Effects of selenium-cadmium co-enriched Cardamine hupingshanensis on bone damage in mice.

Selenium (Se) and cadmium (Cd) usually co-existed in soils, especially in areas with Se-rich soils in China. The potential health consequences for the local populations consuming foods rich in Se and Cd are unknown. Cardamine hupingshanensis (HUP) is Se and Cd hyperaccumulator plant that could be an ideal natural product to assess the protective effects of endogenous Se against endogenous Cd-caused bone damage. Male C57BL/6 mice were fed 5.22 mg/kg cadmium chloride (CdCl2) (Cd 3.2 mg/kg body weight (BW)), or HUP solutions containing Cd 3.2 mg/kg BW and Se 0.15, 0.29 or 0.50 mg/kg BW (corresponding to the HUP0, HUP1 and HUP2 groups) interventions. Se-enriched HUP1 and HUP2 significantly decreased Cd-induced femur microstructure damage and regulated serum bone osteoclastic marker levels and osteogenesis-related genes. In addition, endogenous Se significantly decreased kidney fibroblast growth factor 23 (FGF23) protein expression and serum parathyroid hormone (PTH) levels, and raised serum calcitriol (1,25(OH)2D3). Furthermore, Se also regulated gut microbiota involved in skeletal metabolism disorder. In conclusion, endogenous Se, especially with higher doses (the HUP2 group), positively affects bone formation and resorption by mitigating the damaging effects of endogenous Cd via the modulation of renal FGF23 expression, circulating 1,25(OH)2D3 and PTH and gut microbiota composition.

Protective effects and mechanism of chemical- and plant-based selenocystine against cadmium-induced liver damage.

Although selenium (Se) and cadmium (Cd) often coexist naturally in the soil of China, the health risks to local residents consuming Se-Cd co-enriched foods are unknown. In the present study, we investigated the effects of chemical-based selenocystine (SeCys2) on cadmium chloride-induced human hepatocarcinoma (HepG2) cell injury and plant (Cardamine hupingshanensis)-derived SeCys2 against Cd-induced liver injury in mice. We found that chemical- and plant-based SeCys2 showed protective effects against Cd-induced HepG2 cell injury and liver damage in mice, respectively. Compared with Cd intervention group, co-treatment with chemical- or plant-based SeCys2 both alleviated liver toxicity and ferroptosis by decreasing ferrous iron, acyl-CoA synthetase long-chain (ACSL) family member 4, lysophosphatidylcholine acyltransferase 3, reactive oxygen species and lipid peroxide levels, and increasing ACSL3, peroxisome proliferator-activated receptor α, solute carrier family 7 member 11 (SLC7A11) and glutathione and glutathione peroxidase 4 (GPX4) levels. In conclusion, chemical- and plant-based SeCys2 alleviated Cd-induced hepatotoxicity and ferroptosis by regulating SLC7A11/GPX4 signaling and lipid peroxidation. Our findings indicate that potential Cd toxicity from consuming foods grown in Se- and Cd-rich soils should be re-evaluated. This study offers a new perspective for the development of SeCys2-enriched agricultural products.

Coffee Consumption and Incidence of Cardiovascular and Microvascular Diseases in Never-Smoking Adults with Type 2 Diabetes Mellitus.

The relationship between coffee consumption and diabetes-related vascular complications remains unclear. To eliminate confounding by smoking, this study assessed the relationships of coffee consumption with major cardiovascular disease (CVD) and microvascular disease (MVD) in never-smokers with type 2 diabetes mellitus (T2DM). Included were 9964 never-smokers with T2DM from the UK Biobank without known CVD or cancer at baseline (7781 were free of MVD). Participants were categorized into four groups according to daily coffee consumption (0, 0.5-1, 2-4, ≥5 cups/day). CVD included coronary heart disease (CHD), myocardial infarction (MI), stroke, and heart failure (HF). MVD included retinopathy, peripheral neuropathy, and chronic kidney disease (CKD). Cox regression models were used to estimate hazard ratios (HRs) and 95% confidential intervals (CIs) of total CVD and MVD and the component outcomes associated with coffee consumption. During a median of 12.7 years of follow-up, 1860 cases of CVD and 1403 cases of MVD were identified. Coffee intake was nonlinearly and inversely associated with CVD (P-nonlinearity = 0.023) and the component outcomes. Compared with no coffee intake, HRs (95% CIs) associated with a coffee intake of 2 to 4 cups/day were 0.82 (0.73, 0.93) for CVD, 0.84 (0.73, 0.97) for CHD, 0.73 (0.57, 0.92) for MI, 0.76 (0.57, 1.02) for stroke, and 0.68 (0.55, 0.85) for HF. Higher coffee intake (≥5 cups/day) was not significantly associated with CVD outcomes. Coffee intake was linearly and inversely associated with risk of CKD (HR for ≥5 vs. 0 cups/day = 0.64; 95% CI: 0.45, 0.91; P-trend = 0.0029) but was not associated with retinopathy or peripheral neuropathy. Among never-smoking individuals with T2DM, moderate coffee consumption (2-4 cups/day) was associated with a lower risk of various CVD outcomes and CKD, with no adverse associations for higher consumption.

