6 glial cells (rats glioma cell lines) were preincubated with or without GEN for 2 h following incubation with Aß25-35 for another 24 h. Then, methylthiazolyl tetrazolium (MTT) assay was used to assess the cell viability. Immunofluorescence staining was used to identify the C6 cells. Inflammatory factors tumor necrosis factor (TNF)-α and interleukin (IL)-1ß were analyzed by using enzyme-linked immunosorbent assay (ELISA). Western blot analysis and reverse transcription-polymerase chain reaction analysis were performed to assess the expression of Toll-like receptors 4 (TLR4), inhibitor of kappaB-alpha (IκB-α). The current results showed that GEN could alleviate Aß25-35-induced cell apoptosis and prevent Aß25-35-induced TNF-α and IL-1ß release from C6 cells. In addition, GEN prevented Aß25-35-induced upregulation of the gene and protein expression of TLR4, and GEN significantly upregulated the expression of IκB-α in C6 cells damaged by Aß25-35. These results suggest that GEN can alleviate the inflammatory stress caused by Aß25-35 treatment, which might be associated with the neuroprotective effect of GEN regulating the TLR4/NFκB signaling pathway.

The effects of phytosterol supplementation on serum LDL-C levels and learning ability in mice fed a high-fat, high-energy diet from gestation onward.

A high-fat, high-energy (HFE) diet may be deleterious to the cardiovascular system and mental health. We previously reported that serum cholesterol levels and escape latency were significantly increased in mice by feeding them an HFE diet from gestation onward. In this study, we examined whether an HFE diet supplemented with phytosterols fed to pregnant C57BL/6j dams and their offspring would protect the HFE-diet-induced compromise of the offspring's learning capability. We measured serum cholesterol levels, brain N-methyl-D-aspartate receptor (NMDAR1) mRNA and protein expression and liver sterol 27-hydroxylase (Cyp27a1) mRNA expression, as well as a Morris water maze performance. The results showed that, compared to mice consuming the HFE diet alone, those also consuming phytosterols (the HFE + PS diet) significantly decreased mean serum low-density lipoprotein cholesterol levels and altered brain NMDAR1 mRNA and protein expression and liver Cyp27a1 mRNA expression. The Morris water maze experiments indicated that dietary phytosterol supplementation slightly decreased the escape latency (p = 0.07). Collectively, these observations suggest that consumption of phytosterols from early in life may help alleviate the detrimental effects of HFE diets in mice.

Impact of apple and grape juice consumption on the antioxidant status in healthy subjects.

It is reported that consumption of antioxidant-rich foods significantly increased plasma total antioxidant capacity (T-AOC) in humans. Also, it is proved that the antioxidants from plant foods improve the body's antioxidant defence by acting additively and synergistically. As a result, rational combination of antioxidant-rich foods is recommended to population in the prevention of oxidative stress-related diseases. Both apple and grape are antioxidant-rich fruits. In this study, 2 weeks dietary intervention study was carried out in 25 healthy subjects to investigate the influences of apple and grape juices consumption on body antioxidant status. Our results indicated that 2 weeks of apple and grape juice consumption increased the plasma T-AOC and decreased the concentration of malondialdehyde. However, no change was found in the content of plasma carbonyl. Erythrocyte glutathione peroxidase and catalase activities were enhanced by 2 weeks of fruit juice consumption; however, no change was found in the activity of erythrocyte superoxide dismutase. The in vitro comet assay results indicated that apple and grape juice consumption did not influence lymphocyte damage upon hydrogen peroxide treatment. Urinary 8-hydroxy-2-deoxyguanosine content was not affected by 2 weeks of fruit juice intervention. These findings indicated that concomitant intake of apple and grape juice was efficient in enhancing the body's antioxidant status.

Folic acid and soybean isoflavone combined supplementation protects the post-neural tube closure defects of rodents induced by cyclophosphamide in vivo and in vitro.

