Onion peel extracts ameliorate hyperglycemia and insulin resistance in high fat diet/streptozotocin-induced diabetic rats

<p>Abstract</p> <p>Background</p> <p>Quercetin derivatives in onions have been regarded as the most important flavonoids to improve diabetic status in cells and animal models. The present study was aimed to examine the hypoglycemic and insulin-sensitizing capacity of onion peel extract (OPE) containing high quercetin in high fat diet/streptozotocin-induced diabetic rats and to elucidate the mechanism of its insulin-sensitizing effect.</p> <p>Methods</p> <p>Male Sprague-Dawley rats were fed the AIN-93G diet modified to contain 41.2% fat and intraperitoneally injected with a single dose of streptozotocin (40 mg/kg body weight). One week after injection, the rats with fasting blood glucose levels above 126 mg/dL were randomly divided into 4 groups to treat with high fat diet containing 0 (diabetic control), 0.5, or 1% of OPE or 0.1% quercetin (quercetin equivalent to 1% of OPE) for 8 weeks. To investigate the mechanism for the effects of OPE, we examined biochemical parameters (insulin sensitivity and oxidative stresses) and protein and gene expressions (pro-inflammatory cytokines and receptors).</p> <p>Results</p> <p>Compared to the diabetic control, hypoglycemic and insulin-sensitizing capability of 1% OPE were demonstrated by significant improvement of glucose tolerance as expressed in incremental area under the curve (<it>P </it>= 0.0148). The insulin-sensitizing effect of OPE was further supported by increased glycogen levels in liver and skeletal muscle (<it>P </it>< 0.0001 and <it>P </it>= 0.0089, respectively). Quantitative RT-PCR analysis showed increased expression of insulin receptor (<it>P </it>= 0.0408) and GLUT4 (<it>P </it>= 0.0346) in muscle tissues. The oxidative stress, as assessed by superoxide dismutase activity and malondialdehyde formation, plasma free fatty acids, and hepatic protein expressions of IL-6 were significantly reduced by 1% OPE administration (<it>P </it>= 0.0393, 0.0237, 0.0148 and 0.0025, respectively).</p> <p>Conclusion</p> <p>OPE might improve glucose response and insulin resistance associated with type 2 diabetes by alleviating metabolic dysregulation of free fatty acids, suppressing oxidative stress, up-regulating glucose uptake at peripheral tissues, and/or down-regulating inflammatory gene expression in liver. Moreover, in most cases, OPE showed greater potency than pure quercetin equivalent. These findings provide a basis for the use of onion peel to improve insulin insensitivity in type 2 diabetes.</p

Representative levels of blood lead, mercury, and urinary cadmium in youth: Korean Environmental Health Survey in Children and Adolescents (KorEHS-C), 2012–2014

AbstractBackgroundThis study examined levels of blood lead and mercury, and urinary cadmium, and associated sociodemographic factors in 3–18 year-old Korean children and adolescents.Materials and methodsWe used the nationally representative Korean Environmental Health Survey in Children and Adolescents data for 2012–2014 and identified 2388 children and adolescents aged 3–18 years. The median and 95th percentile exposure biomarker levels with 95% confidence intervals (CIs) were calculated. Multivariate regression analyses were performed on log transformed exposure biomarker levels adjusted for age, sex, area, household income, and father’s education level. The median exposure biomarker levels were compared with data from Germany, the US, and Canada, as well as the levels of Korean children measured at different times.ResultsThe median levels of blood lead and mercury, as well as urinary cadmium were 1.23μg/dL, 1.80μg/L, and 0.40μg/L (95% CIs, 1.21–1.25, 1.77–1.83, and 0.39–0.41, respectively). The blood lead levels were significantly higher in boys and younger children (p<0.0001) and children with less educated fathers (p=0.004) after adjusting for covariates. Urinary cadmium level increased with age (p<0.0001). The median levels of blood mercury and urinary cadmium were much higher in Korean children and adolescents than those in their peers in Germany, the US, and Canada. Blood lead levels tended to decrease with increasing age and divergence between the sexes, particularly in the early teen years. Median levels of blood lead and urinary cadmium decreased since 2010.ConclusionSociodemographic factors, including age, sex, and father’s education level were associated with environmental exposure to heavy metals in Korean children and adolescents. These biomonitoring data are valuable for ongoing surveillance of environmental exposure in this vulnerable population