The skeletal safety of milk-derived proteins: A meta-analysis of randomized controlled trials.

PURPOSE: There has been a persistent claim that dairy products contain calcium-leaching proteins, although the soundness of such a claim has been challenged. A meta-analysis of randomized controlled trials (RCTs) on the effects of milk-derived protein supplementation on bone health indices in adults was performed to reconcile the controversy surrounding the potential skeletal safety concerns of proteins of dairy origin. METHODS: The PubMed and Web of Science databases were searched for relevant RCTs. A random-effects model was used to generate pooled effect sizes and 95% confidence intervals. RESULTS: Milk-derived protein supplementation did not significantly affect whole-body BMD (n = 7 RCTs) and BMD at the lumbar spine (n = 10), hip (n = 8), femoral neck (n = 9), trochanter (n = 5), intertrochanter (n = 2), and ultradistal radius (n = 2). The concentrations of bone formation markers (bone-specific alkaline phosphatase [n = 11], osteocalcin [n = 6], procollagen type 1 amino-terminal propeptide [n = 5]), bone resorption markers (N-terminal telopeptide of type 1 collagen [n = 7], C-terminal telopeptide of type 1 collagen [n = 7], deoxypyridinoline [n = 4]), and parathyroid hormone (n = 7) were not significantly affected. However, increased insulin-like growth factor-1 (IGF-1) concentrations (n = 13) were observed. Reduced IGF-1 concentrations were observed when soy protein was used as a comparator, and increased IGF-1 concentrations were observed when carbohydrate was used. CONCLUSION: Our findings do not support the claim that proteins of dairy origin are detrimental to bone health.

The Effects of Dairy Product Supplementation on Bone Health Indices in Children Aged 3 to 18 Years: A Meta-Analysis of Randomized Controlled Trials.

Childhood and adolescence are critical periods for optimizing skeletal growth. Dairy products are valuable sources of bone-beneficial nutrients, particularly calcium and protein. A random-effects meta-analysis of published randomized controlled trials was performed to quantitatively assess the effects of dairy supplementation on bone health indices in children and adolescents. The PubMed and Web of Science databases were searched. Dairy supplementation increased whole-body bone mineral content (BMC) (+25.37 g) and areal bone mineral density (aBMD) (+0.016 g/cm2), total hip BMC (+0.49 g) and aBMD (+0.013 g/cm2), femoral neck BMC (+0.06 g) and aBMD (+0.030 g/cm2), lumbar spine BMC (+0.85 g) and aBMD (+0.019 g/cm2), and height (0.21 cm). When expressed as a percentage difference, whole-body BMC was increased by 3.0%, total hip BMC by 3.3%, femoral neck BMC by 4.0%, lumbar spine BMC by 4.1%, whole-body aBMD by 1.8%, total hip aBMD by 1.2%, femoral neck aBMD by 1.5%, and lumbar spine aBMD by 2.6%. Dairy supplementation increased serum insulin-like growth factor I concentrations (19.89 nmol/L) and reduced concentrations of urinary deoxypyridinoline (-1.78 nmol/mmol creatinine) and serum parathyroid hormone (-10.46 pg/mL) but did not significantly affect the serum concentrations of osteocalcin, bone alkaline phosphatase, and C-terminal telopeptide of type 1 collagen. Serum 25-hydroxyvitamin D concentrations (+4.98 ng/mL) increased with vitamin D-fortified dairy supplementation. The positive effects on bone mineral mass parameters and height were generally consistent across subgroups defined by sex, geographical region, baseline calcium intake, calcium from the supplementation, trial duration, and Tanner stages. In summary, dairy supplementation during growth leads to a small but significant increase in bone mineral mass parameters, and these findings are generally supported by the changes in several biochemical parameters related to bone health.