To evaluate the neuroprotective effect of folic acid (FA) and soybean isoflavone (SIF) combined supplementation on the post-neural tube closure of rodents induced by cyclophosphamide (CPA) in vitro and in vivo, pregnant rats were randomly divided into control, model, solo-FA intervention, solo-SIF intervention and co-intervention of FA and SIF groups. Rats in solo-intervention groups and co-intervention group were treated with FA 0.7 mg/kg, SIF 160 mg/kg and FA 0.7 mg/kg+SIF 160 mg/kg at the duration of pregnancy, respectively. On the 13th day of gestation, control rats were given physiological saline and the other four groups were treated with CPA12.5mg/kg. On the 14th day of gestation, three rats selected randomly from every group were executed and the ultrastructure, DNA damage and the proteins expressions of Bcl-2, Bax and P53 on embryo brains were checked. The rest of the rats were executed on the 20th day, the frequency of neural tube closure defects and fetus' development indices were measured. In addition, T-SOD, MDA and NO in serum of the pregnant rats were checked. In vitro, the effect of FA and genistein on the apoptosis was determined. Compared with the model group, the malformation incidence was lower but fetus' development indices were higher in the combination treated group. The combination decreased the damage of CPA, such as damaged nuclear DNA, early apoptotic morphological changes, Bax and P53 expressions on embryo brains and in vivo. Furthermore, T-SOD activity in serum of the pregnant rats increased and the levels of MDA and NO decreased in the combined supplementation group. Our study indicates the neuroprotection of FA and SIF combined administration is superior to solo treatment. Decrease of DNA damage and neuron apoptosis involved in the mechanisms. Furthermore, the up-regulation of Bcl-2 and the down-regulation of Bax and P53 proteins also participate in the effect.

Long-term effects of high lipid and high energy diet on serum lipid, brain fatty acid composition, and memory and learning ability in mice.

OBJECTIVE: It is well known that high lipid and high energy diet is harmful to health. But the different effects of high lipid diet composed of either saturated fatty acids or unsaturated fatty acids have not been distinguished. METHOD: Eighteen pregnant C57BL/6j (22-25g) mice were randomly divided into three groups of six each and fed with chow or high lipid diet composed of either flaxseed oil (chow diet 84%, cholesterol 0.2%, flaxseed oil 15.8%) or lard fat (chow diet 84%, cholesterol 0.2%, lard fat 15.8%). After weaning, the offspring were fed the same diet as their mothers were fed during the experiment, and their spatial memory and learning ability were evaluated by Morris water maze when they were 8 weeks old. Next, the blood and tissues were sampled when they were 9 weeks old. Serum lipids were determined using kits, and brain fatty acids were measured using a gas chromatograph. RESULTS: Compared to chow diet (control), high flaxseed oil diet (HFO) increased high density lipoprotein cholesterol level (HDL-C) in the mothers but not in offspring; high lard fat diet (HLF) increased serum total cholesterol level (TC) and low density lipoprotein cholesterol level (LDL-C) both in mothers and offspring. Brain fatty acids profile was altered by HLF compared with chow diet. Polyunsaturated fatty acids and long-chain polyunsaturated fatty acids content were significantly lower in the HLF group than in the control group, but saturated fatty acids content were significantly higher in HLF group than those in control group. The changed fatty acids composition affected the spatial memory and learning ability of adult offspring. CONCLUSIONS: A long-term high lard diet increased offspring serum TC and LDL-C levels and affected the brain's fatty acid composition, and memory and learning ability. The polyunsaturated fatty acid content of the brain may be correlated with serum cholesterol levels.

[Fundamental study on the cholesterol-lowering effect of whole turtle egg powder in SD rats].

OBJECTIVE: In order to study the cholesterol-lowering effects of whole turtle egg powder. METHODS: Fifty male SD rats were randomly divided into 5 groups according to body weight and serum cholesterol levels. They were fed one of five diets, a chow diet, a high fat supplemented diet (HF) and a HF diet supplemented with 0.75, 1.50 and or 3.00 g/kg BW whole turtle egg powder. After 24 weeks, collecting of the fecal and blood, serum total cholesterol (TC), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) levels were determined by enzymic methods on an automatic analyzer. RESULTS: The serum TC levels were significantly decreased in both 1.50 g/kg BW group and 3.00 g/kg BW group compared with the HF rats (P < 0.05). Both 1.50 g/kg BW and 3.00 g/kg BW whole turtle egg powder increased fecal cholesterol, coprostanol and coprostanone excretion as well as total bile acids. CONCLUSION: The whole turtle egg powder lowered serum cholesterol by increasing the fecal steroids and turtle bile acids excretion.

[Effects of turtle egg powder mixture on serum lipids of experimental hyperlipidemia rats].

OBJECTIVE: To study the lipid-lowering effects of a mixture composed of turtle egg powder, safflower oil, garlic powder and VE. METHODS: Fifty male SD rats were randomly divided into 5 groups according to body weight and serum cholesterol levels. They were fed one of five diets, a reference diet, a high fat supplemented diet (HF) and a HF diet supplemented with 0.5 g/kg BW, 1.5 g/kg BW and 5.0 g/kg BW TEM. After 7 weeks, serum total cholesterol (TC), high density lipoprotein cholesterol (HDL-C) and triglyceride (TG) levels were determined by enzymatic methods on an automatic analyzer. RESULTS: Serum TC and TG levels were significantly decreased in the 5.0 g/kg BW group compared with the HF rats (P < 0.05), and at the same time, HDL-C level and its ratio to TC were not affected in groups fed high fat diet.