Circulating microRNAs in sera correlate with soluble biomarkers of immune activation but do not predict mortality in ART treated individuals with HIV-1 infection: A case control study

Introduction: The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals. Materials and Methods: A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed. Results: None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR- 145 correlated with nadir CD4+ T cell count. Discussion: No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection

Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe

Selected Phytochemicals and Culinary Plant Extracts Inhibit Fructose Uptake in Caco-2 Cells

This study compared the ability of nine culinary plant extracts containing a wide array of phytochemicals to inhibit fructose uptake and then explored the involvement of intestinal fructose transporters and phytochemicals for selected samples. The chemical signature was characterized by high performance liquid chromatography with mass spectrometry. Inhibition of [14C]-fructose uptake was tested by using human intestinal Caco-2 cells. Then, the relative contribution of the two apical-facing intestinal fructose transporters, GLUT2 and GLUT5, and the signature components for fructose uptake inhibition was confirmed in naive, phloretin-treated and forskolin-treated Caco-2 cells. HPLC/MS analysis of the chemical signature revealed that guava leaf contained quercetin and catechin, and turmeric contained curcumin, bisdemethoxycurcumin and dimethoxycurcumin. Similar inhibition of fructose uptake (by ~50%) was observed with guava leaf and turmeric in Caco-2 cells, but with a higher contribution of GLUT2 for turmeric and that of GLUT5 for guava leaf. The data suggested that, in turmeric, demethoxycurcumin specifically contributed to GLUT2-mediated fructose uptake inhibition, and curcumin did the same to GLUT5-mediated fructose uptake inhibition, but GLUT2 inhibition was more potent. By contrast, in guava leaf, catechin specifically contributed to GLUT5-mediated fructose uptake inhibition, and quercetin affected both GLUT5- and GLUT2-mediated fructose uptake inhibition, resulting in the higher contribution of GLUT5. These results suggest that demethoxycurcumin is an important contributor to GLUT2-mediated fructose uptake inhibition for turmeric extract, and catechin is the same to GLUT5-mediated fructose uptake inhibition for guava leaf extract. Quercetin, curcumin and bisdemethoxycurcumin contributed to both GLUT5- and GLUT2-mediated fructose uptake inhibition, but the contribution to GLUT5 inhibition was higher than the contribution to GLUT2 inhibition

PUERARIA LOBATA/REHMANNIA GLUTINOSA AND EXERCISE INTERACTIONS ON INSULIN RESISTANCE AND METABOLIC INFLEXIBILITY USING 1H-NMR-BASED METABOLOMICS IN ESTROGEN-DEPRIVED ANIMAL MODEL

Lifestyle modifications, such as diet and exercise, are becoming increasingly recognized as important strategies to reduce the cardiometabolic risks during menopausal transition because the concern about safety issues in the use of hormone therapy. The present study aimed to investigate the effect and interaction of a combination supplement of Pueraria Lobata/Rehmannia Glutinosa (PR) and aerobic exercise on insulin resistance and metabolic inflexibility observed in an estrogen-deprived animal model. Ovariectomized (OVX) Sprague-Dawley rats fed with a high-fat diet (HFD) were randomly assigned to receive placebo, PR (400 mg/kg body weight), or estradiol (0.2 mg/kg body weight) by oral gavage with or without aerobic exercise for 8 weeks. Indices related to insulin resistance and cardiometabolism were determined in the blood, adipose tissue and muscle. Furthermore, 1H-NMR metabolites were measured in urine. The PR supplementation significantly improved insulin responsiveness in adipose tissue and muscle, leading to a restoration of metabolic flexibility. Adipose tissue became smaller, had more GLUT4 protein in membrane, less macrophage infiltration and higher hormone-sensitive lipase mRNA expression. The metabolic profiles before and after PR supplementation and aerobic exercise were separated based on multivariant analyses of principal component analysis (PCA) and orthogonal partial least square-discriminant analysis (OPLS-DA). Thirty-six metabolites from variable importance plots were screened before and after PR supplementation and aerobic exercise. The 23 metabolites had significantly increased the levels of choline and taurine but significantly decreased levels of ethylene glycol, fumarate and phenylalanine after PR supplementation. Taken together, the results suggest that PR supplement with aerobic exercise has a potential to relieve insulin resistance and its related metabolic defects in postmenopausal women, reflecting changes in metabolite composition.Acknowledgements: This work was supported by the Bio-Synergy Research Project (NRF-2012M3A9C4048761) of the Ministry of Science, ICT and Future Planning through the National Research Foundatio