Effect of 3,3'-diselenodipropionic Acid on Dextran Sodium Sulfate-Induced Ulcerative Colitis in Mice.

3,3'-Diselenodipropionic acid (DSePA), a synthetic organoselenium compound, has received considerable attention because of its antioxidant properties and safety. Its protective effect against dextran sodium sulfate (DSS)-induced mouse ulcerative colitis (UC) and the role of T helper 17 (Th17) cell proliferation were investigated. Fifty C57BL/6 male mice were randomly assigned to one of five groups: control (Con), DSePA, DSS, low-dose DSePA (LSe), and high-dose DSePA (HSe). Mice in the DSS, LSe, and HSe groups drank 2% DSS to induce UC, and received normal saline, 1 and 2 mg/mL DSePA solution by intraperitoneal injection, respectively. The DSePA group only received 2 mg/mL DSePA solution. After 5 weeks, DSS challenge induced UC in the mice, which manifested as decreased body weight, shortened colon length, the loss of goblet cells, activated proliferating cells, and multiple signs of intestinal lesions by histological observation, all of which were reversed to varying degrees by DSePA administration. DSS upregulated the colonic protein expression of the macrophage marker F4/80 and proinflammatory cytokines (IL-1ß, IL-6, and TNFα), whereas DSePA administration downregulated the expression of these factors. DSS upregulated the mRNA expression of retinoic acid receptor-related orphan receptor γt (RORγt, mainly expressed in Th17 cells), IL-17A, and IL-17F and the levels of IL-17A and IL-17F in the colon, whereas DSePA administration decreased them. No difference was observed between the Con group and the DSePA group without DSS induction. Thus, DSePA administration ameliorated DSS-induced UC by regulating Th17-cell proliferation and the secretion of proinflammatory cytokines.

Protective effects of epigallocatechin-3-o-gallate combined with organic selenium against transforming growth factor-beta 1-induced fibrosis in LX-2 cells.

In this study, we investigated the protective effects and possible mechanism of epigallocatechin-3-o-gallate (EGCG) combined with organic selenium in transforming growth factor (TGF)-ß1-activated LX-2 cells. After 12 h of starvation, LX-2 cells were treated with 10 ng/ml of recombinant TGF-ß1 and different concentrations of EGCG, L-selenomethionine (L-SeMet), or L-selenomethylcysteine (L-SeMC) for 24 h. We found that 100 and 200 µM EGCG combined with 1 mM L-SeMet or L-SeMC showed a synergistic effect in decreasing the survival rate of activated LX-2 cells. In addition, the combination of 100 mM EGCG and 1 mM L-SeMet or L-SeMC promoted the apoptosis of activated LX-2 cells. Compared with the EGCG treatment group, the combination intervention group had significantly suppressed levels of hepatic stellate cell activation markers including alpha-smooth muscle actin, collagen type I alpha 1, collagen type III alpha 1, 5-hydroxytryptophan (5-HT), and 5-HT receptors 2A and 2B. Moreover, interleukin-10 levels were decreased, while TGF-ß1 levels were increased after TGF-ß1 activation in LX-2 culture medium, whereas the combin1ation intervention reversed this phenomenon. The combination treatment had a more pronounced effect than any single treatment at the same dose. These results demonstrated that the combination of EGCG and organic selenium synergistically improves the TGF-ß1-induced fibrosis of LX-2 cells to some extent by promoting apoptosis and inhibiting cell activation. PRACTICAL APPLICATIONS: Here, we found that the effects of epigallocatechin-3-o-gallate (EGCG) + L-selenomethionine or L-selenomethylcysteine were more pronounced than those of EGCG alone. Future studies should investigate the protective effects of green tea and selenium-enriched green tea against hepatic fibrosis and explore the differences in their molecular mechanisms. The results of this study will be helpful for the development and utilization of selenium-enriched tea for food processing and health supplement production.

Lactoferrin improves hepatic insulin resistance and pancreatic dysfunction in high-fat diet and streptozotocin-induced diabetic mice.

Lactoferrin (Lf) is an iron-binding glycoprotein with potentially beneficial biological functions. However, the interaction between Lf and type 2 diabetes mellitus (T2DM) remains unclear. We hypothesized that Lf would improve hepatic insulin resistance and pancreatic dysfunction in diabetic mice. Male C57BL/6J mice were fed a high-fat diet for 15 weeks and injected with streptozotocin (STZ) for 5 consecutive days to establish a T2DM model. One week after STZ injection, mice with ≥11.1 mmol/L fasting blood glucose concentration were considered T2DM mice. These mice received 0.5% or 2% Lf solution for another 12 weeks. Biochemical parameters were measured, and histopathological examination of the pancreas and liver was performed. Hepatic protein expression related to the insulin signalling pathway was also assessed. Diabetic mice showed insulin resistance and abnormal glucolipid metabolism. Lf decreased serum concentrations of glycated serum protein, fasting insulin, cholesterol, and triglyceride and increased liver insulin sensitivity. Hematoxylin-eosin staining showed that Lf reversed the abnormal pancreatic islets of diabetic mice. Lf improved pancreatic dysfunction by reducing oxidative stress and inflammation responses. Furthermore, Lf upregulated the protein expression of insulin receptor, insulin receptor substrate-1, glucose transporter 4, phosphor phosphatidylinositol 3-kinase/phosphatidylinositol 3-kinase (PI3K), and phosphor protein kinase B/protein kinase B (AKT) in the liver. This study indicated that Lf supplementation improved hepatic insulin resistance and pancreatic dysfunction, possibly by regulating the PI3K/AKT signaling pathway in T2DM mice.

The Effects of Milk Supplementation on Bone Health Indices in Adults: A Meta-Analysis of Randomized Controlled Trials.

Milk contains a number of bone-beneficial nutrients. However, milk, due to the D-galactose content, might have unfavorable effects on bone health. A meta-analysis of randomized controlled trials (RCTs) was performed to clarify the effects of milk supplementation on bone mineral density (BMD), bone turnover markers [N-terminal telopeptide of type I collagen (NTx), C-terminal telopeptide of type 1 collagen (CTx), osteocalcin, bone alkaline phosphatase (BALP), and procollagen type 1 N-propeptide (P1NP)], and hormonal indices related to bone metabolism [parathyroid hormone (PTH), 25-hydroxyvitamin D [25(OH)D], and insulin-like growth factor 1 (IGF-1)] in adults. The PubMed and Web of Science databases were searched. A random-effects model was used to estimate the pooled effect sizes. A total of 20 RCTs were included. The trial duration ranged from 1 mo to 36 mo. Milk supplementation resulted in a small but significant increase in BMD at the hip (+0.004 g/cm2; n = 9 RCTs) and lumbar spine (+0.025 g/cm2; n = 7), but did not significantly affect whole-body BMD (n = 3) and femoral neck BMD (n = 7). Milk supplementation reduced the concentrations of P1NP (-5.20 ng/mL; n = 9), CTx (-0.16 ng/mL; n = 9), and NTx (-8.66 nmol bone collagen equivalents/mmol creatinine; n = 3). The concentrations of osteocalcin (n = 9) and BALP (n = 3) were not affected by milk supplementation. Reduced parathyroid hormone PTH (-1.01 pg/mL; n = 13) concentrations and increased IGF-1 (+1.79 nmol/l; n = 4) concentrations were observed with milk supplementation. 25(OH)D (+3.73 ng/mL; n = 11) concentrations were increased with vitamin-D fortified milk supplementation. The addition of milk to the diet may potentially increase the likelihood of preventing bone loss by restoring bone homeostasis through the modulation of the calcium-vitamin D-PTH axis, bone remodeling rate, and growth hormone/IGF-1 axis.

Protective Effect of Selenium-Enriched Green Tea on Carbon Tetrachloride-Induced Liver Fibrosis.