Comparison of Statistical Models for Cross-over design

Cross-over designs have been widely used in clinical trials to investigate the efficacy of new treatments. In cross-over design, each subject is treated subsequently with different treatments. Many methods such as linear mixed models (LMMs) and generalized estimating equation (GEE) models have been used to analyze the repeated measurements from cross-over design. When we consider repeated measured response variables, estimation of random components for LMMs is not always easy. In this article, we applied the GEE method to cross-over design to overcome the limitation of LMMs. To apply the GEE model to the data from the cross-over designs, we need to switch the role of variables in LMM such a way that the independent variable in LMMs is considered as a response variable in GEE model and vice versa. The purpose of this study is to compare the performance of these GEE models and LMMs for cross-over designs. Through simulation studies, we checked the type I errors and compared power to evaluate the performance of the proposed GEE model and LMMs.N

Daily Nutritional Dose Supplementation with Antioxidant Nutrients and Phytochemicals Improves DNA and LDL Stability: A Double-Blind, Randomized, and Placebo-Controlled Trial

Reactive oxygen species are important risk factors for age-related diseases, but they also act as signaling factors for endogenous antioxidative defense. The hypothesis that a multi-micronutrient supplement with nutritional doses of antioxidant nutrients and phytochemicals (MP) may provide protection against oxidative damage and maintain the endogenous antioxidant defense capacity was assessed in subjects with a habitually low intake of fruits and vegetables. In a randomized, placebo-controlled, and parallel designed trial, 89 eligible subjects were assigned to either placebo or MP for eight weeks. Eighty subjects have completed the protocol and included for the analysis. MP treatment was superior at increasing serum folate (p &lt; 0.0001) and resistance to DNA damage (p = 0.006, tail intensity; p = 0.030, tail moment by comet assay), and LDL oxidation (p = 0.009) compared with the placebo. Moreover, the endogenous oxidative defense capacity was not weakened after MP supplementation, as determined by the levels of glutathione peroxidase (p = 0.442), catalase (p = 0.686), and superoxide dismutase (p = 0.804). The serum folate level was negatively correlated with DNA damage (r = −0.376, p = 0.001 for tail density; r = −0.329, p = 0.003 for tail moment), but no correlation was found with LDL oxidation (r = −0.123, p = 0.275). These results suggest that MP use in healthy subjects with habitually low dietary fruit and vegetable intake may be beneficial in providing resistance to oxidative damage to DNA and LDL without suppressing the endogenous defense mechanisms

METABOLOMIC AND CLINICAL BIOMARKERS ANALYSIS OF THE IMPACT OF SANGHUANG-DANSHEN ON PLATELET HYPERACTIVITY IN HUMANS

The postprandial condition is recognized as a procoagulant state. Postprandial platelet hyperactivity plays a crucial role in the pathogenesis of metabolic syndrome. Botanical foods typically contain a multi-component composition derived from herbal practices. Therefore, it is difficult to determine which components regulate platelet hyperactivity. Metabolomic analysis is a valid and powerful tool with which to further define the mechanisms. We therefore aimed to assess the effect of Sanghuang-Danshen (SD) in the metabolome and clinical biomarkers on platelet hyperactivity after an acute challenge with high-lipid/glucose formula in healthy subjects. In a crossover randomized and placebo-controlled intervention study, fifty-six subjects received three doses of SD or placebo. Platelet aggregation and mRNA expression of cyclooxygenase-1 and vascular cell adhesion molecule-1 were all decreased in the SD group. SD administration appears to reduce the platelet hyperactivity associated with a postprandial condition. These changes are accompanied by alterations of the metabolomics. A total of 13 metabolites were found to be significantly different between placebo and the high-dose SD group, which were strongly involved in linoleic acid metabolism, alanine, aspartate and glutamate metabolism, arachidonic acid metabolism, and glycine, serine and threonine metabolism. By integrating components in SD, markers, and phenotype, we find that SD may modulate the platelet hyperactivity occurring in the postprandial state