The major pathogenic feature of liver fibrosis is that oxidative stress motivation of hepatic stellate cells (HSCs) alters the balance between the synthesis and degradation of extracellular matrix (ECM) and HSCs into proliferative myofibroblasts. Green tea and selenium (Se) can protect the liver from damage; however, the precise mechanism of green tea and the action of Se in green tea on hepatic fibrosis remain unclear. Several studies have demonstrated the profibrogenic role of 5-hydroxytryptamine (5-HT) and 5-hydroxytryptamine receptor (5-HTR) 2A/2B in the liver. The current study aimed to investigate the protective effects and possible mechanisms of selenium-enriched green tea on carbon tetrachloride (CCl4)-induced liver fibrosis in male C57BL/6 J mice. After a 4-week intervention with tea solution, histological analysis of the liver showed that green tea interventions alleviated hepatic fibrosis, which was supported by the changes in collagen type I, collagen type III, and α-smooth muscle actin in the liver. Tea interventions significantly inhibited the CCl4-provoked increase of duodenal 5-HT and tryptophan hydroxylase and hepatic 5-HT and 5-HTR2A/2B levels. All of them were lower in the selenium-enriched green tea group than in regular green tea group. Se-enriched green tea had a more pronounced improvement in liver ECM deposition and scar formation and peripheral 5-HT signals than regular green tea. Thus, green tea, especially those enriched with selenium, can improve liver fibrosis through intestinal 5-HT-hepatic 5-HTR signaling.

Association of Oily and Nonoily Fish Consumption and Fish Oil Supplements With Incident Type 2 Diabetes: A Large Population-Based Prospective Study.

OBJECTIVE: To evaluate associations of oily and nonoily fish consumption and fish oil supplements with incident type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: We included 392,287 middle-aged and older participants (55.0% women) in the UK Biobank who were free of diabetes, major cardiovascular disease, and cancer and had information on habitual intake of major food groups and use of fish oil supplements at baseline (2006-2010). Of these, 163,706 participated in one to five rounds of 24-h dietary recalls during 2009-2012. RESULTS: During a median 10.1 years of follow-up, 7,262 incident cases of T2D were identified. Compared with participants who reported never consumption of oily fish, the multivariable-adjusted hazard ratios of T2D were 0.84 (95% CI 0.78-0.91), 0.78 (0.72-0.85), and 0.78 (0.71-0.86) for those who reported <1 serving/week, weekly, and ≥2 servings/week of oily fish consumption, respectively (P-trend < 0.001). Consumption of nonoily fish was not associated with risk of T2D (P-trend = 0.45). Participants who reported regular fish oil use at baseline had a 9% (95% CI 4-14%) lower risk of T2D compared with nonusers. Baseline regular users of fish oil who also reported fish oil use during at least one of the 24-h dietary recalls had an 18% (8-27%) lower risk of T2D compared with constant nonusers. CONCLUSIONS: Our findings suggest that consumption of oily fish but not nonoily fish was associated with a lower risk of T2D. Use of fish oil supplements, especially constant use over time, was also associated with a lower risk of T2D.

Green Tea Consumption May Be Associated with Cardiovascular Disease Risk and Nonalcoholic Fatty Liver Disease in Type 2 Diabetics: A Cross-Sectional Study in Southeast China.

Dietary factors play a crucial role in the management of type 2 diabetes mellitus (T2DM) by reducing cardiovascular disease (CVD) risk. Therefore, we aimed to examine the associations between habitual green tea consumption and risk factors of CVD among T2DM patients. A total of 1013 patients with T2DM were included in a community-based cross-sectional study. Data on dietary habits, including tea consumption, were collected using a food frequency questionnaire. A multivariable logistic regression model was used to analyze the associations. In men, as compared with nongreen tea drinkers, odds ratios (ORs) (95% confidence interval [CI]) of nonalcoholic fatty liver disease (NAFLD) were 2.06 (95% CI, 1.20-3.55) for those with green tea consumption of once per day and 2.45 (95% CI, 1.31-4.58) for more than or equal to twice per day (P-trend = .004); ORs (95% CI) of general obesity were 2.19 (95% CI, 1.02-4.68) and 2.70 (95% CI, 1.18-6.21), respectively (P-trend = .021); whereas no such association was found in women. Sensitivity analysis according to self-awareness of their T2DM status revealed that the positive association between green tea consumption and general obesity was not reliable. Higher intake of green tea was still positively associated with NAFLD, but it only persisted in participants aged ≥52 years or the lower dietary quality subgroup in further analyses. Our findings suggest that tea consumption was associated with an increased risk of NAFLD among male T2DM patients aged 52 years or older, and those with lower dietary quality, which needs to be confirmed in future prospective studies.

Lactoferrin Alleviates the Progression of Atherosclerosis in ApoE-/- Mice Fed with High-Fat/Cholesterol Diet Through Cholesterol Homeostasis.

Lactoferrin (LF) is a multifunctional glycoprotein and has beneficial effects on the regulation of lipid metabolism. However, whether LF supplementation alleviates the development of atherosclerosis (AS) remains unclear. In the present study, all of 48 male Apolipoprotein E-/- mice were fed with high-fat diet with 1.25% added cholesterol and divided to four treatment groups with either distilled water (HFCD), LF solutions at 2 mg/mL (low LF), 10 mg/mL (middle LF or MLF), or 20 mg/mL (high LF or HLF) for 12 weeks. Oral glucose tolerance tests (OGTT) were performed at weeks 0, 4, 8, and 12. At the end of the experiment, lipids in serum, liver, and feces were determined. The livers, whole aortas, and aortic sinuses were pathologically examined. The protein expression of factors related to cholesterol synthesis, absorption, and excretion were detected through western blot. No significant difference in body weight, food intake, and OGTT was observed among the four groups. Compared with the HFCD group, the MLF and HLF groups had significantly decreased serum and hepatic cholesterol levels and significantly increased fecal cholesterol contents. LF alleviated the hepatic steatosis and lipid droplet, especially in the MLF group. LF also significantly decreased the average lesion areas in the whole aorta, especially in the MLF group. On the other hand, LF downregulated hepatic protein expression of HMG-CoA reductase (the rate-limiting enzyme in cholesterol synthesis) and upregulated cholesterol 7-alpha hydroxylase (the rate-limiting enzyme in bile acid synthesis from cholesterol). LF also downregulated the intestinal expression of Niemann-Pick C1-like 1 protein, which is known to bind to a critical mediator of cholesterol absorption. In conclusion, LF supplementation alleviates the AS in mice on HFCD likely by reducing the synthesis and absorption of cholesterol and increasing cholesterol excretion.

Effects of fatty and lean fish intake on stroke risk: a meta-analysis of prospective cohort studies.

BACKGROUND: Fish intake has been postulated to reduce the risk of stroke. However, whether the beneficial effect of fish are mainly linked to fat content, as a source of omega-3 polyunsaturated fatty acids, remains unclear. We conducted a meta-analysis to compare the effect of fatty and lean fish intake on stroke risk. METHODS: We performed a literature search on four database (PubMed, Embase, Scopus, and Cochrane Library) through February 1, 2018 to identify prospective studies of fatty and lean fish in relation to stroke risk. A random-effects model was used to calculate the summary estimates. RESULTS: We identified five prospective studies, including 7 comparisons for fatty fish intake and 5 comparisons for lean fish intake. Compared with the highest category of intake with lowest category, the summary relative risk was 0.88 [95% confidence interval (CI), 0.74-1.04] for fatty fish intake and 0.81 (95% CI, 0.67-0.99) for lean fish intake. No heterogeneity across studies and publication bias were observed. CONCLUSION: Our findings demonstrated that fatty and lean fish intake has beneficial effects on stroke risk, especially lean fish intake. Additional prospective studies are necessary to confirm these observations.

Effects of Quercetin Intervention on Cognition Function in APP/PS1 Mice was Affected by Vitamin D Status.

SCOPE: To explore how quercetin will affect memory impairments in APP/PS1 mice under different vitamin D status. METHODS AND RESULTS: APP/PS1 mice are divided into four groups, i.e., control (CON), low (LVD), medium, and high vitamin D supplemented with quercetin. During Morris Water Maze test, mice of the LVD group function best for improving cognitive function demonstrated by reduced latency to platform, and increased number of crossing and swimming distance in the target quadrant. Compared to the CON group, in both hippocampus and cortex, the LVD group has significant reduction in Aß plaques, p-Tau at Ser396&Ser404, and neuroinflammation. In the hippocampus, BDNF is elevated, miR-26a and miR-125b is decreased, while miR-132 is increased in the LVD group. The LVD group demonstrates increased gut microbial diversity and elevated relative abundance of Glutamicibacter, Facklamia and Aerocorrus. In the hippocampus, p-Tau at ser396&404, GFAP, Ibα1, miR-26a, and miR-132 are negatively correlated with Aerococcus; and p-Tau at ser404 and Ibα1 are negatively correlated with Facklamia. CONCLUSION: Quercetin is more efficacious for improving cognitive function under low vitamin D status. This might be owing to that interventions reduce Aß plaques, tau phosphorylation, and neuroinflammation, upregulate BDNF, reduce miR-26a and miR-125b, increase miR-132, and elevate gut microbial diversity including Facklamia and Aerococcus.

Effects of Chronic Whey Protein Supplementation on Atherosclerosis in ApoE-/- Mice.

Whey protein is associated with improvement of metabolic syndrome. This study aimed to evaluate effects of whey protein on atherosclerosis in ApoE-/- mice. Male ApoE-/- mice were fed with a high-fat/cholesterol diet (HFCD), or HFCD supplemented with 10% or 20% whey protein for 18 wk. At the end of experiment, serum lipid profiles and inflammatory cytokines were assayed. Livers were examined using HE staining and Oil Red O staining. Aortas were used for en face and cryosection analyses to observe aortic lesions. Western blotting analysis was used to assess relative protein expression of cholesterol metabolism in the liver and aorta. No significant differences were observed in body weight or food intake among the three groups. Liver examination demonstrated decreased lipid droplets and cholesterol content in the whey-protein-supplemented groups. En face lesion of the aorta revealed a 21.51% and 31.78% lesion reduction in the HFCD supplemented with 10% and 20% whey groups, respectively. Decreased lesion was also observed in cryosection analysis. Whey protein significantly increased the serum high-density lipoprotein cholesterol level by 46.43% and 67.86%. The 20% whey protein significantly decreased serum IL-6 (a proinflammatory cytokine) by 70.99% and increased serum IL-10 (an anti-inflammatory cytokine) by 83.35%. Whey protein potently decreased lipogenic enzymes (ACC and FAS) in the liver and NF-κB expression in the liver and aorta. Whey protein significantly increased protein expression of two major cholesterol transporters (ABCA1 and ABCG1) in the liver and aorta. Thus, chronic whey protein supplementation can improve HFCD-induced atherosclerosis in ApoE null mice by regulating circulating lipid and inflammatory cytokines and increasing expressions of ABCA1 and ABCG1.

Chia Seed Supplementation Reduces Senescence Markers in Epididymal Adipose Tissue of High-Fat Diet-Fed SAMP8 Mice.

Adipose tissue is a key organ with substantial senescent cell accumulation under both obesity and aging conditions. Chia seed is an ancient seed and is the richest plant source of α-linolenic acid. We aimed to determine how cellular senescence markers will be altered in adipose tissue of senescence-accelerated mouse-prone 8 (SAMP8) mice fed with high-fat diets (HFDs); and how chia seed can affect the above markers. SAMP8 mice and their control senescence-accelerated mouse-resistant 1 (SAMR1) were divided into four groups, that is, SAMR1 low-fat diet group (R1LF), SAMP8LF group (P8LF), SAMP8 high-fat group (P8HF), and SAMP8HF group supplemented with 10% chia seed (P8HC). At the end of the intervention, body composition was measured through T1-weighted magnetic resonance imaging, and epididymal (EPI) and subcutaneous (SC) adipose tissues were dissected for further analysis. Compared with the R1LF group, the P8HF and P8HC groups had significantly increased body fat mass. In EPI fat, p16, CD68 and PAI-1 mRNA expression from P8HF group were significantly increased; chia seed partially reduced p16 and CD68 mRNA expression. The P8LF group has increased p16 and CD68, and the P8HF group has increased p16, p21, and CD68; and P8HC group has increased p16 mRNA expression. The protein expression of p-AMPK in EPI and SC fat from the P8HF group was reduced. In conclusion, reductions in AMPK activity might be partially responsible for elevation in HFD-induced senescence markers in both EPI and SC fat, and chia seed supplementation is able to reduce senescence-associated markers at least in EPI adipose tissue.

Effect of omega-3 long-chain polyunsaturated fatty acid supplementation on heart rate: a meta-analysis of randomized controlled trials.

BACKGROUND: Elevated resting heart rate (HR) has emerged as a new risk factor for all-cause and cardiovascular mortality. The effect of marine-derived omega-3 long-chain polyunsaturated fatty acid (n-3 LCPUFAs) supplementation on HR was investigated as an outcome in many clinical trials. The present study was to provide an updated meta-analysis on the HR-slowing effect of n-3 LCPUFAs, and to differentiate the chronotropic effect between eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). METHODS: PubMed and Cochrane databases were searched for relevant articles examining the effects of n-3 PUFAs on HR through May 2017. A random-effects model was used to generate the pooled effect sizes and 95% confidence intervals (CIs). The pooled effect sizes were presented as weighted mean differences (WMDs). RESULTS: A total of 51 randomized controlled trials (RCTs) with approximately 3000 participants were included in this meta-analysis. Compared to placebo, n-3 PUFA supplementation mildly but significantly reduced HR (-2.23 bpm; 95% CI: -3.07, -1.40 bpm). Moderate evidence of heterogeneity was observed among included trials (I 2 = 49.1%, P heterogeneity < 0.001). When DHA and EPA were separately administered, modest HR reduction was observed in trials that supplemented with DHA (-2.47 bpm; 95% CI: -3.47, -1.46 bpm), but not in trials with EPA. CONCLUSIONS: The present meta-analysis provides strong clinical evidence demonstrating the effect of heart rate reduction by n-3 LCPUFA supplementation. When DHA or EPA administered alone, heart rate was slowed by DHA rather than by EPA.

Effects of coenzyme Q10 supplementation on inflammatory markers: A systematic review and meta-analysis of randomized controlled trials.

The aims of this meta-analysis were to evaluate the effects of coenzyme Q10 (CoQ10) supplementation on inflammatory mediators including C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) by analyzing published randomized controlled trials (RCTs). A systematic search in PubMed, Cochrane Library and Clinicaltrials.gov was performed to identify eligible RCTs. Data synthesis was performed using a random- or a fixed-effects model depending on the results of heterogeneity tests, and pooled data were displayed as weighed mean difference (WMD) and 95% confidence interval (CI). Seventeen RCTs were selected for the meta-analysis. CoQ10 supplementation significantly reduced the levels of circulating CRP (WMD: -0.35mg/L, 95% CI: -0.64 to -0.05, P=0.022), IL-6 (WMD: -1.61pg/mL, 95% CI: -2.64 to -0.58, P=0.002) and TNF-α (WMD: -0.49pg/mL, 95% CI: -0.93 to -0.06, P=0.027). The results of meta-regression showed that the changes of CRP were independent of baseline CRP, treatment duration, dosage, and patients characteristics. In the meta-regression analyses, a higher baseline IL-6 level was significantly associated with greater effects of CoQ10 on IL-6 levels (P for interaction=0.006). In conclusion, this meta-analysis of RCTs suggests significant lowering effects of CoQ10 on CRP, IL-6 and TNF-α. However, results should be interpreted with caution because of the evidence of heterogeneity and limited number of studies.

Effects of milk proteins on blood pressure: a meta-analysis of randomized control trials.

Certain foods or their components are widely used in the prevention and/or management of cardiovascular disease. Milk proteins have been suggested to have hypotensive properties. A number of clinical trials have been carried out to evaluate the effect of milk proteins from whole foods and supplements on blood pressure (BP). However, the effect of milk proteins on BP is not well understood. Therefore, we conducted a meta-analysis of randomized control trials to provide insight into and robust evidence concerning the overall impact of milk proteins on BP. The PubMed and Cochrane databases were searched for literature concerning the effects of milk proteins on BP up to May 2016. A random effects model was used to calculate the pooled estimates and 95% confidence intervals of effect sizes. The final analysis included seven randomized control trials involving 412 participants. Overall, milk protein interventions significantly lowered systolic BP by -3.33 mm Hg (95% confidence interval -5.62, -1.03) and diastolic BP by -1.08 mm Hg (95% confidence interval -3.38, -0.22). There was no statistical evidence of publication bias across the studies. In conclusion, this meta-analysis provides further evidence that milk proteins slightly but significantly lower both systolic and diastolic BP.